Notes

Varied functional components in RNA predicted transcriptome-wide by simply orthogonal RNA structure probing.
Additionally, Crag/Rab10/Ehbp1 colocalized with AP1/clathrin on the trans-side of Golgi stacks. Taken together, these results indicated that AP1/clathrin and Crag/Rab10/Ehbp1 collaborated in polarized basolateral transport, presumably in the budding process in the trans-Golgi network. © 2020. Published by The Company of Biologists Ltd.It has become increasingly evident that T cell functions are subject to translational control in addition to transcriptional regulation. Here, by using live imaging of CD8+ T cells isolated from the Lifeact-EGFP mouse, we show that T cells exhibit a gain in fluorescence intensity following engagement of cognate tumour target cells. The GFP signal increase is governed by Erk1/2-dependent distal T cell receptor (TCR) signalling and its magnitude correlates with IFN-γ and TNF-α production, which are hallmarks of T cell activation. Enhanced fluorescence was due to increased translation of Lifeact-EGFP protein, without an associated increase in its mRNA. Activation-induced gains in fluorescence were also observed in naïve and CD4+ T cells from the Lifeact-EGFP reporter, and were readily detected by both flow cytometry and live cell microscopy. This unique, translationally controlled reporter of effector T cell activation simultaneously enables tracking of cell morphology, F-actin dynamics and activation state in individual migrating T cells. It is a valuable addition to the limited number of reporters of T cell dynamics and activation, and opens the door to studies of translational activity and heterogeneities in functional T cell responses in situ. © 2020. Published by The Company of Biologists Ltd.To investigate the mechanisms underlying initiation of the sexual cell cycle in eukaryotes, we have focused on cyclins and cyclin-dependent kinases (CDKs) in the well-studied model ciliate, Tetrahyhymena thermophila We identified two genes, CDK19 and CYC9, which are highly co-expressed with the mating-associated factors, MTA, MTB, and HAP2 Both CDK19 and CYC9 were found to be essential for mating in T. thermophila Subcellular localization experiments suggested these proteins are located at the oral area, including the conjugation junction area, and that CDK19 or CYC9 knockout prevents mating. We found that CDK19 and CYC9 form a complex and also identified several additional subunits, which may have regulatory or constitutive functions. RNA-Seq analyses and cytological experiments showed that mating is abnormal both in ΔCDK19 and ΔCYC9, mainly at the entry to the costimulation stage. These results indicate that the CDK19/CYC9 complex initiates the sexual cell cycle in T. thermophila. © 2020. Published by The Company of Biologists Ltd.OBJECTIVE We examined the association of lactation duration with incident type 2 diabetes among women with a history of gestational diabetes mellitus (GDM). SB431542 cell line RESEARCH DESIGN AND METHODS We monitored 4,372 women with a history of GDM participating in the Nurses' Health Study II for incident type 2 diabetes over 25 years up to 2017. Lactation history was obtained through follow-up questionnaires to calculate lactation duration. Follow-up blood samples were collected from a subset of these women at median age of 58 years through the Diabetes & Women's Health Study. RESULTS We documented 873 incident cases of type 2 diabetes during 87,411 person-years of follow-up. Longer duration of lactation was associated with lower risk of type 2 diabetes for both total lactation (hazard ratio 1.05 [95% CI 0.83-1.34] for up to 6 months, 0.91 [0.72-1.16] for 6-12 months, 0.85 [0.67-1.06] for 12-24 months, and 0.73 [0.57-0.93] for >24 months, compared with 0 months; P-trend = 0.003) and exclusive breastfeeding (P-trend = 0.002) after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy BMI. Longer duration of lactation was also associated with lower HbA1c, fasting plasma insulin, and C-peptide concentrations among women without type 2 diabetes at follow-up (all adjusted P-trend ≤0.04). CONCLUSIONS Longer duration of lactation is associated with a lower risk of type 2 diabetes and a favorable glucose metabolic biomarker profile among women with a history of GDM. The underlying mechanisms and impact on diabetes complications, morbidity, and mortality remain to be determined. © 2020 by the American Diabetes Association.OBJECTIVE There is a paucity of data evaluating recent changes in clinical and prescriber characteristics of patients initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA). RESEARCH DESIGN AND METHODS U.S.-based administrative-claims data (July 2013 to June 2018) were used to identify initiators of SGLT2i and GLP-1RA. RESULTS Over 5 years, empagliflozin initiation (as a proportion of SGLT2i) increased by 57.1% (P less then 0.001 for trend), while canagliflozin initiation declined by 75.1% (P less then 0.001). Empagliflozin was the only agent within SGLT2i with an increase in the proportion of patients with myocardial infarction, stroke, or heart failure (collectively called CVD-HF) (P less then 0.001). Liraglutide initiation (as a proportion of total GLP-1RA) declined by 32.1% (P less then 0.001), and dulaglutide initiation increased by 34.1% (P less then 0.001); the proportion of patients with CVD-HF increased the most in liraglutide initiators (5.1% increase; P less then 0.001). Most prescribers were internists or endocrinologists; cardiologist prescribing remained low ( less then 1%). CONCLUSIONS For SGLT2i, shifts in preference for empagliflozin followed changes in drug labels and guidelines, while in GLP-1RA, other factors such as price or ease of administration may have led to a preference for dulaglutide over liraglutide. © 2020 by the American Diabetes Association.Cardiovascular exercise (CE) is a promising intervention strategy to facilitate cognition and motor learning in healthy and diseased populations of all ages. CE elevates humoral parameters, such as growth factors, and stimulates brain changes potentially relevant for learning and behavioral adaptations. However, the causal relationship between CE-induced brain changes and human's ability to learn remains unclear. We tested the hypothesis that CE elicits a positive effect on learning via alterations in brain structure (morphological changes of gray and white matter) and function (functional connectivity and cerebral blood flow in resting state). We conducted a randomized controlled trial with healthy, male and female human participants to compare the effects of a two-week CE intervention against a non-CE control group on subsequent learning of a challenging new motor task (dynamic balancing, DBT) over six consecutive weeks. We used multimodal neuroimaging (T1-weighted MRI, diffusion-weighted MRI, perfusion-weighted MRI, and resting state functional MRI) to investigate the neural mechanisms mediating between CE and learning.
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