Biology Open最新文献

Voice deficits are common in Parkinson's disease (PD) and significantly impact quality of life by increasing stress, social isolation, and caregiver burden. However, despite this impact, there are currently no treatments that target the underlying pathophysiology of PD in the vocalization system. The goal of this study was to examine the effect of one possible underlying mechanism responsible for the complex voice deficits that exist in PD; overexpression of the protein alpha-synuclein. Results show that overexpression of alpha-synuclein, prior to the development of alpha-synuclein aggregate pathology, does not result in significant vocalization deficits. A small but statistically significant increase in the total number of complex vocalizations was found in mice overexpressing alpha-synuclein compared to wild-type mice, but there were no differences in complexity ratio or any of the other specific vocalization parameters tested. Results provide a critical foundational understanding of the impact of overexpression versus aggregation of alpha-synuclein on voice deficits in PD. Future work will focus on manipulation of alpha-synuclein aggregate pathology, and not overexpression alone, to reduce or eliminate the burden of PD specific voice disorders.

Global warming threatens biodiversity, particularly affecting ectothermic animals, which must seek refuge to avoid overheating when ambient temperatures exceed their critical thresholds. Extended shelter use limits the time for essential activities such as foraging, social interactions, and reproduction, potentially reducing survival and increasing local extinction risk. Viviparous Liolaemids inhabiting cold-temperate Andean regions are considered vulnerable to rising temperatures and are predicted to experience local extinctions this century. We evaluated the effects of thermal restriction on pregnancy outcomes and offspring in the viviparous lizard Liolaemus pictus under two conditions. One group of pregnant females experienced simulated future thermal restrictions (restriction group, RG; n=12), while another group experienced identical laboratory conditions without thermal restrictions (no-restriction group, NRG; n=14). In RG females, 41.7% were removed due to feeding cessation or spontaneous abortions (versus 12.3% in NRG), reflecting the consequences of thermal restriction. The remaining RG females selected lower preferred body temperatures after 2 weeks of experimentation and maintained a stable body condition throughout pregnancy. However, both groups of offspring showed similar body condition and locomotor performance, suggesting physiological compensation by RG females. This physiological plasticity of L. pictus may help buffer the adverse effects of global warming on reproductive success.

Vitamin B12 is an essential micronutrient produced only by prokaryotes, and animals must acquire it from their diet. Vitamin B12 is critical for the synthesis of methionine and propionyl-CoA metabolism. In humans, vitamin B12 deficiency has been linked to many disorders, including infertility and developmental abnormalities. The growing trend towards plant-based diets and ageing populations increases the risk of vitamin B12 deficiency, and, therefore, there is an increasing interest in understanding vitamin B12 biology. Accurate approaches for detecting and quantifying vitamin B12 are essential in studying its complex biology, from its biogenesis in Bacteria and Archaea to its effects in complex organisms. Here, we present an approach using the commonly available E. coli methionine auxotroph strain B834 (DE3) and a multi-well spectrophotometer to detect and estimate the levels of vitamin B12 from biological samples at picomolar concentrations. We further show that our method is sufficient to reveal important differences in the production of vitamin B12 from vitamin B12-synthesising bacteria commonly found in the microbiome of wild Caenorhabditis elegans isolates. Our results establish a high-throughput and simple assay platform for detecting and estimating vitamin B12 levels using the E. coli B834 (DE3) strain.

The B16 murine melanoma cell lines are considered the gold standard for testing melanoma immunotherapies due to low treatment success rates. However, the clinical relevance of these models has been questioned due to a mutational landscape void of driver mutations typically seen in human melanomas and a tendency to form necrotic cores at high tumor volumes. Creating the YUMM1.7 line addressed these limitations by providing an additional contextually consistent model with a more clinically relevant genetic background. The combined use of both models can generate stronger studies in melanoma immunology and immunotherapy. However, to date, there have been no direct functional comparisons of the characteristics of these two models to inform the design of such studies. To address this, we conducted a series of functional experiments to characterize the kinetics of tumor growth, chemotherapeutic sensitivity, and immunogenicity of these models. We found that the B16F0 model had faster intrinsic tumor growth rates, was more susceptible to lysis by tumor-specific CD8+ T cells, and secreted higher levels of the angiogenic factors VEGF and Ang2. Meanwhile, the YUMM1.7 model was more sensitive to chemotherapeutic treatment, secreted higher levels of chemokines CCL2, CXCL1, and CX3CL1, and showed higher infiltration of lymphocyte and myeloid subsets at the same tumor size. Overall, YUMM1.7 model may be better suited for in vivo studies of mechanisms that require a wider observation window and intervention than the B16F0 model, such as immune response. However, angiogenesis and immunotherapy studies may benefit from a more in-depth comparative analyses of both models.

Potato (Solanum tuberosum L.) is a global crop with a vital role in food security and economic significance in many countries. Potato virus Y (PVY) is one of its major viral threats, causing severe yield and quality losses when not controlled properly. PVY spreads primarily through aphids and infected tubers, and current management relies on insecticides and protective oils. Novel detection methods are needed to identify infected plants accurately at an early stage of plant development, thus reducing pesticide use. Trained honeybees (Apis mellifera L.) can detect specific volatiles emitted by plants infected by viruses like PVY. Using associative conditioning and the proboscis extension reflex, we tested the capacity of harnessed worker bees to distinguish PVY-infected and healthy potato leaves as a first step towards field application. As a whole, the results were impeded by low response levels and no significant result was obtained. However, we were able to show the capability of honeybees to learn and differentiate between two conditioned stimuli (healthy potato leaves versus clean air). Our findings therefore suggest that honeybees, as a globally accessible resource, have the potential to be used as a cost-effective solution in crop health monitoring, with further investigation and protocol refinement needed to achieve accurate PVY detection in agricultural settings.

Reactivation of transposable elements (TEs) in somatic tissues, particularly of LINE-1, is associated with disease by causing gene mutations and DNA damage. Previous work has shown that the PIWI pathway is crucial for TE suppression in the germline. However, the status and function of this pathway is not well characterized in differentiated somatic cells and there is a lack of consensus on the role of the pathway in somatic tumorigenesis. To shed light on this conundrum, we examined the PIWI pathway in colon cancer through combining bioinformatic analyses and cell-based assays. Shifted weighted annotation network (SWAN) analysis revealed that the pathway experiences significant allelic losses in colon cancer and that PIWIL2, the main catalytic component of the pathway responsible for TE silencing, experiences the highest percent deletions. PIWIL2 is downregulated in colon tumors of advanced stage, nodal metastasis, and in certain subtypes, correlating with poor survival, while it is also downregulated in ulcerative colitis, an inflammatory bowel disease that predisposes to colon cancer. PIWIL2 depletion in colon epithelial Caco2 cells leads to increased anchorage-independent growth, decreased levels of TE-targeting non-canonical piRNAs, increased LINE-1 levels and activity, and in DNA damage, altogether highlighting a tumor-suppressing role of PIWIL2 in the colon.

Results of recent research show that bats perform flights with continual altitude changes rather than flying at a constant altitude. However, the current state of knowledge suggests that the reason for these altitude changes is not known, and it is stated in the literature that further study is necessary in order to understand this behaviour. The goal of this paper is to provide an explanation by showing that flights with continual altitude changes constitute a fuel-saving flight mode in bats. The descents in the altitude changes - which were analysed using flight measurement data - show a power support by flapping the wings to yield a powered glide. Accordingly, this flight mode may be termed powered-gliding/climbing flight. Corresponding to the described flight characteristics, powered-gliding/climbing flight can be seen as an extension of flap-gliding flight, which is a flight mode known in the research on animal flight. This paper shows that the powered glide enables a decrease in aerodynamic drag, as well as an explanation of the underlying physical mechanism. I also developed a flight mechanics model of powered/gliding climbing flight in bats. Results based on this model show that fuel consumption can be reduced. Thus, a substantial fuel saving can be achieved when compared with the best flight at constant altitude, which is classically considered as the flight mode requiring the lowest fuel consumption.

Loss of structural habitat complexity associated with habitat degradation in marine systems may expose early life stages of fishes to harsh environmental conditions. Specifically, loss of coral cover means less suitable refuge is available for some reef fish species to lay their eggs, exposing them to pervasive stressors such as ultraviolet radiation (UVR). Here, using laboratory experiments, we exposed embryos of the clownfish Amphiprion ocellaris for 2 h daily to two UVR levels reflective of their depth at settlement; high UVR (280 µW m-2), reflective of shallow depths, and low UVR (80 µW m-2), reflective of deeper depths over their embryonic period, and then measured changes in mass, yolk sac volume, DNA damage, and survival. Despite being exposed to ecologically relevant levels of UV radiation, there was 100% mortality before hatching and inflated yolk sacs in both high and low UVR-treated animals. Exposure to UVR also resulted in DNA damage, albeit only in high UVR treatments. It is evident from our results that the protection that the reef can offer from UVR is critical for the survival of clownfish. Our results also underscore the need for future work to consider this often-neglected stressor and the role of adequate refuge for the healthy development of early-life stages of reef organisms.

The thalamic dorsolateral geniculate nucleus (dLGN) receives visual input from the retina via the optic nerve, and projects to the cortical visual area, where eye-derived signals are elaborated. The transcription factors SOX2 and NR2F1 are directly involved in the differentiation of dLGN neurons, based on mouse work and patient mutations leading to vision defects. However, whether they regulate each other, or control common targets is still unclear. By RNA-seq analysis of neonatal dLGN from thalamo-specific Sox2 and Nr2f1 mouse mutants, we found a striking overlap of deregulated genes. Among them, Vgf, encoding a cytokine transported along thalamic-cortical axons is strongly downregulated in both mutants. Direct SOX2 binding to some of these genes was confirmed by CUT&RUN, which identified a SOX2 chromatin-binding pattern characteristic of the dLGN. Collectively, our genetic and molecular analyses on the SOX2 and NR2F1-coregulated genes contribute to our understanding of the gene regulatory network driving the differentiation and connectivity of thalamic neurons, and the vision impairments caused by mutations in these genes.