Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults

Impaired glucose tolerant (IGT) adults are at elevated risk for cardiovascular disease (CVD). Exercise or metformin reduce CVD risk, but the efficacy of combining treatments is unclear.

Objective:

To determine the effects of exercise training plus metformin (EM), compared with each treatment alone, on CVD risk factors in IGT adults.

Design and Methods:

Subjects were assigned to placebo (P), metformin (M), exercise training plus placebo (EP), or EM (8/group). In a double‐blind design, P or 2,000 mg/d of M were administered for 12 weeks and half performed aerobic and resistance training 3 days/week for ～60 min/day at 70% pretraining heart rate peak. Outcomes included adiposity, blood pressure (BP), lipids, and high sensitivity C‐reactive protein (hs‐CRP). Z‐scores were calculated to determine metabolic syndrome severity.

Results:

M and EM, but not EP, decreased body weight compared with P (P < 0.05). M and EP lowered systolic blood pressure by 6% (P < 0.05), diastolic blood pressure by 6% (P < 0.05), and hs‐CRP by 20% (M: trend P = 0.06; EP: P < 0.05) compared with P. Treatments raised high‐density lipoprotein cholesterol (P < 0.05; EM: trend P = 0.06) compared with P and lowered triacyglycerol (P < 0.05) and metabolic syndrome Z‐score compared with baseline (EP; trend P = 0.07 and EM or M; P < 0.05).

Conclusions:

Although exercise and/or metformin improve some CVD risk factors, only training or metformin alone lowered hs‐CRP and BP. Thus, metformin may attenuate the effects of training on some CVD risk factors and metabolic syndrome severity in IGT adults.     

A review of taeniasis and cysticercosis in the Lao People's Democratic Republic

Taeniasis and cysticercosis are important but underreported parasitic zoonoses in the Lao People's Democratic Republic (Lao PDR). Reports of human and pig cysticercosis are rather limited and based largely on anecdotal evidence. To date, no structured surveys of disease prevalence or incidence have been reported. However, one unpublished pilot survey of pig cysticercosis in a slaughterhouse in northern Laos estimated prevalence to be 1.7%, without speciation of parasite cysts. Over the past 20 years, nine surveys of intestinal helminthic infection have been conducted; the prevalence of human taeniasis ranged from 0 to 14.0%. The study designs and sample sizes varied greatly, however a high degree of spatial and age variation in taeniasis prevalence was evident. These results are however inconclusive as the species of tapeworm infecting the people was not determined. To further our knowledge of taeniasis and cysticercosis in Lao PDR, structured community-based surveys in high-risk areas are required in combination with the use of sensitive and specific diagnostic tests capable of identifying the pork tapeworm, Taenia solium. This will enable the development and implementation of control measures that are both appropriate and sustainable if T. solium is shown to be a public health threat.     

Mechanisms underlying modulation of podocyte TRPC6 channels by suPAR: Role of NADPH oxidases and Src family tyrosine kinases

The soluble urokinase receptor (suPAR) has been implicated in the pathogenesis of chronic kidney diseases (CKD) and may function as a circulating “permeability factor” driving primary focal and segmental glomerulosclerosis (FSGS). Here we examined the mechanisms whereby suPAR causes mobilization and increased activation of Ca²⁺-permeable TRPC6 channels, which are also implicated in FSGS. Treatment of immortalized mouse podocytes with recombinant suPAR for 24?h caused a marked increase in cytosolic reactive oxygen species (ROS) that required signaling through integrins. This effect was associated with increased assembly of active cell surface NADPH oxidase 2 (Nox2) complexes and was blocked by the Nox2 inhibitor apoycynin. Treatment with suPAR also evoked a functionally measurable increase in TRPC6 channels that was blocked by concurrent treatment with the ROS-quencher TEMPOL as well as by inhibition of Rac1, an essential component of active Nox2 complexes. Elevated ROS evoked by exposing cells to suPAR or H₂O₂ caused a marked increase in the abundance of tyrosine-phosphorylated proteins including Src, and suPAR-evoked Src activation was blocked by TEMPOL. Moreover, mobilization and increased activation of TRPC6 by suPAR or H₂O₂ was blocked by concurrent exposure to PP2, an inhibitor of Src family tyrosine kinases. These data suggest that suPAR induces oxidative stress in podocytes that in turn drives signaling through Src family kinases to upregulate TRPC6 channels. The combination of oxidative stress and altered Ca²⁺ signaling may contribute to loss of podocytes and progression of various forms of CKD.     

Avian diversity and function across the world's most populous cities

Understanding the composition of urban wildlife communities is crucial to promote biodiversity, ecosystem function and links between nature and people. Using crowdsourced data from over five million eBird checklists, we examined the influence of urban characteristics on avian richness and function at 8443 sites within and across 137 global cities. Under half of the species from regional pools were recorded in cities, and we found a significant phylogenetic signal for urban tolerance. Site-level avian richness was positively influenced by the extent of open forest, cultivation and wetlands and avian functional diversity by wetlands. Functional diversity co-declined with richness, but groups including granivores and aquatic birds occurred even at species-poor sites. Cities in arid areas held a higher percentage of regional species richness. Our results indicate commonalities in the influence of habitat on richness and function, as well as lower niche availability, and phylogenetic diversity across the world's cities.     

Flyway‐scale analysis reveals that the timing of migration in wading birds is becoming later

1. Understanding the implications of climate change for migratory animals is paramount for establishing how best to conserve them. A large body of evidence suggests that birds are migrating earlier in response to rising temperatures, but many studies focus on single populations of model species.
2. Migratory patterns at large spatial scales may differ from those occurring in single populations, for example because of individuals dispersing outside of study areas. Furthermore, understanding phenological trends across species is vital because we need a holistic understanding of how climate change affects wildlife, especially as rates of temperature change vary globally.
3. The life cycles of migratory wading birds cover vast latitudinal gradients, making them particularly susceptible to climate change and, therefore, ideal model organisms for understanding its effects. Here, we implement a novel application of changepoint detection analysis to investigate changes in the timing of migration in waders at a flyway scale using a thirteen‐year citizen science dataset (eBird) and determine the influence of changes in weather conditions on large‐scale migratory patterns.
4. In contrast to most previous research, our results suggest that migration is getting later in both spring and autumn. We show that rates of change were faster in spring than autumn in both the Afro‐Palearctic and Nearctic flyways, but that weather conditions in autumn, not in spring, predicted temporal changes in the corresponding season. Birds migrated earlier in autumn when temperatures increased rapidly, and later with increasing headwinds.
5. One possible explanation for our results is that migration is becoming later due to northward range shifts, which means that a higher proportion of birds travel greater distances and therefore take longer to reach their destinations. Our findings underline the importance of considering spatial scale when investigating changes in the phenology of migratory bird species.

     

High-sensitivity stable-isotope probing by a quantitative terminal restriction fragment length polymorphism protocol

Stable-isotope probing (SIP) has proved a valuable cultivation-independent tool for linking specific microbial populations to selected functions in various natural and engineered systems. However, application of SIP to microbial populations with relatively minor buoyant density increases, such as populations that utilize compounds as a nitrogen source, results in reduced resolution of labeled populations. We therefore developed a tandem quantitative PCR (qPCR)-TRFLP (terminal restriction fragment length polymorphism) protocol that improves resolution of detection by quantifying specific taxonomic groups in gradient fractions. This method combines well-controlled amplification with TRFLP analysis to quantify relative taxon abundance in amplicon pools of FAM-labeled PCR products, using the intercalating dye EvaGreen to monitor amplification. Method accuracy was evaluated using mixtures of cloned 16S rRNA genes, DNA extracted from low- and high-G+C bacterial isolates (Escherichia coli, Rhodococcus, Variovorax, and Microbacterium), and DNA from soil microcosms amended with known amounts of genomic DNA from bacterial isolates. Improved resolution of minor shifts in buoyant density relative to TRFLP analysis alone was confirmed using well-controlled SIP analyses.