Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiotensin-II-Evoked Ca2+ Entry in Murine Cardiac Fibroblasts Does Not Depend on TRPC Channels

TRPC proteins form cation conducting channels regulated by different stimuli and are regulators of the cellular calcium homeostasis. TRPC are expressed in cardiac cells including cardiac fibroblasts (CFs) and have been implicated in the development of pathological cardiac remodeling including fibrosis. Using Ca2+ imaging and several compound TRPC knockout mouse lines we analyzed the involvement of TRPC proteins for the angiotensin II (AngII)-induced changes in Ca2+ homeostasis in CFs isolated from adult mice. Using qPCR we detected transcripts of all Trpc genes in CFs; Trpc1, Trpc3 and Trpc4 being the most abundant ones. We show that the AngII-induced Ca2+ entry but also Ca2+ release from intracellular stores are critically dependent on the density of CFs in culture and are inversely correlated with the expression of the myofibroblast marker α-smooth muscle actin. Our Ca2+ measurements depict that the AngII- and thrombin-induced Ca2+ transients, and the AngII-induced Ca2+ entry and Ca2+ release are not affected in CFs isolated from mice lacking all seven TRPC proteins (TRPC-hepta KO) compared to control cells. However, pre-incubation with GSK7975A (10 µM), which sufficiently inhibits CRAC channels in other cells, abolished AngII-induced Ca2+ entry. Consequently, we conclude the dispensability of the TRPC channels for the acute neurohumoral Ca2+ signaling evoked by AngII in isolated CFs and suggest the contribution of members of the Orai channel family as molecular constituents responsible for this pathophysiologically important Ca2+ entry pathway.
Targeting CD38-Expressing Multiple Myeloma and Burkitt Lymphoma Cells In Vitro with Nanobody-Based Chimeric Antigen Receptors (Nb-CARs)

The NAD-hydrolyzing ecto-enzyme CD38 is overexpressed by multiple myeloma and other hematological malignancies. We recently generated CD38-specific nanobodies, single immunoglobulin variable domains derived from heavy-chain antibodies naturally occurring in llamas. Nanobodies exhibit high solubility and stability, allowing easy reformatting into recombinant fusion proteins. Here we explore the utility of CD38-specific nanobodies as ligands for nanobody-based chimeric antigen receptors (Nb-CARs). We cloned retroviral expression vectors for CD38-specific Nb-CARs. The human natural killer cell line NK-92 was transduced to stably express these Nb-CARs. As target cells we used CD38-expressing as well as CRISPR/Cas9-generated CD38-deficient tumor cell lines (CA-46, LP-1, and Daudi) transduced with firefly luciferase. With these effector and target cells we established luminescence and flow-cytometry CAR-dependent cellular cytotoxicity assays (CARDCCs). Finally, the cytotoxic efficacy of Nb-CAR NK-92 cells was tested on primary patient-derived CD38-expressing multiple myeloma cells. NK-92 cells expressing CD38-specific Nb-CARs specifically lysed CD38-expressing but not CD38-deficient tumor cell lines. Moreover, the Nb-CAR-NK cells effectively depleted CD38-expressing multiple myeloma cells in primary human bone marrow samples. Our results demonstrate efficacy of Nb-CARs in vitro. The potential clinical efficacy of Nb-CARs in vivo remains to be evaluated.
Community Structure, Diversity and Potential of Endophytic Bacteria in the Primitive New Zealand Medicinal Plant Pseudowintera colorata

Although the importance of the plant microbiome in commercial plant health has been well established, there are limited studies in native medicinal plants. Pseudowintera colorata (horopito) is a native New Zealand medicinal plant recognized for its antimicrobial properties. Denaturing gradient gel electrophoresis (DGGE) and Illumina MiSeq analysis of P. colorata plants from ten sites across New Zealand showed that tissue type strongly influenced the diversity and richness of endophytic bacteria (PERMANOVA, P < 0.05). In addition, two OTUs belonging to the genus Pseudomonas (Greengenes ID: 646549 and 138914) were found to be present in >75% of all P. colorata leaf, stem and root samples and were identified as the members of the P. colorata “core endomicrobiome”. Culture-independent analysis was complemented by the recovery of 405 endophytic bacteria from the tissues of P. colorata. Some of these cultured endophytic bacteria (n = 10) showed high antagonism against four different phytopathogenic fungi tested. The influence of endophytic bacteria on plant growth was assessed by inoculating P. colorata seedlings. The mean shoot height of seedlings treated with Bacillus sp. TP1LA1B were longer (1.83×), had higher shoot dry weight (1.8×) and produced more internodes (1.8×) compared to the control.
Child Development Outcomes of DIR/Floortime TM-based Programs: A Systematic Review

Background. Occupational therapy is often part of the multi-disciplinary approach within the Developmental, Individual-differences, Relationship-based (DIR) FloortimeTM Model. The model addresses the emotional development of children, which is considered to be critical for the other child developmental areas. Purpose. This review serves to inform practitioner decision-making about the use of this model, as no systematic reviews exist on child development outcomes. Methods. The systematic search included Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Cochrane. For critical appraisal, the McMaster Critical Review was utilized. Findings. Nine studies were identified with varying quality levels. Outcomes were mostly reported for increased socio-emotional development. Implications. The evidence base for this model is emerging from a published research perspective. It is recommended that the use of this model be supported by sound clinical reasoning processes, intervention fidelity, use of valid outcome measures, and regular monitoring. Higher quality research is urgently needed to progress the research base for this intervention.
The Unfinished Agenda for Food Fortification in Low- and Middle-Income Countries: Quantifying Progress, Gaps and Potential Opportunities

Large-scale food fortification (LSFF) is a cost-effective intervention that is widely implemented, but there is scope to further increase its potential. To identify gaps and opportunities, we first accessed the Global Fortification Data Exchange (GFDx) to identify countries that could benefit from new fortification programs. Second, we aggregated Fortification Assessment Coverage Toolkit (FACT) survey data from 16 countries to ascertain LSFF coverage and gaps therein. Third, we extended our narrative review to assess current innovations. We identified 84 countries as good candidates for new LSFF programs. FACT data revealed that the potential of oil/ghee and salt fortification is not being met due mainly to low coverage of adequately fortified foods (quality). Wheat, rice and maize flour fortification have similar quality issues combined with lower coverage of the fortifiable food at population-level (<50%). A four-pronged strategy is needed to meet the unfinished agenda: first, establish new LSFF programs where warranted; second, systems innovations informed by implementation research to address coverage and quality gaps; third, advocacy to form new partnerships and resources, particularly with the private sector; and finally, exploration of new fortificants and vehicles (e.g. bouillon cubes; salt fortified with multiple nutrients) and other innovations that can address existing challenges.
Acetaminophen‐induced hepatotoxicity of cultured hepatocytes depends on timing of isolation from light‐cycle controlled mice

Most physiological changes follow a daily cycle in animals because their circadian rhythm is adjusted to and synchronized with sunlight. In particular, the circadian rhythm affects liver functions, including pharmacokinetics and metabolism. The influence of circadian rhythm has not been included in hepatotoxicity assays used in drug discovery and development. In this study, the contribution of circadian rhythm was investigated in acetaminophen‐induced hepatotoxicity in mice and primary cultured hepatocytes. Hepatotoxicity was induced via the intraperitoneal administration of acetaminophen to a greater extent at night than during the day in mice. The sensitivity of acetaminophen‐induced hepatotoxicity was consistent with the expression levels of acetaminophen‐metabolizing enzyme and circadian genes. The host‐derived circadian rhythm was still evident in the primary cultured hepatocytes within a day after their isolation from the liver. Primary cultured hepatocytes isolated at night were significantly more sensitive to acetaminophen than those isolated during the day. The sensitivity toward acetaminophen‐induced hepatotoxicity depended on the circadian rhythm of the expression of acetaminophen‐metabolizing genes and intracellular glutathione levels in primary cultured hepatocytes. These results obtained from cultured cells correspond to those in mice, suggesting that the timing of hepatocyte isolation is important when investigating drug metabolism and toxicity tests in culture.
Enhancing Activity of Pleurotus sajor-caju (Fr.) Sing β-1,3-Glucanoligosaccharide (Ps-GOS) on Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells through the Involvement of BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway

Osteoporosis is a leading world health problem that results from an imbalance between bone formation and bone resorption. β-glucans has been extensively reported to exhibit a wide range of biological activities, including antiosteoporosis both in vitro and in vivo. However, the molecular mechanisms responsible for β-glucan-mediated bone formation in osteoblasts have not yet been investigated. The oyster mushroom Pleurotus sajor-caju produces abundant amounts of an insoluble β-glucan, which is rendered soluble by enzymatic degradation using Hevea glucanase to generate low-molecular-weight glucanoligosaccharide (Ps-GOS). This study aimed to investigate the osteogenic enhancing activity and underlining molecular mechanism of Ps-GOS on osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. In this study, it was demonstrated for the first time that low concentrations of Ps-GOS could promote cell proliferation and division after 48 h of treatment. In addition, Ps-GOS upregulated the mRNA and protein expression level of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2), which are both involved in BMP signaling pathway, accompanied by increased alkaline phosphatase (ALP) activity and mineralization. Ps-GOS also upregulated the expression of osteogenesis related genes including ALP, collagen type 1 (COL1), and osteocalcin (OCN). Moreover, our novel findings suggest that Ps-GOS may exert its effects through the mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/β-catenin signaling pathways.
Apoptotic Effect of 1800 MHz Electromagnetic Radiation on NIH/3T3 Cells

To investigate the effect of 1800 MHz electromagnetic radiation (EMR) on apoptosis, we exposed NIH/3T3 cells at 1800 MHz with a specific absorption rate (SAR) of 2 W/kg intermittently for 12, 24, 36, and 48 h. After exposure, Cell Counting Kit-8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis; the expression of p53, a molecule with the key role in apoptosis, was measured by real-time qPCR, western blot, and immunofluorescence; and images of the structure of the mitochondria, directly reflecting apoptosis, were captured by electron microscopy. The results showed that the viability of cells in the 12, 36, and 48 h exposure groups significantly decreased compared with the sham groups; after 48 h of exposure, the percentage of late apoptotic cells in the exposure group was significantly higher. Real-time qPCR results showed that p53 mRNA in the 48 h exposure group was 1.4-fold of that in the sham group; significant differences of p53 protein fluorescence expression were observed between the exposure groups and the sham groups after 24 h and 48 h. The mitochondrial swelling and vesicular morphology were found in the electron microscopy images after 48 h exposure. These findings demonstrated 1800 MHz, SAR 2 W/kg EMR for 48 h may cause apoptosis in NIH/3T3 cells and that this apoptosis might be attributed to mitochondrial damage and upregulation of p53 expression.
Putting soil invertebrate diversity on the map

Ecologists have had a very good foundational knowledge of the global distribution of plants and aboveground animals for many decades. But despite the immense diversity of soil organisms, our knowledge of the global distribution, drivers and threats to soil biodiversity is very limited. In this issue of Molecular Ecology, Bastida et al. (2020) produce the first global maps of soil invertebrate diversity that have been sampled at 83 locations, across six continents, using standardised methods and DNA sequencing. Using data from nematodes, arachnids and rotifers, and structural equation models, they find that diversity of these taxa is primarily driven by vegetation and climate. Given the anthropogenic changes that are occurring, and are projected to continue, this study provides important baseline information for future soil biodiversity and function monitoring, as well as exciting working hypotheses for targeted experiments.
Influencing Factors on Health-Promotion Lifestyle of Nurses

Purpose: This study has been attempted in order to confirm the factors that affect the healthpromotion lifestyle of nurses. Method: Data was collected by questionnaires from 324 nurses at 5 university hospitals located in Seoul. The instrument tools utilized in this study was health-promotion lifestyle, perceived health status, perceived benefits, perceived barriers, self-efficacy, and social support, and validity and reliability of the tool have been verified with literature studies and pre-study examinations. The collected data have been analyzed using SPSS PC 12 program. Result: The factors that affect health-promotion lifestyle of nurses were perceived health status (= .320), self-efficacy (= .248), social support (= .139), perceived benefits (= .207), and age (= .089), that altogether explained 41.1%. Conclusion: It has been confirmed that th regression equation model of this research may serve as a health- promotion lifestyle prediction factors in nurses.
Study of correlations between metabolic risk factors, PWV and hypertension in college students

ABSTRACT Objective: Obesity, dyslipidemia and diabetes have been recognized as risk factors of hypertension in the general population. This study focused on college students and correlations between serum lipids, serum uric acid, fasting plasma glucose, serum creatinine, body mass index, brachial-ankle pulse wave velocity and hypertension. The results suggested that there was no relevance between serum lipids and hypertension. However, it came out that hypertension is associated with normal fasting plasma glucose, BMI (thinness and normal weight), normal serum creatinine. Methods: A total of 5185 students were enrolled, and their blood pressure, height and weight were measured. 285 of the students were selected to take physical examinations including serum uric acid, total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, fasting plasma glucose, serum creatinine, blood urea nitrogen, ankle-brachial index and brachial-ankle pulse wave velocity measured. Results: The values of systolic blood pressure(SBP), diastolic blood pressure(DBP), serum uric acid, fasting plasma glucose(FPG), serum creatinine, body mass index(BMI), and brachial-ankle pulse wave velocity(baPWV) were higher in hypertension group than those in non-hypertension group (P < .001, <0.001, <0.001, = 0.009, = 0.07, <0.001, <0.001, respectively). Logistic regression showed correlations between hypertension and hyperuricemia (OR = 2.975, 95%CI: 1.672–5.291), obesity (OR = 2.814, 95%CI: 1.297–6.105), fasting plasma glucose (OR = 2.184, 95%CI: 1.090–4.378) and brachial-ankle pulse wave velocity (OR = 1.005, 95%CI: 1.003–1.007). The AUC was 0.786 (95%CI: 0.729–0.842, P < .0001). We can draw a conclusion that hyperuricemia, obesity, fasting plasma glucose and brachial-ankle pulse wave velocity, listed in descending order of influence, are risk factors for hypertension in college students.
Neuromuscular Activity Induces Paracrine Signaling and Triggers Axonal Regrowth after Injury in Microfluidic Lab-On-Chip Devices

Peripheral nerve injuries, including motor neuron axonal injury, often lead to functional impairments. Current therapies are mostly limited to surgical intervention after lesion, yet these interventions have limited success in restoring functionality. Current activity-based therapies after axonal injuries are based on trial-error approaches in which the details of the underlying cellular and molecular processes are largely unknown. Here we show the effects of the modulation of both neuronal and muscular activity with optogenetic approaches to assess the regenerative capacity of cultured motor neuron (MN) after lesion in a compartmentalized microfluidic-assisted axotomy device. With increased neuronal activity, we observed an increase in the ratio of regrowing axons after injury in our peripheral-injury model. Moreover, increasing muscular activity induces the liberation of leukemia inhibitory factor and glial cell line-derived neurotrophic factor in a paracrine fashion that in turn triggers axonal regrowth of lesioned MN in our 3D hydrogel cultures. The relevance of our findings as well as the novel approaches used in this study could be useful not only after axotomy events but also in diseases affecting MN survival.
Biomarker-Based Preoperative Risk Stratification for Patients Undergoing Non-Cardiac Surgery

Perioperative morbidity and mortality remains a substantial problem and is strongly associated with patients’ cardiac comorbidities. Guidelines for the cardiovascular assessment and management of patients at risk of cardiac issues while undergoing non-cardiac surgery are traditionally based on the exclusion of active or unstable cardiac conditions, determination of the risk of surgery, the functional capacity of the patient, and the presence of cardiac risk factors. In the last two decades, strong evidence showed an association between cardiac biomarkers and adverse cardiac events, with newer guidelines incorporating this knowledge. This review describes a biomarker-based risk-stratification pathway and discusses potential treatment strategies for patients suffering from postoperative myocardial injury or infarction.
The cost and benefit of anti-TNF therapy from a population perspective-for what it's worth.

Anti-tumor necrosis factor therapy (ant-TNF) has dramatically changed the treatment of both Crohn’s disease (CD) and ulcerative colitis (UC). The efficacy of this class of therapy has been established since the late 1990s when infliximab was shown to be effective in the treatment of moderate to severe CD and later fistulizing CD and UC (1-4). Since this time, additional anti-TNF agents have demonstrated efficacy in moderate to severe inflammatory bowel disease (IBD), including adalimumab (5,6) for both CD and UC and golimumab (7,8) for UC. In addition, several studies have further demonstrated the long-term efficacy of these agents based on both randomized controlled trials (RCT) and real-world data (9-11). While anti-TNF therapy has offered an effective treatment option for both CD and UC, the associated high costs of using these agents is often considered a drawback from a population standpoint. Several studies have demonstrated that the increased cost associated with using anti-TNF therapy has now surpassed hospitalization and surgery as the highest healthcare expenditure in patients with IBD (12-14).
Synonymous codon substitutions perturb cotranslational protein folding in vivo and impair cell fitness

Significance Many proteins that are incapable of refolding in vitro nevertheless fold efficiently to their native state in the cell. This suggests that more information than the amino acid sequence is required to properly fold these proteins. Here we show that synonymous mRNA mutations can alter a protein folding mechanism in vivo, leading to changes in cellular fitness. This work demonstrates that synonymous codon selection can play an important role in supporting efficient protein production in vivo. In the cell, proteins are synthesized from N to C terminus and begin to fold during translation. Cotranslational folding mechanisms are therefore linked to elongation rate, which varies as a function of synonymous codon usage. However, synonymous codon substitutions can affect many distinct cellular processes, which has complicated attempts to deconvolve the extent to which synonymous codon usage can promote or frustrate proper protein folding in vivo. Although previous studies have shown that some synonymous changes can lead to different final structures, other substitutions will likely be more subtle, perturbing predominantly the protein folding pathway without radically altering the final structure. Here we show that synonymous codon substitutions encoding a single essential enzyme lead to dramatically slower cell growth. These mutations do not prevent active enzyme formation; instead, they predominantly alter the protein folding mechanism, leading to enhanced degradation in vivo. These results support a model in which synonymous codon substitutions can impair cell fitness by significantly perturbing cotranslational protein folding mechanisms, despite the chaperoning provided by the cellular protein homeostasis network.
Characterization of the MinD/ParA‐type ATPase FlhG in Vibrio alginolyticus and implications for function of its monomeric form

FlhG is a MinD/ParA‐type ATPase that works as a negative regulator for flagellar biogenesis. In Vibrio alginolyticus, FlhG functions antagonistically with the positive regulator FlhF to generate a single polar flagellum. Here, we examined the effects of ADP and ATP on the aggregation and dimerization of Vibrio FlhG. Purified FlhG aggregated after exposure to low NaCl conditions, and its aggregation was suppressed in the presence of ADP or ATP. FlhG mutants at putative ATP‐binding (K31A) or catalytic (D60A) residues showed similar aggregation profiles to the wild type, but ATP caused strong aggregation of the ATPase‐stimulated D171A mutant although ADP significantly suppressed the aggregation. Results of size exclusion chromatography of purified FlhG or Vibrio cell lysates suggested that FlhG exists as a monomer in solution, and ATP does not induce FlhG dimerization. The K31A and D60A mutants eluted at monomer fractions regardless of nucleotides, but ATP shifted the elution peak of the D171A mutant to slightly earlier, presumably because of a subtle conformational change. Our results suggest that monomeric FlhG can function in vivo, whose active conformation aggregates easily.