Miracle-dz/UniFAR-FTUs huggingface dataset:
Análisis del papel del pie de la RNA polimerasa II de Saccharomyces cerevisiae y su importancia en múltiples etapas de la transcripción

espanolSe conoce poco sobre los mecanismos que gobiernan el ensamblaje nuclear, estabilidad, degradacion y reciclaje de la RNA polimerasa II. Demostramos que el pie de la RNA pol II es crucial para su ensamblaje y estabilidad, asegurando la correcta asociacion de Rpb I-Rpb6 Y del dimero Rpb4/7. Mutaciones en el pie afectan al ensamblaje y estabilidad de la enzima, lo que es suprimido por la sobreexpresion de RPB6, provocan degradacion nuclear de Rpbl dependiente de Rsp5 y conducen a alteraciones de diversas etapas transcripcionales. El defecto de ensamblaje altera la actividad transcripcional, la cantidad de enzima asociada a los genes, la fosforilacion del CTD, la maquinaria de capping del mRNA, sugiere un incremento en la RNA pol II parada y altera la estabilidad del PIe. Los mutantes del pie muestran una respuesta a estres asi como una reduccion en la cantidad de mRNA unidos a Rpb4/7 que altera su degradacion. EnglishLittle is known about the mechanisms governing the nuclear assembly, stability, degradation, and recycling of RNA polymerase II. We demonstrate that the foot ofthe RNA pol II is crucial for the assembly and stability ofthe complex, by ensuring the correct association of Rpb l-Rpb6, and of the dimer Rpb4/7. Mutations at the foot affect the assembly and stability ofthe enzyme, a defect that is offset by RPB6 overexpression, cause Rpbl degradation in the nuc\eus by an Rsp5-dependent mechanism, and leads to alterations in several transcription steps. Assembly defect alter transcriptional activity, the amount of enzyme associated with the genes, the CTD phosphorylation, interferes with mRNA capping machinery, suggest an increase in stalled RNA pol II and alter the PIC stability. Foot mutants show a stress response and a reduction in the amount of mRNA bound to Rpb4/7, affecting the mRNA decay.
ENVIRONMENTAL POLLUTION AND

Living beings are the part of environment. A good environment helps all round development of one’s personality and bad environment inhibits it. Both human beings and animals are effected by environmental pollution directly and indirectly. Environmental conservation is important because when we protect the environment, we are not protecting some distinct, distant entity but ourselves. Degradation of the is going on unabated. It is our duty to protect and preserve the environment and the ecological balance. This menace can be prevented only be creating awareness among the people. Rapid deforestation has been the main cause of environmental degradation. Many forests belts has been cleared away to set up industrial units. Rapid urbanisation swallowed the remaining green belts. Deforestation has led to disastrious results. Floods, soil erosion and landslides have destroyed the ecological balance. It is the call of time to plant more and more trees as it brings rain and keep the upper soil intact. Our rivers and lakes have become dumping grounds for industrial wastes, garbage and dirt. Those water has not remained fit for human consumption. Our cities are dirtier every day. The emission of some smoke from factories have converted our cities into big gas chambers. Educational institutions plays a major role to learn and bring awareness about the environmental pollution and protection among young stars which will be discussed in the paper. Only a concerted effort by all can help in maintaining the ecological balance for proper environment. So it is important that we spread the message through other social institutions to make greater change in the society. Different sources through which young stars will learn about the environmental pollution, specially air, water and soil pollution and about the environmental protection will also be discussed in the paper.
Design and Implementation of an Autofocusing Algorithm for the Goniometric Robotic Apparatus for Compound Eye

The Goniometer Robotic apparatus for compound eye at the Computational Physics Laboratory at the University of Groningen is requiring an autofocus algorithm that is able to capture focused images for the analysis of compound eye insect for characterization. In the absence of an adequate algorithm that manages to place the camera in the right place, GRACE automation has difficulty searching for the respective image. Through the present article you will find the design and implementation of algorithm autofocus structured in modules which improve the organization of the process to achieve an adequate analysis of compound eyes. An algorithm has been proposed which executes five techniques of autofocus capability to determine the sharpness in images in several channels, as well as to use some of those techniques to improve the positioning of the camera and acquire focused images.
The cyclin‐like protein SPY1 overrides reprogramming induced senescence through EZH2 mediated H3K27me3

Fully differentiated cells can be reprogrammed through ectopic expression of key transcription factors to create induced pluripotent stem cells. These cells share many characteristics of normal embryonic stem cells and have great promise in disease modeling and regenerative medicine. The process of remodeling has its limitations, including a very low efficiency due to the upregulation of many antiproliferative genes, including cyclin dependent kinase inhibitors CDKN1A and CDKN2A, which serve to protect the cell by inducing apoptotic and senescent programs. Our data reveals a unique cell cycle mechanism enabling mouse fibroblasts to repress cyclin dependent kinase inhibitors through the activation of the epigenetic regulator EZH2 by a cyclin‐like protein SPY1. This data reveals that the SPY1 protein is required for reprogramming to a pluripotent state and is capable of increasing reprogramming efficiency.
Ct values required for degradation of microcystin-LR by free chlorine

Recently, there has been increased interest in microcystin-LR and other fresh water cyanotoxins because of their toxicity and occurrence throughout the world. Although previous studies have shown that free chlorine can degrade microcystin-LR, there are insufficient data to develop the contact times and free chlorine doses that achieve targeted levels of microcystin-LR degradation. Furthermore, there are insufficient microcystin-LR degradation data that would allow for the development of feasible microcystin-LR criteria or standards. To systematically develop this critical information, a total of 34 batch chlorination experiments were performed at different pH values, chlorine doses, and toxin concentrations. For all conditions, Ct (C = chlorine concentration, t = contact time) values required for degradation of microcystin-LR were calculated and safety factors were estimated. Twenty seven of the 34 experiments were conducted with reagent-grade water and seven of the 34 experiments were conducted with natural waters. At all pH values tested, the degradation of microcystin-LR increased with increasing Ct . For Ct values usually observed in drinking water treatment, a 1-log degradation of microcystin-LR in reagent-grade water was observed only at pH 6.0. The results also suggest that the Ct values obtained from reagent-grade water experiments are appropriate for application to natural waters that have been subjected to conventional coagulation, flocculation, sedimentation, and filtration prior to chlorine addition.
Beliefs, Understanding, and Barriers Related to Dementia Research Participation Among Older African Americans

Background: United States Census Bureau projects African Americans (AAs) will be one of the fastest growing populations over the next 30 years. Research suggests they are at higher risk for developing dementia. It is important to know about AA adults’ beliefs about, and knowledge of, dementia; and how these beliefs and knowledge impact participation in dementia research. Methods: Four focus groups were completed with 51 older AA adults (76.5% female; mean age=68) in Baton Rouge, Louisiana to examine understanding of dementia and barriers influencing willingness to participate in a clinical trial on dementia risk reduction. Findings: Participants exhibited awareness of several risk and protective factors related to dementia, including family history of dementia, lack of cognitive engagement, and sedentary lifestyles. They were willing to participate in interventions to lower the risk of developing dementia. Barriers to participation included invasive procedures, pharmaceutical interventions, mistrust of investigators, inadequate compensation, and long study duration. Discussion: Given the high relevance of dementia research to older AAs, their knowledge of dementia, and their willingness to participate in dementia research once barriers are addressed, it is imperative to continue to identify and remediate factors contributing to the poor representation of AAs in dementia research.
Detecting Preanalytical Errors Using Quality Indicators in a Hematology Laboratory

Background and Objectives: Monitoring laboratory performance continuously is crucial for recognizing errors and fostering further improvements in laboratory medicine. This study aimed to review the quality indicators (QIs) and describe the laboratory errors in the preanalytical phase of hematology testing in a clinical laboratory. Methods: All samples received in the Hematology Laboratory of the Maternity and Pediatric Hospital in Hail for 3 years were retrospectively reviewed and evaluated for preanalytical issues using a set of QIs. The rate of each QI was compared to the quality specifications cited in the literature. Results: A total of 95002 blood samples were collected for analysis in the hematology laboratory from January 2017 through December 2019. Overall, 8852 (9.3%) were considered to show preanalytical errors. The most common were “clotted specimen” (3.6%) and “samples not received” (3.5%). Based on the quality specifications, the preanalytical QIs were classified generally as low and medium level of performance. In contrast, the sigma-based performance level indicates acceptable performance on all the key processes. Further analysis of the study showed a decreasing rate of preanalytical errors from 11.6% to 6.5%. Conclusions: Preanalytical errors remain a challenge to hematology laboratories. The errors in this case were predominantly related to specimen collection procedures that compromised the specimen quality. Quality indicators are a valuable instrument in the preanalytical phase that allows an opportunity to improve and explore clinical laboratory process performance and progress. Continual monitoring and management of QI data are critical to ensure ongoing satisfactory performance and to enhance the quality in the preanalytical phase.
Call for emergency action to limit global temperature increases, restore biodiversity, and protect health

Editor in Chief, East African Medical Journal; Editor in Chief, Journal of Health, Population and Nutrition; Editor in Chief, Danish Medical Journal; Editor in Chief, PLOS Medicine; Editor in Chief, The BMJ; Editor in Chief, British Dental Journal; Editor in Chief, The Lancet; Senior Adviser, UK Health Alliance on Climate Change; Editor in Chief, Revista de Saúde Pública; Editor in Chief, International Journal of Nursing Studies; Interim Editor in Chief, CMAJ; Executive Editor, Pharmaceutical Journal; Editor in Chief, Dutch Journal of Medicine; Editor in Chief, NEJM; Editor in Chief, National Medical Journal of India; Chair, UK Health Alliance on Climate Change; Editor in Chief, Medical Journal of Australia; Editor in Chief, International Nursing Review; Editor in Chief, Pan American Journal of Public Health
The Cognitive Function at Work Questionnaire (CFWQ): A new scale for measuring cognitive complaints in occupational population

Abstract Cognitive functioning is a relevant work and health related topic, however, validated methods to assess subjective cognitive complaints (SCC) at work are lacking. We introduce the Cognitive Function at Work Questionnaire (CFWQ) for measuring SCC in occupational settings. 1-year follow-up data of 418 employees from a Finnish public media service company was analyzed. Participants completed web-based CFWQ, cognitive tests and a broad set of questionnaires for evaluating depression, anxiety, insomnia, daytime sleepiness, burnout, stress, mental job burden, work ability, cognitive errors, and perceived health. The factor analysis yielded a model with the CFWQ subdomains: Memory, Language, Executive Function, Speed of Processing, Cognitive Control and Name Memory. The internal consistency (Cronbach’s alpha = .87) and the test-retest constancy (ICC = .84) reflected good reliability. Correlation between the CFWQ and cognitive errors at work ranged from . 25 to . 64 indicating adequate concurrent validity. Employees with depression, insomnia and burnout symptoms had higher (p < .001) CFWQ scores than participants without these symptoms. Depression and burnout symptom severity as well as accumulation of mood, sleep, and psychosocial stressors were associated with higher CFWQ scores (p < .001 in all). The CFWQ appears psychometrically sound measure for the assessment of SCC in occupational population.
Muse cells have higher stress tolerance than adipose stem cells due to the overexpression of the CCNA2 gene.

This study aimed to investigate the stress tolerance mechanism of Muse (multilineage-differentiating stress enduring) cells and elucidate the means to improve the stress tolerance of mesenchymal stem cells. Cell viability, apoptosis, and senescence-related protein expression were detected under H2O2 stress by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay, flow cytometry in combination with Annexin V-FITC/PI staining, and Western blotting analysis, respectively. A significant increase in the CCNA2 gene-level within Muse cells relative to ASCs (adipose stem cells) was observed. In the H2O2 stress environment in vitro, the survival rate of Muse cells remarkably increased compared to the survival rate of the ASCs. Additionally, a reduced level of apoptosis and senescence-related protein expression of Muse cells relative to ASCs was documented. The miR-29b-3p¬-induced negative regulation of CCNA2 gene expression was confirmed by in vitro luciferase assay. A significant upregulation of CCNA2 gene expression in ASCs, transfected with antagomir-29b-3p, improved the survival rate of ASCs under H2O2 stress but dramatically reduced the apoptosis and expression of the senescence-related gene; agomir-29b-3p could partially reverse these effects. In conclusion, high expression of the CCNA2 gene is associated with an increased stress tolerance of Muse cells. Regulating the expression of CCNA2 by miR-29b-3p can alter the stress tolerance of ASCs.
Multi‐modal adaptor‐clathrin contacts drive coated vesicle assembly

Clathrin‐coated pits are formed by the recognition of membrane and cargo by the AP2 complex and the subsequent recruitment of clathrin triskelia. A role for AP2 in coated‐pit assembly beyond initial clathrin recruitment has not been explored. Clathrin binds the β2 subunit of AP2, and several binding sites have been identified, but our structural knowledge of these interactions is incomplete and their functional importance during endocytosis is unclear. Here, we analysed the cryo‐EM structure of clathrin cages assembled in the presence of β2 hinge‐appendage (β2HA). We find that the β2‐appendage binds in at least two positions in the cage, demonstrating that multi‐modal binding is a fundamental property of clathrin‐AP2 interactions. In one position, β2‐appendage cross‐links two adjacent terminal domains from different triskelia. Functional analysis of β2HA‐clathrin interactions reveals that endocytosis requires two clathrin interaction sites: a clathrin‐box motif on the hinge and the “sandwich site” on the appendage. We propose that β2‐appendage binding to more than one triskelion is a key feature of the system and likely explains why assembly is driven by AP2.
BPA-induced prostatic hyperplasia in vitro is correlated with the unbalanced gene expression of AR and ER in the epithelium and stroma

As a typical environmental endocrine disruptor (EED), bisphenol A (BPA) can induce pathological hyperplasia of the prostatic epithelium and stroma. This study concentrates mainly on the effect and underlying mechanisms of BPA on prostatic hyperplasia, which is based on the culture of primary human prostate epithelial cells (HPEpiC) and human prostate fibroblasts (HPrF). In an effect to screen the optimal pro-survival BPA levels, HPEpiC and HPrF were, respectively, exposed to concentration gradients of BPA (10−12 M–10−4 M) solution diluted with two corresponding medium and incubated for 72 h at 37°C. CCK-8 assay showed that 10−9 M–10−5 M BPA could facilitate the proliferation of HPEpiC, while similar proliferative effect of HPrF only needed 10−11 M–10−7 M BPA. HPrF were more sensitive to BPA than HPEpiC. The qualification of PCNA gene expression measured using quantitative real-time polymerase chain reaction (qRT-PCR) also mirrored the BPA-induced cell proliferation. Additionally, our results considered that androgen receptor (AR), estrogen receptor (ERα, ERβ), and NFKB1 gene expressions exhibited up-regulation in HPEpiC treated with 10−9 M BPA for 72 h. However, in HPrF, the identical BPA treatment could activate ERα, ERβ, and NFKB1 gene expressions and down-regulated the expression of AR levels. It is further confirmed that low-dose BPA can indeed promote the proliferation of human prostate cells in vitro, and the mechanisms of BPA for prostatic epithelial and stromal hyperplasia may not be consistent.
Influence of Age on 2040 Cancer Burden in the Older Population of the Gulf Cooperation Council (GCC) Countries: Public Health Implications

Introduction and Study Aims: The underlying population of global regions varies widely and is a major determinant of regional cancer differences. The aims were to: (1) estimate the cancer burden in Gulf Cooperation Council (GCC) countries in 2040 for the ≥70 population and (2) assess the public health implications for this cancer increase. Methods: We used Global Cancer Observatory (GLOBOCAN) estimates of cancer incidence and mortality for people aged 70 years or more in GCC countries from 2018 to 2040 from the International Agency for Research on Cancer. For population growth, we used data for the same period from the Population Division of the United Nations Department of Economic and Social Affairs. From these, we calculated the predicted increase in the number of cancer cases and cancer deaths from 2018 to 2040 and the proportion of cases/deaths represented by those aged 70+ for the 2 time periods. Findings: In the GCC countries, the predicted number of newly diagnosed cancers and cancer deaths in the older population will increase by 465% and 462% respectively due to demographic changes—greater than other countries in the World Health Organization Eastern Mediterranean Region, or in countries of similar economic development. The largest predicted increases will be for Qatar and the United Arab Emirates. Based on the predicted population age, cancer burden among older people in the GCC countries will increase by approximately 460%. Conclusion: By the year 2040, the relationship between cancer and age will cause a 4- to 5-fold increase in the cancer burden in the GCC. These predictable changes will require additional planning and resources to provide appropriate healthcare.
1-Oxo-3,4-dihydroisoquinoline-4-carboxamides as novel druglike inhibitors of poly(ADP-ribose) polymerase (PARP) with favourable ADME characteristics

Abstract A novel 3,4-dihydroisoquinol-1-one-4-carboxamide scaffold was designed as the basis for the development of novel inhibitors of poly(ADP-ribose) polymerase (PARP). Synthesis of 3,4-dihydroisoquinol-1-one-4-carboxylic acids was achieved using the previously developed protocol based on the modified Castagnoli-Cushman reaction of homophthalic anhydrides and 1,3,5-triazinanes as formaldimine synthetic equivalents. Employment of 2,4-dimethoxy groups on the nitrogen atom of the latter allowed preparation of 2,3-unsubatituted 3,4-dihydroquinolone core building blocks. Iterative synthesis and in vitro biological testing of the amides resulting from the amidation of these carboxylic acids allowed not only drawing important structure-activity generalisations (corroborated by in silico docking simulation) but also the identification of the lead compound, 4-([1,4'-bipiperidine]-1'-carbonyl)-7-fluoro-3,4-dihydroisoquinolin-1(2H)-one, as the candidate for further preclinical development. The lead compound as well as its des-fluoro analog were compared to the approved PARP1 inhibitor, anticancer drug Olaparib, in terms of their molecular characteristics defining druglikeness as well as experimentally determined ADME parameters. The newly developed series demonstrated clear advantages over Olaparib in terms of molecular weight, hydrophilicity, human liver microsomal and plasma stability as well as plasma protein binding. Further preclinical investigation of the lead compound is highly warranted.
Surgically treated genital chronic graft‐versus‐host disease in women: A report of three cases

Hematopoietic stem cell transplantation (HSCT) is a crucial treatment for hematological malignancy. Gonadal dysfunction occurs at an early stage after this treatment, and such patients may require hormone replacement therapy. Genital chronic graft‐versus‐host disease is a lesser‐known complication of HSCT that begins with vulvar discomfort and dysuria and progresses to sexual dysfunction and retention of menstrual blood due to vaginal stenosis and obstruction; thus, significantly impairing the patient's quality of life. We describe three women who underwent vaginal reconstruction because of genital chronic graft‐versus‐host disease. We discuss the surgical techniques, including double cross plasty that were performed in each case. Surgical interventions enabled the continuation of HRT and facilitated sexual intercourse. In conclusion, gynecologists should be aware that genital chronic graft‐versus‐host disease can occur after HSCT, and that surgical treatment options are available to improve patients' symptoms and quality of life.
Expression Characteristics and Clinical Correlations of BRD1 in Colorectal Cancer Samples

The incidence of colorectal cancer (CRC), as well as subsequent patient mortality, has increased in the last decade; an unhealthy diet is considered to be the leading cause. Previous studies have shown the potential of the bromodomain containing 1 (BRD1) gene as a therapeutic target for CRC based on its specificity; however, the genetic mode of action and expression in CRC cells are yet to be investigated. In this study, target genes were screened from single-cell transcriptome sequencing data, and the collected clinical specimens were subjected to immunohistochemistry (IHC) to identify the protein expression of target genes; the results were verified in the GSE17536 array set. Receiver operating characteristic curves (ROC) and overall survival (OS) were used to test target genes as biomarkers and independent predictive markers for CRC. Based on these results, BRD1 was screened as a target gene, and IHC results showed that BRD1 protein expression in CRC was higher than that in normal tissues and was significantly upregulated in poorly differentiated (PD) CRC. ROC analysis showed that the area under the curve in the collected clinical specimens and GSE17536 were 0.6062 and 0.6094, respectively. OS analysis showed that higher BRD1 protein expression was associated with a significantly shorter survival time. In conclusion, BRD1 expression was positively correlated with PD CRC and negatively correlated with OS, indicating that BRD1 could predict the differentiation state of CRC and may be a novel predictive biomarker.