Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Porcine Versus Human Mesenchymal Stromal Cells From Three Distinct Donor Locations for Cytotherapy

Background: Mesenchymal stromal cell (MSC)-based cytotherapies fuel the hope for reduction of chronic systemic immunosuppression in allotransplantation, and our group has previously shown this capability for both swine and human cells. MSCs harvested from distinct anatomical locations may have different behavior and lead to different outcomes in both preclinical research and human trials. To provide an effective reference for cell therapy studies, we compared human and porcine MSCs from omental fat (O-ASC), subcutaneous fat (SC-ASC) and bone marrow (BM-MSC) under rapid culture expansion with endothelial growth medium (EGM). Methods: MSCs isolated from pigs and deceased human organ donors were compared for yield, viability, cell size, population doubling times (PDT), surface marker expression and differentiation potential after rapid expansion with EGM. Immunosuppressant toxicity on MSCs was investigated in vitro for four different standard immunosuppressive drugs. Immunomodulatory function was compared in mixed lymphocyte reaction assays (MLR) with/without immunosuppressive drug influence. Results: Human and porcine omental fat yielded significantly higher cell numbers than subcutaneous fat. Initial PDT was significantly shorter in ASCs than BM-MSCs and similar thereafter. Viability was reduced in BM-MSCs. Porcine MSCs were positive for CD29, CD44, CD90, while human MSCs expressed CD73, CD90 and CD105. All demonstrated confirmed adipogenic differentiation capacity. Cell sizes were comparable between groups and were slightly larger in human cells. Rapamycin revealed slight, mycophenolic acid strong and significant dose-dependent toxicity on viability/proliferation of almost all MSCs at therapeutic concentrations. No relevant toxicity was found for Tacrolimus and Cyclosporin A. Immunomodulatory function was dose-dependent and similar between groups. Immunosuppressants had no significant adverse effect on MSC immunomodulatory function. Discussion: MSCs from different harvest locations and donor species differ in terms of isolation yields, viability, PDT, and size. We did not detect relevant differences in immunomodulatory function with or without the presence of immunosuppressants. Human and pig O-ASC, SC-ASC and BM-MSC share similar immunomodulatory function in vitro and warrant confirmation in large animal studies. These findings should be considered in preclinical and clinical MSC applications.
Effect of Alert Level 4 on effective reproduction number: review of international COVID-19 cases

The effective reproduction number, Reff, is an important measure of transmission potential in the modelling of epidemics. It measures the average number of people that will be infected by a single contagious individual. A value of Reff > 1 suggests that an outbreak will occur, while Reff< 1 suggests the virus will die out. In response to the COVID-19 pandemic, countries worldwide are implementing a range of intervention measures, such as population-wide social distancing and case isolation, with the goal of reducing Reff to values below one, to slow or eliminate transmission. We analyse case data from 25 international locations to estimate their Reff values over time and to assess the effectiveness of interventions, equivalent to New Zealand's Alert Levels 1-4, for reducing transmission. Our results show that strong interventions, equivalent to NZ's Alert Level 3 or 4, have been successful at reducing Reff below the threshold for outbreak. In general, countries that implemented strong interventions earlier in their outbreak have managed to maintain case numbers at lower levels. These estimates provide indicative ranges of Reff for each Alert Level, to inform parameters in models of COVID-19 spread under different intervention scenarios in New Zealand and worldwide. Predictions from such models are important for informing policy and decisions on intervention timing and stringency during the pandemic.
The Transcription Factor Foxc1 Promotes Osteogenesis by Directly Regulating Runx2 in Response of Intermittent Parathyroid Hormone (1–34) Treatment

Parathyroid hormone (PTH) is crucial for bone remodeling. Intermittent PTH (1–34) administration stimulates osteogenesis and promotes bone formation; however, the possible targets and underlying mechanisms still remain unclear. In this study, functional links between PTH and Foxc1, a transcription factor reported to be predominant in skeletal development and formation, were indicated. We determined the impacts of Foxc1 on in vitro osteogenic differentiation and in vivo bone regeneration under intermittent PTH induction, and further explored its possible targets. We found that the expression level of Foxc1 was upregulated during osteogenic induction by intermittent PTH treatment, and the elevated expression of Foxc1 induced by PTH was inhibited by PTH1R silencing, while rescued by intermittent PTH supplement. By gain- and loss-of-function strategies targeting Foxc1 in MC3T3-E1 cells, we demonstrated that Foxc1 could promote in vitro osteogenic differentiation by intermittent PTH induction. Moreover, immunofluorescence analysis indicated the nuclear co-localization of Foxc1 with Runx2. Luciferase-reporter and chromatin immunoprecipitation analysis further confirmed that Foxc1 could bind to the P1 promoter region of Runx2 directly, which plays an indispensable part in osteogenic differentiation and bone mineralization. Meanwhile, we also revealed that Foxc1 could promote bone regeneration induced by intermittent PTH treatment in vivo. Taken together, this study revealed the role and mechanism of Foxc1 on in vitro osteogenic differentiation and in vivo bone regeneration in response of intermittent PTH treatment.
Inferring Unseen Causes: Developmental and Evolutionary Origins

Human adults can infer unseen causes because they represent the events around them in terms of their underlying causal mechanisms. It has been argued that young preschoolers can also make causal inferences from an early age, but whether or not non-human apes can go beyond associative learning when exploiting causality is controversial. However, much of the developmental research to date has focused on fully-perceivable causal relations or highlighted the existence of a causal relationship verbally and these were found to scaffold young children’s abilities. We examined inferences about unseen causes in children and chimpanzees in the absence of linguistic cues. Children (N = 129, aged 3–6 years) and zoo-living chimpanzees (N = 11, aged 7–41 years) were presented with an event in which a reward was dropped through an opaque forked-tube into one of two cups. An auditory cue signaled which of the cups contained the reward. In the causal condition, the cue followed the dropping event, making it plausible that the sound was caused by the reward falling into the cup; and in the arbitrary condition, the cue preceded the dropping event, making the relation arbitrary. By 4-years of age, children performed better in the causal condition than the arbitrary one, suggesting that they engaged in reasoning. A follow-up experiment ruled out a simpler associative learning explanation. Chimpanzees and 3-year-olds performed at chance in both conditions. These groups’ performance did not improve in a simplified version of the task involving shaken boxes; however, the use of causal language helped 3-year-olds. The failure of chimpanzees could reflect limitations in reasoning about unseen causes or a more general difficulty with auditory discrimination learning.
Analysis of molecular pathways in sporadic neuroendocrine tumors of the gastro‐entero‐pancreatic system

Little is known about the molecular pathogenesis of neuroendocrine tumors (NET) of the gastro‐entero‐pancreatic (GEP) system. We analyzed genetic and epigenetic alterations as well as the CpG island methylator phenotype (CIMP). The study comprised 118 well‐differentiated fore‐ and mid‐gut GEP‐NET from 71 patients. In addition to loss of heterozygosity (LOH), microsatellite instability (MSI) and the methylation status of various tumor associated genes were examined. The expression profile of p16, APC and MENIN was investigated by immunohistochemistry. None of the tumors was highly microsatellite unstable, LOH was found in 22.2%. Significant differences in promoter hypermethylation were identified in the RUNX3 and the O6‐MGMT genes. We found a significant loss of p16 expression in insulinomas (p = 0.05) and functional NET (p = 0.01), respectively. APC was expressed less in gastrinomas (p = 0.01) and functional GEP‐NET (p = 0.05) vs. nonfunctional tumors. MENIN expression was reduced in pancreatic vs. extrapancreatic NET (p = 0.008) and in insulinomas vs. nonfunctional GEP‐NET (p = 0.019) and NET associated with the carcinoid syndrome (p = 0.029). Further CIMP and a Ki‐67 index >10% showed a close correlation. Outcome analysis of 19 patients showed a better survival for CIMP‐negative patients. The analyses identified significant genetic and epigenetic alterations in well‐differentiated fore‐ and mid‐gut NET. CIMP, similar to Ki‐67, might turn out to be of prognostic relevance. © 2007 Wiley‐Liss, Inc.
Histopathological changes in the gill, liver and intestine of Heteropneustes fossilis (Bloch) treated with three dry seed extracts

Acute toxicity tests were carried out with aqueous and ethanolic extracts of three botanicals Lagerstroemia speciosa (L.) Pers, Dipterocarpus turbinatus Gaertn and Hevea brasiliensis (Willd. Ex Juss) on Heteropneustes fossilis (Bloch) under normal laboratory conditions. Extracts of L. speciosa were more potent than the extracts of D. turbinatus and H. brasiliensis. Histopathological changes in gill, liver and intestine of exposed fishes caused subtle cellular damages like disintegration of gill filaments and lamellae, degeneration of hepatocytes and blood vessels and necrosis of the intestinal epithelia. Different seed extracts showed histopathological variations in the different organs depending on the toxicity of the plant extracts. On the basis of histopathology, effectivity of the extract was in the order: Absolute ethyl alcohol > 50% ethyl alcohol > distilled water and the effectivity of the seed extracts on the studied organs was: L. speciosa > D. turbinatus > H. brasiliensis seed extracts. DOI: http://dx.doi. org/10.3329/jasbs.v38i2. 15612 J. Asiat. Soc. Bangladesh, Sci. 38(2): 217-226, December 2012
Detection of Transforming Growth Factor-β1 in Coxsackie B3 Virus-Induced Murine Myocarditis

To clarify the role of TGF-β1 in myocardial healing process after virus-induced myocarditis, we have examined the time course of TGF-β1 expression and its localization in myocardial healing process after Coxsackie B3-induced murine myocarditis. TGF-β1 immunoreactivity increased in parallel with its mRNA level and reached a peak at 10 days after Coxsackie B3 virus inoculation. Immunohistochemically, TGF-β1 was localized at pre-necrotic area at an early phase (5 days); it increased and extended to the area around the necrotic foci when necrosis became manifest (10 days); it decreased when macrophages and fibroblasts migrated to the necrotic foci (15 days); and then it reached a normal level and localized a little in perivascular and calcified regions (30 days). To our knowledge, this is the first study which demonstrates that TGF-β1 mRNA increases in viral-induced myocarditis at acute inflammatory phase. This result suggests that TGF-β1 promotes the migration of macrophages and fibroblasts to necrotic foci and induces fibrosis.
Effect of genetic resistance to gastrointestinal nematodes on plasma concentrations of insulin-like growth factor-1 and leptin in Merino sheep

Gastrointestinal nematode infection in sheep changes the nutritional economy of the host, but little is known about the effects of infection on the hormonal systems that regulate the metabolism of the animal. This study examined two key hormones, insulin-like growth factor-1 (IGF-1) and leptin, in genetically resistant and random bred control Merino sheep in the presence or absence of nematode infection. Sixty-four 10-month-old Rylington Merino wethers, half from the parasite-resistant line and half from unselected control line, were initially maintained at two body conditions (body condition scores averaged 1.7 and 2.5) in individual pens in an animal house. The animals were kept parasite-free for 9 weeks, then ‘trickle-infected’ with Trichostrongylus colubriformis and Teladorsagia circumcincta larvae, each at a rate of 10 000 per week, for 13 weeks. Each body condition score group was subdivided into two groups at the beginning of the infection procedure and feed supply was controlled at 1× or 1.5× the maintenance metabolisable energy requirement. Plasma IGF-1 concentrations decreased marginally by day 21 of infection, then markedly by day 49, and then remained low until day 84. Plasma leptin concentrations tended to increase during the infection period. Both body condition and feed intake had significant effects on IGF-1 and leptin concentrations, and the higher concentrations were related to the good body condition or high feed intake. The parasite-resistant sheep had consistently higher concentrations of IGF-1 compared with the controls, whereas the concentrations of leptin were similar. The significant changes in IGF-1 but not leptin suggest that infection may have a more significant impact on protein anabolism, and least impact on lipid metabolism. Selection for parasite resistance appears to result in enhanced protein anabolism.
Acute induction of histone acetylation on the jejunal sucrase–isomaltase gene by dietary fructose

We have previously reported that dietary fructose rapidly induces jejunal sucrase–isomaltase (SI) gene expression in rats. In this study, we confirmed in mice that SI mRNA was induced 6 h after force-feeding fructose, but not glucose. Using the chromatin immunoprecipitation assay, we revealed that histones H3 and H4 on the promoter/enhancer regions of the SI gene in mice given fructose were highly acetylated, compared with those given glucose or water. These results suggest that acute induction of SI gene expression by dietary fructose is associated with acetylation of histones H3 and H4 on the SI gene.
PRODUCTION OBJECTIVES, SELECTION CRITERIA AND BREEDING PRACTICES OF AFAR SHEEP IN ABA’ALA, AFAR REGION, ETHIOPIA

The aims of this study was to identify production purposes, selection criteria and breeding practices for Afar sheep in Aba’ala district, Afar region, Ethiopia. A purposive sampling technique was used to identify research sites and respondents. A total of 90 households from agro-pastoral and pastoral production systems were selected. Individual interview, group discussion and own-flock ranking experiment were used to collect data. The collected data were analyzed using SPSS statistical software. There was no significant difference in sheep flock size and structure between the two production systems. In the agro-pastoral areas, sheep were mainly kept for income generation, milk, and meat production, while income generation, milk production and saving were for the pastoral production system. All flock owners utilized breeding rams that are born in their flock. Sharing of breeding rams among sheep producers is commonly practiced in the study area, especially during the dry season. Selection of breeding male is done starting from very young age with main focus on coat colour. However, selection of breeding female is non-existent though few farmers look for milk producing ability after the birth of the first offspring. Milk yield, coat colour, and appearance were the most mentioned attributes for selecting a breeding female, whereas breeding male selection criteria are coat colour followed by fast body growth and appearance. Awareness creation on selective breeding and retaining best male lambs for breeding purpose is needed.
Nutrient levels and the development of diatom and blue-green algal blooms in a shallow Australian estuary

In the Peel-Harvey estuary system, Western Australia, some 90% of riverflow and nutrient loading occurs in three winter months. Diatom blooms follow riverflow, but are replaced by blooms of the blue-green Nodularia spumigena Mert. , especially in Harvey Estuary. By analysis of time series data from 1977-1983, it is shown that the magnitude of the Nodularia bloom in summer is related to the minimum salinity of the estuary (and hence total river flow), maximum phosphate concentration and total riverine phosphorus loading, in the previous winter. The relationships have a predictive capacity. It is argued that diatom blooms trap phosphorus, which is sedimented largely as faecal pellets; the phosphorus is recycled and supports Nodularia growth under warmer conditions, and the amount available determines Nodularia biomass. Nodularia blooms collapse when summer salinities reach 30‰
Effect of Hand and Rotary Instruments on the Fracture Resistance of Teeth: An In Vitro Study

Objective: Endodontic treatment should be both conservative and effective. Endodontic instruments with a greater taper are used for coronal flaring, for proper debridement with efficient irrigation. However, increased taper of an instrument can remove a larger amount of pericervical dentin, compromising the strength of the tooth. The aim of this study was to determine the effect of hand files, ProTaper Universal, ProTaper Next, and V Taper rotary instrument systems on the fracture resistance of teeth. Materials and Methods: In total, 60 extracted human maxillary first premolars were divided into four groups—Group I (Hand Files; HF), Group II (ProTaper Universal; PT), group III (ProTaper Next; PTN) and Group IV (V Taper; VT) (N = 15). Each group was instrumented with the respective instrument system, irrigated, obturated, restored, and mounted in cold cure acrylic. A universal load-testing machine (Shimadzu, Japan) was used to apply a vertical compressive load. The maximum force was recorded in Newton. Analysis of variance (ANOVA) and Independent t-tests were applied to compare the maximum mean force required to fracture the tooth. Results: There was a statistically significant difference in fracture resistance between Group I (HF) and Group II (PT) and between Group II (PT) and Group IV (VT) (p < 0.001). Similarly, a significant difference was observed between Group II (PT) and Group III (PTN) (p < 0.01). Furthermore, a significant difference was observed between Group I (HF) and Group III (PTN), and between Group III (PTN) and Group IV (VT) (p < 0.05), too. However, there was no statistically significant difference between Group I (HF) and group IV (VT) (p > 0.05). Conclusion: Rotary files with more taper seem to remove more pericervical dentin than traditional manual and rotary files with less taper, thus altering the strength of the tooth.
A compositional neural code in high-level visual cortex can explain jumbled word reading

We read jubmled wrods effortlessly, but the neural correlates of this remarkable ability remain poorly understood. We hypothesized that viewing a jumbled word activates a visual representation that is compared to known words. To test this hypothesis, we devised a purely visual model in which neurons tuned to letter shape respond to longer strings in a compositional manner by linearly summing letter responses. We found that dissimilarities between letter strings in this model can explain human performance on visual search, and responses to jumbled words in word reading tasks. Brain imaging revealed that viewing a string activates this letter-based code in the lateral occipital (LO) region and that subsequent comparisons to stored words are consistent with activations of the visual word form area (VWFA). Thus, a compositional neural code potentially contributes to efficient reading.
Primary Aldosteronism: Where Are We Now? Where to from Here?

Abstract The past nine years have seen major advances in establishing the etiology of unilateral primary aldosteronism, and very possibly that of bilateral hyperaldosteronism, in response to somatic mutations in aldosterone synthase expressing cells. Though there have been important advances in the management of primary aldosteronism, in small but convincing studies, they represent minor changes to current guidelines. What has been totally absent is consideration of the public health issue that primary aldosterone represents, and the public policy issues that would be involved in addressing the disorder. In his introduction to PiPA 6, Martin Reincke calculated that only one in a thousand patients in Germany with primary aldosteronism were treated appropriately, an astounding figure for any disease in the 21st century. Towards remedying this totally unacceptable public health issue, the author proposes a radical simplification and streamlining of screening for primary aldosteronism, and the management of most patients by general practitioners. The second bottle-neck in current management is that of mandatory adrenal venous sampling for all but 1–2% of patients, a costly procedure requiring rare expertise. Ideally, it should be reserved – on the basis of likelihood, enhanced imaging, or peripheral steroid profiles – for a small minority of patients with clear evidence for unilateral disease. Only when costs are minimized and roadblocks removed will primary aldosteronism be properly treated as the public health issue that it is.
Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8

Methyltransferase-like protein 3 (METTL3) regulates multiple cell functions and diseases by modulating N6-methyladenosine (m6A) modifications. However, it is still unclear whether METTL3 involves in the pathogenesis of diabetic retinopathy (DR). In the present study, we found that high-glucose inhibited RPE cell proliferation, promoted cell apoptosis and pyroptosis in a time-dependent manner. In addition, both METTL3 mRNA and miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. As expected, upregulation of METTL3 and miR-25-3p alleviated the cytotoxic effects of high-glucose on RPE cells, and knock-down of METTL3 and miR-25-3p had opposite effects. Additionally, METTL3 overexpression increased miR-25-3p levels in RPE cells in a microprocessor protein DGCR8-dependent manner, and miR-25-3p ablation abrogated the effects of overexpressed METTL3 on cell functions in high-glucose treated RPE cells. Furthermore, PTEN could be negatively regulated by miR-25-3p, and overexpression of METTL3 increased phosphorylated Akt (p-Akt) levels by targeting miR-25-3p/PTEN axis. Consistently, upregulation of PTEN abrogated the protective effects of METTL3 overexpression on RPE cells treated with high-glucose. Collectively, METTL3 rescued cell viability in high-glucose treated RPE cells by targeting miR-25-3p/PTEN/Akt signaling cascade.