Quantitative Metaproteomics and Activity-based Protein Profiling of Patient Fecal Microbiome Identifies Host and Microbial Serine-type Endopeptidase Activity Associated With Ulcerative Colitis

The gut microbiota plays an important yet incompletely understood role in the induction and propagation of ulcerative colitis (UC). Organism-level efforts to identify UC-associated microbes have revealed the importance of community structure, but less is known about the molecular effectors of disease. We performed 16S rRNA gene sequencing in parallel with label-free data-dependent LC-MS/MS proteomics to characterize the stool microbiomes of healthy (n = 8) and UC (n = 10) patients. Comparisons of taxonomic composition between techniques revealed major differences in community structure partially attributable to the additional detection of host, fungal, viral, and food peptides by metaproteomics. Differential expression analysis of metaproteomic data identified 176 significantly enriched protein groups between healthy and UC patients. Gene ontology analysis revealed several enriched functions with serine-type endopeptidase activity overrepresented in UC patients. Using a biotinylated fluorophosphonate probe and streptavidin-based enrichment, we show that serine endopeptidases are active in patient fecal samples and that additional putative serine hydrolases are detectable by this approach compared with unenriched profiling. Finally, as metaproteomic databases expand, they are expected to asymptotically approach completeness. Using ComPIL and de novo peptide sequencing, we estimate the size of the probable peptide space unidentified (“dark peptidome”) by our large database approach to establish a rough benchmark for database sufficiency. Despite high variability inherent in patient samples, our analysis yielded a catalog of differentially enriched proteins between healthy and UC fecal proteomes. This catalog provides a clinically relevant jumping-off point for further molecular-level studies aimed at identifying the microbial underpinnings of UC.     

Evolutionary rescue by beneficial mutations in environments that change in space and time

A factor that may limit the ability of many populations to adapt to changing conditions is the rate at which beneficial mutations can become established. We study the probability that mutations become established in changing environments by extending the classic theory for branching processes. When environments change in time, under quite general conditions, the establishment probability is approximately twice the ‘effective selection coefficient’, whose value is an average that gives most weight to a mutant''s fitness in the generations immediately after it appears. When fitness varies along a gradient in a continuous habitat, increased dispersal generally decreases the chance a mutation establishes because mutations move out of areas where they are most adapted. When there is a patch of favourable habitat that moves in time, there is a maximum speed of movement above which mutations cannot become established, regardless of when and where they first appear. This critical speed limit, which is proportional to the mutation''s maximum selective advantage, represents an absolute constraint on the potential of locally adapted mutations to contribute to evolutionary rescue.     

Environmental Exchange Box

In this activity, teachers in one state create and share an “exchange box” of environmental and cultural items with students of another state. The Environmental Exchange Box activity enables teachers to improve students' skills in scientific inquiry and develop attitudes and values conducive to science learning such as wonder, curiosity, and respect for different social perceptions. Teachers will be able to work beyond the limits of the classroom and introduce outside resources to help increase students' global awareness and promote respect for the culture and environment of diverse populations. Specifically, this activity can help teachers fulfill national Teaching Standards B, D, and E.     

Evaluation of the sustainability of contrasted pig farming systems: breeding programmes

The sustainability of breeding activities in 15 pig farming systems in five European countries was evaluated. One conventional and two differentiated systems per country were studied. The Conventional systems were the standard systems in their countries. The differentiated systems were of three categories: Adapted Conventional with focus on animal welfare, meat quality or environment (five systems); Traditional with local breeds in small-scale production (three systems) and Organic (two systems). Data were collected with a questionnaire from nine breeding organisations providing animals and semen to the studied farming systems and from, on average, five farmers per farming system. The sustainability assessment of breeding activities was performed in four dimensions. The first dimension described whether the market for the product was well defined, and whether the breeding goal reflected the farming system and the farmers’ demands. The second dimension described recording and selection procedures, together with genetic change in traits that were important in the system. The third dimension described genetic variation, both within and between pig breeds. The fourth dimension described the management of the breeding organisation, including communication, transparency, and technical and human resources. The results show substantial differences in the sustainability of breeding activities, both between farming systems within the same category and between different categories of farming systems. The breeding activities are assessed to be more sustainable for conventional systems than for differentiated systems in three of the four dimensions. In most differentiated farming systems, breeding goals are not related to the system, as these systems use the same genetic material as conventional systems. The breeds used in Traditional farming systems are important for genetic biodiversity, but the small scale of these systems renders them vulnerable. It is hoped that, by reflecting on different aspects of sustainability, this study will encourage sustainable developments in pig production.     

Microcystic adnexal carcinoma of the scalp treated with surgical resection along with chemoradiation: A case report and review of the literature

Microcystic adnexal carcinoma (MAC) is an infiltrative rare cutaneous neoplasm for which there are no consensus management guidelines because of the paucity of evidence-based practice; hence, the utility of their management is based only on previously published case reports. We report a case of a scalp lesion that was successfully treated using a combination of surgical resection, chemotherapy, and radiotherapy.     

反毒为药：精准控制河鲀毒素用作局部麻醉药的新进展

钠离子通道阻断剂河鲀毒素(TTX)是致命的毒素之一,却是极具价值的神经生物学和生理学等生命科学研究领域的工具药.近年来,越来越多的研究指出,TTX具有强大的局部麻醉潜能,有望成为替代氨基酯类和氨基酰胺类局部麻醉药、避免阿片类药物滥用的新型麻醉药物.本文综述TTX局部麻醉应用的辅助药物、TTX缓释及控释给药系统等相关研究,旨在为局部麻醉新药研发提供参考并探讨新的思路.     

Structural dynamics bridge the gap between the genetic and functional levels of GPCRs

G protein–coupled receptors (GPCRs) are implicated in nearly all physiological processes in the human body and represent an important drug targeting class. The genes encoding the different GPCR (sub)types determine their specific functionality, which can be altered by natural genetic variants and isoforms. Deciphering the molecular link between sequence diversity and its functional consequences is a current challenge and critical for the comprehension of the physiological response of GPCRs. It requires a global understanding of how protein sequence translates into protein structure, how this impacts the structural motions of the protein, and, finally, how all these factors determine the receptor functionality. Here, we discuss available resources and state-of-the-art computational approaches to address this question.     

Influence of learning on range expansion and adaptation to novel habitats

Learning has been postulated to ‘drive’ evolution, but its influence on adaptive evolution in heterogeneous environments has not been formally examined. We used a spatially explicit individual‐based model to study the effect of learning on the expansion and adaptation of a species to a novel habitat. Fitness was mediated by a behavioural trait (resource preference), which in turn was determined by both the genotype and learning. Our findings indicate that learning substantially increases the range of parameters under which the species expands and adapts to the novel habitat, particularly if the two habitats are separated by a sharp ecotone (rather than a gradient). However, for a broad range of parameters, learning reduces the degree of genetically‐based local adaptation following the expansion and facilitates maintenance of genetic variation within local populations. Thus, in heterogeneous environments learning may facilitate evolutionary range expansions and maintenance of the potential of local populations to respond to subsequent environmental changes.     

Trophic resource partitioning among five flatfish species (Actinopterygii, Pleuronectiformes) in a tropical bay in south-eastern Brazil

Five species of flatfishes in a tropical bay in south-eastern Brazil were studied to test the hypothesis that resource partitioning along the spatial and size dimensions has been used as a mechanism to enable coexistence. Three zones in the study area were defined according to environmental characteristics (inner, middle and outer). Sampling was conducted by otter trawl tows during daylight hours, between October 1998 and September 1999. Achiridae species ( Achirus lineatus and Trinectes paulistanus ) showed narrow niche width, indicating a specialized feeding strategy, preying on Polychaeta, and occurring mainly in the inner bay zone. Paralichthyidae ( Citharichthys spilopterus and Etropus crossotus ) and the Cynoglossidae ( Symphurus tessellatus ) showed broad niche width and a generalized feeding strategy preying on a large number of Crustacea. Symphurus tessellatus did not change diet with size-dimension feeding on Amphipoda and Polychaeta, whereas C. spilopterus and E. crossotus shifted diet with growth. Citharichthys spilopterus fed mainly on Mysida and secondarily on shrimps, with juvenile preying on large amounts of Calanoida, whereas adults consumed large amounts of fishes. Isaeidae amphipods were a significant prey for both small and large E. crossotus , whereas Polychaeta Errantia were used mainly by large fishes. Etropus crossotus and S. tessellatus share similar feeding resources in outer bay zone preying on Isaeidae and Polychaeta Errantia. Differences in the Pleuronectiformes diet composition along with spatial and size changes in the use of the available resources contributed to allow the organisms' coexistence in Sepetiba Bay. The high item diversity used by flatfishes indicates that the system plays an important role as a feeding ground, and that interspecific competition for food was unlikely.     

LOCAL ADAPTATION AND AGENTS OF SELECTION IN A MOBILE INSECT

The deme-formation hypothesis states that selection can produce adaptive genetic variation within and among phytophagous insect populations. We conducted three field experiments and tested this prediction by transferring eggs and measuring performance of a mobile leafmining insect, Stilbosis quadricustatella. In Experiment 1, we compared the rate of mine initiation of leafminers transferred to natal and novel sites. In Experiment 2, we compared mine-initiation rate of leafminers transferred to natal and novel host-plant species. In Experiment 3, we compared the mine-initiation rate, mine-completion rate, and sources of mortality of miners transferred to neighboring natal and novel Quercus geminata trees. In the first, second, and third experiments, leafminer larvae initiated significantly more mines at the natal site, on the natal plant species, and on the natal Q. geminata tree, evidence for adaptive differentiation. Furthermore, plant-mediated mortality was significantly lower among miners transferred to natal Q. geminata trees. This result supports a key assumption of the deme-formation hypothesis: insects adapt to the defensive phenotypes of individual trees. However, natural-enemy mortality was significantly higher among miners transferred to natal trees, essentially reversing the plant effect. Therefore, rates of successful mine completion were similar on natal (19%) and novel (17%) trees. This experiment suggests that host plants and natural enemies may represent opposing forces of selection. Leafminers adapted to individual trees may realize a selective advantage only when natural-enemy densities are low.