Change and Aging Senescence as an adaptation

Understanding why we age is a long-lived open problem in evolutionary biology. Aging is prejudicial to the individual and evolutionary forces should prevent it, but many species show signs of senescence as individuals age. Here, I will propose a model for aging based on assumptions that are compatible with evolutionary theory: i) competition is between individuals; ii) there is some degree of locality, so quite often competition will between parents and their progeny; iii) optimal conditions are not stationary, mutation helps each species to keep competitive. When conditions change, a senescent species can drive immortal competitors to extinction. This counter-intuitive result arises from the pruning caused by the death of elder individuals. When there is change and mutation, each generation is slightly better adapted to the new conditions, but some older individuals survive by random chance. Senescence can eliminate those from the genetic pool. Even though individual selection forces always win over group selection ones, it is not exactly the individual that is selected, but its lineage. While senescence damages the individuals and has an evolutionary cost, it has a benefit of its own. It allows each lineage to adapt faster to changing conditions. We age because the world changes.Comment: 19 pages, 4 figure

Rugged Single Domain Antibody Detection Elements for Bacillus anthracis Spores and Vegetative Cells

Significant efforts to develop both laboratory and field-based detection assays for an array of potential biological threats started well before the anthrax attacks of 2001 and have continued with renewed urgency following. While numerous assays and methods have been explored that are suitable for laboratory utilization, detection in the field is often complicated by requirements for functionality in austere environments, where limited cold-chain facilities exist. In an effort to overcome these assay limitations for Bacillus anthracis, one of the most recognizable threats, a series of single domain antibodies (sdAbs) were isolated from a phage display library prepared from immunized llamas. Characterization of target specificity, affinity, and thermal stability was conducted for six sdAb families isolated from rounds of selection against the bacterial spore. The protein target for all six sdAb families was determined to be the S-layer protein EA1, which is present in both vegetative cells and bacterial spores. All of the sdAbs examined exhibited a high degree of specificity for the target bacterium and its spore, with affinities in the nanomolar range, and the ability to refold into functional antigen-binding molecules following several rounds of thermal denaturation and refolding. This research demonstrates the capabilities of these sdAbs and their potential for integration into current and developing assays and biosensors

Population Genetic Differences along a Latitudinal Cline between Original and Recently Colonized Habitat in a Butterfly

BACKGROUND: Past and current range or spatial expansions have important consequences on population genetic structure. Habitat-use expansion, i.e. changing habitat associations, may also influence genetic population parameters, but has been less studied. Here we examined the genetic population structure of a Palaeartic woodland butterfly Pararge aegeria (Nymphalidae) which has recently colonized agricultural landscapes in NW-Europe. Butterflies from woodland and agricultural landscapes differ in several phenotypic traits (including morphology, behavior and life history). We investigated whether phenotypic divergence is accompanied by genetic divergence between populations of different landscapes along a 700 km latitudinal gradient. METHODOLOGY/PRINCIPAL FINDINGS: Populations (23) along the latitudinal gradient in both landscape types were analyzed using microsatellite and allozyme markers. A general decrease in genetic diversity with latitude was detected, likely due to post-glacial colonization effects. Contrary to expectations, agricultural landscapes were not less diverse and no significant bottlenecks were detected. Nonetheless, a genetic signature of recent colonization is reflected in the absence of clinal genetic differentiation within the agricultural landscape, significantly lower gene flow between agricultural populations (3.494) than between woodland populations (4.183), and significantly higher genetic differentiation between agricultural (0.050) than woodland (0.034) pairwise comparisons, likely due to multiple founder events. Globally, the genetic data suggest multiple long distance dispersal/colonization events and subsequent high intra- and inter-landscape gene flow in this species. Phosphoglucomutase deviated from other enzymes and microsatellite markers, and hence may be under selection along the latitudinal gradient but not between landscape types. Phenotypic divergence was greater than genetic divergence, indicating directional selection on some flight morphology traits. MAIN CONCLUSIONS/SIGNIFICANCE: Clinal differentiation characterizes the population structure within the original woodland habitat. Genetic signatures of recent habitat expansion remain, notwithstanding high gene flow. After differentiation through drift was excluded, both latitude and landscape were significant factors inducing spatially variable phenotypic variation

Self-Organizing Circuit Assembly through Spatiotemporally Coordinated Neuronal Migration within Geometric Constraints

Neurons are dynamically coupled with each other through neurite-mediated adhesion during development. Understanding the collective behavior of neurons in circuits is important for understanding neural development. While a number of genetic and activity-dependent factors regulating neuronal migration have been discovered on single cell level, systematic study of collective neuronal migration has been lacking. Various biological systems are shown to be self-organized, and it is not known if neural circuit assembly is self-organized. Besides, many of the molecular factors take effect through spatial patterns, and coupled biological systems exhibit emergent property in response to geometric constraints. How geometric constraints of the patterns regulate neuronal migration and circuit assembly of neurons within the patterns remains unexplored.We established a two-dimensional model for studying collective neuronal migration of a circuit, with hippocampal neurons from embryonic rats on Matrigel-coated self-assembled monolayers (SAMs). When the neural circuit is subject to geometric constraints of a critical scale, we found that the collective behavior of neuronal migration is spatiotemporally coordinated. Neuronal somata that are evenly distributed upon adhesion tend to aggregate at the geometric center of the circuit, forming mono-clusters. Clustering formation is geometry-dependent, within a critical scale from 200 µm to approximately 500 µm. Finally, somata clustering is neuron-type specific, and glutamatergic and GABAergic neurons tend to aggregate homo-philically.We demonstrate self-organization of neural circuits in response to geometric constraints through spatiotemporally coordinated neuronal migration, possibly via mechanical coupling. We found that such collective neuronal migration leads to somata clustering, and mono-cluster appears when the geometric constraints fall within a critical scale. The discovery of geometry-dependent collective neuronal migration and the formation of somata clustering in vitro shed light on neural development in vivo

Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation

Pheromones and Other Semiochemicals for Monitoring Rare and Endangered Species

As global biodiversity declines, biodiversity and conservation have become ever more important research topics. Research in chemical ecology for conservation purposes has not adapted to address this need. During the last 10-15 years, only a few insect pheromones have been developed for biodiversity and conservation studies, including the identification and application of pheromones specifically for population monitoring. These investigations, supplemented with our knowledge from decades of studying pest insects, demonstrate that monitoring with pheromones and other semiochemicals can be applied widely for conservation of rare and threatened insects. Here, I summarize ongoing conservation research, and outline potential applications of chemical ecology and pheromone-based monitoring to studies of insect biodiversity and conservation research. Such applications include monitoring of insect population dynamics and distribution changes, including delineation of current ranges, the tracking of range expansions and contractions, and determination of their underlying causes. Sensitive and selective monitoring systems can further elucidate the importance of insect dispersal and landscape movements for conservation. Pheromone-based monitoring of indicator species will also be useful in identifying biodiversity hotspots, and in characterizing general changes in biodiversity in response to landscape, climatic, or other environmental changes

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries