Miracle-dz/UniFAR-FTUs huggingface dataset:
Malaysian brown macroalga Padina australis mitigates lipopolysaccharide-stimulated neuroinflammation in BV2 microglial cells

Objective(s): Neuroinflammation and microglial activation are pathological features in central nervous system disorders. Excess levels of reactive oxygen species (ROS) and pro-inflammatory cytokines have been implicated in exacerbation of neuronal damage during chronic activation of microglial cells. Padina australis, a brown macroalga, has been demonstrated to have various pharmacological properties such as anti-neuroinflammatory activity. However, the underlying mechanism mediating the anti-neuroinflammatory potential of P. australis remains poorly understood. We explored the use of Malaysian P. australis in attenuating lipopolysaccharide (LPS)-stimulated neuroinflammation in BV2 microglial cells. Materials and Methods: Fresh specimens of P. australis were freeze-dried and subjected to ethanol extraction. The ethanol extract (PAEE) was evaluated for its protective effects against 1 µg/ml LPS-stimulated neuroinflammation in BV2 microglial cells. Results: LPS reduced the viability of BV2 microglia cells and increased the levels of nitric oxide (NO), prostaglandin E2 (PGE2), intracellular reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). However, the neuroinflammatory response was reversed by 0.5–2.0 mg/ml PAEE in a dose-dependent manner. Analysis of liquid chromatography-mass spectrometry (LC-MS) of PAEE subfractions revealed five compounds; methyl α-eleostearate, ethyl α-eleostearate, niacinamide, stearamide, and linoleic acid. Conclusion: The protective effects of PAEE against LPS-stimulated neuroinflammation in BV2 microglial cells were found to be mediated by the suppression of excess levels of intracellular ROS and pro-inflammatory mediators and cytokines, denoting the protective role of P. australis in combating continuous neuroinflammation. Our findings support the use of P. australis as a possible therapeutic for neuroinflammatory and neurodegenerative diseases.
Protein production from HEK293 cell line-derived stable pools with high protein quality and quantity to support discovery research

Antibody-based therapeutics and recombinant protein reagents are often produced in mammalian expression systems, which provide human-like post-translational modifications. Among the available mammalian cell lines used for recombinant protein expression, Chinese hamster ovary (CHO)-derived suspension cells are generally utilized because they are easy to culture and tend to produce proteins in high yield. However, some proteins purified from CHO cell overexpression suffer from clipping and display undesired non-human post translational modifications (PTMs). In addition, CHO cell lines are often not suitable for producing proteins with many glycosylation motifs for structural biology studies, as N-linked glycosylation of proteins poses challenges for structure determination by X-ray crystallography. Hence, alternative and complementary cell lines are required to address these issues. Here, we present a robust method for expressing proteins in human embryonic kidney 293 (HEK293)-derived stable pools, leading to recombinant protein products with much less clipped species compared to those expressed in CHO cells and with higher yield compared to those expressed in transiently-transfected HEK293 cells. Importantly, the stable pool generation protocol is also applicable to HEK293S GnTI- (N-acetylglucosaminyltransferase I–negative) and Expi293F GnTI- suspension cells, facilitating production of high yields of proteins with less complex glycans for use in structural biology projects. Compared to HEK293S GnTI- stable pools, Expi293F GnTI- stable pools consistently produce proteins with similar or higher expression levels. HEK293-derived stable pools can lead to a significant cost reduction and greatly promote the production of high-quality proteins for diverse research projects.
Long-term mammal herbivory on arthropod assemblages at Kruger National Park, South Africa

Protected savannas are essential reserves for biological diversity, including endangered arthropod species, however, extreme grazing by mammals has cascading impacts on the communities and disrupts the functioning of these ecosystems globally. The current study assessed the abundance, species richness and composition of arthropods at the long-term grazing exclosures of Kruger National Park, South Africa. Pitfall traps and active searches were used to sample arthropods at the ungrazed, moderately, and heavily grazed exclosures. We found that Hymenoptera, Coleoptera, Diptera and Araneae were the most abundant orders of arthropods sampled. The abundance of multi-taxon, Diptera and Hymenoptera was significantly different between exclosures. In contrast, Coleoptera had high numbers of morphospecies compared to Hymenoptera, Araneae and Diptera. Species richness for multi-taxon, Diptera and Hymenoptera was significantly high at the heavily grazed compared to moderately grazed and ungrazed exclosures. Up to 22.2%, 41.2%, and 44.4% of the morphospecies were unique to the ungrazed, moderately and heavily grazed exclosures, respectively. A high proportion of morphospecies shared between exclosures were Coleoptera (41.0%) and Hymenoptera (38.5%) compared to Diptera and Araneae with less than 5% recorded across exclosures. Thus, morphospecies within the least abundant orders, namely Diptera and Araneae, were represented by singletons that were unique to particular exclosures compared to the most abundant arthropod orders (e.g., Coleoptera and Hymenoptera). We conclude that long-term mammal grazing enhances species richness and niche composition together with sparse and unique arthropods in the protected savannas. Therefore, managed grazing regimes can serve as a tool for maintaining the integrity of the protected savannas.
A new method for estimating growth and fertility rates using age-at-death ratios in small skeletal samples: The effect of mortality and stochastic variation

The common procedure for reconstructing growth and fertility rates from skeletal samples involves regressing a growth or fertility rate on the age-at-death ratio, an indicator that captures the proportion of children and juveniles in a skeletal sample. Current methods derive formulae for predicting growth and fertility rates in skeletal samples from modern reference populations with many deaths, although recent levels of mortality are not good proxies for prehistoric populations, and stochastic error may considerably affect the age distributions of deaths in small skeletal samples. This study addresses these issues and proposes a novel algorithm allowing a customized prediction formula to be produced for each target skeletal sample, which increases the accuracy of growth and fertility rate estimation. Every prediction equation is derived from a unique reference set of simulated skeletal samples that match the target skeletal sample in size and assumed mortality level of the population that the target skeletal sample represents. The mortality regimes of reference populations are based on model life tables in which life expectancy can be flexibly set between 18 and 80 years. Regression models provide a reliable prediction; the models explain 83–95% of total variance. Due to stochastic variation, the prediction error is large when the estimate is based on a small number of skeletons but decreases substantially with increasing sample size. The applicability of our approach is demonstrated by a comparison with baseline estimates, defined here as predictions based on the widely used Bocquet-Appel (2002, doi: 10.1086/342429) equation.
Morpho-biometric characterization of indigenous chicken ecotypes in north-western Ethiopia

Morphological characterization of Animal Genetic Resources is the first step to documenting diversity and designing breed specific breeding programs. The current study characterized the morpho-biometric variation of indigenous chicken ecotypes prevailing in northwestern Ethiopia. A multi-stage purposive, stratified, and random sampling method was employed to select the study areas and chickens. A total of 1200 adult chickens were sampled and characterized for 12 qualitative and 11 quantitative traits. Univariate and multivariate data analysis methods were employed to analyze the data using SAS and R statistical software. Red plumage colour (33.2%), white and red earlobe colour (73.8%) and yellow shank colour (57.0%) were the most predominant colour trait categories. Sex, agro-ecology, location, and the interaction of sex and location had a highly significant (p<0.001) effect on all body measurements. Shank traits were found to have the highest discriminating power in both sexes. The overall classification rates for the female and male sample populations were 57.47% and 69.97%, respectively. The squared Mahalanobis distances between sites were significant (p<0.001) for both sexes. The longest distance was obtained between North Achefer and Banja (19.25) and between North Achefer and Dembecha (16.80) in female and male chickens, respectively. In female chickens, canonical variates 1 (CAN 1) and 2 (CAN 2) explained 82% of total variation and distinctly separated the sample populations of North Achefer and Jawi from others. In male chickens, 90% of the total variance is explained by CAN1, CAN2, and CAN3, which distinctly separate the sample populations of the North Achefer, Sinan, and Jawi, among others. Using cluster analysis, the indigenous chickens found in the study area could be classified into four ecotypes: ecotype 1 (Banja, Dembecha, and Aneded), ecotype 2 (North Achefer), ecotype 3 (Sinan), and ecotype 4 (Jawi).
Pregnancy outcomes in women with gestational hypertension and preeclampsia at Paropakar Maternity and Women’s Hospital, Nepal: A retrospective study

Introduction Gestational hypertension and preeclampsia are the most common types of hypertensive disorder in pregnancy and these conditions are associated with adverse maternal and fetal outcomes. This study aims to determine the differences in pregnancy outcomes in women with gestational hypertension and preeclampsia. Methods A retrospective study was done at The Paropakar Maternity and Women’s Hospital, a tertiary level hospital, in the Kathmandu, Nepal. Pregnant women who had given birth at the hospital between September 17 and December 18 of 2017 were included. Data were obtained from the non-digitalized hospital records. The adjusted odds ratio (AOR) and 95% confidence interval were computed using logistic regression analysis. Multivariable analysis of pregnancy outcomes (cesarean sections, low birth weight, and preterm birth) was adjusted for maternal age, parity, twin birth, gestational age, calcium supplementation, and maternal co-morbidity. Results Preeclampsia was strongly associated with cesarean section compared to normal pregnancies (OR = 8.11, p<0.001). Whereas the odds of cesarean section among women with gestational hypertension was almost 2 times (OR = 1.89, p<0.001). Preterm birth was not significantly associated with gestational hypertension but was associated with preeclampsia (OR = 3.39, p<0.001). Gestational hypertension and preeclampsia were not associated with low birth weight. Conclusion In Nepal, women who develop preeclampsia seem at higher risk of having adverse pregnancy outcomes than women with gestational hypertension. These findings should be considered by national health authorities and other health organizations when setting new priorities to improve pregnancy outcomes.
Corridor quality buffers extinction under extreme droughts in experimental metapopulations

Abstract Corridors with good‐quality habitats maintain the spatial dynamics of metapopulations by promoting dispersal between habitat patches, potentially buffering populations, and communities against continued global change. However, this function is threatened by habitats becoming increasingly fragmented, and habitat matrices becoming increasingly inhospitable, potentially reducing the resilience and persistence of populations. Yet, we lack a clear understanding of how reduced corridor quality interacts with rates of environmental change to destabilize populations. Using laboratory microcosms containing metapopulations of the Collembola Folsomia candida, we investigate the impact of corridor quality on metapopulation persistence under a range of simulated droughts, a key stressor for this species. We manipulated both drought severity and the number of patches affected by drought across landscapes connected by either good‐ or poor‐quality corridors. We measured the time of metapopulation extinction, the maximum rate of metapopulation decline, and the variability of abundance among patches as criteria to evaluate the persistence ability of metapopulations. We show that while drought severity negatively influenced the time of metapopulation extinction and the increase in drought patches caused metapopulation decline, these results were mitigated by good‐quality corridors, which increased metapopulation persistence time and decreased both how fast metapopulations declined and the interpatch variability in abundances. Our results suggest that enhancing corridor quality can increase the persistence of metapopulations, increasing the time available for conservation actions to take effect, and/or for species to adapt or move in the face of continued stress. Given that fragmentation increases the isolation of habitats, improving the quality of habitat corridors may provide a useful strategy to enhance the resistance of spatially structured populations.
Protective effect of astaxanthin and metformin in the liver of rats in which the polycystic ovary syndrome model was formed by giving letrozole

Objective(s): In this study, the effects of astaxanthin on liver tissue in rats with polycystic ovary syndrome (PCOS) were evaluated. Materials and Methods: Fifty-four Spraque-Dawley rats were divided into 9 groups: Groups: Control, PCOS, PCOS+Metformin (Met), PCOS+ Astaxanthin (ASX)10, PCOS+ASX20, PCOS+ASX40, PCOS+Met+ASX10, PCOS+Met+ASX20, and PCOS+Met+ASX40. PCOS was induced in female rats by oral administration of letrozole (1 mg/kg) for 21 days. Rats were treated with ASX (10 mg/kg), ASX (20 mg/kg), ASX (40 mg/kg), and metformin (20 mg/kg) for 7 days after PCOS induction. At the end of the experiment, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured in the liver tissue. The liver was stained with hematoxylin/eosin for histological examination. Additionally, NF-kB and caspase 3 were analyzed immunohistochemically. Results: A remarkable abnormality was observed in the biochemical and histological parameters in the liver tissue of the PCOS model rats. Astaxanthin dose-dependently normalized the MDA level. Additionally, astaxanthin showed a protective effect by increasing the SOD level and increasing its antioxidant activities. We observed that administration of astaxanthin in addition to metformin applied in the standard was more effective. Caspase 3 and NF-kB immune positivity was lower in the groups given astaxanthin compared with PCOS. Histologically, it was observed that astaxanthin improved the deteriorated liver morphology in the letrozole-induced PCOS group. Conclusion: According to our results, it was observed that astaxanthin had antioxidant, anti-inflammatory and anti-apoptotic effects on PCOS in the treatment groups. Therefore, it was concluded that astaxanthin may have a protective effect against PCOS side effects.
Evaluation of the Impact of BaP Exposure on the Gut Microbiota and Allergic Responses in an OVA-Sensitized Mouse Model

Background: Exposure to environmental pollutants, including benzo[a]pyrene (BaP), has been implicated in allergic diseases and intestinal microbiota homeostasis, but the environment–microbiota–immunity triangular relationship and to what extent BaP-induced remodeling of the gut microbiota contributes to intestinal allergic inflammation remain to be established. Objectives: We investigated the impact of BaP on intestinal allergic inflammation and examined the relationship between this effect and gut microbiota dysbiosis. We explored the potential ability of intestinal bacteria to degrade BaP and alleviate cytotoxicity as a detoxification strategy to counteract the effects of BaP exposure. Methods: We combined microbiome shotgun metagenomics with animal histological and intestinal allergic inflammatory responses to assess the effects of BaP (50μg/mouse per day) in a 23-d toxicity test in antigen-induced allergic female mice. In addition, genome annotation, quantitative analysis of BaP, and in vitro cytotoxicity-tests using CaCo-2 cells were conducted to infer the role of intestinal bacteria in BaP detoxification. Results: BaP exposure impacted the taxonomic composition and the functional potential of the gut microbiota and aggravated antigen-induced intestinal allergic inflammatory responses. The level of inflammatory cytokines correlated with the abundance of specific bacterial taxa, including Lachnospiraceae bacterium 28-4 and Alistipes inops. We identified 614 bacteria harboring genes implicated in the degradation of BaP, and 4 of these bacterial strains were shown to significantly reduce the cytotoxicity of BaP to CaCo-2 cells in vitro. Discussion: Using allergic female mice as a model, we investigated the relationship between BaP, microbiota, and host immune reactions, highlighting the role of gut bacteria in BaP-aggravated allergic reactions. Our findings offer novel insight toward establishing the causal relationship between BaP exposure and the occurrence of allergic disorders. Identifying gut bacteria that degrade BaP may provide new strategies for ameliorating BaP cytotoxicity. https://doi.org/10.1289/EHP11874
Gestational trophoblastic neoplasia of intermediate trophoblasts: Epithelioid trophoblastic tumor and placental site trophoblastic tumor, a study of morphologic, immunohistochemical, and next generation sequencing

Objective: Gestational trophoblastic tumors are very rare neoplasms. We determined the distinctive morphological, immunohistochemical, and clinical features of placental site trophoblastic tumors (PSTT) and epithelioid trophoblastic tumors (ETT) in our cohort. Materials and Methods: Nine cases of PSTT and four cases of ETT were retrieved from the archives. Histomorphologic, immunohistochemical, and clinical features were noted. A molecular study was performed on one PSTT and one ETT case using next-generation sequencing. Results: While the nodular pattern, geographic necrosis, and extracellular eosinophilic globules were peculiar to ETTs, vessel wall affinity, marked pleomorphism, intranuclear pseudoinclusion, spindle tumor cell, and vacuolar degeneration were more specific for PSTTs in our series. An immunohistochemical panel of p63, hPL, and CD146 were helpful for the exact typing of the tumor. p63 positivity supports the ETT and diffuse staining of hPL and CD146 supports the PSTT diagnosis. Three of the patients with metastatic disease (lung and brain metastasis) except one have a high mitotic count (12 and 8) and a long interval between (8 and 10 years) antecedent pregnancy and diagnosis. While KIT and TP53 mutations were observed only in PSTT, amino acid changes in KDR, APC, and SMAD4 genes were detected both in the ETT and PSTT cases. Conclusion: In the prediction of metastasis, the long intervals between antecedent pregnancy and diagnosis, deep myometrial invasion, mitotic count, and Ki67 proliferation index were involved rather than other histomorphological parameters, but none of the parameters is an absolute predictor of the metastasis.
The role of different Doppler parameters in predicting adverse neonatal outcomes in fetuses with late-onset fetal growth restriction

Objective: The aim of this study is to clarify the role of different Doppler parameters such as umbilicocerebral ratio (UCR), cerebroplacentouterine ratio (CPUR), aortic isthmus, renal artery, and umbilical vein flow Doppler in predicting adverse neonatal outcomes in fetuses with late -onset fetal growth restriction. Materials and Methods: The study included all patients diagnosed with fetal growth restriction at 32-39 weeks’ gestation between 01/02/2020 and 01/02/2022 and treated at the Department of Obstetrics and Gynecology, Inonu University School of Medicine. Results: Patients included in the study had a median gestational week at delivery of 37 (minimum 33+0-maximum 39+0), median CPR of 1.42 (minimum-maximum 0.43-3.57), and median UCR of 0.7 (minimum-maximum 0.28-2.3). Receiver operating characteristic analysis was performed to determine the performance of the measured obstetric Doppler parameters in predicting the development of adverse neonatal outcomes. Umbilical venous blood flow showed the best performance in predicting adverse neonatal outcomes [area under the curve 0.952, 95% confidence interval (CI) 0.902-0.981, p<0.001]. Multivariate logistic regression analysis showed that fetuses with abnormal CPUR had a 4.5-fold (95% CI 0.084-0.583, p=0.02) increased risk of adverse neonatal outcome, whereas fetuses with abnormal umbilical venous flow had a 1.07-fold (95% CI 0.903-0.968, p<0.001) increased risk of adverse neonatal outcome. Conclusion: The results of this study demonstrate that the use of UCR, CPUR, umbilical venous flow, and aortic isthmus PI Doppler parameters along with umbilical artery PI and CPR are effective in predicting adverse neonatal outcomes in fetuses with late -onset fetal growth restriction.
Metformin-Induced Receptor Turnover Alters Antibody Accumulation in HER-Expressing Tumors

Visual Abstract Metformin has effects beyond its antihyperglycemic properties, including altering the localization of membrane receptors in cancer cells. Metformin decreases human epidermal growth factor receptor (HER) membrane density. Depletion of cell-surface HER decreases antibody–tumor binding for imaging and therapeutic approaches. Here, we used HER-targeted PET to annotate antibody–tumor binding in mice treated with metformin. Methods: Small-animal PET annotated antibody binding in HER-expressing xenografts on administration of an acute versus a daily dose schedule of metformin. Analyses at the protein level in the total, membrane, and internalized cell extracts were performed to determine receptor endocytosis, HER surface and internalized protein levels, and HER phosphorylation. Results: At 24 h after injection of radiolabeled anti-HER antibodies, control tumors had higher antibody accumulation than tumors treated with an acute dose of metformin. These differences were temporal, and by 72 h, tumor uptake in acute cohorts was similar to uptake in control. Additional PET imaging revealed a sustained decrease in tumor uptake on daily metformin treatment compared with control and acute metformin cohorts. The effects of metformin on membrane HER were reversible, and after its removal, antibody–tumor binding was restored. The time- and dose-dependent effects of metformin-induced HER depletion observed preclinically were validated with immunofluorescence, fractionation, and protein analysis cell assays. Conclusion: The findings that metformin decreases cell-surface HER receptors and reduces antibody–tumor binding may have significant implications for the use of antibodies targeting these receptors in cancer treatment and molecular imaging.