Miracle-dz/UniFAR-FTUs huggingface dataset:
comCDE (Competence) Operon Is Regulated by CcpA in Streptococcus pneumoniae D39

Streptococcus pneumoniae is a major cause of bacterial infections in humans, such as pneumonia, bacteremia, meningitis, otitis media, and sinusitis. Like most streptococci, S. pneumoniae is naturally competent and employs this ability to augment its adaptive evolution. ABSTRACT Natural transformation plays an important role in the formation of drug-resistant bacteria. Exploring the regulatory mechanism of natural transformation can aid the discovery of new antibacterial targets and reduce the emergence of drug-resistant bacteria. Competence is a prerequisite of natural transformation in Streptococcus pneumoniae, in which comCDE operon is the core regulator of competence. To date, only ComE has been shown to directly regulate comCDE transcription. In this study, a transcriptional regulator, the catabolite control protein A (CcpA), was identified that directly regulated comCDE transcription. We confirmed that CcpA binds to the cis-acting catabolite response elements (cre) in the comCDE promoter region to regulate comCDE transcription and transformation. Moreover, CcpA can coregulate comCDE transcription with phosphorylated and dephosphorylated ComE. Regulation of comCDE transcription and transformation by CcpA was also affected by carbon source signals. Together, these insights demonstrate the versatility of CcpA and provide a theoretical basis for reducing the emergence of drug-resistant bacteria. IMPORTANCE Streptococcus pneumoniae is a major cause of bacterial infections in humans, such as pneumonia, bacteremia, meningitis, otitis media, and sinusitis. Like most streptococci, S. pneumoniae is naturally competent and employs this ability to augment its adaptive evolution. The current study illustrates CcpA, a carbon catabolite regulator, can participate in the competence process by regulating comCDE transcription, and this process is regulated by different carbon source signals. These hidden abilities are likely critical for adaptation and colonization in the environment.
Activation of the Plasmodium Egress Effector Subtilisin-Like Protease 1 Is Mediated by Plasmepsin X Destruction of the Prodomain

Malaria parasites replicate inside a parasitophorous vacuole within the host red blood cells. The exit of mature progeny from the infected host cells is essential for further dissemination. ABSTRACT Following each round of replication, daughter merozoites of the malaria parasite Plasmodium falciparum escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by a parasite serine protease, subtilisin-like protease 1 (SUB1), regulates the membrane breakdown. SUB1 activation involves primary autoprocessing of the 82-kDa zymogen to a 54-kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) postcleavage. A second processing step converts p54 to the terminal 47-kDa (p47) form of SUB1. Although the aspartic protease plasmepsin X (PM X) has been implicated in the activation of SUB1, the mechanism remains unknown. Here, we show that upon knockdown of PM X, the inhibitory p31-p54 complex of SUB1 accumulates in the parasites. Using recombinant PM X and SUB1, we show that PM X can directly cleave both p31 and p54. We have mapped the cleavage sites on recombinant p31. Furthermore, we demonstrate that the conversion of p54 to p47 can be effected by cleavage at either SUB1 or PM X cleavage sites that are adjacent to one another. Importantly, once the p31 is removed, p54 is fully functional inside the parasites, suggesting that the conversion to p47 is dispensable for SUB1 activity. Relief of propiece inhibition via a heterologous protease is a novel mechanism for subtilisin activation. IMPORTANCE Malaria parasites replicate inside a parasitophorous vacuole within the host red blood cells. The exit of mature progeny from the infected host cells is essential for further dissemination. Parasite exit is a highly regulated, explosive process that involves membrane breakdown. To do this, the parasite utilizes a serine protease called SUB1 that proteolytically activates various effector proteins. SUB1 activity is dependent on an upstream protease called PM X, although the mechanism was unknown. Here, we describe the molecular basis for PM X-mediated SUB1 activation. PM X proteolytically degrades the inhibitory segment of SUB1, thereby activating it. The involvement of a heterologous protease is a novel mechanism for subtilisin activation.
Cr(III) and Cr(VI) removal in floating treatment wetlands (FTWs) using Typha domingensis

Abstract Floating treatment wetlands (FTWs) are a cost-effective ecological engineering tool for the restoration of polluted water bodies. The aims of this work were to evaluate the removal of Cr(III) and Cr(VI) by FTWs using Typha domingensis, and to assess Cr accumulation and distribution in plant tissues and sediment. Treatments were 5 and 10 mg L−1 of Cr(III), and 5 and 10 mg L−1 of Cr(VI), with and without FTWs, and biological control (BC) with FTW without Cr addition. Both Cr species were efficiently removed from water in all treatments (Cr removal > 80%). Cr concentration in sediments of treatment without FTWs was significantly higher than in sediments of treatments with FTWs, indicating that T. domingensis was directly involved in Cr removal. In sediment, Cr was mainly bound to the organic matter in all treatments with a low risk of future release under FTW conditions. T. domingensis demonstrated tolerance to both Cr species at 5 and 10 mg L−1 with Cr accumulated mainly in the roots in all treatments. The use of FTWs planted with T. domingensis is a suitable tool to remediate water bodies contaminated with Cr. NOVELTY STATEMENT This study evaluates the removal efficiency of Cr(III) and Cr(V) in Floating Treatment Wetlands planted with Typha domingensis in greenhouse experiments. Cr accumulation and distribution in plant tissues and different sediment fractions were also assessed
MmuPV1 E7’s interaction with PTPN14 delays Epithelial differentiation and contributes to virus-induced skin disease

Human papillomaviruses (HPVs) contribute to approximately 5% of all human cancers. Species-specific barriers limit the ability to study HPV pathogenesis in animal models. Murine papillomavirus (MmuPV1) provides a powerful tool to study the roles of papillomavirus genes in pathogenesis arising from a natural infection. We previously identified Protein Tyrosine Phosphatase Non-Receptor Type 14 (PTPN14), a tumor suppressor targeted by HPV E7 proteins, as a putative cellular target of MmuPV1 E7. Here, we confirmed the MmuPV1 E7-PTPN14 interaction. Based on the published structure of the HPV18 E7/PTPN14 complex, we generated a MmuPV1 E7 mutant, E7K81S, that was defective for binding PTPN14. Wild-type (WT) and E7K81S mutant viral genomes replicated as extrachromosomal circular DNAs to comparable levels in mouse keratinocytes. E7K81S mutant virus (E7K81S MmuPV1) was generated and used to infect FoxN/Nude mice. E7K81S MmuPV1 caused neoplastic lesions at a frequency similar to that of WT MmuPV1, but the lesions arose later and were smaller than WT-induced lesions. The E7K81S MmuPV1-induced lesions also had a trend towards a less severe grade of neoplastic disease. In the lesions, E7K81S MmuPV1 supported the late (productive) stage of the viral life cycle and promoted E2F activity and cellular DNA synthesis in suprabasal epithelial cells to similar degrees as WT MmuPV1. There was a similar frequency of lateral spread of infections among mice infected with E7K81S or WT MmuPV1. Compared to WT MmuPV1-induced lesions, E7K81S MmuPV1-induced lesions had a significant expansion of cells expressing differentiation markers, Keratin 10 and Involucrin. We conclude that an intact PTPN14 binding site is necessary for MmuPV1 E7’s ability to contribute to papillomavirus-induced pathogenesis and this correlates with MmuPV1 E7 causing a delay in epithelial differentiation, which is a hallmark of papillomavirus-induced neoplasia.
Whole body vibration condition evaluation of aero-engine on grey correlation degree

A condition evaluation method for aero-engine using whole body vibration based on grey correlation degree has been put forward,and the mathematic principles and arithmetic are also introduced in this paper.Furthermore,the standard database was built up using whole body vibration data of aero-engines as samples.Herewith the concordance degree of aero-engine's actual state to the standard state was evaluated,by calculating the grey correlation degree between the state parameter sequence of the aero-engine being evaluated and its standard parameter sequence.Thus,quantified evaluation of an aero-engine is realized.The calculation results show that the method can be used for correct quantified state evaluation of aero-engine and possess the advantages of simplicity,low computing time consumption,self learning and higher reliability.
Gender differences in the association of polygenic risk and divergent depression trajectories from mid to late life: a national longitudinal study

ABSTRACT Our research fills a critical gap in the depression literature by utilizing a life course perspective to examine gender–gene interactions in association with depression trajectories over time. Using data from the Health and Retirement Study, we estimated multi-level negative binomial and logistic mixed models to analyze gender-specific trajectories of depressive symptoms (CESD-8) and potential clinical depression risk from middle to late adulthood in relation to gender-by-polygenic-risk (PRS) interactions. We found increasingly greater female-male gaps in the CESD-8 scale and a higher probability of clinical depression risk with increasing polygenic risk scores. Furthermore, females’ higher genetic vulnerabilities to depressive conditions than males vary from ages 51 to 90 years, with most salient larger differences at oldest old ages at 76–85 (e.g. 0.28 higher CESD-8 scale for females at ages 76–85 years than for similar-aged males; higher 3.44% probability of depression risk for females at ages 81–85 compared to similar-aged males) followed by old ages at 61–70 years (e.g. about 2.40% higher probability of depression risk for females at ages 61–70 years than for similar-aged males) in comparison to younger ages during middle adulthood. This study contributes to new knowledge of how gender-by-polygenic-risk interactions are associated with depression trajectories across the life course.
Stay or Go: Sulfolobales Biofilm Dispersal Is Dependent on a Bifunctional VapB Antitoxin

Biofilms allow microbes to resist a multitude of stresses and stay proximate to vital nutrients. The mechanisms of entering and leaving a biofilm are highly regulated to ensure microbial survival, but are not yet well described in archaea. ABSTRACT A type II VapB14 antitoxin regulates biofilm dispersal in the archaeal thermoacidophile Sulfolobus acidocaldarius through traditional toxin neutralization but also through noncanonical transcriptional regulation. Type II VapC toxins are ribonucleases that are neutralized by their proteinaceous cognate type II VapB antitoxin. VapB antitoxins have a flexible tail at their C terminus that covers the toxin’s active site, neutralizing its activity. VapB antitoxins also have a DNA-binding domain at their N terminus that allows them to autorepress not only their own promoters but also distal targets. VapB14 antitoxin gene deletion in S. acidocaldarius stunted biofilm and planktonic growth and increased motility structures (archaella). Conversely, planktonic cells were devoid of archaella in the ΔvapC14 cognate toxin mutant. VapB14 is highly conserved at both the nucleotide and amino acid levels across the Sulfolobales, extremely unusual for type II antitoxins, which are typically acquired through horizontal gene transfer. Furthermore, homologs of VapB14 are found across the Crenarchaeota, in some Euryarchaeota, and even bacteria. S. acidocaldarius vapB14 and its homolog in the thermoacidophile Metallosphaera sedula (Msed_0871) were both upregulated in biofilm cells, supporting the role of the antitoxin in biofilm regulation. In several Sulfolobales species, including M. sedula, homologs of vapB14 and vapC14 are not colocalized. Strikingly, Sulfuracidifex tepidarius has an unpaired VapB14 homolog and lacks a cognate VapC14, illustrating the toxin-independent conservation of the VapB14 antitoxin. The findings here suggest that a stand-alone VapB-type antitoxin was the product of selective evolutionary pressure to influence biofilm formation in these archaea, a vital microbial community behavior. IMPORTANCE Biofilms allow microbes to resist a multitude of stresses and stay proximate to vital nutrients. The mechanisms of entering and leaving a biofilm are highly regulated to ensure microbial survival, but are not yet well described in archaea. Here, a VapBC type II toxin-antitoxin system in the thermoacidophilic archaeon Sulfolobus acidocaldarius was shown to control biofilm dispersal through a multifaceted regulation of the archaeal motility structure, the archaellum. The VapC14 toxin degrades an RNA that causes an increase in archaella and swimming. The VapB14 antitoxin decreases archaella and biofilm dispersal by binding the VapC14 toxin and neutralizing its activity, while also repressing the archaellum genes. VapB14-like antitoxins are highly conserved across the Sulfolobales and respond similarly to biofilm growth. In fact, VapB14-like antitoxins are also found in other archaea, and even in bacteria, indicating an evolutionary pressure to maintain this protein and its role in biofilm formation.
Production and Characterization of Two Specific ZIKV Antigens Based on Bioinformatic Analysis and Serological Screening

ABSTRACT Background The high structural similarity between the Zika virus (ZIKV) and other flaviviruses, such as Dengue Virus (DENV), complicates the identification of the infecting virus due to the occurrence of cross-reactions in serological assays. This phenomenon has increased the demand for more specific antigens for immunodiagnostic applications. Methods The present work aimed to identify specific regions of ZIKV and produce unique antigens through computational methods, molecular and microbiological techniques. Results Based on the computational analysis we successfully expressed two recombinant proteins derived from specific regions of the ZIKV. Through serological assays using characterized sera, we observed that the region 146–182 of ZIKV’s E protein, expressed in tandem, was not reactive despite the predictive sensitivity and specificity observed by computer analyses. On the other hand, the non-denatured fraction 220–352 of ZIKV’s NS1 showed greater specificity to IgG+ sera of ZIKV by dot blot and western blot, which highlights its properties as a possible tool in the diagnosis of ZIKV. Conclusion These findings demonstrate that ZIKV NS1 fraction 220–352 is a potential tool that may be applied in the development of serological diagnosis. We also provided data that suggest the non-applicability of the region 146–182 of ZIKV’s protein E in serological assays despite previous indications about its potential based on computational analysis.
Evaluation of mono and combined nitrofurantoin therapy for toxoplasmosis in vivo using murine model

ABSTRACT Toxoplasmosis is a frequent disease with an estimated prevalence of more than one billion human cases worldwide and over one million new infections each year. It is classified as a neglected tropical disease by the CDC since 2019. The disease may pass unnoticed in healthy individuals but could be fatal in the immunocompromised. Moreover, no effective treatment is available against the chronic form of the disease. Available anti-Toxoplasma drugs are associated with many side effects. Therefore, search for new more reliable, more efficient, and less toxic therapeutic agents is a continuous endeavor. This study assesses the potential use of nitrofurantoin, a compound with well-established antimicrobial properties, as a potential anti-Toxoplasma drug in vivo. It compares its efficacy to the commonly used anti-Toxoplasma agent spiramycin by molecular and histopathological methods in acute and chronic infection. The results demonstrate a significant ability to eliminate the parasite (P < 0.001) whether used as mono- or combined therapy with spiramycin in the acute and chronic stages. When compared to the anti-Toxoplasma drug spiramycin, nitrofurantoin achieved similar efficacy in the acute and chronic infection (P = 0.65 and P = 0.096, respectively). However, better results were obtained when using a combination of both drugs (P < 0.001). Additionally, nitrofurantoin showed good inhibitory effects on the inflammatory process in the liver, kidney, and uterus of the experimentally infected animals. In conclusion, nitrofurantoin can be considered as a potential anti-Toxoplasma agent. Nevertheless, further studies are recommended before consideration for clinical trials.
Genome Sequence of a Bangladeshi Strain of Raoultella ornithinolytica, a Pathogen with Metal and Antimicrobial Resistance Genes Isolated from a Pet Cat

Raoultella ornithinolytica is an emerging pathogen that causes human infections. We report the isolation and genome sequencing of R. ornithinolytica from an oral swab of a Persian pet cat in Dhaka, Bangladesh. The genome length was 5,375,160 bp, with 55.9% G+C content. It carries putative genes associated with resistance to antibiotics and metals. ABSTRACT Raoultella ornithinolytica is an emerging pathogen that causes human infections. We report the isolation and genome sequencing of R. ornithinolytica from an oral swab of a Persian pet cat in Dhaka, Bangladesh. The genome length was 5,375,160 bp, with 55.9% G+C content. It carries putative genes associated with resistance to antibiotics and metals.
The need for consensus guidelines to address the mixed legacy of genetic damage assessments for radiofrequency fields

Abstract Purpose This review considers issues related to interpreting the mixed legacy of >300 papers published during the past three decades on possible genotoxic effects of exposure of human and animal tissues to radiofrequency electromagnetic fields (RF-EMF). The main paper reviews the evolution of consensus guidelines for genotoxicity testing and the increasing emphasis on systematic reviews for evaluation of scientific studies for use in health risk assessments. An Appendix considers some issues in assessing the bioeffects literature by examining a subset of genotoxicity publications that employed the comet assay. While most studies found no statistically significant effects of exposure, a significant minority of studies (chiefly, in vivo studies) reported statistically significant effects of exposure. The quality of the studies was highly variable; while several studies were meticulously done and documented, none of these studies were compliant with currently accepted guidelines such as those of the Organization for Economic Cooperation and Development (OECD). Evaluation of the studies using risk of bias (RoB) criteria showed that, in this sample of studies, higher quality studies were less likely to find statistically significant results than those of lower quality. Conclusion The authors conclude that statistical significance should be only one consideration in evaluation of bioeffects studies. Simply listing ‘statistically’ significant effects identified using null hypothesis testing and the criterion p < 0.05 for statistical significance is misleading and uninformative in assessing health risks of exposure. A careful synthesis of evidence is needed, including assessment of study validity, biological significance of reported effects, and coherence of study results with those of other related studies. The authors recommend that all future RF genotoxicity studies intended for use in human health risk assessments and evaluations of the literature should be done in compliance with accepted quality guidelines, i.e. OECD or equivalent guidelines for genotoxicity screening studies and PRISMA or other accepted guideline for reviews of the literature. The positive studies in this group should be redone with tighter quality control to establish the reliability of the findings.
Efficacy of very early interventions on neurodevelopmental outcomes for infants and toddlers at increased likelihood of or diagnosed with autism: A systematic review and meta‐analysis

The aim of this systematic review was to determine the efficacy of very early interventions for infants and toddlers at increased likelihood of or diagnosed with autism for autism symptomatology, developmental outcomes and/or neurocognitive markers. Eight databases were searched (14 April 2022) with inclusion criteria: (i) RCTs with care as usual (CAU) comparison group, (ii) participants at increased likelihood of or diagnosed with autism and aged <24 months corrected age (CA), (iii) parent‐mediated and/or clinician directed interventions, and (iv) outcome measures were autism symptomatology, cognition, language, adaptive skills, or neurocognitive assessments (EEG and eye tracking). Quality was assessed using Risk of Bias 2 and GRADE. Nineteen publications from 12 studies reported on 715 infants and toddlers. There was low to moderate certainty evidence that clinician‐assessed outcomes did not show significant treatment effects for: autism symptomatology (ADOS CSS: MD −0.08, 95% CI −0.61, 0.44, p = 0.75), cognitive outcome (Mullen Scales of Early Learning‐Early Learning Composite (MSEL‐ELC): SMD 0.05, 95% CI −0.19, 0.29, p = 0.67), receptive language (MSEL—Receptive Language: SMD 0.04, 95% CI −0.21, 0.3, p = 0.74) or expressive language (MSEL‐Expressive Language: SMD 0.06, 95% CI −0.1, 0.23, p = 0.45). Neurocognitive outcomes (EEG and eye tracking) were heterogeneous, with inconsistent findings. There is low to moderate certainty evidence that very early interventions have limited impact on neurodevelopmental outcomes by age 3 years.
Phage resistance of Salmonella enterica obtained by transposon Tn5‐mediated SefR gene silent mutation

Salmonella enterica contamination is a primary cause of global food poisoning. Using phages as bactericidal alternatives to antibiotics could confront the issue of drug resistance. However, the problem of phage resistance, especially mutant strains with multiple phage resistance, is a critical barrier to the practical application of phages. In this study, a library of EZ‐Tn5 transposable mutants of susceptible host S. enterica B3‐6 was constructed. After the infestation pressure of a broad‐spectrum phage TP1, a mutant strain with resistance to eight phages was obtained. Analysis of the genome resequencing results revealed that the SefR gene was disrupted in the mutant strain. The mutant strain displayed a reduced adsorption rate of 42% and a significant decrease in swimming and swarming motility, as well as a significantly reduced expression of the flagellar‐related FliL and FliO genes to 17% and 36%, respectively. An uninterrupted form of the SefR gene was cloned into vector pET‐21a (+) and used for complementation of the mutant strain. The complemented mutant exhibited similar adsorption and motility as the wild‐type control. These results suggest that the disrupted flagellar‐mediated SefR gene causes an adsorption inhibition, which is responsible for the phage‐resistant phenotype of the S. enterica transposition mutant.