Why did she send it in the first place? Victim blame in the context of ‘revenge porn’

‘Revenge porn’ or ‘cyber rape’ occurs when intimate images that were previously sent with permission are leaked to a wider audience without consent. This research investigated the perceptions that individuals form about ‘revenge porn’ victims, aiming to gain more understanding from a victimisation perspective as a first step towards improving victim outcomes. One hundred and twenty-two individuals were presented with a scenario depicting a leaked intimate image with a female victim. Two distinct nudity levels: low (lingerie) and high (bare-chest, breasts exposed) were included, and participants’ responses to the Sexual Double Standards Scale were analysed to determine whether acceptance of the traditional sexual double standard was correlated with victim perception. Results indicated that victims were perceived as more promiscuous and more blameworthy when they were more naked, and by participants with more traditional gender roles. There is a need for policy to address potential stigma directed at ‘revenge porn’ victims.     

Panoramic view of a superfamily of phosphatases through substrate profiling

Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified iso-functional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process.Since the first genomes were sequenced, there has been an exponential increase in the number of protein sequences deposited into databases worldwide. At the time of this writing the UniProtKB/TrEMBL database contains over 32 million protein sequences. Although this increase in sequence data has dramatically enhanced our understanding of the genomic organization of organisms, as the number of protein sequences grows, the proportion of firm functional assignments diminishes. Traditionally, methods of functional annotation involve comparing sequence identity between experimentally characterized proteins and newly sequenced ones, typically via BLAST (1). In cases where significant sequence similarity cannot be ascertained, proteins are annotated as “hypothetical” or “putative.” Moreover, the decrease in sequence identity leads to an increased uncertainty in functional assignment, especially as the phylogenetic distance between organisms grows, limiting iso-functional ortholog discovery.As the number of newly sequenced genomes grows larger, more protein sequences are likely to be misannotated, oftentimes resulting in the propagation of incorrect functional annotation across newly identified sequences. To tackle the problem of unannotated or misannotated proteins, newer methods for computational assignment have been created with varying degrees of success (2). Although these methods outperform historical methods, continued improvement is necessary to ensure accurate annotation of function (2). A greater swath of functional space can be covered by screening substrates in a high-throughput manner on multiple enzymes from a family (3, 4). Family-wide substrate profiling offers a data-rich resource. The use of sparse screening of sequence space and a diversified library permits the determination of substrate specificity profiles to provide a family-wide view of the range of substrates and insight into the structure of the prototypical substrate. Where structures are available, correlation between substrate range and structural determinants of specificity can be achieved. In addition, the approach has utility in genomic annotation (inferred function), iso-functional ortholog assignment, and the assignment of in vitro substrate profiles to orphaned PDB entries (enzymes with structure but no function, or SNFs). Here we report the application of in vitro high-throughput functional screening of metabolites and related compounds at the superfamily level. We use as an example prokaryotic members of the haloalkanoic acid dehalogenase superfamily (HADSF), a diverse superfamily of enzymes (5) that catalyze a wide range of reactions involving the formation of a covalent intermediate with an active-site aspartate. Reactions catalyzed by this superfamily include dehalogenation (6) as well as Mg²⁺-dependent phosphoryltransfer, although the vast majority (∼99%) are phosphotransferases (7). Members of the HADSF share a Rossmannoid fold “core” domain that contains the phosphoryl transfer site (8, 9) and a “cap” domain that provides substrate specificity determinants (10). There are three major types of caps in the HADSF (C0, C1, and C2A/C2B; see SI Appendix, Fig. S1) based on size, position of insert within the Rossmann fold, and overall topology (7). At the time of writing, the HADSF is known to comprise over 120,000 members across the three domains of life with at most 3% associated with an EC identifier (11).In this study, the functional space of the HADSF was sampled by screening a customized substrate library of 167 compounds against over 200 enzymes from numerous prokaryotic species. The study revealed that a large number of family members show a broad substrate range, with the majority of the HADSF enzymes reacting with five or more substrates. Thus, widespread promiscuity is not incompatible with participation in cell metabolism and may be advantageous to the evolution of new enzyme activities. The activity profiling when applied to putative iso-functional orthologs allowed us to infer annotation for ∼35% of the HADSF. Intriguingly, the HADSF subfamily with the least structural elaboration of the core catalytic Rossmann fold was the most specific with respect to substrate range and number, implying that domain insertions drive the evolution of new functions and that the broad specificity observed in the HADSF may be a relic of this process.     

An efficient,multiply promiscuous hydrolase in the alkaline phosphatase superfamily

We report a catalytically promiscuous enzyme able to efficiently promote the hydrolysis of six different substrate classes. Originally assigned as a phosphonate monoester hydrolase (PMH) this enzyme exhibits substantial second-order rate accelerations ((k_cat/K_M)/k_w), ranging from 10⁷ to as high as 10¹⁹, for the hydrolyses of phosphate mono-, di-, and triesters, phosphonate monoesters, sulfate monoesters, and sulfonate monoesters. This substrate collection encompasses a range of substrate charges between 0 and -2, transition states of a different nature, and involves attack at two different reaction centers (P and S). Intrinsic reactivities (half-lives) range from 200 days to 10⁵ years under near neutrality. The substantial rate accelerations for a set of relatively difficult reactions suggest that efficient catalysis is not necessarily limited to efficient stabilization of just one transition state. The crystal structure of PMH identifies it as a member of the alkaline phosphatase superfamily. PMH encompasses four of the native activities previously observed in this superfamily and extends its repertoire by two further activities, one of which, sulfonate monoesterase, has not been observed previously for a natural enzyme. PMH is thus one of the most promiscuous hydrolases described to date. The functional links between superfamily activities can be presumed to have played a role in functional evolution by gene duplication.     

376例性乱者乙型肝炎感染状况调查分析

目的：了解大连市性乱人群乙型肝炎感染状况，为今后加强对该类人群的监督检测工作提供依据。方法：对该人群进行流行病学调查及采集血清样本进行相关检测。结果：性乱者乙肝感染率明显高于正常人群，且随着年龄的增长而增加。结论：性乱人群是乙肝的高危人群，性传播HBV是成人慢性HBV感染的潜在来源，不容忽视。     

Cellular crowding imposes global constraints on the chemistry and evolution of proteomes

In living cells, functional protein–protein interactions compete with a much larger number of nonfunctional, or promiscuous, interactions. Several cellular properties contribute to avoiding unwanted protein interactions, including regulation of gene expression, cellular compartmentalization, and high specificity and affinity of functional interactions. Here we investigate whether other mechanisms exist that shape the sequence and structure of proteins to favor their correct assembly into functional protein complexes. To examine this question, we project evolutionary and cellular abundance information onto 397, 196, and 631 proteins of known 3D structure from Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens, respectively. On the basis of amino acid frequencies in interface patches versus the solvent-accessible protein surface, we define a propensity or “stickiness” scale for each of the 20 amino acids. We find that the propensity to interact in a nonspecific manner is inversely correlated with abundance. In other words, high abundance proteins have less sticky surfaces. We also find that stickiness constrains protein evolution, whereby residues in sticky surface patches are more conserved than those found in nonsticky patches. Finally, we find that the constraint imposed by stickiness on protein divergence is proportional to protein abundance, which provides mechanistic insights into the correlation between protein conservation and protein abundance. Overall, the avoidance of nonfunctional interactions significantly influences the physico-chemical and evolutionary properties of proteins. Remarkably, the effects observed are consistently larger in E. coli and S. cerevisiae than in H. sapiens, suggesting that promiscuous protein–protein interactions may be freer to accumulate in the human lineage.     

2007—2011年无锡市惠山区性乱人群STD/AIDS监测结果分析

目的了解无锡市惠山区性乱人群性传播疾病(STD)和艾滋病(AIDS)监测情况,为制定STD/AIDS防控措施提供依据。方法利用2007—2011年惠山区性乱人群的STD/AIDS的监测结果,分析全区高危人群STD/AIDS疫情。结果在931例性乱人群中监测出STD/AIDS 85例(男17例,女68例),男女之比1∶4。暗娼30岁者占69.12%(47/68),嫖客50岁者占47.06%(8/17)。梅毒68例,感染率为7.30%(68/931);尖锐湿疣14例,感染率为1.50%(14/931);淋病1例,感染率为0.11%(1/931);HIV 2例,感染率为0.21%(2/931)。暗娼人群外来人口占95.59%(65/68),嫖客人群本地区占41.18%(7/17)。结论无锡市惠山区2007—2011年性乱人群中STD/AIDS的感染率处于低水平,但梅毒的感染率呈上升趋势,感染STD/AIDS的危险因素普遍存在,需加大STD/AIDS的监测,降低其传播和流行。     

Female extrapair mating behavior can evolve via indirect selection on males

In many species that form socially monogamous pair bonds, a considerable proportion of the offspring is sired by extrapair males. This observation has remained a puzzle for evolutionary biologists: although mating outside the pair bond can obviously increase the offspring production of males, the benefits of such behavior to females are less clear, yet females are known to actively solicit extrapair copulations. For more than two decades adaptionist explanations have dominated the discussions, yet remain controversial, and genetic constraint arguments have been dismissed without much consideration. An intriguing but still untested hypothesis states that extrapair mating behavior by females may be affected by the same genetic variants (alleles) as extrapair mating behavior by males, such that the female behavior could evolve through indirect selection on the male behavior. Here we show that in the socially monogamous zebra finch, individual differences in extrapair mating behavior have a hereditary component. Intriguingly, this genetic basis is shared between the sexes, as shown by a strong genetic correlation between male and female measurements of extrapair mating behavior. Hence, positive selection on males to sire extrapair young will lead to increased extrapair mating by females as a correlated evolutionary response. This behavior leads to a fundamentally different view of female extrapair mating: it may exist even if females obtain no net benefit from it, simply because the corresponding alleles were positively selected in the male ancestors.     

药物的杂泛性

成功的药物应具备两个要素:足够强度和选择性的药理作用,适宜的物理化学、药代、安全和结构新颖的成药性。药物的杂泛性涉及到这两个方面。杂泛性是指一种药物与多种靶标发生相互作用,而引起相同或不同的药理作用的现象,药物的杂泛性是多重药理学的基础,也是药物产生副作用和药代动力学不合理的原因。药物产生杂泛性的根源是蛋白的杂泛性,在进化过程中,为了结合、代谢和清除结构多样的内源和外源性物质,蛋白具有广泛和可变的结构容纳性,无需对每种化合物都准备特异的蛋白,体现了受体的杂泛性。靶标蛋白具有保守性和多样性。保守性体现在折叠成二级结构的结构域比较固定和保守,因而与配体分子的结合互有交盖,发生交叉反应性。多样性体现在精细的结构内涵,相似的结构域因为有不同的氨基酸序列,功能是不同的,体现了特异性,因而靶标多为一专多能的蛋白。利用杂泛性以设计(design in)治疗复杂疾病的多靶标药物,摒弃(design out)杂泛性的不利因素以完善成药性。所以认真分析和处置功过参半的杂泛性是提高药物设计成功率的重要保证,正确预测配体的杂泛性也是分子设计的终极目标。本文对受体、酶、离子通道和细胞色素CYP450等与配体的杂泛性和药物设计的关系进行...     

Promiscuous T cell recognition of an H-2 IA-presented mycobacterial epitope

Genetically permissive T cell epitopes are an important prerequisite for the development of peptide-based vaccines or immunodiagnostic reagents. We have investigated the structural requirements of permissive T cell recognition of peptide p350—369 from the 38-kDa antigen of Mycobacterium tuberculosis. This peptide was found to be immunogenic in mice of the H-2^{b, bm12, d. s and k}, but not of the H-2^f genotype. T cell responses were restricted by I-A class II molecules. The same epitope core was recognized in the H-2^{b, d and k} genotypes. T cell hybrids from BALB/c and C57BL/10 mice were used to determine: (i) the critical residues using substituted peptide derivatives and (ii) the degree of T cell promiscuity. Two out of five BALB (H-2^d)-derived hybridomas tested displayed promiscuous peptide recognition in the context of H-2^b and H-2^bm12 antigen-presenting cells. The recognition of critical residues was found to be uniform for all five hybridomas when tested with syngeneic antigen-presenting cells; additional critical residues were identified when the peptide was recognized in the context of allogeneic antigen-presenting cells. Only one of the four tested C57BL/10 (H-2^b) hybridomas showed promiscuity in the context of H-2^bm12. Each of these C57BL/10-derived clones had a distinct response profile toward the critical residues. We propose that the demonstrated T cell promiscuity involves peptide interaction with polymorphic H-2 I-A residues.