Miracle-dz/UniFAR-FTUs huggingface dataset:
PDZD8 mediates a Rab7-dependent interaction of the ER with late endosomes and lysosomes

Significance Membrane lipid homeostasis within cells requires a cooperation of vesicular transport and of lipid transfer proteins that mediate lipid exchange between membranes independent of bilayer fusion. Many such proteins also function as tethers connecting adjacent bilayers. For membranes that travel along the exo- and endocytic pathways, these tethers must be regulated to ensure their action selectively at specific stations of their journey. Here we identify a mechanism that recruits the endoplasmic reticulum (ER) to late endosomes/lysosomes and that may promote exchange of lipids between their membranes. These contacts rely on the binding of an ER-anchored lipid transfer protein to a key player in endosomal maturation, the small GTPase Rab7, thus explaining how their formation is regulated in time and space. Contacts between the endoplasmic reticulum (ER) and other membranes are hot spots for protein-mediated lipid transport between the 2 adjacent bilayers. Compiling a molecular inventory of lipid transport proteins present at these sites is a premise to the elucidation of their function. Here we show that PDZD8, an intrinsic membrane protein of the ER with a lipid transport module of the SMP domain family, concentrates at contacts between the ER and late endosomes/lysosomes, where it interacts with GTP-Rab7. These findings suggest that PDZD8 may cooperate with other proteins that function at the ER–endo/lysosome interface in coordinating endocytic flow with lipid transport between endocytic membranes and the ER.
Diurnal Regulation of Renal Electrolyte Excretion: The Role of Paracrine Factors.

Many physiological processes, including most kidney-related functions, follow specific rhythms tied to a 24-h cycle. This is largely because circadian genes operate in virtually every cell type in the body. In addition, many noncanonical genes have intrinsic circadian rhythms, especially within the liver and kidney. This new level of complexity applies to the control of renal electrolyte excretion. Furthermore, there is growing evidence that paracrine and autocrine factors, especially the endothelin system, are regulated by clock genes. We have known for decades that excretion of electrolytes is dependent on time of day, which could play an important role in fluid volume balance and blood pressure control. Here, we review what is known about the interplay between paracrine and circadian control of electrolyte excretion. The hope is that recognition of paracrine and circadian factors can be considered more deeply in the future when integrating with well-established neuroendocrine control of excretion. Expected final online publication date for the Annual Review of Physiology, Volume 82 is February 10, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.
Intrinsically Disordered SRC-3/AIB1 Protein Undergoes Homeostatic Nuclear Extrusion by Nuclear Budding While Ectopic Expression Induces Nucleophagy

SRC-3/AIB1 (Amplified in Breast Cancer-1) is a nuclear receptor coactivator for the estrogen receptor in breast cancer cells. It is also an intrinsically disordered protein when not engaged with transcriptional binding partners and degraded upon transcriptional coactivation. Given the amplified expression of SRC-3 in breast cancers, the objective of this study was to determine how increasing SRC-3 protein levels are regulated in MCF-7 breast cancer cells. We found that endogenous SRC-3 was expelled from the nucleus in vesicle-like spheres under normal growth conditions suggesting that this form of nuclear exclusion of SRC-3 is a homeostatic mechanism for regulating nuclear SRC-3 protein. Only SRC-3 not associated with CREB-binding protein (CBP) was extruded from the nucleus. We found that overexpression in MCF-7 cells results in aneuploid senescence and cell death with frequent formation of nuclear aggregates which were consistently juxtaposed to perinuclear microtubules. Transfected SRC-3 was SUMOylated and caused redistribution of nuclear promyelocytic leukemia (PML) bodies and perturbation of the nuclear membrane lamin B1, hallmarks of nucleophagy. Increased SRC-3 protein-induced autophagy and resulted in SUMO-1 localization to the nuclear membrane and formation of protrusions variously containing SRC-3 and chromatin. Aspects of SRC-3 overexpression and toxicity were recapitulated following treatment with clinically relevant agents that stabilize SRC-3 in breast cancer cells. We conclude that amplified SRC-3 levels have major impacts on nuclear protein quality control pathways and may mark cancer cells for sensitivity to protein stabilizing therapeutics.
Effects of the Herbicide Glyphosate on Honey Bee Sensory and Cognitive Abilities: Individual Impairments with Implications for the Hive

The honeybee Apis mellifera is an important pollinator in both undisturbed and agricultural ecosystems. Its great versatility as an experimental model makes it an excellent proxy to evaluate the environmental impact of agrochemicals using current methodologies and procedures in environmental toxicology. The increase in agrochemical use, including those that do not target insects directly, can have deleterious effects if carried out indiscriminately. This seems to be the case of the herbicide glyphosate (GLY), the most widely used agrochemical worldwide. Its presence in honey has been reported in samples obtained from different environments. Hence, to understand its current and potential risks for this pollinator it has become essential to not only study the effects on honeybee colonies located in agricultural settings, but also its effects under laboratory conditions. Subtle deleterious effects can be detected using experimental approaches. GLY negatively affects associative learning processes of foragers, cognitive and sensory abilities of young hive bees and promotes delays in brood development. An integrated approach that considers behavior, physiology, and development allows not only to determine the effects of this agrochemical on this eusocial insect from an experimental perspective, but also to infer putative effects in disturbed environments where it is omnipresent.
Interference-Aware Subcarrier Allocation for Massive Machine-Type Communication in 5G-Enabled Internet of Things

Massive machine-type communication (mMTC) is investigated as one of three typical scenes of the 5th-generation (5G) network. In this paper, we propose a 5G-enabled internet of things (IoT) in which some enhanced mobile broadband devices transmit video stream to a centralized controller and some mMTC devices exchange short packet data with adjacent devices via D2D communication to promote inter-device cooperation. Since massive MTC devices have data transmission requirements in 5G-enabled IoT with limited spectrum resources, the subcarrier allocation problem is investigated to maximize the connectivity of mMTC devices subject to the quality of service (QoS) requirement of enhanced Mobile Broadband (eMBB) devices and mMTC devices. To solve the formulated mixed-integer non-linear programming (MINLP) problem, which is NP-hard, an interference-aware subcarrier allocation algorithm for mMTC communication (IASA) is developed to maximize the number of active mMTC devices. Finally, the performance of the proposed algorithm is evaluated by simulation. Numerical results demonstrate that the proposed algorithm outperforms the three traditional benchmark methods, which significantly improves the utilization of the uplink spectrum. This indicates that the proposed IASA algorithm provides a better solution for IoT application.
Wheeler's Dental Anatomy, Physiology and Occlusion

1. Introduction to dental anatomy 2. Development and eruption of the teeth 3. The primary (deciduous) teeth 4. Forensics, comparative anatomy, geometries, and form and function 5. Orofacial complex: form and function 6. The permanent maxillary incisors 7. The permanent mandibular incisors 8. The permanent canines, maxillary and mandibular 9. The permanent maxillary premolars 10. The permanent mandibular premolars 11. The permanent maxillary molars 12. The permanent mandibular molars 13. Pulp chambers and canals 14. Dento-osseous structures, blood vessels and nerves 15. The temporomandibular joints, teeth, and muscles and their functions 16. Occlusion
Application of Two-Photon-Absorption Pulsed Laser for Single-Event-Effects Sensitivity Mapping Technology

Single-event effects (SEEs) in integrated circuits and devices can be studied by utilizing ultra-fast pulsed laser system through Two Photon Absorption process. This paper presents technical ways to characterize key factors for laser based SEEs mapping testing system: output power from laser source, spot size focused by objective lens, opening window of Pockels cell, and calibration of injected laser energy. The laser based SEEs mapping testing system can work in a stable and controllable status by applying these methods. Furthermore, a sensitivity map of a Static Random Access Memory (SRAM) cell with a 65 nm technique node was created through the established laser system. The sensitivity map of the SRAM cell was compared to a map generated by a commercial simulation tool (TFIT), and the two matched well. In addition, experiments in this paper also provided energy distribution profile along Z axis that is the direction of the pulsed laser injection and threshold energy for different SRAM structures.
Advancing the Science of Tick and Tick-Borne Disease Surveillance in the United States

Globally, vector-borne diseases are an increasing public health burden; in the United States, tick-borne diseases have tripled in the last three years. The United States Centers for Disease Control and Prevention (CDC) recognizes the need for resilience to the increasing vector-borne disease burden and has called for increased partnerships and sustained networks to identify and respond to the most pressing challenges that face vector-borne disease management, including increased surveillance. To increase applied research, develop communities of practice, and enhance workforce development, the CDC has created five regional Centers of Excellence in Vector-borne Disease. These Centers are a partnership of public health agencies, vector control groups, academic institutions, and industries. This special issue on tick and tick-borne disease surveillance is a collection of research articles on multiple aspects of surveillance from authors that are affiliated with or funded by the CDC Centers of Excellence. This body of work illustrates a community-based system of research by which participants share common problems and use integrated methodologies to produce outputs and effect outcomes that benefit human, animal and environmental health.
lncRNA/mRNA profiling of endometriosis rat uterine tissues during the implantation window

Endometriosis is associated with changes in long non-coding RNA (lncRNA) and mRNA expression, but the exact changes during the implantation window are unknown. Therefore, this study aimed to explore the lncRNA and mRNA expression profiles in the uterus of rats with endometriosis during the implantation window. A total of 35 non-pregnant female rats were randomized to the endometriosis (n=13), adipose tissue control (n=8) and blank control (n=14) groups. On the 5th day of pregnancy, the rats were sacrificed to obtain uterine tissues. lncRNA and mRNA were analyzed using gene chips. A total of five differentially expressed lncRNA and four mRNA were validated by reverse transcription-quantitative (RT-q)PCR. Immunohistochemistry and western blotting were used to determine the expression of the ADAM metal-lopeptidase with thrombospondin type 1 motif 7 (Adamts7), tumor protein p53 (Tp53), distal-less homeobox 3 (Dlx3) and pyrimidinergic receptor P2Y6 (P2ry6) proteins. There were 115 upregulated lncRNAs, 51 downregulated lncRNAs, 97 upregulated mRNAs and 85 downregulated mRNAs in the endometriosis group. RT-qPCR confirmed the trends for five lncRNAs and four mRNAs (Adamts7, Tp53, Dlx3 and P2ry6). The relative protein expression levels of Adamts7, P2ry6, Dlx3 and TP53 were significantly different in the endometriosis group (P<0.05 vs. controls). Bioinformatics predicted the co-expression relationship of the selected five lncRNA and four mRNA. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes predicted that Adamts7, P2ry6, Dlx3 and TP53 were involved in endometriosis-related inflammation and reproductive pathways. In conclusion, the changes in the expression of lncRNAs, mRNAs and proteins (Adamts7, P2ry6, Dlx3 and TP53) may possibly affect endometrial receptivity in rats with endometriosis during the implantation window, probably resulting in implantation failure of the embryo.
A Generic Quality Control Framework for Fetal Ultrasound Cardiac Four-Chamber Planes

Quality control/assessment of ultrasound (US) images is an essential step in clinical diagnosis. This process is usually done manually, suffering from some drawbacks, such as dependence on operator's experience and extensive labors, as well as high inter- and intra-observer variation. Automatic quality assessment of US images is therefore highly desirable. Fetal US cardiac four-chamber plane (CFP) is one of the most commonly used cardiac views, which was used in the diagnosis of heart anomalies in the early 1980s. In this paper, we propose a generic deep learning framework for automatic quality control of fetal US CFPs. The proposed framework consists of three networks: (1) a basic CNN (B-CNN), roughly classifying four-chamber views from the raw data; (2) a deeper CNN (D-CNN), determining the gain and zoom of the target images in a multi-task learning manner; and (3) the aggregated residual visual block net (ARVBNet), detecting the key anatomical structures on a plane. Based on the output of the three networks, overall quantitative score of each CFP is obtained, so as to achieve fully automatic quality control. Experiments on a fetal US dataset demonstrated our proposed method achieved a highest mean average precision (mAP) of 93.52% at a fast speed of 101 frames per second (FPS). In order to demonstrate the adaptability and generalization capacity, the proposed detection network (i.e., ARVBNet) has also been validated on the PASCAL VOC dataset, obtaining a highest mAP of 81.2% when input size is approximately 300 × 300.
Tinidazole efficacy for amebic colitis therapeutic prophylaxis in patients with de novo acute leukemia receiving intensive chemotherapy.

Introduction In Mexico, seroprevalence of Entamoeba histolytica is 8.4%. The intestinal amebiasis in patients with acute leukemia of novo, after the start of chemotherapy (CT) in the Hematology Service of the CMN 20 de Noviembre is 12%, even if patients show a negative baseline coprological test. Objective To find out if the administration of tinidazole, in patients with acute leukemia and negative coprological test, at the beginning of the CT, decreases the incidence of amoebic colitis during the induction to remission. Method Prospective and not comparative study. Patients with de novo diagnosis of acute leukemia who initiate induction and initial coprological CT. Tinidazole was indicated, 2 g/day for 5 days in the first week of CT started. They were monitored until the induction was concluded and hematopoietic recovery started. Results 38 patients, 15 women and 23 men with a mean age of 44 years (16-72), with acute lymphoblastic leukemia 19, myeloblastic 16 and promyelocytic 3. Cases without and with intestinal amebiasis were 35 and 3, respectively. Patients with amebiasis only received tinidazole for 3 days and it was given 2 days after the CT started. Conclusion Tinidazole, in patients with acute de novo leukemia who initiate induction CT, is effective in the prevention of intestinal amebiasis, during the induction stage, if administered at 2 g/day, for five days, starting on day 1 of the CT.
Role for the splicing factor TCERG1 in Cajal body integrity and snRNP assembly

ABSTRACT Cajal bodies are nuclear organelles involved in the nuclear phase of small nuclear ribonucleoprotein (snRNP) biogenesis. In this study, we identified the splicing factor TCERG1 as a coilin-associated factor that is essential for Cajal body integrity. Knockdown of TCERG1 disrupts the localization of the components of Cajal bodies, including coilin and NOLC1, with coilin being dispersed in the nucleoplasm into numerous small foci, without affecting speckles, gems or the histone locus body. Furthermore, the depletion of TCERG1 affects the recruitment of Sm proteins to uridine-rich small nuclear RNAs (snRNAs) to form the mature core snRNP. Taken together, the results of this study suggest that TCERG1 plays an important role in Cajal body formation and snRNP biogenesis. Highlighted Article: The results suggest a new role for TCERG1 in the formation of Cajal bodies and the biogenesis of snRNPs, which may have a functional consequence for pre-mRNA processing.
Dietary supplementation of a fiber-prebiotic and saccharin-eugenol blend in extruded diets fed to dogs

Abstract Prebiotics and dietary fibers are nondigestible ingredients that may confer benefits to the host by selectively stimulating beneficial intestinal bacteria and microbial-derived metabolites that support gut and host health. This experiment evaluated the effects of a blend of prebiotics and dietary fibers on apparent total tract digestibility (ATTD) and fecal metabolites related to gastrointestinal health in adult dogs. Four diets containing either 5% cellulose (control; CT), 5% dietary fiber and prebiotic blend (FP), 0.02% saccharin and eugenol (SE), or 5% fiber blend plus 0.02% saccharin and eugenol (FSE) were formulated to meet or exceed the AAFCO (2017) nutritional requirements for adult dogs. Eight adult female beagles (mean age 4.2 ± 1.1 yr; mean BW = 10.8 ± 1.4 kg; mean BCS = 5.8 ± 0.6) were randomly assigned to 1 of the 4 dietary treatments using a replicated 4 × 4 Latin square design. Each experimental period consisted of 14 d (10 d of diet adaptation and 4 d of total and fresh fecal and total urine collection). All animals remained healthy throughout the study, with serum metabolites being within reference ranges for adult dogs. All diets were well accepted by the dogs, resulting in similar (P > 0.05) daily food intakes among treatments. Likewise, fecal output and scores did not differ (P > 0.05) among dietary treatments, with the latter being within the ideal range (2.5–2.9) in a 5-point scale. All diets were highly digestible and had similar (P > 0.05) ATTD of dry matter (81.6%–84.4%), organic matter (86.4%–87.3%), and crude protein (86.6%–87.3%). However, total dietary fiber (TDF) digestibility was greater for dogs fed the FSE diet (P < 0.05) in contrast with dogs fed the CT and SE diets, whereas dogs fed FP diets had intermediate TDF digestibility, but not different from all other treatments. Fecal acetate and propionate concentrations were greater (P < 0.05) for dogs fed FP and FSE diets. Fecal concentrations of isobutyrate and isovalerate were greater for dogs fed CT (P < 0.05) compared with dogs fed the other three treatments. No shifts in fecal microbial richness and diversity were observed among dietary treatments. Overall, the data suggest that dietary supplementation of fiber and prebiotic blend was well tolerated by dogs, did not cause detrimental effects on fecal quality or nutrient digestibility, and resulted in beneficial shifts in fecal metabolites that may support gut health.
Potential and Challenges of Aptamers as Specific Carriers of Therapeutic Oligonucleotides for Precision Medicine in Cancer

Due to the progress made in the area of precision and personalized medicine in the field of cancer therapy, strategies to selectively and specifically identify target molecules causative of the diseases are urgently needed. Efforts are being made by a number of different laboratories, companies, and researchers to develop therapeutic molecules that selectively recognize the tissues and the cells of interest, exhibit few or no off-target and side effects, are non-immunogenic, and have a strong action. Aptamers, artificially selected single-stranded DNA or RNA oligonucleotides, are promising molecules satisfying many of the requirements needed for diagnosis and precision medicine. Aptamers can also couple to their native mechanism of action the delivery of additional molecules (oligonucleotides, siRNAs, miRNAs) to target cells. In this review, we summarize recent progress in the aptamer-mediated strategy for the specific delivery of therapeutic oligonucleotides.
Evaluation of a Technological Image-Based Dietary Assessment Tool for Children during Pubertal Growth: A Pilot Study

We designed an image-based dietary assessment tool called COFIT, which means “fit together” and pilot-tested it in the Taipei Puberty Longitudinal Study (TPLS). Children aged 6–17 years were invited to use COFIT over three days for recording all instances of eating in addition to maintaining written food records (FR). Spearman’s correlation and Bland–Altman analysis were used to compare the intake of macronutrients and micronutrients estimated using the image-based dietary assessment and the FR method. Intra-class correlation coefficients were used to estimate reliability between dietitians. In the final analysis, 23 children (mean age: 10.47 ± 0.47 years) with complete data obtained using two dietary assessment methods were included. Reliability among dietitians was high. Most assessments of macronutrients and micronutrients revealed moderate correlations between the two methods (range: 0.27–0.94); moreover, no significant differences in nutrients assessments were observed between the two methods, except for energy and fat. The average difference in energy intake between the methods was 194 kcal/day. Most limits of agreement were within an acceptable range. The Bland–Altman plots showed robust agreement with minimum bias. The limitation was the small sample size and not dividing the population into children and teenagers since the two groups may have different food consumption habits. Overall, the results showed that the image-based assessment tool is suitable for assessing children’s dietary intake of macronutrients and micronutrients during pubertal growth.