Miracle-dz/UniFAR-FTUs huggingface dataset:
In-silico analysis of Calcium Dependent Protein Kinase 6 of Cryptosporidium parvum through molecular modeling, docking, and dynamics simulation study

Abstract Calcium Dependent Protein Kinases are found in the Apicomplexan, algae, and plants; however, they are not reported in vertebrates and are regarded as excellent drug targets for pharmaceutical interventions. Calcium Dependent Protein Kinases of Cryptosporidium are probably involved in the regulation of invasion and egress process during the infection of the host cells. The previous study reported that after the Calcium Dependent Protein Kinase 1 gene, Calcium Dependent Protein Kinase 6 of Cryptosporidium parvum is expressed in all stages of the parasite (merozoites/schizonts as well as sexual stages) at a comparable level and makes it as a valid drug target. In this study, an attempt is made to address the similarity in sequences and phylogenetic study of Calcium Dependent Protein Kinase 6 (CDPK6) among Calcium Dependent Protein Kinases of Apicomplexans. Further, the three-dimensional structure determination of CDPK6 of C. parvum was performed through a molecular modeling approach followed by virtual screening of small-molecule inhibitors from different datasets. The best inhibitor from Tres Cantos Antimalarial Set with ID 11730 reported a binding affinity of −8.2 kcal/mol against CDPK6 of C. parvum. Furthermore, the reliability of the binding mode of the inhibitor is validated through a complex molecular dynamics simulation study for a time interval of 100 ns. The simulation study advocates that the inhibitor Tres Cantos Antimalarial Set_11730 formed a stable interaction with the predicted active site residues and can be considered for industrial pharmaceutical research in future. Communicated by Ramaswamy H. Sarma
Description of a new microhylid frog species of the genus Xenorhina (Amphibia: Anura: Microhylidae) from the Fakfak Mountains, far western New Guinea

Based on morphological, bioacoustic, and molecular traits, a new species in the microhylid genus Xenorhina is described. It was recently discovered in the Fakfak Mountains, northwestern corner of the Bomberai Peninsula, Papua Province, Indonesia. This new species has no vomero-palatine spikes. According to molecular traits of the 12S and 16S rRNA genes, the new taxon is most closely related to a syntopic Xenorhina cf. oxycephala. It belongs to the smallest species in its genus and to those with the longest hind legs. Its advertisement call consists of a series of melodious notes lasting 5 – 6 seconds; mean note length 77 milliseconds, mean internote interval length 438 ms, and mean repetition rate 2.1 notes per second. The new species is fossorial and it occurs in primary and secondary rain forest at an elevation of from 400 m to 900 m a.s. l.
Microglia modulate gliotransmission through the regulation of VAMP2 proteins in astrocytes

Vesicular release is one of the release mechanisms of various signaling molecules. In neurons, the molecular machinery involved in vesicular release has been designed through evolution to trigger fast and synchronous release of neurotransmitters. Similar machinery with a slower kinetic and a slightly different molecular assembly allows astrocytes to release various transmitters such as adenosine triphosphate (ATP), glutamate, and D‐serine. Astrocytes are important modulators of neurotransmission through gliotransmitter release. We recently demonstrated that microglia, another type of glia, release ATP to modulate synaptic transmission using astrocytes as intermediate. We now report that microglia regulate astrocytic gliotransmission through the regulation of SNARE proteins in astrocytes. Indeed, we found that gliotransmission triggered by P2Y1 agonist is impaired in slices from transgenic mice devoid of microglia. Using total internal reflection fluorescence imaging, we found that the vesicular release of gliotransmitter by astrocytes was different in cultures lacking microglia compared to vesicular release in astrocytes cocultured with microglia. Quantification of the kinetic of vesicular release indicates that the overall release appears to be faster in pure astrocyte cultures with more vesicles close to the membrane when compared to astrocytes cocultured with microglia. Finally, biochemical investigation of SNARE protein expression indicates an upregulation of VAMP2 in absence of microglia. Altogether, these results indicate that microglia seems to be involved in the regulation of an astrocytic phenotype compatible with proper gliotransmission. The mechanisms described in this study could be of importance for central nervous system diseases where microglia are activated.
EFFECT OF AQUEOUS EXTRACT OF ABRUS PRECATORIUS LEAF ON DNBS - INDUCED INFLAMMATORY BOWEL DISEASE (IBD)

In certain tribal regions people chew Abrus precatorius leaf for the relief of the month ulcer. Therapeutic properties of Abrus precatorius leaf was reported in ancient literature as anti-inflammatory or ulcer healing. Hence, the present research work performs study of aqueous leaf extract of A. precatorius to achieve optimum inflammatory bowel disease activity. Here, 2, 4 dinitrobenzenesulphonic acid induction of inflammatory bowel (DNBS) - induced inflammatory bowel disease experimental model used to evaluate the aqueous extract of leaf of A. precatorius for its anti-inflammatory activity. Treatment of animals with aqueous extract of A. precatorius leaf with two different dose levels (300mg/kg and 500mg/kg) was performed and found that animals treated with A. precatorius possess marked activity to cure of inflammatory bowel disease and could have a promising role in the treatment of inflammatory bowel disease induced by DNBS. In the colon homogenate malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and nitric oxide (NO) levels were measured. Rats treated with only DNBS showed higher MDA, NO and lower SOD, GSH, and CAT activity as compared to the control group. Treatment with aqueous extract of Abrus precatorius leaf significantly declined CMDI score and decreased the MDA, NO and increased the SOD, GSH, CAT activity. Based on our results we concluded that aqueous extract of A. precatorius leaf has a significant protective effect in the IBD in rats that was comparable to that of 5-amino salicylic acid (100 mg/kg) and may be because of the presence of saponins, flavonoids, terpenoids, and phenolic compounds.
Mutations at the Serine Hydroxymethyltransferase Impact Its Interaction with a Soluble NSF Attachment Protein and a Pathogenesis-Related Protein in Soybean

Resistance to soybean cyst nematodes (SCN) in “Peking-type” resistance is bigenic, requiring Rhg4-a and rhg1-a. Rhg4-a encodes a serine hydroxymethyltransferase (GmSHMT08) and rhg1-a encodes a soluble NSF attachment protein (GmSNAP18). Recently, it has been shown that a pathogenesis-related protein, GmPR08-Bet VI, potentiates the interaction between GmSHMT08 and GmSNAP18. Mutational analysis using spontaneously occurring and ethyl methanesulfonate (EMS)-induced mutations was carried out to increase our knowledge of the interacting GmSHMT08/GmSNAP18/GmPR08-Bet VI multi-protein complex. Mutations affecting the GmSHMT08 protein structure (dimerization and tetramerization) and interaction sites with GmSNAP18 and GmPR08-Bet VI proteins were found to impact the multi-protein complex. Interestingly, mutations affecting the PLP/THF substrate binding and catalysis did not affect the multi-protein complex, although they resulted in increased susceptibility to SCN. Most importantly, GmSHMT08 and GmSNAP18 from PI88788 were shown to interact within the cell, being potentiated in the presence of GmPR08-Bet VI. In addition, we have shown the presence of incompatibility between the GmSNAP18 (rhg1-b) of PI88788 and GmSHMT08 (Rhg4-a) from Peking. Components of the reactive oxygen species (ROS) pathway were shown to be induced in the SCN incompatible reaction and were mapped to QTLs for resistance to SCN using different mapping populations.
Long-term outcomes of patients with ulcerative proctitis: Analysis from a large referral centre cohort

Introduction Long-term outcomes of patients with ulcerative proctitis (UP) have been poorly investigated, since these patients are excluded from participation in randomized controlled clinical trials. Objective The aim of this study was to investigate the prognostic and therapeutic long-term outcomes of patients with UP. Methods A retrospective study of patients with UP followed at our referral centre between 1 January 1998 and 1 January 2019 was performed. Treatment success was defined as clinical response (significant improvement in UP-related symptoms) and endoscopic response (mayo endoscopic sub-score of 0 or 1) if available at last follow-up. Results From a total of 1561 patients with ulcerative colitis, 118 patients with UP were identified. A total of 36 (31%) patients were refractory to rectal and oral therapy with 5-ASA and corticosteroids, necessitating azathioprine as monotherapy in 19 (16%) patients and/or biological therapies in 33 (28%) patients. After a median follow-up of 71 months (interquartile range 29–149 months), treatment success was observed in 103/118 (87%) UP patients and in 25/36 (69%) patients with refractory UP. Clinical response rates were significantly higher for refractory UP patients treated with biologicals (23/33; 70%) compared to ones treated with azathioprine (2/19; 11%; p = 0.001). Conclusion Good clinical outcomes were recorded in UP, with treatment success in 87% of patients. Nevertheless, 28% needed escalation to biologicals. Long-term outcome in patients on biologicals was superior to azathioprine.
Analogues of a Cyclic Antimicrobial Peptide with a Flexible Linker Show Promising Activity against Pseudomonas aeruginosa and Staphylococcus aureus

The emergence of multi-drug resistant bacteria is becoming a major health concern. New strategies to combat especially Gram-negative pathogens are urgently needed. Antimicrobial peptides (AMPs) found in all multicellular organisms act as a first line of defense in immunity. In recent years, AMPs have attracted increasing attention as potential antibiotics. Naturally occurring antimicrobial cyclic lipopeptides include colistin and daptomycin, both of which contain a flexible linker. We previously reported a cyclic AMP BSI-9 cyclo(Lys-Nal-Lys-Lys-Bip-O2Oc-Nal-Lys-Asn) containing a flexible linker, with a broad spectrum of activity against bacterial strains and low hemolytic activity. In this study, improvement of the antimicrobial activity of BSI-9, against the European Committee on Antimicrobial Susceptibility Testing (EUCAST) strains of S. aureus, E. coli, A. baumannii, and P. aeruginosa was examined. This led to synthesis of eighteen peptide analogues of BSI-9, produced in four individual stages, with a different focus in each stage; cyclization point, hydrophobicity, cationic side-chain length, and combinations of the last two. Specifically the modified compound 11, exhibited improved activity against Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 4 µg/mL and 8 µg/mL, respectively, compared to the original BSI-9, which had an MIC of 16–32 µg/mL.
Putative Roles for Peptidylarginine Deiminases in COVID-19

Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. In addition, BioProject Data PRJNA631753, analysing patients tissue biopsy data (n = 5), was utilised. We report a high individual variation observed for all PADI isozymes in the patients’ tissue biopsies, including lung, in response to SARS-CoV-2 infection, while PADI2 and PADI4 mRNA showed most variability in lung tissue specifically. The other tissues assessed were heart, kidney, marrow, bowel, jejunum, skin and fat, which all varied with respect to mRNA levels for the different PADI isozymes. In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells. In A549 cells, PADI2 mRNA was elevated, PADI3 and PADI6 mRNA was downregulated, and no effect was observed on the PADI4 or PADI6 mRNA levels in infected cells, compared with control mock cells. Our findings indicate a link between PADI expression changes, including modulation of PADI2 and PADI4, particularly in lung tissue, in response to SARS-CoV-2 infection. PADI isozyme 1–6 expression in other organ biopsies also reveals putative links to COVID-19 symptoms, including vascular, cardiac and cutaneous responses, kidney injury and stroke. KEGG and GO pathway analysis furthermore identified links between PADs and inflammatory pathways, in particular between PAD4 and viral infections, as well as identifying links for PADs with a range of comorbidities. The analysis presented here highlights roles for PADs in-host responses to SARS-CoV-2, and their potential as therapeutic targets in COVID-19.
Elongation Patterns of the Posterior Cruciate Ligament after Total Knee Arthroplasty

This study aimed to understand the ability of fixed-bearing posterior cruciate ligament (PCL)-retaining implants to maintain functionality of the PCL in vivo. To achieve this, elongation of the PCL was examined in six subjects with good clinical and functional outcomes using 3D kinematics reconstructed from video-fluoroscopy, together with multibody modelling of the knee. Here, length-change patterns of the ligament bundles were tracked throughout complete cycles of level walking and stair descent. Throughout both activities, elongation of the anterolateral bundle exhibited a flexion-dependent pattern with more stretching during swing than stance phase (e.g., at 40° flexion, anterolateral bundle experienced 3.9% strain during stance and 9.1% during swing phase of stair descent). The posteromedial bundle remained shorter than its reference length (defined at heel strike of the level gait cycle) during both activities. Compared with loading patterns of the healthy ligament, postoperative elongation patterns indicate a slackening of the ligament at early flexion followed by peak ligament lengths at considerably smaller flexion angles. The reported data provide a novel insight into in vivo PCL function during activities of daily living that has not been captured previously. The findings support previous investigations reporting difficulties in achieving a balanced tension in the retained PCL.
Non-right-handedness in children born extremely preterm: Relation to early neuroimaging and long-term neurodevelopment

Objective This study aimed to define the prevalence and predictors of non-right-handedness and its link to long-term neurodevelopmental outcome and early neuroimaging in a cohort of children born extremely preterm (<28 weeks gestation). Methods 179 children born extremely preterm admitted to the Neonatal Intensive Care Unit of our tertiary centre from 2006–2013 were included in a prospective longitudinal cohort study. Collected data included perinatal data, demographic characteristics, neurodevelopmental outcome measured by the Bayley Scales of Infant and Toddler Development at 2 years and the Movement Assessment Battery for Children at 5 years, and handedness measured at school age (4–8 years). Magnetic resonance imaging performed at term-equivalent age was used to study overt brain injury. Diffusion tensor imaging scans were analysed using tract-based spatial statistics to assess white matter microstructure in relation to handedness and neurodevelopmental outcome. Results The prevalence of non-right-handedness in our cohort was 22.9%, compared to 12% in the general population. Weaker fine motor skills at 2 years and paternal non-right-handedness were significantly associated with non-right-handedness. Both overt brain injury and fractional anisotropy of white matter structures on diffusion tensor images were not related to handedness. Fractional anisotropy measurements showed significant associations with neurodevelopmental outcome. Conclusions Our data show that non-right-handedness in children born extremely preterm occurs almost twice as frequently as in the general population. In the studied population, non-right-handedness is associated with weaker fine motor skills and paternal non-right-handedness, but not with overt brain injury or microstructural brain development on early magnetic resonance imaging.
A Modified Thresholding Method based on Relative Homogeneity

Image binarization method focusing on objects can overcome some short-comings of famous Otsu’s method. In this paper, applying with the gray and neighborhood average gray information, a more detailed description of thresholding algorithm is presented. Using relative homogeneity information both of foreground and background, a new threshold discriminant criterion is proposed. For better adaptability, valley point neighborhood histogram information is introduced, a modiﬁed threshold criterion is constructed. The results show that, comparing with Otsu’s and focusing on objects methods, the proposed method has better segmentation accuracy, especially, for images with large gray distribution diﬀerence of classes, the adaptability is much better.
Joint Spatio-Temporal Domain for Adaptive Kronecker Compressive Sensing

Compressive Sensing (CS) theory tells that a sparse or compressible signal can be recovered exactly from a few sampling measurements via solving a convex problem although the sampling rate is lower than the Nyquist rate. However, the CS literature has mostly focused on problems involving 1-D signals and 2-D images, many important applications involve multidimensional signals such as video signal. In this paper, based on the Kronecker compressive sensing (KCS), a novel joint spatio-temporal domain for Adaptive Kronecker Compressive Sensing (AKCS) method is proposed. Firstly, video sequences are divided into space domain and time domain. Secondly, in the space domain, adaptive sampling scheme is formulated based on statistical information of the image block, and a new measurement matrix is designed by using Kronecker product. Lastly, high-quality video can be reconstructed by applying AKCS in spatio-temporal domain. The improved BCS-IST algorithm is used to calculate the residual error of each block, and the current frame is combined with the predicted frame to reconstruct the current frame. When reconstructing the video signal, the time correlation between frames should be fully utilized besides considering the spatial correlation in the frame. Kronecker product can well describe the correlation between pixels in spatio-temporal domain, and is often used in frame rate lifting algorithm and edge information estimation algorithm.The experimental results demonstrate that the proposed method can eﬀectively improve the peak-signal-to-noise ratio (PSNR) and running eﬃciency compared with other methods.
A Hybrid Localization Algorithm Based on Clustering for WSNs

This paper presents a hybrid localization algorithm based on clustering for wireless sensor networks (WSNs) called HLBC, which is suitable for dynamic proactive wireless sensor networks. A novel clustering algorithm is used to generate the speciﬁed number of cluster nodes in WSNs, considering connectivity and remaining energy of nodes. An original multilateral correction algorithm is introduced to ﬁlter and correct them which have large error calculated by MDS-MAP algorithm, after ﬁnding the bad node of the network by matching degree function. The running time of HLBC is obviously lower and more stable than that of the centralized MDS-MAP, especially when the number of nodes increases. Results in extensive simulation experiments of square and C-type networks show that the proposed algorithm is more accurate and more eﬃcient than the MDS-MAP algorithm.
Glochidial Morphology of Two Species of the Genus Schistodesmus (Bivalvia: Unionidae) from Lake Poyang, China

Abstract: Glochidial morphology of two unionid species of the genus Schistodesmus Simpson, 1900 from Lake Poyang (China), Schistodesmus lampreyanus (Baird and Adams, 1867) and S. spinosus Simpson, 1900 were studied for the first time under light and scanning electron microscopy. Glochidial characters, including shape, size, hook, sensory hair tufts and exterior minute sculpture, are presented and compared with some allied species for the identification of glochidia. Schistodesmus has small and ovate subtriangular glochidia with styliform hook. Glochidia of the two species of Schistodesmus Simpson, 1900 differed from each other in relative abundance of microstylets and micropoints, and valve sculpture.
A New Hybrid Task Scheduling Algorithm Designed Based on ACO and GA

As known to us all, task scheduling is one of the most important problems in Cloud Computing. For this, a new hybrid algorithm named GAPACO which considers both cost-saving and time-saving has been proposed in this paper. Especially, it combines two advantages of ACO and GA. It takes advantage of rapid convergence of ACO and simpleness of GA. A large number of experiments data shows that this hybrid algorithm is available and can be applied at community cloud environment. The experimental results show its eﬃciency.
Inhibition of ITGB1 enhance the anti-tumor effect of cetuximab in colorectal cancer cell

Supplemental Digital Content is available in the text Abstract Background: Colorectal cancer is the second commonly seen cancer around the world and accounts for 13% of all human cancers. Among them, 25% of all case were diagnosed with metastasis and 50% occurs metastasis during the development of disease. Cetuximab is a chimeric monoclonal antibody against epidermal growth factor receptor, and is used for treatment of metastatic colorectal cancer alone or combined with chemotherapy or radiation therapy. Integrin-beta 1 (ITGB1), which is also known as CD29, and plays an important role in development of malignant cancers. However, the effect of ITGB1 in promoting the anti-tumor effect of cetuximab is not fully understand. Methods: The model of ITGB1 inhibition and overexpression was firstly constructed in LS174T cells, and the viability of cells in each group was detected using CCK-8 assay. The expression of key factors in tumor formation process at transcription level was detected using real-time quantitative polymerase chain reaction method. The expression of key proteins in metastasis process, cell apoptosis and activation of Ras/Raf/MEK signaling pathway was detected using western blotting analysis. And the concentration of key factors of in tumor formation process in cultured medium of LS174T cells were detected using enzyme-linked immunosorbent assay method. Results: We found that cetuximab could inhibit the proliferation of LS174T cells, and inhibition of ITGB1 enhanced this effect while overexpression of ITGB1 reduced this effect. We further found that cetuximab could inhibit the expression and secretion of extracellular matrix degradation related molecules in cultured medium and transcription level. Besides, we also found that the expression of key factors in angiogenesis and extracellular matrix degradation related proteins were also reduced after cetuximab treatment. These effects might be mediated by Ras/Raf/MAPK signaling pathway and enhanced after inhibition of ITGB1 expression. Conclusion: Inhibition of ITGB1 might be a new therapeutic method in colorectal cancer.