Frustraevo: a web server to localize and quantify the conservation of local energetic frustration in protein families.

According to the Principle of Minimal Frustration, folded proteins can only have a minimal number of strong energetic conflicts in their native states. However, not all interactions are energetically optimized for folding but some remain in energetic conflict, i.e. they are highly frustrated. This remaining local energetic frustration has been shown to be statistically correlated with distinct functional aspects such as protein-protein interaction sites, allosterism and catalysis. Fuelled by the recent breakthroughs in efficient protein structure prediction that have made available good quality models for most proteins, we have developed a strategy to calculate local energetic frustration within large protein families and quantify its conservation over evolutionary time. Based on this evolutionary information we can identify how stability and functional constraints have appeared at the common ancestor of the family and have been maintained over the course of evolution. Here, we present FrustraEvo, a web server tool to calculate and quantify the conservation of local energetic frustration in protein families.

Cadaveric study of the ultrasound-guided erector spinae plane block over the transverse process of the twelfth thoracic vertebra in dogs: Transversal vs longitudinal approach.

This study describes a transversal (TV) ultrasound-guided erector spinae plane (ESP) block technique over the transverse process of T12. And evaluates the distribution of the dye and affected nerves branches compared to a longitudinal (LNG) approach over the transverse process of T12 in canine cadavers. Secondly, it also compares de anatomy and dimensions of the transverse processes of T12 with T9 and T5. For this double-masked, cadaveric experimental study, 12 adult Beagle cadavers were injected with 0.6 mL/kg of dye/contrast. Spread was evaluated by computed tomography (CT) and dissection. Mean bodyweight was 9.76 (±0.59) kg. The TV and LNG approaches stained a median (range) of four (2-6) and three (1-6) medial branches of the dorsal rami of the spinal nerves, three (2-6) and three (2-5) lateral branches, and one (0-3) and one (0-4) ventral branches, respectively. Dye was detected in the epidural space in 55.6% and 66.7% of cases for the TV and LNG approaches, respectively (P=0.63). And in the ventral paravertebral compartment in 22.2% and lymphatics in 88.8% in both approaches. There were no statistical differences for the spread. The dorsolateral edge of the transverse process (TP) was not visible with CT at T12. The mean (±SD) length of the TP was significantly shorter at T12 [3.34 (±0.22)] mm, compared to T9 [6.08 (±0.47)] mm and T5 [5.93 (±0.62)] mm (P <0.001). This study showed similar distribution whether using a TV or LNG approach and differences in the anatomy and length of the T12 TP.

Three decades after the publication of the Lamendin method for adult age-at-death estimation: Methodological evolution of the procedure and interpretations.

More than three decades have passed since the publication of Lamendin et al.'s proposal in 1992. Over this time, numerous investigations have been conducted to assess the applicability of the technique in different populations with acceptable results in terms of estimation errors. The proposal by Lamendin and colleagues remains relevant today, and has made a significant contribution to adult age-at-death estimation due to its simplicity, repeatability, replicability, and high performance. Indeed, significant progress towards systematizing and strengthening the procedure has been reported in the published literature. One noteworthy advancement is the development of an international database that supports the use of Bayesian statistics for age-at-death estimation. This resource plays a crucial role in standardizing the methodology and improving the reliability for obtaining more reliable results on a global scale. The aim of this study is to investigate the historical evolution of the technique, to assess the accuracy of the results obtained by different analytic procedures, and to explore its impact in forensic applications through a systematic analysis of the specialized literature on this field. The current state of research indicates that this type of methodological research is an ongoing process, far from being completed. Many questions and challenges that require further attention to address effectively these issues remain unanswered, such as the development of non-linear regressions and probabilistic approaches, the deepening of procedures that improve global approximations, and the intensification of research focused on achieving more accurate estimations among individuals over 70 years-old. However, studies generally agree that the Lamendin technique works well for individuals between the ages of 30-60 years. It is still in force today, although the method has been significantly perfected. Despite the degree of research development in this area, further efforts are needed to improve the understanding and performance of these kinds of procedures. This will ultimately lead to an improvement in the accuracy and reliability of forensic investigation results worldwide.

Distribution of diversity of fishes in an Andean fluvial network

Introduction: The distribution of freshwater fishes in the Colombian Andes results from the interaction between historical and recent factors. Currently, the Andean landscape is facing rapid transformation processes. However, the knowledge regarding species distribution and environmental requirements is advancing slower than the transformations underway in the fluvial networks. Objective: To understand the conformation of the fish assemblage in the middle and lower Cauca River basin, considering the local environmental context before the construction of the Ituango Dam, and quantifying β diversity and its two components (turnover and nestedness) amongst local fish communities. Methods: 58 localities were monitored during nine years (between February 2010 and November 2018), the period before the dam's operation. The species richness (α-diversity), species turnover (β-diversity), and assemblage composition were estimated for the given localities. Results: 114 species were recorded, representing ~ 49 % of the total richness of known species for the Magdalena basin. The richness distribution showed that the number of species varies among the aquatic environments. Swamps presented the most significant number of species, followed by the Cauca River, while streams had the lowest values of richness. The spatial analyses of β-diversity revealed a high variation component in the study area due to species replacement between the aquatic environments. Conclusions: The implementation of long-term monitoring allowed us to recognize that the Cauca River basin conserves a great variety of species-rich environments. The species turnover indicates a high proportion of endemism or multiple sites with unique species. Finally, our study will serve as a baseline to verify, over time, whether the dam's construction is associated with essential changes in the structure of fish communities.

Introducción: La distribución de los peces de agua dulce en los Andes colombianos es el resultado de la interacción entre factores históricos y recientes. Actualmente, el paisaje Andino enfrenta procesos de rápida transformación. Sin embargo, el conocimiento sobre la distribución de las especies y sus requerimientos ambientales no avanza tan rápido como las transformaciones en curso en las redes fluviales. Objetivo: Comprender la conformación del ensamble de peces en la cuenca media y baja del río Cauca, considerando el contexto ambiental local antes de la construcción de la represa de Ituango, y cuantificar la diversidad beta y sus dos componentes (recambio y anidamiento) entre las comunidades de peces locales. Métodos: Se analizaron 58 localidades durante nueve años (entre febrero 2010 y noviembre 2018), período previo a la operación de la represa. La riqueza de especies (diversidad α), el recambio de especies (diversidad β) y la composición del conjunto se estimaron para las localidades dadas. Resultados: Se registraron 114 especies, que representan ~ 49 % de la riqueza total de especies conocidas para la cuenca del Magdalena. La distribución de la riqueza mostró que el número de especies varía entre los ambientes acuáticos. Las ciénagas presentaron el mayor número de especies, seguidas por el río Cauca, mientras que las quebradas presentaron los valores más bajos de riqueza. Los análisis espaciales de la diversidad β revelaron un alto componente de variación en el área de estudio debido al reemplazo de especies entre los ambientes acuáticos. Conclusiones: La implementación del monitoreo a largo plazo permitió reconocer que la cuenca del río Cauca conserva una gran variedad de ambientes ricos en especies. El recambio de especies indica una alta proporción de endemismo o múltiples sitios con especies únicas. Finalmente, nuestro estudio servirá como línea base para verificar, con el tiempo, si la construcción de la represa está asociada con cambios esenciales en la estructura de las comunidades de peces.

Local energetic frustration conservation in protein families and superfamilies.

Energetic local frustration offers a biophysical perspective to interpret the effects of sequence variability on protein families. Here we present a methodology to analyze local frustration patterns within protein families and superfamilies that allows us to uncover constraints related to stability and function, and identify differential frustration patterns in families with a common ancestry. We analyze these signals in very well studied protein families such as PDZ, SH3, ɑ and ß globins and RAS families. Recent advances in protein structure prediction make it possible to analyze a vast majority of the protein space. An automatic and unsupervised proteome-wide analysis on the SARS-CoV-2 virus demonstrates the potential of our approach to enhance our understanding of the natural phenotypic diversity of protein families beyond single protein instances. We apply our method to modify biophysical properties of natural proteins based on their family properties, as well as perform unsupervised analysis of large datasets to shed light on the physicochemical signatures of poorly characterized proteins such as the ones belonging to emergent pathogens.

Exploring the CO2 photocatalytic evolution onto the CuO (1 1 0) surface: A combined theoretical and experimental study.

A combined theoretical and experimental study was performed to elucidate the photocatalytic potential of tenorite, CuO (1 1 0) and to assess the evolution pathway of carbon dioxide (CO2) evolution pathway. The calculations were performed with density functional theory (DFT) at a DFT + U + J0 and spin polarized level. The CuO was experimentally synthesized and characterized with structural and optical methodologies. The band structure and density of states revealed the rise of band gaps at 1.24 and 1.03 eV with direct and indirect band gap nature, respectively. These values are in accordance with the experimental evidence at 1.28 and 0.96 eV; respectively, which were obtained by UV-Vis DRS. Such a behavior could be related to enhanced photocatalytic activity among copper oxide materials. Experimental evidence such as SEM images and work function measurements were also performed to evaluate the oxide. The redox potential suggests a catalytic character of tenorite (1 1 0) for the CO2 transformation through aldehydes (methanal) intermediate formation. Furthermore, a route through methylene glycol CH2(OH)2 was also explored with the theoretical methodology. The reaction path exhibits an immediate reduction of Image 1 into a •OH radical and an [OH]- anion, in the first step. This •OH radical attacks a double bond (C = O) of Image 2 to form bicarbonate ([Image 3]-) and subsequently, carbonic acid (Image 4). The carbonic acid reacts with other •OH radical to finally form orthocarbonic acid (Image 5).

Lipedema: What we don't know.

BACKGROUND: Lipedema is a loose connective tissue disease characterized by a disproportionate accumulation of adipose tissue in the limbs of women. Despite its incidence of 10-20%, lipedema is often underdiagnosed and misdiagnosed. OBJECTIVES: This review aims to outline current, available evidence regarding this enigmatic syndrome and gives a synopsis of the subjects that are still unknown. MATERIALS AND METHODS: PubMed and Embase searches were conducted to identify relevant articles on lipedema pathophysiology, clinical presentation, diagnosis, and treatment. RESULTS: Lipedema can be considered a disease of the adipocytes or a circulatory disorder of the lymphatics. The relationship between lymphatics and adipose tissue remains controversial. The clinical distinction between lipedema, lymphedema, phlebolymphedema, and lipolymphedema can be difficult. Diagnoses often coexist, further complicating the diagnosis of lipedema, which is currently made on clinical grounds alone. The value of diagnostic imaging studies is unclear. Liposuction appears to be an effective treatment and significantly improves symptoms. CONCLUSION: Diagnosing lipedema remains a challenge due to its heterogeneous presentation, co-existing diseases, and lack of objective diagnostic imaging. Further directions for research include the effect of excess skin resection surgery on lymphatic drainage.

1st ASCS: Expanding the ISCB Student Council Symposia to Asia.

Since 2004, the ISCB Student Council (ISCB-SC) has successfully organized Student Council Symposia across several continents, including North America, Latin America, Europe, and Africa, as well as local events led by more than 25 Regional Student Groups (RSG) across the world. The ISCB-SC Symposia provide students and early career researchers the chance to showcase their work at an international venue in a format that includes keynote talks, round table discussions, workshops, and more. After several efforts spanning several years to build enough critical mass in the region, we have successfully organized the first Asian Student Council Symposium (1st ASCS). This article discusses the organizational details of this unprecedented event, the challenges faced, and the lessons learned.

ISCB Student Council Symposium 2021, a virtual global venue: challenges and lessons learned.

Since 2004, the ISCB Student Council has been organizing different symposia worldwide, gathering together the community of young computational biologists. Due to the coronavirus disease 2019 (COVID-19) pandemic situation, the world scientific community was forced to cancel in-person meetings for almost two years, imposing the adoption of virtual formats instead. After the successful editions of our continental symposia in 2020 in the USA, Latin America, and Europe, we organized our flagship global event, the Student Council Symposium (SCS) 2021, trying to apply all previous lessons learned and to exploit the advantages that virtuality has to offer.

Robotic versus open lateral abdominal hernia repair: a multicenter propensity score matched analysis of perioperative and 1-year outcomes.

PURPOSE: Lateral abdominal hernias are inherently challenging surgical entities. As such, there has been an increase in the adoption of robotic platforms to approach these challenging hernias. Our study aims to assess and compare outcomes between open (oLAHR) and robotic (rLAHR) lateral abdominal hernia repair using a national hernia-specific database. METHODS: A retrospective review of prospectively collected data from the Abdominal Core Health Quality Collaborative was performed to include all adult patients who underwent elective lateral hernia repair. A propensity score match analysis was conducted, and univariate analyses were conducted to compare these two surgical modalities across perioperative timeframes. RESULTS: The database identified 2569 patients. Our analysis matched 665 patients to either the open or robotic groups. The median length of stay, surgical site occurrences (SSO), and surgical site occurrences requiring procedural interventions (SSOPI) were higher in the oLAHR versus the rLAHR group. Overall, oLAHR had a significantly higher rate of having any post-operative complications or any SSO/SSOPI. There was no difference in quality-of-life measures between groups at 30 days and 1 year. CONCLUSION: Robotic abdominal hernia repair is a safe alternative compared to the open repair of lateral abdominal hernias with better perioperative outcomes. Despite having a longer operative time, the robotic approach can offer a significantly shorter length of stay and an overall lower rate of complications. Ultimately, there is no difference in the quality-of-life measures both at 30 days and 1 year between the open and robotic approaches.

Resolving the fine structure in the energy landscapes of repeat proteins.

Ankyrin (ANK) repeat proteins are coded by tandem occurrences of patterns with around 33 amino acids. They often mediate protein-protein interactions in a diversity of biological systems. These proteins have an elongated non-globular shape and often display complex folding mechanisms. This work investigates the energy landscape of representative proteins of this class made up of 3, 4 and 6 ANK repeats using the energy-landscape visualisation method (ELViM). By combining biased and unbiased coarse-grained molecular dynamics AWSEM simulations that sample conformations along the folding trajectories with the ELViM structure-based phase space, one finds a three-dimensional representation of the globally funnelled energy surface. In this representation, it is possible to delineate distinct folding pathways. We show that ELViMs can project, in a natural way, the intricacies of the highly dimensional energy landscapes encoded by the highly symmetric ankyrin repeat proteins into useful low-dimensional representations. These projections can discriminate between multiplicities of specific parallel folding mechanisms that otherwise can be hidden in oversimplified depictions.

Conventional and advanced echocardiographic assessment of systolic function in dogs sedated with dexmedetomidine or acepromazine.

Dexmedetomidine and acepromazine, sedatives commonly used in dogs have opposite vascular effects, resulting in afterload increase and decrease, respectively. This could variably affect systolic myocardial function. Previous echocardiographic studies assessing the cardiovascular effects of these drugs used conventional echocardiography, while advanced techniques such as speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI), which are known to provide a more accurate assessment of systolic function, have been rarely used for this aim. Moreover, in the few studies using advanced techniques, the drugs where combined with opioids. Therefore, the main objective of this prospective study was to assess systolic myocardial function by conventional and advanced echocardiography (STE and TDI), in dogs sedated exclusively with dexmedetomidine or acepromazine not combined with other drugs. Twenty healthy dogs were randomly divided into two groups, Group A (acepromazine, 20 µg/kg IM), and Group D (dexmedetomidine, 5 µg/kg IM), cardiovascular parameters were assessed before sedation (T0), and thirty minutes afterwards (T1). Systolic arterial pressure and heart rate decreased in both groups at T1 as compared to T0. Only one conventional echocardiographic raw variable (left ventricular internal dimension in systole) and three out of five advanced echocardiographic variables (radial TDI systolic velocities at the epicardial region of the left ventricular free wall, longitudinal TDI systolic velocities of the septal mitral valve annulus and the STE-derived left ventricular global strain), were affected in Group D. A systolic impairment was observed in Group D and better estimated by advanced echocardiography. In Group A, only the end diastolic voume index (conventional echocardiography) was decreased. Both protocols seem to induce echocardiographic changes more likely secondary to their vascular action.

FrustratometeR: an R-package to compute local frustration in protein structures, point mutants and MD simulations.

SUMMARY: Once folded, natural protein molecules have few energetic conflicts within their polypeptide chains. Many protein structures do however contain regions where energetic conflicts remain after folding, i.e. they are highly frustrated. These regions, kept in place over evolutionary and physiological timescales, are related to several functional aspects of natural proteins such as protein-protein interactions, small ligand recognition, catalytic sites and allostery. Here, we present FrustratometeR, an R package that easily computes local energetic frustration on a personal computer or a cluster. This package facilitates large scale analysis of local frustration, point mutants and molecular dynamics (MD) trajectories, allowing straightforward integration of local frustration analysis into pipelines for protein structural analysis. AVAILABILITY AND IMPLEMENTATION: https://github.com/proteinphysiologylab/frustratometeR. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

6th European Student Council Symposium (ESCS): overcoming obstacles to enhance virtuality, connectivity, inclusivity and community engagement.

This editorial summarises the organisation, activities, and scientific content of the 6th European Student Council Symposium (ESCS) organised by the International Society for Computational Biology Student Council (ISCB-SC). The event was held on September 6, 2020, as a satellite event preceding the ISCB's  19th European Conference in Computational Biology. Both events were first planned to be held in-person in Sitges, Spain, but moved virtually as a strategy to face the SARS-CoV2 sanitary crisis. This completely unforeseen situation has posed several challenges that have been successfully addressed thanks to the robust ISCB Student Council community structure and the strong commitment of the organisers. Despite all the obstacles and challenges, we have found that virtuality has several advantages that can continue to be kept to improve in-person meetings in the future and make conferences more inclusive allowing a larger audience to participate.

Optimal treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with castration-resistant metastatic prostate cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate the impact of the hormonal treatment sequencing including abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) in mCRPC, and determine which sequence provides more benefits for patients. METHODS: Studies published in English between 1 January 2013 and 30 September 2017 were identified in PubMed and EMBASE electronic databases. Studies assessing the efficacy of treatment sequences, based on AAP and ENZ, in mCRPC patients, were eligible for analysis. RESULTS: Seventeen studies met the inclusion criteria. Two assessed both treatment sequences AAP â†’ ENZ and ENZ â†’ AAP; it was found that sequence of AAP â†’ ENZ showed a statistically significantly longer PSA-PFS than the observed in ENZ â†’ AAP (pooled HR: 0,54; 95% CI; 0,36-0,82; p < 0,05). The nine studies analysing Doc â†’ AAP â†’ ENZ sequence, revealed favourable results in terms of PFS. The 5 studies which analysed AAP â†’ ENZ sequence, show a decrease in PSA levels ≥ 50% in 11-41% of patients treated with enzalutamide after previous treatment with AAP. In the two studies that analysed the Doc â†’ ENZ â†’ AAP sequence, PSA response rates were much lower than those reported with Doc â†’ AAP â†’ ENZ, with decreases in PSA ≥ 30 of 3-18% and PSA ≥ 50 of 8-11%. CONCLUSION: Significant clinical efficacy of AAP administered as the first-line treatment in mCRPC patients followed by enzalutamide, delaying disease progression, compared with the ENZ â†’ AAP sequence. However, more studies and randomized trials are needed, to validate the best treatment sequencing.

Diagnostic challenges in von Willebrand disease. Report of two cases with emphasis on multimeric and molecular analysis.

Identification of qualitative variants of von Willebrand disease (VWD) can be a diagnostic challenge because of discrepant results obtained in the multiple laboratory tests available for its appropriate classification. We report two cases of infrequent inherited variants of VWD with unclear preliminary results with the test panel available at the time of first consultation and that were finally diagnosed as a VWD type 2A/IID with a c.8318 G > C, p.Cys2773Ser mutation and a VWD type 2M with c.4225 T > G, p.Val1409Phe mutation, respectively. The description of these two cases highlights that despite the limited diagnostic panel for the evaluation of von Willebrand Factor (VWF) functionality, the multimeric analysis and genetic family studies were fundamental tools to achieve the final diagnosis.

4th ISCB Latin American Student Council Symposium: a virtual and inclusive experience during COVID-19 times.

Since 2014, the ISCB Latin American Student Council Symposium (LA-SCS) serves as the main biannual activity where students from all levels, postdocs and early researchers from the entire Latin American region can gather to discuss recent advances in the fields of bioinformatics and computational biology. This time we faced a major unexpected obstacle, a worldwide pandemic that has completely disrupted human activities at a planetary scale. Countless conferences have been either canceled, reprogrammed for the next year or moved to a virtual format. However, thanks to an important strengthening of the Latin American student network and the creation of several new RSGs in the continent, we were able to get together a fearless team that aimed to overcome the pandemic obstacles and still organise the 4th LA-SCS. Here we summarize our experiences in our first virtual symposium.

Successful transcatheter pulmonary valve implantation in a dog: first clinical report.

Transcatheter pulmonary valve (TPV) implantation is a therapeutic approach approved by the United States Food and Drug Administration for human patients with failing pulmonary conduits in 2010 and for failing bioprosthetic surgical pulmonary valves in 2017. We report here the first successful transcatheter implantation of a stented valve in a pulmonary position in a dog with congenital pulmonary valve disease. A 3-year-old, 10.9 kg, client-owned Beagle dog was referred for a follow-up visit after a percutaneous balloon valvuloplasty performed 22 months before for treatment of a severe type A valvular pulmonary stenosis. The Doppler-derived peak pressure gradient was 348 mmHg before the procedure and 66 mmHg 24 h after. The dog was lethargic. Echocardiography revealed a mild pulmonary stenosis (pressure gradient-43 mmHg), severe pulmonary regurgitation, and secondary severe right ventricular and right atrial dilation. Worsening of right heart dilation was observed 2 months later despite medical therapy. A TPV implantation was performed using a prestented Melody bovine jugular bioprosthetic valve. The dog recovered uneventfully and was discharged 10 days after the procedure. Right heart dilation resolved within 15 days. The dog was doing well 7 months after valve implantation. This case demonstrates that TPV implantation with a stented valve is technically feasible in dogs with severe pulmonary valve disease. Stringent postoperative care, with particular attention to thrombosis and infectious endocarditis, and appropriate sizing and positioning of the valve stent are keys to the success of this procedure.