Evolutionary and demographic history among Maghrebian Medicago species (Fabaceae) based on the nucleotide sequences of the chloroplast DNA barcode trnH-psbA

Data from trnH-psbA intergenic spacer (cpDNA) were analyzed to elucidate molecular evolution within and among Maghrebian species of Medicago. The spacer highlighted a high interspecific variation and a low intraspecific diversity among species. Haplotype and nucleotide diversities revealed high level of variation. Parsimony and median-joining Network methods revealed (1) the segregation into 17 haplotypes; (2) the ancestral behaviour of the annual Medicago minima and (3) the clusters are independent of the geographic origin. The neutral evolution of Wright and Fisher is rejected since the Tajima's D values deviated from 0. Besides, the statistical analyses are in agreement with an evolution into stable populations' size.     

Variable phenotype in 17q12 microdeletions: Clinical and molecular characterization of a new case

Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer–Rokitansky–Küster–Hauser Syndrome (MRKH, OMIM 277000) in females and, recently, were associated with intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms.     

Role and importance of polymorphisms with respect to DNA methylation for the expression of CYP2E1 enzyme

Different individuals possess slightly different genetic information and show genetically-determined differences in several enzyme activities due to genetic variability. Following an integrated approach, we studied the polymorphisms and methylation of sites contained in the 5′ flanking region of the metabolizing enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about the influence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and a demethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, was not consistently associated with the increase of enzyme expression. Interestingly, the Rsa/Pst haplotype differentially influenced CYP2E1 enzyme expression. In addition, regarding the Variable Number of Tandem Repeats polymorphism, cells with A4/A4 genotype showed a greater expression inhibition (ranging from 20% to 30%) compared with others carrying the A2/A2 one, while those cells bringing A2/A3 genotype showed an increase of expression (of 25%, about). Finally, we demonstrated for the first time that the A2 and A3 CYP2E1 alleles play a more important role in the expression of the enzyme, compared with other (epi)genetic factors, since they are binding sites for trans-acting proteins.     

Expression analysis of ATAD3 isoforms in rodent and human cell lines and tissues

ATAD3 (ATPase family AAA-Domain containing protein 3) is a mitochondrial inner membrane ATPase with unknown but vital functions. Initial researches have focused essentially on the major p66-ATAD3 isoform, but other proteins and mRNAs are described in the data banks. Using a set of anti-peptide antibodies and by the use of rodent and human cell lines and organs, we tried to detail ATAD3 gene expression profiles and to verify the existence of the various ATAD3 isoforms. In rodent, the single ATAD3 gene is expressed as a major isoform of 67 kDa, (ATAD3l; long), in all cells and organs studied. A second isoform, p57-ATAD3s (small), is expressed specifically throughout brain development and in adult, and overexpressed around the peri-natal period. p57-ATAD3s is also expressed in neuronal and glial rodent cell lines, and during in vitro differentiation of primary cultured rat oligodendrocytes. Other smaller isoforms were also detected in a tissue-specific manner. In human and primates, ATAD3 paralogues are encoded by three genes (ATAD3A, 3B and 3C), each of them presenting several putative variants. Analyzing the expression of ATAD3A and ATAD3B with four specific anti-peptide antibodies, and comparing their expressions with in vitro expressed ATAD3 cDNAs, we were able to observe and define five isoforms. In particular, the previously described p72-ATAD3B is confirmed to be in certain cases a phosphorylated form of ATAD3As. Moreover, we observed that the ATAD3As phosphorylation level is regulated by insulin and serum. Finally, exploring ATAD3 mRNA expression, we confirmed the existence of an alternative splicing in rodent and of several mRNA isoforms in human.     

A mitogenomic phylogeny and genetic history of sable (Martes zibellina)

We assessed phylogeny of sable (Martes zibellina, Linnaeus, 1758) by sequence analysis of nearly complete, new mitochondrial genomes in 36 specimens from different localities in northern Eurasia (Primorye, Khabarovsk and Krasnoyarsk regions, the Kamchatka Peninsula, the Kuril Islands and the Urals). Phylogenetic analysis of mtDNA sequences demonstrates that two clades, A and BC, radiated about 200–300 thousand years ago (kya) according to results of Bayesian molecular clock and RelTime analyses of different mitogenome alignments (nearly complete mtDNA sequences, protein-coding region, and synonymous sites), while the age estimates of clades A, B and C fall within the Late Pleistocene (~ 50–140 kya). Bayesian skyline plots (BSPs) of sable population size change based on analysis of nearly complete mtDNAs show an expansion around 40 kya in the warm Karganian time, without a decline of population size around the Last Glacial Maximum (21 kya). The BSPs based on synonymous clock rate indicate that M. zibellina experienced demographic expansions later, approximately 22 kya. The A2a clade that colonized Kamchatka ~ 23–50 kya (depending on the mutation rate used) survived the last glaciation there as demonstrated by the BSP analysis. In addition, we have found evidence of positive selection acting at ND4 and cytochrome b genes, thereby suggesting adaptive evolution of the A2a clade in Kamchatka.     

Is Sp1 binding site polymorphism within COL1A1 gene associated with tennis elbow?

Tennis elbow defines a condition of pain and tenderness over the lateral epicondyle of the humerus. The exact aetiology of the injury is not yet fully understood. The major constituent of tendons is type 1 collagen which is encoded by COL1A1 gene. The aim of the study was to determine whether Sp1 binding site polymorphism (SNP rs1800012; 1546G/T) within the intronic region of COL1A1 gene is associated with tennis elbow. One hundred and three tennis elbow patients and one hundred and three healthy subjects without any history of previous ligament or tendon injuries were recruited for this genetic association study. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism by using PCR–RFLP method. There were no observed statistical differences in the genotype (p = 0.17) or allele (p = 0.11) distributions between the groups. G allele frequency in patients and controls was 82.5% and 76.21%, and T allele frequency was 17.5% and 23.79% respectively. This study has shown that there is no association between this polymorphism and tennis elbow within the population studied.     

Systems biology unravels interferon responses to respiratory virus infections

Interferon production is an important defence against viral replication and its activation is an attractive therapeutic target. However, it has long been known that viruses perpetually evolve a multitude of strategies to evade these host immune responses. In recent years there has been an explosion of information on virusinduced alterations of the host immune response that have resulted from data-rich omics technologies. Unravelling how these systems interact and determining the overall outcome of the host response to viral infection will play an important role in future treatment and vaccine development. In this review we focus primarily on the interferon pathway and its regulation as well as mechanisms by which respiratory RNA viruses interfere with its signalling capacity.     

Innate immune recognition of respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in infants and young children. Severe clinical manifestation of RSV infection is a bronchiolitis, which is common in infants under six months of age. Recently, RSV has been recognized as an important cause of respiratory infection in older populations with cardiovascular morbidity or immunocompromised patients. However, neither a vaccine nor an effective antiviral therapy is currently available. Moreover, the interaction between the host immune system and the RSV pathogen during an infection is not well understood. The innate immune system recognizes RSV through multiple mechanisms. The first innate immune RSV detectors are the pattern recognition receptors (PRRs), including toll-like receptors (TLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-biding oligomerization domain (NOD)-like receptors (NLRs). The following is a review of studies associated with various PRRs that are responsible for RSV virion recognition and subsequent induction of the antiviral immune response during RSV infection. [BMB Reports 2014; 47(4): 184-191]     

肺炎支原体肺炎患儿口咽部菌群的改变

目的 比较健康儿童与肺炎支原体肺炎患儿口咽部菌群的差异,分析肺炎支原体感染对儿童口咽部菌群变化的可能影响。方法 采用高通量测序技术,对30例肺炎支原体肺炎患儿及30例健康儿童16S rDNA进行测序分析,比较两组间的菌群多样性及在门、属水平上菌群结构差异。结果 健康儿童与肺炎支原体肺炎患儿在性别、年龄、抗生素使用等方面差异无统计学意义。肺炎支原体肺炎患儿口咽部菌群多样性比健康儿童明显降低。在门水平上,Proteobacteria（变形菌门）、Bacteroidetes（拟杆菌门）和Fusobacteria（梭杆菌门）在健康儿童中相对丰度显著高于肺炎支原体肺炎患儿组,而Firmicutes（厚壁菌门）、Tenericutes（柔膜菌门）和Actinobacteria（放线菌门）在肺炎支原体肺炎患儿组中相对丰度均显著高于健康儿童组;在属水平上,两组排在相对丰度前10位的属差异具有统计学意义,共有6个属在肺炎支原体肺炎患儿中显著增加,分别为Staphylococcus（葡萄球菌）、Actinomyces（放线菌属）、Acinetobacter（不动细菌属）、Atopobium（阿托波菌属）、Corynebacterium（棒状杆菌）和Abiotrophia（营养缺陷菌属）。结论 肺炎支原体肺炎患儿口咽部菌群存在明显的改变,其口咽部菌群多样性比健康儿童明显降低,在门、属水平肺炎支原体肺炎患儿与健康儿童差异均有统计学意义。     

呼吸道合胞病毒肺炎患儿血清NRAV水平及临床意义

探讨呼吸道合胞病毒（RSV）肺炎患儿血清中抗病毒应答负性调节因子（NRAV）的表达水平及临床意义。

选取我院收治的RSV肺炎患儿100例作为RSV组,并将RSV肺炎患儿根据肺炎严重指数（PSI）分为低危组（62例）、中危组（24例）及高危组（14例）。另选取同期于本院体检的102例健康儿童作为对照组。采用荧光定量PCR法检测血清NRAV水平,用肺功能仪检测受试儿童肺功能,采用Pearson法分析血清NRAV水平与RSV肺炎患儿肺功能的相关性;采用Logistics回归分析RSV肺炎患儿病情严重程度的影响因素;采用ROC曲线分析血清NRAV水平对RSV肺炎的诊断价值。

RSV组患儿血清NRAV水平高于对照组,第1秒用力呼气容积占预计值百分比（FEV₁%）及FEV₁/用力肺活量（FVC）均低于对照组（均P＜0.05）。不同严重程度RSV肺炎患儿血清NRAV水平、FEV₁%及FEV₁/FVC比较差异有统计学意义（均P＜0.05）。低危组、中危组、高危组RSV肺炎患儿血清NRAV水平依次升高,FEV₁%及FEV₁/FVC均依次下降,组间两两比较差异有统计学意义（均P＜0.05）。RSV肺炎患儿血清NRAV水平与FEV₁%及FEV₁/FVC均呈负相关（均P＜0.05）。Logistics分析显示,血清NRAV水平升高、FEV₁%及FEV₁/FVC水平下降均是影响RSV肺炎严重程度的独立危险因素（均P＜0.05）。ROC曲线分析显示,血清NRAV水平诊断RSV肺炎的曲线下面积为0.843,敏感度为76.0%,特异度为88.2%,最佳截断值为1.14。

RSV肺炎患儿血清NRAV水平升高且随着疾病严重程度的加重而升高,其水平可反映肺功能,对RSV肺炎具有一定诊断价值。