Miracle-dz/UniFAR-FTUs huggingface dataset:
DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells

Abstract DNMT3B is known as a de novo DNA methyltransferase. However, its preferential target sites for DNA methylation are largely unknown. Our analysis on ChIP-seq experiment in human embryonic stem cells (hESC) revealed that DNMT3B, mCA and H3K36me3 share the same genomic distribution profile. Deletion of DNMT3B or its histone-interacting domain (PWWP) demolished mCA in hESCs, suggesting that PWWP domain of DNMT3B directs the formation of mCA landscape. In contrast to the common presumption that PWWP guides DNMT3B-mediated mCG deposition, we found that deleting PWWP does not affect the mCG landscape. Nonetheless, DNMT3B knockout led to the formation of 2985 de novo hypomethylated regions at annotated promoter sites. Upon knockout, most of these promoters gain the bivalent marks, H3K4me3 and H3K27me3. We call them spurious bivalent promoters. Gene ontology analysis associated spurious bivalent promoters with development and cell differentiation. Overall, we found the importance of DNMT3B for shaping the mCA landscape and for maintaining the fidelity of the bivalent promoters in hESCs.
Motivation as a mechanism underpinning exercise-based falls prevention programmes for older adults with cognitive impairment: a realist review

Objectives This review aimed to identify mechanisms underlying participation in falls prevention interventions, in older adults with cognitive impairment. In particular we studied the role of motivation. Design A realist review of the literature. Data sources EMBASE, MEDLINE, CINAHL, the Cochrane Library, PsycINFO and PEDRO. Eligibility criteria Publications reporting exercise-based interventions for people with cognitive impairment, including dementia, living in the community. Data extraction and synthesis A ‘rough programme theory’ (a preliminary model of how an intervention works) was developed, tested against findings from the published literature and refined. Data were collected according to elements of the programme theory and not isolated to outcomes. Motivation emerged as a key element, and was prioritised for further study. Results An individual will access mechanisms to support participation when they think that exercise will be beneficial to them. Supportive mechanisms include having a ‘gate-keeper’, such as a carer or therapist, who shares responsibility for the perception of exercise as beneficial. Lack of access to support decreases adherence and participation in exercise. Motivational mechanisms were particularly relevant for older adults with mild-to-moderate dementia, where the exercise intervention was multicomponent, in a preferred setting, at the correct intensity and level of progression, correctly supported and considered, and flexibly delivered. Conclusion Motivation is a key element enabling participation in exercise-based interventions for people with cognitive impairment. Many of the mechanisms identified in this review have parallels in motivational theory. Clinically relevant recommendations were derived and will be used to further develop and test a motivationally considered exercise-based falls intervention for people with mild dementia. PROSPERO registration number CRD42015030169.
Ranking the NTCIR ACLIA IR4QA Systems without Relevance Assessments

We consider the problem of ranking information retrieval systems without relevance assessments in the context of collaborative evaluation forums such as NTCIR and TREC. Our short-term goal is to provide the NTCIR participants with a “system ranking forecast” prior to conducting manual relevance assessments, thereby reducing researchers’ “idle time” and accelarating research. The long term goal is to semi-automate repeated evaluation of search engines. Our experiments using the NTCIR-7 ACLIA IR4QA test collections show that pseudo-systemrankings based on a simple method are highly correlated with the “true” rankings. Encouraged by this positive finding, we plan to release system ranking forecasts to participants of the next round of IR4QA at NTCIR-8.
Optic nerve regeneration in larval zebrafish exhibits spontaneous capacity for retinotopic but not tectum specific axon targeting

In contrast to mammals, retinal ganglion cells (RGC) axons of the optic nerve even in mature zebrafish exhibit a remarkable capacity for spontaneous regeneration. One constraint of using adult zebrafish is the limited ability to visualize the regeneration process in live animals. To dynamically visualize and trace the degree of target specific optic nerve regeneration, we took advantage of the optical transparency still preserved in post developmental larval zebrafish. We developed a rapid and robust assay to physically transect the larval optic nerve and find that by 96 hours post injury RGC axons have robustly regrown onto the optic tectum. We observe functional regeneration by 8 days post injury, and demonstrate that similar to adult zebrafish, optic nerve transection in larval zebrafish does not prominently induce cell death or proliferation of RGC neurons. Furthermore, we find that partial optic nerve transection results in axonal growth predominantly to the original, contralateral tectum, while complete transection results in innervation of both the correct contralateral and ‘incorrect’ ipsilateral tectum. Axonal tracing reveals that although regenerating axons innervate the ‘incorrect’ ipsilateral tectum, they successfully target their topographically appropriate synaptic areas. Combined, our results validate post developmental larval zebrafish as a powerful model for optic nerve regeneration, and reveal intricate mechanistic differences between axonal growth, midline guidance and synaptic targeting during zebrafish optic nerve regeneration.
Hindbrain neurovascular anatomy of adult goldfish (Carassius auratus)

The goldfish hindbrain develops from a segmented (rhombomeric) neuroepithelial scaffold, similar to other vertebrates. Motor, reticular and other neuronal groups develop in specific segmental locations within this rhombomeric framework. Teleosts are unique in possessing a segmental series of unpaired, midline central arteries that extend from the basilar artery and penetrate the pial midline of each hindbrain rhombomere (r). This study demonstrates that the rhombencephalic arterial supply of the brainstem forms in relation to the neural segments they supply. Midline central arteries penetrate the pial floor plate and branch within the neuroepithelium near the ventricular surface to form vascular trees that extend back towards the pial surface. This intramural branching pattern has not been described in any other vertebrate, with blood flow in a ventriculo‐pial direction, vastly different than the pial‐ventricular blood flow observed in most other vertebrates. Each central arterial stem penetrates the pial midline and ascends through the floor plate, giving off short transverse paramedian branches that extend a short distance into the adjoining basal plate to supply ventromedial areas of the brainstem, including direct supply of reticulospinal neurons. Robust r3 and r8 central arteries are significantly larger and form a more interconnected network than any of the remaining hindbrain vascular stems. The r3 arterial stem has extensive vascular branching, including specific vessels that supply the cerebellum, trigeminal motor nucleus located in r2/3 and facial motoneurons found in r6/7. Results suggest that some blood vessels may be predetermined to supply specific neuronal populations, even traveling outside of their original neurovascular territories in order to supply migrated neurons.
Prevalence of human T-cell lymphotropic virus type-1 infection among blood donors in mainland China: a systematic review and meta-analysis of the last 20 years

ABSTRACT Background: The southeastern coastal area of China has a high prevalence of HTLV-1 infection among blood donors. However, the estimation of HTLV-1 prevalence on a national and regional level is little known. The aim of this study is to understand and explore the estimation of HTLV-1 infection prevalence among blood donors on a national and regional level in mainland China by using a systematic review and meta-analysis. Study design and methods: All relevant publications of the past two decades (1998–2017), which were reported in both English and Chinese languages, were adopted and systematically assessed. The estimation of prevalence and its 95% confidence interval (CI) at the level of provinces/municipalities and overall were estimated using meta-analysis method. Results: From the 327 studies searched, 60 met the inclusion criteria. These were from 18 provinces and four municipalities and included 1,420,079 blood donors. The overall estimation of the HTLV-1 prevalence in blood donors was 0.169‰, and its 95% CI was 0.121‰-0.240‰. Conclusion: A disproportionate distribution of HTLV-1 infection among blood donors in different provinces/municipalities regarding its prevalence has been reported. This study recommends developing appropriate HTLV-1 screening strategies of blood donors in various regions of China considering regional prevalence, and cost-effectiveness.
Implementasi Data Mining Untuk Memprediksi Kelulusan Mahasiswa Fakultas Komunikasi Dan Informatika UMS Menggunakan Metode Naive Bayes

Fakultas Komunikasi dan Informatika Universitas Muhammadiyah Surakarta memiliki jumlah 2358 mahasiswa dengan jumlah lulusan 388 mahasiswa, Dengan bertambah pesatnya jumlah mahasiswa baru setiap tahunnya dengan demikian secara otomatis akan terciptanya data-data yang sangat banyak dan akan menambah melimpahnya data yang tersimpan tapi minim informasi. Agar data yang awalnya tidak terpakai tersebut dapat diubah menjadi suatu informasi data yang sangat bermanfaat dengan menggunakan teknik data mining. Salah satunya dapat untuk memprediksi lama studi mahasiswa apakah dapat lulus kurang dari 4 tahun atau lebih dari 4 tahun dengan berdasarkan atribut-atribut yang digunakan. Metode Naive Bayes digunakan untuk menganalisis data dalam pengenalan pola dan memprediksi kelulusan mahasiswa. Data yang diperlukan yaitu data-data mahasiswa yang sudah lulus sebagai data training sedangkan data-data mahasiswa yang masih menempuh studi kuliah sebagai data uji. Dengan adanya penelitian ini dapat memberikan informasi yang berguna sehingga dapat meningkatkan kualitas atau dijadikan suatu acuan bagi mahasiswa untuk memprediksi kelulusan dengan tepat waktu. Berdasarkan hasil prediksi dari jumlah 342 data sampel yang diuji hanya 86 mahasiswa yang akan lulus tepat waktu atau hanya sekitar 25,15 %, sedangkan mahasiswa yang akan lulus terlambat berjumlah 256 mahasiswa mencapai 74,85% dari jumlah data sampel.
Transforming lives and empowering communities: evidence, harm reduction and a holistic approach to people who use drugs.

PURPOSE OF REVIEW We reviewed the global state of harm reduction for people who use and/or inject drugs. KEY FINDINGS Although harm reduction is now the key response to HIV among people who use drugs globally, intervention coverage remains suboptimal, exacerbated by chronic under-funding, declining donor support and limited domestic investment, particularly in low-income and middle-income countries. We describe the current environment and review recent innovations and responses, including peer distribution of naloxone, low dead space syringes, drug consumption rooms and drug-checking services. However, despite efforts by people who use drugs and supporting partners to sustain harm reduction services and to develop and implement novel interventions, programmes are often under-scaled and under-resourced and people who use drugs continue to face significant barriers to accessing services. SUMMARY There is an urgent need to bring existing harm reduction programmes to scale and to broaden their scope, as well to complement them with innovative interventions targeting new populations and new substances. Under and disinvestment in harm reduction and the absence of enabling legal environments threatens to undermine the global HIV response and exacerbate the morbidity and mortality associated with the current epidemic of opioid overdose.
Development of Personalized Therapeutic Strategies by Targeting Actionable Vulnerabilities in Metastatic and Chemotherapy-Resistant Breast Cancer PDXs

Human breast cancer is characterized by a high degree of inter-patients heterogeneity in terms of histology, genomic alterations, gene expression patterns, and metastatic behavior, which deeply influences individual prognosis and treatment response. The main cause of mortality in breast cancer is the therapy-resistant metastatic disease, which sets the priority for novel treatment strategies for these patients. In the present study, we demonstrate that Patient Derived Xenografts (PDXs) that were obtained from metastatic and therapy-resistant breast cancer samples recapitulate the wide spectrum of the disease in terms of histologic subtypes and mutational profiles, as evaluated by whole exome sequencing. We have integrated genomic and transcriptomic data to identify oncogenic and actionable pathways in each PDX. By taking advantage of primary short-term in vitro cultures from PDX tumors, we showed their resistance to standard chemotherapy (Paclitaxel), as seen in the patients. Moreover, we selected targeting drugs and analyzed PDX sensitivity to single agents or to combination of targeted and standard therapy on the basis of PDX-specific genomic or transcriptomic alterations. Our data demonstrate that PDXs represent a suitable model to test new targeting drugs or drug combinations and to prioritize personalized therapeutic regimens for pre-clinal and clinical tests.
Posttranscriptional regulation of Ghd7 protein stability by phytochrome and OsGI in photoperiodic control of flowering in rice.

Rice (Oryza sativa) is a facultative short-day (SD) plant, flowering early under SD and late under long-day (LD) conditions. Ghd7 is a major regulator of flowering time in rice, which strongly delays flowering under LD. Induction of Ghd7 expression by phytochromes has been shown to contribute to photoperiodic regulation of flowering in rice. Here, we show that Ghd7 is also regulated by phytochromes at a post-transcriptional level. We found that constitutive expression of Ghd7 delays flowering in the wild type background, but not in the se5 mutant background (deficient in functional phytochromes) under LD and that Ghd7 protein fails to accumulate in the se5 mutant. We also found that co-expressing OsGI with Ghd7 causes reduced accumulation of Ghd7 protein and partially suppresses the delayed flowering phenotype in the wild type background, suggesting that phytochromes and OsGI play antagonist roles in regulating Ghd7 protein stability and flowering time. We show that OsPHYA, OsPHYB and OsGI could directly interact with Ghd7. Interestingly, OsPHYA and OsPHYB could inhibit the interaction between OsGI and Ghd7, and thus helping to stabilize Ghd7 protein. Our results revealed a new level of Ghd7 regulation by phytochromes and OsGI in photoperiodic control of flowering in rice. This article is protected by copyright. All rights reserved.
Evaluation of the repair of diaphyseal fracture of femoral bone using bone marrow mesenchymal stem cells in nicotine-bearing rat.

OBJECTIVE Following bone fractures during accidents, some patients suffer from poor repair of bone fractures and subsequent aesthetic and psychological problems. One of the treatments is based on transplantation of stem cells (seeded on scaffolds) to the lesion site. Bone marrow stromal cells (BMSCs) are multivalent stem cells which are able to reproduce and differentiate into osteogenic cells. The objective of this study was to evaluate the treatment of bone fractures by means of transplantation of the latter cells in rats. METHODS In this study, the therapeutic effect of mesenchymal stem cells from bone marrow adipocytes was evaluated in bone fractures. BMSCs were isolated from rat femur. Two sources of differentiated and non-differentiated osteocyte cells were provided and mixed with collagen in order to be transferred to animals divided in three main groups of model: nicotine, non-nicotine and control groups. After four weeks, the repair of the fracture that had been inflicted by a 2‑mm drill into the diaphyseal region of the femoral bone was investigated by radiographic tests and histopathologic staining. RESULTS The radiographic results as well as those of histopathologic staining showed that osteogenesis was more intensive in the non-nicotine group than in the nicotine group with differentiated and non-differentiated osteocyte cells. CONCLUSION The transplantation of differentiated BMSCs to a bone lesion affected the repair of bone fractures while the nicotine agent played an important role in delaying the bone regeneration (Tab. 1, Fig. 8, Ref. 31).
MLatom: A program package for quantum chemical research assisted by machine learning

MLatom is a program package designed for computationally efficient simulations of atomistic systems with machine‐learning (ML) algorithms. It can be used out‐of‐the‐box as a stand‐alone program with a user‐friendly online manual. The use of MLatom does not require extensive knowledge of machine learning, programming, or scripting. The user need only prepare input files and choose appropriate options. The program implements kernel ridge regression and supports Gaussian, Laplacian, and Matérn kernels. It can use arbitrary, user‐provided input vectors and can convert molecular geometries into input vectors corresponding to several types of built‐in molecular descriptors. MLatom saves and re‐uses trained ML models as needed, in addition to estimating the generalization error of ML setups. Various sampling procedures are supported and the gradients of output properties can be calculated. The core part of MLatom is written in Fortran, uses standard libraries for linear algebra, and is optimized for shared‐memory parallel computations. © 2019 Wiley Periodicals, Inc.
The exocyst complex and Rab5 are required for abscission by localizing ESCRT III subunits to the cytokinetic bridge

ABSTRACT Cytokinesis is the final step of cell division following chromosome segregation that generates two daughter cells. The conserved exocyst complex is required for scission of the intercellular cytokinetic bridge, although the molecular mechanisms it employs in this process are unclear. We identify and validate the early endocytic GTPase Rab5 as interacting with the exocyst complex in mammalian cells. Rab5 localizes in the cytokinetic bridge and on the midbody ring in a manner similar to the exocyst complex. Depletion of Rab5 led to delayed abscission. Caenorhabditis elegans orthologs of both exocyst complex subunits and Rab5 localize along the cleavage furrow and are required for cytokinesis in early embryos. Cytokinetic cells depleted of either Rab5 or the exocyst subunits Exoc3 and Exoc4 showed impaired deposition of the endosomal sorting complexes required for transport (ESCRT) III subunits CHMP2B and/or CHMP4B near the midbody ring. The study reveals an evolutionarily conserved role for the early endocytic marker Rab5 in cytokinetic abscission. In addition, it uncovers a key requirement of the exocyst and Rab5 for the delivery of components of the membrane-severing ESCRT III machinery to complete cytokinesis. Summary: The conserved exocytic vesicle-tethering exocyst complex and the endocytic master regulator Rab5 mutually interact and are required to deliver the ESCRT III membrane scission apparatus for completion of cytokinesis.
A New Approach for Functional Connectivity via Alignment of Blood Oxygen Level-Dependent Signals

Due to technological advances, spatially indexed objects, such as blood oxygen level-dependent time series or electroencephalography data, are commonly observed across different scientific disciplines. Such object data are typically high dimensional and therefore challenging to handle. We propose a new approach for spatially indexed object data by mapping their spatial locations to a targeted one-dimensional interval so objects that are similar are placed near each other on the new target space. The proposed alignment not only provides a visualization tool for such complex object data but also facilitates a new way to study brain functional connectivity. Specifically, we introduce a new concept of path length to quantify the functional connectivity and a new community detection method. The advantages of the proposed methods are illustrated by simulations and in a study of functional connectivity for Alzheimer's disease.
A reliable algorithm for image matching based on SIFT

A novel algorithm is presented to make the results of image matching more reliable and accurate based on SIFT (Scale Invariant Feature Transform). SIFT algorithm has been identified as the most resistant matching algorithm to common image deformations; however, if there are similar regions in images, SIFT algorithm still generates some analogical descriptors and provides many mismatches. This paper examines the local image descriptor used by SIFT and presents a new algorithm by integrating SIFT with two-dimensional moment invariants and disparity gradient to improve the matching results. In the new algorithm, decision tree is used, and the whole matching process is divided into three levels with different primitives. Matching points are considered as correct ones only when they satisfy all the three similarity measurements. Experiment results demonstrate that the new approach is more reliable and accurate.
Comparative analysis of the metal-dependent structural and functional properties of mouse and human SMP30

Senescence Marker Protein (SMP30) is a metalloenzyme that shows lactonase activity in the ascorbic acid (AA) biosynthesis pathway in non-primate mammals such as a mouse. However, AA biosynthesis does not occur in the primates including humans. Several studies have shown the role of SMP30 in maintaining calcium homeostasis in mammals. In addition, it is also reported to have promiscuous enzyme activity with an organophosphate (OP) substrate. Hence, this study aims to recombinantly express and purify the SMP30 proteins from both mouse and human, and to study their structural alterations and functional deviations in the presence of different divalent metals. For this, mouse SMP30 (MoSMP30) as well as human SMP30 (HuSMP30) were cloned in the bacterial expression vector. Proteins were overexpressed and purified from soluble fractions as well as from inclusion bodies as these proteins were expressed largely in insoluble fractions. The purified proteins were used to study the folding conformations in the presence of different divalent cations (Ca2+, Co2+, Mg2+, and Zn2+) with the help of circular dichroism (CD) spectroscopy. It was observed that both MoSMP30 and HuSMP30 acquired native folding conformations. To study the metal-binding affinity, dissociation constant (Kd values) were calculated from UV-VIS titration curve, which showed the highest affinity of MoSMP30 with Zn2+. However, HuSMP30 showed the highest affinity with Ca2+, suggesting the importance of HuSMP30 in maintaining calcium homeostasis. Enzyme kinetics were performed with γ-Thiobutyrolactone and Demeton-S in the presence of different divalent cations. Interestingly, both the proteins showed lactonase activity in the presence of Ca2+. In addition, MoSMP30 and HuSMP30 also showed lactonase activity in the presence of Co2+ and Zn2+ respectively. Moreover, both the proteins showed OP hydrolase activities in the presence of Ca2+ as well as Zn2+, suggesting the metal-dependent promiscuous nature of SMP30.