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Use of a mouse model for the isolation of Borrelia puertoricensis from soft ticks
The isolation of tick-borne relapsing fever (TBRF) spirochetes has proven to be a useful tool to understand their distribution in geographic areas where the tick vectors inhabit. However, their isolation and culture are not easy and in general an animal model is needed to achieve this task. Here, argasid ticks were collected from a neighborhood in Ciudad Caucel, and they were identified as Ornithodoros (Alectorobius) puertoricensis. To determine whether these were infected with TBRF bacteria they were fed with healthy mice but only a low burden of spirochetes was observed. An immunosuppressed mouse model was used to feed the ticks suspected to be infected with spirochetes. After tick feeding, a higher number of bacteria was observed in blood samples, and spirochetes were successfully cultivated in Barbour-Stoenner-Kelly (BSK)-IIB media. Molecular analyses indicated that the isolate was Borrelia puertoricensis, while whole genome sequencing confirmed the finding. In summary, the present report shows that A. puertoricensis is present in Ciudad Caucel, an urban neighborhood in the outskirts of Merida city, and these ticks are infected with B. puertoricensis. Despite the fact that this species has not been directly associated with TBRF it represents a potential medical and veterinary health risk.
Ecology of vertical tumor transmission in the freshwater cnidarian Hydra oligactis
Should we be careful with exercise in post-exertional malaise after long COVID?
Spatiotemporal variation in fish species distribution and abundance in the Vaishav stream, Kashmir Himalaya–India
Exploring the intricate dynamics of aquatic ecosystems present study investigates the spatio-temporal variations in the ecological parameters of the fish community within the Vaishav stream, Kashmir Himalayas. Monthly field investigations were conducted at three distinct sites (SI, SII & SIII) throughout the four seasons (winter, spring, summer, autumn) from November 2019 to October 2020. The findings encompass a total of 630 specimens belonging to 11 fish species, three orders Cypriniformes, Siluriforms and Salmoniformes and four families including Cyprinidae, Nemachelidae, Siluridae and Salmonidae were reported from the study sites. Among collected specimens, Cypriniformes were dominant with nine species followed by order Siluriformes and Salmoniformes with one species each. Out of eleven fish species, six fish species belongs to family Cyprinidae, three to Nemachelidae, one to Siluridae and Salmonidae each. The analysis, employing non-metric multidimensional scaling (NMDS), Principal component analysis (PCA), Analysis of similarity (ANOSIM) and Per-mutational multivariate analysis of variance (PERMANOVA) on fish abundance data highlighted significant differences among the various sites but not across seasons. The results unveil a diverse occurrence and distribution pattern of fishes from upstream to downstream. Furthermore, diversity metrics confirm higher diversity index values downstream, indicating a more conducive environment for fish survival. Jaccard’s index reveals greater similarity in fish fauna between site-II and site-III than site-I and site-III in terms of overlap of fish species composition. The study concludes that anthropogenic activities in the stream catchment area have led to a reduction in fish diversity and abundance, with landscape features significantly influencing fish abundance in this unique Himalayan ecosystem.
Prediction of new onset atrial fibrillation in acute myocardial infarction using fragmented QRS complex combined with HEART score
Rhodamine6G and Hœchst33342 narrow BmrA conformational spectrum for a more efficient use of ATP
Abstract Multidrug ABC transporters harness the energy of ATP binding and hydrolysis to translocate substrates out of the cell and detoxify them. While this involves a well-accepted alternating access mechanism, molecular details of this interplay are still elusive. Rhodamine6G binding on a catalytic inactive mutant of the homodimeric multidrug ABC transporter BmrA triggers a cooperative binding of ATP on the two identical nucleotide-binding-sites, otherwise michaelian. Here, we investigate this asymmetric behavior via a structural-enzymology approach, solving cryoEM structures of BmrA at defined ATP ratios, highlighting the plasticity of BmrA as it undergoes the transition from inward to outward facing conformations. Analysis of continuous heterogeneity within cryoEM data and structural dynamics, reveals that Rhodamine6G narrows the conformational spectrum explored by the nucleotide-binding domains. We observe the same behavior for the other drug Hœchst33342. Following on these findings, the effect of drug-binding showed an ATPase stimulation and a maximal transport activity of the wild-type protein at the concentration-range where the cooperative transition occurs. Altogether, these findings provide a description of the influence of drug binding on the ATP-binding sites through a change in conformational dynamics.
Integration of pharmacodynamics, network pharmacology and metabolomics to elucidate the effect and mechanism of Jingfang Granule in the treatment of Paraquat induced Pulmonary fibrosis
Objective One of the main risk factors of COVID-19 is Pulmonary fibrosis (PF). The protective effect of Jingfang Granule (JF) to bleomycin-induced PF has been confirmed in our previous studies. This work was designed to reveal the effect and mechanism of JF on PF which induced by Paraquat (PQ). Methods In this study, the PF mice model was induced by PQ with the administration of 1, 0.5, and 0.25 g/kg JF or Nintedanib (NTNB) 45 mg/kg by oral administration. The ameliorating effects of JF were reflected by the survival curve and lung coefficient. And the pathological alterations of lung were observed by H&E, Masson and Sirius red staining. Then, the expression of fibrosis-associated protein α-SMA and TGFβ1/Smad2,3 signaling pathway was detected by immunohistochemistry and western blot. An integrated approach combined metabolomics with network pharmacology was applied to recognize the mechanism of JF on ameliorated the PQ-induced PF, and the result of integrated was verified by western blot. Results The experiment results showed that JF could inhibit the progression of PQ-induced PF and delay the death of mice after PQ poisoning, and the inhibit effect was similar to NTNB. JF also reduced fibroblasts in lung tissue of the PF mice model by significantly down- regulated the expression of α-SMA and TGFβ1/Smad2,3 signaling pathway. In addition, JF intervened 16 serum metabolites compared with PQ-induced PF mice, and the differential metabolites were linked 241 corresponding targeted proteins obtained by database, which have 79 common targets to JF related targets. The integrated results of metabolomics, network pharmacology and western blot showed that apoptosis was a crucial way for JF to relieve the PQ-induced PF, and JF regulated the signals of Bcl-2, Bax, Caspase-3 protein and PI3k/Akt pathway to inhibit the apoptosis. Conclusion These findings demonstrate that JF down-regulated the TGFβ1/Smad2,3 signaling pathway to reduce the fibroblasts, regulate the expression of Bcl-2, Bax, Caspase-3 and PI3k/Akt pathway to inhibit the apoptosis, and display a favorable effect on inhibiting the development of pulmonary fibrosis and delaying the death of PQ-induced PF mice.
Using feral pigeon (Columba livia) to monitor anthropogenic debris in urban areas: a case study in Taiwan’s capital city
Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans
Changes in vaginal Ureaplasma and Lactobacillus due to antibiotic regimen for premature rupture of membranes
Preterm premature rupture of membranes (PPROM) is associated with preterm delivery and neonatal complications. PPROM is often complicated by intra-amniotic inflammation and/or microbial invasion of the amniotic cavity with Ureaplasma or Mycoplasma. Various prophylactic antibiotic therapies have been proposed to prolong latency between PPROM and delivery, reduce the risk of clinical chorioamnionitis, and improve neonatal complications. However, information on the potential of azithromycin administration to reduce the microbial load of vaginal Ureaplasma and Mycoplasma remains lacking. This prospective cohort study included singleton pregnancies managed with prophylactic antibiotics for PPROM at less than 36 weeks of gestation. All patients received the standard antibiotic regimen for PPROM, which consisted of a single oral azithromycin and intravenous ampicillin every for 2 days followed by 5 days of oral amoxicillin. Vaginal swabs samples were collected when PPROM was confirmed and after the antibiotic regimen administration. The main outcome measures were to investigate the changes in vaginal Ureaplasma, Mycoplasma, and Lactobacillus spp. due to the antibiotic regimen. In addition, the association between the presence and changes in vaginal Ureaplasma and Mycoplasma, pregnancy outcomes, and neonatal complications were examined. Out of 82 eligible PPROM, 51 had positive vaginal Ureaplasma. Thirty-six patients (52.2%) completed the antibiotic regimen. Among those with positive vaginal Ureaplasma who completed the antibiotic regimen, 75% experienced an increase in vaginal Ureaplasma levels. For those who delivered before completing all antibiotic doses, 40% had increased vaginal Ureaplasma levels. Furthermore, the antibiotic regimen resulted in decreased Lactobacillus spp. in almost all cases. It was suggested that azithromycin and ampicillin may not be effective when targeting Ureaplasma or Mycoplasma. Since this study did not search for resistance genes, it cannot be determined that azithromycin resistance in Ureaplasma or Mycoplasma is responsible for the present results. In addition, vaginal Ureaplasma changes were not found to be associated with neonatal sepsis or bronchopulmonary dysplasia. Future studies are needed to revalidate current antibiotic therapy for PPROM.
Compressive transmission scheme for power regulation of embedded 5G communication devices
Highly selective upcycling of plastic mixture waste by microwave-assisted catalysis over Zn/b-ZnO
Decentralized energy optimization using blockchain with battery storage and electric vehicle networks
Virtual fragment screening for DNA repair inhibitors in vast chemical space
Abstract Fragment-based screening can catalyze drug discovery by identifying novel scaffolds, but this approach is limited by the small chemical libraries studied by biophysical experiments and the challenging optimization process. To expand the explored chemical space, we employ structure-based docking to evaluate orders-of-magnitude larger libraries than those used in traditional fragment screening. We computationally dock a set of 14 million fragments to 8-oxoguanine DNA glycosylase (OGG1), a difficult drug target involved in cancer and inflammation, and evaluate 29 highly ranked compounds experimentally. Four of these bind to OGG1 and X-ray crystallography confirms the binding modes predicted by docking. Furthermore, we show how fragment elaboration using searches among billions of readily synthesizable compounds identifies submicromolar inhibitors with anti-inflammatory and anti-cancer effects in cells. Comparisons of virtual screening strategies to explore a chemical space of 1022 compounds illustrate that fragment-based design enables enumeration of all molecules relevant for inhibitor discovery. Virtual fragment screening is hence a highly efficient strategy for navigating the rapidly growing combinatorial libraries and can serve as a powerful tool to accelerate drug discovery efforts for challenging therapeutic targets.
Results of digitised blood smear differentiations by veterinary students using item analysis
Abstract Familiarisation with manual blood examination methods and the morphologies of leukocytes in peripheral blood contributes to routine veterinary practice. It enables veterinarians to verify automated analysis results and to examine blood cell morphology using the microscope. Third-year students therefore participated in an online module including 10 clinical cases of various mammal species with a haematological focus. Each case required the differentiation of 100 leukocytes using digitised cell images (= items) photographed from corresponding blood films. The study aims to provide insights into student difficulties with different leukocyte morphologies by calculating the Difficulty Index (DI) values. Out of 247 participating students, 96% completed the course in full, contributing 2197 differential white blood count (dWBC) responses for evaluation. The mean DI for all items (n = 1033) was 0.95 (± 0.09 SD), indicating overall low difficulty. Nucleated red blood cells (nRBC) (DI 0.98 ± 0.03 SD), segmented neutrophils (0.98 ± 0.07), and lymphocytes (0.97 ± 0.05) obtained high scores, whereas DIs for myelocytes (0.72 ± 0.14) and monocytes (0.82 ± 0.20) posed a greater challenge for the students to recognise these types of cells. Basophils, metamyelocytes, band neutrophils, platelets, and eosinophils ranged between DIs of 0.83 (± 0.12) to 0.94 (± 0.08). In contrast to hands-on microscopy, this digital format provided valuable training to gain routine in leukocyte differentiation and presentation, particularly of uncommon cell types. These should, however, be reliably distinguished by the examiner from the more common cell types, as they usually have a relatively high clinical significance even if they occur in small numbers. Nevertheless, the lack of dynamic manual adjustments during the microscopic examination emphasises the need for hands-on microscopy in combination with a digital format.
Strong and early monkeypox virus-specific immunity associated with mild disease after intradermal clade-IIb-infection in CAST/EiJ-mice
Abstract Monkeypox virus (MPXV) is a zoonotic poxvirus long endemic in West and Central Africa. Outbreaks, first the global spread of clade II outside Africa in 2022, and since 2023 the accelerating spread of clade I in central Africa, point to MPXV adaptations that pose the risk of it becoming more transmissible in humans. Animal models mimicking the clinical disease outcome in humans are important to better understand pathogenesis, host tropism, and the contribution of genetic mutations. Here, we demonstrate that MPXV infection via tail scarification in CAST/EiJ mice is an appropriate animal model to mimic human mpox. In our study, disease outcome is milder in clade IIb than clade IIa-infected mice, which is associated with enhanced immunogenicity early during infection. This suggests that clade IIb more efficiently activates host immune responses, highlighting how this animal model could facilitate studying new MPXV variants to help develop efficient antivirals and preventive measures.
Impact of short wavelength light exposure on body weight, mobility, anxiety like behaviour and cytokine expression
Efficient hybrid numerical modeling of the seismic wavefield in the presence of solid-fluid boundaries
Abstract Applying full-waveform methods to image small-scale structures of geophysical interest buried within the Earth requires the computation of the seismic wavefield over large distances compared to the target wavelengths. This represents a considerable computational cost when using state-of-the-art numerical integration of the equations of motion in three-dimensional earth models. “Box Tomography” is a hybrid method that breaks up the wavefield computation into three parts, only one of which needs to be iterated for each model update, significantly saving computational time. To deploy this method in remote regions containing a fluid-solid boundary, one needs to construct artificial sources that confine the seismic wavefield within a small region that straddles this boundary. The difficulty arises from the need to combine the solid-fluid coupling with a hybrid numerical simulation in this region. Here, we report a reconciliation of different displacement potential expressions used for solving the acoustic wave equation and propose a unified framework for hybrid simulations. This represents a significant step towards applying ’Box Tomography’ in arbitrary regions inside the Earth, achieving a thousand-fold computational cost reduction compared to standard approaches without compromising accuracy. We also present examples of benchmarks of the hybrid simulations in the case of target regions at the ocean floor and the core-mantle boundary.