Miracle-dz/UniFAR-FTUs huggingface dataset:
Symmetry breaking and structural polymorphism in a bacterial microcompartment shell protein for choline utilization

Bacterial microcompartments are protein‐based organelles that carry out specialized metabolic functions in diverse bacteria. Their outer shells are built from several thousand protein subunits. Some of the architectural principles of bacterial microcompartments have been articulated, with lateral packing of flat hexameric BMC proteins providing the basic foundation for assembly. Nonetheless, a complete understanding has been elusive, partly owing to polymorphic mechanisms of assembly exhibited by most microcompartment types. An earlier study of one homologous BMC shell protein subfamily, EutS/PduU, revealed a profoundly bent, rather than flat, hexameric structure. The possibility of a specialized architectural role was hypothesized, but artifactual effects of crystallization could not be ruled out. Here we report a series of crystal structures of an orthologous protein, CutR, from a glycyl‐radical type choline‐utilizing microcompartment from the bacterium Streptococcus intermedius. Depending on crystal form, expression construct, and minor mutations, a range of novel quaternary architectures was observed, including two spiral hexagonal assemblies. A new graphical approach helps illuminate the variations in BMC hexameric structure, with results substantiating the idea that the EutS/PduU/CutR subfamily of BMC proteins may endow microcompartment shells with flexible modes of assembly.
Glufosinate constrains synchronous and metachronous metastasis by promoting anti‐tumor macrophages

Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages, GS activity, driven by IL10, associates to the acquisition of M2‐like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti‐tumor, M1‐like, tumor‐associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages toward an M1‐like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vessel sprouting. This was also accompanied to a reduction in cancer cell intravasation and extravasation, leading to synchronous and metachronous metastasis growth inhibition, but no effects on primary tumor growth. Glufosinate treatment was well‐tolerated, without liver and brain toxicity, nor hematopoietic defects. These results identify GS as a druggable enzyme to rewire macrophage functions and highlight the potential of targeting metabolic checkpoints in macrophages to treat cancer metastasis.
The sequence of the protozoan fauna of hay infusions

1. In hay infusions, seeded with representative forms of the chief groups of Protozoa, there is a definite sequence of appearance of the dominant types at the surface of the infusion, i. e. , Monad, Colpoda, Hypotrichida, Paramœcium, Vorticella and Amœba. 2. The sequence of maximum numbers and of disappearance is identical with that of appearance, except that apparently the position of Amœba advances successively from the last (sixth) place to the fifth place and then to the fourth place. 3. A definite sequence of forms is not apparent at the middle or bottom of the infusions. 4. The middle of the infusions is tenanted chiefly by a freeswimming population brought there by an overcrowding at the top or bottom. 5. All of the protozoan forms considered (except Amœba) are chiefly surface dwellers and it is evident that when they pass their greatest development at the surface this maximum is seldom approached again, and their cycle is practically over. 6. The major rise and fall in numbers at the surface are usually about equally rapid, though the final disappearance of an organism may be long deferred. 7. The appearance of any of the protozoan forms under consideration, excepting Ameba, in appreciable numbers at the bottom is most often coincident with, or immediately subsequent to, its surface maximum, and portends its more or less rapid elimination as an important factor in the life of the infusion. 8. Numerous abnormal individuals and cysts are frequently to be found at the bottom in great abundance immediately after the surface maximum. 9. Emphasis is put upon the strictly biological interrelations (e.g., those involving food and specific excretion products) of the various forms as the most important determining factors in the observed sequence.
Factors Affecting the Efficiency of the Area Search Method of Censusing Birds in Open Forests and Woodlands

This paper examines factors that influence the ability of area searches to census the complete bird population at a site. Such factors included duration and repetition of census periods, density of vegetation, density of individuals of species, weather and time of day. Total time spent on the site was found to be more important than the duration or the number of repetitions of the census period, especially in sites with a dense understorey. In sites with a sparse understorey, more repetitions of censuses of short duration were more effective. To obtain a complete species list, a total time of around 100 census minutes was required in sparse sites compared with 150 minutes in dense sites. Birds occurring at high density were not necessarily encountered early in the censusing, probably due to their mobility. Increasing wind strength, time after sunrise and minimum temperature adversely affected the number of species found.
Break-induced replication promotes fragile telomere formation

In this study, Yang et al. investigated how lagging-strand telomeres lacking TRF1 or BLM form fragile telomeres, structures that resemble common fragile sites (CFSs). They found that fragile telomeres in BLM-deficient cells involved double-strand break (DSB) formation by the SLX4/SLX1 nuclease, and the DSBs were repaired by POLD3/POLD4-dependent break-induced replication (BIR), resulting in fragile telomeres containing conservatively replicated DNA.
Lactoferrin-Derived Peptides as a Control Strategy against Skinborne Staphylococcal Biofilms

Coagulase-negative staphylococci (CoNS) widely colonize the human skin and play an active role in host defense. However, these bacteria may cause malodours and increase infection incidence rate in immune-compromised patients and individuals with catheters and implants. CoNS spreading is favored by biofilm formation that also promotes the release of virulence factors and drug resistance. Biofilm control or eradication by antimicrobial peptides (AMPs) represents an attractive strategy which is worth investigating. In this work, bovine lactoferrin (BLF) hydrolysate (HLF) was in vitro evaluated for its antimicrobial and antibiofilm activities against skin-related coagulase negative and positive staphylococci. Despite a minimal inhibitory concentration (MIC) recorded for HLF ranging from 10 to more than 20 mg/mL, a minimal biofilm inhibitory concentration (MIBC) equal to 2.5 mg/mL was found for most target strains. Conversely, MIBC values referred to the individual peptides, LFcinB or LFmpin (herein purified and identified) were significantly lower. Finally, the application of 2.5 mg/mL HLF solution by dipping and spraying on biofilm-attached glass surfaces also caused a high biofilm eradication rate depending on the incubation time, thus attracting interest for future applications in cosmetic formulation for skin care.
Effect of soy protein containing isoflavones on endothelial and vascular function in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials

Abstract Importance: The beneficial role of soy protein in cardiovascular health has been well documented in observational studies. However, evidence from clinical trials on effects of soy protein on endothelial function in postmenopausal women has been conflicting. Objective: We aimed to systematically review and conduct a meta-analysis of randomized controlled trials (RCTs) investigating the impact of soy protein supplement containing isoflavones on endothelial function in postmenopausal women. Evidence review: We searched PubMed-Medline, SCOPUS, Embase, and Google Scholar until March 2020 to find RCTs evaluating the impact of soy protein supplementation on endothelial function parameters. Random effects model (using DerSimonian-Laird method) was applied to synthesize quantitative data. We performed the leave-one-out method for sensitivity analysis. To quantitatively assess heterogeneity, the I2 index was applied. Findings: From a total of 267 studies identified from the initial search 15 and 5 studies were considered appropriate for inclusion into the systematic review and meta-analysis, respectively. In the meta-analysis, an insignificant enhancement in flow-mediated dilation (FMD) after soy protein supplementation (0.882%; 95% CI: −1.059 to 2.822; P = 0.373) was found. However, subgroup analysis showed that supplementation of isolated soy protein had significant effect on FMD (3.39%; 95% CI: 0.733-6.01; P = 0.01). Conclusions and Relevance: Our findings suggest that soy protein supplementation does not lead to meaningful improvement in FMD in postmenopausal women. However, this finding is based on a limited number of studies. Additional high-quality large-scale RCTs are warranted.
Effects of propylthiouracil-induced hypothyroidism on nonalcoholic fatty liver disease in rats fed a high-fat and high-cholesterol diet.

Received: Revised: Accepted: February 27, 2014 April 21, 2014 May 09, 2014 Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that manifests as a wide range of pathological conditions ranging from fat accumulation to inflammation, fibrosis and finally cirrhosis. Recently, it suggested that hypothyroidism is closely associated with NAFLD. In addition, 11.7% of hepatocellular carcinoma (HCC) patients were shown to have hypothyroidism. In this study, Wistar rats were fed different high-fat diets (with or without propylthiouracil) and allowed to develop NAFLD. At the end of the experiments, the serum and liver were collected for the analysis of lipid and cholesterol metabolism parameters. Our results showed that the hypothyroid rats had a fleshless body, significantly higher concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the serum and an increased serum alanine transaminase (ALT) level. In addition, the concentration of serum triglycerides and the expression of ApoB100, MTP, SREBP-2 and ABCA1 in the hypothyroid rats showed fluctuating patterns similar to that of liver triglycerides. This finding suggested that propylthiouracil-induced hypothyroidism plays an important role in progressive NAFLD. ©2014 PVJ. All rights reserved
A Toll-Spätzle Pathway in the Immune Response of Bombyx mori

Simple Summary The Toll-Spätzle pathway is a crucial defense mechanism in insect innate immunity through inducing the expression of antimicrobial peptides (AMPs) against pathogens. As an important economical insect, Bombyx mori (B. mori) has been used as an insect model of Lepidoptera. However, the recognition of the Toll-Spätzle pathway in silkworm is very limited. In this study, we reported that B. mori Spätzle2 (BmSpz2) could be activated by pathogens. The activated BmSpz2 could bind with B. mori Toll11 (BmToll11) or B. mori Toll9-1 (BmToll9–1). Further investigations showed that overexpression of BmToll11 or BmToll9–1 could significantly upregulate AMPs expression. The findings of this study confirmed that a Toll-Spz pathway regulated immune response to microbial infection in B. mori and may help improve the understanding of the signaling pathways involved in the innate immune responses of Lepidoptera insect. Abstract The Toll-Spätzle pathway is a crucial defense mechanism in insect innate immunity, it plays an important role in fighting against pathogens through the regulation of antimicrobial peptide gene expression. Although Toll and Spätzle (Spz) genes have been identified in Bombyx mori, little is known regarding the specific Spz and Toll genes members involved in innate immunity. There is also limited direct evidence of the interaction between Spz and Toll. In this study, the dual-luciferase reporter assay results showed that BmToll11 and BmToll9–1 could activate both drosomycin and diptericin promoters in S2 cells. Furthermore, BmToll11, BmToll9–1, and five BmSpzs genes were found to be significantly upregulated in B. mori infected by Escherichia coli and Staphylococcus aureus. Additionally, the yeast two-hybrid assay results confirmed that BmSpz2, but not other BmSpzs, could interact with both BmToll11 and BmToll9–1. These findings suggest that the activated BmSpz2 can bind with BmToll11 and BmToll9–1 to induce the expression of AMPs after the silkworm is infected by pathogens.
Mediating effects of nursing organizational climate on the relationships between empathy and burnout among clinical nurses.

AIMS AND OBJECTIVES To investigate how nurses who worked in Guangdong province in China perceived empathy, nursing organization climate and burnout. DESIGN A cross-sectional quantitative research design was used. We carried out the research in accordance with the Strengthening the Reporting of Observational studies in Epidemiology checklist. METHODS The study was carried out from August-October of 2018 using a structured electronic questionnaire. A total of 965 participants were selected with convenience sampling in Guangdong province. RESULTS A total of 786 valid questionnaires were collected in this study. The average burnout score of participants was 38.19 (SD 13.32) and 67.4% of them rated their burnout as more than 30 points, while 5.7% were higher than 60 points. The multi-variable linear regression model explained 9.4% of the variance in burnout related to sociodemographic variables (p < 0.001). Empathy was significantly and positively associated with nursing organizational climate and emotional exhaustion while negatively associated with reduced personal accomplishment. In addition, nursing organizational climate mediated the relationship between empathy and reduced personal accomplishment. CONCLUSION Our findings suggest that both empathy and nursing organizational climate are protective factors that prevent burnout in this population. Managers can alleviate nurses' burnout through developing empathy and improving the organizational climate. IMPACT This study demonstrates that empathy is not the cause of burnout; rather, it can prevent nurses from experiencing burnout. Nursing organizational climate is another protective factor that has a mediating effect on empathy and burnout. Improving empathy and nursing organizational climate could help reduce nurse burnout.
The origin of Wx la provides new insights into the improvement of grain quality in rice

Abstract Appearance and taste are important factors in rice (Oryza sativa) grain quality. Here, we investigated the taste scores and related eating‐quality traits of 533 diverse cultivars to assess the relationships between—and genetic basis of—rice taste and eating‐quality. A genome‐wide association study highlighted the Wx gene as the major factor underlying variation in taste and eating quality. Notably, a novel waxy (Wx) allele, Wx la, which combined two mutations from Wx b and Wx in, exhibited a unique phenotype. Reduced GBSSI activity conferred Wx la rice with both a transparent appearance and good eating quality. Haplotype analysis revealed that Wx la was derived from intragenic recombination. In fact, the recombination rate at the Wx locus was estimated to be 3.34 kb/cM, which was about 75‐fold higher than the genome‐wide mean, indicating that intragenic recombination is a major force driving diversity at the Wx locus. Based on our results, we propose a new network for Wx evolution, noting that new Wx alleles could easily be generated by crossing genotypes with different Wx alleles. This study thus provides insights into the evolution of the Wx locus and facilitates molecular breeding for quality in rice.
An algorithm for Botulinum toxin A injection for upper eyelid retraction associated with thyroid eye disease: long-term results

ABSTRACT Purpose To evaluate the efficacy and complications of transconjunctival Botulinum toxin A injections performed according to an algorithm, for the management of upper eyelid retraction associated with thyroid eye disease. Methods Seventy one eyes of 60 patients at the inactive stage, who had undergone Botulinum toxin A injection were reviewed retrospectively. Botulinum toxin A was injected transconjunctivally, just above the superior tarsal border of the upper eyelid in doses between 2–15 units according to an algorithm, depending on the amount of retraction. Margin-reflex distances were measured according to the photographs taken under standard conditions before and after the injections at the tenth day, then the second month and the fourth month. Additional Botulinum toxin A injections were performed in patients who had an undercorrection on the tenth day. Complications such as diplopia and ptosis were recorded. Results The study included 38 females, 22 males with a mean age of 43.3 ± 13.1. Normal margin-reflex distances (3–4 mm) were reached in the 58 of 71 eyes (81.7%). Additional injections were needed in eight eyes (11.2%) for residual retraction on the tenth day. Ptosis was the major complication in four eyes for 1–3 weeks after injection. Upper eyelid retraction recurred after 5.1 ± 0.9 months in all patients. Conclusion In the treatment of upper eyelid retraction due to thyroid eye disease, transconjunctival injection of Botulinum toxin A is an effective, safe, transient, and repeatable method with few complications in patients. The algorithm used in this study resulted in high success rate in long-term follow-up.
Using 164 Million Google Street View Images to Derive Built Environment Predictors of COVID-19 Cases

The spread of COVID-19 is not evenly distributed. Neighborhood environments may structure risks and resources that produce COVID-19 disparities. Neighborhood built environments that allow greater flow of people into an area or impede social distancing practices may increase residents’ risk for contracting the virus. We leveraged Google Street View (GSV) images and computer vision to detect built environment features (presence of a crosswalk, non-single family home, single-lane roads, dilapidated building and visible wires). We utilized Poisson regression models to determine associations of built environment characteristics with COVID-19 cases. Indicators of mixed land use (non-single family home), walkability (sidewalks), and physical disorder (dilapidated buildings and visible wires) were connected with higher COVID-19 cases. Indicators of lower urban development (single lane roads and green streets) were connected with fewer COVID-19 cases. Percent black and percent with less than a high school education were associated with more COVID-19 cases. Our findings suggest that built environment characteristics can help characterize community-level COVID-19 risk. Sociodemographic disparities also highlight differential COVID-19 risk across groups of people. Computer vision and big data image sources make national studies of built environment effects on COVID-19 risk possible, to inform local area decision-making.
Frontline Management of Epithelial Ovarian Cancer—Combining Clinical Expertise with Community Practice Collaboration and Cutting-Edge Research

Epithelial ovarian cancer (EOC) is the most common histology of ovarian cancer defined as epithelial cancer derived from the ovaries, fallopian tubes, or primary peritoneum. It is the fifth most common cause of cancer-related death in women in the United States. Because of a lack of effective screening and non-specific symptoms, EOC is typically diagnosed at an advanced stage (FIGO stage III or IV) and approximately one third of patients have malignant ascites at initial presentation. The treatment of ovarian cancer consists of a combination of cytoreductive surgery and systemic chemotherapy. Despite the advances with new cytotoxic and targeted therapies, the five-year survival rate for all-stage EOC in the United States is 48.6%. Delivery of up-to-date guideline care and multidisciplinary team efforts are important drivers of overall survival. In this paper, we review our frontline management of EOC that relies on a multi-disciplinary approach drawing on clinical expertise and collaboration combined with community practice and cutting edge clinical and translational research. By optimizing partnerships through team medicine and clinical research, we combine our cancer center clinical expertise, community practice partnership, and clinical and translational research to understand the biology of this deadly disease, advance therapy and connect our patients with the optimal treatment that offers the best possible outcomes.
Effectiveness of insecticide-impregnated dog collars in reducing incidence rate of canine visceral leishmaniasis: A systematic review and meta-analysis

Canines are proven reservoir hosts of Leishmania infantum, the causative agent of human zoonotic visceral leishmaniasis, and therefore domestic dogs play a central role in transmitting the disease to humans. Studies on the effect of insecticide-impregnated dog collars for controlling canine visceral leishmaniasis (CanL) have been increasing; however, meta-analysis has not been conducted. This study assessed the effectiveness of insecticide-impregnated dog collars for preventing CanL. We searched (PubMed, Web of Science, Scopus, Embase, Ovid Medline(R), and Cochrane library), from inception until 2 May 2020. Two authors independently performed articles screening and data extraction. We applied the RoB 2.0 tool to evaluate the risk of bias in randomized trials, while the ROBINS-I tool was used for non-randomized trials. I-squared statistics(I2) and funnel plot and Egger’s test, respectively, were used to assesses heterogeneity between studies and publication bias. Relative Risk (RR) and 95% Confidence Interval (CI) were calculated using the random-effects model in Stata 14 software. Out of 242 citations identified, 14 studies comprising 3786 collared dogs and 3428 uncollared dogs were eligible for meta-analysis. The use of deltamethrin-impregnated dog collars(DMC) showed an overall effectiveness of 54% (95%CI: 35–65%, I2 = 63.2%, P = 0.002) in decreasing incidence of CanL, while 10% imidacloprid and 4.5% flumethrin collars provided an overall effectiveness of 90% (95%CI: 80–96%, I2 = 0.0%, P = 0.376). DMC efficacy stratified by follow-up duration was estimated to be 58% (RR = 0.42, 95%CI: 0.20–0.87), 54% (RR = 0.46, 95%CI: 0.31–0.68), 53% (RR = 0.47, 95%CI: 0.29–0.82) for follow-up periods of 5 to 6 months, 1 year and 2 years, respectively. The current evidence indicates that using insecticide-impregnated dog collars can reduce the risk of CanL caused by L. infantum. Therefore, insecticide-impregnated dog collars could be a viable alternative for inclusion as a public health measure for controlling CanL.
Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19?

Zn(II) is an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and chloroquine and hydroxychloroquine are Zn(II) ionophores–this statement gives a curious mind a lot to think about. We show results of the first clinical trials on chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of COVID-19, as well as earlier reports on the anticoronaviral properties of these two compounds and of Zn(II) itself. Other FDA-approved Zn(II) ionophores are given a decent amount of attention and are thought of as possible COVID-19 therapeutics.