RNA genome packaging and capsid assembly of bluetongue virus visualized in host cells.

Unlike those of double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and ssRNA viruses, the mechanism of genome packaging of dsRNA viruses is poorly understood. Here, we combined the techniques of high-resolution cryoelectron microscopy (cryo-EM), cellular cryoelectron tomography (cryo-ET), and structure-guided mutagenesis to investigate genome packaging and capsid assembly of bluetongue virus (BTV), a member of the Reoviridae family of dsRNA viruses. A total of eleven assembly states of BTV capsid were captured, with resolutions up to 2.8 Å, with most visualized in the host cytoplasm. ATPase VP6 was found underneath the vertices of capsid shell protein VP3 as an RNA-harboring pentamer, facilitating RNA packaging. RNA packaging expands the VP3 shell, which then engages middle- and outer-layer proteins to generate infectious virions. These revealed "duality" characteristics of the BTV assembly mechanism reconcile previous contradictory co-assembly and core-filling models and provide insights into the mysterious RNA packaging and capsid assembly of Reoviridae members and beyond.

Mechanism of DNA translocation underlying chromatin remodelling by Snf2.

Chromatin remodellers include diverse enzymes with distinct biological functions, but nucleosome-sliding activity appears to be a common theme1,2. Among the remodelling enzymes, Snf2 serves as the prototype to study the action of this protein family. Snf2 and related enzymes share two conserved RecA-like lobes3, which by themselves are able to couple ATP hydrolysis to chromatin remodelling. The mechanism by which these enzymes couple ATP hydrolysis to translocate the nucleosome along the DNA remains unclear2,4-8. Here we report the structures of Saccharomyces cerevisiae Snf2 bound to the nucleosome in the presence of ADP and ADP-BeFx. Snf2 in the ADP-bound state adopts an open conformation similar to that in the apo state, and induces a one-base-pair DNA bulge at superhelix location 2 (SHL2), with the tracking strand showing greater distortion than the guide strand. The DNA distortion propagates to the proximal end, leading to staggered translocation of the two strands. The binding of ADP-BeFx triggers a closed conformation of the enzyme, resetting the nucleosome to a relaxed state. Snf2 shows altered interactions with the DNA in different nucleotide states, providing the structural basis for DNA translocation. Together, our findings suggest a fundamental mechanism for the DNA translocation that underlies chromatin remodelling.

Structurally diverse triterpenoids with antibacterial activities from Euphorbia humifusa.

An exploration of antibacterial components from the whole plant of Euphorbia humifusa led to the isolation of 14 new triterpenoids, euphohumifusoids A-N (1-7 and 9-15), as well as four known analogues (8 and 16-18). Their structures were elucidated by extensively analysis of the spectroscopic data and X-ray crystallography using Cu Kα radiation. Among them, euphohumifusoid A (1) bears an unique 6(7 â†’ 8)abeo scaffold originated from a D:C-friedo-oleanane skeleton for the first time, euphohumifusoids H and I (9 and 10) possess a rare α,ß-unsaturated-γ-lactone chain originated from 25,26,27-trinordammaranes, and euphohumifusoid L (13) is a highly modified 3,4-seco-25,26,27-trinorcycloartane. Notably, in antibacterial bioassay, compound 1 displayed excellent antibacterial activities against Bacillus cereus, Staphylococcus aureus, and S.epidermidis with MIC of 12.5, 25, and 25 µg/mL, comparable to the positive controls. Upon exposure to 1 and 2 MIC of 1, B.cereus underwent drastic morphological changes, resulting in complete disruption of the cells. Meanwhile, compound 1 also exhibited remarkable antibiofilm activity against B.cereus at 1 MIC and 2 MIC.

Protein target highlights in CASP15: Analysis of models by structure providers.

We present an in-depth analysis of selected CASP15 targets, focusing on their biological and functional significance. The authors of the structures identify and discuss key protein features and evaluate how effectively these aspects were captured in the submitted predictions. While the overall ability to predict three-dimensional protein structures continues to impress, reproducing uncommon features not previously observed in experimental structures is still a challenge. Furthermore, instances with conformational flexibility and large multimeric complexes highlight the need for novel scoring strategies to better emphasize biologically relevant structural regions. Looking ahead, closer integration of computational and experimental techniques will play a key role in determining the next challenges to be unraveled in the field of structural molecular biology.

Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure.

Chromatin remodellers are helicase-like, ATP-dependent enzymes that alter chromatin structure and nucleosome positions to allow regulatory proteins access to DNA. Here we report the cryo-electron microscopy structure of chromatin remodeller Switch/sucrose non-fermentable (SWI2/SNF2) from Saccharomyces cerevisiae bound to the nucleosome. The structure shows that the two core domains of Snf2 are realigned upon nucleosome binding, suggesting activation of the enzyme. The core domains contact each other through two induced Brace helices, which are crucial for coupling ATP hydrolysis to chromatin remodelling. Snf2 binds to the phosphate backbones of one DNA gyre of the nucleosome mainly through its helicase motifs within the major domain cleft, suggesting a conserved mechanism of substrate engagement across different remodellers. Snf2 contacts the second DNA gyre via a positively charged surface, providing a mechanism to anchor the remodeller at a fixed position of the nucleosome. Snf2 locally deforms nucleosomal DNA at the site of binding, priming the substrate for the remodelling reaction. Together, these findings provide mechanistic insights into chromatin remodelling.

Microbial mechanisms to transform the super-trace element tellurium: a systematic review and discussion of nanoparticulate phases.

Tellurium is a super-trace metalloid on Earth. Owing to its excellent physical and chemical properties, it is used in industries such as metallurgy and manufacturing, particularly of semiconductors and - more recently - solar panels. As the global demand for tellurium rises, environmental issues surrounding tellurium have recently aroused concern due to its high toxicity. The amount of tellurium released to the environment is increasing, and microorganisms play an important role in the biogeochemical cycling of environmental tellurium. This review focuses on novel developments on tellurium transformations driven by microbes and includes the following sections: (1) history and applications of tellurium; (2) toxicity of tellurium; (3) microbial detoxification mechanisms against soluble tellurium anions including uptake, efflux and methods of reduction, and reduced ability to cope with oxidation stress or repair damaged DNA; and (4) the characteristics and applications of tellurium nanoparticles (TeNPs) produced by microbes. This review raises the awareness of microorganisms in tellurium biogeochemical cycling and the growing applications for microbial tellurium nanoparticles.

Combining QTL mapping and gene co-expression network analysis for prediction of candidate genes and molecular network related to yield in wheat.

BACKGROUND: Wheat (Triticum aestivum L.) is an important cereal crop. Increasing grain yield for wheat is always a priority. Due to the complex genome of hexaploid wheat with 21 chromosomes, it is difficult to identify underlying genes by traditional genetic approach. The combination of genetics and omics analysis has displayed the powerful capability to identify candidate genes for major quantitative trait loci (QTLs), but such studies have rarely been carried out in wheat. In this study, candidate genes related to yield were predicted by a combined use of linkage mapping and weighted gene co-expression network analysis (WGCNA) in a recombinant inbred line population. RESULTS: QTL mapping was performed for plant height (PH), spike length (SL) and seed traits. A total of 68 QTLs were identified for them, among which, 12 QTLs were stably identified across different environments. Using RNA sequencing, we scanned the 99,168 genes expression patterns of the whole spike for the recombinant inbred line population. By the combined use of QTL mapping and WGCNA, 29, 47, 20, 26, 54, 46 and 22 candidate genes were predicted for PH, SL, kernel length (KL), kernel width, thousand kernel weight, seed dormancy, and seed vigor, respectively. Candidate genes for different traits had distinct preferences. The known PH regulation genes Rht-B and Rht-D, and the known seed dormancy regulation genes TaMFT can be selected as candidate gene. Moreover, further experiment revealed that there was a SL regulatory QTL located in an interval of about 7 Mbp on chromosome 7A, named TaSL1, which also involved in the regulation of KL. CONCLUSIONS: A combination of QTL mapping and WGCNA was applied to predicted wheat candidate genes for PH, SL and seed traits. This strategy will facilitate the identification of candidate genes for related QTLs in wheat. In addition, the QTL TaSL1 that had multi-effect regulation of KL and SL was identified, which can be used for wheat improvement. These results provided valuable molecular marker and gene information for fine mapping and cloning of the yield-related trait loci in the future.

Structure and regulation of the chromatin remodeller ISWI.

ISWI is a member of the SWI2/SNF2 family of chromatin remodellers, which also includes Snf2, Chd1, and Ino80. ISWI is the catalytic subunit of several chromatin remodelling complexes, which mobilize nucleosomes along genomic DNA, promoting replication progression, transcription repression, heterochromatin formation, and many other nuclear processes. The ATPase motor of ISWI is an autonomous remodelling machine, whereas its carboxy (C)-terminal HAND-SAND-SLIDE (HSS) domain functions in binding extranucleosomal linker DNA. The activity of the catalytic core of ISWI is inhibited by the regulatory AutoN and NegC domains, which are in turn antagonized by the H4 tail and extranucleosomal DNA, respectively, to ensure the appropriate chromatin landscape in cells. How AutoN and NegC inhibit ISWI and regulate its nucleosome-centring activity remains elusive. Here we report the crystal structures of ISWI from the thermophilic yeast Myceliophthora thermophila and its complex with a histone H4 peptide. Our data show the amino (N)-terminal AutoN domain contains two inhibitory elements, which collectively bind the second RecA-like domain (core2), holding the enzyme in an inactive conformation. The H4 peptide binds to the core2 domain coincident with one of the AutoN-binding sites, explaining the ISWI activation by H4. The H4-binding surface is conserved in Snf2 and functions beyond AutoN regulation. The C-terminal NegC domain is involved in binding to the core2 domain and functions as an allosteric element for ISWI to respond to the extranucleosomal DNA length.

Hepatoprotective Polysaccharides from Geranium wilfordii: Purification, Structural Characterization, and Their Mechanism.

Traditional Chinese Medicine is generally used as a decoction to guard health. Many active ingredients in the decoction are chemical ingredients that are not usually paid attention to in phytochemical research, such as polysaccharides, etc. Based on research interest in Chinese herbal decoction, crude polysaccharides from G. wilfordii (GCP) were purified to obtain two relatively homogeneous polysaccharides, a neutral polysaccharide (GNP), and an acid polysaccharide (GAP) by various chromatographic separation methods, which were initially characterized by GC-MS, NMR, IR, and methylation analysis. Studies on the hepatoprotective activity of GCP in vivo showed that GCP might be a potential agent for the prevention and treatment of acute liver injury by inhibiting the secretion levels of ALT, AST, IL-6, IL-1ß, TNF-α, and MDA expression levels, increasing SOD, and the GSH-Px activity value. Further, in vitro assays, GNP and GAP, decrease the inflammatory response by inhibiting the secretion of IL-6 and TNF-α, involved in the STAT1/T-bet signaling pathway.

USP31 acetylation at Lys1264 is essential for its activity and cervical cancer cell growth.

Ubiquitin-specific protease 31 (USP31) is a member of deubiquitinase family that is involved in nuclear factor-κB activation and sarcomagenesis. However, little is known about posttranslational modification in the regulation of its activity and cervical cancer cell growth. In our study, we found that the Lys1264 residue of USP31 can be modified with an acetyl group by high-resolution mass spectrometry in HeLa cell line, and site-specific mutagenesis can significantly increase USP31 ubiquitin hydrolase activity and decrease the expression of p65. When being transfected with a plasmid expressing mutated USP31, the number of cancer cells was significantly decreased. We also observed that mutated USP31 could promote apoptosis but not cell cycle by flow cytometer analysis. Overexpression of mutated USP31 could reverse the effect in USP31 knockdown cell line. To further investigate its activity in tumorigenesis, deacetylase sirtuin 1 (Sirt1) was shown to interact with USP31 by co-immunoprecipitation and blocking the function of Sirt1 by knockdown or the inhibitor nicotinamide could increase the acetylation of USP31. When Lys1264 of USP31 mutated, Sirt1 could not remove its acetylation and alter the expression level of p65. Finally, inhibition or knockdown of Sirt1 suppressed USP31 activity in HeLa cell line, leading to cisplatin-induced apoptosis resistance. Therefore, acetylation at Lys1264 suppresses USP31 activity and plays a protective role in cancer cell growth. Our study contributes to understanding the mechanism of USP31 activity regulation and its role in tumorigenesis.

Transcriptome analyses of rhesus monkey preimplantation embryos reveal a reduced capacity for DNA double-strand break repair in primate oocytes and early embryos.

Preimplantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell-fate commitment. The molecular basis of these processes remains obscure in primates in which there is a high rate of embryo wastage. Thus, understanding the factors involved in genome reprogramming and ZGA might help reproductive success during this susceptible period of early development and generate induced pluripotent stem cells with greater efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution. By using RNA-seq in single and pooled oocytes and embryos, we defined the transcriptome throughout preimplantation development in rhesus monkey. In comparison to archival human and mouse data, we found that the transcriptome dynamics of monkey oocytes and embryos were very similar to those of human but very different from those of mouse. We identified several classes of maternal and zygotic genes, whose expression peaks were highly correlated with the time frames of genome reprogramming, ZGA, and cell-fate commitment, respectively. Importantly, comparison of the ZGA-related network modules among the three species revealed less robust surveillance of genomic instability in primate oocytes and embryos than in rodents, particularly in the pathways of DNA damage signaling and homology-directed DNA double-strand break repair. This study highlights the utility of monkey models to better understand the molecular basis for genome reprogramming, ZGA, and genomic stability surveillance in human early embryogenesis and may provide insights for improved homologous recombination-mediated gene editing in monkey.

Effects of small nucleolar RNA SNORD44 on the proliferation, apoptosis and invasion of glioma cells.

To master the effect of small nucleolar RNA, SNORD44, on the proliferation, apoptosis and invasion of glioma cells and its relevant mechanism. SNORD44 and GAS5 expression in glioma tissues and cells was detected through qRT-PCR. Then, the glioma cell lines (U87 and U251) were divided into different groups with different treatments. Cell proliferation was determined by MTT assay, while the abilities of the cell migration and invasion were measured by wound-healing test and Transwell assay, respectively. Cell apoptosis were detected by flow cytometry and TUNEL assay. The expression of apoptosis proteins was quantified through Western blotting. Finally, the xenograft models were established on nude mice to investigate the effects of SNORD44 on the growth of glioma and the expressions of Ki67, MMP2 and MMP9 in vivo. SNORD44 and GAS5 were down-regulated in glioma tissues and cells in a positive correlation. Either SNORD44 or GAS5 overexpression decreased the proliferation, invasion and migration of U87 and U251 cells with the up-regulation of apoptosis rates, as well as the expressions of cleaved PARP, caspase 3, caspase 8 and caspase 9. Moreover, the in vivo experiment showed that overexpression of SNORD44 blocked the growth of glioma xenograft in nude mice accompanying with the inhibition of Ki67, MMP2 and MMP9 expressions. The combination overexpression of SNORD44 and GAS5 gained better inhibitory effects on glioma cells. Overexpression of SNORD44 and GAS5 activate the caspase-dependent apoptosis pathway to facilitate the apoptosis with the inhibited proliferation, invasion and migration of glioma cells.

Larkinella punicea sp. nov., isolated from manganese mine soil.

Strain ZZJ9T is a Gram-stain-negative, rod-shaped, aerobic bacterium isolated from manganese mine soil. Strain ZZJ9T showed the highest 16S rRNA gene sequence similarities with Larkinella rosea 15J16-1T3AT (97.1%), Larkinella terrae 15J8-8T (97.0%), Larkinella knui 15J6-3T6T (96.8%), and Larkinella ripae 15J11-1T (95.3%). The genome size of strain ZZJ9T was 8.01 Mb and the DNA G+C content was 51.8 mol%. ANI values among strain ZZJ9T and Larkinella rosea 52004 T, Larkinella knui KCTC 42998T, and Larkinella terrae 52001T were 80.5%, 82.7%, and 80.5%, respectively. dDDH values among strain ZZJ9T and Larkinella rosea 52004T, Larkinella knui KCTC 42998T, and Larkinella terrae 52001T were 23.5%, 26.0%, and 23.6%, respectively. Furthermore, the genome of strain ZZJ9T contained 6302 predicted protein-coding genes and 3114 (49%) of them had classificatory functions. The major quinone of strain ZZJ9T was menaquinone-7 and the main cellular fatty acids were C16:1ω5c (39.5%), iso-C15:0 (25.6%), and iso-C17:0 3OH (11.5%). The polar lipids of strain ZZJ9T were phosphatidylethanolamine, unidentified lipid, and two unidentified aminolipids. Based on the results of phylogenetic, genome, phenotypic, and chemotaxonomic analytical, strain ZZJ9T represents a novel species of the genus Larkinella, for which the name Larkinella punicea sp. Nov. is proposed. The type strain is ZZJ9T (= KCTC 62876T = CCTCC AB 2018215T).

Nocardioides gansuensis sp. nov., isolated from geopark soil.

A novel bacterial strain, designated WSJ-1T, was isolated from geopark soil in Gansu province, PR China. The highest 16S rRNA gene sequence similarities were to those of Nocardioides sediminis MSL-01T (97.10 %), Nocardioides aquiterrae GW-9T (97.08 %) and Nocardioides terrigena DS-17T (96.94 %). Strain WSJ-1T grouped with N. terrigena DS-17T and N. sediminis MSL-01T in 16S rRNA gene-based phylogenetic trees. The DNA-DNA relatedness of WSJ-1T/N. sediminis JCM19559T and WSJ-1T/N. aquiterrae JCM11813T were 44.8 and 29.2 %, respectively. Average nucleotide identity values of whole genome sequences of WSJ-1T/N. terrigena KCTC19217T and WSJ-1T/N. sediminis KCTC19271T were 78.83 and 78.83 %, respectively. Its genome size was 4.76 Mb, comprising 4517 predicted genes with a DNA G+C content of 70.9 %. Strain WSJ-1T contained menaquinone-8(H4) as the major respiratory quinone and ll-2,6-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol. The major cellular fatty acids were iso-C16 : 0, C18 : 1ω9c and C17 : 1ω8c. Based on the polyphasic analyses, the isolate is considered to represent a novel species of the genus Nocardioides, for which the name Nocardioidesgansuensis sp. nov. is proposed. The type strain is WSJ-1T (=KCTC 49117T=CCTCC AB 2018027T).

Mucilaginibacter terrenus sp. nov., isolated from manganese mine soil.

Strain ZH6T is a Gram-stain-negative, rod-shaped, aerobic bacterium isolated from manganese mine soil. Strain ZH6T had highest 16S rRNA gene sequence similarities to Mucilaginibacter yixingensis YX-36T (96.9 %) and Mucilaginibacter psychrotolerans NH7-4T (96.8 %). The genome size of strain ZH6T was 4.61 Mb with a DNA G+C content of 44.0 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain ZH6T and M. yixingensis DSM 26809T were 70.6 and 19.2 %, respectively. Strain ZH6T had menaquinone-7 as a major quinone and main cellular fatty acids of iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The polar lipids of strain ZH6T were a phosphatidylethanolamine, an unidentified glycolipid, an unidentified phospholipid, three unidentified aminophospholipids and four unidentified lipids. Based on the phenotypic, chemotaxonomic and phylogenetic results, strain ZH6T represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacterterrenus sp. nov., is proposed. The type strain is ZH6T (=CCTCC AB 2018373T=KCTC 72075T).

Gene function and expression regulation of RuvRCAB in bacterial Cr(VI), As(III), Sb(III), and Cd(II) resistance.

Alishewanella sp. WH16-1 is a heavy metal-resistant bacterium. Previously, a putative YebC family regulator gene, designated ruvR, was associated with Cr(VI) resistance. In this study, comprehensive analyses were performed to study the role of ruvR and its adjunct putative DNA repairing genes, ruvCAB, in the heavy metal resistance of Alishewanella sp. WH16-1. RT-PCR analysis showed that ruvR is cotranscribed with ruvCAB. Gene mutation and complementation experiments indicated that ruvRCAB contributes to Cr(VI), As(III), Sb(III), and Cd(II) resistance in vivo. Random amplification of polymorphic DNA-PCR revealed that ruvCAB is associated with DNA repair mediated by these metals, and the presence of the metals in the cells was confirmed by elemental mapping and energy-dispersive X-ray spectrograph analysis. In addition, qRT-PCR, reporter gene assay, and in vivo and in vitro protein-DNA interaction experiments indicated that RuvR positively regulates the transcription of ruvCAB and is induced by Cr(VI). Finally, site-directed mutagenesis demonstrated that Asp103 is essential for the DNA binding ability of RuvR. The above results suggest that RuvR is involved in Cr(VI) resistance and resistance to other metals and that RuvR positively regulates the expression of ruvCAB. Based on our study and literatures, a model of RuvRCAB detailing bacterial heavy metal resistance is proposed. The RuvRCAB system plays an important role in the ability of Alishewanella sp. WH16-1 to survive in environments with heavy metals.

How I do it: Flexible 3-D endoscope for endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is technically challenging as a result of a lack of depth perception. The present article investigated the 3-D endoscope for carrying out ESD and translated the technique from bench to clinical use. In a preclinical porcine experiment, ESD using a 3-D endoscope was compared between an experienced and a novice endoscopist. All ESD were completed without perforation. Median operative time per surface area was significantly lower for the experienced endoscopist than for the novice (197.9 s/cm2 vs 434.7 s/cm2 ; P = 0.05). The second part was a prospective clinical experience to evaluate use of the 3-D endoscope for carrying out ESD. Ten patients received ESD using the 3-D endoscope. Four patients had gastric ESD, two had duodenal ESD and four had sigmoid and rectal ESD. There were no complications, whereas ESD failed in one patient who had gastric neoplasia at anastomosis. Mean operative time was 99.4 min, and operative time per surface area resection was 391 s/cm2 . The operating endoscopist did not complain of motion sickness, whereas the assistants had some dizziness upon prolonged ESD procedure. This study showed that carrying out ESD was safe and effective using a 3-D endoscope with an excellent 3-D view enhancing depth perception. Future study should be conducted to compare 3-D against 2-D endoscopes for ESD.

Avian Influenza A Virus Infection among Workers at Live Poultry Markets, China, 2013-2016.

We conducted a 3-year longitudinal serologic survey on an open cohort of poultry workers, swine workers, and general population controls to assess avian influenza A virus (AIV) seroprevalence and seroincidence and virologic diversity at live poultry markets (LPMs) in Wuxi City, Jiangsu Province, China. Of 964 poultry workers, 9 (0.93%) were seropositive for subtype H7N9 virus, 18 (1.87%) for H9N2, and 18 (1.87%) for H5N1. Of 468 poultry workers followed longitudinally, 2 (0.43%), 13 (2.78%), and 7 (1.5%) seroconverted, respectively; incidence was 1.27, 8.28, and 4.46/1,000 person-years for H7N9, H9N2, and H5N1 viruses, respectively. Longitudinal surveillance of AIVs at 9 LPMs revealed high co-circulation of H9, H7, and H5 subtypes. We detected AIVs in 726 (23.3%) of 3,121 samples and identified a high diversity (10 subtypes) of new genetic constellations and reassortant viruses. These data suggest that stronger surveillance for AIVs within LPMs and high-risk populations is imperative.

In vitro antimicrobial susceptibility testing of human Brucella melitensis isolates from Ulanqab of Inner Mongolia, China.

BACKGROUND: Brucellosis is an endemic disease in the Inner Mongolia Autonomous Region of China and Ulanqab exhibits the highest prevalence of brucellosis in this region. Due to the complex nature of Brucellosis, a cure for this disease has proven to be elusive. Furthermore, the reduced susceptibility of Brucella spp. to antimicrobial agents has been reported as a potential cause of therapeutic failure. However, detailed in vitro antimicrobial susceptibility patterns pertaining to Brucella isolates from this region have not yet been published. The aim of this study was to evaluate the antibiotic susceptibility profile of Brucella melitensis clinical isolates from Ulanqab, Inner Mongolia, China. METHODS: A total of 85 B. melitesis isolates were obtained from humans in Ulanqab of Inner Mongolia, China; the antimicrobial susceptibility of 85 clinical isolates to nine antibiotics was assessed using the E-test method according to the CLSI (Clinical and Laboratory Standards Institute) guidelines. RESULTS: All of the tested isolates were susceptible to minocycline, sparfloxacin, doxycycline, tetracycline, ciprofloxacin, gentamicin and levofloxacin. Resistance to rifampin and cotrimoxazole was observed in 1.0% (1/85) and 7.0% (6/85) of the isolates, respectively. However, rpoB gene mutations were not observed in single isolates exhibiting resistance to rifampin. CONCLUSIONS: We observed that B. melitensis isolates are susceptible to the majority of the tested antibiotics. Furthermore, minocycline and sparfloxacin exhibited extremely high bactericidal effects in relation to the B. melitensis isolates. The sensitivity of commonly used drugs for the treatment of brucellosis should be regularly monitored. To the best of our knowledge, this is the first report of rifampin and cotrimoxazole resistant isolates of B. melitensis in China. In summary, based on the findings from this study, we suggest that antibiotic administration and use should be rationalized to prevent future drug resistance.

Systems Biology in Aging Research.

Systems biology is an approach to collect high-dimensional data and analyze in an integrated manner. As aging is a complicated physiological functional decline in biological system, the methods in systems biology could be utilized in aging studies. Here we reviewed recent advances in systems biology in aging research and divide them into two major parts. One is the data resource, which includes omics data from DNA, RNA, proteins, epigenetic changes, metabolisms, and recently single-cell-level variations. The other is the data analysis methods consisting of network and modeling approaches. With all the data and the tools to analyze them, we could further promote our understanding of the systematic aging.