Showing papers by "University of California, San Francisco published in 2001"
Royal College of Physicians1, University of Cambridge2, University of California, San Francisco3, University of Graz4, Icahn School of Medicine at Mount Sinai5, National Institutes of Health6, University of British Columbia7, VU University Amsterdam8, National Multiple Sclerosis Society9, Lund University10, University of Arizona11, University College London12, University of California, Irvine13, Mayo Clinic14, University of Texas Health Science Center at Houston15
TL;DR: The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including “monosymptomatic” disease suggestive of MS, disease with a typical relapsing‐remitting course, and disease with insidious progression, without clear attacks and remissions.
Abstract: The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."
6,720 citations
TL;DR: Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems, and control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.
Abstract: Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems. Neurotrophins activate two different classes of receptors, the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. Through these, neurotrophins activate many signaling pathways, including those mediated by ras and members of the cdc-42/ras/rho G protein families, and the MAP kinase, PI-3 kinase, and Jun kinase cascades. During development, limiting amounts of neurotrophins function as survival factors to ensure a match between the number of surviving neurons and the requirement for appropriate target innervation. They also regulate cell fate decisions, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. These proteins also regulate many aspects of neural function. In the mature nervous system, they control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.
3,968 citations
TL;DR: Recent advances shed light on how the structure and function of the MMPs are related and on how their transcription, secretion, activation, inhibition, localization, and clearance are controlled.
Abstract: ▪ Abstract The matrix metalloproteinases (MMPs) constitute a multigene family of over 25 secreted and cell surface enzymes that process or degrade numerous pericellular substrates. Their targets include other proteinases, proteinase inhibitors, clotting factors, chemotactic molecules, latent growth factors, growth factor–binding proteins, cell surface receptors, cell-cell adhesion molecules, and virtually all structural extracellular matrix proteins. Thus MMPs are able to regulate many biologic processes and are closely regulated themselves. We review recent advances that help to explain how MMPs work, how they are controlled, and how they influence biologic behavior. These advances shed light on how the structure and function of the MMPs are related and on how their transcription, secretion, activation, inhibition, localization, and clearance are controlled. MMPs participate in numerous normal and abnormal processes, and there are new insights into the key substrates and mechanisms responsible for regula...
3,839 citations
TL;DR: The authors regret the inability to cite all of the primary literature contributing to this review due to length considerations, but wish to thank F. Chan, T. Migone, and J. Wang for insightful comments on the manuscript.
3,756 citations
TL;DR: Deregulated cell proliferation provides a minimal 'platform' necessary to support further neoplastic progression and should be targeted withroit targeting to have potent and specific therapeutic consequences.
Abstract: Beneath the complexity and idiopathy of every cancer lies a limited number of 'mission critical' events that have propelled the tumour cell and its progeny into uncontrolled expansion and invasion One of these is deregulated cell proliferation, which, together with the obligate compensatory suppression of apoptosis needed to support it, provides a minimal 'platform' necessary to support further neoplastic progression Adroit targeting of these critical events should have potent and specific therapeutic consequences
3,151 citations
TL;DR: Efforts to determine how primary sensory neurons detect pain-producing stimuli of a thermal, mechanical or chemical nature have revealed new signalling mechanisms and brought us closer to understanding the molecular events that facilitate transitions from acute to persistent pain.
Abstract: The sensation of pain alerts us to real or impending injury and triggers appropriate protective responses. Unfortunately, pain often outlives its usefulness as a warning system and instead becomes chronic and debilitating. This transition to a chronic phase involves changes within the spinal cord and brain, but there is also remarkable modulation where pain messages are initiated - at the level of the primary sensory neuron. Efforts to determine how these neurons detect pain-producing stimuli of a thermal, mechanical or chemical nature have revealed new signalling mechanisms and brought us closer to understanding the molecular events that facilitate transitions from acute to persistent pain.
2,416 citations
TL;DR: The role of TGF-β is evaluated as both a tumor suppressor pathway and a promoter of tumor progression and invasion and the positive and negative effects of T GF-β in carcinogenesis are attempted.
Abstract: Epithelial and hematopoietic cells have a high turnover and their progenitor cells divide continuously, making them prime targets for genetic and epigenetic changes that lead to cell transformation and tumorigenesis. The consequent changes in cell behavior and responsiveness result not only from genetic alterations such as activation of oncogenes or inactivation of tumor suppressor genes, but also from altered production of, or responsiveness to, stimulatory or inhibitory growth and differentiation factors. Among these, transforming growth factor β (TGF-β) and its signaling effectors act as key determinants of carcinoma cell behavior. The autocrine and paracrine effects of TGF-β on tumor cells and the tumor micro-environment exert both positive and negative influences on cancer development. Accordingly, the TGF-β signaling pathway has been considered as both a tumor suppressor pathway and a promoter of tumor progression and invasion. Here we evaluate the role of TGF-β in tumor development and attempt to reconcile the positive and negative effects of TGF-β in carcinogenesis.
2,132 citations
TL;DR: The structure of telomeres, the protective DNA-protein complexes at eukaryotic chromosomal ends, and several molecular mechanisms involved in telomere functions are described.
2,000 citations
TL;DR: The current criteria for OLT based on tumor size may be modestly expanded while still preserving excellent survival after OLT, and only pT4 stage and total tumor diameter remained statistically significant in multivariate analysis.
1,934 citations
TL;DR: The authors in this article reported that ICH constitutes 10% to 15% of all strokes and remains without a treatment of proven benefit, despite several existing outcome prediction models for ICH.
Abstract: Background and Purpose—Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes and remains without a treatment of proven benefit. Despite several existing outcome prediction models for...
1,735 citations
TL;DR: Strains of methicillin-resistant Staphylococcus aureus, which had been largely confined to hospitals and long-term care facilities, are emerging in the community, and the prevalence of these strains in thecommunity seems likely to increase substantially.
Abstract: Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community. The changing epidemiology of MRSA bears striking similarity to the emergence of penicillinase-mediated resistance in S. aureus decades ago. Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially.
TL;DR: The transient suppression of GABA-mediated transmission that follows depolarization of hippocampal pyramidal neurons is mediated by retrograde signalling through release of endogenous cannabinoids, indicating that the function of endogenous cannabinoid released by depolarized hippocampal neurons might be to downregulate GABA release.
Abstract: Marijuana affects brain function primarily by activating the G-protein-coupled cannabinoid receptor-1 (CB1)1,2,3, which is expressed throughout the brain at high levels4. Two endogenous lipids, anandamide and 2-arachidonylglycerol (2-AG), have been identified as CB1 ligands5,6. Depolarized hippocampal neurons rapidly release both anandamide and 2-AG in a Ca2+-dependent manner6,7,8. In the hippocampus, CB1 is expressed mainly by GABA (γ-aminobutyric acid)-mediated inhibitory interneurons, where CB1 clusters on the axon terminal9,10,11. A synthetic CB1 agonist depresses GABA release from hippocampal slices10,12. These findings indicate that the function of endogenous cannabinoids released by depolarized hippocampal neurons might be to downregulate GABA release. Here we show that the transient suppression of GABA-mediated transmission that follows depolarization of hippocampal pyramidal neurons13 is mediated by retrograde signalling through release of endogenous cannabinoids. Signalling by the endocannabinoid system thus represents a mechanism by which neurons can communicate backwards across synapses to modulate their inputs.
TL;DR: It is shown that SGL cells, which express glial fibrillary acidic protein and have the characteristics of astrocytes, divide and generate new neurons under normal conditions or after the chemical removal of actively dividing cells.
Abstract: Neurogenesis in the dentate gyrus of the hippocampus persists throughout life in many vertebrates, including humans. The progenitors of these new neurons reside in the subgranular layer (SGL) of the dentate gyrus. Although stem cells that can self-renew and generate new neurons and glia have been cultured from the adult mammalian hippocampus, the in vivo primary precursors for the formation of new neurons have not been identified. Here we show that SGL cells, which express glial fibrillary acidic protein and have the characteristics of astrocytes, divide and generate new neurons under normal conditions or after the chemical removal of actively dividing cells. We also describe a population of small electron-dense SGL cells, which we call type D cells and are derived from the astrocytes and probably function as a transient precursor in the formation of new neurons. These results reveal the origins of new neurons in the adult hippocampus.
TL;DR: The goal of this meeting was to propose guidelines that would enable clinicians to recognize patients with FTD and, if appropriate, expedite their referral to a diagnostic center.
Abstract: An international group of clinical and basic scientists participated in the Frontotemporal Dementia and Pick's Disease Criteria Conference at the National Institutes of Health in Bethesda, Md, on July 7, 2000, to reassess clinical and neuropathological criteria for the diagnosis of frontotemporal dementia (FTD). Previous criteria for FTD have primarily been designed for research purposes. The goal of this meeting was to propose guidelines that would enable clinicians (particularly neurologists, psychiatrists, and neuropsychologists) to recognize patients with FTD and, if appropriate, to expedite their referral to a diagnostic center. In addition, recommendations for the neuropathological criteria of FTD were reviewed, relative to classical neuropathology and modern molecular biology.
TL;DR: The cloning of this receptor, designated P2Y12, is described and evidence that a patient with a bleeding disorder has a defect in this gene is provided, which should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.
Abstract: Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb–IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators1. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes2,3. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation4,5. The second ADP receptor required for aggregation (variously called P2YADP, P2YAC, P2Ycyc or P2TAC) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel6,7,8 and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder10 has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.
TL;DR: Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance and public health prevention programmes are the most cost-effective means of decreasing the global burden.
Abstract: Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance. The epidemiology of corneal blindness is complicated and encompasses a wide variety of infectious and inflammatory eye diseses that cause corneal scarring, which ultimately leads to functional blindness. In addition, the prevalence of corneal disease varies from country to country and even from one population to another. While cataract is responsible for nearly 20 million of the 45 million blind people in the world, the next major cause is trachoma which blinds 4.9 million individuals, mainly as a result of corneal scarring and vascularization. Ocular trauma and corneal ulceration are significant causes of corneal blindness that are often underreported but may be responsible for 1.5-2.0 million new cases of monocular blindness every year. Causes of childhood blindness (about 1.5 million worldwide with 5 million visually disabled) include xerophthalmia (350,000 cases annually), ophthalmia neonatorum, and less frequently seen ocular diseases such as herpes simplex virus infections and vernal keratoconjunctivitis. Even though the control of onchocerciasis and leprosy are public health success stories, these diseases are still significant causes of blindness--affecting a quarter of a million individuals each. Traditional eye medicines have also been implicated as a major risk factor in the current epidemic of corneal ulceration in developing countries. Because of the difficulty of treating corneal blindness once it has occurred, public health prevention programmes are the most cost-effective means of decreasing the global burden of corneal blindness.
TL;DR: It is shown that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons, and biochemical studies suggest that VR1 associates with this complex.
Abstract: Tissue injury generates endogenous factors that heighten our sense of pain by increasing the response of sensory nerve endings to noxious stimuli. Bradykinin and nerve growth factor (NGF) are two such pro-algesic agents that activate G-protein-coupled (BK2) and tyrosine kinase (TrkA) receptors, respectively, to stimulate phospholipase C (PLC) signalling pathways in primary afferent neurons. How these actions produce sensitization to physical or chemical stimuli has not been elucidated at the molecular level. Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons. Diminution of plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) levels through antibody sequestration or PLC-mediated hydrolysis mimics the potentiating effects of bradykinin or NGF at the cellular level. Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel activity, and biochemical studies suggest that VR1 associates with this complex. These studies delineate a biochemical mechanism through which bradykinin and NGF produce hypersensitivity and might explain how the activation of PLC signalling systems regulates other members of the TRP channel family.
TL;DR: It is reported that excitatory neurons lacking VGLUT1 express a closely related protein that has also been implicated in phosphate transport and localizes to synaptic vesicles and functions as a vesicular glutamate transporter (VGLUT2).
TL;DR: It is demonstrated that the RelA subunit of NF-κB is subject to inducible acetylation and that acetylated forms of RelA interact weakly, if at all, with IκBα.
Abstract: The nuclear expression and action of the nuclear factor kappa B (NF-κB) transcription factor requires signal-coupled phosphorylation and degradation of the IκB inhibitors, which normally bind and sequester this pleiotropically active factor in the cytoplasm. The subsequent molecular events that regulate the termination of nuclear NF-κB action remain poorly defined, although the activation of de novo IκBα gene expression by NF-κB likely plays a key role. Our studies now demonstrate that the RelA subunit of NF-κB is subject to inducible acetylation and that acetylated forms of RelA interact weakly, if at all, with IκBα. Acetylated RelA is subsequently deacetylated through a specific interaction with histone deacetylase 3 (HDAC3). This deacetylation reaction promotes effective binding to IκBα and leads in turn to IκBα-dependent nuclear export of the complex through a chromosomal region maintenance-1 (CRM-1)–dependent pathway. Deacetylation of RelA by HDAC3 thus acts as an intranuclear molecular switch that both controls the duration of the NF-κB transcriptional response and contributes to the replenishment of the depleted cytoplasmic pool of latent NF-κB–IκBα complexes.
TL;DR: A self-report physical activity questionnaire for older men and women developed to evaluate the outcomes of the Community Healthy Activities Model Program for Seniors (CHAMPS), an intervention to increase physical activity, finds the CHAMPS measure may be useful for evaluating the effectiveness of programs aimed at increasing levels of physical activity in older adults.
Abstract: STEWART, A L, K M MILLS, A C KING, W L HASKELL, D GILLIS, and P L RITTER CHAMPS Physical Activity Questionnaire for Older Adults: outcomes for interventions Med Sci Sports Exerc, Vol 33, No 7, 2001, pp 1126–1141PurposeTo evaluate effectively interventions to increase physical act
TL;DR: It is shown that mice carrying mutations in the tumour suppressor gene p53 were highly predisposed to a range of tumour types, predominantly early onset lung cancer.
Abstract: About 30% of human tumours carry ras gene mutations. Of the three genes in this family (composed of K-ras, N-ras and H-ras), K-ras is the most frequently mutated member in human tumours, including adenocarcinomas of the pancreas ( approximately 70-90% incidence), colon ( approximately 50%) and lung ( approximately 25-50%). To construct mouse tumour models involving K-ras, we used a new gene targeting procedure to create mouse strains carrying oncogenic alleles of K-ras that can be activated only on a spontaneous recombination event in the whole animal. Here we show that mice carrying these mutations were highly predisposed to a range of tumour types, predominantly early onset lung cancer. This model was further characterized by examining the effects of germline mutations in the tumour suppressor gene p53, which is known to be mutated along with K-ras in human tumours. This approach has several advantages over traditional transgenic strategies, including that it more closely recapitulates spontaneous oncogene activation as seen in human cancers.
TL;DR: The incremental construction and the random search strategy are evaluated as database docking techniques with a database of 51 molecules docked to two of the crystallographic testcases and are fast enough to reliably rank the database of compounds within 15 s per molecule on an SGI R10000 cpu.
Abstract: In this paper we describe the search strategies developed for docking flexible molecules to macomolecular sites that are incorporated into the widely distributed DOCK software, version 40 The search strategies include incremental construction and random conformation search and utilize the existing Coulombic and Lennard-Jones grid-based scoring function The incremental construction strategy is tested with a panel of 15 crystallographic testcases, created from 12 unique complexes whose ligands vary in size and flexibility For all testcases, at least one docked position is generated within 2 A of the crystallographic position For 7 of 15 testcases, the top scoring position is also within 2 A of the crystallographic position The algorithm is fast enough to successfully dock a few testcases within seconds and most within 100 s The incremental construction and the random search strategy are evaluated as database docking techniques with a database of 51 molecules docked to two of the crystallographic testcases Incremental construction outperforms random search and is fast enough to reliably rank the database of compounds within 15 s per molecule on an SGI R10000 cpu
TL;DR: Three-dimensional structures of the Trk receptors, in one instance in association with a neurotrophin, have revealed the structural bases underlying specificity in neurotrophIn signaling, where key intermediates are localized to different membrane compartments.
TL;DR: It is shown that a prominent form of synaptic plasticity can be elicited by a single in vivo exposure to cocaine and therefore may be involved in the early stages of the development of drug addiction.
Abstract: How do drugs of abuse modify neural circuitry and thereby lead to addictive behaviour? As for many forms of experience-dependent plasticity, modifications in glutamatergic synaptic transmission have been suggested to be particularly important Evidence of such changes in response to in vivo administration of drugs of abuse is lacking, however Here we show that a single in vivo exposure to cocaine induces long-term potentiation of AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid)-receptor-mediated currents at excitatory synapses onto dopamine cells in the ventral tegmental area Potentiation is still observed 5 but not 10 days after cocaine exposure and is blocked when an NMDA (N-methyl-d-aspartate) receptor antagonist is administered with cocaine Furthermore, long-term potentiation at these synapses is occluded and long-term depression is enhanced by in vivo cocaine exposure These results show that a prominent form of synaptic plasticity can be elicited by a single in vivo exposure to cocaine and therefore may be involved in the early stages of the development of drug addiction
TL;DR: It is demonstrated that nuclear EGFR is strongly correlated with highly proliferating activities of tissues and associated with promoter region of cyclin D1 in vivo, suggesting that EGFR might function as a transcription factor to activate genes required for highly proliferationating activities.
Abstract: Epidermal growth factor receptor (EGFR) has been detected in the nucleus in many tissues and cell lines. However, the potential functions of nuclear EGFR have largely been overlooked. Here we demonstrate that nuclear EGFR is strongly correlated with highly proliferating activities of tissues. When EGFR was fused to the GAL4 DNA-binding domain, we found that the carboxy terminus of EGFR contained a strong transactivation domain. Moreover, the receptor complex bound and activated AT-rich consensus-sequence-dependent transcription, including the consensus site in cyclin D1 promoter. By using chromatin immunoprecipitation assays, we further demonstrated that nuclear EGFR associated with promoter region of cyclin D1 in vivo. EGFR might therefore function as a transcription factor to activate genes required for highly proliferating activities.
TL;DR: It is shown that the D AF-2 pathway prevents DAF-16 accumulation in nuclei, and it is found that both sensory neurons and germline activity regulate DAF/IGF-1 signaling, but the nuclear localization patterns are different, which reveal unexpected complexity in the Daf-16-dependent pathways that regulate aging.
Abstract: The lifespan of Caenorhabditis elegans is regulated by the insulin/insulin-like growth factor (IGF)-1 receptor homolog DAF-2, which signals through a conserved phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Mutants in this pathway remain youthful and active much longer than normal animals and can live more than twice as long. This lifespan extension requires DAF-16, a forkhead/winged-helix transcription factor. DAF-16 is thought to be the main target of the DAF-2 pathway. Insulin/IGF-1 signaling is thought to lead to phosphorylation of DAF-16 by AKT activity, which in turn shortens lifespan. Here, we show that the DAF-2 pathway prevents DAF-16 accumulation in nuclei. Disrupting Akt-consensus phosphorylation sites in DAF-16 causes nuclear accumulation in wild-type animals, but, surprisingly, has little effect on lifespan. Thus the DAF-2 pathway must have additional outputs. Lifespan in C. elegans can be extended by perturbing sensory neurons or germ cells. In both cases, lifespan extension requires DAF-16. We find that both sensory neurons and germline activity regulate DAF-16 accumulation in nuclei, but the nuclear localization patterns are different. Together these findings reveal unexpected complexity in the DAF-16-dependent pathways that regulate aging.
TL;DR: The arrays provide precise measurement in cell lines and clinical material, so that they can reliably detect and quantify high-level amplifications and single-copy alterations in diploid, polyploid and heterogeneous backgrounds.
Abstract: We have assembled arrays of approximately 2,400 BAC clones for measurement of DNA copy number across the human genome. The arrays provide precise measurement (s.d. of log2 ratios=0.05-0.10) in cell lines and clinical material, so that we can reliably detect and quantify high-level amplifications and single-copy alterations in diploid, polyploid and heterogeneous backgrounds.
TL;DR: Evidence is provided that the biosynthetic pathway and biochemical intermediates in AI‐2 biosynthesis are identical in Escherichia coli, Salmonella typhimurium, V. harveyi, Vibrio cholerae and Enterococcus faecalis, suggesting thatAI‐2 is a unique, ‘universal' signal that could be used by a variety of bacteria for communication among and between species.
Abstract: Many bacteria control gene expression in response to cell population density, and this phenomenon is called quorum sensing. In Gram-negative bacteria, quorum sensing typically involves the production, release and detection of acylated homoserine lactone signalling molecules called autoinducers. Vibrio harveyi, a Gram-negative bioluminescent marine bacterium, regulates light production in response to two distinct autoinducers (AI-1 and AI-2). AI-1 is a homoserine lactone. The structure of AI-2 is not known. We have suggested previously that V. harveyi uses AI-1 for intraspecies communication and AI-2 for interspecies communication. Consistent with this idea, we have shown that many species of Gram-negative and Gram-positive bacteria produce AI-2 and, in every case, production of AI-2 is dependent on the function encoded by the luxS gene. We show here that LuxS is the AI-2 synthase and that AI-2 is produced from S-adenosylmethionine in three enzymatic steps. The substrate for LuxS is S-ribosylhomocysteine, which is cleaved to form two products, one of which is homocysteine, and the other is AI-2. In this report, we also provide evidence that the biosynthetic pathway and biochemical intermediates in AI-2 biosynthesis are identical in Escherichia coli, Salmonella typhimurium, V. harveyi, Vibrio cholerae and Enterococcus faecalis. This result suggests that, unlike quorum sensing via the family of related homoserine lactone autoinducers, AI-2 is a unique, 'universal' signal that could be used by a variety of bacteria for communication among and between species.
TL;DR: The mental health difficulties experienced by many gay and bisexual Latino men in the United States are directly related to a social context of oppression that leads to social alienation, low self-esteem, and symptoms of psychologic distress.
Abstract: OBJECTIVES: This study assessed the relation between experiences of social discrimination (homophobia, racism, and financial hardship) and symptoms of psychologic distress (anxiety, depression, and suicidal ideation) among self-identified gay and bisexual Latino men in the United States. METHODS: Data were collected from a probability sample of 912 men (self-identified as both Latino and nonheterosexual) recruited from the venues and public social spaces identified as both Latino and gay in the cities of Miami, Los Angeles, and New York. RESULTS: The study showed high prevalence rates of psychologic symptoms of distress in the population of gay Latino men during the 6 months before the interview, including suicidal ideation (17% prevalence), anxiety (44%), and depressed mood (80%). In both univariate and multivariate analyses, experiences of social discrimination were strong predictors of psychologic symptoms. CONCLUSIONS: The mental health difficulties experienced by many gay and bisexual Latino men in the United States are directly related to a social context of oppression that leads to social alienation, low self-esteem, and symptoms of psychologic distress.
TL;DR: The introduction of highly active antiretroviral therapy (HAART) has produced a dramatic reduction in mortality among HIV-infected individuals, and the level of adherence to HAART is closely associated with suppression of the HIV viral load in plasma.
Abstract: The introduction of highly active antiretroviral therapy (HAART) has produced a dramatic reduction in mortality among HIV-infected individuals [1–4]. Whereas the level of adherence to HAART is closely associated with suppression of the HIV viral load in plasma [5–14], a relationship between adherenc