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The successful recent application of machine learning methods to scientific problems includes the learning of flexible and accurate atomic-level force-fields for materials and biomolecules from quantum chemical data. In parallel, the machine learning of force-fields at coarser resolutions is rapidly gaining relevance as an efficient way to represent the higher-body interactions needed in coarse-grained force-fields to compensate for the omitted degrees of freedom. Coarse-grained models are important for the study of systems at time and length scales exceeding those of atomistic simulations. However, the development of transferable coarse-grained models via machine learning still presents significant challenges. Here, we discuss recent developments in this field and current efforts to address the remaining challenges.  相似文献   

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Background

The ‘gynodioecy–dioecy pathway’ is considered to be one of the most important evolutionary routes from hermaphroditism to separate sexes (dioecy). Despite a large accumulation of evidence for female seed fertility advantages in gynodioecious species (females and hermaphrodites coexist) in support of the first step in the gynodioecy–dioecy pathway, we still have very little evidence for the second step, i.e. the transition from gynodioecy to dioecy.

Scope

We review the literature to evaluate whether basic predictions by theory are supported. To establish whether females'' seed fertility advantage and frequencies are sufficient to favour the invasion of males, we review these for species along the gynodioecy–dioecy pathway published in the last 5 years. We then review the empirical evidence for predictions deriving from the second step, i.e. hermaphrodites'' male fertility increases with female frequency, selection favours greater male fertility in hermaphrodites in gynodioecious species, and, where males and hermaphrodites coexist with females (subdioecy), males have greater male fertility than hermaphrodites. We review how genetic control and certain ecological features (pollen limitation, selfing, plasticity in sex expression and antagonists) influence the trajectory of a population along the gynodioecy–dioecy pathway.

Conclusions

Females tend to have greater seed fertility advantages over hermaphrodites where the two coexist, and this advantage is positively correlated with female frequency across species, as predicted by theory. A limited number of studies in subdioecious species have demonstrated that males have an advantage over hermaphrodites, as also predicted by theory. However, less evidence exists for phenotypic selection to increase male traits of hermaphrodites or for increasing male function of hermaphrodites in populations with high female frequency. A few key case studies underline the importance of examining multiple components of male fertility and the roles of pollen limitation, selfing and plasticity, when evaluating advantages. We conclude that we do not yet have a full understanding of the transition from gynodioecy to dioecy.  相似文献   

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The generation and targeting of appropriate numbers and types of neurons to where they are needed in the brain is essential for the establishment, maintenance and modification of neural circuitry. This review aims to summarize the patterns, mechanisms and functional significance of neuronal migration in the postnatal brain, with an emphasis on the migratory events that persist in the mature brain.  相似文献   

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Network models of infectious disease epidemiology can potentially provide insight into how to tailor control strategies for specific regions, but only if the network adequately reflects the structure of the region's contact network. Typically, the network is produced by models that incorporate details about human interactions. Each detail added renders the models more complicated and more difficult to calibrate, but also more faithful to the actual contact network structure. We propose a statistical test to determine when sufficient detail has been added to the models and demonstrate its application to the models used to create a synthetic population and contact network for the USA.  相似文献   

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CD4+ T cells die in individuals infected with HIV, either as a result of direct HIV infection or as uninfected innocent bystanders. Possible mechanisms for bystander killing include generation of viral products such as Tat or gp120 and expression of death receptor ligands, such as FasL, that engage functional death receptors on uninfected cells. This review covers the sometimes conflicting in vitro and ex vivo studies that address these possible mechanisms of HIV-associated cell death. It is an intriguing possibility that manipulation of cell death processes, to decrease bystander death or increase death of infected cells, in patients infected with HIV might provide a useful adjunct to antiretroviral therapy.  相似文献   

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Derivation of insulin producing cells (IPCs) from embryonic stem (ES) cells provides a potentially innovative form of treatment for type 1 diabetes. Here, we discuss the current state of the art, unique challenges, and future directions on generating IPCs.  相似文献   

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Exposure to Cryptosporidium parvum in healthy individuals results in transient infection that may be asymptomatic or can result in self-limited diarrhoea. In contrast, acquired immune deficiency syndrome patients with cryptosporidiosis can experience severe manifestations of disease. Volunteer studies have demonstrated that as few as 10 oocysts can cause infection in otherwise healthy adults and that isolates from geographically diverse regions differ in infectivity and, perhaps, virulence. Variability in isolate pathogenicity and infectivity has also been seen in bovine and murine models, respectively. Furthermore, isolate specific differences in protein composition and in host immunoreactivity have been observed. The molecular basis for differences in pathogenicity is not understood. Determining which factors are responsible for host selectivity and for the initiation, establishment, and perpetuation of infection with Cryptosporidium is key to rational drug design and vaccine development. To date, no specific virulence factors have been unequivocally shown to individually cause direct or indirect damage to host tissues nor have mutant strains been produced that could prove that particular deletions result in less virulent strains. Nevertheless, a number of candidate molecules have been identified by immunological and molecular methods. Here, we review the salient characteristics of some of these putative virulence determinants, including molecules that are involved in adhesion, protein degradation and the modulation of the host responses.  相似文献   

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Are we there yet? Tracking the development of new model systems   总被引:2,自引:0,他引:2  
It is increasingly clear that additional 'model' systems are needed to elucidate the genetic and developmental basis of organismal diversity. Whereas model system development previously required enormous investment, recent advances including the decreasing cost of DNA sequencing and the power of reverse genetics to study gene function are greatly facilitating the process. In this review, we consider two aspects of the development of new genetic model systems: first, the types of questions being advanced using these new models; and second, the essential characteristics and molecular tools for new models, depending on the research focus. We hope that researchers will be inspired to explore this array of emerging models and even consider developing new molecular tools for their own favorite organism.  相似文献   

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ABSTRACT

If the postracial is a coherent formation, it is produced not by ideological lock-step but by distributed affinities and relations in a transnational space of interconnection and exchange. The neoliberal erasure of ‘?…?the structural conditions of racial reproduction and racist articulation’ (34) and the clouding of the historicity of racisms produces postraciality as ‘the illusion that the dream of the nonracial has already been realized’ (180). This illusion is familiar in writing on the postracial that focuses on the denial – be it through the averted gaze of ‘color-blindness’, or the official state prohibition of racism, or the triumphalism of strategic declarations of the ‘end of racism’ – of enduring racialized inequality. Goldberg’s advance is to explore how the illusion has become increasingly weaponized; that far from signalling the end of race, it represents an emergent ‘neo-raciality, racism’s extension if not resurrection’ (24).  相似文献   

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The ability to solubilize and digest protein extracts and recover peptides with high efficiency is of paramount importance in proteomics. A novel proteomic sample preparation protocol by Krijgsveld and colleagues (Hughes et al, 2014) provides significant advantages by enabling all sample processing steps to be carried out in a single tube to minimize sample losses, thereby enhancing sensitivity, throughput, and scalability of proteomics analyses.  相似文献   

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Understanding gibberellic acid signaling--are we there yet?   总被引:4,自引:0,他引:4  
The phytohormone gibberellic acid (GA) controls important aspects of plant growth such as seed germination, elongation growth, and flowering. The key components of the GA signaling pathway have been identified over the past 10 years. The current view is that GA binds to a soluble GID1 receptor, which interacts with the DELLA repressor proteins in a GA-dependent manner and thereby induces DELLA protein degradation via the E3 ubiquitin ligase SCF(GID2/SLY1). GA-dependent growth responses can generally be correlated with and be explained by changes in DELLA repressor abundance, where the DELLA repressor exerts a growth restraint that is relieved upon its degradation. However, it is obvious that other mechanisms must exist that control the activity of this pathway. This review discusses recent advances in the understanding of GA signaling, of its homeostasis, and of its cross-talk with other signaling pathways.  相似文献   

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Grove EA 《Neuron》2005,48(4):522-524
Normal brain function requires the development of precise connections between thalamus and cerebral cortex. In this issue of Neuron, Cang et al. and Tori and Levitt argue that EphA/ephrin-A signaling in the target tissue guides sensory thalamic axons to the correct cortical area, and sensory cortical axons to precise thalamic targets. Although EphA/ephrin-A signaling organizes sensory maps within areas, and thalamocortical axons in the internal capsule, both papers argue that each developmental event is dissociable from the others.  相似文献   

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