Comparisons between venoms from snakes kept under captivity or collected at the natural environment are of fundamental importance in order to obtain effective antivenoms to treat human victims of ...snakebites. In this study, we compared composition and biological activities of Bothrops atrox venom from snakes collected at Tapajós National Forest (Pará State, Brazil) or maintained for more than 10 years under captivity at Instituto Butantan herpetarium after have been collected mostly at Maranhão State, Brazil. Venoms from captive or wild snakes were similar except for small quantitative differences detected in peaks correspondent to phospholipases A2 (PLA2), snake venom metalloproteinases (SVMP) class PI and serine proteinases (SVSP), which did not correlate with fibrinolytic and coagulant activities (induced by PI-SVMPs and SVSPs). In both pools, the major toxic component corresponded to PIII-SVMPs, which were isolated and characterized. The characterization by mass spectrometry of both samples identified peptides that matched with a single PIII-SVMP cDNA characterized by transcriptomics, named Batroxrhagin. Sequence alignments show a strong similarity between Batroxrhagin and Jararhagin (96%). Batroxrhagin samples isolated from venoms of wild or captive snakes were not pro-coagulant, but inhibited collagen-induced platelet-aggregation, and induced hemorrhage and fibrin lysis with similar doses. Results suggest that in spite of environmental differences, venom variability was detected only among the less abundant components. In opposition, the most abundant toxin, which is a PIII-SVMP related to the key effects of the venom, is structurally conserved in the venoms. This observation is relevant for explaining the efficacy of antivenoms produced with venoms from captive snakes in human accidents inflicted at distinct natural environments.
•Bothrops atrox venom from Brazilian wild snakes or kept under captivity were compared.•Variability in protein composition was observed only in the less abundant components.•Differences in venom composition did not correlate to major venom functions.•Venoms shared the same major toxin: Bathoxrhagin, a hemorrhagic metalloproteinase.
Tumor-induced osteomalacia Aoyama, N; Nishiyama, M; Namba, H ...
QJM : An International Journal of Medicine,
02/2023, Letnik:
116, Številka:
1
Journal Article
In this paper, we present a wearable sensing glove with embedded hetero-core fiber-optic nerve sensors that detect finger flexion to achieve unconstrained hand motion monitoring. The hetero-core ...fiber sensor is suited to the wearable sensing glove because it is capable of optical intensity-based measurements with excellent stability and repeatability using single-mode transmission fibers and is unaffected by temperature fluctuations. The hetero-core sensor elements are located on the back of the hand so that they are not affected by random wrinkles in the glove at the joints. As a result, the hetero-core flexion sensor after calibration is capable of detecting the joint angles of the fingers regardless of differences in hand size, and the hetero-core sensing technique enables the sensing glove to be constructed with a minimum number of sensor points. The optical loss performance of the hetero-core sensors reveals monotonic characteristics with respect to the flexion angle of joints. The optical loss is 1.35 dB for a flexion angle of approximately 97.2deg with accuracy of 0.89deg in the detected flexion angle. Real-time hand motion capture was demonstrated by means of the proposed sensing glove without restricting natural human behavior.
Abstract Objectives A new diagnostic imaging technique that can assess lymph function is needed as a screening test in daily practice. This study assessed the use of indocyanine green (ICG) ...fluorescence lymphography in subjects without leg oedema. Methods 0.3 ml of ICG (0.5 %) was injected subcutaneously at the dorsum of the foot. Subsequently, the movement of ICG dye from the injection site to the groin was traced by visualizing its fluorescence signal with an infrared light camera. The time for the dye to reach the knee and groin were measured (Transit time to knee: TTK , Transit time to groin: TTG ). TTG was measured while standing, lying at a supine position, standing with massage, and sitting while using a cycle ergometer exercise at an intensity of 50 W at 50 rpm in ten healthy volunteers at intervals of 14 days. Results Mean TTG during standing was 357 ± 289 and 653 ± 564 seconds for the right and left legs respectively. Compared to TTG in the standing position, all other conditions shortened TTG . In another seventeen subjects without leg oedema, we compared transit time obtained with ICG fluorescence lymphography to that with dynamic lymphoscintigraphy. A significant correlation between transit time measured with ICG lymphography and dynamic lymphoscintigraphy was identified (r2 = 0.64, p < 0.01). Conclusions ICG fluorescence lymphography has the potential to become an alternative lymphatic imaging technique to assess lymph function.
Haemocyanins (Hcs) are copper-containing, respiratory proteins that occur in the haemolymph of many arthropod species. Here, we report the presence of Hcs in the chilopode Myriapoda, demonstrating ...that these proteins are more widespread among the Arthropoda than previously thought. The analysis of transcriptome of
reveals the presence of two distinct subunits of Hc, where the signal peptide is present, and six of prophenoloxidase (PPO), where the signal peptide is absent, in the 75 kDa range. Size exclusion chromatography profiles indicate different quaternary organization for Hc of both species, which was corroborated by TEM analysis:
Hc is a 6 × 6-mer and
Hc is a 3 × 6-mer, which resembles the half-structure of the 6 × 6-mer but also includes the presence of phenoloxidases, since the 1 × 6-mer quaternary organization is commonly associated with hexamers of PPO. Studies with Chelicerata showed that PPO activity are exclusively associated with the Hcs. This study indicates that
may have different proteins playing oxygen transport (Hc) and PO function, both following the hexameric oligomerization observed in Hcs.
“AIJ Standard for Structural Design and Construction of Prestressed Concrete Structures” was first published in 1961 and has been revised a number of times over the course of the nearly 60 years ...since then. More than 20 years have passed since the last revision in 1998, and a number of issues have been pointed out in the current standard. Moreover, taking into account inconsistencies between the latest information in the “Guidelines for Structural Design and Construction of Prestressed Concrete Building Based on Performance Evaluation Concept (Draft)” published in 2015, it was decided to issue a major revision of the standard, including its organization. This commentary provides an overview of this latest revision of the standard, which is scheduled to be published in March 2022, and its major changes.
Tumor hypoxia has been reported to cause a functional loss in DNA mismatch repair (MMR) system as a result of downregulation of MMR genes, although the precise molecular mechanisms remain unclear. In ...this study, we focused on the downregulation of a key MMR gene, MLH1, and demonstrated that hypoxia-inducible transcription repressors, differentiated embryo chondrocytes (DEC1 and 2), participated in its transcriptional regulation via their bindings to E-box-like motif(s) in MLH1 promoter region. In all cancer cell lines examined, hypoxia increased expression of DEC1 and 2, known as hypoxia-inducible genes, but decreased MLH1 expression in an exposure time-dependent manner at both the mRNA and protein levels. Co-transfection reporter assay revealed that DEC1 and, to greater extent, DEC2 as well as hypoxia-repressed MLH1 promoter activity. We further found that the action was remarkably inhibited by trichostatin A, and identified a possible DEC-response element in the MLH1 promoter. In vitro electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that DEC1 or 2 directly bounds to the suggested element, and transient transfection assay revealed that overexpression of DEC2 repressed endogenous MLH1 expression in the cells. Hypoxia-induced DEC may impair MMR function through repression of MLH1 expression, possibly via the histone deacethylase-mediated mechanism in cancer cells.
Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been ...reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients.
PDF
