Contrasting changes in the abundance and diversity of North American bird assemblages from 1971 to 2010

Although it is generally recognized that global biodiversity is declining, few studies have examined long‐term changes in multiple biodiversity dimensions simultaneously. In this study, we quantified and compared temporal changes in the abundance, taxonomic diversity, functional diversity, and phylogenetic diversity of bird assemblages, using roadside monitoring data of the North American Breeding Bird Survey from 1971 to 2010. We calculated 12 abundance and diversity metrics based on 5‐year average abundances of 519 species for each of 768 monitoring routes. We did this for all bird species together as well as for four subgroups based on breeding habitat affinity (grassland, woodland, wetland, and shrubland breeders). The majority of the biodiversity metrics increased or remained constant over the study period, whereas the overall abundance of birds showed a pronounced decrease, primarily driven by declines of the most abundant species. These results highlight how stable or even increasing metrics of taxonomic, functional, or phylogenetic diversity may occur in parallel with substantial losses of individuals. We further found that patterns of change differed among the species subgroups, with both abundance and diversity increasing for woodland birds and decreasing for grassland breeders. The contrasting changes between abundance and diversity and among the breeding habitat groups underscore the relevance of a multifaceted approach to measuring biodiversity change. Our findings further stress the importance of monitoring the overall abundance of individuals in addition to metrics of taxonomic, functional, or phylogenetic diversity, thus confirming the importance of population abundance as an essential biodiversity variable.     

Spectral analysis of a series of partially protected and deprotected tetrapeptides, analogues of AS-I phytotoxin

Summary A series of six tetrapeptides, analogues of AS-I phytotoxin, pathogenic to sunflower, have been synthesized either in solution and/or by solid phase methods and have been tested for phytotoxic activity in various plants and cytotoxic activity in three cancer cell lines. These peptides were identified as model compounds by fast atom bombardment (FAB), plasma desorption (PD), electrospray ionization (ESI) mass spectrometry and by¹H,¹H-¹H,¹³C and¹H-¹³C NMR. The data presented show that in protected tetrapeptides the molecular ion was easily identified whereas some difficulties appeared with the fully deprotected peptides. NMR spectra are given.     

Associations of the PTEN − 9C>G polymorphism with insulin sensitivity and central obesity in Chinese

Background

Phosphatase and tensin homolog on chromosome 10 gene (PTEN) is known as a tumor-suppressor gene. Previous studies demonstrated that PTEN dysfunction affects the function of insulin. However, investigations of PTEN single nucleotide polymorphisms (SNPs) and IR-related disease associations are limited. The aim of the present study was to investigate whether its polymorphism could be involved in the risk of metabolic syndrome (MetS).

Methods

The genotype frequency of PTEN − 9C>G polymorphism was determined by using a Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) method in 530 subjects with MetS and 202 healthy control subjects of the Han Ethnic Chinese population in a case–control analysis.

Results

The PTEN − 9C>G polymorphism was not associated with MetS or its hyperglycemia, hypertension and hypertriglyceridemia components. In the control individuals aged < 60 years or ≥ 60 years, the CG genotype individuals had lower insulin sensitivity than CC individuals (P < 0.05). In the < 60-year-old MetS group and normal glucose tolerance (NGT) subgroup, the CG individuals had lower insulin sensitivity and higher waist circumference (WC) and waist-height-ratio (WHtR) than CC individuals (P < 0.05). Multiple linear regression analysis showed that the PTEN polymorphism (P = 0.001) contributed independently to 4.2% (adjusted R²) of insulin sensitivity variance (estimated by Matsuda ISI), while age (P = 0.004), gender (P = 0.000) and the PTEN polymorphism (P = 0.032) contributed independently to 5.6% (adjusted R²) of WHtR variance.

Conclusions

The CG genotype of PTEN − 9C>G polymorphism was not associated with MetS and some of its components as well. However, it may not only decrease insulin sensitivity in the healthy control and MetS in pre-elderly or NGT subjects, but may also increase the risk of central obesity among these MetS individuals.     

Polydatin alleviated radiation‐induced lung injury through activation of Sirt3 and inhibition of epithelial–mesenchymal transition

Radiation‐induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. It is characterized with two main features including early radiation pneumonitis and fibrosis in later phase. This study was to investigate the potential radioprotective effects of polydatin (PD), which was shown to exert anti‐inflammation and anti‐oxidative capacities in other diseases. In this study, we demonstrated that PD‐mitigated acute inflammation and late fibrosis caused by irradiation. PD treatment inhibited TGF‐β1‐Smad3 signalling pathway and epithelial–mesenchymal transition. Moreover, radiation‐induced imbalance of Th1/Th2 was also alleviated by PD treatment. Besides its free radical scavenging capacity, PD induced a huge increase of Sirt3 in culture cells and lung tissues. The level of Nrf2 and PGC1α in lung tissues was also elevated. In conclusion, our data showed that PD attenuated radiation‐induced lung injury through inhibiting epithelial–mesenchymal transition and increased the expression of Sirt3, suggesting PD as a novel potential radioprotector for RILI.     

Fivefold increase in derivation rates of mouse embryonic stem cells after supplementation of the media with multiple factors

The objective of this study was to determine the ability of multiple-factor supplementation to augment derivation of mouse embryonic stem (mES) cells. Three factors, leukemia inhibitory factor (LIF), Parke-Davis 98059 (PD98059), and 6-bromoindirubin-3′-oxime (BIO), were added as supplements (individually or in a combination of all three) at two consecutive stages of culture; that is, from the start of blastocyst culture to the outgrowth stage, and from putting disaggregated outgrowth into culture medium to generation of primary mES colonies, respectively. The main outcome measure was the percentage of derivable mES cell lines, based on the number of blastocysts initially cultured. Three experiments demonstrated the following: (1) For the addition of individual single factor, only LIF yielded mES cell lines (6.2%), whereas a combination of all three factors resulted in the greatest number of mES cell lines (31.3%). (2) The advantages of a combination of multiple factors (LIF + PD98059 + BIO) were manifested only when they were used during the first stage of the culture and not during the second stage (31.6% vs. 6.2%, respectively). (3) The quality of the inner cell mass (ICM) outgrowth obtained from first-stage culture was studied. After alkaline phosphatase and Oct-4 staining, which documented pluripotency of the embryonic stem cells, outgrowths cultured in multiple factors (LIF + PD98059 + BIO) stained much stronger and in higher proportions than did those obtained after supplementation only with LIF (80% vs. 30%, respectively).     

β-Sheet-breaking peptides inhibit the fibrillation of human α-synuclein

α-Synuclein is the major components of the intracellular protein-aggregates, found in the dopaminergic neurons of Parkinson’s disease patients. Previously, we screened for α-synuclein substitution mutants that prevent fibril formation of both wild-type and Parkinson’s disease-linked α-synuclein variants. In the present study, we show that short synthetic peptides derived from these mutant sequences not only prevented α-synuclein fibrillation but also dissolved preformed α-synuclein aggregates in vitro. The hexapeptide PGVTAV, which was the shortest peptide that retained the ability to block α-synuclein fibrillation, may serve as a lead compound for the development of therapeutics for Parkinson’s disease.     

Molecular Insights into the Interaction between α-Synuclein and Docosahexaenoic Acid

α-Synuclein (α-syn) is a 140-residue protein of unknown function, involved in several neurodegenerative disorders, such as Parkinson's disease. Recently, the possible interaction between α-syn and polyunsaturated fatty acids has attracted a strong interest. Indeed, lipids are able to trigger the multimerization of the protein in vitro and in cultured cells. Docosahexaenoic acid (DHA) is one of the main fatty acids (FAs) in cerebral gray matter and is dynamically released following phospholipid hydrolysis. Moreover, it has been found in high levels in brain areas containing α-syn inclusions in patients affected by Parkinson's disease. Debated and unsolved questions regard the nature of the molecular interaction between α-syn and DHA and the effect exerted by the protein on the aggregated state of the FA. Here, we show that α-syn is able to strongly interact with DHA and that a mutual effect on the structure of the protein and on the physical state of the lipid derives from this interaction. α-Syn acquires an α-helical conformation in a simple two-state transition. The binding of the protein to the FA leads to a reduction of the size of the spontaneously formed aggregated species of DHA as well as of the critical aggregate concentration of the lipid. Specifically, biophysical methods and electron microscopy observations indicated that the FA forms oil droplets in the presence of α-syn. Limited proteolysis experiments showed that, when the protein is bound to the FA oil droplets, it is initially cleaved in the 89-102 region, suggesting that this chain segment is sufficiently flexible or unfolded to be protease-sensitive. Subsequent proteolytic events produce fragments corresponding to the first 70-80 residues that remain structured and show high affinity for the lipid. The fact that a region of the polypeptide chain remains accessible to proteases, when interacting with the lipid, suggests that this region could be involved in other interactions, justifying the ambivalent propensity of α-syn towards folding or aggregation in the presence of FAs.     

Heat shock protein 70 inhibits alpha-synuclein fibril formation via interactions with diverse intermediates

alpha-Synuclein (AS) is a main component of Lewy bodies in midbrain dopamine neurons pathologically characteristic of Parkinson's disease. We show that heat shock protein (Hsp) 70 inhibits AS fibril formation via preventing the formation of prefibrillar AS (PreAS), binding with PreAS to impede nuclei formation, and binding with nuclei to retard fibril elongation. Also, Hsp70 suppresses the PreAS-induced permeabilization of vesicular membrane through interactions with PreAS. The substrate-binding domain alone is sufficient for Hsp70 to inhibit AS fibril formation. The binding of Hsp70 with PreAS only requires the substrate-binding subdomain, and the binding with AS nuclei requires the C-terminal lid subdomain as well. The results may form the molecular basis for elucidating the mechanism of AS fibril formation and the crucial roles of chaperones in protecting proteins from toxic conversion in many conformational diseases.     

异常激活的葡萄糖-6-磷酸脱氢酶通过上调周期蛋白D1表达促进肾透明细胞癌增殖

葡萄糖6-磷酸脱氢酶（glucose 6-phosphate dehydrogenase,G6PD）为磷酸戊糖途径的调节酶。研究表明,G6PD与多种恶性肿瘤的发生密切相关。然而,G6PD在肾透明细胞癌（clear cell renal cell carcinoma, ccRCC）中的功能及其作用机制却鲜有报道。本研究通过TCGA数据分析发现,G6PD在肾透明细胞癌TNM Ⅲ/Ⅳ期mRNA表达水平显著升高,与患者的性别、原发肿瘤直径、淋巴结转移、远端转移、病灶一侧的偏重性、病理分级以及TNM临床分期密切相关。并且,G6PD异常激活有可能成为评价肾透明细胞癌患者不良预后的分子。细胞系检测结果提示,与对照293T细胞及恶性程度较低的786-O细胞相比,恶性程度较高的Caki-1细胞中的G6PD表达及活性明显增加。基因稳定转染结合CCK8分析结果显示,G6PD过表达或异常激活可显著提高293T及786-O细胞的增殖能力,并且促进786-O细胞中周期蛋白D1基因表达上调。综上,本研究通过TCGA数据库分析和稳定细胞系检测及CCK8分析,结果显示,G6PD在肾透明细胞癌中异常激活,并可上调细胞周期蛋白D1表达,进而促进肿瘤细胞增殖。该研究为进一步揭示肾透明细胞癌分子发病机制以及开发有效的靶向治疗方案提供了借鉴。