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Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is essential to assess whether and how peripheral clocks are disturbed during shift work and to what extent this is linked to the central suprachiasmatic nuclei (SCN) pacemaker and/or misaligned behavioral time cues. Investigating rhythms in circulating metabolites as biomarkers of peripheral clock disturbances may offer new insights. We evaluated the impact of misaligned sleep/wake and feeding/fasting cycles on circulating metabolites using a targeted metabolomics approach. Sequential plasma samples obtained during a 24-h constant routine that followed a 3-d simulated night-shift schedule, compared with a simulated day-shift schedule, were analyzed for 132 circulating metabolites. Nearly half of these metabolites showed a 24-h rhythmicity under constant routine following either or both simulated shift schedules. However, while traditional markers of the circadian clock in the SCN—melatonin, cortisol, and PER3 expression—maintained a stable phase alignment after both schedules, only a few metabolites did the same. Many showed reversed rhythms, lost their rhythms, or showed rhythmicity only under constant routine following the night-shift schedule. Here, 95% of the metabolites with a 24-h rhythmicity showed rhythms that were driven by behavioral time cues externally imposed during the preceding simulated shift schedule rather than being driven by the central SCN circadian clock. Characterization of these metabolite rhythms will provide insight into the underlying mechanisms linking shift work and metabolic disorders.

Telomeres shorten with each cell division, serving as biomarkers of aging, with human tissues exhibiting short telomeres and restricted telomerase expression. In contrast, mice have longer telomeres and widespread telomerase activity, limiting their relevance as models for human telomere biology. To address this, we engineer a mouse strain with a humanized mTert gene ( hmTert ), replacing specific non-coding sequences with human counterparts. The hmTert gene, which is repressed in adult tissues except the gonads and thymus, closely mimics human TERT regulation. This modification rescues telomere dysfunction in mTert-knockout mice. Successive intercrosses of Tert h/- mice stabilized telomere length below 10 kb, while Tert h/h mice achieve a human-like average length of 10–12 kb, compared to 50 kb in wildtype mice. Despite shortened telomeres, Tert h/h mice maintain normal body weight and cell homeostasis. These mice, with humanized telomere regulation, represent a valuable model to study human aging and cancer. Mice models often fail to reflect human telomere biology. Here, the authors engineer a mouse strain with a humanized mTert gene, restoring telomere length regulation to a human-like pattern. This model might provide insights into aging and cancer.

Epidemiological evidence suggests that females have an advantage over males in cases of melanoma incidence, progression, and survival. However, the biological mechanisms underlying these sex differences remain unclear. With the knowledge that females generally have a more robust immune system than males, we investigated sex differences in melanoma progression in a B16-F10/BL6 syngeneic mouse model. We observed significantly less tumor volume and growth rate over 14 days in female mice compared to male mice. Furthermore, higher populations of CD4+ and CD8+ T cells, which indicate adaptive immune responses, were found in the circulating blood and tumors of females and corresponded with less tumor growth, and vice versa in males. Our results highlight a mouse model that represents melanoma progression in the human population and displays a higher immune response to melanoma in females compared to males. These findings suggest that the immune system may be one of the mechanisms responsible for sex differences in melanoma.

Understanding the role of different rainfall scenarios on faecal indicator organism (FIO) dynamics under variable field conditions is important to strengthen the evidence base on which regulators and land managers can base informed decisions regarding diffuse microbial pollution risks. We sought to investigate the impact of low intensity summer rainfall on Escherichia coli- discharge ( Q ) patterns at the headwater catchment scale in order to provide new empirical data on FIO concentrations observed during baseflow conditions. In addition, we evaluated the potential impact of using automatic samplers to collect and store freshwater samples for subsequent microbial analysis during summer storm sampling campaigns. The temporal variation of E. coli concentrations with Q was captured during six events throughout a relatively dry summer in central Scotland. The relationship between E. coli concentration and Q was complex with no discernible patterns of cell emergence with Q that were repeated across all events. On several occasions, an order of magnitude increase in E. coli concentrations occurred even with slight increases in Q , but responses were not consistent and highlighted the challenges of attempting to characterise temporal responses of E. coli concentrations relative to Q during low intensity rainfall. Cross-comparison of E. coli concentrations determined in water samples using simultaneous manual grab and automated sample collection was undertaken with no difference in concentrations observed between methods. However, the duration of sample storage within the autosampler unit was found to be more problematic in terms of impacting on the representativeness of microbial water quality, with unrefrigerated autosamplers exhibiting significantly different concentrations of E. coli relative to initial samples after 12-h storage. The findings from this study provide important empirical contributions to the growing evidence base in the field of catchment microbial dynamics.

Background: The natural day-night cycle synchronizes our circadian rhythms, but modern work practices like night shifts disrupt this pattern, leading to increased exposure to nighttime light. This exposure is linked to various health issues. While some studies have explored the effects of night shifts on human circadian rhythms, there is limited research on the consequences of long-term exposure to shift-work light conditions. Rodents can provide valuable insights into these effects. This study aimed to examine how short- or long-term exposure to rotating shifts and chronic jetlag affects the core circadian oscillators in the liver and skin of mammals. Methods: C57BL/6J male mice were subjected to simulated shift-work light conditions, including short-term or long-term rotating shifts and chronic jet-lag conditions. Liver and skin samples were collected every four hours over a 24-hour period on the second day of constant darkness. RNA was extracted and qRT-PCR analysis was conducted to measure the circadian gene expression in liver and skin tissues. Circadian rhythm analysis using CircaCompare compared the control group to mice exposed to shift-work light conditions. Results: The liver's circadian clock is significantly altered in mice under long-term rotating shift conditions, with a lesser but still noticeable impact in mice experiencing chronic jetlag. However, short-term rotating shift conditions do not significantly affect the liver's circadian clock. Conversely, all three simulated shift conditions affect the skin's circadian clock, indicating that the skin clock is more sensitive to shift-work light conditions than the liver clock. Compared to the liver, the skin's circadian clock is greatly affected by long-term rotating shift conditions. Conclusions: The study findings indicate more pronounced disturbances in the canonical clock genes of the skin compared to the liver under simulated shift-work light conditions. These results suggest that the skin clock is more vulnerable to the effects of shift-work.

Background: The natural day-night cycle synchronizes our circadian rhythms, but modern work practices like night shifts disrupt this pattern, leading to increased exposure to nighttime light. This exposure is linked to various health issues. While some studies have explored the effects of night shifts on human circadian rhythms, there is limited research on the consequences of long-term exposure to shift-work light conditions. Rodents can provide valuable insights into these effects. This study aimed to examine how short- or long-term exposure to rotating shifts and chronic jetlag affects the core circadian oscillators in the liver and skin of mammals. Methods: C57BL/6J male mice were subjected to simulated shift-work light conditions, including short-term or long-term rotating shifts and chronic jet-lag conditions. Liver and skin samples were collected every four hours over a 24-hour period on the second day of constant darkness. RNA was extracted and qRT-PCR analysis was conducted to measure the circadian gene expression in liver and skin tissues. Circadian rhythm analysis using CircaCompare compared the control group to mice exposed to shift-work light conditions. Results: The liver's circadian clock is significantly altered in mice under long-term rotating shift conditions, with a lesser but still noticeable impact in mice experiencing chronic jetlag. However, short-term rotating shift conditions do not significantly affect the liver's circadian clock. Conversely, all three simulated shift conditions affect the skin's circadian clock, indicating that the skin clock is more sensitive to shift-work light conditions than the liver clock. Compared to the liver, the skin's circadian clock is greatly affected by long-term rotating shift conditions. Conclusions: The study findings indicate more pronounced disturbances in the canonical clock genes of the skin compared to the liver under simulated shift-work light conditions. These results suggest that the skin clock is more vulnerable to the effects of shift-work.

Background The pig is a biomedical model to study human and livestock traits. Many of these traits are controlled by neuropeptides that result from the cleavage of prohormones by prohormone convertases. Only 45 prohormones have been confirmed in the pig. Sequence homology can be ineffective to annotate prohormone genes in sequenced species like the pig due to the multifactorial nature of the prohormone processing. The goal of this study is to undertake the first complete survey of prohormone and prohormone convertases genes in the pig genome. These genes were functionally annotated based on 35 gene expression microarray experiments. The cleavage sites of prohormone sequences into potentially active neuropeptides were predicted. Results We identified 95 unique prohormone genes, 2 alternative calcitonin-related sequences, 8 prohormone convertases and 1 cleavage facilitator in the pig genome 10.2 assembly and trace archives. Of these, 11 pig prohormone genes have not been reported in the UniProt, UniGene or Gene databases. These genes are intermedin , cortistatin , insulin-like 5 , orexigenic neuropeptide QRFP , prokineticin 2 , prolactin-releasing peptide , parathyroid hormone 2 , urocortin , urocortin 2 , urocortin 3 , and urotensin 2-related peptide . In addition, a novel neuropeptide S was identified in the pig genome correcting the previously reported pig sequence that is identical to the rabbit sequence. Most differentially expressed prohormone genes were under-expressed in pigs experiencing immune challenge relative to the un-challenged controls, in non-pregnant relative to pregnant sows, in old relative to young embryos, and in non-neural relative to neural tissues. The cleavage prediction based on human sequences had the best performance with a correct classification rate of cleaved and non-cleaved sites of 92% suggesting that the processing of prohormones in pigs is similar to humans. The cleavage prediction models did not find conclusive evidence supporting the production of the bioactive neuropeptides urocortin 2 , urocortin 3 , torsin family 2 member A , tachykinin 4 , islet amyloid polypeptide , and calcitonin receptor-stimulating peptide 2 in the pig. Conclusions The present genomic and functional characterization supports the use of the pig as an effective animal model to gain a deeper understanding of prohormones, prohormone convertases and neuropeptides in biomedical and agricultural research.