Metagenomic tools in microbial ecology research

Ability to directly sequence DNA from the environment permanently changed microbial ecology. Here, we review the new insights to microbial life gleaned from the applications of metagenomics, as well as the extensive set of analytical tools that facilitate exploration of diversity and function of complex microbial communities. While metagenomics is shaping our understanding of microbial functions in ecosystems via gene-centric and genome-centric methods, annotating functions, metagenome assembly and binning in heterogeneous samples remains challenging. Development of new analysis and sequencing platforms generating high-throughput long-read sequences and functional screening opportunities will aid in harnessing metagenomes to increase our understanding of microbial taxonomy, function, ecology, and evolution in the environment.publishedVersio

Effect of High-Fat Diet on Peripheral Neuropathy in C57BL/6 Mice

Objective. Dyslipidemia may contribute to the development of peripheral neuropathy, even in prediabetics; however, few studies have evaluated vascular dysfunction and oxidative stress in patients with peripheral neuropathy. Methods. Using high-fat diet- (HFD-) induced prediabetic C57BL/6 mice, we assessed motor and sensory nerve conduction velocity (NCV) using a BIOPAC System and thermal algesia with a Plantar Test (Hargreaves’ method) Analgesia Meter. Intraepidermal nerve fiber density and mean dendrite length were tested following standard protocols. Vascular endothelial growth factor-A (VEGF-A) and 12/15-lipoxygenase (12/15-LOX) were evaluated by immunohistochemistry and Western blot, respectively. Results. HFD-fed mice showed deficits in motor and sensory NCV, thermal hyperalgesia, reduced mean dendrite length, and VEGF-A expression in the plantar skin and increased 12/15-LOX in the sciatic nerve (P<0.05 compared with controls). Conclusion. HFD may cause large myelinated nerve and small sensory nerve fiber damage, thus leading to neuropathy. The mean dendrite length may be a more sensitive marker for early detection of peripheral neuropathy. Reduced blood supply to the nerves and increased oxidative stress may contribute to the development and severity of peripheral neuropathy

Thickness of Extraocular Muscle and Orbital Fat in MRI Predicts Response to Glucocorticoid Therapy in Graves’ Ophthalmopathy

33 patients with active, moderate-severe Graves’ ophthalmopathy (GO) received 4.5 g methylprednisolone for 12 weeks and were divided by efficacy into two groups (responsive and unresponsive). All patients and 10 controls underwent orbital MRI examination at baseline. No significant difference was seen in baseline clinical characteristics between the two GO groups. The values of exophthalmos were higher in both GO groups than in the control and were higher in the responsive group versus the unresponsive group. Compared to the unresponsive group, the responsive group had a thicker inferior rectus as well as thinner orbital fat. The inferior rectus/fat ratio was significantly higher in the responsive group versus the unresponsive group. Multivariate logistic regression analysis showed that the exophthalmos value and inferior rectus/fat ratio were significantly associated with the response to glucocorticoid (GC). ROC analysis revealed that the cut-off points of the inferior rectus/fat ratio combined with the exophthalmos value to indicate efficacy were 1.42 and 20.78. For moderate-severe GO patients with CAS > 3, the combined inferior rectus/fat ratio and exophthalmos value in MRI may be a valuable indicator to predict the response to GC therapy

MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice

MiR-455 has been verified a key regulator of brown adipose tissue and adipose tissue-specific overexpression of miR-455 (ap2-miR-455) mice could combat high-fat-diet-induced obesity. This study is to verify overexpression of miR-455 could ameliorate the lipid accumulation and metabolism in the liver of db/db diabetic mice and explore the potential mechanisms. Diabetic mice (db/db) and control mice (db/m) were randomly divided into four groups. After overexpression of miR-455 in the liver of db/db mice, the triglycerides level in both serum and liver decreased, the lipid deposit in liver was improved, the expression of fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase (ACCα) was also significantly down-regulated. TargetScan indicated that suppressor of cytokine signalling 3 (SOCS3) is predicated to target miR-455 and the protein of SOCS3 in the liver of db/db mice after intervention was significantly decreased. The dual luciferase reporter assay showed that SOCS3 was target gene of miR-455. In vitro, in Palmitate (PA)-stimulated human normal liver (LO2) cells, transfected miR-455 mimic could significantly inhibit the expression of SOCS3, while transfected miR-455 inhibitor could up-regulate the expression of SOCS3. Transfecting LO2 cells with siRNA of SOCS3 could significantly down-regulate the protein expression of SREBP-1c and ACCα. Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene SOCS3

The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy

MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Bioinformatic analyses and luciferase assays further demonstrated that both miR-26a and miR-30c targeted connective tissue growth factor (CTGF); additionally, Snail family zinc finger 1 (Snail1), a potent epithelial-to-mesenchymal transition (EMT) inducer, was targeted by miR-30c. Overexpression of miR-26a and miR-30c coordinately decreased CTGF protein levels and subsequently ameliorated TGFβ1-induced EMT in NRK-52E cells. Co-silencing of miR-26a and miR-30c exhibited the opposite effect. Moreover, miR-26a and miR-30c co-silenced CTGF to decrease ERK1/2 and p38 MAPK activation. Furthermore, miR-26a was up-regulated in urinary extracellular vesicles of diabetic nephropathy patients. Our study provides evidence for the cooperative roles of miR-26a and miR-30c in the pathogenesis of diabetic nephropathy, and the co-targeting of miR-26a and miR-30c could provide a new direction for diabetic nephropathy treatment

Global maximal inequality to a class of oscillatory integrals

Abstract In the present paper, we give the global Lq $L^{q}$ estimates for maximal operators generated by multiparameter oscillatory integral St,Φ $S_{t,\varPhi}$, which is defined by St,Φf(x)=(2π)−n∫Rneix⋅ξei(t1ϕ1(|ξ1|)+t2ϕ2(|ξ2|)+⋯+tnϕn(|ξn|))fˆ(ξ)dξ,x∈Rn, $$S_{t,\varPhi}f(x)=(2\pi)^{-n} \int_{\mathbb{R}^{n}} e^{ix\cdot\xi}e^{i(t_{1} \phi_{1}(|\xi_{1}|)+t_{2}\phi_{2}(|\xi_{2}|)+ \cdots+t_{n}\phi_{n}(|\xi_{n}|))}\hat{f}(\xi)\,d\xi,\quad x\in\mathbb{R}^{n},$$ where n≥2 $n\geq2$ and f is a Schwartz function in S(Rn) $\mathcal{S}(\mathbb {R}^{n})$, t=(t1,t2,…,tn) $t=(t_{1},t_{2},\ldots,t_{n})$, Φ=(ϕ1,ϕ2,…,ϕn) $\varPhi=(\phi_{1},\phi_{2},\ldots,\phi_{n})$, ϕi $\phi_{i}$ (i=1,2,3,…,n) $(i=1,2,3,\ldots, n)$ is a function on R+→R $\mathbb {R}^{+}\rightarrow\mathbb{R}$, which has a suitable growth condition. These estimates are apparently good extensions to the results of Sjölin and Soria (J. Math. Anal. Appl 411:129–143, 2014) for the multiparameter fractional Schrödinger equation

Land–Climate Interaction Over the Tibetan Plateau

The Tibetan Plateau (TP) is the largest and highest plateau on Earth. Due to its elevation, it receives much more downward shortwave radiation than other areas, which results in very strong diurnal and seasonal changes of the surface energy components and other meteorological variables, such as surface temperature and the convective atmospheric boundary layer. With such unique land process conditions on a distinct geomorphic unit, the TP has been identified as having the strongest land/atmosphere interactions in the mid-latitudes. Three major TP land/atmosphere interaction issues are presented in this article: (1) Scientists have long been aware of the role of the TP in atmospheric circulation. The view that the TP’s thermal and dynamic forcing drives the Asian monsoon has been prevalent in the literature for decades. In addition to the TP’s topographic effect, diagnostic and modeling studies have shown that the TP provides a huge, elevated heat source to the middle troposphere, and that the sensible heat pump plays a major role in the regional climate and in the formation of the Asian monsoon. Recent modeling studies, however, suggest that the south and west slopes of the Himalayas produce a strong monsoon by insulating warm and moist tropical air from the cold and dry extratropics, so the TP heat source cannot be considered as a factor for driving the Indian monsoon. The climate models’ shortcomings have been speculated to cause the discrepancies/controversies in the modeling results in this aspect. (2) The TP snow cover and Asian monsoon relationship is considered as another hot topic in TP land/atmosphere interaction studies and was proposed as early as 1884. Using ground measurements and remote sensing data available since the 1970s, a number of studies have confirmed the empirical relationship between TP snow cover and the Asian monsoon, albeit sometimes with different signs. Sensitivity studies using numerical modeling have also demonstrated the effects of snow on the monsoon but were normally tested with specified extreme snow cover conditions. There are also controversies regarding the possible mechanisms through which snow affects the monsoon. Currently, snow is no longer a factor in the statistic prediction model for the Indian monsoon prediction in the Indian Meteorological Department. These controversial issues indicate the necessity of having measurements that are more comprehensive over the TP to better understand the nature of the TP land/atmosphere interactions and evaluate the model-produced results. (3) The TP is one of the major areas in China greatly affected by land degradation due to both natural processes and anthropogenic activities. Preliminary modeling studies have been conducted to assess its possible impact on climate and regional hydrology. Assessments using global and regional models with more realistic TP land degradation data are imperative. Due to high elevation and harsh climate conditions, measurements over the TP used to be sparse. Fortunately, since the 1990s, state-of-the-art observational long-term station networks in the TP and neighboring regions have been established. Four large field experiments since 1996, among many observational activities, are presented in this article. These experiments should greatly help further research on TP land/atmosphere interactions