Nuevos retos moleculares en la conservación animal

The contribution of genetics to wildlife conservation has been stressed often forgetting the existing theoretical and empirical limitations in the use of genetic information to solve ecological and demographic problems. The possibilities of molecular analyses are extensive and the automation of procedures is increasing the efficiency and reducing the cost of molecular technology. With large amounts of molecular data already available, the interest is switching towards the analysis of these data and the interpretation of genetic variability within and across species from a functional perspective. The understanding of the link between genetic variation and fitness or survival is essential in conservation biology and this understanding needs the combination of molecular data with non–molecular (e.g. physiological, behavioural and ecological) data. Progress in this promising field will depend on the trust and collaboration between molecular and field biologists.La contribución de la genética a la conservación de la vida salvaje ha sido enfatizada, olvidándose a menudo que existen limitaciones teóricas y empíricas sobre el uso de la información genética para solucionar problemas ecológicos y demográficos. Los análisis moleculares ofrecen numerosas posibilidades y la automatización de los procesos está incrementando la eficiencia y reduciendo los costes de la tecnología molecular. Con grandes cantidades de datos moleculares ya disponibles, el interés se está desplazando hacia el análisis de dichos datos y la interpretación de la variabilidad genética intraespecífica e interespecífica desde una perspectiva funcional. La comprensión del vínculo entre variabilidad genética y eficacia biológica o supervivencia es esencial en la biología de la conservación, requiriendo esta comprensión la combinación de datos moleculares con datos no moleculares (por ejemplo fisiológicos, de comportamiento y ecológicos). El progreso en este campo tan prometedor debe basarse en la confianza y la colaboración entre biólogos moleculares y de campo

Effects of thymbra capitate essential oil on in vitro fermentation end-products and ruminal bacterial communities

13 páginas, 5 figuras, 3 tablas.An in vitro trial was carried out to investigate the effects of natural Thymbra capitata essential oil (NEO) and its main compounds [including carvacrol, p-cymene, γ-terpinene given alone or in a synthetic combination (SEO)] on ruminal fermentation and the bacterial community using batch cultures inoculated with ruminal digesta and incubating two different basal diets [high-forage (F) and high-concentrate (C) diet]. After 24 h of incubation, primary fermentation end-products [gas, methane, volatile fatty acids (VFAs) and ammonia] and rumen microbial diversity were determined. NEO reduced the total VFA concentration (P  0.05) by any of the experimental treatments or diets evaluated. Microbial diversity analysis showed only a moderate effect of carvacrol and SEO on 13 genera, including, mainly, Atopobium and Blautia (involved in subacute ruminal acidosis) or Candidatus Saccharimonas (related to laminitis). In conclusion, T. capitata EO has a limited potential to attain nutritional or environmental benefits, but further research should be carried out to clarify its effects on animal health and microbial food safety.Tis work was funded by CSIC (Proyectos Intramurales Especiales, 201940E115) and MUR (Direzione Generale dell’internazionalizzazione e della comunicazione Programma cooperazione internazionale PRIMA—Decreto Ministeriale 26 luglio 2016 n. 593) in the context of the MILKQUA-H2020-PRIMA 2018—Section 2. Alba Martín gratefully acknowledges receipt of a pre-doctoral grant (PRE2019-089288) from Ministerio de Ciencia e Innovación (MCIN/AEI/10.13039/501100011033, "El FSE invierte en tu futuro").Peer reviewe

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl− channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis

Modifiable risk factors associated with prediabetes in men and women: A cross-sectional analysis of the cohort study in primary health care on the evolution of patients with prediabetes

Background: Prediabetes is a high-risk state for diabetes development, but little is known about the factors associated with this state. The aim of the study was to identify modifiable risk factors associated with the presence of prediabetes in men and women. Methods: Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS-Study) is a prospective study on a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects without glucose metabolism disorders. It is being conducted by 125 general practitioners in Spain. Data for this analysis were collected during the baseline stage in 2012. The modifiable risk factors included were: smoking habit, alcohol consumption, low physical activity, inadequate diet, hypertension, dyslipidemia, and obesity. To assess independent association between each factor and prediabetes, odds ratios (ORs) were estimated using logistic regression models. Results: Abdominal obesity, low plasma levels of high-density lipoprotein cholesterol (HDL-cholesterol), and hypertension were independently associated with the presence of prediabetes in both men and women. After adjusting for all factors, the respective ORs (95% Confidence Intervals) were 1.98 (1.41-2.79), 1.88 (1.23-2.88) and 1.86 (1.39-2.51) for men, and 1.89 (1.36-2.62), 1.58 (1.12-2.23) and 1.44 (1.07-1.92) for women. Also, general obesity was a risk factor in both sexes but did not reach statistical significance among men, after adjusting for all factors. Risky alcohol consumption was a risk factor for prediabetes in men, OR 1.49 (1.00-2.24). Conclusions: Obesity, low HDL-cholesterol levels, and hypertension were modifiable risk factors independently related to the presence of prediabetes in both sexes. The magnitudes of the associations were stronger for men than women. Abdominal obesity in both men and women displayed the strongest association with prediabetes. The findings suggest that there are some differences between men and women, which should be taken into account when implementing specific recommendations to prevent or delay the onset of diabetes in adult population

Arthropod Phylogenetics in Light of Three Novel Millipede (Myriapoda: Diplopoda) Mitochondrial Genomes with Comments on the Appropriateness of Mitochondrial Genome Sequence Data for Inferring Deep Level Relationships

Background Arthropods are the most diverse group of eukaryotic organisms, but their phylogenetic relationships are poorly understood. Herein, we describe three mitochondrial genomes representing orders of millipedes for which complete genomes had not been characterized. Newly sequenced genomes are combined with existing data to characterize the protein coding regions of myriapods and to attempt to reconstruct the evolutionary relationships within the Myriapoda and Arthropoda. Results The newly sequenced genomes are similar to previously characterized millipede sequences in terms of synteny and length. Unique translocations occurred within the newly sequenced taxa, including one half of the Appalachioria falcifera genome, which is inverted with respect to other millipede genomes. Across myriapods, amino acid conservation levels are highly dependent on the gene region. Additionally, individual loci varied in the level of amino acid conservation. Overall, most gene regions showed low levels of conservation at many sites. Attempts to reconstruct the evolutionary relationships suffered from questionable relationships and low support values. Analyses of phylogenetic informativeness show the lack of signal deep in the trees (i.e., genes evolve too quickly). As a result, the myriapod tree resembles previously published results but lacks convincing support, and, within the arthropod tree, well established groups were recovered as polyphyletic. Conclusions The novel genome sequences described herein provide useful genomic information concerning millipede groups that had not been investigated. Taken together with existing sequences, the variety of compositions and evolution of myriapod mitochondrial genomes are shown to be more complex than previously thought. Unfortunately, the use of mitochondrial protein-coding regions in deep arthropod phylogenetics appears problematic, a result consistent with previously published studies. Lack of phylogenetic signal renders the resulting tree topologies as suspect. As such, these data are likely inappropriate for investigating such ancient relationships

Mutations disrupting neuritogenesis genes confer risk for cerebral palsy

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy

Step-wise evolution of complex chemical defenses in millipedes: a phylogenomic approach

With fossil representatives from the Silurian capable of respiring atmospheric oxygen, millipedes are among the oldest terrestrial animals, and likely the first to acquire diverse and complex chemical defenses against predators. Exploring the origin of complex adaptive traits is critical for understanding the evolution of Earth’s biological complexity, and chemical defense evolution serves as an ideal study system. The classic explanation for the evolution of complexity is by gradual increase from simple to complex, passing through intermediate “stepping stone� states. Here we present the first phylogenetic-based study of the evolution of complex chemical defenses in millipedes by generating the largest genomic-based phylogenetic dataset ever assembled for the group. Our phylogenomic results demonstrate that chemical complexity shows a clear pattern of escalation through time. New pathways are added in a stepwise pattern, leading to greater chemical complexity, independently in a number of derived lineages. This complexity gradually increased through time, leading to the advent of three distantly related chemically complex evolutionary lineages, each uniquely characteristic of each of the respective millipede groups

Deciphering the quality of SARS-CoV-2 specific T-cell response associated with disease severity, immune memory and heterologous response

SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study, we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-γ with the absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalised and previously hospitalised patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalised patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 healthy donors’ samples. These results could have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies.NIH (contract to AS, DW), Grant/AwardNumber: 75N9301900065; “Contratación de Personal Investigador Doctor”supported by the European Social Fund and Junta de Andalucía (PAIDIDOCTOR- Convocatoria 2019-2020 toFJO, SB); Instituto de Salud Carlos III,Fondos FEDER. ERM was supported bythe Spanish Research Council (CSIC);Consejería de Transformación Económica, Industria, Conocimiento y Universidades Junta de Andalucía (research project to ERM), Grant/AwardNumber: CV20-85418; Red Temática de Investigación Cooperativa en SIDA, whichis included in the Acción Estratégica en Salud, Plan Nacional de InvestigaciónCientífica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016,Grant/Award Numbers: RD16/0025/0020,RD16/0025/0026; Consejeria de Salud Junta de Andalucia (Research contract toJV), Grant/Award Number:RH-0037-2020; Instituto de Salud CarlosIII (PI19/01127 to ERM, CP19/00159 toAGV, FI17/00186 to MRJL, FI19/00083 toCGC, CM20/00243 to APG andCOV20/00698 to support COHVID-GS)Peer reviewe

Description of SARS-CoV-2 T-cell polyfunctionality features

SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-gamma; with absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalized and previously hospitalized patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalized patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses, were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 samples from healthy donors. These results have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies.Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades Junta de Andalucia (research Project CV20-85418) (ERM) NIH contract 75N9301900065 (AS, DW) Consejeria de Salud Junta de Andalucia (Research Contract RH-0037-2020 to JV) Instituto de Salud Carlos III (CP19/00159 to AGV, FI17/00186 to MRJL, FI19/00083 to CGC, CM20/00243 to APG and COV20/00698 to support COHVID-GS) Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020; RD16/0025/0026), which is included in the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016 Instituto de Salud Carlos III, Fondos FEDER. ERM was supported by the Spanish Research Council (CSIC). “Contratación de Personal Investigador Doctor” supported by the European Social Fund and Junta de Andalucía (PAIDI DOCTOR- Convocatoria 2019-2020). (FJO, SB).N