Upside-down swimming behaviour of free-ranging narwhals

© 2007 Dietz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Ecology 7 (2007): 14, doi:10.1186/1472-6785-7-14.Free-ranging narwhals (Monodon monoceros) were instrumented in Admiralty Inlet, Canada with both satellite tags to study migration and stock separation and short-term, high-resolution digital archival tags to explore diving and feeding behaviour. Three narwhals were equipped with an underwater camera pod (Crittercam), another individual was equipped with a digital archival tag (DTAG), and a fifth with both units during August 2003 and 2004. Crittercam footage indicated that of the combined 286 minutes of recordings, 12% of the time was spent along the bottom. When the bottom was visible in the camera footage, the narwhals were oriented upside-down 80% of the time (range: 61 100%). The DTAG data (14.6 hours of recordings) revealed that during time spent below the surface, the two tagged narwhals were supine an average of 13% (range: 9–18%) of the time. Roughly 70% of this time spent in a supine posture occurred during the descent. Possible reasons for this upside-down swimming behaviour are discussed. No preference for a clockwise or counter-clockwise direction of roll was observed, discounting the possibility that rolling movements contribute to the asymmetric left-handed helical turns of the tusk.This study was funded by the National Environmental Research Institute, the Greenland Institute of Natural Resources (organized by Mads Peter Heide-Jørgensen), the Department of Fisheries and Oceans, the Nunavut Wildlife Research Trust Fund and the Danish Cooperation for the Environment in the Arctic (DANCEA). Ari D. Shapiro received financial support from the WHOI Academic Programs Office, the National Science Foundation Research Fellowship and the National Defense Science & Engineering Graduate Fellowship

Depletion of the m1A writer TRMT6/TRMT61A reduces proliferation and resistance against cellular stress in bladder cancer

BackgroundBladder cancer (BLCA) is a common and deadly disease that results in a reduced quality of life for the patients and a significant economic burden on society. A better understanding of tumorigenesis is needed to improve clinical outcomes. Recent evidence places the RNA modification m1A and its regulatory proteins TRMT6/TRMT61A and ALKBH3 in BLCA pathogenesis.MethodsTRMT6/TRMT61A, ALKBH1, and ALKBH3 expression was examined in human BLCA cell lines and a normal urinary tract epithelium cell line through qRT-PCR and western blot analysis. Prestoblue Cell Viability Reagent, wound-healing assay, and live-cell imaging-based cell displacement analysis, were conducted to assess proliferation, migration, and displacement of this BLCA cell line panel. Cell survival was assessed after inducing cellular stress and activating the unfolded protein response (UPR) with tunicamycin. Moreover, siRNA-mediated gene silencing in two BLCA cell lines (5637 and HT1197) was conducted to investigate the biological roles of TRMT6/TRMT61A.ResultsHeterogeneous morphology, proliferation, displacement, tunicamycin sensitivity, and expression levels of m1A regulators were observed among the panel of cell lines examined. In general, TRMT61A expression was increased in BLCA cell lines when compared to SV-HUC-1. Depletion of TRMT6/TRMT61A reduced proliferation capacity in both 5637 and HT1197 cell lines. The average cell displacement of 5637 was also reduced upon TRMT6/TRMT61A depletion. Interestingly, TRMT6/TRMT61A depletion decreased mRNA expression of targets associated with the ATF6-branch of the UPR in 5637 but not in HT1197. Moreover, cell survival after induction of cellular stress was compromised after TRMT6/TRMT61A knockdown in 5637 but not in HT1197 cells.ConclusionThe findings suggest that TRMT6/TRMT61A plays an oncogenic role in BLCA and is involved in desensitizing BLCA cells against cellular stress. Further investigation into the regulation of TRMT6/TRMT61A expression and its impact on cellular stress tolerance may provide insights for future BLCA treatment

L-Cell Expression of Melanocortin-4-Receptor Is Marginal in Most of the Small Intestine in Mice and Humans and Direct Stimulation of Small Intestinal Melanocortin-4-Receptors in Mice and Rats Does Not Affect GLP-1 Secretion.

The molecular sensors underlying nutrient-stimulated GLP-1 secretion are currently being investigated. Peripheral administration of melanocortin-4 receptor (MC4R) agonists have been reported to increase GLP-1 plasma concentrations in mice and humans but it is unknown whether this effect results from a direct effect on the GLP-1 secreting L-cells in the intestine, from other effects in the intestine or from extra-intestinal effects. We investigated L-cell expression of MC4R in mouse and human L-cells by reanalyzing publicly available RNA sequencing databases (mouse and human) and by RT-qPCR (mouse), and assessed whether administration of MC4R agonists to a physiologically relevant gut model, isolated perfused mouse and rat small intestine, would stimulate GLP-1 secretion or potentiate glucose-stimulated secretion. L-cell MC4R expression was low in mouse duodenum and hardly detectable in the ileum and MC4R expression was hardly detectable in human L-cells. In isolated perfused mouse and rat intestine, neither intra-luminal nor intra-arterial administration of NDP-alpha-MSH, a potent MC4R agonist, had any effect on GLP-1 secretion (P ≥0.98, n = 5-6) from the upper or lower-half of the small intestine in mice or in the lower half in rats. Furthermore, HS014-an often used MC4R antagonist, which we found to be a partial agonist-did not affect the glucose-induced GLP-1 response in the rat, P = 0.62, n = 6). Studies on transfected COS7-cells confirmed bioactivity of the used compounds and that concentrations employed were well within in the effective range. Our combined data therefore suggest that MC4R-activated GLP-1 secretion in rodents either exclusively occurs in the colon or involves extra-intestinal signaling

Transfer of gut microbiota from lean and obese mice to antibiotic-treated mice

Transferring gut microbiota from one individual to another may enable researchers to “humanize” the gut of animal models and transfer phenotypes between species. To date, most studies of gut microbiota transfer are performed in germ-free mice. In the studies presented, it was tested whether an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gut microbiota from lean or obese donors. The gut microbiota and clinical parameters of the recipients was characterized one and six weeks after inoculation. The results demonstrate, that the donor gut microbiota was introduced, established, and changed the gut microbiota of the recipients. Six weeks after inoculation, the differences persisted, however alteration of the gut microbiota occurred with time within the groups. The clinical parameters of the donor phenotype were partly transmissible from obese to lean mice, in particularly β cell hyperactivity in the obese recipients. Thus, a successful inoculation of gut microbiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions to conventional antibiotic-treated mice was possible at least for a time period during which the microbiota may permanently modulate important host functions

Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis

The phenotypes of B lineage cells that produce oligoclonal IgG in multiple sclerosis have not been unequivocally determined. Here, we utilized single-cell RNA-seq data of intrathecal B lineage cells in combination with mass spectrometry of intrathecally synthesized IgG to identify its cellular source. We found that the intrathecally produced IgG matched a larger fraction of clonally expanded antibody-secreting cells compared to singletons. The IgG was traced back to two clonally related clusters of antibody-secreting cells, one comprising highly proliferating cells, and the other consisting of more differentiated cells expressing genes associated with immunoglobulin synthesis. These findings suggest some degree of heterogeneity among cells that produce oligoclonal IgG in multiple sclerosis

Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics

Abstract In the apolipoprotein E–deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe tm1sage (Apoe −/−) rats fed either a Western diet or a low-fat control diet with or without gluten, which is known to promote gut microbiota changes, until 20 weeks of age. We hypothesized that the manifestation of atherosclerosis would be more severe in Apoe −/− rats fed the Western high-fat diet, as compared with rats fed the low-fat diet, and that atherosclerosis would be accelerated by gluten. Both Western diet-feeding and gluten resulted in significant changes in gut microbiota, but the microbiota impact of gluten was transient. Compared with Apoe −/− rats fed a low-fat diet, Western diet-fed Apoe −/− rats were heavier and became glucose intolerant with increased levels of oxidative stress. They developed early fatty streak lesions in their aortic sinus, while there was no evidence of atherosclerosis in the thoracic aorta. No conclusions could be made on the impact of gluten on atherosclerosis. Although Western diet-fed Apoe −/− rats exhibited a more human-like LDL dominated blood lipid profile, signs of obesity, type 2 diabetes and cardiovascular disease were modest