Serotype-specific Differences in Dengue Virus Non-structural Protein 5 Nuclear Localization

The four serotypes of dengue virus (DENV-1 to -4) cause the most important arthropod-borne viral disease of humans. DENV non-structural protein 5 (NS5) contains enzymatic activities required for capping and replication of the viral RNA genome that occurs in the host cytoplasm. However, previous studies have shown that DENV-2 NS5 accumulates in the nucleus during infection. In this study, we examined the nuclear localization of NS5 for all four DENV serotypes. We demonstrate for the first time that there are serotypic differences in NS5 nuclear localization. Whereas the DENV-2 and -3 proteins accumulate in the nucleus, DENV-1 and -4 NS5 are predominantly if not exclusively localized to the cytoplasm. Comparative studies on the DENV-2 and -4 NS5 proteins revealed that the difference in DENV-4 NS5 nuclear localization was not due to rapid nuclear export but rather the lack of a functional nuclear localization sequence. Interaction studies using DENV-2 and -4 NS5 and human importin-α isoforms failed to identify an interaction that supported the differential nuclear localization of NS5. siRNA knockdown of the human importin-α isoform KPNA2, corresponding to the murine importin-α isoform previously shown to bind to DENV-2 NS5, did not substantially affect DENV-2 NS5 nuclear localization, whereas knockdown of importin-β did. The serotypic differences in NS5 nuclear localization did not correlate with differences in IL-8 gene expression. The results show that NS5 nuclear localization is not strictly required for virus replication but is more likely to have an auxiliary function in the life cycle of specific DENV serotypes.     

Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study

Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m²) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m². The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin-associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients.     

lncRNA在动物脂肪沉积中的研究进展*

长链非编码RNA(long non-coding RNA,lncRNA),是一种长度大于200个核苷酸的调控性非编码RNA,能在转录水平、转录后水平及表观遗传水平等多个层面影响基因的表达。脂肪生成是一个复杂而有序的过程。大量研究表明,lncRNA在脂肪生成过程中扮演着重要角色,它可以影响脂质代谢及成脂分化等多种生物过程,从而间接影响肉品质。这对于提高畜禽肉品质、避免养殖业饲料过多转化成脂肪所导致的浪费以及对预防和治疗与脂肪代谢相关的疾病都具有重要意义。对lncRNA的基本特征、在动物脂肪沉积中的作用进展进行了综述,以期为培育优质畜禽,预防和治疗与脂肪代谢相关的疾病提供理论依据。     

Influence of ecological and edaphic factors on biodiversity of soil nematodes

Nematodes are the most diverse and highly significant group of soil-inhabiting microorganisms that play a vital role in organic material decomposition and nutrient recycling.Diverse geographical locations and environmental gradients show a significant impact on the diversity of nematodes. Present study aims to assess the effects of ecological (altitude, temperature, moisture) and edaphic (soil pH, nutrients, soil patches) factors on the soil nematode diversity and structure at five different landscape patches (forests, apple orchards, rice fields, pastures, and alpine zone) from ten different sites of Kashmir valley (India). Differences in the altitudinal gradients results in the shift of generic nematode population. Among the soil patches, highest nematode diversity was observed in forest soil and least in alpine soil; however, bacteriovorous nematodes dominated all the soil patches. The temperature and moisture have a significant effect on nematode diversity, the highest nematode trophic levels were observed above 21°C temperature, and 30% moisture. Nematode abundance decreased from alkaline to acidic pH of the soil. Soil nutrients such as, nitrogen (N) and phosphorus (P) have shown a detrimental effect in nematode richness at each site, where nematode diversity and richness of genera were higher at abundant soil N and P but decreased at low soil nutrients. Ecological indices like diversity index (DI), Shannon-Wiener Index (H'), enrichment index (EI), and maturity Index (MI) values demonstrated forest soil more favourable for nematodes and high soil health status than other soil patches. This study suggested that these indices may be helpful as soil monitoring tools and assessing ecosystem sustainability and biodiversity.     

Pregnenolone derivatives as potential anticancer agents

Pregnenolone (1) was used as a template to develop new anticancer compounds. Ring-D modification of 1 resulted in the synthesis of benzylidenes 2-17, pyrazolines 18-76, pyrazoles 85-91, hydrazones 77-84, and oximes 92-107 derivatives. The structure of compound 107 was also deduced through single crystal X-ray diffraction studies. The inclusion of furanyl and pyridyl rings to pregnenolone skeleton increases the cytotoxicity of all compounds significantly. Among benzylidene derivatives, only heterocyclic enone 8 (IC₅₀ = 0.74 μM/mL against HepG2), and 17 (IC₅₀ = 4.49 μM/mL against HepG2, IC₅₀ = 5.01 μM/mL against MDA-MB-230 cancer cell line) exhibited a significant activity. The cytotoxicity data of pyrazoline derivatives 18-76 revealed that only furanyl bearing pyrazolines 40, 42-44, 48, and 49 exhibited significant activities. While all (O-carboxymethyl) oximes, hydazones, and pyrazoles derivatives of pregnenolone did not show any significant activity against both the cell lines. Thus the furanyl bearing enone 8 (IC₅₀ = 0.74 μM/mL against HepG2), and its pyrazoline derivative 48 (IC₅₀ = 0.91 μM/mL against MDA-MB-230 cancer cell lines) were identified as the most active compounds in all derivatives of pregnenolone.     

Application of targeted metagenomics to explore abundance and diversity of CO2-fixing bacterial community using cbbL gene from the rhizosphere of Arachis hypogaea

Sequestration of CO₂ by autotrophic bacteria is a key process of biogeochemical carbon cycling in soil ecosystem. Rhizosphere is a rich niche of microbial activity and diversity, influenced by change in atmospheric CO₂. Structural changes in rhizosphere composition influence microbial communities and the nutrient cycling. In the present study, the bacterial diversity and population dynamics were established using cbbL and 16S rRNA gene targeted metagenomics approach from the rhizosphere of Arachis hypogaea. A total of 108 cbbL clones were obtained from the rhizospheric soil which revealed predominance of cbbL sequences affiliated to Rhizobium leguminosarum, Bradyrhizobium sp., Sinorhizobium meliloti, Ochrobactrum anthropi and a variety of uncultured cbbL harboring bacteria. The 16S rRNA gene clone library exhibited the dominance of Firmicutes (34.4%), Proteobacteria (18.3%), Actinobacteria (17.2%) and Bacteroidetes (16.1%). About 43% nucleotide sequences of 16S rRNA gene clone library were novel genera which showed < 95% homology with published sequences. Gene copy number of cbbL and 16S rRNA genes, determined by quantitative real‐time PCR (qRT PCR), was 9.38 ± 0.75 × 10⁷ and 5.43 ± 0.79 × 10⁸ (per g dry soil), respectively. The results exhibited bacterial community structure with high bacterial diversity and abundance of CO₂‐fixing bacteria, which can be explored further for their role in carbon cycling, sustainable agriculture and environment management.     

When the transmission of culture is child's play

Background

Humans frequently engage in arbitrary, conventional behavior whose primary purpose is to identify with cultural in-groups. The propensity for doing so is established early in human ontogeny as children become progressively enmeshed in their own cultural milieu. This is exemplified by their habitual replication of causally redundant actions shown to them by adults. Yet children seemingly ignore such actions shown to them by peers. How then does culture get transmitted intra-generationally? Here we suggest the answer might be ‘in play’.

Principal Findings

Using a diffusion chain design preschoolers first watched an adult retrieve a toy from a novel apparatus using a series of actions, some of which were obviously redundant. These children could then show another child how to open the apparatus, who in turn could show a third child. When the adult modeled the actions in a playful manner they were retained down to the third child at higher rates than when the adult seeded them in a functionally oriented way.

Conclusions

Our results draw attention to the possibility that play might serve a critical function in the transmission of human culture by providing a mechanism for arbitrary ideas to spread between children.     

Functional genomics based prioritization of potential nsSNPs in EPHX1, GSTT1, GSTM1 and GSTP1 genes for breast cancer susceptibility studies

In the present study, nsSNPs in EPHX1, GSTT1, GSTM1 and GSTP1 genes were screened for their functional impact on concerned proteins and their plausible role in breast cancer susceptibility. Initially, SNPs were retrieved from dbSNP, followed by identification of potentially deleterious nsSNPs using PolyPhen and SIFT. Functional analysis was done with SNPs3D, SNPs&GO and MutPred methods. Prediction and evaluation of the functional impact on the 3D structure of proteins were performed with Swiss PDB viewer and NOMAD-Ref servers. On analysis, 13 nsSNPs were found to be highly deleterious and damaging to the protein structure, of which 6 nsSNPs, rs45549733, rs45506591 and rs4986949 of GSTP1, rs72549341 and rs148240980 of EPHX1 and rs17856199 of GSTT1 were predicted to be potentially polymorphic. It is therefore hypothesized that the 6 identified nsSNPs may alter the detoxification process and elevate carcinogenic metabolite accumulation thus modifies the risk of breast cancer susceptibility in a group of women.     

Effects of water quality and trophic status on helminth infections in the cyprinid fish, Schizothorax niger Heckel, 1838 from three lakes in the Kashmir Himalayas

Water quality greatly influences the population density of aquatic biota, including parasites. In order to evaluate the relationship between fish parasites and water quality in Kashmir Himalayas, we assessed helminth parasite densities in Schizothorax niger Heckel, 1838 (an endemic cyprinid fish of Kashmir) from three lakes, namely Anchar, Manasbal and Dal, which reflected the varied stages of eutrophication. The overall prevalence of helminth infections was higher in the hypertrophic Anchar Lake (prevalence = 18.6%) compared to Manasbal Lake, which was the least eutrophied (prevalence = 6.4%). Furthermore, mean prevalence of monoxenous and heteroxenous parasites was higher in lakes containing higher levels of water degradation (Anchar and Dal). The mean number of helminth species per fish host was the highest in the hypertrophic lake (1.3 ± 0.3) in comparison to the least eutrophic lake (0.2 ± 1.5). Variability of calculated infection indices (prevalence, mean intensity and mean abundance) revealed that helminth parasite composition in the fish was affected by the lakes' environmental stress (degraded water quality). Therefore, data on the density of helminth parasites in fish can provide supplementary information on the pollution status of a water body.