The correlation between CT features and insulin resistance levels in patients with T2DM complicated with primary pulmonary tuberculosis

The aim is to investigate the correlation between computed tomography (CT) features and insulin resistance levels in patients with type 2 diabetes mellitus (T2DM) complicated with primary pulmonary tuberculosis (PTB). Nearly, 268 untreated PTB patients complicated with T2DM were divided into two groups according to the optimal cutoff value of HOMA-IR score for the Chinese population: HOMA-IR ≤ 2.69 (Group I: 74 patients), >2.69 (Group II: 194 patients). The basic characteristics and changes of CT manifestations were analyzed. In the two groups, the detection rate of large segmented leafy shadow was 39.2% and 78.9%; the air bronchogram sign detection rate was 40.5% and 80.9%; the discovery rate of mouth-eaten cavity was 33.8% and 73.7%; the thin-walled cavity detection rate was 2.7% and 16.0%; the rate of multiple cavities was 35.1% and 69.6%; and bronchial tuberculosis was found in 4.1% and 35.6%, respectively. The detection rates of lesions in Group II were significantly higher than in Group I (p < .05). HOMA-IR was found independently associated with large segmented leafy shadow, air bronchial sign, thin-walled cavity, and bronchial tuberculosis. The level of insulin resistance can effectively reflect the severity of PTB patients with T2DM. CT scan can directly provide image information in clinics. These two examinations can guide clinicians to accurately formulate subsequent treatment plans.     

A review of the allozyme data set for the Canarian endemic flora: causes of the high genetic diversity levels and implications for conservation

Background and Aims

Allozyme and reproductive data sets for the Canarian flora are updated in order to assess how the present levels and structuring of genetic variation have been influenced by the abiotic island traits and by phylogenetically determined biotic traits of the corresponding taxa; and in order to suggest conservation guidelines.

Methods

Kruskal–Wallis tests are conducted to assess the relationships of 27 variables with genetic diversity (estimated by A, P, H_o and H_e) and structuring (G_ST) of 123 taxa representing 309 populations and 16 families. Multiple linear regression analyses (MLRAs) are carried out to determine the relative influence of the less correlated significant abiotic and biotic factors on the genetic diversity levels.

Key Results and Conclusions

The interactions between biotic features of the colonizing taxa and the abiotic island features drive plant diversification in the Canarian flora. However, the lower weight of closeness to the mainland than of (respectively) high basic chromosome number, partial or total self-incompatibility and polyploidy in the MLRAs indicates substantial phylogenetic constraint; the importance of a high chromosome number is feasibly due to the generation of a larger number of linkage groups, which increase gametic and genotypic diversity. Genetic structure is also more influenced by biotic factors (long-range seed dispersal, basic chromosome number and partial or total self-incompatibility) than by distance to the mainland. Conservation-wise, genetic structure estimates (F_ST/G_ST) only reflect endangerment under intensive population sampling designs, and neutral genetic variation levels do not directly relate to threat status or to small population sizes. Habitat protection is emphasized, but the results suggest the need for urgent implementation of elementary reproductive studies in all cases, and for ex situ conservation measures for the most endangered taxa, even without prior studies. In non-endangered endemics, multidisciplinary research is needed before suggesting case-specific conservation strategies. The molecular information relevant for conservation should be conserved in a standardized format to facilitate further insight.     

皇甫川流域中小型土壤动物对不同水土治理措施的响应

2007年9月至2008年9月,选择皇甫川流域人工松树林、人工杨树林、人工锦鸡儿灌木林、人工沙打旺草地和撂荒地等不同水土治理措施植被为采样地,以耕作农田为对照,研究了中小型土壤动物对不同水土治理措施的响应。结果表明,共捕获中小型土壤动物14 747只,隶属于5门7纲10类。优势类群为线虫,占群落总个体数的比例为95.53%,常见类群为螨类和弹尾类。不同水土治理措施样地中,中小型土壤动物群落个体数较农田有提高趋势,但无显著差异（P >0.05）;螨类和弹尾类个体数显著提高（P<0.05）;线虫个体数在人工沙打旺草地中显著高于农田（P<0.05）;中小型土壤动物垂直分布的表聚性较农田增强,并以地表凋落物覆盖显著的人工林最为明显。RDA分析表明,中小型土壤动物群落、螨类和弹尾类个体数与凋落物厚度、树（草）高和土壤有机质的变化之间呈显著正相关。以上结果说明,研究地区采取的几种水土治理植被均有利于中小型土壤动物群落的恢复;相比较,地表凋落物层显著的人工松树林、人工杨树林更加有益于螨类和弹尾类的恢复。     

Potential distribution of vulnerable Entandrophragma angolense (Welw.) C. DC. (Meliaceae) in East Africa

The various human‐induced threats imposed on nature have recently triggered the study of species' distributions. We developed potential suitability models using two algorithms for a threatened African mahogany, Entandrophragma angolense, in three East African countries; Kenya, Tanzania and Uganda. The effect of features selection and modelling algorithm selection on potential suitability predictions was explored. Occurrence records and high‐resolution environmental data were used. The two species distribution modelling techniques were genetic algorithm rule for prediction; and maximum entropy modelling. With Maxent, the area under the receiver characteristic operating curve (AUC) for potential distribution models tested on independent data ranged from 0.942 to 0.972 when using automatic features and from 0.974 to 0.666 with target or specific features. With GARP, AUC for potential distribution models ranged from 0.591 to 0.736 with all rule types and from 0.388 to 0.805 for specific rule types (Tables  1  and 2 ). The area under the E. angolense potential suitability was best predicted by soil, rainfall and aspect using GARP. Potential suitability increased with increasing aspect and decreased with increasing slope. Low rainfall and elevation increased potential suitability, while high levels of either variable decreased potential suitability. Potential suitability maps for vulnerable species require using a multi‐algorithm, fine scale data approach and incorporation of environmental variables like soil, slope, land use and elevation. Species distribution models can offer insight on the distribution requirements of vulnerable species and help guide the development of management plans. Results of this study suggest that E. angolense management plans should promote the protection of terrestrial forests surrounding water bodies including Mabira forest in Uganda.     

Facilitated Hyperpolarization Signaling in Vascular Smooth Muscle-overexpressing TRIC-A Channels

The TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation-specific channels and likely mediate counterion movements to support efficient Ca²⁺ release from the sarco/endoplasmic reticulum. Vascular smooth muscle cells (VSMCs) contain both TRIC subtypes and two Ca²⁺ release mechanisms; incidental opening of ryanodine receptors (RyRs) generates local Ca²⁺ sparks to induce hyperpolarization and relaxation, whereas agonist-induced activation of inositol trisphosphate receptors produces global Ca²⁺ transients causing contraction. Tric-a knock-out mice develop hypertension due to insufficient RyR-mediated Ca²⁺ sparks in VSMCs. Here we describe transgenic mice overexpressing TRIC-A channels under the control of a smooth muscle cell-specific promoter. The transgenic mice developed congenital hypotension. In Tric-a-overexpressing VSMCs from the transgenic mice, the resting membrane potential decreased because RyR-mediated Ca²⁺ sparks were facilitated and cell surface Ca²⁺-dependent K⁺ channels were hyperactivated. Under such hyperpolarized conditions, L-type Ca²⁺ channels were inactivated, and thus, the resting intracellular Ca²⁺ levels were reduced in Tric-a-overexpressing VSMCs. Moreover, Tric-a overexpression impaired inositol trisphosphate-sensitive stores to diminish agonist-induced Ca²⁺ signaling in VSMCs. These altered features likely reduced vascular tonus leading to the hypotensive phenotype. Our Tric-a-transgenic mice together with Tric-a knock-out mice indicate that TRIC-A channel density in VSMCs is responsible for controlling basal blood pressure at the whole-animal level.     

Insulin Secretion and Ca2+ Dynamics in β-Cells Are Regulated by PERK (EIF2AK3) in Concert with Calcineurin

Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) (EIF2AK3) is essential for normal development and function of the insulin-secreting β-cell. Although genetic ablation of PERK in β-cells results in permanent neonatal diabetes in humans and mice, the underlying mechanisms remain unclear. Here, we used a newly developed and highly specific inhibitor of PERK to determine the immediate effects of acute ablation of PERK activity. We found that inhibition of PERK in human and rodent β-cells causes a rapid inhibition of secretagogue-stimulated subcellular Ca²⁺ signaling and insulin secretion. These dysfunctions stem from alterations in store-operated Ca²⁺ entry and sarcoplasmic endoplasmic reticulum Ca²⁺-ATPase activity. We also found that PERK regulates calcineurin, and pharmacological inhibition of calcineurin results in similar defects on stimulus-secretion coupling. Our findings suggest that interplay between calcineurin and PERK regulates β-cell Ca²⁺ signaling and insulin secretion, and that loss of this interaction may have profound implications in insulin secretion defects associated with diabetes.     

The Dok-3/Grb2 Protein Signal Module Attenuates Lyn Kinase-dependent Activation of Syk Kinase in B Cell Antigen Receptor Microclusters

Recruitment of the growth factor receptor-bound protein 2 (Grb2) by the plasma membrane-associated adapter protein downstream of kinase 3 (Dok-3) attenuates signals transduced by the B cell antigen receptor (BCR). Here we describe molecular details of Dok-3/Grb2 signal integration and function, showing that the Lyn-dependent activation of the BCR transducer kinase Syk is attenuated by Dok-3/Grb2 in a site-specific manner. This process is associated with the SH3 domain-dependent translocation of Dok-3/Grb2 complexes into BCR microsignalosomes and augmented phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5′ phosphatase. Hence, our findings imply that Dok-3/Grb2 modulates the balance between activatory and inhibitory Lyn functions with the aim to adjust BCR signaling efficiency.     

Caveolin-1 Facilitates the Direct Coupling between Large Conductance Ca2+-activated K+ (BKCa) and Cav1.2 Ca2+ Channels and Their Clustering to Regulate Membrane Excitability in Vascular Myocytes

L-type voltage-dependent Ca²⁺ channels (LVDCC) and large conductance Ca²⁺-activated K⁺ channels (BK_Ca) are the major factors defining membrane excitability in vascular smooth muscle cells (VSMCs). The Ca²⁺ release from sarcoplasmic reticulum through ryanodine receptor significantly contributes to BK_Ca activation in VSMCs. In this study direct coupling between LVDCC (Cav1.2) and BK_Ca and the role of caveoline-1 on their interaction in mouse mesenteric artery SMCs were examined. The direct activation of BK_Ca by Ca²⁺ influx through coupling LVDCC was demonstrated by patch clamp recordings in freshly isolated VSMCs. Using total internal reflection fluorescence microscopy, it was found that a large part of yellow fluorescent protein-tagged BK_Ca co-localized with the cyan fluorescent protein-tagged Cav1.2 expressed in the plasma membrane of primary cultured mouse VSMCs and that the two molecules often exhibited FRET. It is notable that each BKα subunit of a tetramer in BK_Ca can directly interact with Cav1.2 and promotes Cav1.2 cluster in the molecular complex. Furthermore, caveolin-1 deficiency in knock-out (KO) mice significantly reduced not only the direct coupling between BK_Ca and Cav1.2 but also the functional coupling between BK_Ca and ryanodine receptor in VSMCs. The measurement of single cell shortening by 40 mm K⁺ revealed enhanced contractility in VSMCs from KO mice than wild type. Taken together, caveolin-1 facilitates the accumulation/clustering of BK_Ca-LVDCC complex in caveolae, which effectively regulates spatiotemporal Ca²⁺ dynamics including the negative feedback, to control the arterial excitability and contractility.