The Interaction of Caldesmon with the COOH Terminus of Actin

Caldesmon interacts with the NH2-terminal region of actin. It is now shown in airfuge centrifugation experiments that modification of the penultimate cysteine residue of actin significantly weakens its binding to caldesmon both in the presence and absence of tropomyosin. Furthermore, as revealed by fluorescence measurements, caldesmon increases the exposure of the COOH-terminal region of actin to the solvent. This effect of caldesmon, like its inhibitory effect on actomyosin ATPase activity, is enhanced in the presence of tropomyosin. Proteolytic removal of the last three COOH-terminal residues of actin, containing the modified cysteine residue, restores the normal binding between caldesmon and actin. These results establish a correlation between the binding of caldesmon to actin and the conformation of the COOH-terminal region of actin and suggest an indirect rather than direct interaction between caldesmon and this part of actin. Originally published Journal of Biological Chemistry, Vol. 266, No. 30, Oct 199

Extended Parental Care in Communal Social Groups

Recent developments in social insect research have challenged the need for close kinship as a prerequisite for the evolution of stable group living. In a model communal bee species, Lasioglossum (Chilalictus) hemichalceum, previous allozyme work indicated that groups of cooperating adult females are not relatives. Yet at any given time, not all group members perform the risky task of foraging. We previously hypothesized that tolerance for non-foragers was a component of extended parental care, previously known only for kin based social systems. DNA microsatellites were used to study colony genetic structure in order to test this hypothesis. Microsatellite polymorphism was substantial (He = 0.775). Overall intracolony relatedness, mainly of immatures, was low but significant in nine, late season nests (r = 0.136 ± 0.023), indicating that broods contain five to six unrelated sib ships. Detailed analyses of kinship between pairs of individuals revealed that most pairs were unrelated and most related pairs were siblings. Mothers are absent for 89–91% of the developing immature females, and 97% of developing males. Alternatively, 46% of adult females had neither sibs nor offspring in their nests. These findings indicate that the extended parental care model applies broadly to both kin based and nonkin based social systems in the Hymenoptera

Conditional mutualism emerges from a largely antagonistic species network

O correcto estadiamento do cancro do pulmão é importante porque as opções terapêuticas e o prognóstico variam significativamente com o estadio da doença. Este, tal como é feito para outros tumores sólidos, baseia-se no sistema TNM. A tomografia computorizada torácica é importante no estudo anatómico do tumor, da sua proximidade com estruturas locais e na invasão dos gânglios linfáticos hilares e mediastínicos. A tomografia por emissão de positrões fornece informação acerca da actividade funcional dos tecidos, tendo maiores sensibilidade e especificidade que a tomografia computorizada no estadiamento do mediastino. A avaliação clínica, que é composta pela história aprofundada e exame físico, continua a ser o melhor meio de predizer acerca de doença metastática. Se esta for negativa, estudos de imagem posteriores como a tomografia computorizada cerebral, cintigrama ósseo ou tomografia computorizada abdominal são desnecessários e a pesquisa de doença metastática está completa. Caso existam sinais ou sintomas de metastização, deverá ser iniciada uma sequência de exames de imagem, de acordo com aos dados obtidos na avaliação clínica. Uma grande variedade de exames invasivos está disponível para o estadiamento do cancro do pulmão. Cada um deles tem especificidades técnicas e de acuidade diagnóstica que os tornam mais ou menos apropriados consoante a localização da lesão. Assim, a comparação directa entre estes testes invasivos não é possível e o problema é definir qual dos procedimentos é mais útil em cada situação. O estadiamento molecular pode vir a ser um importante meio no estadiamento e estratificação prognóstica dos doentes com cancro do pulmão. No entanto ainda existem alguns problemas que têm limitado a aplicação deste conceito.The correctly staging of lung cancer is important because the treatment options and prognosis differ significantly with the stage of disease. This, as is done for other solid tumors, based on the TNM system. Chest TC imaging is important in the study of the anatomy of tumor, its proximity with local structures and the invasion of mediastinal and hilar lymph nodes. Positron emission tomography provides information about the functional activity of tissues with greater sensitivity and specificity than chest CT in the staging of the mediastinum. The clinical evaluation, which is made by thorough history and physical examination, remains the best way to predict about metastatic disease. If this is negative, further imaging studies such as CT scan of the head, bone scan or abdominal CT scan are unnecessary and the search for metastatic disease is complete. If there are signs or symptoms of metastasis, should be initiated a series of imaging tests, according to data obtained in the clinical evaluation. A variety of invasive tests are available for the staging of lung cancer. Each of them has specific technical and diagnostic accuracy that makes them more or less appropriate depending on the location of the lesion. Thus, direct comparisons between these invasive tests are not possible and the problem is to define which procedures are most useful in each situation. Molecular staging may prove to be an important tool in the staging and prognostic stratification of patients with lung cancer. However, there are still some problems that have limited the application of the concept

The emerging field of venom-microbiomics for exploring venom as a microenvironment, and the corresponding Initiative for Venom Associated Microbes and Parasites (iVAMP)

Venom is a known source of novel antimicrobial natural products. The substantial, increasing number of these discoveries have unintentionally culminated in the misconception that venom and venom-producing glands are largely sterile environments. Culture-dependent and -independent studies on the microbial communities in venom microenvironments reveal the presence of archaea, algae, bacteria, endoparasites, fungi, protozoa, and viruses. Venom-centric microbiome studies are relatively sparse to date and the adaptive advantages that venom-associated microbes might offer to their hosts, or that hosts might provide to venom-associated microbes, remain unknown. We highlight the potential for the discovery of venom-microbiomes within the adaptive landscape of venom systems. The considerable number of known, convergently evolved venomous animals juxtaposed with the comparatively few studies to identify microbial communities in venom provides new possibilities for both biodiversity and therapeutic discoveries. We present an evidence-based argument for integrating microbiology as part of venomics to which we refer to as venom-microbiomics. We also introduce iVAMP, the Initiative for Venom Associated Microbes and Parasites (https://ivamp-consortium.github.io/), as a growing consortium for interested parties to contribute and collaborate within this subdiscipline. Our consortium seeks to support diversity, inclusion and scientific collaboration among all researchers interested in this subdiscipline

Biogeography of mutualistic fungi cultivated by leafcutter ants

Leafcutter ants propagate co-evolving fungi for food. The nearly 50 species of leafcutter ants (Atta, Acromyrmex) range from Argentina to the United States, with the greatest species diversity in southern South America. We elucidate the biogeography of fungi cultivated by leafcutter ants using DNA sequence and microsatellite-marker analyses of 474 cultivars collected across the leafcutter range. Fungal cultivars belong to two clades (Clade-A and Clade-B). The dominant and widespread Clade-A cultivars form three genotype clusters, with their relative prevalence corresponding to southern South America, northern South America, Central and North America. Admixture between Clade-A populations supports genetic exchange within a single species, Leucocoprinus gongylophorus. Some leafcutter species that cut grass as fungicultural substrate are specialized to cultivate Clade-B fungi, whereas leafcutters preferring dicot plants appear specialized on Clade-A fungi. Cultivar sharing between sympatric leafcutter species occurs frequently such that cultivars of Atta are not distinct from those of Acromyrmex. Leafcutters specialized on Clade-B fungi occur only in South America. Diversity of Clade-A fungi is greatest in South America, but minimal in Central and North America. Maximum cultivar diversity in South America is predicted by the Kusnezov–Fowler hypothesis that leafcutter ants originated in subtropical South America and only dicot-specialized leafcutter ants migrated out of South America, but the cultivar diversity becomes also compatible with a recently proposed hypothesis of a Central American origin by postulating that leafcutter ants acquired novel cultivars many times from other nonleafcutter fungus-growing ants during their migrations from Central America across South America. We evaluate these biogeographic hypotheses in the light of estimated dates for the origins of leafcutter ants and their cultivars

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder