Age,growth and reproductive traits of invasive goby Taenioides cirratus in the Chaohu Lake,China

The eel goby Taenioides cirratus (Blyth, 1,860) is a small fish inhabits muddy bottoms of brackish-water in the Indo-West Pacific. It has invaded many inland freshwater lakes in China, such as the Chaohu Lake, Gaoyou Lake and Nansi Lake, and its population increased rapidly in these freshwater lakes in recent years. The age, growth and reproductive traits of T. cirratus invading the Chaohu Lake were studied. A total of 482 specimens (210 females, 204 males and 68 juveniles) with total length (TL) ranging from 9.4 to 20.6 cm were collected using the benthic fyke nets at monthly intervals from March 2018 to February 2019. The sagittal otolith was used for age determination. Monthly variation of marginal increment ratio indicated that the annual forming of opaque band on sagittal otolith was completed during March and April. For both sexes, only four (from 0+ to 3+ years) age groups were observed and 1+ and 2+ years age individuals dominated the population. Back calculated length at age showed males grew faster than females. Both sexes reached maturity at 1+ year age and the TL at first maturity (TL₅₀) was 12.6 cm for females and 11.9 cm for males. Monthly variation of gonado-somatic index indicated that the spawning occurred from May to August. The fecundity ranged from 967 ova to 5,114 ova, with a mean of 3,205 ova. Our study provides a comprehensive data on the key life history traits of T. cirratus for the first time.     

Factors Associated with Patient and Provider Delays for Tuberculosis Diagnosis and Treatment in Asia: A Systematic Review and Meta-Analysis

Background

Delays in tuberculosis (TB) diagnosis and treatment is a major barrier to effective management of the disease. Determining the factors associated with patient and provider delay of TB diagnosis and treatment in Asia may contribute to TB prevention and control.

Methods

We searched the PubMed, EMBASE and Web of Science for studies that assessed factors associated with delays in care-seeking, diagnosis, or at the beginning of treatment, which were published from January 1992 to September 2014. Two reviewers independently identified studies that were related to our meta-analysis and extracted data from each study. Independent variables were categorized in separate tables for patient and provider delays.

Results

Among 45 eligible studies, 40 studies assessed patient delay whereas 30 assessed provider delay. Cross-sectional surveys were used in all but two articles, which included 17 countries and regions. Socio-demographic characteristics, TB-related symptoms and medical examination, and conditions of seeking medical care in TB patients were frequently reported. Male patients and long travel time/distance to the first healthcare provider led to both shorter patient delays [odds ratio (OR) (95% confidence intervals, CI) = 0.85 (0.78, 0.92); 1.39 (1.08, 1.78)] and shorter provider delays [OR (95%CI) = 0.96 (0.93, 1.00); 1.68 (1.12, 2.51)]. Unemployment, low income, hemoptysis, and positive sputum smears were consistently associated with patient delay [ORs (95%CI) = 1.18 (1.07, 1.30), 1.23 (1.02, 1.49), 0.64 (0.40, 1.00), 1.77 (1.07, 2.94), respectively]. Additionally, consultation at a public hospital was associated with provider delay [OR (95%CI) = 0.43 (0.20, 0.91)].

Conclusions

We propose that the major opportunities to reduce delays involve enabling socio-demographic factors and medical conditions. Male, unemployed, rural residence, low income, hemoptysis, positive sputum smear, and long travel time/distance significantly correlated with patient delay. Male, long travel time/distance and consultation at a public hospital were related to provider delay.     

Design of antibody-maytansinoid conjugates allows for efficient detoxification via liver metabolism

Antibody-maytansinoid conjugates (AMCs) are targeted chemotherapeutic agents consisting of a potent microtubule-depolymerizing maytansinoid (DM1 or DM4) attached to lysine residues of a monoclonal antibody (mAb) using an uncleavable thioether linker or a stable disulfide linker. Most of the administered dose of an antibody-based therapeutic is slowly catabolized by the liver and other tissues of the reticuloendothelial system. Maytansinoids released from an AMC during this catabolic process could potentially be a source of toxicity. To investigate this, we isolated and identified liver metabolites in mice for three different [(3)H]AMCs with structures similar to those currently undergoing evaluation in the clinic. We then synthesized each metabolite to confirm the identification and assessed their cytotoxic potencies when added extracellularly. We found that the uncleavable mAb-SMCC-[(3)H]DM1 conjugate was degraded to a single major maytansinoid metabolite, lysine-SMCC-[(3)H]DM1, that was nearly 50-fold less cytotoxic than maytansine. The two disulfide-linked conjugates, mAb-SPP-[(3)H]DM1 and mAb-SPDB-[(3)H]DM4, were also found to be catabolized to the analogous lysine-linked maytansinoid metabolites. However, subsequent reduction, S-methylation, and NADPH-dependent oxidation steps in the liver yielded the corresponding S-methyl sulfoxide and S-methyl sulfone derivatives. The cytotoxic potencies of the oxidized maytansinoids toward several human carcinoma cell lines were found to be 5- to 50-fold less potent than maytansine. Our results suggest that liver plays an important role in the detoxification of both cleavable and uncleavable AMCs.     

Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein

Heptad repeat regions (HR1 and HR2) are highly conserved sequences located in the glycoproteins of enveloped viruses. They form a six-helix bundle structure and are important in the process of virus fusion. Peptides derived from the HR regions of some viruses have been shown to inhibit the entry of these viruses. SARS-CoV was also predicted to have HR1 and HR2 regions in the S2 protein. Based on this prediction, we designed 25 peptides and screened them using a HIV-luc/SARS pseudotyped virus assay. Two peptides, HR1-1 and HR2-18, were identified as potential inhibitors, with EC(50) values of 0.14 and 1.19microM, respectively. The inhibitory effects of these peptides were validated by the wild-type SARS-CoV assay. HR1-1 and HR2-18 can serve as functional probes for dissecting the fusion mechanism of SARS-CoV and also provide the potential of further identifying potent inhibitors for SARS-CoV entry.     

Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-O-galloyl-beta-D-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 microM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells.     

Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development

Glycosaminoglycans (GAGs) play a central role in embryonic development by regulating the movement and signaling of morphogens. We have previously demonstrated that GAGs are the co-receptors for Fgf10 signaling in the lacrimal gland epithelium, but their function in the Fgf10-producing periocular mesenchyme is still poorly understood. In this study, we have generated a mesenchymal ablation of UDP-glucose dehydrogenase (Ugdh), an essential biosynthetic enzyme for GAGs. Although Fgf10 RNA is expressed normally in the periocular mesenchyme, Ugdh mutation leads to excessive dispersion of Fgf10 protein, which fails to elicit an FGF signaling response or budding morphogenesis in the presumptive lacrimal gland epithelium. This is supported by genetic rescue experiments in which the Ugdh lacrimal gland defect is ameliorated by constitutive Ras activation in the epithelium but not in the mesenchyme. We further show that lacrimal gland development requires the mesenchymal expression of the heparan sulfate N-sulfation genes Ndst1 and Ndst2 but not the 6-O and 2-O-sulfation genes Hs6st1, Hs6st2 and Hs2st. Taken together, these results demonstrate that mesenchymal GAG controls lacrimal gland induction by restricting the diffusion of Fgf10.     

Drought-induced root aerenchyma formation restricts water uptake in rice seedlings supplied with nitrate

Previous studies demonstrated that ammonium nutrition results in higher water uptake rate than does nitrate nutrition under water stress, and thus enhances the tolerance of rice plants to water stress. However, the process by which water uptake is related to nitrogen form under water stress remains unknown. A hydroponic experiment with simulated water stress induced by polyethylene glycol (PEG6000) was conducted in a greenhouse to study the relationship between root aerenchyma formation and water uptake rate, such as xylem sap flow rate and hydraulic conductance, in two different rice cultivars (cv. 'Shanyou 63' hybrid indica and cv. 'Yangdao 6' indica, China). The results showed that root aerenchyma tissue increased in water-stressed plants of both cultivars fed by nitrate. No significant difference was found in root hydraulic conductivity and/or xylem sap flow rate between the two rice cultivars fed by ammonium regardless of water status, whereas these parameters decreased significantly in water-stressed plants fed by nitrate. It was concluded that aerenchyma that formed in the root cortex impeded the radial transport of water in the root cylinder and decreased water uptake in water-stressed rice plants fed by nitrate. Water transport occurred mainly through Hg-sensitive water channels in rice roots supplied with ammonium.     

CD and NMR investigation of collagen peptides mimicking a pathological Gly–Ser mutation and a natural interruption in a similar highly charged sequence context

Even a single Gly substitution in the triple helix domain of collagen leads to pathological conditions while natural interruptions are suggested to play important functional roles. Two peptides—one mimicking a pathological Gly–Ser substitution (ERSEQ) and the other one modeling a similar natural interruption sequence (DRSER)—are designed to facilitate the comparison for elucidating the molecular basis of their different biological roles. CD and NMR investigation of peptide ERSEQ indicates a reduction of the thermal stability and disruption of hydrogen bonding at the Ser mutation site, providing a structural basis of the OI disease resulting from the Gly–Ser mutation in the highly charged RGE environment. Both CD and NMR real‐time folding results indicate that peptide ERSEQ displays a comparatively slower folding rate than peptide DRSER, suggesting that the Gly–Ser mutation may lead to a larger interference in folding than the natural interruption in a similar RSE context. Our studies suggest that unlike the rigid GPO environment, the abundant R(K)GE(D) motif may provide a more flexible sequence environment that better accommodates mutations as well as interruptions, while the electrostatic interactions contribute to its stability. These results shed insight into the molecular features of the highly charged motif and may aid the design of collagen biomimetic peptides containing important biological sites.