An article published in BMCBiology discusses REIMS: a rapid method to create species and age profiles of mosquitoes using supervised machine learning approaches and help implement and assess the impact of vector control strategies.
]. Likewise, MIRS prediction of chronological age is highly variable with the very young and very old mosquitoes being more accurately predicted than intermediate ages. A deep-learning MIRS model achieved an accuracy of 89% for the resolution of wild-derived]. Thus, REIMS delivers a species and age-predictive accuracy that is comparable to other analytical methods.
Secondly, age predictions must not be unduly influenced by temperature and humidity, diet, intraspecific phenotypic variation or physiological status . Whilst results fromsampled from the UK are encouraging, further studies of the robustness of the predictions under field conditions are needed. Fourthly, at present, the robustness of the models that are created is not fully resolved. Apart from issues such as instrument drift and source variation, the extent to which time-dependent or geography-dependent differences in subjects might influence responsiveness to a single model is unclear. It is possible that ‘local’ models might improve separation.
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Systematic characterization of seed overlap microRNA cotargeting associated with lupus pathogenesis - BMC BiologyBackground Combinatorial gene regulation by multiple microRNAs (miRNAs) is widespread and closely spaced target sites often act cooperatively to achieve stronger repression (“neighborhood” miRNA cotargeting). While miRNA cotarget sites are suggested to be more conserved and implicated in developmental control, the pathological significance of miRNA cotargeting remains elusive. Results Here, we report the pathogenic impacts of combinatorial miRNA regulation on inflammation in systemic lupus erythematosus (SLE). In the SLE mouse model, we identified the downregulation of two miRNAs, miR-128 and miR-148a, by TLR7 stimulation in plasmacytoid dendritic cells. Functional analyses using human cell lines demonstrated that miR-128 and miR-148a additively target KLF4 via extensively overlapping target sites (“seed overlap” miRNA cotargeting) and suppress the inflammatory responses. At the transcriptome level, “seed overlap” miRNA cotargeting increases susceptibility to downregulation by two miRNAs, consistent with additive but not cooperative recruitment of two miRNAs. Systematic characterization further revealed that extensive “seed overlap” is a prevalent feature among broadly conserved miRNAs. Highly conserved target sites of broadly conserved miRNAs are largely divided into two classes—those conserved among eutherian mammals and from human to Coelacanth, and the latter, including KLF4-cotargeting sites, has a stronger association with both “seed overlap” and “neighborhood” miRNA cotargeting. Furthermore, a deeply conserved miRNA target class has a higher probability of haplo-insufficient genes. Conclusions Our study collectively suggests the complexity of distinct modes of miRNA cotargeting and the importance of their perturbations in human diseases.
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Lentiviral in situ targeting of stem cells in unperturbed intestinal epithelium - BMC BiologyBackground Methods for the long-term in situ transduction of the unperturbed murine intestinal epithelium have not been developed in past research. Such a method could speed up functional studies and screens to identify genetic factors influencing intestinal epithelium biology. Here, we developed an efficient method achieving this long-sought goal. Results We used ultrasound-guided microinjections to transduce the embryonic endoderm at day 8 (E8.0) in utero. The injection procedure can be completed in 20 min and had a 100% survival rate. By injecting a small volume (0.1–0.2 μl) of concentrated virus, single shRNA constructs as well as lentiviral libraries can successfully be transduced. The new method stably and reproducibly targets adult intestinal epithelium, as well as other endoderm-derived organs such as the lungs, pancreas, liver, stomach, and bladder. Postnatal analysis of young adult mice indicates that single transduced cells at E8.0 gave rise to crypt fields that were comprised of 20–30 neighbouring crypts per crypt-field at 90 days after birth. Lentiviral targeting of ApcMin/+ mutant and wildtype mice revealed that heterozygous loss of Apc function suppresses the developmental normal growth pattern of intestinal crypt fields. This suppression of crypt field sizes did not involve a reduction of the crypt number per field, indicating that heterozygous Apc loss impaired the growth of individual crypts within the fields. Lentiviral-mediated shRNA knockdown of p53 led to an approximately 20% increase of individual crypts per field in both Apc+/+ and ApcMin/+ mice, associating with an increase in crypt size in ApcMin/+ mice but a slight reduction in crypt size in Apc+/+ mice. Overall, p53 knockdown rescued the reduction in crypt field size in Apc-mutant mice but had no effect on crypt field size in wildtype mice. Conclusions This study develops a novel technique enabling robust and reproducible in vivo targeting of intestinal stem cells in situ in the unperturb
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The swan genome and transcriptome, it is not all black and white - Genome BiologyBackground The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related northern hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious diseases, notably infectious diseases from which Australia has been largely shielded. Unlike mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to highly pathogenic avian influenza. Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. Results Here, we generate the first chromosome-length black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We use these genomes and transcriptomes to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to highly pathogenic avian influenza. We also implicate genetic differences in SLC45A2 gene in the iconic plumage of the black swan. Conclusion Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat, the black swan would be in a significant peril.
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How did UK social distancing restrictions affect the lives of women experiencing intimate partner violence during the COVID-19 pandemic? A qualitative exploration of survivor views - BMC Public HealthBackground Increased numbers of domestic abuse cases were reported at the start of the COVID-19 pandemic. Many people experiencing abuse faced barriers to seeking support with service closures affecting the sector. Available evidence suggests women are overrepresented in the reported cases of intimate partner violence (IPV) and we aimed to learn more about how their lives were impacted by social distancing restrictions. Methods We conducted an online qualitative interview study, using reflexive thematic analysis. Interviews were conducted between April 2021 and March 2022. 18 women in the UK with past experiences of IPV provided informed consent and participated in this study. Results During the analysis, we identified five themes relating to the impact of lockdown restrictions on participants’ lives, including: (1) Lockdown meant being confined to a place where abuse was escalating, (2) Barriers to accessing support, including “cancelled” services and missed opportunities to intervene during interactions in lockdown with frontline workers. (3) Increased feelings of fear, isolation, and loss of control, particularly during the early stages of the pandemic from the combination of abuse and pandemic-related changes to daily life. (4) Some forms of support were more accessible during the pandemic, such as provision of online psychological support and social groups. Participants also accessed new forms of support for the first time during the pandemic, in some cases sparked by posts and content on social media about abuse awareness. (5) For some, psychosocial wellbeing transformed during the pandemic, with several participants using the word “freedom” when reflecting on their experience of simultaneously escaping abuse and living through the COVID-19 pandemic. Conclusions In this study, we explored the views of female survivors of IPV in the UK during the COVID-19 pandemic. Our results highlight the importance of combined public awareness campaigns and community interve
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Understanding endemic and novel zoonotic spillovers from rodent trapping studiesThe global impact of novel zoonotic pathogen spillovers has been highlighted through the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the rapid outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. In the past, similar effects were recorded during the HIV/AIDs and Spanish Influenza pandemics.
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