Social environment as a cause of litter loss in laboratory mouse: A behavioural study

Perinatal mortality is a widespread problem in laboratory mouse breeding and is often manifested by the loss of the entire litter within the first days of life. High mortality is an animal health and welfare concern that violates the 3R principles of reduction and refinement. High pup mortality is often considered “normal” in mouse breeding and the underlying causes are poorly understood. This study investigated the role of the social environment on pup survival and parental behaviour in C57BL/6 mice. Before parturition, multiparous females were allocated to three treatments: single-housing (SH, n=54) or group-housing in trios of two females and a male, with group-housing further divided into trios with (GH1, n=20) or without (GH0, n=35) the presence of another litter. Mouse behaviour was recorded from 24h before to 24h after parturition. Mouse breeding performance (offspring survival and weight) was analysed using logistic and generalized linear models, and behaviours using logistic and multivariable linear models. We confirmed previous findings of high mortality rates for all treatments, but the highest rates were found in GH1 where half of the litters were lost entirely. Social environment had an impact on breeding performance. On the one hand, the presence of adult cagemates in GH0 did not affect litter survival nor pup body weight at 20 days. Adult cagemates shared the work of breeding by performing nest building before and after litter birth, and parental care after birth. GH0 and GH1 dams were less frequently seen performing nest building before and after parturition than SH dams. GH0 and GH1 dams were also less frequently seen inside the nest and performing parental behaviour after parturition than were SH dams. On the other hand, the risks for litter and pup loss were dramatically increased by 2.3 and 1.8 times, respectively, in GH1 compared to GH0. Parturition lasted longer in GH1 than in GH0 treatment. While dam behaviour did not differ between GH1 and GH0, GH1 adult cagemates spent less time performing parental care than did GH0 cagemates. Plausible reasons for the higher mortality in the presence of another litter are insufficient parental care, competition for milk access, poor nest quality, and crushing of newborns by older pups in the nest. This study indicates that being born in a cage where there is already an older litter, so-called reproductive asynchrony, is a major risk factor for litter loss.The authors would like to thank Paula Sofia Vilares Gouveia and Sara Capas Peneda who participated in the behavioural analyses, and all the staff at the Biological Support Unit of the Babraham Institute for their interest and support in the project and the care of the animals. This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/CVT-WEL/1202/2014 (POCI-01- 0145-FEDER-016591)

Antimicrobial peptides as potential anti-tubercular leads: A concise review

Despite being considered a public health emergency for the last 25 years, tuberculosis (TB) is still one of the deadliest infectious diseases, responsible for over a million deaths every year. The length and toxicity of available treatments and the increasing emergence of multidrugresistant strains of Mycobacterium tuberculosis renders standard regimens increasingly inefficient and emphasizes the urgency to develop new approaches that are not only cost-and time-effective but also less toxic. Antimicrobial peptides (AMP) are small cationic and amphipathic molecules that play a vital role in the host immune system by acting as a first barrier against invading pathogens. The broad spectrum of properties that peptides possess make them one of the best possible alternatives for a new “post-antibiotic” era. In this context, research into AMP as potential anti-tubercular agents has been driven by the increasing danger revolving around the emergence of extremely-resistant strains, the innate resistance that mycobacteria possess and the low compliance of patients towards the toxic anti-TB treatments. In this review, we will focus on AMP from various sources, such as animal, non-animal and synthetic, with reported inhibitory activity towards Mycobacterium tuberculosis.This research was funded by Fundação para a Ciência e Tecnologia (FCT), Portugal, through projects UIDB/50006/2020, and PTDC/BTM-SAL/29786/2017

The influence of socioeconomic, biogeophysical and built environment on old-age survival in a Southern European city

Old-age survival is a good indicator of population health and regional development. We evaluated the spatial distribution of old-age survival across Porto neighbourhoods and its relation with physical (biogeophysical and built) and socioeconomic factors (deprivation). Smoothed survival rates and odds ratio (OR) were estimated using Bayesian spatial models. There were important geographical differentials in the chances of survival after 75 years of age. Socioeconomic deprivation strongly impacted old-age survival (Men: least deprived areas OR=1.31(1.05-1.63); Women OR=1.53(1.24-1.89)), explaining over 40% of the spatial variance. Walkability and biogeophysical environment were unrelated to old-age survival and also unrelated to socioeconomic deprivation, being fairly evenly distributed through the city

Genome-wide signatures of complex introgression and adaptive evolution in the big cats.

The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages

The E3 ubiquitin ligase SCF(Fbxo7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-κB signaling pathway.

BACKGROUND: Ubiquitously eXpressed Transcript isoform 2 (UXTV2) is a prefoldin-like protein involved in NF-κB signaling, apoptosis, and the androgen and estrogen response. UXT-V2 is a cofactor in the NF-κB transcriptional enhanceosome, and its knockdown inhibits TNF-α -induced NF-κB activation. Fbxo7 is an F-box protein that interacts with SKP1, Cullin1 and RBX1 proteins to form an SCF(Fbxo7) E3 ubiquitin ligase complex. Fbxo7 negatively regulates NF-κB signaling through TRAF2 and cIAP1 ubiquitination. METHODS: We combine co-immunoprecipitation, ubiquitination in vitro and in vivo, cycloheximide chase assay, ubiquitin chain restriction analysis and microscopy to investigate interaction between Fbxo7 and overexpressed UXT-V2-HA. RESULTS: The Ubl domain of Fbxo7 contributes to interaction with UXTV2. This substrate is polyubiquitinated by SCF(Fbxo7) with K48 and K63 ubiquitin chain linkages in vitro and in vivo. This post-translational modification decreases UXT-V2 stability and promotes its proteasomal degradation. We further show that UXTV1, an alternatively spliced isoform of UXT, containing 12 additional amino acids at the N-terminus as compared to UXTV2, also interacts with and is ubiquitinated by Fbxo7. Moreover, FBXO7 knockdown promotes UXT-V2 accumulation, and the overexpression of Fbxo7-ΔF-box protects UXT-V2 from proteasomal degradation and enhances the responsiveness of NF-κB reporter. We find that UXT-V2 colocalizes with Fbxo7 in the cell nucleus. CONCLUSIONS: Together, our study reveals that SCF(Fbxo7) mediates the proteasomal degradation of UXT-V2 causing the inhibition of the NF-κB signaling pathway. GENERAL SIGNIFICANCE: Discovering new substrates of E3 ubiquitin-ligase SCF(Fbxo7) contributes to understand its function in different diseases such as cancer and Parkinson.Biotechnology and Biological Science Research Council [BB/J007846/1]

Solução glicosada hipertônica no mesentério e no peritônio de ratos: estudo macroscópico e microscópico

PURPOSE: The objective of the experimental study is to detect the macroscopic and microscopic alterations of the mesenterium and parietal peritoneum when hypertonic glucose aqueous solution 10%-25% is administrated into the peritoneal cavity of the rat. METHODS: 90 Wistar females young rats adults were used weighin between 180-250 g, numbered 1 to 90, establishing unique group and divided in three groups (A, B, C) of 30 animals chosen aleatory manner. 0,9% saline solution was used called control group, or group A, 10% glucose solution named group B, and in the others 30 was used 25% glucose solution named group C, differing in the observation period, (06h, 24h and 48h), but with the same procedure. A midline abdominal wall laparotomy was made and in the animals of the control group was injected 2 ml of a 0,9% saline solution into the peritoneal cavity. After, we made a suture in mass without to include the peritoneum. For the others groups (B, C) the rats received 10% glucose solution and 25% glucose solution injected into the peritoneal cavity respectively. All groups were kept under observation and the results were submitted to statistical analysis by a longitudinal and transversal comparative study. RESULTS: A new surgery was done in 6h, 24h and 48h, and we observed in macroscopic evaluation, the presence of fluid, serous uniforme and rosy all over the cavity. Vascular congestion was present. We dried out 90 fragments of mesenterium and 90 fragments of parietal peritonium bilateral. In the microscopic study, necrosis was not present. For the mesenterium histological study we observed 16 cases (17,8%) unspecific chronic inflammation, 30 cases (33,4%) hiperplasic linfonod, 10 cases (11,1%) high vascular congestion, 6 cases (6,6%) reaction fibrosis and 28 cases (31,1%) no alteration. For the parietal peritonium histological study we observed 6 cases (3,3%) reaction fibrosis and 174 cases (96,7%) no alteration. Giant cell was not present. In the statistical analisys statistic there is no significance between the groups (p>0,05). CONCLUSION: Hypertonic glucose solution and NaCl 0,9% on the mesenterium and parietal peritonium do not produce tissue necrosis in a rat and the inflammation process has the same intensity.OBJETIVO: Investigar as alterações macroscópicas e microscópicas do mesentério e do peritônio parietal quando se administra a solução aquosa de glicose hipertônica a 10% e a 25% na cavidade peritoneal de rato. MÉTODOS: 90 ratos fêmeas (n=90), adultos, Wistar, jovens, com peso variando de 180 a 250 gramas foram divididos em 3 sub-grupos (A, B e C) contendo cada um 30 animais com procedimentos idênticos, diferindo apenas no período de observação. Os números de 1 a 30 constituem o grupo A ou grupo-controle (NaCl 0,9%), os números de 31 a 60 constituem o grupo B ou grupo-glicose a 10% e os números de 61 a 90 constituem o grupo C ou grupo- glicose a 25%. Realizando-se posteriormente laparotomia com incisão mediana longitudinal de pele a 2 cm abaixo do processo Xiphoideus sterni, estendendo-se por 3 cm caudalmente na linha média ventral. A escolha do procedimento a ser realizado para introdução na cavidade peritoneal de 2 ml de uma solução de cloreto de sódio 0,9% (controle), de glicose hipertônica a 10% e de glicose hipertônica a 25%. Em períodos correspondentes às 6h, 24h e 48h de pós-operatório, os animais de cada grupo foram reoperados, sendo realizada avaliação macroscópica e microscópica além dos registros das alterações histológicas do mesentério e peritônio parietal. RESULTADOS: Na microscopia do mesentério observou-se que 30 animais (33,4%) apresentaram linfonodos hiperplásicos; 6 animais (6,6%) com fibrose reacional; 10 animais (11,1%) com intensa congestão vascular; 16 animais (17,8%) com inflamação crônica inespecífica; 28 casos (31,1%) sem alteração. A microscopia do peritônio revelou 6 casos com fibrose reacional (3,3%) 174 casos (96,7%) sem alteração histológica. CONCLUSÃO: As soluções de glicose a 10% e a 25% não causam necrose tecidual quando introduzidas na cavidade peritoneal. O processo reacional inflamatório é de igual intensidade tecidual comparando-se ao uso da solução de NaCl a 0,9%.UNCISAL DepartmentUFAL Morphology Department and Human AnatomyUNIFESP-EPM Surgery DepartmentUNIFESP, EPM, Surgery DepartmentSciEL