In patients with Huntington disease, vesicular monoamine transporter 2 inhibitors (VMAT2is) treatment improved chorea without significant changes in adverse effects or depressive symptoms.
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Aedes aegypti, commonly known as the yellow fever mosquito, is a highly adapted, invasive mosquito species recognized as a major global health threat that acts as the primary vector for several severe diseases, most notably dengue fever, as well as yellow fever, chikungunya and Zika virus. Local government agencies conduct routine molecular surveillance of these mosquitoes to detect and track viruses. However, they are primarily limited to using conventional reverse transcription polymerase chain reaction methodologies, which can only detect known pathogens that have already been identified and for which specific genetic primers have been developed.
Recent research efforts applying high-throughput RNA sequencing have led to a large expansion in the mosquito virome (the entire collection of viruses contained within mosquitoes). However, questions remain as to how persistent insect viruses are within mosquito colonies, how insect viruses interact with mosquito immune responses and how frequently insect viruses can be transmitted.
A new study by Boston University Chobanian & Avedisian School of Medicine researchers looked at the mosquitoes’ immune response to discover many more insect viruses and they hope to someday use the mosquitoes’ own immune system to battle some of the most pervasive and antagonistic human viruses. The findings are published in the journal Nature Communications.
Xiaochang Zhang & team introduce exon annotation for nonsense-mediated mRNA (EANMD) and report on alternatively spliced exons in the brain that trigger mRNA decay, noting modulation of such exons in disease-causal genes can potentially treat neurodevelopmental disorders.
Address correspondence to: Xiaochang Zhang, University of Chicago, Cummings Life Science Center 507A, 920 E. 58th St., Chicago, Illinois 60,637, USA. Phone: 773.834.5369; Email: [email protected].
Among adults with Prediabetes, vitamin D3 supplementation was associated with lower diabetes risk only in those with specific ApaI vitamin D receptor genotypes.
This genetic association analysis of the D2d study suggests that genetic variation in the VDR, specifically the ApaI polymorphism, is associated with diabetes risk at higher intratrial 25(OH)D levels and is associated with response to 4,000 IU/d of vitamin D3 supplementation among adults with prediabetes. Participants carrying the ApaI AA genotype did not experience a reduction in diabetes risk, either when achieving higher intratrial 25(OH)D concentrations or while being treated with 4,000 IU/d of vitamin D3. In contrast, those carrying the ApaI CC and AC genotypes, representing 71% of the D2d study population, had progressively lower risk of type 2 diabetes at intratrial 25(OH)D levels of 40 ng/mL or higher. Participants with these genotypes randomized to vitamin D3 had a 19% reduction in the risk of progression to diabetes compared with placebo, whereas those with ApaI AA alleles did not respond to treatment with vitamin D3. The BsmI polymorphism also appeared to play a role in the association between the achieved intratrial 25(OH)D level and diabetes risk, as expected given the high linkage disequilibrium of ApaI and BsmI (D’ = 1.0 and r2 = 1.0) among people of European ancestry.15 Because there was a near complete overlap between participants carrying the nonresponsive Bsml TT genotype and those carrying the nonresponsive ApaI AA genotype, knowing the ApaI genotype alone was sufficient to identify individuals who were likely—or unlikely—to respond to supplementation with 4,000 IU/d of vitamin D3. These exploratory genetic association findings support our hypothesis that a common VDR variant modulates the link between high intratrial 25(OH)D levels and diabetes risk, and the association between relatively high-dose vitamin D3 supplementation and diabetes risk among adults with prediabetes. The distributions of alleles of the 3 polymorphisms in the D2d study were similar to those reported in the UK Biobank of participants with prediabetes.5 Consistent with the UK Biobank study and other studies,5,16,17 the 25(OH)D levels achieved during the D2d trial did not differ significantly among participants with different VDR polymorphisms.
In the UK Biobank study, among adults with prediabetes and a median 25(OH)D level of 19.2 ng/mL (a value below our referent range of 20–29.9 ng/mL), there was a stepwise decrease in the risk of diabetes at 25(OH)D levels of lower than 10 (the study’s referent), 10 to 20, 20 to 30, and 30 ng/mL or higher.5 Risk reduction was present in all VDR genotypes of the 4 examined polymorphisms (ApaI, BsmI, TaqI, and FokI), but it was more prominent among those carrying the T allele of BsmI. There were too few participants in the D2d study with sufficiently low 25(OH)D levels to address this range of the 25(OH)D spectrum. Conversely, there were too few participants with sufficiently high 25(OH)D levels in the UK Biobank study to address the question posed in our study. To our knowledge, no other high-dose vitamin D trials among adults with prediabetes have examined how VDR polymorphisms may modify the effect of vitamin D supplementation on diabetes risk.
Our exploratory findings, if confirmed, hold promise for high-dose vitamin D3 as a targeted, personalized approach to reducing the risk of type 2 diabetes among selected adults with prediabetes. The magnitude of the observed risk reduction among participants with AC and CC alleles of the ApaI polymorphism, if confirmed in an independent clinical trial, would have clinical implications for the management of prediabetes. In the original report of the D2d trial,2 the HR for conversion to type 2 diabetes with vitamin D supplementation was 0.88 (95% CI, 0.72−1.04). The HR decreased to 0.81 (95% CI, 0.66−0.99) in our exploratory analysis when genetically nonresponsive participants (those with AA alleles of the ApaI polymorphism, comprising 29.5% of all participants) were excluded. If confirmed, a 19% risk reduction in conversion to type 2 diabetes with vitamin D3 supplementation would not be trivial. First, assessment of a single VDR polymorphism is inexpensive and now widely available.
For centuries, the inability to regrow lost body parts has been considered a defining limitation of humans and other mammals. While animals like salamanders can regenerate entire limbs, humans are left with scar tissue. But new research from the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) suggests that this limitation may not be permanent. Instead, the capacity for regeneration may still exist—hidden within the body’s normal healing process.
“Why some animals can regenerate and others, particularly humans, can’t is a big question that has been asked since Aristotle,” said Dr. Ken Muneoka, a professor in the VMBS’ Department of Veterinary Physiology & Pharmacology (VTPP). “I’ve spent my career trying to understand that.”
In their study, published in Nature Communications, Muneoka and his colleagues detail a newly developed two-step treatment that led to the regeneration of bone, joint structures and ligaments. While the results were imperfect, the team believes this approach could be used more immediately to reduce scarring and improve tissue repair after amputations.
Daniel J. Drucker & team identify the vascular smooth muscle GLP-1 receptor as a key cellular target for the actions of GLP-1 medicines to lower blood pressure.
The figure: Renal GLP1R/Glp1r is expressed in human and murine vascular smooth muscle cells (VSMCs) and Glp1rVSM-/- mice have reduced Glp1r transcripts in renal tissues.
1Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
2Section of Nephrology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Address correspondence to: Daniel J. Drucker, Mt. Sinai Hospital, 600 University Ave. Mailbox 39, Toronto, Ontario, Canada, M5G1X5. Phone: 416.361.2661; Email: [email protected].
Scientists build an atlas of the blood vessel in diabetes and decipher crosstalk between “foamy” phagocytes and endothelial cells, showing that TREM2 drives vessel dysfunction in peripheral artery disease.
Read more in Science TranslationalMedicine.
Diabetes-driven TREM2-endothelial cross-talk impairs vascular repair in peripheral arterial disease.