Miracle-dz/UniFAR-FTUs huggingface dataset:
Cannabinoid and planar cell polarity signaling converges to direct placentation

Significance During placentation, some trophoblast cells, termed spiral artery trophoblast giant cells (SpA-TGCs), invade the maternal decidua and replace arterial endothelial cells to increase blood supply to the placenta; how this directional trophoblast migration occurs remains unknown. We show here that planar cell polarity (PCP) signaling mediated by VANGL2 in SpA-TGCs plays a key role in trophoblast movement and successful placentation. Mice with SpA-TGC progenitors deficient in Vangl2 had pregnancy termination in mid-gestation due to increased random cell protrusion and compromised cell migration. We also found endocannabinoid signaling intersects with PCP signaling in directing trophoblast migration by direct association of CB1 and VANGL2. These results demonstrated that trophoblast invasion in placentation requires organized PCP. Directed trophoblast migration toward the maternal mesometrial pole is critical for placentation and pregnancy success. Trophoblasts replace maternal arterial endothelial cells to increase blood supply to the placenta. Inferior trophoblast invasion results in pregnancy complications including preeclampsia, intrauterine growth restriction, miscarriage, and preterm delivery. The maternal chemotactic factors that direct trophoblast migration and the mechanism by which trophoblasts respond to these factors are not clearly understood. Here, we show that invasive trophoblasts deficient in Vangl2, a core planar cell polarity (PCP) component, fail to invade in maternal decidua, and this deficiency results in middle-gestational fetal demise. Previously, we have shown that tightly regulated endocannabinoids via G protein–coupled cannabinoid receptor CB1 are critical to the invasion of trophoblasts called spiral artery trophoblast giant cells (SpA-TGCs). We find that CB1 directly interacts with VANGL2. Trophoblast stem cells devoid of Cnr1 and/or Vangl2 show compromised cell migration. To study roles of VANGL2 and CB1 in trophoblast invasion in vivo, we conditionally deleted Cnr1 (coding CB1) and Vangl2 in progenitors of SpA-TGCs using trophoblast-specific protein alpha (Tpbpa)-Cre. We observed that signaling mediated by VANGL2 and CB1 restrains trophoblasts from random migration by keeping small GTPases quiescent. Our results show that organized PCP in trophoblasts is indispensable for their directed movement and that CB1 exerts its function by direct interaction with membrane proteins other than its canonical G protein–coupled receptor role.
Super-resolution microscopy reveals photoreceptor-specific subciliary location and function of ciliopathy-associated protein CEP290

Mutations in the cilium-associated protein CEP290 cause retinal degeneration as part of multiorgan ciliopathies or as retina-specific diseases. The precise location and the functional roles of CEP290 within cilia and, specifically, the connecting cilia (CC) of photoreceptors, remain unclear. We used super-resolution fluorescence microscopy and electron microscopy to localize CEP290 in the CC and in the primary cilia of cultured cells with subdiffraction resolution and to determine effects of CEP290 deficiency in 3 mutant models. Radially, CEP290 localizes in close proximity to the microtubule doublets in the region between the doublets and the ciliary membrane. Longitudinally, it is distributed throughout the length of the CC whereas it is confined to the very base of primary cilia in human retinal pigment epithelium-1 cells. We found Y-shaped links, ciliary substructures between microtubules and membrane, throughout the length of the CC. Severe CEP290 deficiencies in mouse models did not prevent assembly of cilia or cause obvious mislocalization of ciliary components in early stages of degeneration. There were fewer cilia and no normal outer segments in the mutants, but the Y-shaped links were clearly present. These results point to photoreceptor-specific functions of CEP290 essential for CC maturation and stability following the earliest stages of ciliogenesis.
APOBEC3B Potently Restricts HIV-2 but Not HIV-1 in a Vif-Dependent Manner

Primate lentiviruses encode a series of accessory genes that facilitate virus adaptation to its host. Among those, the vif-encoded protein functions primarily by targeting the APOBEC3 (A3) family of cytidine deaminases. ABSTRACT Vif is a lentiviral accessory protein that counteracts the antiviral activity of cellular APOBEC3 (A3) cytidine deaminases in infected cells. The exact contribution of each member of the A3 family for the restriction of HIV-2 is still unclear. Thus, the aim of this work was to identify the A3s with anti-HIV-2 activity and compare their restriction potential for HIV-2 and HIV-1. We found that A3G is a strong restriction factor of both types of viruses and A3C restricts neither HIV-1 nor HIV-2. Importantly, A3B exhibited potent antiviral activity against HIV-2, but its effect was negligible against HIV-1. Whereas A3B is packaged with similar efficiency into both viruses in the absence of Vif, HIV-2 and HIV-1 differ in their sensitivity to A3B. HIV-2 Vif targets A3B by reducing its cellular levels and inhibiting its packaging into virions, whereas HIV-1 Vif did not evolve to antagonize A3B. Our observations support the hypothesis that during wild-type HIV-1 and HIV-2 infections, both viruses are able to replicate in host cells expressing A3B but using different mechanisms, probably resulting from a Vif functional adaptation over evolutionary time. Our findings provide new insights into the differences between Vif protein and their cellular partners in the two human viruses. Of note, A3B is highly expressed in some cancer cells and may cause deamination-induced mutations in these cancers. Thus, A3B may represent an important therapeutic target. As such, the ability of HIV-2 Vif to induce A3B degradation could be an effective tool for cancer therapy. IMPORTANCE Primate lentiviruses encode a series of accessory genes that facilitate virus adaptation to its host. Among those, the vif-encoded protein functions primarily by targeting the APOBEC3 (A3) family of cytidine deaminases. All lentiviral Vif proteins have the ability to antagonize A3G; however, antagonizing other members of the A3 family is variable. Here, we report that HIV-2 Vif, unlike HIV-1 Vif, can induce degradation of A3B. Consequently, HIV-2 Vif but not HIV-1 Vif can inhibit the packaging of A3B. Interestingly, while A3B is packaged efficiently into the core of both HIV-1 and HIV-2 virions in the absence of Vif, it only affects the infectivity of HIV-2 particles. Thus, HIV-1 and HIV-2 have evolved two distinct mechanisms to antagonize the antiviral activity of A3B. Aside from its antiviral activity, A3B has been associated with mutations in some cancers. Degradation of A3B by HIV-2 Vif may be useful for cancer therapies.
Inflammatory markers are associated with quality of life, physical activity, and gait speed but not sarcopenia in aged men (40–79 years)

Age‐related chronic low‐grade inflammation (inflammaging) is one of the proposed mechanisms behind sarcopenia. However, findings regarding inflammatory markers in sarcopenic older adults are conflicting. This study aimed to determine the association between inflammatory markers, prevalent as well as incident sarcopenia, sarcopenia‐defining parameters, quality of life (QoL), and physical activity in middle‐aged and older men.
Evaluating Cancer Care Networks; A Case Study of a Lung Cancer Care Network

Background: Networks are promoted as an organizational form that enables integrated care as well as enhanced patient outcomes. However, implementing networks is complex. It is therefore important to evaluate the quality and effectiveness of networks to ensure it is worth developing and maintaining them. This article describes the development of an evaluation tool for cancer care networks and the results of a pilot study with a regional lung cancer care network. Methods: This study used a combination of qualitative and quantitative evaluation methods. The qualitative evaluation was based on a framework with 10 standards for the organization of an oncological (tumor-specific) care network. Data for the quantitative evaluation were obtained from the Dutch Cancer Registry. The evaluation was performed at a network of three hospitals collaborating in the field of lung oncology. Results: The qualitative evaluation framework consisted of 10 standards/questions which were divided into 38 sub-questions. The evaluation showed that in general patients are satisfied with the collaboration in the network. However, some improvement points were found such as the need for more attention for the implementation and periodic evaluation of a regional care pathway. The start of a regional multidisciplinary meeting has been a major step for improving the collaboration. Conclusion: An evaluation tool for (lung) cancer care networks was successfully developed and piloted within a cancer care network. The tool has proven to be a useful method for evaluating collaboration within an oncological network. It helped network partners to understand what they see as important and allowed them to learn about their program’s dynamics. Improvement opportunities were successfully identified. To keep the tool up to date continuous improvement is needed, following the Plan Do Check Act (PDCA) cycle.
Methyl linked pyrazoles: Synthetic and Medicinal Perspective.

Pyrazoles, an important and well known class of the azole family, have been found to show a large number of applications in various fields specially of medicinal chemistry. Among pyrazole derivatives, particularly, methyl substituted pyrazoles have been reported as the potent medicinal scaffolds that exhibit a wide spectrum of biological activities. The present review is an attempt to highlight the detailed synthetic approaches for methyl substituted pyrazoles along with in depth analysis of their respective medical significances till March2021. It is hoped that literature sum-up in the form of present review article would certainly be a great tool to assist the medicinal chemists for generating new leads possessing pyrazole nucleus with high efficacy and less microbial resistance.
INDUCTION OF HEMOLYSIS AND ERYPTOSIS BY OCCUPATIONAL POLLUTANT NICKEL CHLORIDE IS MEDIATED THROUGH CALCIUM INFLUX AND P38 MAP KINASE SIGNALING

Objectives: Nickel (Ni) is an abundant environmental hazard and an occupational pollutant. Exposure to Ni compounds is prevalent in electroplating workers and in the printing industry, among others. The toxicity of Ni manifests as dermatological, gastrointestinal, respiratory, allergic, and cardiovascular symptoms. In particular, hyperbilirubinemia and reticulocytosis have been detected in intoxicated subjects; an observation possibly implicating selective red blood cell (RBC) toxicity. Herein, the interaction of nickel chloride (NiCl2) with human RBCs and associated molecular mechanisms are described. Material and Methods: Cells from healthy donors were incubated for 24 h at 37°C in the presence or absence of 0.5–10 mM of NiCl2, and cytotoxicity was determined through hemoglobin leakage by colorimetry under different experimental conditions. Eryptotic markers were also identified by flow cytofluorometry using Annexin-V-FITC tagging for phosphatidylserine (PS) exposure, light scatter properties for cellular dimensions, Fluo4/AM labeling for intracellular calcium, and H2DCFDA staining for reactive oxygen species (ROS). Additionally, small molecule inhibitors were used to probe the signaling pathways involved. Results: It was found that NiCl2 at 10 mM caused profound intracellular calcium overload and significant calcium-dependent hemolysis. Also, NiCl2 reduced forward scatter and increased side scatter, Annex-in-positive cells, and ROS levels. Importantly, NiCl2-induced hemolysis was significantly attenuated by the exclusion of extracellular calcium, and in the presence of p38 MAP kinase (MAPK) inhibitor SB203580. Conclusions: It is concluded that NiCl2 induces p38 MAPK-dependent hemolysis, and stimulates the canonical features of premature eryptosis. This report presents the first description of the molecular mechanisms underlying the hemolytic and eryptotic potential of NiCl2 and, thus, may explain changes in hematological parameters observed in poisoning victims.
The Potential of Pancreatic Organoids for Diabetes Research and Therapy

ABSTRACT The success of clinical transplantation of pancreas or isolated pancreatic islets supports the concept of cell-based cure for diabetes. One limitation is the shortage of cadaver human pancreata. The demand–supply gap could potentially be bridged by harnessing the self-renewal capacity of stem cells. Pluripotent stem cells and adult pancreatic stem cells have been explored as possible cell sources. Recently, a system for long-term culture of proposed adult pancreatic stem cells in a form of organoids was developed. Generated organoids partially mimic the architecture and cell-type composition of pancreatic tissue. Here, we review the attempts over the past decade, to utilize the organoid cell culture principles in order to identify, expand, and differentiate the adult pancreatic stem cells from different compartments of mouse and human pancreata. The development of the culture conditions, effects of specific growth factors and small molecules is discussed. The potential utility of the adult pancreatic stem cells is considered in the context of other cell sources.
The chromatin remodeler Chd1 supports MRX and Exo1 functions in resection of DNA double-strand breaks

Repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) requires that the 5’-terminated DNA strands are resected to generate single-stranded DNA overhangs. This process is initiated by a short-range resection catalyzed by the MRX (Mre11-Rad50-Xrs2) complex, which is followed by a long-range step involving the nucleases Exo1 and Dna2. Here we show that the Saccharomyces cerevisiae ATP-dependent chromatin-remodeling protein Chd1 participates in both short- and long-range resection by promoting MRX and Exo1 association with the DSB ends. Furthermore, Chd1 reduces histone occupancy near the DSB ends and promotes DSB repair by HR. All these functions require Chd1 ATPase activity, supporting a role for Chd1 in the opening of chromatin at the DSB site to facilitate MRX and Exo1 processing activities.
Blockchain-enabled IoT platform for end-to-end supply chain risk management

After being legalized as an agricultural commodity by the 2018 U.S. Farm Bill, the Industrial Hemp production is moved from limited pilot programs to a regulated agriculture production system, and the market keeps increasing since then. However, Industrial Hemp Supply Chain (IHSC) faces several critical challenges, including high complexity and variability, data tampering, and lack of immutable information tracking system. In this paper, we develop a blockchain enabled internet-of-things (IoT) platform for IHSC to support process tracking, scalability, interoperability, and risk management. Basically, we create a two-layer blockchain with proof-of-authority based smart contract, which can leverage local authorities with state/federal regulators to ensure and accelerate quality control verification and regulatory compliance. Then, we develop a user-friendly mobile app so that each participant can use smart phone to real-time collect and upload their data to the cloud, and further share the process verification and tracking information through the blockchain network. Our study indicates the proposed platform can support interoperability, improve the efficiency of quality control verification, and ensure the safety of regulated IHSC.
Customer Segmentation and Buyer Targeting Approach

Nowadays, maintaining customer loyalty and attention span of the customers are major challenges faced by the retail industry. The availability of varied options in the market for similar purposes increases the competition between organizations, to market their product, tremendously. This leads to the need for reinforcement of marketing strategies from time to time. With the advancement of technology, this can be made possible. This paper proposes a systematic approach for targeting customers and providing maximum profit to the organizations. An important initial step is to analyze the data of sales acquired from the purchase history and determine the parameters that have the maximum correlation. We focus on the parameters recency and frequency of the purchases made by the customers to perform clustering. Based on respective clusters, proper resources can be channeled towards profitable customers using machine learning algorithms. This paper also deals with the draw- backs of the recommender system like cold start problem, sparsity, etc and how they can be overcome. K-Means clustering is used for customer segmentation and Singular Value Decomposition is used for providing appropriate recommendations to the customers.
Use and usability of software verification methods to detect behaviour interference when teaching an assistive home companion robot: A proof-of-concept study

Abstract When studying the use of assistive robots in home environments, and especially how such robots can be personalised to meet the needs of the resident, key concerns are issues related to behaviour verification, behaviour interference and safety. Here, personalisation refers to the teaching of new robot behaviours by both technical and non-technical end users. In this article, we consider the issue of behaviour interference caused by situations where newly taught robot behaviours may affect or be affected by existing behaviours and thus, those behaviours will not or might not ever be executed. We focus in particular on how such situations can be detected and presented to the user. We describe the human–robot behaviour teaching system that we developed as well as the formal behaviour checking methods used. The online use of behaviour checking is demonstrated, based on static analysis of behaviours during the operation of the robot, and evaluated in a user study. We conducted a proof-of-concept human–robot interaction study with an autonomous, multi-purpose robot operating within a smart home environment. Twenty participants individually taught the robot behaviours according to instructions they were given, some of which caused interference with other behaviours. A mechanism for detecting behaviour interference provided feedback to participants and suggestions on how to resolve those conflicts. We assessed the participants’ views on detected interference as reported by the behaviour teaching system. Results indicate that interference warnings given to participants during teaching provoked an understanding of the issue. We did not find a significant influence of participants’ technical background. These results highlight a promising path towards verification and validation of assistive home companion robots that allow end-user personalisation.
The person-animacy connection: Evidence from Algonquian and Dene

This squib presents evidence from the Algonquian and Dene language families to support a connection between person and animacy. A range of morphosyntactic patterns in these languages, including pronoun inventories, agreement restrictions, and hierarchy effects, are argued to indicate that inanimate nominals lack formal person features. This proposal allows the morphosyntactic patterning of inanimates to fall out from grammatical principles that are independently required to account for person effects. We conclude that the often-assumed model in which third persons are “personless” must be revised to allow for languages in which only inanimate third persons lack formal person features. The squib is organized as follows. Section 1 provides background on person features and the notion of personlessness. Section 2 shows that various patterns in Algonquian and Dene morphosyntax follow from an analysis in which inanimate third persons are personless but animate third persons are specified for person. Section 3 considers whether the proposed person-animacy connection is conditioned by semantic animacy or grammatical animacy.
Diagnosing indirect relationships in multivariate calibration models

Problems concerning covariance among independent variables are well understood and dealt with by inverse regression methods like partial least squares regression. However, covariance between dependent variables has only received minor attention. Biological samples are often complex mixtures of multiple covarying compounds. During multivariate calibration, analyte predictions may be mediated through relationships with interfering compounds, which implies that the calibration model is not providing a direct link between the multivariate measurements and the analyte of interest. This compromises robustness and validity of the calibration model—important aspects when applying the model to future samples and data sets. This study discusses issues of calibration modeling when strong covariance structures exist among the analyte of interest and interfering compounds.
Gsx2, but not Gsx1, is necessary for early forebrain patterning and long‐term survival in zebrafish

Homeobox transcription factor encoding genes, genomic screen homeobox 1 and 2 (gsx1 and gsx2), are expressed during neurodevelopment in multiple vertebrates. However, we have limited knowledge of the dynamic expression of these genes through developmental time and the gene networks that they regulate in zebrafish.
Heterogeneous Mutation Rates and Spectra in Yeast Hybrids

Mutation rates and spectra vary between species and among populations. Hybridization can contribute to this variation, but its role remains poorly understood. Estimating mutation rates requires controlled conditions where the effect of natural selection can be minimized. One way to achieve this is through mutation accumulation experiments coupled with genome sequencing. Here we investigate 400 mutation accumulation lines initiated from 11 genotypes spanning intra-lineage, inter-lineage and interspecific crosses of the yeasts Saccharomyces paradoxus and S. cerevisiae and propagated for 770 generations. We find significant differences in mutation rates and spectra among crosses, which are not related to the level of divergence of parental strains but are specific to some genotype combinations. Differences in number of generations and departures from neutrality play a minor role, whereas polyploidy and loss of heterozygosity impact mutation rates in some of the hybrid crosses in an opposite way.
An Effective Burst Access Scheme for Lossless Frame Buffer Compression on a Video Decoder

For decoding high-resolution image stored in external memory after lossless compression, it is inevitable necessary to allow variable-length data types and this may decreases the efficiency in real time read of arbitrary compressed macro block without burst-mode in memory. This paper proposes a cache architecture for a video decoder that has a burst mode capability for accessing lossless compressed frame data in the memory. In the proposed cache architecture, the write and read caches employ the concept of fixed-length burst groups, allowing efficient burst write and read operations. The experimental results show that the proposed cache architecture can decrease memory access times by an average of 70.92%
Schema Ontology Model to Support Semantic Interoperability in Healthcare Applications: Use Case of Depressive Disorder

The provision of semantic interoperability among heterogeneous data is important issue to cope with a tremendous potential of diverse healthcare applications. This paper describes schema ontology models to support semantic interoperability in healthcare applications of depressive disorder (DD) using the framework of Web of Objects (WoO). And the implementation aspects of semantics interoperability with required schema ontology models and their integrated associations are defined to characterize the target interoperable ontology of affective DD states.