Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure of Bacterial Community with Resistance to Antibiotics in Aquatic Environments. A Systematic Review

Aquatic environments have been affected by the increase in bacterial resistant to antibiotics. The aim of this review is to describe the studies carried out in relation to the bacterial population structure and antibiotic resistance genes in natural and artificial water systems. We performed a systematic review based on the PRISMA guideline (preferred reporting items for systematic reviews and meta-analyzes). Articles were collected from scientific databases between January 2010 and December 2020. Sixty-eight papers meeting the inclusion criteria, i.e., “reporting the water bacterial community composition”, “resistance to antibiotics”, and “antibiotic resistance genes (ARG)”, were evaluated according to pre-defined validity criteria. The results indicate that the predominant phyla were Firmicutes and Bacteroidetes in natural and artificial water systems. Gram-negative bacteria of the family Enterobacteraceae with resistance to antibiotics are commonly reported in drinking water and in natural water systems. The ARGs mainly reported were those that confer resistance to β-lactam antibiotics, aminoglycosides, fluoroquinolones, macrolides and tetracycline. The high influence of anthropogenic activity in the environment is evidenced. The antibiotic resistance genes that are mainly reported in the urban areas of the world are those that confer resistance to the antibiotics that are most used in clinical practice, which constitutes a problem for human and animal health.
Economic Stressors, COVID-19 Attitudes, Worry, and Behaviors among U.S. Working Adults: A Mixture Analysis

Since the unfolding of the novel coronavirus global pandemic, public health research has increasingly suggested that certain groups of individuals may be more exposed to the virus. The aim of this contribution was to investigate whether workers grouped into several latent classes, based on two perceived economic stressors, would report different levels of enactment of the Centers for Disease Control (CDC) recommended behaviors to prevent the spread of such virus. We also tested propositions regarding the potential differential predictors of compliance behavior, differentiating between cognitive (i.e., attitudes toward the CDC guidelines) and affective (i.e., COVID-specific worry) predictors. Using a longitudinal dataset of 419 U.S. workers, we did not find significant differences among the levels of CDC guidelines enactment across three latent classes, representing a range of economic vulnerability. We found that cognitive attitudes were a significantly stronger predictor of compliance with CDC guidelines for workers in the most economically secure class, whereas worry was a significantly stronger predictor of compliance for the most vulnerable counterpart. We discuss these findings in light of the Conservation of Resources theory and other health behavior theories, being mindful of the need to further understand the differential impact of this health and economic crisis on employees facing economic stressors.
Measurements of atmospheric CO2 from a meteorological tower in Tsukuba, Japan

Since February 1992, measurements of atmospheric CO2 at 200 m above the ground have been taken from a meteorological tower (lat 36°04′N, long 140°07′E, 25 m a.s.l.) in Tsukuba, central Japan. A diurnal variation of atmospheric CO2 at 200 m was clearly observed in summer and less clearly in winter. In summer, the maximum occurred a few hours after dawn and the minimum in the late afternoon; in winter, the CO2 mixing ratio was fairly constant because of temperature inversion below 200 m. The daily mean values of atmospheric CO2 in the afternoon (1300–1600 JST), selected as they were close to the representative values in the planetary boundary layer, were as high as 4 to 6 ppm greater than at stations in remote areas of the same latitudinal zone. This was mainly due to CO2 emissions from anthropogenic sources in central Japan. The peak-to-trough amplitude of the seasonal variation, caused by the CO2 exchange between the air and the land biosphere, ranged from 11 to 14 ppm. Year-to-year changes in the seasonal variation of atmospheric CO2 during the period from May to July were correlated well with the surface air temperature among climate variables that affect the photosynthesis/respiration of the land biosphere. The change in CO2 mixing ratio of the detrended seasonal variation from May to July increased with the surface air temperature, which was suggestive of the larger temperature dependence of respiration rate as compared with that of photosynthesis rate. Over the period from 1993 to 1999, the annual mean of the CO2 mixing ratio increased from 363.0 ppm to 374.6 ppm. The growth rate from February 1992 to January 2000 showed a large interannual variability ranging from −0.8 to 4.6 ppm yr−1 with a mean rate of 2.0 ppm yr−1.
Protective Effect of Oligonol on Dimethylnitrosamine-Induced Liver Fibrosis in Rats via the JNK/NF-κB and PI3K/Akt/Nrf2 Signaling Pathways

Oligonol is a low molecular weight polyphenol product derived from lychee fruit by a manufacturing process. We investigated oligonol’s anti-fibrotic effect and the underlying mechanism in dimethylnitrosamine (DMN)-induced chronic liver damage in male Sprague–Dawley rats. Oral administration of oligonol (10 and 20 mg/kg body weight) ameliorated the DMN-induced abnormalities in liver histology and serum parameters in rats. Oligonol prevented the DMN-induced elevations of TNF-α, IL-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase expressions at the mRNA level. NF-κB activation and JNK phosphorylation in DMN-treated rats were ablated by oligonol. Oligonol reduced the enhanced production of hepatic malondialdehyde and reactive oxygen species and recovered protein SH, non-protein SH levels, and catalase activity in the DMN treated liver. Nrf2 translocation into the nucleus was enhanced, and PI3K and phosphorylated Akt levels were increased by administering oligonol. The level of hepatic fibrosis-related factors such as α-smooth muscle actin, transforming growth factor-β1, and type I collagen was reduced in rats treated with oligonol. Histology and immunohistochemistry analysis showed that the accumulation of collagen and activation of hepatic stellate cells (HSCs) in liver tissue were restored by oligonol treatment. Taken together, oligonol showed antioxidative, hepatoprotective, and anti-fibrotic effects via JNK/NF-κB and PI3K/Akt/Nrf2 signaling pathways in DMN-intoxicated rats. These results suggest that antioxidant oligonol is a potentially useful agent for the protection against chronic liver injury.
A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis

Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.
Validating a Methodology That Associates Minimum Detectable Activity with Detector Velocity

Abstract Mobile radiation detection systems are used widely in remediation and nuclear security. However, their detection efficiency and thus their minimum detectable activity is not completely understood. It is recognized that the detector’s velocity will affect its detection efficiency. At lower speeds, detection efficiency will be higher than a detector moving at higher speeds. The relationship describing how speed and efficiency are related was only recently quantified using a modified four-parameter logistic function (M4PL). The current research verifies the M4PL function in a controlled laboratory setting using a 5.08 cm × 5.08 cm sodium iodide detector at speeds between 20-120 cm s−1. As expected, the M4PL function indicates a detection system’s highest efficiency at low speeds and its lowest efficiency at higher speed. In between is a transition region of decreasing detector efficiency. This decrease is gradual within initial speeds but quickly steepens and then approaches a minimum at higher detector speeds. This general shape was observed in the experimental data and validated the M4PL function as a predictive tool. To conclude this research and to demonstrate the function’s usefulness, a relationship between speed and minimum detectable activity (MDA) was developed. Using this function and the methods described in this research, planners can now optimize surveys by controlling velocity to maintain MDA. It is also possible to use this technique to accelerate surveys while having the ability to predict the reduction in MDA. This foundational relationship between detector speed and detection efficiency has the potential to improve detector performance in various applications for both the academic and operational fields.
Role of the NUDT Enzymes in Breast Cancer

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.
Prodigiosin Sensitizes Sensitive and Resistant Urothelial Carcinoma Cells to Cisplatin Treatment

Cisplatin-based treatment is the standard of care therapy for urothelial carcinomas. However, complex cisplatin resistance mechanisms limit the success of this approach. Both apoptosis and autophagy have been shown to contribute to this resistance. Prodigiosin, a secondary metabolite from various bacteria, exerts different biological activities including the modulation of these two cellular stress response pathways. We analyzed the effect of prodigiosin on protein levels of different autophagy- and apoptosis-related proteins in cisplatin-sensitive and -resistant urothelial carcinoma cells (UCCs). Furthermore, we investigated the effect on cell viability of prodigiosin alone or in combination with cisplatin. We made use of four different pairs of cisplatin-sensitive and -resistant UCCs. We found that prodigiosin blocked autophagy in UCCs and re-sensitized cisplatin-resistant cells to apoptotic cell death. Furthermore, we found that prodigiosin is a potent anticancer agent with nanomolar IC50 values in all tested UCCs. In combination studies, we observed that prodigiosin sensitized both cisplatin-sensitive and -resistant urothelial carcinoma cell lines to cisplatin treatment with synergistic effects in most tested cell lines. These effects of prodigiosin are at least partially mediated by altering lysosomal function, since we detected reduced activities of cathepsin B and L. We propose that prodigiosin is a promising candidate for the therapy of cisplatin-resistant urothelial carcinomas, either as a single agent or in combinatory therapeutic approaches.
Imaging Techniques to Study Plant Virus Replication and Vertical Transmission

Plant viruses are obligate parasites that need to usurp plant cell metabolism in order to infect their hosts. Imaging techniques have been used for quite a long time to study plant virus–host interactions, making it possible to have major advances in the knowledge of plant virus infection cycles. The imaging techniques used to study plant–virus interactions have included light microscopy, confocal laser scanning microscopy, and scanning and transmission electron microscopies. Here, we review the use of these techniques in plant virology, illustrating recent advances in the area with examples from plant virus replication and virus plant-to-plant vertical transmission processes.
Matrix decomposition in meta‐analysis for extraction of adverse event pattern and patient‐level safety profile

The purpose of assessing adverse events (AEs) in clinical studies is to evaluate what AE patterns are likely to occur during treatment. In contrast, it is difficult to specify which of these patterns occurs in each patient. To tackle this challenging issue, we constructed a new statistical model including nonnegative matrix factorization by incorporating background knowledge of AE‐specific structures such as severity and drug mechanism of action. The model uses a meta‐analysis framework for integrating data from multiple clinical studies because insufficient information is derived from a single trial. We demonstrated the proposed method by applying it to real data consisting of three Phase III studies, two mechanisms of action, five anticancer treatments, 3317 patients, 848 AE types, and 99,546 AEs. The extracted typical treatment‐specific AE patterns coincided with medical knowledge. We also demonstrated patient‐level safety profiles using the data of AEs that were observed by the end of the second cycle.
Does Vigorous Physical Activity Contribute to Adolescent Life Satisfaction?

Background: Physical and mental health are the basis of life satisfaction (LS), even during adolescence. The aim of this study was to identify the associations between LS and types of physical activity (PA) in Czech and Polish boys and girls. Methods: The research involved 933 girls and 663 boys aged 15–19 years. LS was diagnosed using the Bern Subjective Well-Being Questionnaire and the WHO-5 Well-Being Index. The International Physical Activity Questionnaire-long form (IPAQ-LF) questionnaire was used to identify the types of weekly PA. Results: Adolescents with the highest LS had more recreational, moderate, vigorous, and total weekly PA. The strongest associations between LS and PA were in the Czech and Polish boys and girls who participated in vigorous PA (VPA). The recommendations for VPA were fulfilled by 45% of Czech and 46% of Polish boys and 40% of Czech and 50% of Polish girls, with the highest LS. The most significant positive moderator between LS and PA was participation in organized PA. Boys with the highest LS were 1.94 times more likely to meet the weekly recommendation of VPA than boys with the lowest LS. Similarly, girls with the highest LS were 1.77 times more likely to meet these recommendations. Conclusions: Promoting both current subjective well-being and organized PA, with an emphasis on achieving the VPA recommendations, may support general LS and a healthy lifestyle in adolescents.
Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR/Cas9-Corrected Mutation

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.
Animals selected for postweaning weight gain rate have similar maintenance energy requirements regardless of their residual feed intake classification.

Data of comparative slaughter were used to determine Nellore bulls' net energy requirements classified as efficient or inefficient according to residual feed intake (RFI) and selection lines (SL). Sixty-seven Nellore bulls from the selected (SE) and control (CO) lines of the selection program for postweaning weight gain were used. The animals underwent digestibility trials before being submitted to the finishing trial. Sixteen bulls were slaughtered at the beginning of the finishing trial, and their body composition were used as the baseline for the remaining animals. For body composition determinations, whole empty body components were weighed, ground, and subsampled for chemical analyses. Initial body composition was determined with equations developed from the baseline group using shrunk body weight, fat, and protein. The low RFI (LRFI) and CO animals had a lower dry matter (DMI) and nutrient intake (P < 0.05) than high RFI (HRFI) and SE animals, without alterations in digestibility coefficients (P > 0.05). During the finishing trial, DMI remained lower for LRFI and CO animals. Growth performance was similar between RFI classes, except for empty body weight gain that tended to be higher for LRFI than HRFI (P = 0.091). The SE animals had less fat content on the empty body (P = 0.005) than CO. Carcasses tended to be leaner for LRFI than HRFI (P = 0.080) and for SE than CO (P = 0.066) animals. LRFI animals retained more energy (P = 0.049) and had lower heat production (HP; P = 0.033) than the HRFI ones. Retained energy was not influenced by SL (P = 0.165), but HP tended to be higher for SE when compared to CO (P = 0.075) animals. Net energy requirement for maintenance (NEm) was lower for LRFI than HRFI (P = 0.009), and higher for SE than CO (P = 0.046) animals. There was an interaction tendency between RFI and SL (P = 0.063), suggesting that NEm was lower for LRFI+CO than HRFI+CO (P = 0.006), with no differences for SE (P = 0.527) animals. The efficiency of ME utilization for maintenance (km) of LRFI and HRFI animals were 62.6 and 58.4%, respectively, and for SE and CO were 59.0 and 62.1%, respectively. The breeding program for postweaning weight has not improved feed efficiency over the years, with RFI classification not being a promising selection tool for SE animals. Classification based on RFI seems to be useful in animals that have not undergone the breeding program, with LRFI animals having lower energy requirements than the HRFI ones.
Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma

Simple Summary Glioblastomas are high-grade brain tumours and are the most common form of malignancy arising in the brain. Patient survival has improved little over the last 40 years, highlighting an urgent unmet need for more effective treatments for these tumours. Current standard-of-care treatment involves surgical removal of as much of the tumour as possible followed by a course of chemo-/radiotherapy. The main chemotherapeutic drug used is called temozolomide, however even with this treatment regimen, the average patient survival following diagnosis is around 15 months. We have identified a protein called ERK5 which is present at higher levels in these high-grade brain tumours compared to normal brain tissue, and which is also associated with resistance to temozolomide and poor patient survival. Additionally, we show that targeting ERK5 in brain tumour cells can improve the effectiveness of temozolomide in killing these tumour cells and offers potential much-needed future clinical benefit to patients diagnosed with glioblastoma. Abstract Brain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)—the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease.