Miracle-dz/UniFAR-FTUs huggingface dataset:
Cloning and Functional Characterization of Putative Escherichia coli ABC Multidrug Efflux Transporter YddA

A putative multidrug efflux gene, yddA, was cloned from the Escherichia coli K-12 strain. A drug- sensitive strain of E. coli missing the main multidrug efflux pump AcrB was constructed as a host and the yddA gene was knocked out in wild-type (WT) and drug-sensitive E. coliΔacrB to study the yddA function. Sensitivity to different substrates of WT E.coli, E. coliΔyddA, E. coliΔacrB and E. coliΔacrBΔyddA strains was compared with minimal inhibitory concentration (MIC) assays and fluorescence tests. MIC assay and fluorescence test results showed that YddA protein was a multidrug efflux pump that exported multiple substrates. Three inhibitors, ortho-vanadate, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and reserpine, were used in fluorescence tests. Ortho-vanadate and reserpine significantly inhibited the efflux and increased accumulation of ethidium bromide and norfloxacin, while CCCP had no significant effect on YddA-regulated efflux. The results indicated that YddA relies on energy released from ATP hydrolysis to transfer the substrates and YddA is an ABC-type multidrug exporter. Functional study of unknown ATP-binding cassette (ABC) superfamily transporters in the model organism E. coli is conducive to discovering new multidrug resistance-reversal targets and providing references for studying other ABC proteins of unknown function.
Examining the role of fundamental psychological needs in the development of metadehumanization: A multi-population approach.

In the present paper, we investigate dehumanization processes from a victim perspective. We propose that dehumanization experiences, that is metadehumanization, arise from people's feelings that their fundamental human needs are thwarted and that such experiences influence their emotions, self-esteem, and coping strategies. Our model is put at test in three contexts involving different types of dehumanization victims: Women (Study 1a, N = 349), patients with severe alcohol use disorder (Study 1b, N = 120), and employees in organizations (Study 1c, N = 347). Our integrated model of metadehumanization, which considers both its antecedents and consequences, proved stable across contexts and populations and therefore helps building bridges between different psychological disciplines in which dehumanization occurs.
Oncobiosis and Microbial Metabolite Signaling in Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma is one of the most lethal cancers in both men and women, with a median five-year survival of around 5%. Therefore, pancreatic adenocarcinoma represents an unmet medical need. Neoplastic diseases, such as pancreatic adenocarcinoma, often are associated with microbiome dysbiosis, termed oncobiosis. In pancreatic adenocarcinoma, the oral, duodenal, ductal, and fecal microbiome become dysbiotic. Furthermore, the pancreas frequently becomes colonized (by Helicobacter pylori and Malassezia, among others). The oncobiomes from long- and short-term survivors of pancreatic adenocarcinoma are different and transplantation of the microbiome from long-term survivors into animal models of pancreatic adenocarcinoma prolongs survival. The oncobiome in pancreatic adenocarcinoma modulates the inflammatory processes that drive carcinogenesis. In this review, we point out that bacterial metabolites (short chain fatty acids, secondary bile acids, polyamines, indole-derivatives, etc.) also have a role in the microbiome-driven pathogenesis of pancreatic adenocarcinoma. Finally, we show that bacterial metabolism and the bacterial metabolome is largely dysregulated in pancreatic adenocarcinoma. The pathogenic role of additional metabolites and metabolic pathways will be identified in the near future, widening the scope of this therapeutically and diagnostically exploitable pathogenic pathway in pancreatic adenocarcinoma.
Kinesin family member 11 is a potential therapeutic target and is suppressed by microRNA‐30a in breast cancer

Kinesin family member 11 (KIF11) is a plus end‐directed kinesin indispensable for the formation of the bipolar spindle in metaphase, where it objects to the action of minus end‐directed molecular motors. Here, we hypothesize that KIF11 might be a therapeutic target of breast cancer and regulated by miR‐30a. Cell Counting Kit 8 assays were used to investigate cell proliferation. Invasion assays were used to survey the motility of cells. Kaplan‐Meier and Cox proportional analyses were employed for this outcome study. The prognostic significance and performance of KIF11 were validated on 17 worldwide independent microarray datasets and two The Cancer Genome Atlas‐Breast Invasive Carcinoma sets. microRNA was predicted targeting KIF11 through sequence alignment in microRNA.org and confirmed by coexpression analysis in human breast cancer samples. Dual‐luciferase reporter assays were employed to validate the interaction between miR‐30a and KIF11 further. Higher KIF11 mRNA levels and lower miR‐30a were significantly associated with poor survival of breast cancer patients. Inhibition of KIF11 by small‐hairpin RNA significantly reduced the proliferation and invasion capabilities of the breast cancer cells. Meanwhile, downregulation of KIF11 could enhance the cytotoxicity of adriamycin in breast cancer cell lines MCF‐7 and MDA‐MB‐231. A population study also validated that chemotherapy and radiotherapy significantly improved survival in early‐stage breast cancer patients with low KIF11 expression levels. Further bioinformatics analysis demonstrated that miR‐30a could interact with KIF11 and validated by dual‐luciferase reporter assays. Therefore, KIF11 is a potential therapeutic target of breast cancer. miR‐30a could specifically interact with KIF11 and suppress its expression in breast cancer.
Genomic Analysis Using Bayesian Methods under Different Genotyping Platforms in Korean Duroc Pigs

Simple Summary This study investigated the informative regions and the efficiency of genomic predictions for backfat thickness, days to 90 kg body weight, loin muscle area, and lean percentage in Korean Duroc pigs. The several regions of the genome were identified and a significant marker was found near the MC4R gene for growth and production-related traits. No differences in genomic accuracy were identified on the basis of the Bayesian approaches in these four growth and production-related traits. The genomic accuracy is improved by using deregressed estimated breeding values including parental information as a response variable in Korean Duroc pigs. Abstract Genomic evaluation has been widely applied to several species using commercial single nucleotide polymorphism (SNP) genotyping platforms. This study investigated the informative genomic regions and the efficiency of genomic prediction by using two Bayesian approaches (BayesB and BayesC) under two moderate-density SNP genotyping panels in Korean Duroc pigs. Growth and production records of 1026 individuals were genotyped using two medium-density, SNP genotyping platforms: Illumina60K and GeneSeek80K. These platforms consisted of 61,565 and 68,528 SNP markers, respectively. The deregressed estimated breeding values (DEBVs) derived from estimated breeding values (EBVs) and their reliabilities were taken as response variables. Two Bayesian approaches were implemented to perform the genome-wide association study (GWAS) and genomic prediction. Multiple significant regions for days to 90 kg (DAYS), lean muscle area (LMA), and lean percent (PCL) were detected. The most significant SNP marker, located near the MC4R gene, was detected using GeneSeek80K. Accuracy of genomic predictions was higher using the GeneSeek80K SNP panel for DAYS (Δ2%) and LMA (Δ2–3%) with two response variables, with no gains in accuracy by the Bayesian approaches in four growth and production-related traits. Genomic prediction is best derived from DEBVs including parental information as a response variable between two DEBVs regardless of the genotyping platform and the Bayesian method for genomic prediction accuracy in Korean Duroc pig breeding.
Survival of Drosophila germline stem cells requires the chromatin-binding protein Barrier-to-autointegration factor

ABSTRACT The nuclear lamina (NL) is an extensive protein network that underlies the inner nuclear envelope. This network includes LAP2-emerin-MAN1 domain (LEM-D) proteins that associate with the chromatin and DNA-binding protein Barrier-to-autointegration factor (BAF). Here, we investigate the partnership between three NL Drosophila LEM-D proteins and BAF. In most tissues, only Emerin/Otefin is required for NL enrichment of BAF, revealing an unexpected dependence on a single LEM-D protein. Prompted by these observations, we studied BAF contributions in the ovary, a tissue where Emerin/Otefin function is essential. We show that germ cell-specific BAF knockdown causes phenotypes that mirror emerin/otefin mutants. Loss of BAF disrupts NL structure, blocks differentiation and promotes germ cell loss, phenotypes that are partially rescued by inactivation of the ATR and Chk2 kinases. These data suggest that, similar to emerin/otefin mutants, BAF depletion activates the NL checkpoint that causes germ cell loss. Taken together, our findings provide evidence for a prominent NL partnership between the LEM-D protein Emerin/Otefin and BAF, revealing that BAF functions with this partner in the maintenance of an adult stem cell population. Summary: Emerin/Otefin, a Drosophila nuclear lamina LEM-D protein, plays a major role in localizing Barrier-to-autointegration factor to the nuclear lamina, a partnership that contributes to stem cell maintenance.
HIITing the brain with exercise: mechanisms, consequences and practical recommendations

The increasing number of older adults has seen a corresponding growth in those affected by neurovascular diseases, including stroke and dementia. Since cures are currently unavailable, major efforts in improving brain health need to focus on prevention, with emphasis on modifiable risk factors such as promoting physical activity. Moderate‐intensity continuous training (MICT) paradigms have been shown to confer vascular benefits translating into improved musculoskeletal, cardiopulmonary and cerebrovascular function. However, the time commitment associated with MICT is a potential barrier to participation, and high‐intensity interval training (HIIT) has since emerged as a more time‐efficient mode of exercise that can promote similar if not indeed superior improvements in cardiorespiratory fitness for a given training volume and further promote vascular adaptation. However, randomised controlled trials (RCTs) investigating the impact of HIIT on the brain are surprisingly limited. The present review outlines how the HIIT paradigm has evolved from a historical perspective and describes the established physiological changes including its mechanistic bases. Given the dearth of RCTs, the vascular benefits of MICT are discussed with a focus on the translational neuroprotective benefits including their mechanistic bases that could be further potentiated through HIIT. Safety implications are highlighted and components of an optimal HIIT intervention are discussed including practical recommendations. Finally, statistical effect sizes have been calculated to allow prospective research to be appropriately powered and optimise the potential for detecting treatment effects. Future RCTs that focus on the potential clinical benefits of HIIT are encouraged given the prevalence of cognitive decline in an ever‐ageing population.
Prevalence of polypoidal choroidal vasculopathy in Indian population: Risk factors, clinical and imaging characteristics

Aim To assess prevalence, clinical presentation and multimodal imaging characteristics of polypoidal choroidal vasculopathy (PCV) in a hospital-based setting in South India. Methods Electronic medical records (EMR) of new patients presenting with suspected clinical signs of wet age-related macular degeneration (AMD) in a tertiary hospital from January to December 2016 were retrospectively analyzed using keywords and filtered for patient who underwent multimodal imaging. Clinical presentations were categorized into predominantly hemorrhagic, exudative or mixed pattern. The imaging features were compared in these clinical groups. The multimodal images were graded by two masked graders and discrepancies between them were settled by a senior arbitrator. Results Of the 147 clinically suspicious cases of PCV out of 785 patients with clinical presentation of AMD as recorded in the EMR, 73 (49.7%) patients had a multimodal imaging diagnosis of PCV. There was no difference in the demography, distribution of polyps, ICGA and OCT characteristics in eyes presenting with hemorrhagic, exudative or mixed clinical features. Conclusion Approximately half of South Asian patients presenting with clinical features of neovascular AMD harbor PCV irrespective of their clinical presentation and so we recommend that multimodal imaging is done in all cases of suspicious neovascular AMD in Indian population.
IL-36 signaling in keratinocytes controls early IL-23 production in psoriasis-like dermatitis

IL-36 signaling in keratinocytes is crucial for Aldara-induced psoriasis-like dermatitis by controlling IL-23/IL-17A/IL-22 production and neutrophil recruitment at the third day of treatment. IL-36R signaling plays an important role in the pathogenesis of psoriasis. We ought to assess the specific function of IL-36R in keratinocytes for the pathology of Aldara-induced psoriasis-like dermatitis. Il36rΔK mice presenting deletion of IL-36R in keratinocytes were similarly resistant to Aldara-induced ear inflammation as Il36r−/− mice, but acanthosis was only prevented in Il36r−/− mice. FACS analysis revealed that IL-36R signaling in keratinocytes is mandatory for early neutrophil infiltration in Aldara-treated ears. RNASeq and qRT-PCR experiments demonstrated the crucial role of IL-36R signaling in keratinocytes for induction of IL-23, IL-17, and IL-22 at early time points. Taken together, our results demonstrate that IL-36R signaling in keratinocytes plays a major role in the induction of Aldara-induced psoriasis-like dermatitis by triggering early production of IL-23/IL-17/IL-22 cytokines and neutrophil infiltration.
Formation of aggregates, icosahedral structures and percolation clusters of fullerenes in lipids bilayers: The key role of lipid saturation

Carbon nanoparticles (CNPs) are attractive materials for a great number of applications but there are serious concerns regarding their influence on health and environment. Here, our focus is on the behavior of fullerenes in lipid bilayers with varying lipid saturations, chain lengths and fullerene concentrations using coarse-grained molecular dynamics (CG-MD) simulations. Our findings show that the lipid saturation level is a key factor in determining how fullerenes behave and where the fullerenes are located inside a lipid bilayer. In saturated and monounsaturated bilayers fullerenes aggregated and formed clusters with some of them showing icosahedral structures. In polyunsaturated lipid bilayers, no such structures were observed: In polyunsaturated lipid bilayers at high fullerene concentrations, connected percolation-like networks of fullerenes spanning the whole lateral area emerged at the bilayer center. In other systems only separate isolated aggregates were observed. The effects of fullerenes on lipid bilayers depend strongly on fullerene aggregation. When fullerenes aggregate, their interactions with the lipid tails change.
Melatonin ameliorates excessive PINK1/Parkin-mediated mitophagy by enhancing SIRT1 expression in granulosa cells of PCOS.

Mitochondrial injury in granulosa cells is associated with the pathogenesis of polycystic ovary syndrome (PCOS). However, the protective effects of melatonin against mitochondrial injury in the granulosa cells of PCOS remain unclear. In this study, decreased mitochondrial membrane potential and mtDNA content, increased number of autophagosomes were found in the granulosa cells of PCOS patients and the DHT-treated KGN cells, with decreased protein level of the autophagy substrate P62 and increased levels of the cellular autophagy markers Beclin-1 and LC3B-II, while the protein levels of PINK1 and Parkin were increased and the level of SIRT1 was decreased. DHT-induced PCOS-like mice also showed enhanced mitophagy and decreased SIRT1 mRNA expression. Melatonin treatment significantly increased the protein level of SIRT1 and decreased the levels of PINK1/Parkin, while ameliorated the mitochondrial dysfunction and PCOS phenotype in vitro and in vivo. However, when the KGN cells were treated with SIRT1 siRNA to knock down SIRT1 expression, melatonin treatment failed to repress the excessive mitophagy. In conclusion, melatonin protects against mitochondrial injury in granulosa cells of PCOS by enhancing SIRT1 expression to inhibit excessive PINK1/Parkin-mediated mitophagy.
In vitro spectroscopic investigation of groove binding interaction of Fe3O4@CaAl-LDH@L-Dopa with calf thymus DNA

Abstract The principal goal of this study is to evaluate the interaction of Fe3O4@CaAl-LDH@L-Dopa and Fe3O4@CaAl-LDH nanoparticles with calf thymus DNA. The magnetic nanoparticles were previously prepared by a chemical co-precipitation method, and the surface of the Fe3O4 nanoparticles was coated with CaAl layered double hydroxides. The antiparkinsonian drug “L-Dopa” was carried by this core–shell nanostructure to achieve the drug delivery system with suitable properties for biological applications. Also, the interaction of Fe3O4@CaAl-LDH@L-Dopa and Fe3O4@CaAl-LDH nanoparticles with CT-DNA was studied using, UV–Visible spectroscopy, viscosity, circular dichroism (CD), and fluorescence spectroscopy techniques. The results of investigations demonstrated that Fe3O4@CaAl-LDH@L-Dopa and Fe3O4@CaAl-LDH nanoparticles have interacted via minor groove binding and intercalated to CT-DNA, respectively.
Plasma hormone levels in the cow

Abstract Progesterone and oestradiol concentrations in the peripheral plasma of 12 dairy cows during the oestrous cycle were determined by competitive protein-binding and radioimmunoassay respectively. The levels of progesterone reached a peak of 6-7 ng/ml in mid-cycle, then began to fall 4 days before oestrus to values of about 1 ng/ml at oestrus and remained low for a further 4 days. Peak levels of oestradiol (11.2 ± 1.3 pg/ml, s.e.) occurred on the day before oestrus and a second peak (7.9 ± 2.9 pg/ml) occurred on Days 6-8 of the cycle.
An Examination of Ability Emotional Intelligence and Its Relationships with Fluid and Crystallized Abilities in a Student Sample

This study investigated correlative, factorial, and structural relationships between scores for ability emotional intelligence in the workplace (measured with the Geneva Emotional Competence Test), as well as fluid and crystallized abilities (measured with the Intelligence Structure Battery), carried out by a 188-participant student sample. Confirming existing research, recognition, understanding, and management of emotions were related primarily to crystallized ability tests measuring general knowledge, verbal fluency, and knowledge of word meaning. Meanwhile, emotion regulation was the least correlated with any other cognitive or emotional ability. In line with research on the trainability of emotional intelligence, these results may support the notion that emotional abilities are subject to acquired knowledge, where situational (i.e., workplace-specific) emotional intelligence may depend on accumulating relevant experiences.
Impact of Electronic Alternatives to Tobacco Cigarettes on Indoor Air Particular Matter Levels

An aerosol study was carried out in a test room measuring particulate matter (PM) with an aerodynamic diameter smaller than 10, 4, 2.5 and 1 µm (PM10, PM4, PM2.5, PM1) before and during the use of electronic alternatives to tobacco cigarettes (EATC) IQOS®, GLO®, JUUL®, with different kinds of sticks/pods, as well as during the smoking of a conventional tobacco cigarette. The aerosol was mainly in the PM1 size range (>95%). All studied EATCs caused lower indoor PM1 concentrations than conventional tobacco cigarettes. Nevertheless, they determined a worsening of indoor-PM1 concentration that ranged from very mild for JUUL®—depending on the pod used—to considerably severe for IQOS® and GLO®. Median values ranged from 11.00 (Iqos3 and Juul2) to 337.5 µg m−3 (Iqos4). The high variability of particle loadings was attributed both to the type of stick/pod used and to the different way of smoking of volunteers who smoked/vaped during the experiments. Moreover, during vaping IQOS® and GLO® indoor PM1 concentrations reach levels by far higher than outdoor concentrations that range from 14 to 21 µg m−3, especially during the exhalation of the smoke. From these results emerge an urgent need of a legislative regulation limiting the use of such devices in public places.
Covid-19: concerns grow over inflammatory syndrome emerging in children

Doctors in the UK have been warned over a rising number of children presenting with a multisystem inflammatory state and needing intensive care. In an urgent alert shared by North Central London Clinical Commissioning Group and the Paediatric Intensive Care Society,1 doctors were told that while the unspecified number of cases may be connected to the current pandemic, the symptoms have been observed in both children who have tested positive and negative for covid-19. “There is a growing concern that a SARS-CoV-2 related inflammatory syndrome is emerging in children in the UK or that there may be another as yet unidentified infectious pathogen associated with these cases,” the letter said. Child health leaders have stressed that there is currently a small number of cases and that advice to …
Validating the Chinese geriatric trigger tool and analyzing adverse drug event associated risk factors in elderly Chinese patients: A retrospective review

Objective The aim was to evaluate the performance of the initial Chinese geriatric trigger tool to detect adverse drug events (ADEs) in Chinese older patients, to attempt to shorten this list for improving the efficiency of the trigger tool, and to study the incidence and characteristics of ADEs in this population. Methods A sample of 25 cases was randomly selected per half a month from eligible patients who aged 60 years and older, hospitalized more than 24 hours, and discharged or died between January 1, 2015 and December 31, 2017 in West China hospital. A two-stage retrospective chart review of the included inpatients were conducted. ADEs were detected using a list of 42 triggers previously selected by an expert panel by means of a Delphi method. The number of triggers identified and ADEs detected were recorded and the positive predictive value (PPV) of each trigger was calculated to select the most efficient triggers. Several variables were recorded, including age, sex, number of diseases, length of hospital stay and so on, to analyze the risk factor of ADEs. Results Among 1800 patients, 1646 positive triggers and 296 ADEs were detected in 234 (13.00%) patients. Older patients who were younger, had more medications, longer stays or more admission, and did not experience surgical operation more likely experienced ADEs. Triggers with PPV less than 5% were eliminated, which resulted in the upgraded version of Chinese geriatric trigger tool of 20 triggers with a PPV of 28.50%. This upgraded tool accounted for 99.66% of all ADEs detected. Conclusions The upgraded version of Chinese geriatric trigger tool was an efficient tool for identifying ADEs in Chinese older patients. Future, the trigger tool could be incorporated into routine screen systems to provide real-time identification of ADEs, thereby enabling timely clinical interventions.