Sulphamerazine toxicity in cut-throat trout broodfish Salmo clarki (Richardson)

Treatment of cut-throat trout broodfish Salmo clarki (Richardson) with Sulphamerazine at 220 mg/kg (10 g/100 1b) of fish/day for 14 days resulted in severe kidney histopathology and increased mortality among males. Experimental data presented showed that cut-throat trout broodfish were extremely sensitive to Sulphamerazine toxicity. Hydropic degeneration of renal tubule epithelium and haemorrhage into tubule lumens were observed in kidneys of both male and female trout, but was more severe in the former. Death, which occurred only in males, was correlated with spawning stress and impaired renal function.     

Carnosine,homocarnosine and anserine: could they act as antioxidants in vivo?

Carnosine, homocarnosine and anserine have been proposed to act as antioxidants in vivo. Our studies show that all three compounds are good scavengers of the hydroxyl radical (.OH) but that none of them can react with superoxide radical, hydrogen peroxide or hypochlorous acid at biologically significant rates. None of them can bind iron ions in ways that interfere with 'site-specific' iron-dependent radical damage to the sugar deoxyribose, nor can they restrict the availability of Cu2+ to phenanthroline. Homocarnosine has no effect on iron ion-dependent lipid peroxidation; carnosine and anserine have weak inhibitory effects when used at high concentrations in some (but not all) assay systems. However, the ability of these compounds to interfere with a commonly used version of the thiobarbituric acid (TBA) test may have led to an overestimate of their ability to inhibit lipid peroxidation in some previous studies. By contrast, histidine stimulated iron ion-dependent lipid peroxidation. It is concluded that, because of the high concentrations present in vivo, carnosine and anserine could conceivably act as physiological antioxidants by scavenging .OH, but that they do not have a broad spectrum of antioxidant activity, and their ability to inhibit lipid peroxidation is not well established. It may be that they have a function other than antioxidant protection (e.g. buffering), but that they are safer to accumulate than histidine, which has a marked pro-oxidant action upon iron ion-dependent lipid peroxidation. The inability of homocarnosine to react with HOCl, interfere with the TBA test or affect lipid peroxidation systems in the same way as carnosine is surprising in view of the apparent structural similarity between these two molecules.     

Detection and kinetic studies of triplex formation by oligodeoxynucleotides using real-time biomolecular interaction analysis (BIA).

Real-time biomolecular interaction analysis (BIA) has been applied to triplex formation between oligodeoxynucleotides. 5'-Biotinylated oligonucleotides were immobilised on the streptavidin-coated surface of a biosensor chip and subsequently hybridised to their complementary strand. Sequence-specific triplex formation was observed when a suitable third-strand oligopyrimidine was injected over the surface-bound duplex. In addition, a single-stranded oligonucleotide immobilised on the chip surface was able to capture a DNA duplex by triplex recognition. The presence of spermine increases the rate of association between the third strand and immobilised duplex, but at elevated spermine concentrations non-specific association is observed. A preliminary kinetic analysis of triplex formation at pH 5.2 by an 11mer third strand containing thymine, cytosine and uracil is reported. Values for the association and dissociation rate constants were determined to be (1.9 +/- 0.2) x 10(3) M-1 s-1 and (8.1 +/- 1.9) x 10(-5) s-1, respectively.     

Characteristics of triplex-directed photoadduct formation by psoralen-linked oligodeoxynucleotides.

A triplex-forming oligopyrimidine has been attached at its 5'-end to a photoreactive psoralen derivative and used to target a sequence which forms part of the coding region of the human aromatase gene. The 20 base pair sequence is not a perfect triplex target since it contains three pyrimidine interruptions within the purine-rich strand. Despite this, we have detected triplex-directed photoadduct formation at pH 7.0 between the psoralen-linked oligonucleotide and a 30mer duplex representing the aromatase target. Photoadduct formation was found to be sensitive to pH, temperature, cation concentration and the base composition of the third strand. By varying the base sequence of the target duplex around the psoralen intercalation site, we have characterised the site and mode of psoralen intercalation. The attached psoralen has been found to intercalate at the triplex-duplex junction with a strong preference for one orientation. We have shown that the psoralen will bind at the junction even when there is a preferred TpA step at an adjacent site. We have also compared the binding affinity and photoreactivity of oligodeoxyribonucleotides linked to two different psoralen derivatives and found differences in the rate of crosslinking and the extent of crosslink formation. Finally, we have examined oligodeoxyribonucleotides which are attached to psoralen by polymethylene linkers of different lengths.     

间充质干细胞在2019新型冠状病毒肺炎(COVID-19)中的治疗潜能、临床研究与应用前景*

当前因SARS-CoV-2感染而引起的2019新型冠状病毒肺炎(COVID-19)肆虐全球,严重危害人类健康。SARS-CoV-2感染性强,危重症患者死亡率高,尽管各种各样的治疗正在进行临床试验,但目前尚无有效的治疗方法。间充质干细胞(mesenchymal stem cell,MSC)在临床前试验中对多种疾病有良好的治疗效果,因而受到了广泛地关注。MSC可能利用分化潜能诱导分化成功能性肺样细胞、免疫调节与免疫细胞互作、抑制炎症来降低促炎细胞因子分泌、迁移和归巢靶向损伤肺部、抗病毒作用来减少肺上皮细胞中的病毒复制、产生细胞外囊泡来修复受损的组织,进而使COVID-19患者肺功能逐渐恢复正常,缓解并达到治疗COVID-19的目的。综合讨论了COVID-19的基本特征和当前主要治疗手段,同时总结了MSC在COVID-19中的临床研究和当前面临的挑战,探讨了MSC治疗COVID-19的应用前景,为MSC在COVID-19中的治疗提供了理论基础和现实依据。     

Mangrove blue carbon stocks and dynamics are controlled by hydrogeomorphic settings and land‐use change

Globally, carbon‐rich mangrove forests are deforested and degraded due to land‐use and land‐cover change (LULCC). The impact of mangrove deforestation on carbon emissions has been reported on a global scale; however, uncertainty remains at subnational scales due to geographical variability and field data limitations. We present an assessment of blue carbon storage at five mangrove sites across West Papua Province, Indonesia, a region that supports 10% of the world's mangrove area. The sites are representative of contrasting hydrogeomorphic settings and also capture change over a 25‐years LULCC chronosequence. Field‐based assessments were conducted across 255 plots covering undisturbed and LULCC‐affected mangroves (0‐, 5‐, 10‐, 15‐ and 25‐year‐old post‐harvest or regenerating forests as well as 15‐year‐old aquaculture ponds). Undisturbed mangroves stored total ecosystem carbon stocks of 182–2,730 (mean ± SD: 1,087 ± 584) Mg C/ha, with the large variation driven by hydrogeomorphic settings. The highest carbon stocks were found in estuarine interior (EI) mangroves, followed by open coast interior, open coast fringe and EI forests. Forest harvesting did not significantly affect soil carbon stocks, despite an elevated dead wood density relative to undisturbed forests, but it did remove nearly all live biomass. Aquaculture conversion removed 60% of soil carbon stock and 85% of live biomass carbon stock, relative to reference sites. By contrast, mangroves left to regenerate for more than 25 years reached the same level of biomass carbon compared to undisturbed forests, with annual biomass accumulation rates of 3.6 ± 1.1 Mg C ha^?1 year^?1. This study shows that hydrogeomorphic setting controls natural dynamics of mangrove blue carbon stocks, while long‐term land‐use changes affect carbon loss and gain to a substantial degree. Therefore, current land‐based climate policies must incorporate landscape and land‐use characteristics, and their related carbon management consequences, for more effective emissions reduction targets and restoration outcomes.     

Formation of micro‐spherulitic barite in association with organic matter within sulfidized stromatolites of the 3.48 billion‐year‐old Dresser Formation,Pilbara Craton

The shallow marine and subaerial sedimentary and hydrothermal rocks of the ~3.48 billion‐year‐old Dresser Formation are host to some of Earth's oldest stromatolites and microbial remains. This study reports on texturally distinctive, spherulitic barite micro‐mineralization that occur in association with primary, autochthonous organic matter within exceptionally preserved, strongly sulfidized stromatolite samples obtained from drill cores. Spherulitic barite micro‐mineralization within the sulfidized stromatolites generally forms submicron‐scale aggregates that show gradations from hollow to densely crystallized, irregular to partially radiating crystalline interiors. Several barite micro‐spherulites show thin outer shells. Within stromatolites, barite micro‐spherulites are intimately associated with petrographically earliest dolomite and nano‐porous pyrite enriched in organic matter, the latter of which is a possible biosignature assemblage that hosts microbial remains. Barite spherulites are also observed within layered barite in proximity to stromatolite layers, where they are overgrown by compositionally distinct (Sr‐rich), coarsely crystalline barite that may have been sourced from hydrothermal veins at depth. Micro‐spherulitic barite, such as reported here, is not known from hydrothermal systems that exceed the upper temperature limit for life. Rather, barite with near‐identical morphology and micro‐texture is known from zones of high bio‐productivity under low‐temperature conditions in the modern oceans, where microbial activity and/or organic matter of degrading biomass controls the formation of spherulitic aggregates. Hence, the presence of micro‐spherulitic barite in the organic matter‐bearing Dresser Formation sulfidized stromatolites lend further support for a biogenic origin of these unusual, exceptionally well‐preserved, and very ancient microbialites.     

Identifying the Neurodevelopmental Differences of Opioid Withdrawal

Cellular and Molecular Neurobiology - Stopping opioid medications can result in a debilitating withdrawal syndrome in chronic users. Opioid withdrawal can occur at all ages, but...     

Ecological Modeling from Time-Series Inference: Insight into Dynamics and Stability of Intestinal Microbiota

The intestinal microbiota is a microbial ecosystem of crucial importance to human health. Understanding how the microbiota confers resistance against enteric pathogens and how antibiotics disrupt that resistance is key to the prevention and cure of intestinal infections. We present a novel method to infer microbial community ecology directly from time-resolved metagenomics. This method extends generalized Lotka–Volterra dynamics to account for external perturbations. Data from recent experiments on antibiotic-mediated Clostridium difficile infection is analyzed to quantify microbial interactions, commensal-pathogen interactions, and the effect of the antibiotic on the community. Stability analysis reveals that the microbiota is intrinsically stable, explaining how antibiotic perturbations and C. difficile inoculation can produce catastrophic shifts that persist even after removal of the perturbations. Importantly, the analysis suggests a subnetwork of bacterial groups implicated in protection against C. difficile. Due to its generality, our method can be applied to any high-resolution ecological time-series data to infer community structure and response to external stimuli.