Miracle-dz/UniFAR-FTUs huggingface dataset:
Dispatches from the neighborhood watch: Using citizen science and field survey data to document color morph frequency in space and time

Abstract Heritable color polymorphisms have a long history of study in evolutionary biology, though they are less frequently examined today than in the past. These systems, where multiple discrete, visually identifiable color phenotypes co‐occur in the same population, are valuable for tracking evolutionary change and ascertaining the relative importance of different evolutionary mechanisms. Here, we use a combination of citizen science data and field surveys in the Great Lakes region of North America to identify patterns of color morph frequencies in the eastern gray squirrel (Sciurus carolinensis). Using over 68,000 individual squirrel records from both large and small spatial scales, we identify the following patterns: (a) the melanistic (black) phenotype is often localized but nonetheless widespread throughout the Great Lakes region, occurring in all states and provinces sampled. (b) In Ohio, where intensive surveys were performed, there is a weak but significantly positive association between color morph frequency and geographic proximity of populations. Nonetheless, even nearby populations often had radically different frequencies of the melanistic morph, which ranged from 0% to 96%. These patterns were mosaic rather than clinal. (c) In the Wooster, Ohio population, which had over eight years of continuous data on color morph frequency representing nearly 40,000 records, we found that the frequency of the melanistic morph increased gradually over time on some survey routes but decreased or did not change over time on others. These differences were statistically significant and occurred at very small spatial scales (on the order of hundreds of meters). Together, these patterns are suggestive of genetic drift as an important mechanism of evolutionary change in this system. We argue that studies of color polymorphism are still quite valuable in advancing our understanding of fundamental evolutionary processes, especially when coupled with the growing availability of data from citizen science efforts.
Clinical outcome and predictive factors for docetaxel and epirubicin neoadjuvant chemotherapy of locally advanced breast cancer

Background/Aims We evaluated the efficacy of docetaxel and epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer and assessed the predictive factors for response to neoadjuvant chemotherapy and prognostic factors related to relapse-free survival. Methods Forty patients who received docetaxel and epirubicinas neoadjuvant chemotherapy for locally advanced breast cancer were evaluated retrospectively. Neoadjuvant chemotherapy consisted of intravenous injection of 75 mg/m2 docetaxel and 60 mg/m2 epirubucin on day 1, every 21 days, and two to six cycles. Results Twenty-five (62.5%) patients showed a partial response, and 15 (37.5%) patients showed a stable disease in the first response evaluation after two or three cycles of neoadjuvant chemotherapy. In the second response evaluation of nine patients who received six cycles of neoadjuvant chemotherapy, one patient achieved a complete response, but two patients with hormone receptor-negative, human epidermal growth factor receptor 2-positive breast cancer experienced disease progression. Twenty-five (62.5%) patients experienced downstaging after neoadjuvant chemotherapy. Patients with > 20% pretreatment Ki-67 and decrease of Ki-67 between pre- and post-neoadjuvant chemotherapy showed a trend for better response. In multivariate analysis, advanced pathological stage showed a significant negative effect on relapse-free survival. Conclusions Docetaxel and epirubicin neoadjuvant chemotherapy showed a good response in locally advanced breast cancer. Pretreatment Ki-67 and change of Ki-67 may play a role as predictive factor for response to neoadjuvant chemotherapy.
Evaluation and Management of Dysphagia in Amyotrophic Lateral Sclerosis: A Survey of Speech-Language Pathologists' Clinical Practice

Abstract Objectives: The aim of this study was to determine the evaluation and management of dysphagia in amyotrophic lateral sclerosis (ALS) patients by speech-language pathologists (SLPs). Methods: A 15-question web-based survey sent to SLPs in general clinical practice. Results: Forty-nine SLPs responded. Although only 8 (17.0%) of the SLPs worked in ALS clinics, 46 (93.9%) had worked with ALS patients. A variety of dysphagia evaluation protocols were used by 43 (97.7%) SLPs. Most SLPs, 40 (88.9%), recommended instrumental assessments, but timing and indication varied greatly: 19 (42.2%) SLPs recommended this at baseline even without bulbar symptoms, whereas others recommended this based on symptoms and/or clinical assessments. Conclusions: There is currently no uniform approach as to the indication, timing, and specific methods to use in the evaluation of dysphagia in ALS patients among SLPs. There is need for further research to assist in the development of definitive guideline recommendations for this population.
Neutrophil‐like HL‐60 cells expressing only GFP‐tagged β‐actin exhibit nearly normal motility

Observations of actin dynamics in living cells using fluorescence microscopy have been foundational in the exploration of the mechanisms underlying cell migration. We used CRISPR/Cas9 gene editing to generate neutrophil‐like HL‐60 cell lines expressing GFP‐β‐actin from the endogenous locus (ACTB). In light of many previous reports outlining functional deficiencies of labeled actin, we anticipated that HL‐60 cells would only tolerate a monoallelic edit, as biallelic edited cells would produce no normal β‐actin. Surprisingly, we recovered viable monoallelic GFP‐β‐actin cells as well as biallelic edited GFP‐β‐actin cells, in which one copy of the ACTB gene is silenced and the other contains the GFP tag. Furthermore, the edited cells migrate with similar speeds and persistence as unmodified cells in a variety of motility assays, and have nearly normal cell shapes. These results might partially be explained by our observation that GFP‐β‐actin incorporates into the F‐actin network in biallelic edited cells at similar efficiencies as normal β‐actin in unedited cells. Additionally, the edited cells significantly upregulate γ‐actin, perhaps helping to compensate for the loss of normal β‐actin. Interestingly, biallelic edited cells have only modest changes in global gene expression relative to the monoallelic line, as measured by RNA sequencing. While monoallelic edited cells downregulate expression of the tagged allele and are thus only weakly fluorescent, biallelic edited cells are quite bright and well‐suited for live cell microscopy. The nondisruptive phenotype and direct interpretability of this fluorescent tagging approach make it a promising tool for studying actin dynamics in these rapidly migrating and highly phagocytic cells.
Students’ knowledge on sickle cell disease in Kisangani, Democratic Republic of the Congo

ABSTRACT Background: Education is needed as an action to reduce morbidity and mortality from sickle cell disease (SCD), an important but largely neglected risk to child survival in most African countries as Democratic Republic of Congo (DRC). Objective: To assess the knowledge of Kisangani University students in DRC regarding SCD. Methods: In this non-experimental, cross-sectional study, a validated questionnaire was used to assess the knowledge of 2 112 Kisangani University students in DRC and data were analyzed using SPSS version 20. Results: Most participants, 92.9% (95% confidence interval [CI]: 91.7–93.9) were knowledgeable about SCD and have heard about it through schools and/or universities (46.3%), followed by family (34.5%) and health-care workers (23.5%). Nine hundred and seventy-three (46.1%; 95% CI: 44.0–48.2) and 37.9% (95% CI: 35.9–40.0) subjects indicated, respectively, that SCD is an acquired and hereditary disease. Moreover, 53.6% (95% CI: 51.5–55.7) said that the diagnosis of SCD is made by blood tests, while 46.2% (95% CI: 44.1–48.3) talked about urine tests. About 85.6% were unaware of the risk of children becoming sickle cell patients when both parents have SCD. To prevent SCD, pre-marital screening was cited by only 7.7% (95% CI: 6.6–8.9) of subjects and no measure was known by 25.4% (95% CI: 23.6–27.3). However, 79.6% (95% CI: 77.8–81.3) approved the need of pre-marital screening of SCD. Discussion: This study highlighted that the Kisangani university students’ knowledge regarding SCD is poor and needs to be improved; education programs and motivational campaigns to be enhanced.
Anatomy of a selectively coassembled β-sheet peptide nanofiber

Significance Coassembly, in which peptides A and B selectively associate to form β-sheet structures, is an emerging approach to fabricate multicomponent biomaterials. As coassembly is rare in nature, designing synthetic peptide pairs must be informed by insights into molecular organization within existing systems. For charge-complementary peptide pairs, it is assumed that molecules organize into an alternating arrangement, yet there are no experimental data to support this assumption. Here, a combination of molecular dynamics simulations, biophysical measurements, electron microscopy, and solid-state NMR demonstrates that an established pair of charge-complementary peptides [CATCH(+) and CATCH(−)] coassemble into bilayers of AB-alternating β-sheets. However, significant mismatched AA and BB neighbors do occur. Off-pathway β-barrel oligomers were predicted by simulations, and concentration-dependent oligomer formation was observed experimentally. Peptide self-assembly, wherein molecule A associates with other A molecules to form fibrillar β-sheet structures, is common in nature and widely used to fabricate synthetic biomaterials. Selective coassembly of peptide pairs A and B with complementary partial charges is gaining interest due to its potential for expanding the form and function of biomaterials that can be realized. It has been hypothesized that charge-complementary peptides organize into alternating ABAB-type arrangements within assembled β-sheets, but no direct molecular-level evidence exists to support this interpretation. We report a computational and experimental approach to characterize molecular-level organization of the established peptide pair, CATCH. Discontinuous molecular dynamics simulations predict that CATCH(+) and CATCH(−) peptides coassemble but do not self-assemble. Two-layer β-sheet amyloid structures predominate, but off-pathway β-barrel oligomers are also predicted. At low concentration, transmission electron microscopy and dynamic light scattering identified nonfibrillar ∼20-nm oligomers, while at high concentrations elongated fibers predominated. Thioflavin T fluorimetry estimates rapid and near-stoichiometric coassembly of CATCH(+) and CATCH(−) at concentrations ≥100 μM. Natural abundance 13C NMR and isotope-edited Fourier transform infrared spectroscopy indicate that CATCH(+) and CATCH(−) coassemble into two-component nanofibers instead of self-sorting. However, 13C–13C dipolar recoupling solid-state NMR measurements also identify nonnegligible AA and BB interactions among a majority of AB pairs. Collectively, these results demonstrate that strictly alternating arrangements of β-strands predominate in coassembled CATCH structures, but deviations from perfect alternation occur. Off-pathway β-barrel oligomers are also suggested to occur in coassembled β-strand peptide systems.
NADPH Oxidases: The Vital Performers and Center Hubs during Plant Growth and Signaling

NADPH oxidases (NOXs), mostly known as respiratory burst oxidase homologs (RBOHs), are the key producers of reactive oxygen species (ROS) in plants. A lot of literature has addressed ROS signaling in plant development regulation and stress responses as well as on the enzyme’s structure, evolution, function, regulation and associated mechanisms, manifesting the role of NOXs/RBOHs as the vital performers and center hubs during plant growth and signaling. This review focuses on recent advances of NOXs/RBOHs on cell growth, hormone interaction, calcium signaling, abiotic stress responses, and immunity. Several primary particles, including Ca2+, CDPKs, BIK1, ROPs/RACs, CERK, FER, ANX, SnRK and SIK1-mediated regulatory mechanisms, are fully summarized to illustrate the signaling behavior of NOXs/RBOHs and their sophisticated and dexterous crosstalks. Diverse expression and activation regulation models endow NOXs/RBOHs powerful and versatile functions in plants to maintain innate immune homeostasis and development integrity. NOXs/RBOHs and their related regulatory items are the ideal targets for crop improvement in both yield and quality during agricultural practices.
Genetics of age-related clonal hematopoiesis and atherosclerotic cardiovascular disease.

PURPOSE OF REVIEW While advanced age is the major risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), we have a poor understanding of how aging promotes the progression of this disease. Recent evidence suggests that the age-dependent accumulation of somatic mutations in hematopoietic cells may represent a new causal risk factor for ASCVD. RECENT FINDINGS A hallmark of aging is the accumulation of somatic DNA mutations in all tissues of the body. Accordingly, evidence shows that hematopoietic stem/progenitor cells accumulate somatic mutations as a function of age in nonsymptomatic individuals. When these mutations occur in driver genes that provide a selective advantage to the hematopoietic stem/progenitor cells, they undergo a clonal expansion and progressively give rise to blood leukocytes that harbor these mutations. This phenomenon, referred to as clonal hematopoiesis, has been associated with the increased risk of mortality, hematologic malignancy, ASCVD, and related diseases. Notably, many individuals exhibiting clonal hematopoiesis carry single 'driver' mutations in preleukemic genes including DNA methyltransferase 3a, ten-eleven translocation 2, additional sex combs like 1, and Janus kinase 2. Experimental studies show that these mutations in some of these genes can alter the inflammatory properties of the leukocyte and contribute to the pathogenesis of ASCVD. SUMMARY We review recent epidemiological and experimental findings on the association between age-related clonal hematopoiesis and ASCVD by focusing on prevalent driver gene mutations.
Lipophagy-derived fatty acids undergo extracellular efflux via lysosomal exocytosis

ABSTRACT The autophagic degradation of lipid droplets (LDs), termed lipophagy, is a major mechanism that contributes to lipid turnover in numerous cell types. While numerous factors, including nutrient deprivation or overexpression of PNPLA2/ATGL (patatin-like phospholipase domain containing 2) drive lipophagy, the trafficking of fatty acids (FAs) produced from this pathway is largely unknown. Herein, we show that PNPLA2 and nutrient deprivation promoted the extracellular efflux of FAs. Inhibition of autophagy or lysosomal lipid degradation attenuated FA efflux highlighting a critical role for lipophagy in this process. Rather than direct transport of FAs across the lysosomal membrane, lipophagy-derived FA efflux requires lysosomal fusion to the plasma membrane. The lysosomal Ca2+ channel protein MCOLN1/TRPML1 (mucolipin 1) regulates lysosomal-plasma membrane fusion and its overexpression increased, while inhibition blocked FA efflux. In addition, inhibition of autophagy/lipophagy or MCOLN1, or sequestration of extracellular FAs with BSA attenuated the oxidation and re-esterification of lipophagy-derived FAs. Overall, these studies show that the well-established pathway of lysosomal fusion to the plasma membrane is the primary route for the disposal of FAs derived from lipophagy. Moreover, the efflux of FAs and their reuptake or subsequent extracellular trafficking to adjacent cells may play an important role in cell-to-cell lipid exchange and signaling. Abbreviations: ACTB: beta actin; ADRA1A: adrenergic receptor alpha, 1a; ALB: albumin; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A1; BECN1: beclin 1; BHBA: beta-hydroxybutyrate; BSA: bovine serum albumin; CDH1: e-cadherin; CQ: chloroquine; CTSB: cathepsin B; DGAT: diacylglycerol O-acyltransferase; FA: fatty acid; HFD: high-fat diet; LAMP1: lysosomal-associated membrane protein 1; LD: lipid droplet; LIPA/LAL: lysosomal acid lipase A; LLME: Leu-Leu methyl ester hydrobromide; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MCOLN1/TRPML1: mucolipin 1; MEF: mouse embryo fibroblast; PBS: phosphate-buffered saline; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PLIN: perilipin; PNPLA2/ATGL patatin-like phospholipase domain containing 2; RUBCN (rubicon autophagy regulator); SM: sphingomyelin; TAG: triacylglycerol; TMEM192: transmembrane protein 192; VLDL: very low density lipoprotein.
Mechanical Properties of Concrete Containing Liquefied Red Mud Subjected to Uniaxial Compression Loads

This study used liquefied red mud (RM) sludge, an aluminum industry by-product, as a construction material. Accordingly, various methods were examined that used the fabricated liquefied red mud (LRM) as an admixture for concrete, and the mechanical properties of concrete were then evaluated according to the cement type and the amount of LRM. The LRM mixing methods (replacement and addition) were compared, and the slump and compressive strengths of concrete were evaluated for each method. To examine the mechanical properties according to the cement type and the amount of LRM, two types of cement (ordinary Portland cement and slag cement (SC)) were used, and 20 and 40 wt% LRM (with respect to the cement weight) were added. The mechanical properties of the stress–strain curve (SSC), compressive strength, peak strain, and elastic modulus were quantified. When the slump and compressive strength of concrete were considered based on the experimental results, the addition LRM mixing method was recommended as the appropriate method for LRM. As the addition of LRM increased, the mechanical properties of concrete degraded. However, when SC was used, the mechanical properties did not significantly change when different amounts of LRM were added (up to 20%). In addition, the SSC of LRM concrete could be approximated based on the use of the relationship of the compressive strength and peak strain according to the cement type and the amount of LRM.
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats

Many obese patients are exposed to hypolipidemic and serotonin‐norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin‐treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co‐exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs.
Nfatc1 Promotes Interstitial Cell Formation During Cardiac Valve Development in Zebrafish

Supplemental Digital Content is available in the text. Rationale: The transcription factor NFATC1 (nuclear factor of activated T-cell 1) has been implicated in cardiac valve formation in humans and mice, but we know little about the underlying mechanisms. To gain mechanistic understanding of cardiac valve formation at single-cell resolution and insights into the role of NFATC1 in this process, we used the zebrafish model as it offers unique attributes for live imaging and facile genetics. Objective: To understand the role of Nfatc1 in cardiac valve formation. Methods and Results: Using the zebrafish atrioventricular valve, we focus on the valve interstitial cells (VICs), which confer biomechanical strength to the cardiac valve leaflets. We find that initially atrioventricular endocardial cells migrate collectively into the cardiac jelly to form a bilayered structure; subsequently, the cells that led this migration invade the ECM (extracellular matrix) between the 2 endocardial cell monolayers, undergo endothelial-to-mesenchymal transition as marked by loss of intercellular adhesion, and differentiate into VICs. These cells proliferate and are joined by a few neural crest–derived cells. VIC expansion and a switch from a promigratory to an elastic ECM drive valve leaflet elongation. Functional analysis of Nfatc1 reveals its requirement during VIC development. Zebrafish nfatc1 mutants form significantly fewer VICs due to reduced proliferation and impaired recruitment of endocardial and neural crest cells during the early stages of VIC development. With high-speed microscopy and echocardiography, we show that reduced VIC formation correlates with valvular dysfunction and severe retrograde blood flow that persist into adulthood. Analysis of downstream effectors reveals that Nfatc1 promotes the expression of twist1b—a well-known regulator of epithelial-to-mesenchymal transition. Conclusions: Our study sheds light on the function of Nfatc1 in zebrafish cardiac valve development and reveals its role in VIC formation. It also further establishes the zebrafish as a powerful model to carry out longitudinal studies of valve formation and function.