Smart Parenting Guide

Law Of Attraction For Kids

Winsome Coutts, a mother of two and a grandmother, has a teacher's certification in education and she has taught several schools in Australia and Canada. She has also written hundreds of articles concerning self-development. Winsome has a passion for the Law of attraction, meditation, Self-help of Personal development, goal setting, and the secret movie. She decided to engage in the pursuit of knowledge in the mentioned areas throughout her life. Winsome has considerable experience raising children following her studies in Child psychology at University, and as a past teacher, a parent, and a grandparent. She knows that when children learn how to plan for their future and how to achieve their goals, they have a skill that will last them a lifetime. Winsome personally studied with two popular teachers, John Demartini and Bob Proctor and both are featured in The Secret' movie. For several decades since the early 90s, she has been goal setting for kids, visualizing, and applying the law of attraction. The law of attraction for kids is the first book ever to describe the law of attraction and the term goal setting. The language employed is simple for your children to understand and it will answer any question about the life-changing topics in a more detailed parent's guide. More here...

Law Of Attraction For Kids Summary


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Cross Talk between HDAC Family Members

Members probably do not function independently. In fact, studies have presented ample evidence that several of these deacetylases might work in conjunction and regulate common biological targets and processes. For example, HDAC4 and HDAC5 can associate with HDAC3 (Grozinger et al., 1999 Fischle et al., 2002). These observations led to the hypothesis that HDAC3 might be the catalytic subunit for the HDAC4 deacetylase (Fischle et al., 2002). However, it is important to note that although endogenous HDAC3 is abundantly present in the NcoR and Smrt co-repressor complex, HDAC4 is not part of the complex (Yoon et al., 2003). Thus, it is unlikely that endogenous HDAC4 (or another class IIA HDAC) forms an exclusive complex with HDAC3 in vivo. We have found that HDAC4 and SIRT1 can also form a complex and this complex could be important in regulating MEF2 transcriptional activity (Zhao et al., 2005). As discussed, both HDAC1 and SIRT1 have been shown to promote p53 deacetylation (see above)....

Hsp70 Family Members Danger Signals And Autoimmunity

Abstract The 70 kiloDalton family of heat shock proteins (Hsp70) are known to stimulate immune responses and have been increasingly implicated in autoimmune conditions. Hsp70 proteins are present in pathogens as well as in healthy cells. They can be expressed constitutively or elevated in response to heat or other cellular stress. Immune responses stimulated by Hsp70 family members include triggering of innate inflammatory responses, enhancing antigen presentation to self-reactive T cells, and cross priming of chaperoned tumor and other self antigens. In this chapter, we present an overview of immunomodu-latory activities described for Hsp70 proteins and review the evidence implicating Hsp70 activity in autoimmunity. The ability of Hsp70 to stimulate anti-self tumor immunity and the prospect of using Hsp70 in vaccines or as adjuvants for cancer immunotherapy will be examined. Finally we discuss potential mechanisms by which Hsp70 proteins act as danger signals and regulatory molecules...

Longterm Effects Of Cancer Diagnosis And Treatment On Survivors Family Members

The literature on the effect of cancer diagnosis and treatment on family members is sparse.74 Of studies in this area, most have focused on the impact of cancer soon after diagnosis, during recurrence, or at the terminal phase of the disease.75-77 One study shows that partners of men with prostate cancer, generally from small convenience samples, report more distress than their sick partners, but also believe that their partners are more distressed. The only reviewed study of long-term prostate cancer survivors found that couples' health-related QOL was associated with marital satisfaction.61 Distress was inversely related to levels of family support. The men's focus of concern, on their sexual functioning (i.e., impotence), was not shared to an equal degree by their non-sick partners.78,79 The most relevant study included in our review focusing on family survivorship included families from 1 to 5 years posttreatment,80 thus making specific statements about the long-term effects of...

Catalytic Activities of the PPP Family Members

Figure 2 Domain organization of protein phosphatases in the PPP family. Bacteriophage and eubacteria Ppps show homology to the eukaryotic and archeabacterial protein phosphatases in the amino-terminal half of the catalytic domain, but the carboxy-terminal halves show little similarity. Autoinhibitory regions (AIs), Ca2+-binding EF hands, tetratricopeptide repeats (TPRs), and calmodulin (CaM) binding sites are indicated. The numbers of amino acids in different phosphatases with each type of structure are given on the right. The three invariant amino acid motifs found in all PPP family members are shown at the bottom of the figure (numbers refer to the amino acid position in PP1a1 PP1y1). Figure 2 Domain organization of protein phosphatases in the PPP family. Bacteriophage and eubacteria Ppps show homology to the eukaryotic and archeabacterial protein phosphatases in the amino-terminal half of the catalytic domain, but the carboxy-terminal halves show little similarity. Autoinhibitory...

Domain and Subunit Structure of PPP Family Members

Although Ppp1c (PP1) and Ppp2c (PP2A) possess only very short amino- and carboxy-terminal regions outside the catalytic region, other PPP family members may possess fused amino- and carboxy-terminal domains that, at least in some cases, impart distinct properties to the catalytic domain. Thus, Ppp3c (PP2B, calcineurin) has a carboxy-terminal domain that allows the enzyme to be activated by Ca2+ calmodulin, as well as an autoinhibitory pseudosubstrate domain 26 . Ppp7c has EF hand sequences that confer Ca2+ sensitivity and a calmodulin-binding motif that is distinct from that of Ppp3c 22 . PP5 has an inhibitory amino terminal domain containing three tetratricopeptide repeats (TPRs) that are likely to allow interaction with other proteins 21,27 .

Family Members and Friends

Although most caregivers (primarily family members) are highly motivated and are committed to providing care, caregivers involved with patients who have cancer experience substantial burdens.67-76 Not The majority of the literature concerning caregiver burden has focused on family members and friends of the patient, but an interesting subset of the literature addresses the stresses and trials experienced by members of the health care team when they care for patients with chronic and life-threatening illness. Those health professionals caring for patients with end-of-life issues in the setting of germ cell tumors are frequently caring for those who are young, and death among these individuals is most commonly considered to be unnatural. These specific issues, combined with the stresses encountered in many health care systems today, can serve to create significant stress for health professionals.

Feeding ecology and diet

Foraging strategies among the Old World warblers are diverse. Some species forage singly or in pairs, while others forage in groups of several family members or other conspecifics. Still others readily join mixed-species foraging parties, especially in the nonbreeding season. Cisticola nigriloris forages in groups of 5-8 birds, apparently keeping in contact by group-singing. Many African and nontropical species, join foraging parties in the nonbreeding season.

Vulnerability And Research Consent In The Nursing Home

Understanding the consent process for treatment can be helpful for those who seek research consent in the nursing home. That process can become complex. Staff may have an interest in providing correct health care and in an orderly routine to benefit the residents as a group. Family members of residents may vacillate between wanting the best health care and wanting them to be as free as possible to continue their preferred living patterns. Residents may experience the same ambivalence, complicated occasionally by confusion and forgetfulness. Residents, family members and staff as a group must make decisions that direct health care, respect the autonomy of the resident, and maintain the orderly operation of the nursing home. This is frequently done in care planning meetings in which all groups and interests are represented. Afterwards, it may be difficult to identify a point in this process at which consent actually takes place. In some respects, it is more like a negotiation process...

Elderly Personswillingness To Participate In Research Studies

Reducing participation (Sugarman et al., 1998). Furthermore, some elders refuse to sign, fear the implications of, or are otherwise inexperienced with consent forms, and some may insist that family members be involved in the informed consent process, thereby adding to the efforts of investigators. These factors may frustrate both potential research subjects and investigators and lead to reduced participation (Kaye, J., Lawton, P. and Kaye, D., 1990). Transportation, mobility issues and medical conditions that require frequent attention may reduce participation or cause some elders to drop out of studies (Sachs, G. and Cassel, C., 1990). When recruiting elders for research studies, investigators should consider and address these and other factors that may adversely affect participation.

Spheniscus magellanicus

Behavior and reproduction Like other penguins the Magellanic species breeds in large colonies. They often return to the same nesting site year after year. This bird nests in burrows where possible, in ground nests when not. Both sexes build the nest and share all incubation and parenting duties. The chick from the second laid egg is less likely to survive than its older sibling. The chicks are fed regurgitated food every two to three days.

Sporadic Versus Hereditary Genetic Changes

Cancer is a disease caused by defective or damaged genetic material. Because our genetic material is entirely inherited, it may seem paradoxical that the majority of human cancers are sporadic and affect people at random. In some kindreds, however, numerous family members develop cancers that may be considered familial, the affected individuals being genetically predisposed to develop malignancies. These familial cancer aggregations are relatively uncommon, but they have been extremely helpful in the identification of specific genes involved in some cancers.

Demography Mortality and Health Statistics

The National Center for Health Statistics at the United States Center for Disease Control and Prevention contains a Data Warehouse on Trends in Health and Aging on its aging activities page. Users can view, chart, and download data on life expectancy, disability, insurance utilization, socioeconomic status and other measures for United States citizens over the last century or so. Furthermore, the site provides downloadable software for manipulating the information and tailoring it to individual needs. Some sites document types of demographic data other than mortality trends. For instance, the Utah Population Database contains an extensive set of Utah family histories, including medical information for individual family members. This database contains a cancer registry and information about cause of death. Access is free, but requires advance approval for use of the data.

Possible Maternal UPD3

The only potential case, reported in 1974, is suggested by the duplication in an offspring of the chromosomal heteromorphism of a mother heterozygous for chromosome 3 pericentric inversion, inv(3)(p12 q14), inherited from her own father (Betz et al., 1974). This slightly retarded woman had two nondysmorphic, mentally retarded daughters one was heterozygous but the other homozygous for this chromosome 3 inversion. The father was unavailable for study. To explain this homozygosity, the authors considered the (consanguineous) mating of two closely related carriers of this inversion that was also present in several other nonretarded, family members. Since no DNA polymorphisms were available at the time, there is no formal demonstration of maternal UPD3 in this case.

What Is Hereditary Breast Cancer

In clinical genetics, hereditary cancer is often used in a more practical sense to denote cases with a strong family history of the disease, consistent with the inheritance of a single dominant gene. This is often distinguished from sporadic cancer, meaning no family history and familial cancer, meaning any family history of the disease. Familial by itself is a rather loose concept in that it depends on how detailed a family history has been taken. Since breast cancer is a common disease, some family history of breast cancer will be found in most women if the pedigree is extended far enough. However, if restricted to first-degree relatives, approximately 10 of breast cancer cases would be considered familial. The proportion of women with a strong family history (say two affected first-degree relatives) is much smaller, but again it depends on how comprehensive a family history is available. Distinguishing women with a strong family history is useful in practice, since such individuals...

Biologic Outcome of Jak Stat Activation

Jakl-deficient mice are 40 smaller than littermates and die within 24 h of birth, probably as a result of failure of neurogenesis (1). Signaling was ablated in response to IFN-y, IFN-a, and IL-10, as well as cytokines that use the yC and gp130 chains. The absence of IL-7 signaling is thought to be largely responsible for a failure of lymphocyte development with an absence of T-lymphocyte development and a block in B-cell development at the transition from the pro-B to the pre-B cell. The response of Jakl-deficient macrophages, cardiomyocytes, and neurons to gp130 family members IL-6, CT-1, and LIF was severely perturbed.

Models Of Breast Cancer Susceptibility

There are additional reasons for believing that the polygenic model is reasonable. The frequency of BRCA1 and BRCA2 in breast cancer families is strongly dependent on the degree of family history, so that the majority of families with a strong family history (for example, six or more cases) harbor a mutation in one of these genes. This suggests strongly that most other breast cancer genes will confer lower risks. In addition, further genetic linkage studies in multiple case families have not found evidence of any further susceptibility loci, suggesting that if other high-risk susceptibility loci do exist, the alleles are likely to be rare (15,38). The recent identification of some low-penetrance breast cancer loci is further confirmation that susceptibility to breast cancer does have a substantial polygenic component.

Social Factors In Personality Disorders

A parallel conjecture could be made concerning narcissistic personality disorder (Paris, 2003). Although we have no good community studies of the prevalence of narcissistic personality disorder, some clinicians (e.g., Kohut, 1977) have thought that more cases are presenting for treatment. If this is so, we might hypothesize that heritable narcissistic traits are normally channeled into fruitful ambition by strong family and social structures but that under conditions of rapid social change, the same traits can become dysfunctional.

Host Response To Vaccinia

Understanding vaccinia's immune evasion strategies may help optimize the virus as a vector for clinical use. The virus is effective in suppressing both innate immunity and the development of T-helper cells. Vaccinia virus has adopted genes whose product can block the function of the interferon family members interferon- (IFN) a p,y or that can inhibit chemokines, which are some of the earliest substances produced during the initiation of a viral host immune response (42-47) (Table 1).

The Qualitative Burden Of Cancer Survivorship From The Patients Perspective

Inadequate availability of resources was a common thread. One third of the responders indicated that only limited resources were available to meet their emotional needs 28 lacked resources for practical issues such as financial management and work-related issues 23 lacked resources for physical issues. On the other hand, 86 of responders indicated that resources were available for medical issues directly related to the cancer. Family members and friends provided the bulk of support and were generally viewed as being the most important resource. More than 33 of re-sponders indicated that government agencies were unable to provide support and 30 did not receive assistance from social workers. Twenty-four percent had not received assistance from their insurance company, 25 had some limited interactions,

Indications for MSI Assay

The indications for an MSI assay are listed in chapter 10 (Table 10-1). The primary reason to perform an MSI assay is to rule out HNPCC. HNPCC kindreds may develop multiple cancers of the colorectum or other sites, and the operation of choice in affected individuals is pan-colectomy. Surveillance for cancers of other sites should be considered. Family members of patients with HNPCC are at risk, and genetic counseling for these individuals is recommended. The second reason to perform an MSI assay is that the MSI phenotype in colorectal cancer has prognostic significance.

Regulation of the Jak Stat Pathway

Activated Stat proteins can be negatively regulated by interactions with protein inhibitor of activated Stat (PIAS) proteins, of which there are five family members. PIAS1 and PIAS3 bind to and inhibit Statl and Stat3, respectively (60,61). The functions of the remaining three members of the PIAS family, PIASy, PIASxa and PIASxP, remain unclear. A fundamental negative regulatory mechanism of Jak-Stat cytokine signaling uses the suppressor of cytokine signaling (SOCS) proteins (reviewed in refs. 62 and 63). The SOCS family has eight members CIS (cytokine-induced SRC-homology 2 SH2 protein) and SOCS1-7. This family is characterized by a central SH2 domain, a variable N-terminus, and a SOCS box motif at the C-terminus. Basal expression levels of SOCS family members are generally low but can be rapidly upregulated (often by the Stats themselves) in response to cytokine stimulation, thereby forming part of a classical negative feedback loop. The mechanism of Jak-Stat inhibition by SOCS...

Oncogenic Capacity Of The Jakstat Signaling Pathway

Growth of tumors such as childhood acute lymphoblastic leukemia (ALL) is often dependent on cytokine stimulation, presumably through a paracrine or autocrine pathway, which induces phosphorylation and activation of receptors and associated signaling pathways, including the Jak-Stat pathway. Specific inhibition of Jak2 in ALL and acute myeloid leukemia (AML) by the tyrphostin AG490, a specific tyrosine kinase blocker, inhibited proliferation and induced apoptosis of leukemic cells without significant perturbations in hematopoiesis (83,84). Another form of ALL is associated with a chromosomal translocation fusing the catalytic kinase domain of Jak2 with an ETS transcription factor family member TEL, also known as ETV6. TEL is characterized by a DNA-binding domain (conserved in ETS family members) and importantly, a helix-loop-helix oligomerization domain that allows TEL-Jak2 to dimerize and activate Jak2 kinase activity, thereby activating signaling pathways. Other common cytogenetic...

Evolution of the Nuclear Receptor Superfamily

Mammalian NRs are dispersed throughout multiple chromosomes of the genome, it is likely that early metazoans experienced genomic duplications that facilitated this distribution.8 Despite this diversity, however, NRs share conserved structural elements, which has allowed the identification and cloning of novel receptors by virtue of sequence similarity. The most highly conserved portion of nuclear receptors is the DBD, which often displays 90 amino acid sequence identity between orthologous (functionally identical genes across species) and paralogous (related genes within a species) family members. While the zinc finger DNA-binding motif is present within transcription factors of virtually all eukaryotes, the NR DBD, containing two Cys2 Cys2 zinc fingers, is apparently restricted to metazoans, with orthologous or related genes present in nematodes, arthropods, fish, birds, amphibians, and mammals.5 This finding is supported by polymerase chain reaction-directed searches for more...

Elderly Living Arrangements Ethnic Comparisons

Latinos are less likely to live alone and more likely to live with family members than white and African American elderly. Over three-fourths (76.6 ) of Latino elderly lived with family, compared with two-thirds (67.5 ) of white elderly and approximately 6 out of 10 African American elderly (63.1 ) (U.S. Bureau of the Census, 1990b). About 2 out of 10 elderly Latinos (22.0 ) lived alone, compared to 3 out of 10 white elderly (30.6 ), and one-third of African American elderly (33.4 ) (U.S. Bureau of the Census, 1990b). Latino elderly are more likely than other elderly to live in a multigenerational family where the child is the householder. In 1989, Latino elderly were less likely to be householders (60.2 ) than white (70.7 ) and African American (68.1 ) elderly. Moreover, a larger percentage of elderly Latinos (38.7 ) were nonhouseholders living with family members than white (30.7 ) or African American (27.5 ) elderly (U.S. Bureau of the Census, 1990b).

Receptor Classification by Mode of Action

Nuclear receptors can be grouped into four classes based on their DNA-binding and dimer-ization properties (Fig. 3.4).25 Generally speaking, class I receptors include GRs, mineralcorti-coid receptors (MRs), progesterone receptors (PRs), and androgen receptors (ARs), which function as homodimers and bind to IRs separated by 3 base pairs (i.e., IR-3). An exception to this rule is the estrogen receptors (ERs) which can form either heterodimers or homodimers on IR-3.30-32 Class II receptors require het-erodimerization with RXR family members and bind to DRs, varying from DR-1 to DR-5. The spacing, in general, specifies the identity of the dimerization partner. Class III receptors, including hepatocyte nuclear factor 4 (HNF-4), chicken ovalbumin upstream promoter-transcription factor (COUP-TF), and germ cell nu-

Activation of Inflammatory Cytokines

Such as cytokines or viruses, activation of the canonical NFk-B pathway occurs via signal transduction cascades that promote the phosphorylation and degradation of inhibitor of NFk-B proteins (IkBs), thereby releasing the NFk-B heterodimer. The activated heterodimer of p50 and p65 Rel A is able to translocate to the nucleus and drive the expression of target genes (reviewed in Baldwin 1996). Gene inactivation experiments of individual NFk-B family members have revealed that Rel A proteins are required for lymphocyte activation by controlling proliferation, immu-noglobulin isotype switching, and the expression of cytokines and their receptors (Attar et al. 1997 Gerondakis et al. 1998). Inflammatory cytokines, including TNF-a, IL-1, IL-6, IL-8, IL-12, and IL-18 have a wide range of biological effects on tissues and cells and are believed to be critical for the recruitment and activation of phagocytic leukocytes to the sites of infection (Laroux 2004). Activation of the IC branch of...

Modernization Approach To Aging And Ethnicity

We can gainfully compare the experience of immigrants moving from agricultural to urban-industrial environments to analysis of modernized societies and less modernized ones or the modernization of one society over time. If modernization weakens the extended family and subsequent status of the elderly, likewise, the transplantation of a group from a traditional society to a modern one can be expected to have similar consequences (Markides & Mindel, 1987). Conversely, one could argue that immigrant enclaves are more tightly knit than the communities from which they emigrated because of their minority status. (Recall the notion of ethnogenesis introduced earlier.) Accordingly, immigrants would have strong family ties and commitment to ethnic heritage because of their isolation, subjective feelings of being a cultural outsider, the foreign environment, and the need to reinforce the familiar. Modernization theory aids us in understanding the experiences of the Mexican American elderly...

Project Title Cardiovascular Disease In The Pima Indians

Summary MedStar (formerly Medlantic) Research Institute proposes to continue its participation in the Strong Heart Study to manage the Arizona field center and the core laboratory. For the field center, this proposal describes methodology for 1) morbidity and mortality surveillance of the original Strong Heart Study cohort (1099 surviving out of 1500 original men and women ages 45-74 years in Phase I) 2) recruitment and examination of 30 families of at least 30 members, each 15 years and older and 3) re-examination of the 900 family members from the Phase Ill pilot study. The Arizona field center comprises three American Indian communities Gila River, Salt River, and Ak Chin. The Arizona center had a 71 recruitment rate in Phase I and 90 + completion rates in Phases II and III. Morbidity and mortality surveillance obtained data on 99 of the participants. The core laboratory will provide accurate, reliable, stable, and comparable phenotypic measures of coronary heart disease risk...

Antepartum Postpartum Depression

Pregnancy and the postpartum period are times of heightened depressive risk for patients who may wish to avoid pharmacotherapy. Spinelli & Endicott (2003) compared 16 weeks of IPT to a weekly parenting education control programme in a group of 38 antepartum women with major depression. Pregnancy is deemed a role transition that involves the depressed pregnant woman's self-evaluation as a parent, physiological changes of pregnancy, and altered relationships with the spouse or significant other and with other children. 'Complicated pregnancy' has been added as a fifth potential interpersonal problem area. Session timing and duration are adjusted for bed rest, delivery, obstetrical complications, and child care, and postpartum mothers may bring children to sessions. As with depressed HIV-positive patients, therapists use telephone sessions and hospital visits as necessary (Spinelli, 1997). The IPT group showed significantly greater improvement of depression than the parent education...

Yeast Telomere Protein Components

Of SIR2, SIR3 and SIR4, only SIR2 has orthologs in a large number of other organisms. SIR2 encodes an NAD+-dependent deacetylase that is important in maintaining gene silencing and prolonging yeast lifespan (reviewed by Blander and Guarente (2004)). Many organisms encode multiple SIR2 family members, or sirtuins, and the suggestion has been made that sirtuins may alter protein posttranslational modification to regulate responses to stress that also affect lifespan (Blander and Guarente, 2004).

The Universality of Yeast Aging Mechanisms and Future Outlook

The short telomere senescence phenotypes of yeast have clear parallels with human cells. Both systems utilize telomerase and ATM family members in telomere metabolism and short telomere signaling. Both systems have telomere-associated proteins that can be released to function at other sites (the SIR proteins in yeast and the Rif1 and TRF2 proteins in human cells). Thus, telomere shortening in both systems has the potential to release associated proteins that may play roles in lifespan regulation. While the orthologs affected in these processes may not always show an exact one-to-one correspondence, the conservation of general biological mechanisms from one system can guide the model building in the other.

Patients Description Of Pain And Meaning

The clinician must also be aware of cultural differences. In some Asian cultures, for example, patients are afraid to complain of pain because they believe that pain is a punishment for a family's past wrongdoing. Therefore, they are afraid to discuss pain with the clinician when their family members are around. In this case, the clinician has to be sensitive and keen enough to use translators who are not family members. Often, patient education can improve the patient's understanding of the pain and enable them to take a more active role in their pain management. The more patients understand their pain condition, the more likely they will be compliant with therapy (67-75).

Ethics Framework For Clinicians

Although these four principles provide a framework for identifying relevant concerns, they do not provide a specific approach for addressing ethical dilemmas that arise when the principles appear to generate competing ethical obligations. For example, if a patient does not want to disclose genetic risk information relevant for specific relatives, a clinician may be faced with a conflict between upholding patient autonomy and providing benefit or minimizing harm to family members. Various moral or ethical theories may be helpful in balancing competing ethical claims (2). For example, a utilitarian approach considers which resolution to an ethical conflict benefits the most people whereas a Kantian (deontological) approach considers that some actions must be performed out of obligation, determined in part by the universal implications of such actions (2). For example, what would be the implications of overriding patient autonomy to inform a patient's relatives of positive genetic test...

Occurrence and Functions of Giyyig Enzymes

The GIY-YIG module has now been found in at least 60 proteins, representing a diverse range of family members. They include proteins encoded by group I introns in bacteriophage and in the mitochondrial and chloroplast genomes of fungi, algae and liverworts in intergenic proteins of phage, viruses, and bacteria and the UvrC subunits of archaeal and bacterial (A)BC DNA excision repair complexes (Kowalski et al. 1999). Approximately one-third of the GIY-YIG family members are intron-en-coded proteins, several of which have been shown to have endonuclease activity and therefore most likely function in the mobility of their host intron in a classic homing pathway (see Belfort, this Vol. Dujon, this Vol.). Another one-third are intergenic proteins, most of unknown function. However, a set of seven related intergenic family members in the T-even phages have been characterized (Sharma et al. 1992 Sharma and Hinton 1994 Kadyrov et al. 1997 Belle et al. 2002 Liu et al. 2003). These Seg proteins...

Paramyxoviruses Measles virus and Newcastle Disease Virus

Measles virus (MV) and Newcastle Disease virus (NDV) are members of the negative single-stranded RNA paramyxoviridae family (120). MV is a member of genus Morbillivirus whereas NDV is a member of the Rubulovirus genus that comprises mumps virus. These family members encode 6 to 7 covalently linked genes from a 15-to 16-kb genome and are enveloped viruses (83). In the case of MV, the hemagglutinin (H) attachment protein binds to one of two cellular receptors, CD46 or the signaling activation molecule. CD46 is frequently overexpressed on cancer cells (20). Given that other replicating RNA viruses were becoming noted for their oncolytic effects, it was decided to evaluate whether derivatives of the Edmonston-B-strain of measles virus (MV-Ed), which are live attenuated vaccines that have been effectively used for over 30 yr, exhibited similar properties. Indeed, intratumoral and intravenous inoculation of MV-Ed was found to induce the regression of human lymphoma in xenographed models...

Physical characteristics

The name puffbird is applied to the family because of an unusual propensity of its members to puff up their feathers when alarmed. Even when not alarmed they seem large-headed and large-eyed, with robust, slightly curved or hook-tipped bills. Puffbird wings tend to be short and rounded (there are 10 primaries and 12 rectrices), and their tails tend to be short and narrow, though broader and longer in some nunbirds (Monasa). Plumage is soft and loose. Feet are small and zygodactylous (two toes before and two behind), with the first and fourth digits permanently reversed. The most divergent species is the swallow-winged puffbird (Chelidoptera tenebrosa), which has more tapered wings and a shorter bill than other family members.

Research From Our Approach

To exemplify the ways in which our perspective shapes problems of relevance for contextual aspects of environment behavior research, we now complement previous mention of our studies with a more comprehensive description of our work on six problems. These six problems (three treating the general contexts of the person and three of the environment) are as follows onset of diabetes (physical context of person) changes in experience and action related to psychiatric hospitalization (psychological context of person) transition to parenthood (socio-cultural context of person) urban contexts for children (physical context of environment) protection against AIDS in sexual situations (interpersonal context of environment) and experience and action in the context of automobile driving before and after mandatory legislation (sociocultural context of environment). Transition to Parenthood (Sociocultural Context of Person) Extensive consideration of the sociocultural context of the person with...

Regulation of cell cycle progression by retinoblastomasusceptibilitygene product

The cell cycle regulatory function of rb may involve other transcription factors, such as the Ets family members which are involved in cell cycle progression in activated T cells. The Ets related transcription Elf-1 has been found to bind rb protein by a sequence motif which is related to rb-binding motifs carried by viral oncoproteins (Wang CY et al., 1993). As with E2F, phosphorylation of rb results in the release of Elf-1. The rb protein is also known to bind to other transcription factors such as the ATF2, causing transcription of ATF2 target genes (Kim et al, 1992).

DNABinding Domain Diversity and Conserved Modules

The modular nature of I-TevI has led us to propose that the GIY-YIG catalytic cartridge can acquire specificity by associating with various DNA-bind-ing domains (Derbyshire et al. 1997). The structure of the DNA-binding domain of I-TevI, and comparisons with the sequences of other family members, show this to be the case. This modular organization that separates cleavage and DNA binding into distinct domains is a feature shared with the HNH proteins but not with the LAGLIDADG and His-Cys box endonucleases, which have their catalytic and DNA-binding functions within a single subunit or

Liver X and Farnesoid X Receptors

Oxysterols apparently also upregulate expression of proteins involved in sterol lipid transport. For example, certain ABC transporters involved in lipid transport and cholesterol ester transfer proteins are activated through LXR signaling.419-421 An additional level of regulation may include transcriptional induction of LXRs by PPAR family members activated by certain fatty acids.422 The involvement of these receptors in the tightly regulated process of enterohepatic cholesterol metabolism suggests that pharmacological modulation of their activity could dramatically affect lipo-protein metabolism in disease states such as hypertriglyceridemia, hypercholesterolemia, and atherosclerosis.

Reproductive biology

Despite the male's vigilant parenting skills and the female's vigorous defense of boundaries, juvenile jacanas face low odds of survival. More than 50 never make it out of the nest. Of those that survive, fewer than 50 reach adulthood. In some species, such as the African jacana, the failure rate is as high

Detection and Assessment

In a clinic-based study, the detection of depressive symptomatology in patients with PD more than doubled (21-44 ) when patients were screened using the Beck Depression Inventory (BDI) (15). The assessment and recognition of depression has been ranked highly as an indicator for improving care of PD patients (103). All PD patients should be screened periodically to detect clinically significant depressive symptomatology. If self-reported disability is out of proportion to findings on the neurologic exam, depression should be suspected (73). Caregivers or family members are often valuable sources of information about the patient's psychological well-being, especially when self-report may be unreliable (104).

Experimental Research on Advanced Directives

The use of such instruments assumes, however, that ADs improve the ability of a surrogate decision-maker to substitute judgment on behalf of the patient. Indeed, numerous studies have reported that, without ADs, the ability of family members and healthcare providers to accurately predict treatment-related preferences is very poor (e.g., Ouslander et al, 1989 Seckler et al, 1991). But research had not evaluated whether discussion of ADs between patients and proxies improves the accuracy of substituted judgment. Ditto and colleagues (2001) developed an experimental paradigm to study the agreement between patients and surrogates for different illness scenarios.

Social Support Definitions and Measurement

Another aspect to consider in the measurement of social support is the source of supportive functions. Social support measures vary in the degree of detail collected regarding level and type of support provided by different sources (e.g., intimate partner, family members, friends, co-workers), but often global or average scores that ignore specific sources or divide sources into broad categories (e.g., family versus friends) are used in health research. Although differential health benefits have been found for the presence of different types of social ties (e.g., marital, friends, group membership e.g., Giles et al, 2005), less information is available on the health impact of support from different sources. We should also note that support from paid professionals (e.g., therapists, physicians) may be conducive to health, but we focus solely on support from targets within individuals' natural social networks in this review.

Mutations Affecting GALT and LN Development

Studies in mice with mutations in individual Rel NF-KB family members have demonstrated that both NF-kB1 and NF-kB2 signaling pathways are critical for PP and LN organogenesis and formation of lymphoid tissue architecture, although NF-KB1-deficient mice show a milder phenotype. RelB (NF-KB2-subunit)-deficient mice lack all LNs (Weih et al. 1995). PPs are barely detectable in RelB- -, NF-kB2- -, and IKKa- - mice, whereas in NF-kB1- -mice, LNs are normal, although PPs appear to be reduced in size and number (Matsushima et al. 2001 Paxian et al. 2002 Weih and Caamano 2003 Yilmaz et al. 2003). Weih and colleagues could show that the production of B cell follicle-forming chemokines such as CXCL13 by stromal cells was impaired in the absence of functional RelB (Weih et al. 2001). RelA (NF-KB1-subunit)-deletion is lethal in mice at E15 because of TNF receptor (TNFR)I-mediated apoptosis in hepatocytes. To circumvent this problem, Alcamo and colleagues have generated...

Intervention Research

Outcomes calls into question whether interventions to improve social support might benefit health. A review of 100 interventions of either group- or individual-level formats designed to modify perceptions of support availability and or skills related to seeking and receiving social support documented that a majority of interventions were successful in improving psychosocial (e.g., psychological well-being, perceptions of support availability, or receipt) and behavioral outcomes (e.g., adherence to medical treatments, maintenance of adopted health behaviors Hogan et al, 2002). However, a much smaller body of research has examined physical health impacts of social support interventions. Campbell (2003) noted that interventions for physical health conditions that involve family members, such as interventions which educate families about the target health condition and provide social support skills training, generally support the salutary benefits of family intervention for a number of...

Chronic Progressive External Ophthalmoplegia

CPEO is actually a number of diseases. They have in common a progressive, restricted range of eye movements and ptosis. Some, however, have ptosis only. The patient may know nothing about this. Most of his family members look the same, the diseases are very chronic, and they usually do not cause diplopia. Often, an associated symptom unrelated to the abnormal ocular mobility brings the patient to the doctor. Included in this group of diseases are

Power Of Decision Making

The physician must have a quality relationship with the patient and thus be able to discern the wishes of the patient and to act in his or her best interests. If this is not the case, the physician should talk with someone who can give an assessment of that person. In addition to family and friends, this very often is the patient's pastor and or spiritual mentor. This person is often privy to the most intimate thoughts of his or her parishioners, some that not even family members know. His or her perspective can be extremely helpful in these times. When no other family member or close friend is available, the physician should speak with the clergy person or spiritual mentor, when one exists, in order to make the appropriate decision. The task for the professional is to demonstrate caring and vicarious decision making, not to deliver candid instruction (May, 1983). I would add a fourth principle Know what is most important to you spiritually and communicate this to your family,...

Drug Dependency Assessment

Embarrassed to tell the clinician the truth. Too often, the clinician finds out about the patient's alcohol usage only after the patient starts to experience withdrawal. By then, more aggressive therapeutic and medical interventions may be required, which could easily have been prevented with appropriate medications. At the earlier stages of withdrawal, the patient may only complain of spasms or unrelieved pain in addition to agitation and restlessness. Frequently, the clinicians attribute these symptoms to pain and give more opioids without success. However, appropriate assessment of and judicious use of benzodiazepines by patients with alcohol withdrawal can quickly bring the patient's pain and anxiety under control. The correct assessment will require clinician persistence in pursuing the clinical clues and the assistance of the patient's family members.

Cognitive Development

The psychometric approach to assessing cognitive abilities by means of specific tests has, for the most part, not adhered to any specific theory. Rather, it has been guided by the empirical results of correlational and factor-analytic studies designed to isolate the basic dimensions of intellectual functioning. Recently, more attention has been devoted to establishing certain theoretical foundations, based on research in child development, brain physiology, information-processing, and computer-oriented concepts. For example, construction of the Kaufman Adolescent and Adult Intelligence Test (KAIT) was guided by Cattell's theoretical distinction between fluid and crystallized intelligence. Certain intelligence tests are also based on neuropsychological theories such as Aleksandr Luria's conception of different brain areas as being responsible for simultaneous and successive processing of information (see Das, Naglieri, & Kirby, 1994). Of all conceptions of intelligence, however, the...

Identifying The Genes Underlying Complex Polygenic Disorders

Based on this foundation, the following highly successful approach to positional cloning was developed and codified (1) type a sparse set of markers in multiplex families (those with multiple affected individuals), (2) localize the disease gene to a chromosomal segment showing excess allele sharing, (3) test additional markers to map individual recombinants and more precisely delimit the location of the disease gene, (4) identify candidate genes in this critical region, and (5) screen these genes for mutations (examining affected family members) to identify the etio-logical variants. Typically, proof of causality (for a gene and for the mutations it carries) relies on the discovery of multiple independent mutations (in the different families examined), each of which changes the sequence of the encoded protein, cosegregates with disease, and has a functional consequence that can be recognized based on primary sequence data (e.g., deletions, splice site mutations, stop codons or...

Nature of Id1 Protein

Id proteins belong to a protein family with molecular weights ranging from 13-20 kDa and helix-loop-helix (HLH) domains. There are four family members Id-1 to Id-4. Their function is to inhibit basic HLH transcription factors from binding to DNA by heterodimerization with basic HLH proteins, thus, inhibiting the transcription ofdifferentiation associated genes (9,10). Id-1 was first discovered as a negative regulator of DNA binding and an inhibitor of cell differentiation in myoblasts (7). It is expressed in a variety of cell types including epithelial cells. Recently, Id-1 expression has been reported in many tumor types, i.e., breast and pancreatic cancers. Increased expression of Id-1 has been associated with proliferation potential and invasion ability (11-13). In addition, Id-1 expression does not only restore the ability of DNA synthesis in senescent human fibroblast cells, but, in addition, results in the immortalization ofhuman keratinocytes (9,14), indicating its positive...

Preclinical Parkinsons Disease

Most studies of the preclinical period have focused on potential at risk individuals for PD, such as family members or unaffected twins of PD patients. In a study of hyposmic first-degree relatives of PD patients, it was shown that four of 40 (10 ) hyposmic relatives with no parkinsonian signs converted to PD over a two-year period (113). Of the 40 subjects, seven showed a reduction in 123I P-CIT uptake and the four with the lowest uptake were those converting to PD. Findings from this study suggest that 123I P-CIT and SPECT have the capacity to detect changes in DAT prior to the onset of symptoms.

Molecular Mechanisms ofOncogenes in Carcinogenesis 241 Platelet Derived Growth Factor and Its Receptors

EGF receptors are commonly overexpressed in a number of epithelial malignancies and are often associated with an aggressive phenotype. They are overexpressed in over 50 of non-small-cell lung cancers (NSCLC), head and neck squamous cell carcinoma (HNSCC), and colon cancers, along with overexpression of one or more other EGFR family members (21,23,24).

Oncogenic Transformation

In addition to the large and small T antigens, the third PyV T antigen, middle T antigen, is required for transformation by the mouse virus. While PyV large T antigen does bind to and deregulate pRb family members, working through the same functional domains as the primate TAg (Larose et al., 1991 Freund et al., 1992a Sheng et al., 1997), it does not bind to p53. PyV small t antigen does affect PP2A function and appears to serve an identical function to SV40 small t antigen (Pallas et al., 1988). Middle T antigen acts through a distinctly different mechanism than the other two oncoproteins. Its membrane-bound location puts it in a position to bind to and activate Src family kinases, thereby signaling the cell to grow and divide via a kinase cascade pathway (Kaplan et al., 1989).

Function Of The Medical Examiner

Medical examiners investigate deaths due to homicide, suicide, or accidental violence, and deaths of persons unattended by a physician, or who succumbed to a contagious disease. They also intervene in cases where death occurs amid suspicious circumstances. Examples of the latter include the sudden death of persons in apparently good health, or who die while in the custody of law enforcement officers. The medical examiner is empowered to overrule family members or legal guardians who refuse permission for an autopsy however, in cases where the cause of death becomes obvious upon preliminary review, the medical examiner, at his sole discretion, may decline the case and allow family members to claim the body without an autopsy. The medical examiner investigating a death will conduct an autopsy. The medical examiner must carefully review and record a history and pertinent past medical history, supplied by witnesses, family members, and medical records obtained from the deceased person's...

[1 Exploring Trafficking GTPase Function by mRNA Expression Profiling Use of the Sym Atlas Web Application and the

Traditionally, phylogenetic analysis of proteins in a gene family is commonly used to identify potential functional relationships to other family members, such as that of the Rab GTPases and the SNARE family of docking fusion proteins directing eukaryotic membrane traffic (Bock et al., 2001 Chen and Scheller, 2001 Pereira-Leal and Seabra, 2000, 2001 Ungar and Hughson, 2003). Computational approaches applying hierarchical clustering algorithms to systematic tissue profiling can complement this annotation by providing insights into the physiological activity of close and distant family members, and to different gene families in different cell types (Panda et al., 2002 Su et al., 2004 Walker et al., 2004). We have also recently described the use of steady-state mRNA expression profiling and hierarchical clustering algorithms to generate a global overview of the distribution of Rabs, SNAREs, and coat machinery components, as well as their respective adaptors, effectors, and regulators in...

Supportive therapy and prophylaxis

Opportunistic infections have become rare in perinatally infected children who experience immune reconstitution with successful HAART. In most of these HIV infected children respiratory and other infections are not more common than in healthy children. HIV infected children who are treated with HAART and who are clinically stable can even be given live varicella virus vaccine and show a specific response, which is an impressive sign of successful immune reconstitution (Arme-

Possible Involvement Of Tumor Suppressor Gene Products P53 And Prb In Zebrafish Aging

In addition to p53, zebrafish p53 family members, p63 and p73, have been identified and their cDNAs cloned (Bakkers et al., 2002 Lee and Kimelman, 2002 Rentzsch et al., 2003 Satoh et al., 2004). Furthermore, they appear to be more highly conserved than p53 among vertebrates. Functional analysis of zebrafish p63 in embryonic senescence might be interesting because a recent report showed that p63-deficient mouse embryos express high levels of SA- -gal activity (Keyes et al., 2005).

Familial Parkinsonism

Less common than ARJP are autosomal dominant forms of early onset PD. The best characterized is the Contursi kindred, a familial PD due to a mutation in the a-synuclein gene (62). The pathology of the Contursi kindred is typical Lewy body PD however, given the young age of onset, by the time the individual dies, Lewy body pathology is typically widespread in the brain. Lewy neurites are also prominent in many cortical areas. Some young onset autosomal dominant PD kindreds, such as the Iowa kindred, have atypical clinical presentations and include family members with dementia and psychosis. The Iowa kindred has a multiplication of the a-synuclein gene (63). Families with duplications have a milder phenotype than those with a triplication of the a-synuclein gene, suggesting a role for overexpression of a-synuclein in the pathogenesis of even sporadic PD (64). The pathology in cases with gene triplication is associated with severe Lewy body-related pathology in the cortex, hippocampus,...

Endoflife Decision Making

It is widely held that a competent patient has a right to make decisions about his or her own medical treatment, including a right to consent to treatment or a right to refuse treatment, generally so long as such refusal does not harm any third party or involve a communicable disease. That right is grounded both in common law, following from the ethical principle of autonomy, and in the constitutionally derived right of privacy. Ideally, that right is exercised when a diagnosis and treatment are evident and clear and the patient has been fully informed and is capable of making a decision. However, most situations, particularly for terminally ill elderly patients, are less than ideal. More often than not, unfortunately, many patients experience their final days like Mrs. D, who was treated aggressively for colon cancer, including a number of experimental therapies that caused her to endure intractable pain from the cancer as well as severe pain and nausea from the therapies. She was...

Prevention Of Delinquency

In addition to personality characteristics, there are other factors that have been found to increase the risk of offending, including low intelligence, high impulsivity and hyperactivity, poor parenting, poverty and the influence of a delinquent social environment, including family members, friends, school or neighbourhood (Farrington, 2001). These lead to the possibility of intervention at both the individual, family and community level, which is the aim of the current UK government's policies on community safety partnerships and multi-agency working. There have been a number of attempts to address factors operating at the level of the individual and his or her immediate social environment, leading to both successful and unsuccessful crime prevention initiatives. Some of these are outlined below, but for more comprehensive reviews, see Graham (1998) and Hope (2000).

Scf Gene And Protein Interactions Between Scf And cKit

Thus SCF, M-CSF, and Flt3 ligand are members of the large family of four-helix bundle proteins. The 4-helix bundle family has three subtypes short chain, with relatively short a-helices long chain, with relatively longer a-helices such that the overall 4-helix bundle structure is more elongated and interferon (IFN)-like (27). Many family members, growth hormone being a well studied example, are ligands for receptors of the hematopoietin receptor family (27). These receptors do not have intrinsic kinase activity, but dimerization is necessary for the initiation of intracellular signaling. In the growth hormone growth hormone receptor-binding paradigm, separate regions of monomeric ligand interact with similar regions of two receptor molecules to mediate receptor dimerization (27,28).

Advance Directives Living Wills And Durable Powers Of Attorney

In 1976 California passed the Natural Death Act, the first legally binding living-will act. In general, living wills are written documents that provide instructions to health care providers, family members, and others about the kinds of treatments an individual would want or not want to prolong life. A living will is executed while an individual is still capable of making decisions. Now most states have passed laws to sanction living wills, make them legally binding, and provide guidelines for their preparation. However, there are few, if any, assurances that the declarer's wishes will be carried out. Considerable differences currently exist among the state laws concerning the rights and responsibilities granted to patients and health-care practitioners for withholding or withdrawing life-sustaining procedures. Some of the laws limit the kinds of life-sustaining procedures a patient may refuse. For a living will to become effective, most statutes require that the patient must be...

Crime Prevention And The Individual

Crime prevention initiatives at the individual level have been classified as family-based, school-based and peer group-based (Graham, 1998). Successful interventions from the former category include the famous Perry pre-school programme (Schweinhart and Weikart, 1980) which targeted both children and their parents from low socio-economic families. Providing training in parenting skills is another form of family intervention, with successful examples including Patterson (1982) in the USA, and Utting (1996 unpublished study cited in Graham, 1998) in the UK. Both School-based interventions include the 'Effective Schools Project' (Gottfredson, 1987) which was aimed at changing the organisation and ethos of the schools, including improving the clarity of rules and the consistency with which they were enforced. This parallels the implication of harsh and inconsistent parenting in the development of delinquency (Farrington, 1996) and highlights the importance of providing safe and...

Who Should Make Surrogate Decisions

Whether or not a patient has completed an advance directive, if he or she becomes decisionally incapacitated, some other person will have to act for the patient when health care decisions, including end-of-life decisions, are demanded. Even if a patient has executed a living will, some other person will have to interpret and implement it. If a proxy or agent has been appointed, then that person will have the authority to consent to or refuse medical treatments for the principal in the event the principal becomes decisionally incapacitated. In some states those persons on a priority list of surrogates are authorized to act as decision makers in the event a patient has not completed an advance directive. Provisions for such lists are known as ''surrogate family decisionmaking laws.'' Conventional priority lists have the following order guardian, if appointed, spouse, adult children, parents, and other relatives. Such lists follow a well-known and customary practice in medicine to turn...

Approach to Patients with Suspected HNPCC

It cannot be overemphasized that ample time should be given to genetic counseling prior to genetic testing. A detailed discussion of the potential implications of both a positive and a negative test result should be undertaken. If a number of family members are to be tested, the discussions can be held both privately and for the family as a group. However, we give the results of the testing in private. The patients are contacted 1 and 6 months after the test so that we can answer any questions they may have as well as to give follow-up. An important aspect of genetic counseling is choosing whom to test. As discussed earlier, several criteria help both the clinicians and the genetic counselors in selecting the individuals who most likely will be members of HNPCC kindreds. Nevertheless, any individual who undergoes genetic testing with negative findings for a mutation must understand that if he or she is the first individual to be tested in the family, a negative test result is not...

Structure of Tumor Necrosis Factor

Identity to TNF homologs that would establish an evolutionary relationship (although sTall does assemble into an icosahedral cage). On the other hand, TNF family members have distinct sequence similarity and obvious structural homology to trimeric, globular C1q domains 10 of the het-eromeric molecules that function in the complement pathway. Hence, the TNF and gC1q domains may share an ancient kinship in the early development of the immune response.

Autonomy Of The Dying Person Best Interests And Substituted Judgment

Surrogate decision making (High, 1989). Rather, it is frequently the case that elderly people prefer to rely informally on trusted surrogate decision makers without regard to whether the decision reflects one standard or the other. They are more interested in having the best decision made by whatever means. Frequently, elderly people believe that close family members, particularly spouses and or trusted adult children, can make better decisions at the time of the medical crisis than they could by advance deliberation (High, 1988, 1990 High & Turner, 1987).

Recruitment for family studies

Type of study, i.e. disease-specific or non-disease-specific. For both types, the recruitment process is divided into two parts recruitment of the proband followed by recruitment of other family members. Likewise, for both study types, the recruitment methods for the proband are similar to those for general case-control studies for disease-specific studies the methods for identifying and recruiting cases are likely to be applied, while for non-disease-specific studies, both controls and cases can be recruited. Once the proband has been identified and contacted, two possibilities exist for recruiting other family members. Either the proband approaches family members, and discusses participation with them directly, or the proband provides researchers with their contact details (Beskow et al., 2004). Both methods have ethical and legal implications. In the first scenario, the relatives are contacted by a person known to them, the proband, resulting in a likely reduction of privacy risks....

Feedback for disease prevention

A different legal and ethical problem arises in cases where the researcher is aware that the study participant has a sibling or children who might be affected by an inherited and heritable condition. The researcher may even feel compelled to warn the participant's family members about the possibility of their carrying the disease, possibly against the wishes of the participant. Parker and Lucassen give the example of a woman not wishing her pregnant sister to be informed about the woman's

Segmental Duplications And 22q112 Rearrangement Disorders

Interchromosomal recombination events lead to the 22q11.2 deletion and a reciprocal duplication, both associated with congenital anomalies. Using microsatellite genetic markers and screening more than 150 VCFS DGS patients and their unaffected family members, it was possible to narrow the region containing the common recurrent 1.5- and 3-Mb deletions (23). Further analysis of the breakpoints occurring in VCFS DGS and CES patients suggested that they occurred in the same regions (38). More recently, the constitutional t(11 22) breakpoint on 22q11.2 was placed in the vicinity of the distal deletion breakpoint in VCFS DGS patients with the nested 1.5 Mb deletion (34).

The Role Of Families In Endoflife Decision Making

In general, a presumption in favor of families for surrogate decision making or even assisting with end-of-life decisions exists in law and in some ethical argument. It is also a widely known and commonly accepted practice in the medical profession to rely on family members to make treatment decisions for those relatives who never could or can no longer decide for themselves. Beyond that, families are faced with an enormous number of important decisions during the course of a terminal illness of a relative. In addition to crisis and end-of-life decisions, there are everyday decisions about care and treatment options, including financial decisions and family role responsibilities in relating to the dying relative. These decisions affect not only the patient but also the family members themselves. Moreover, end-of-life and care decisions are most frequently made by the family unit, rather than by the patient in isolation, even if he or she is capable. Ordinarily, family members and the...

Project Title Exercisetraining In Children With Heart Disease

Summary (provided by applicant) The principal investigator will develop expertise in exercise testing and training of children and obtain the experience and skill necessary to initiate independent research projects during the award period. The principal investigator's long-term career goal as an academic pediatric cardiologist is to become a clinical investigator with a research focus in exercise physiology and cardiac rehabilitation. Exercise intolerance is an under-recognized chronic morbidity in children with heart disease. Poor exercise capacity leads to low self-esteem and poor quality of life. Children with single ventricle after the Fontan operation and children after orthotopic heart transplantation (OHT) are among children with the lowest exercise capacity. Whether exercise intolerance in these children is due to cardiopulmonary dysfunction or deconditioning from decreased physical activity remains unclear. The role of skeletal muscle and humoral responses in determining...

Measuring the genetic contribution in developmental disorders

Family studies carry the caveat that sibs share the same maternal environment over precisely the period during which the etiological determinants are exerting their effect i.e. during embryogenesis. Additionally, family members share environmental and socioeconomic status that contribute confounding effects in a transgenerational manner. This reduces the ability to distinguish between genetic and intrauterine environmental factors as causative influences. Twin concordance studies ascertain the difference in concordance of a trait between dizygotic and monozygotic twin pairs and this is interpreted as a measure of the genetic contribution towards aetiology. Such studies are limited by the observation that monozygotic twinning per se is associated with an increase in the prevalence of congenital anomalies (Schinzel et al., 1979 Hall, 1996).

Identifying the multiple epistatic determinants underlying a developmental disorder Hirschsprung disease

A variety of approaches have been utilized to identify the genetic determinants underlying HSCR. Firstly, clinical and epidemiological studies established that long segment disease exhibited higher penetrance and less variable expressivity than short segment disease (Bodian and Carter, 1963 Garver et al., 1985 Badner et al., 1990). The implications for recurrence risk in family members reflect these observations (Table 13.4). The first gene of major effect in both short and long segment HSCR was identified as RET using classical linkage studies to map a deletion encompassing the RET locus in a familial case of the disease and then detection of mutations in isolated cases of HSCR. The characterization of other genes underlying syndromic HSCR has proved more challenging but several others have had mutations identified using similar approaches (Amiel and Lyonnet, 2001). A genome-wide association study in inbred populations with elevated susceptibility to the condition and work using...

Tegument Protein Mediated Signaling

HCMV possesses a number of tegument proteins that are able to modulate the host cell, although many tegument proteins do not have identified functions (Mocarski et al. 2007). Because another chapter will cover tegument proteins in detail (see the chapter by R. Kalejta, this volume), the signaling potential of select tegument proteins will only briefly be summarized. UL83, the major tegument protein, has been shown to block the antiviral response through the inhibition of the cellular transcription factors NFk-B and interferon regulatory factor 1 (Browne and Shenk 2003). Other tegument proteins including UL82 (Schierling et al. 2004 Cantrell and Bresnahan 2006a Saffert and Kalejta 2006), UL35 (Schierling et al. 2004), US24 (Feng et al. 2006) and UL26 (Stamminger et al. 2002 Munger et al. 2006) can also influence the early events involved with MIEP transactivation and IE gene expression. Tegument proteins also alter the cell cycle (reviewed in Kalejta and Shenk 2002 Kalejta 2004...

Novel Features in the Structure of Apo2LTRAIL

Two independent crystal structures of unbound Apo2L TRAIL show that it resembles the TNF trimer in its basic architecture 5,6 . Apo2L TRAIL has two unusual features with respect to other TNF family members. First, it has a distinct, long loop between strands A and A' (residues 130 to 150) that traverses its surface but is poorly ordered or even disordered between residues 131 and 143 (Fig. 1). Second, a novel zinc-binding site buried in the trimer interface is formed by the single cysteine residue from each monomer 6,7 . This binding site appears to be unique to Apo2L TRAIL among TNF family members. Its importance for the structural integrity and biological activity of the protein was revealed when the site was removed using chelating agents or mutation of the cysteine residue 6,8,9 . The resulting protein showed changes in its circular dichroism and trypto-phan fluorescence spectra, indicating a more open trimer, and had reduced thermal stability, receptor-binding affinity, and...

Apo2Ltraildr5 structures

Determined by three different groups 7,10,11 , These three independent structures are in good overall agreement, especially around the receptor binding site. As in the LT-TNF-R1 complex, the three symmetrical binding sites on the ligand are nestled between the monomer-monomer interfaces each site forms two distinct patches, one centered around Tyr 216 and the other around Gln 205 (Fig. 2). Both of these residues have been shown to be critically important for Apo2L TRAIL activity 6 . Two loops from DR5, the 50s loop in CRD2 and the 90s loop in CRD3, make almost all the contacts with the ligand. The conformation of the 90s loop is very different between DR5 and TNF-R1, and its sequence in other TNF-Rs is highly variable. This loop was proposed to be important for defining the specificity and cross-reactivity among TNF-R family members 11 . In contrast, the 50s loop has a backbone conformation very similar to the corresponding loop in TNF-R1 (the Ca atoms of DR5 residues 50 to 62...

Ligand Independent Receptor Assembly

In addition to the role of CRDs 2 and 3 in ligand binding, CRD1 of receptors DR4, FAS, CD40, TNF-R1, and TNF-R2 mediates pre-ligand-binding receptor association into inactive receptor oligomers, which are thought to be altered upon ligand binding to allow intracellular DISC assembly 12-14 . In all DR5 structures, CRD1 is only partially ordered (Fig. 3). Its sequence and structure are very different from the corresponding domain in TNF-R1 furthermore, the sequences of DR4 and DR5 vary most in this CRD, and CRD1 contains no obvious motifs conserved with other TNF-R family members. For these reasons, it is unclear if ligand-independent preas-sociation is a universal feature of the death receptor family.

Twin Studies on Cardiovascular Traits Often Used in Behavioral Medicine

The genetic contribution to cardiovascular disease end points most likely results from the joint effects of risk genes on the large number of biological and behavioral risk factors that impact on the atherosclerotic process. Table 28.8 summarizes the heritabil-ity estimates for many of these risk factors based on the study of twins and their family members registered in the Netherlands Twin Registry (NTR). The NTR was established in 1987 as a resource for prospective studies in behavior genetics and genetic epidemiology ( The adult branch of register now includes over 23,000 participants that can be MZ or DZ twins, parents, siblings, children, or spouses of twins. They have been longitudinally assessed for a large number of behavioral and medical traits using biennial surveys and multiple visits to the laboratory or the university hospital. It is clear from Table 28.8 that all cardiovascular risk factors assessed were

Ongoing Evolution of Structural Equation Models for Twin Family Data

The evolution of twin studies is still very much ongoing because the twin method makes a number of assumptions that, in contrast to the equal environment assumption, have been shown to be invalid for various traits (see Table 28.9). Twin researchers have expanded the twin design to involve a larger amount of family members than just the twins and their siblings to allow an explicit test of some of the assumptions in Table 28.9. (Eaves, 2009). The newer cascade models add the parents, spouses, and the offspring of DZ and MZ twins to obtain estimates of the genetic and environmental (interaction) effects that take potential violations of these assumptions into account as explained in detail elsewhere (Keller et al, 2009 Medland and Keller, 2009). Clearly, to maintain sufficient statistical power to test all assumptions at once, sufficient numbers of twins and of

Typical Transcriptional Activator

Examples mentioned above, recognize short, specific DNA sequences by making elaborate contacts with the bases in the major groove of the DNA double helix (Garvie and Wolberger, 2001 Patikoglou and Burley, 1997). Others, e.g., the high-mobility-group (HMG) domain, recognize DNA sequences by interacting with the minor groove (Travers, 2000).2 While most DNA binding domains recognize DNA sites as dimers (e.g., bZIP and Rel family members), others can bind as monomers (e.g., some homeodomain proteins). For proteins that bind DNA as dimers, many can form both homodimers and heterodimers with other family members. Heterodimer formation can increase the repertoire of DNA sequences recognized by a given family of transcription factors. Many activators can bind DNA cooperatively with one another, which can increase the stability of the protein complexes formed at the enhancers (Adams and Workman, 1995 Ma et al., 1996).

Environment and high penetrance genes

Cover multiple generations, birth cohorts, clinical management schemes and healthcare systems so that comparisons between affected and unaffected carriers are not straightforward and interpretation is difficult. For instance, knowledge of carrier status among family members will depend upon which family members choose to have genetic testing such choices may well depend upon factors such as parity and the interest in acquiring this knowledge for family rather than entirely personal reasons. These confusions about the actual structure of the data may explain why there have been such inconsistencies between studies. For instance, among BRCA1 and BRCA2 mutation carriers, studies of smoking have suggested that smoking influences risk (Brunet et al., 1998) but a subsequent, larger study by the same investigators found no such effect (Ghadirian et al., 2004). For these studies, attempts to make the studies population-based have been discussed as a means to removing such inadequacies in data...

Project Title Genetic Basis Of Congenital Heart Disease

In a kindred mapping to the 59 locus, the clinical status of all family members can be accounted for by a model of incomplete penetrance and variable expressivity. In three kindreds mapping to the 5q locus, there is full disease penetrance, variable expressivity. In three kindreds mapping to the 5q locus, there is full disease penetrance, variable expressivity and affected individuals have associated AV conduction abnormalities. Thus, familial ASD is genetically heterogeneous reduced disease penetrance and variable expressivity occur in some kindreds. A genome-wide search for a third locus is underway in one kindred, and three other kindreds are being clinically evaluated. The following studies are proposed 1. To identify additional kindreds in whom ASD appears to be inherited as an autosomal dominant trait and map the kindreds to known loci on chromosome 5p and 5q. 2. To refine the genetic map of the chromosome 5p and 5q loci, construct a physical map, identify...

Gsk3 Inhibitors And Stem Cells

Human and mouse ESCs (hESCs and mESCs) are pluripotent stem cells. Conventionally, they are maintained on feeder cells and or mixtures of exogenous factors (e.g., serum). Studies have found that the self-renewal of mESCs primarily depends on two key signaling molecules LIF interleukin 6 (IL6) family members and BMP (Fig. 8.1). LIF acts via a membrane-bound gp130-LIFR (LIF receptor) complex to activate Stat (signal transduction and activation of transcription) signaling, which promotes self-renewal of mESCs and inhibits their differentiations to mesoderm and endoderm by a Myc-dependent mechanism. BMP induces expression of Id (inhibitor of differentiation) genes via Smad signaling and inhibits mESC differentiation to neuroectoderm. The combination of BMP and LIF can sustain mESCs self-renewal in the absence of serum and feeder cells. Recently it was shown that Wnt signaling, which is active in undifferentiated mESCs and is downregu-lated upon differentiation, plays an important role in...

Non Cancer Health Care and Health Maintenance

Recognized, although screening recommendations are not well developed. Patients may be offered participation in clinical research looking to better define surveillance strategies for high-risk patients (e.g., EUS screening for patients with heritable risk of pancreas cancer). Documentation of a genetic predisposition to cancer could affect not only recommendations for family members, but surveillance recommendations for the patient. For example, interval cancers are more common among patients with Hereditary Non-Polyposis Colorectal Cancer and so surveillance colonoscopies should be more frequent.

Homosexual Relationships

The conception of aging homosexuals as lonely, depressed, and sexually frustrated is an overgeneralization. Living in a predominantly heterosexual society creates problems for older homosexuals, but there are also compensations. Among the problems are discrimination against homosexuals by society as a whole, disrespect from family members, inability to have their marriages sanctioned by law, and, in some cases, lack of visitation rights with their children by former marriages. One advantage of homosexuality, particularly in older adulthood and especially for lesbians, is the availability of partners (Raphael & Robinson, 1980).

Expression in Adipose Tissue

Following binding of glucocorticoid (GC) receptors to the glucocorticoid response element (GRE) and Sp1 to its site on untranslated exon I.4, activation of transcription of the aromatase gene from promoter I.4 is initiated. Tumor necrosis factor a (TNFa) action is presumed to be through sequential activation of mitogen-activated protein kinases (MAPKs) and early response genes, including the egr-1 family members c-fos and c-jun. GAS, interferon-y-activating sequence OSM, oncostatin M IL, inter-leukin LIFR, leukemia-inhibiting factor receptor. moter I.4. Following binding of glucocorticoid (GC) receptors to the glucocorticoid response element (GRE) and Sp1 to its site on untranslated exon I.4, activation of transcription of the aromatase gene from promoter I.4 is initiated. Tumor necrosis factor a (TNFa) action is presumed to be through sequential activation of mitogen-activated protein kinases (MAPKs) and early response genes, including the egr-1 family members c-fos and...

Evaluation Of Kindreds

Eleven monogenetic PARK loci have been identified (Table 1). The PARK4 locus was reclassified because it shares the same gene (SNCA a-synuclein) as the PARK1 locus (34). The PARK9 locus has been described in the Kufor-Rakeb kindred, with affected family members having atypical parkinsonism associated with dementia, spasticity, and supranuclear palsy (35). Mutations in six genes have been implicated in parkinsonism SNCA (PARK1) in 1997 (34), parkin (PARK2) in 1998 (36), UCHL1 (PARK5) in 1998 (37), DJ-1 (PARK7) in 2001 (38), PINK (PARK6) in 2004 (39), and LRRK2 (PARK8) in 2004 (40,41).

Frequency Of Germ Line P53 Mutations In Breast Cancer

The above cited studies indicate that the only good predictor of a p53 germ line mutation is a cancer family history of LFS or LFL. However for health-care providers to apply those criteria family members must accurately report the family history. Lalloo et al. (48,53) conducted a population-based study of 100 patients with breast cancer diagnosed before age 31 years, with testing for BRCA1, 2, and p53. A three-generation pedigree was collected at diagnosis, with hospital records, cancer registry or death certificate documentation of the 31 familial cases with hospital notes available, only 14 were found to have reported an accurate family history. In the series four p53 mutation carriers were identified, none of whom had an LFS cancer family history identified at diagnosis. Two mutations were in patients later found to have LFS or LFL family histories but not reported at diagnosis, and two were in sporadic patients, including one confirmed de novo mutation. Schneider et al. (54) also...

Clinical Molecular Genetic Testing

Commercial genetic testing for parkinsonian genes should be interpreted with caution. A positive finding contributes only to the probability that the person will become affected, because most mutations gain or lose function and are associated with age-dependent penetrance. Indeed, for most genes and mutations, the age-associated risk to carriers has yet to be formally described. Despite the explosive progress in genetic research, not all mutations in PD have been functionally validated and some rare variants could be benign polymorphisms. Technical problems in test-retest reliability may also occur. These issues should be carefully and comprehensively discussed with physicians and their patients who are seeking genetic advice, as well as with asymptomatic family members who are genealogically at risk.

Advances in medical technology and the threat to patient informational and spatial privacy

In the public realm, advances in genomic research are widely recognised as being in the interests of the collective good. The promise of considerable clinical benefit from genetics is a rarely-questioned given. The ability to gain knowledge about one's own genetic make-up can, however, be a frightening prospect for the individual. Such information might reveal an underlying disease or dysfunction, or indicate a predisposition to future ill health. It could also have implications for one's relatives, given the common genetic heritage that family members share. Moreover, once such information is discovered, a question arises over its use and possible misuse. Family members, the state, researchers, insurers and employers could all claim an interest in knowing the genetic information relating to individuals. The basis and legitimacy of such interests will be discussed in chapter 3. That such claims might be put, however, means that potential invasions of the informational privacy of the...

Regulation and function Regulation of expression

The mechanisms of regulation of TP53 transcription have been less studied than most other aspects of p53 protein function. The TP53 gene does not contain a conventional TATA box but is under control of several ubiquitous transcription factors, including NFkB, Sp1 and c-Jun. The latter acts as a repressor of TP53 expression mouse fibroblasts from cJUN-deficient embryos have difficulties in progressing into the cell cycle due to suppression by an overexpressed p53 (Schreiber et al., 1999). The p53 transcript is 2.8 kb long. The main initiation codon is in exon 2 but there is an alternative initiation site at codon 40, that leads to the production of a protein that lacks the N-terminus containing the transcription activation domain (DeltaNp53) (Courtois et al., 2002). An alternatively spliced transcript that retains intron 2 has been identified (Ghosh et al., 2004). This transcript is unable to encode the full-length protein but supports the synthesis of DeltaNp53. This feature is...

Risk Of Multiple Primary Cancers In Mutation Carriers

In the initial LFS report (1), some family members had multiple primary cancers. Many case reports and series have noted the association of LFS, p53 germ line mutations, and multiple primary tumors (60-69). The increased risk of subsequent neoplasms was clearly demonstrated in the follow-up studies of the 24 LFS kindreds (6,70), citing the high risk for those with young age of first cancer diagnosis, the occurrence not only of second but of third malignant neoplasms, the spectrum of multiple primary tumors that was primarily composed of the same component tumors observed as initial tumors, and the high frequency of tumors arising in radiation-treated areas. The analysis was not based on p53 mutation status but classic LFS, and included 8 p53 mutation kindreds, 8 non-p53 LFS, and 8 unknown genotype LFS. With an additional 10 to 30 years follow-up the cumulative risk of a second malignant neoplasm was 57 ( 10 ) SE at 30 years after the first cancer diagnosis, and for a third malignant...

Discourse Relationships Among Sentences

Evidence of pneumonia, and a variable for a pneumonia diagnosis. An instance of pneumonia described in the radiological findings section of a report is likely to provide radiological evidence of pneumonia, whereas an instance of pneumonia in the discharge diagnosis section probably indicates a diagnosis. Report section identification can also assist in understanding whether the finding occurred in the past history, the current visit, or as a hypothetical finding (e.g., a finding described in the plan section is more likely to be a hypothetical finding), can identify findings for family members (e.g., a finding in the social history section may not be the patient's finding), and can provide insight regarding the anatomic location of an ambiguous finding (e.g., a mass described in the radiology finding section is probably a pulmonary mass). Patient reports tell a story involving various findings, physicians, patients, family members, medications, and treatments that are often referred...

Conclusions And Implications For Practice

There should be a government led process of consultation to review the current age of criminal responsibility in the light of clinical and research evidence about the developmental immaturity and psychiatric disturbance of many young child defendants. All child defendants facing serious criminal charges (murder, manslaughter, abduction, rape or grievous bodily harm) should be assessed by a clinical psychologist and by a child psychiatrist. There should be agreement between clinical psychologists and child psychiatrists as to the principles of such psychological and psychiatric assessments. If appropriate, pre-trial therapy should be provided for all child defendants suffering from identifiable and treatable psychiatric disorders. A child defendant's pack should be made available to inform children facing criminal charges about their rights and the legal process. Relevant training covering the areas of child development, psychiatric and psychological issues, the relevant forensic and...

Parental Behaviors and the Personalities of Children

Authoritarian parents are restrictive, rule-emphasizing individuals who expect children to be obedient and who punish behavior that deviates from their rules. In contrast, permissive parents are nondemand-ing individuals who permit children to establish their own standards of conduct. Finally, authoritative parents set behavioral limits and standards and enforce them with a combination of power and reasoning. The children of authoritative parents are encouraged to conform to these limits, but they are also permitted to contribute their own reasoning concerning them. Baumrind found that the children of both authoritarian and permissive parents behaved similarly in many respects The sons were more hostile than normal, and the daughters were more socially retiring individuals who gave up easily. The children of authoritative parents, whom Baumrind considers the most effective of all three parenting styles, were able to conform to group norms without sacrificing...

Tumor Necrosis Factor Receptors

The specific oligomeric nature of active tumor necrosis factor receptor (TNFR) family members has not been definitively proven. The ligands for these receptors are usually trimeric, suggesting that the functional oligomeric complex of the receptors may also be trimeric however, the receptors may actually function as dimers. At least three different hypotheses have been proposed for the activation of TNFRs. The first, and most widely accepted, involves receptor trimer-ization. The earliest crystallographic studies of TNFR and TNFR1 bound to TNF-P demonstrate that one receptor molecule binds to each of the three monomer-monomer interfaces of the trimeric TNF ligand 34,35 . Interestingly, no direct contacts between any of the receptor monomers other than nonspecific crystal contacts were detected however, the receptor endodomains presumably would be sufficiently close to allow interaction. TNF-receptor-associated factors (TRAFs), primary effectors of TNF-Rs, have been crystallized as...

Recombinant Genes for HSC Expansion

SAG-mediated HSC expansion has also been evaluated in vivo. Zhao et al. recently demonstrated that SAGs derived from Jak family members may be the key to amplifying specific hematopoietic lineages (57). Experiments carried out with a SAG construct containing the JH1 domain of murine Jak2 linked to a tandem binding site for the CID, AP20187, were evaluated in a murine transplant model. Administration of the CID resulted in a rapid expansion of transduced erythrocytes. However, the effect was shortlived, and the transduced erythrocyte population declined to pretreatment levels after CID withdrawal. Another SAG, consisting of the erythropoietin (EPO) receptor dimer-ization domain fused to the thrombopoietin receptor signaling domain, was recently evaluated in cynomogus macaques (58). Transduced CD34+ cells were transplanted directly into irrigated femurs and humeri in unconditioned animals. In the absence of

Single Parenting Becoming the Best Parent For Your Child

Single Parenting Becoming the Best Parent For Your Child

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