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Results for “Gatekeeping”

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At least 343 records · Page 19Linked to original sources
PubMed2007

The astrocyte as a gatekeeper of synaptic information transfer.

We present a simple biophysical model for the coupling between synaptic transmission and the local calcium concentration on an enveloping astrocytic domain. This interaction enables the astrocyte to modulate the information flow from presynaptic to postsynaptic cells in a manner dependent on previous activity at this and other nearby synapses. Our model suggests a novel, testable hypothesis for the spike timing statistics measured for rapidly firing cells in culture experiments.

Animals↗
PubMed2001

The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression.

E-cadherin is a cell-cell adhesion protein fulfilling a prominent role in epithelial differentiation. Data from model systems suggest that E-cadherin is a potent invasion/tumor suppressor of breast cancer. Consistent with this role in breast cancer progression, partial or complete loss of E-cadherin expression has been found to correlate with poor prognosis in breast cancer patients. The E-cadherin gene (CDH1) is located on human chromosome 16q22.1, a region frequently affected with loss of heterozygosity in sporadic breast cancer. Invasive lobular breast carcinomas, which are typically completely E-cadherin-negative, often show inactivating mutations in combination with loss of heterozygosity of the wild-type CDH1 allele. Mutations were found at early noninvasive stages, thus associating E-cadherin mutations with loss of cell growth control and defining CDH1 as the tumor suppressor for the lobular breast cancer subtype. Ductal breast cancers in general show heterogeneous loss of E-cadherin expression, associated with epigenetic transcriptional downregulation. It is proposed that the microenvironment at the invasive front is transiently downregulating E-cadherin transcription. This can be associated with induction of nonepithelial cadherins.

Antigens, CD↗
PubMed1998

Rural women's satisfaction and stress as family health care gatekeepers.

Women shoulder much of the responsibility for their families' health care, making women's satisfaction with available services an important issue for their families and for women's personal stress levels. Lack of services and resulting stress may be acute for rural women, the focus of this study. In a state-wide survey, fewer than one-half of rural women were satisfied with the health services available; dissatisfaction was a strong determinant of women's stress over health care issues. Rural women are at risk for a pile-up of stressors that could impede their ability to care for themselves and their families.

Adolescent↗
PubMed1994

Gatekeeping through media format: strategies of voice for the HIV-positive via human interest news formats and organizations.

This research examines the extent to which HIV-positive voices are marginalized in the mainstream versus the "alternative" press. The central claim of this research is that news media format considerations, constructed around what has come to be called "media logic," leave persons who are HIV-positive with comparatively little voice in the mainstream press. By utilizing techniques of content analysis, the research examines 535 major HIV/AIDS-specific stories published in two oppositional papers toward an assessment of the level of HIV-positive voice in each outlet. While arguments of "homophobia" have been previously used to explain bias in mainstream HIV/AIDS-coverage, this article asserts that "hetero-centric" bias is, in fact, embedded in the routinized practices of mainstream "news production." The article concludes by suggesting that successful future HIV/AIDS activism demands a recognition of "media logic" and an adoption of its tactics.

HIV Seropositivity↗
PubMed1997

Gatekeeping through media format: strategies of voice for the HIV-positive via human interest news formats and organizations.

This research examines the extent to which HIV-positive voices are marginalized in the mainstream versus the "alternative" press. The central claim of this research is that news media format considerations, constructed around what has come to be called "media logic," leave persons who are HIV-positive with comparatively little voice in the mainstream press. By utilizing techniques of content analysis, the research examines 535 major HIV/AIDS-specific stories published in two oppositional papers toward an assessment of the level of HIV-positive voice in each outlet. While arguments of "homophobia" have been previously used to explain bias in mainstream HIV/AIDS-coverage, this article asserts that "heterocentric" bias is, in fact, embedded in the routinized practices of mainstream "news production." The article concludes by suggesting that successful future HIV/AIDS-activism demands a recognition of "media logic" and an adoption of its tactics.

HIV Seropositivity↗
PubMed1998

Groups as gatekeepers to genomic research: conceptually confusing, morally hazardous, and practically useless.

Some argue that human groups have a stake in the outcome of population-genomics research and that the decision to participate in such research should therefore be subject to group permission. It is not possible, however, to obtain prior group permission, because the actual human groups under study, human demes, are unidentifiable before research begins. Moreover, they lack moral standing. If identifiable social groups with moral standing are used as proxies for demes, group approval could be sought, but at the expense of unfairly exposing these surrogates to risks from which prior group approval is powerless to protect them. Unless population genomics can proceed without targeting socially defined groups, or can find other ways of protecting them, it may fall to individuals to protect the interests of the groups they care about, and to scientists to warn their subjects of the need to do so.

Cultural Diversity↗
PubMed1998

Double doors and gatekeepers: HIV co-receptors and chemokines.

The identification of CD4 as the HIV receptor immediately triggered a search for the development of novel therapeutic agents aimed at blocking receptor binding. Initial experimental approaches to this problem failed, but led to the observation that one or more other receptors for HIV, or co-receptors, must be involved in the entry of the virus in cells. In 1996 evidence was reported of a second viral receptor, already known under several names and renamed "fusin." Shortly thereafter the CCR5 molecule was identified as a co-receptor for the second type of HIV strain. This second discovery left no doubts: the second receptor for the virus encompassed at least two members of the chemokine receptor family. The identification of these co-receptors has led to several important new observations about HIV, including the fact that chemokines are potent in vitro inhibitors of viral replication, at least in T lymphocytes; however, there is still little information on their role in vivo. Nevertheless, unlike chemokines, the role of chemokine receptors in vivo has already emerged as being of substantial importance.

Journal Article↗
PubMed2006

The molecular gatekeeper Dexras1 sculpts the photic responsiveness of the mammalian circadian clock.

The mammalian master clock, located in the suprachiasmatic nucleus (SCN), is exquisitely sensitive to photic timing cues, but the key molecular events that sculpt both the phasing and magnitude of responsiveness are not understood. Here, we show that the Ras-like G-protein Dexras1 is a critical factor in these processes. Dexras1-deficient mice (dexras1-/-) exhibit a restructured nighttime phase response curve and a loss of gating to photic resetting during the day. Dexras1 affects the photic sensitivity by repressing or activating time-of-day-specific signaling pathways that regulate extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK). During the late night, Dexras1 limits the capacity of pituitary adenylate cyclase (PAC) activating peptide (PACAP)/PAC1 to affect ERK/MAPK, and in the early night, light-induced phase delays, which are mediated predominantly by NMDA receptors, are reduced as reported previously. Daytime photic phase advances are mediated by a novel signaling pathway that does not affect the SCN core but rather stimulates ERK/MAPK in the SCN shell and triggers downregulation of clock protein expression.

Animals↗
PubMed2001

Oct-4: gatekeeper in the beginnings of mammalian development.

The Oct-4 POU transcription factor is expressed in mouse totipotent embryonic stem and germ cells. Differentiation of totipotent cells to somatic lineages occurs at the blastocyst stage and during gastrulation, simultaneously with Oct-4 downregulation. Stem cell lines derived from the inner cell mass and the epiblast of the mouse embryo express Oct-4 only if undifferentiated. When embryonic stem cells are triggered to differentiate, Oct-4 is downregulated thus providing a model for the early events linked to somatic differentiation in the developing embryo. In vivo mutagenesis has shown that loss of Oct-4 at the blastocyst stage causes the cells of the inner cell mass to differentiate into trophectoderm cells. Recent experiments indicate that an Oct-4 expression level of roughly 50%-150% of the endogenous amount in embryonic stem cells is permissive for self-renewal and maintenance of totipotency. However, upregulation above these levels causes stem cells to express genes involved in the lineage differentiation of primitive endoderm. These novel advances along with latest findings on Oct-4-associated factors, target genes, and dimerization ability, provide new insights into the understanding of the early steps regulating mammalian embryogenesis.

Animals↗
PubMed2005

Ten years of judicial gatekeeping under Daubert.

In the ten years since Daubert v Merrell Dow Pharmaceuticals, Inc, the standards for admissibility at trial of expert testimony in general and scientific evidence in particular have become more demanding. Reviews of recent cases and empirical studies of federal judges' and attorneys' practices indicate that judges are more likely to consider the admissibility of expert evidence prior to trial, to inquire more deeply into the reasoning and methodology that supports the expert opinions, and to limit or exclude such evidence from presentation at trial. Studies of published cases confirm this finding. Recent cases consider more difficult questions arising from the differing methodologies used in various areas of science. The current legal framework that assesses admissibility in terms of professional practice outside the courtroom is poorly suited to cases that require expertise across a wide range of specialties and force judges to choose from among different scientific methodologies. Future research should focus on the pretrial screening of expert testimony and interactions between the attorneys and experts in shaping that testimony.

Drug Industry↗
PubMed2002

CCR5 chemokine receptors: gatekeepers of HIV-1 infection.

With the discovery that CCR5 is the critical protein required for infection by M-tropic HIV, has come huge research efforts, both in academia and industry, to try to exploit this finding. Thus, research advances in the fields of virology, structural protein chemistry, and receptor pharmacology have combined to add a new understanding to the process of HIV fusion and possible mechanisms to prevent HIV entry. This review will approach this field from a receptor pharmacology viewpoint and outline some concepts of receptor allosterism and protein-protein interaction which may be relevant to CCR5 blockade. Many of these ideas may be explored in a practical sense with the advent of new small molecule CCR5 inhibitors currently entering the clinic.

Acquired Immunodeficiency Syndrome↗