Hovmandrode0372

remain unknown. To address this fundamental knowledge gap, we examined the whole-proteomic and phosphoproteomic impacts of PKA on the deadly fungal pathogen Aspergillus fumigatus to uncover novel PKA targets controlling growth and virulence. We also defined the functional consequences of specific posttranslational modifications of these target proteins to characterize the molecular mechanisms of pathogenic effector regulation by PKA. AUNP-12 cost This study constitutes the most comprehensive analysis of the PKA-dependent phosphoproteome of any human pathogen and proposes new and complex roles played by PKA signaling networks in governing infectious disease.The study by Zhao and colleagues, in this issue of Cancer Research, builds on previous work where they showed that transient activation of Hedgehog signaling within the murine submandibular gland rescued radiation-induced salivary gland dysfunction. The current study provides mechanistic insight into this phenomenon by showing that restoration of radiation-depleted resident macrophages through prorepair paracrine interactions with endothelial cells and epithelial progenitors rescued salivary function.See related article by Zhao et al., p. 5531.

The increase in COVID-19 cases is generating fear and concern in society, which generates an emotional response that influences the adoption of health-related behaviors. The objective of the study is to design and validate the Scale of Worry for Contagion of COVID-19 (PRE-COVID-19).

The study had a descriptive cross-sectional design. The population were young people and adults who resided in the cities of Lima and Callao (Perú) during the declaration of the national health emergency due to the COVID-19 pandemic, during the period from March 16 to 27, 2020, who were recruited through a non-probability sample. The PRE-COVID-19, the WHO-Five Well-Being Index, the Generalized Anxiety Disorder Scale-2 and a single item were applied to measure the general perception of health. The scales were shared using a Google form through social networks. An internal consistency reliability analysis and structural equation models were performed, specifically confirmatory factor analysis. The recommendations of the Declaration of Helsinki and the principles that guide the ethical practice of online studies were followed.

Eight hundred and sixteen young people and adults from Lima and Callao (200 men and 616 women; mean age 28.40, SD 7.10) participated. The results show a one-dimensional model with satisfactory goodness-of-fit indices χ

(9)=52.00; CFI=0.99; RMSEA=0.09 [0.07, 0.12]; WRMR=0.85. The λ of the model were higher than 0.50 and the reliability had an excellent value (ω=0.90). Likewise, the convergent and discriminant validity is evident between PRE-COVID-19 and measures of anxiety, well-being and self-reported health.

The results indicate that the PRE-COVID-19 is a valid and reliable instrument to measure concern about the spread of COVID-19 and the emotional impact on people.

The results indicate that the PRE-COVID-19 is a valid and reliable instrument to measure concern about the spread of COVID-19 and the emotional impact on people.

Suicide is an important, understudied public health problem in Bangladesh, where risk factors for suicide have not been investigated by case-control psychological autopsy study.

To identify the major risk factors for suicide in Dhaka, Bangladesh.

We designed a matched case-control psychological autopsy study. We conducted a semi-structured interview with the next-of-kin of 100 individuals who died by suicide and 100 living controls, matched for age, gender and area of residence. The study was conducted from July 2019 to July 2020.

The odds ratios for the risk factors were 15.33 (95% CI, 4.76-49.30) for the presence of a psychiatric disorder, 17.75 (95% CI, 6.48-48.59) for life events, 65.28 (95% CI, 0.75-5644.48) for previous attempts and 12 (95% CI, 1.56-92.29) for sexual abuse.

The presence of a psychiatric disorder, immediate life events, previous suicidal attempts and sexual abuse were found as significant risk factors for suicide in Dhaka, Bangladesh.

The presence of a psychiatric disorder, immediate life events, previous suicidal attempts and sexual abuse were found as significant risk factors for suicide in Dhaka, Bangladesh.The management of bacterial diseases calls for a detailed knowledge about the dynamic changes in host-bacteria interactions. Biological insights are gained by integrating experimental data with mechanistic mathematical models to infer experimentally unobservable quantities. This inter-disciplinary field would benefit from experiments with maximal information content yielding high-precision inference. Here, we present a computationally efficient tool for optimizing experimental design in terms of parameter inference in studies using isogenic-tagged strains. We study the effect of three experimental design factors number of biological replicates, sampling timepoint selection and number of copies per tagged strain. We conduct a simulation study to establish the relationship between our optimality criterion and the size of parameter estimate confidence intervals, and showcase its application in a range of biological scenarios reflecting different dynamics patterns observed in experimental infections. We show that in low-variance systems with low killing and replication rates, predicting high-precision experimental designs is consistently achieved; higher replicate sizes and strategic timepoint selection yield more precise estimates. Finally, we address the question of resource allocation under constraints; given a fixed number of host animals and a constraint on total inoculum size per host, infections with fewer strains at higher copies per strain lead to higher-precision inference.

Gastric and esophageal cancers are 2 of the most prevalent cancer types worldwide. Polymorphisms in the genes that code the methylenetetrahydrofolate reductase (MTHFR) enzyme increase the formation of both cancer types. In this study, it was aimed to research the relationship between the existence of



and

polymorphisms in patients with gastric and esophageal cancer and the lifespans of patients.

This prospective study was performed at Van Yuzuncu Yil University. Included in the study were 30 patients with esophageal tumors, 70 patients with gastric tumors, and 61 healthy volunteers. From each of the patients, 5 mL of blood was drawn. DNA was isolated via kits with spin-column technology.

It was concluded that the risk of developing gastric cancer was 4.13 times higher in individuals who had the

genotype of the

polymorphism when compared to those who had the

genotype, while the risk was 2.91 times higher in individuals who had the

genotype when compared to those who had the

genotypencer in eastern Turkey. These polymorphisms may have no effect on the life spans of the patients.

Acute kidney injury (AKI) is an underestimated yet important risk factor for the development of chronic kidney disease (CKD), characterized by tubulointerstitial fibrosis and tubular dedifferentiation. Tubular dedifferentiation, which is associated with the loss of epithelial markers and the gain of mesenchymal features, is thought to be involved in tubulointerstitial fibrosis. As protein kinase B/Akt is involved in the development of CKD, we investigated the role of Akt1, one of the three Akt isoforms, in a murine model of AKI-to-CKD progression.

We subjected C57BL/6 male mice to unilateral ischemia-reperfusion injury (UIRI) and harvested their kidneys after 6 weeks. Mice were divided into four groups, namely, wild-type (WT) UIRI, Akt1-/- UIRI, WT sham, and Akt1-/- sham.

Akt1 (but not Akt2 or Akt3) was markedly activated in WT UIRI mice than in WT sham mice. Tubulointerstitial fibrosis and tubular dedifferentiation significantly increased in WT UIRI mice, but were attenuated in Akt1-/- UIRI mice. Both WT UIRI and Akt1-/- UIRI mice showed markedly upregulated transforming growth factor-β1 (TGF-β1)/Smad signaling compared with WT sham mice. However, TGF-β1/Smad expression did not differ between the two groups. The levels of phosphorylated GSK-3β, β-catenin, and Snail were attenuated in Akt1-/- UIRI mice compared with those in WT UIRI mice.

Deletion of Akt1 results in the attenuation of renal fibrosis and tubular dedifferentiation, independent of TGF-β1/Smad signaling, during AKI-toCKD progression in a UIRI without contralateral nephrectomy model. Thus, Akt1 may serve as a therapeutic target in AKI-to-CKD progression.

Deletion of Akt1 results in the attenuation of renal fibrosis and tubular dedifferentiation, independent of TGF-β1/Smad signaling, during AKI-toCKD progression in a UIRI without contralateral nephrectomy model. Thus, Akt1 may serve as a therapeutic target in AKI-to-CKD progression.The coronavirus (COVID-19) pandemic has adversely affected individuals' mental health. Social isolation as a result of social distancing during the pandemic potentially affects the associations among perceived available peer support, emotional well-being, and depression in university students. The present study examined the associations among university students' perceived available peer support, emotional well-being (as indicated negatively by loneliness and negative affects and positively by positive affects and hope), and depressive symptoms. During the third wave of the COVID-19 outbreak in July, 2020, 255 students at a public university in Hong Kong participated in an online-based survey that assessed their perceived available peer support, emotional well-being, and depressive symptoms. Results showed that perceived available peer support negatively contributed to depressive symptoms; both negative and positive indicators of emotional well-being mediated the association between perceived available peer support and depressive symptoms. Our results also suggested that university students showed signs of elevated depressive symptoms during the pandemic. Thus, our study advanced the theoretical understanding of university students' mental health in the time of a global pandemic. Our study also highlighted the practical needs for preventive efforts and accessible care to support the psychological and emotional needs of young people during the COVID-19 pandemic.Autophagy is a homeostatic process that regulates and recycles intracellular structures and is a host defense mechanism that facilitates bacterial clearance. Uric acid in plasma is a major antioxidant but in certain conditions acts as an inflammatory danger signal. The aim of this study is to investigate the effect of soluble uric acid on autophagy and the inflammatory responses in macrophages during bacterial infection. Herein, we employed murine RAW264.7 macrophages that express uricase enzyme and human THP-1 cells that are uricase-deficient. Three different strains of Staphylococcus aureus and two different strains of Klebsiella pneumoniae were used to infect macrophages in presence and absence of soluble uric acid. We found that soluble uric acid enhanced autophagy flux in infected macrophages. We observed that IL-1β increased during bacterial infection but decreased when macrophages were co-stimulated with bacteria and uric acid. In contrast to IL-1β, soluble uric acid did not affect TNFα release and there were no dramatic differences when macrophages were infected with S.