Miracle-dz/UniFAR-FTUs huggingface dataset:
Repair of APOBEC3G-Mutated Retroviral DNA In Vivo Is Facilitated by the Host Enzyme Uracil DNA Glycosylase 2

While APOBEC3-mediated mutation of retroviruses is well-established, what role the host base excision repair enzymes play in correcting these mutations is not clear. This question is especially difficult to address in vivo. ABSTRACT Apolipoprotein B mRNA editing enzyme catalytic subunit 3 (APOBEC3) proteins are critical for the control of infection by retroviruses. These proteins deaminate cytidines in negative-strand DNA during reverse transcription, leading to G-to-A changes in coding strands. Uracil DNA glycosylase (UNG) is a host enzyme that excises uracils in genomic DNA, which the base excision repair machinery then repairs. Whether UNG removes uracils found in retroviral DNA after APOBEC3-mediated mutation is not clear, and whether this occurs in vivo has not been demonstrated. To determine if UNG plays a role in the repair of retroviral DNA, we used APOBEC3G (A3G) transgenic mice which we showed previously had extensive deamination of murine leukemia virus (MLV) proviruses. The A3G transgene was crossed onto an Ung and mouse Apobec3 knockout background (UNG−/−APO−/−), and the mice were infected with MLV. We found that virus infection levels were decreased in A3G UNG−/−APO−/− compared with A3G APO−/− mice. Deep sequencing of the proviruses showed that there were significantly higher levels of G-to-A mutations in proviral DNA from A3G transgenic UNG−/−APO−/− than A3G transgenic APO−/− mice, suggesting that UNG plays a role in the repair of uracil-containing proviruses. In in vitro studies, we found that cytoplasmic viral DNA deaminated by APOBEC3G was uracilated. In the absence of UNG, the uracil-containing proviruses integrated at higher levels into the genome than those made in the presence of UNG. Thus, UNG also functions in the nucleus prior to integration by nicking uracil-containing viral DNA, thereby blocking integration. These data show that UNG plays a critical role in the repair of the damage inflicted by APOBEC3 deamination of reverse-transcribed DNA. IMPORTANCE While APOBEC3-mediated mutation of retroviruses is well-established, what role the host base excision repair enzymes play in correcting these mutations is not clear. This question is especially difficult to address in vivo. Here, we use a transgenic mouse developed by our lab that expresses human APOBEC3G and also lacks the endogenous uracil DNA glycosylase (Ung) gene and show that UNG removes uracils introduced by this cytidine deaminase in MLV reverse transcripts, thereby reducing G-to-A mutations in proviruses. Furthermore, our data suggest that UNG removes uracils at two stages in infection—first, in unintegrated nuclear viral reverse-transcribed DNA, resulting in its degradation; and second, in integrated proviruses, resulting in their repair. These data suggest that retroviruses damaged by host cytidine deaminases take advantage of the host DNA repair system to overcome this damage.
ICOS expression is required for maintenance but not the formation of germinal centers in the spleen in response to P. yoelii infection

Inducible T cell co-stimulator (ICOS) plays a key role in the differentiation and maintenance of follicular helper T (Tfh) cells and thus germinal center (GC) formation. Previously, our lab showed in a Plasmodium chabaudi infection model that Icos-/- mice did not form GCs despite a persistent infection and thus a continued antigen (Ag) load. Here, we show that resolution of a primary infection with P. yoelii, was delayed in Icos-/- mice. This phenotype was associated with a reduction in the accumulation of Tfh-like and GC Tfh cells and an early deficiency in Ag-specific antibody (Ab) production. However, Icos-/- mice maintained their ability to form GCs, though they were less frequent in number than in wild-type (WT) mice. Furthermore, while Ab production in Icos-/- mice matched that of WT mice after the infection cleared, the Abs lacked signs of affinity maturation, suggesting functional defects associated with these GCs. Eventually, these GC structures dissipated more rapidly in Icos-/- mice than in WT mice. Moreover, the ability of Icos-/- mice to form these GC structures is not reliant on the high Ag load associated with P. yoelii infections, as GC formation was preserved in Icos-/- mice treated with early with atovaquone. Finally, mice were unable to form secondary GCs in the absence of ICOS after re-challenge. Overall, these data demonstrate the necessity of ICOS in the maintenance of Tfh cells, the formation and maintenance of sufficient numbers of functioning GCs, and the ability to generate new GC structures after re-infection with P. yoelii.
The Omega-3-fatty acid docosahexaenoic acid modulates intracellular myo-inositol and its biosynthetic genes

Bipolar disorder is a debilitating mood disorder characterized by recurring episodes of mania and depression. It affects 2.6% of adults and has a lifetime prevalence among adults of 3.9%. Current mood stabilizers are not always effective and/or are not well tolerated by many patients; thus, there is a need to develop or identify more effective and less harmful treatments. Omega-3-fatty acids have been shown to be effective in the treatment of bipolar disorder; however, their mechanism of action is unknown. Myo-inositol depletion has been hypothesized as the mechanism by which mood stabilizers exert their therapeutic effect. Using an enzymatic assay, we determined intracellular myo-inositol levels increased more than 2-fold when cells were grown in the presence of the omega-3 fatty acid docosahexaenoic acid (DHA). RT-qPCR was used to characterize the effects of DHA on genes in the myo-inositol biosynthetic pathway. We show DHA increases relative expression and has a concentration-dependent impact on INO1 and INM1, which encode myo-inositol-1-phosphate synthase and myo-inositol monophosphate 1-phosphatase, respectively. We therefore conclude that the omega-3-fatty acid DHA exerts its therapeutic effect on bipolar disorder by increasing intracellular myo-inositol, which may be accomplished by upregulating its biosynthetic genes.
Physical localization of 45S rDNA in Cymbopogon and the analysis of differential distribution of rDNA in homologous chromosomes of Cymbopogon winterianus

Cymbopogon, commonly known as lemon grass, is one of the most important aromatic grasses having therapeutic and medicinal values. FISH signals on somatic chromosome spreads off Cymbopogon species indicated the localization of 45S rDNA on the terminal region of short arms of a chromosome pair. A considerable interspecific variation in the intensity of 45S rDNA hybridization signals was observed in the cultivars of Cymbopogon winterianus and Cymbopogon flexuosus. Furthermore, in all the varieties of Cymbopogon winterianus namely Bio-13, Manjari and Medini, a differential distribution of 45S rDNA was observed in a heterologous pair of chromosome 1. The development of Cymbopogon winterianus var. Manjari through gamma radiation may be responsible for breakage of fragile rDNA site from one of the chromosomes of this heterologous chromosome pair. While, in other two varieties of Cymbopogon winterianus (Bio-13 and Medini), this variability may be because of evolutionary speciation due to natural cross among two species of Cymbopogon which was fixed through clonal propagation. However, in both the situations these changes were fixed by vegetative method of propagation which is general mode of reproduction in the case of Cymbopogon winterianus.
The entomopathogenic nematode Steinernema hermaphroditum is a self-fertilizing hermaphrodite and a genetically tractable system for the study of parasitic and mutualistic symbiosis

Entomopathogenic nematodes, including Heterorhabditis and Steinernema, are parasitic to insects and contain mutualistically symbiotic bacteria in their intestines (Photorhabdus and Xenorhabdus, respectively) and therefore offer opportunities to study both mutualistic and parasitic symbiosis. The establishment of genetic tools in entomopathogenic nematodes has been impeded by limited genetic tractability, inconsistent growth in vitro, variable cryopreservation, and low mating efficiency. We obtained the recently described Steinernema hermaphroditum strain CS34 and optimized its in vitro growth, with a rapid generation time on a lawn of its native symbiotic bacteria Xenorhabdus griffiniae. We developed a simple and efficient cryopreservation method. Previously, S. hermaphroditum isolated from insect hosts was described as first-generation hermaphroditic and second-generation gonochoristic. We discovered that CS34, when grown in vitro, produced consecutive generations of autonomously reproducing hermaphrodites accompanied by rare males. We performed mutagenesis screens in S. hermaphroditum that produced mutant lines with visible and heritable phenotypes. Genetic analysis of the mutants demonstrated that this species reproduces by self-fertilization rather than parthenogenesis and that its sex is determined chromosomally. Genetic mapping has thus far identified markers on the X chromosome and three of four autosomes. We report that S. hermaphroditum CS34 is the first consistently hermaphroditic entomopathogenic nematode and is suitable for genetic model development to study naturally occurring mutualistic symbiosis and insect parasitism.
High-grade ovarian cancer associated H/ACA snoRNAs promote cancer cell proliferation and survival

Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, the nature and extent of snoRNAs contribution to the biology of cancer cells remain largely unexplored. In this study, we examined the abundance patterns of snoRNA in high-grade serous ovarian carcinomas (HGSC) and serous borderline tumours (SBT) and identified a subset of snoRNA associated with increased invasiveness. This subgroup of snoRNA accurately discriminates between SBT and HGSC underlining their potential as biomarkers of tumour aggressiveness. Remarkably, knockdown of HGSC-associated H/ACA snoRNAs, but not their host genes, inhibits cell proliferation and induces apoptosis of model ovarian cancer cell lines. Wound healing and cell migration assays confirmed the requirement of these HGSC-associated snoRNA for cell invasion and increased tumour aggressiveness. Together our data indicate that H/ACA snoRNAs promote tumour aggressiveness through the induction of cell proliferation and resistance to apoptosis.
A Qualitative Review of Strengths, Weaknesses, Opportunities and Threats of Clinical Pharmacy Services Provided by Tirunesh Beijing General Hospital

Background: Clinical pharmacy services are patient oriented services developed to promote the rational use of medicines by maximizing therapeutic effect of medicines in individual patients. It has a positive impact on medical, economic and humanistic outcomes of the patients. In Ethiopia, the service is at its infant stage and there is lack of objective evidence on the strength, weakness, opportunity and threats. Therefore, the aim of this study was to undergo situational analysis of clinical pharmacy services in Tirunesh Beijing General Hospital using SWOT frame work. Methods: A qualitative study was conducted in Tirunesh Beijing General Hospital from March 1 to March 14, 2016. An in-depth interview with flexible probing techniques was designed to collect the data from twenty key informants. A semi structured interview guide was prepared to explore ideas of key informants about situation of clinical pharmacy service, internal factors (strength & weakness), and external factors (opportunity & threats). A thematic analysis was then used to analyze the data. Results: Internal factors such as presence of clinical pharmacists in the hospital and interest & willingness of the managers to support and give assistance to the services were found as the major strengths, while lack of adequate facilities & equipment; poor performance of clinical pharmacists in implementing the service; poor collaboration working relationship between the pharmacists and physicians and weak evaluation mechanism of the hospital management were found as the major weaknesses. External factors such as increasing number of graduating clinical pharmacists from different colleges and universities and availability of post graduate program in clinical pharmacy in the country were identified as opportunity. However, low coverage of promotion about the service by the responsible body was mentioned as threat for the hospital. Conclusion: The study identified that clinical pharmacy services had a lot of limitations as compared to its strengths in the hospital. It is recommended that the hospital should expand and implement the service in all wards and facilitate experience sharing programs with other model hospitals in clinical pharmacy to strength the service.
Surgical difficulty assessment in patients undergoing impacted mandibular third molar extraction. A single center evaluation in Najran, Kingdom of Saudi Arabia

Introduction: The evaluation of surgical difficulty preoperatively is important during mandibular third molar (MTM) extraction. This study aimed to evaluate the difficulty index for the removal of impacted MTM using Pederson difficulty index (PDI), Parant Scale (PS), and total operation time (TOT). Materials and Methods: This was a prospective study of patients referred for the extraction of impacted MTM between April, 2019 and July, 2020. Estimated level of difficulty was done before a standardized surgery using the PDI and classified as: Minimally difficult (I), moderately difficult (II), and very difficult (III). Intraoperatively, it was classified as extraction requiring ostectomy only (II); extraction requiring ostectomy and coronal section (III); and complex extraction requiring coronal and root sectioning (IV) using the Modified PS. TOT was recorded by a resident with stopwatch. Results: A total of 502 patients (203 [40.4%] males and 299 [59.6%] females) with an M:F of 1:1.5. The age ranged from 17 to 69 years with a mean age ± standard deviation (SD) (31.6 ± 9.6) years. The majority of the patients were in the age group of 21–40 years. TOT ranged from 10 to 35 min with mean TOT ± SD (15.35 ± 7.02) min. The mean TOT according to PDI was 11.30 ± 2.22, 12.74 ± 4.14, and 26.44 ± 4.39 min in I, II, and III, respectively, while according to PS were 10.91 ± 0.9, 19.60 ± 4.5, 28.82 ± 3.5 min in II, III, and IV, respectively. The observed correlation coefficients® for PDI and PS were 0.716 and 0.870, respectively. Conclusion: Analysis of the surgical difficulty of impacted MTM extraction is essential for treatment planning and patient satisfaction. PS has been found to be significantly associated with TOT.
Comparison of hypotensive properties of dexmedetomidine versus clonidine for induced hypotension during functional endoscopic sinus surgery: A randomised, double-blind interventional study

Background and Aims:Excessive bleeding is a major concern in functional endoscopic sinus surgery (FESS) under general anaesthesia; this can be decreased by various hypotensive agents. This study was conducted to compare the hypotensive effectiveness and haemodynamic stability of dexmedetomidine and clonidine in patients undergoing elective FESS. Methods:In this prospective double-blinded interventional study, 70 adult patients of either sex, 20–50 years of age, posted for elective FESS were randomly assigned to two groups. Group A received a loading dose of intravenous (IV) dexmedetomidine 1 μg/kg, followed by infusion of 1 μg/kg/h, and group B received a loading dose of IV clonidine 2 μg/kg, followed by 1 μg/kg/h infusion. Surgical field quality, emergence time, sedation score, visual analogue score, recovery profile and haemodynamic parameters were recorded. Statistical analysis was done by Student's unpaired t-test to evaluate the significance of normally distributed variables, whereas Mann–Whitney test and Chi-square test were used for ordinal data and categorical variables and proportions, respectively. Results:In both the groups, target mean arterial pressure (MAP) of 65–70 mmHg and improved surgical field quality were achieved. MAP and heart rate (HR) were statistically significantly lower in the dexmedetomidine group with a longer duration of post-operative analgesia (P = 0.001). None of the groups showed any statistically significant adverse effects. Conclusions:Both dexmedetomidine and clonidine can be used for controlled hypotension to improve surgical field quality in FESS. Dexmedetomidine provides more haemodynamic stability and an additional benefit of post-operative analgesia and conscious sedation.
Make Your Own Luck: The Wage Gains from Starting College in a Bad Economy

Using data for nearly 40 cohorts of American college graduates and exploiting regional variation in economic conditions, we show robust evidence of a positive relationship between the unemployment rate at the time of college enrollment and subsequent annual earnings, particularly for women. This positive relationship cannot be explained by selection into employment or by economic conditions at the time of labor market entry. Up to one quarter of the eﬀect is accounted for by changes in ﬁeld of study choices and by sorting towards more remunerative locations. The results are consistent with a behavioral change that induces individuals who experience bad economic times at the beginning of their studies to exert more eﬀort towards obtaining higher-paying jobs
Microwave induced activated carbon for the removal of metal ions in fixed-bed column study: modelling and mechanisms

The continuous discharge of metal-containing wastes into the aquatic system leads to a hazardous impact onto the environment and human health. This study investigated the preparation of activated carbon derived from palm-date stone using H2SO4 and KOH impregnation followed by microwave-induced irradiation for the adsorption of Fe3+, Cd2+, and Cu2+ from solution onto the fixed-bed column. The characterization of prepared adsorbents using scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy showed changes in the structure functional groups between adsorbents according to the used activating agent. Factors that characterize the breakthrough curves and influence the adsorption capacity including bed depth, flow rate, and initial ion concentration were studied. The maximum adsorption capacity is from 11.45 for Cd2+ to 85.12 mg/g for Cu2+ onto H2SO4 impregnated activated carbon (AC1). Adsorption kinetics were analyzed using Thomas, Adam–Bohart, and Yoon–Nelson models at a flow rate of 1 mL/ min, bed depth of 3 cm, and initial concentrations of 12.5, 1.5, and 3.3 mg/L for Fe3+, Cd2+, and Cu2+, respectively. Models exhibited good agreement with results experimentally obtained. Statistics showed that both KOH impregnation obtained adsorbent (AC2) and AC1 have similar (p > 0.05) fixed-bed adsorption performance.
FOUR-ELEMENT LOW-BAND MIMO ANTENNA FOR MOBILE PHONES WITH SMALL CLEARANCE

—This letter presents a four-element Multiple-Input Multiple-Output (MIMO) phone antenna with a metallic rim and 2-mm ground clearance that operates in the low-frequency band. Characteristic mode analysis is used to design the metallic rim so that the structure supports four resonating modes that can be excited separately to obtain MIMO operation in the desired frequency range below 1 GHz. Four exciter elements with matching circuits are designed so that the coupling between the ports is moderate. The prototype is manufactured, and measurement results are shown to corroborate the increased capacity compared to traditional two-element MIMO solutions.
One-shot to Weakly-Supervised Relation Classification using Language Models

Relation classiﬁcation aims at detecting a particular relation type between two entities in text, whose methods mostly requires annotated data. Data annotation is either a manual process for supervised learning, or automated, using knowledge bases for distant learning. Unfortunately, both annotation methodologies are costly and time-consuming since they depend on intensive human labour for annotation or for knowledge base creation. With recent evidence that language models capture some sort of relational facts as knowledge bases, one-shot relation classiﬁcation using language models has been proposed via matching a given instance against examples. The only requirement is that each relation type is associated with an exemplar. However, the matching approach often yields incorrect predictions. In this work, we propose NoelA, an auto-encoder using a noisy channel, to improve the accuracy by learning from the matching predictions. NoelA outperforms BERT matching and a bootstrapping baseline on TACRED and reWiki80.
Hyperuricemia in Renal patients: Treat or not to treat

Hyperuricemia management in chronic kidney disease is a challenging task. We encounter this dilemma on regular basis. Kidney disease patients have wide range (CKD population, Hemodialysis & peritoneal dialysis cohort and renal transplant patients). In clinical practice wide range of opinions exists. This dubious area intrigued us to look into it. Looking into available published data majority of studies are observational and few are randomized control trials. All studies favor that high uric acid level has accelerated effect on CKD progression. Controversy is on its management, whether by treating it we are able to slow down CKD progression or not. Data supports that CKD progression is not slowed down but needs more studies to give conclusive answer. In dialysis and renal transplant patients studies showed inverse relationship of high uric levels with all-cause mortality. However, in peritoneal dialysis data suggests linear relationship of hyperuricemia with mortality. A pro as well as anti-oxidant effect of uric acid has been discussed in literature. Variable cut off for hyperuricemia has been used but more census is on 7 mg/dl. Symptomatic gout defi nitely needs uric acid lowering therapy but in asymptomatic hyperuricemia no conclusion so far. There is paucity of data in maintenance dialysis and renal transplant patients. Review article Hyperuricemia in Renal patients: Treat or not to treat Muhammad Tanzeel Abbasi* Muhammad Rashid Asghar, Khuram Bashir and Muhammad Nauman Hashmi Consultant Nephrologist, Department of Nephrology, Multan institute of kidney diseases, Multan, Pakistan Received: 16 July, 2021 Accepted: 05 August, 2021 Published: 06 August, 2021 *Corresponding author: Dr. Muhammad Tanzeel Abbasi, Consultant Nephrologist, Department of Nephrology, Multan institute of kidney diseases, Multan, Pakistan, Tel: 00923336106372; E-mail: