Abstract:
:The rates and properties of new mutations affecting fitness have implications for a number of outstanding questions in evolutionary biology. Obtaining estimates of mutation rates and effects has historically been challenging, and little theory has been available for predicting the distribution of fitness effects (DFE); however, there have been recent advances on both fronts. Extreme-value theory predicts the DFE of beneficial mutations in well-adapted populations, while phenotypic fitness landscape models make predictions for the DFE of all mutations as a function of the initial level of adaptation and the strength of stabilizing selection on traits underlying fitness. Direct experimental evidence confirms predictions on the DFE of beneficial mutations and favors distributions that are roughly exponential but bounded on the right. A growing number of studies infer the DFE using genomic patterns of polymorphism and divergence, recovering a wide range of DFE. Future work should be aimed at identifying factors driving the observed variation in the DFE. We emphasize the need for further theory explicitly incorporating the effects of partial pleiotropy and heterogeneity in the environment on the expected DFE.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Bataillon T,Bailey SFdoi
10.1111/nyas.12460subject
Has Abstractpub_date
2014-07-01 00:00:00pages
76-92eissn
0077-8923issn
1749-6632journal_volume
1320pub_type
杂志文章,评审abstract::The human organism is in a state of dynamic equilibrium, homeostasis. The stress system is activated when homeostasis is challenged by extrinsic or intrinsic forces, the stressors. This system, whose central component is the central nervous system (CNS) and includes corticotropin-releasing hormone (CRH) and noradrener...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.1995.tb44666.x
更新日期:1995-12-29 00:00:00
abstract::Jackson's Personality Research Form E (PRF) was administered to a large, heterogeneous group of adult inpatients with diagnoses of alcohol and/or drug dependence. Cluster analysis of PRF factor scores yielded five distinct patient subtypes: hostile-dependent, cooperative-nonreflective, socially uninvolved, impulsive-u...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1994.tb24694.x
更新日期:1994-02-28 00:00:00
abstract::These findings support the hypothesis that a frontal-subcortical abnormality is necessary to produce symptoms of depression (e.g., mood-related signs, behavioral disturbances, neurovegetative signs) in dementia. Behavioral disturbances (e.g., disinhibition, agitation, social withdrawal) were more likely to occur in FL...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1995.tb38153.x
更新日期:1995-12-15 00:00:00
abstract::Aging is the major risk factor for both the development of chronic diseases and loss of functional capacity. Geroscience provides links among the biology of aging, the biology of disease, and the physiology of frailty, three fields where enormous progress has been made in the last few decades. While, previously, the f...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13297
更新日期:2016-12-01 00:00:00
abstract::We investigated the molecular mechanism by which Sph-1-P affects the FN-dependent haptotactic motility of serum-starved mouse melanoma B16/F10 cells. We found that EDG-5-induced Rho activation followed by enhanced tyrosine phosphorylation of FAK and paxillin, and beta 1-integrin activation leading to overexpression of...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2000.tb06566.x
更新日期:2000-04-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a structurally highly conserved neuropeptide and displays pleiotropic activity, including functioning as a neurotransmitter, neuromodulator, and neurotrophic factor. A series of recent experiments, including genetic manipulation of PACAP and its receptors, ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1317.038
更新日期:2006-07-01 00:00:00
abstract::We have demonstrated a far more widespread and selective ischemic cell damage than previously thought. In area CA3, a distinct subpopulation of interneurons, characterized by their spiny dendrites and their calretinin content, was selectively vulnerable in the absence of any other CA3 involvement. In the dentate hilus...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.1994.tb55790.x
更新日期:1994-11-14 00:00:00
abstract::Although pancreatic adenocarcinoma has become one of the best characterized malignant diseases, severe diagnostic and therapeutic problems are still associated with this disease. The establishment of a molecular model of pancreatic carcinogenesis may provide tools that could result in earlier diagnosis of this disease...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1999.tb09509.x
更新日期:1999-06-30 00:00:00
abstract::Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder caused by antibodies directed against the voltage-gated calcium channels that provide the calcium ion flux that triggers acetylcholine release at the neuromuscular junction. To study the pathophysiology of LEMS and test candidate therapeutic strategies...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13512
更新日期:2018-01-01 00:00:00
abstract::Aberrant cell cycle activity and DNA damage have been observed in neurons in association with various neurodegenerative conditions. While there is strong evidence for a causative role for these events in neurotoxicity, it is unclear how they are triggered and why they are toxic. Here, we introduce a brief background o...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04105.x
更新日期:2009-07-01 00:00:00
abstract::Biologics are playing an increasingly significant role in the practice of modern medicine and surgery in general and orthopedics in particular. Cell-based approaches are among the most important and widely used modalities in orthopedic biologics, with mesenchymal stem cells and other multi/pluripotent cells undergoing...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13575
更新日期:2017-12-01 00:00:00
abstract::To test whether the development of emotional resilience is a function of sensitive caregiving and child negative affect, we tested the joint contributions of 7-month maternal sensitivity and infant negative affect to the prediction of 33-month emotional resilience across the first 3 years of life. The aims of this stu...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1376.033
更新日期:2006-12-01 00:00:00
abstract::Many studies have now indicated that micronutrients, such as the carotenoids, tocopherols, and ascorbic acid, can prevent mutagenesis, genotoxic effects, or malignant transformation in bacteria and mammalian tissue, either in cell culture or in organ culture. In addition, multiple papers report that some of these micr...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.1993.tb39180.x
更新日期:1993-05-28 00:00:00
abstract::The mechanisms controlling ATP generation in the transition from normal resting conditions to either high work states or ischemia are poorly understood. ATP generation depends upon compartmentation between the mitochondria and cytosol of metabolic pathways and key energy transfer species that cannot be easily assessed...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1380.012
更新日期:2006-10-01 00:00:00
abstract::Results of therapeutic trials of transfer factor in a number of laboratories suggest clinical benefit and enhancement of immunological reactivity in patients with primary or secondary immunodeficiency diseases. Long term follow-up of 32 patients with the Wiskott-Aldrich syndrome suggested that transfer factor caused c...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1979.tb47116.x
更新日期:1979-01-01 00:00:00
abstract::Coccidioides causes coccidioidomycosis in the southwestern United States. Its clinical manifestations range from the primary asymptomatic to progressive pulmonary and extrapulmonary disease. Because of endemicity, frequent relapse, and virulent nature of Coccidioides, there is an urgent need for the development of eff...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1406.013
更新日期:2007-09-01 00:00:00
abstract::Growing evidence indicates that deregulation of the epigenetic machinery comprising the microRNA (miRNA) network is a critical factor in the progression of various diseases, including cancer. Concurrently, dietary phytochemicals are being intensively studied for their miRNA-mediated health-beneficial properties, such ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13372
更新日期:2017-09-01 00:00:00
abstract::Especially since the (re-)discovery of T cell subpopulations with specialized regulatory activities, mechanisms of anti-inflammatory T cell regulation are studied very actively and are expected to lead to the development of novel immunotherapeutic approaches, especially in chronic inflammatory diseases. Heat shock pro...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1391.020
更新日期:2007-10-01 00:00:00
abstract::The proto-oncogene c-myc is involved in multiple cell pathways with opposite effects on cell outcome of death or proliferation. It has been proposed that these different roles depend on the sequestration of c-Myc protein in cellular compartments and/or its phosphorylation. We speculated that subcellular localization o...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1397.021
更新日期:2007-01-01 00:00:00
abstract::Increase in the dosage of cellular oncogenes by DNA amplification is a frequent genetic alteration of cancer cells. In neuroblastoma, amplification of the gene MYCN has been associated with aggressively growing cancers and is an indicator for poor prognosis. MYCN amplification is of predictive value in identifying pat...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::The entorhinal cortex, subiculum, and hippocampus have been regions of great interest in both clinical and neuropathological investigations of schizophrenia. Postmortem studies have identified numerous abnormalities, although many remain controversial or unconfirmed. Among the cellular and molecular neuropathological ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2000.tb06732.x
更新日期:2000-06-01 00:00:00
abstract::The envelope glycoprotein complex (Env), encoded by the human immunodeficiency virus (HIV-1), kills uninfected cells expressing CD4 and/or the chemokine receptor CXCR4 or CCR5, via at least three independent mechanisms. First, the soluble Env product gp120 can induce the apoptotic cell death of lymphocytes, neurons, a...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1299.004
更新日期:2003-12-01 00:00:00
abstract::Na+/Ca2+-K+ exchangers (NCKX) are plasma membrane transporters that are thought to mainly mediate Ca2+ extrusion (along with K+) at the expense of the Na+ electrochemical gradient. However, because they are bidirectional, most assays have relied on measuring their activity in the reverse (Ca2+ import) mode. Herein we ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1387.056
更新日期:2007-03-01 00:00:00
abstract::Pain is a subjective symptom whose prevalence can be grossly underestimated. The high proportion of adults with thalassemia who experience chronic pain is evident from recent surveys. However, pain has not received enough attention in the overall management of thalassemia. The association of pain with the type and tre...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13061
更新日期:2016-03-01 00:00:00
abstract::Population trends indicate that in the near future the size of the elderly population will increase. This will result in a large increment in the numbers of persons suffering mild to severe levels of cognitive impairment. While considerable efforts continue to be made to explain brain changes associated with Alzheimer...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1996.tb34395.x
更新日期:1996-01-17 00:00:00
abstract::During the annual Ramazzini Days, the Mayor of Carpi confers the Ramazzini Award on scientists deemed by the Collegium Ramazzini to have made outstanding contributions to furthering the aims of Bernardino Ramazzini in safeguarding public health. Dr. Lorenzo Tomatis was the Ramazzini Award recipient in 2005, and the pr...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1371.039
更新日期:2006-09-01 00:00:00
abstract::This communication summaries a series of observations of the transport function of the crypt of the rat distal colon. Development of methods to study both 22Na uptake by apical membrane vesicles prepared from crypt cells and intracellular pHi (pHi), fluid movement (Jv), and bicarbonate secretion during microperfusion ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2000.tb05222.x
更新日期:2000-01-01 00:00:00
abstract::Oxidative stress is a common response of epidermal cells to a variety of noxious stimuli such as ultraviolet (UV) radiation from solar light and proinflammatory cytokines from skin-infiltrating leukocytes. Here, we report that two types of plant-derived antioxidants, the phenylpropanoid glycoside verbascoside as well ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04684.x
更新日期:2009-08-01 00:00:00
abstract::The formation of metastasis is a dreadful complication of cancer that is associated with a poor prognosis. Several clinical observations and experimental findings indicate that the metastatic process is nonrandom and involves a sequence of multistep events that may all be targeted for therapy. This includes angiogenes...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2002.tb04702.x
更新日期:2002-11-01 00:00:00
abstract::Endometriosis is a common gynecologic disorder that affects approximately 14% of all women and 30% to 50% of infertile women. Since the most common symptoms of endometriosis--progressive dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility--are also symptoms of multiple disorders, a diagnosis of endometrios...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2002.tb02795.x
更新日期:2002-03-01 00:00:00