Gundersenthomas5296

A key miRNA (rno-miR-665) was identified by constructing a circRNA-miRNA-mRNA co-expression network. In summary, the study illustrated that circRNAs differentially expressed in fetal heart tissues during formaldehyde exposure has potential biological functions and may be a biomarker or therapeutic target for CHD.Acquired resistance to vemurafenib (PLX4032) is a thorny issue in BRAFV600E mutant melanoma therapy. Ferroptotic programmed cell death is a potential strategy for combating therapy-resistant cancers. This study uncovers the adaptation and abnormal upregulation of PUFAs and bioactive oxylipin metabolism in PLX4032 resistant melanoma cells. Phyto-sesquiterpene lactone, DET, and its derivative, DETD-35, induced lipid ROS accumulation and triggered ferroptotic cell death in PLX4032 sensitive (A375) and resistant (A375-R) BRAFV600E melanoma cells by reprogramming glutathione and primary metabolisms, lipid/oxylipin metabolism, and causing mitochondrial damage in which DETD-35 showed superior efficiency to DET. We discovered that DET and DETD-35 are a new type of GPX4 enzyme inhibitor through non-covalent binding. This study provides new insight into the therapeutic mechanisms of both DET and DETD-35 to combat PLX4032 sensitive/resistant BRAFV600E mutant melanomas via targeting GPX4 and ferroptosis.Cowpea [Vigna unguiculata (L.) Walp.] is one of the most tolerant legume crops to drought and salt stresses. WRKY transcription factor (TF) family members stand out among plant transcriptional regulators related to abiotic stress tolerance. However, little information is currently available on the expression of the cowpea WRKY gene family (VuWRKY) in response to water deficit. Thus, we analyzed genomic and transcriptomic data from cowpea to identify VuWRKY members and characterize their structure and transcriptional response under root dehydration stress. Ninety-two complete VuWRKY genes were found in the cowpea genome based on their domain characteristics. They were clustered into three groups I (15 members), II (58), and III (16), while three genes were unclassified. Domain analysis of the encoded proteins identified four major variants of the conserved heptapeptide motif WRKYGQK. In silico analysis of VuWRKY gene promoters identified eight candidate binding motifs of cis-regulatory elements, regulated mainly by six TF families associated with abiotic stress responses. Ninety-seven VuWRKY modulated splicing variants associated with 55 VuWRKY genes were identified via RNA-Seq analysis available at the Cowpea Genomics Consortium (CpGC) database. qPCR analyses showed that 22 genes are induced under root dehydration, with VuWRKY18, 21, and 75 exhibiting the most significant induction levels. Given their central role in activating signal transduction cascades in abiotic stress response, the data provide a foundation for the targeted modification of specific VuWRKY family members to improve drought tolerance in this important climate-resilient legume in the developing world and beyond.RNase E-mediated RNA processing and degradation are involved in bacterial adaptation to environmental changes. The RraA regulatory protein, which is highly conserved in γ-proteobacteria, differentially modulates RNase E activity. Recent studies have revealed the association of Salmonella enterica serovar Typhimurium RNase E (STRNase E) with bacterial pathogenicity; however, the molecular mechanisms are unknown. Here, we show that the expression levels of STRraA, a protein regulator of STRNase E activity, affect S. Typhimurium pathogenicity. RNA-sequencing and RT-PCR analyses indicated positive effects of STRraA levels on the abundance of mRNA species from class II flagellar operons. Primer extension analysis further identified STRraA-regulated STRNase E cleavage in the 5' untranslated region of fliDST mRNA. The cleavage affected the stability of this polycistronic mRNA, suggesting that STRraA protects fliDST mRNA from STRNase E cleavage, leading to enhanced flagellar assembly. Accordingly, STRraA positively regulated flagellar assembly and motility. In addition, STrraA-deleted cells showed decreased invasion ability and cytotoxicity in infection of human cervical epithelial carcinoma cells and reduced mortality in a mouse infection model compared to wild-type cells. These results support an active role of STRraA in RNase E-mediated modulation of pathogenesis in S. Typhimurium.Cryptosporidium spp. is recognized as an opportunistic zoonotic parasite that infects humans, wild and domestic animals, and is also a major cause of diarrhea-related disease in immunocompromised individuals, considered a global public health concern. Pig is considered as one of the reservoir hosts of Cryptosporidium spp. can transmit cryptosporidiosis to humans and other animals. However, limited studies on the distribution of Cryptosporidium spp. in diarrheic pigs have been published. Objective of the current study was to investigate the infection and species/genotypes of Cryptosporidium spp. from feces of diarrheic pigs in southern China. A total of 1254 fresh fecal samples were collected from 37 intensive pig farms in Jiangxi, Hunan and Fujian provinces, and were screened for Cryptosporidium spp. infection using a nested PCR assay targeted the small subunit rRNA (SSU rRNA) genes. The overall infection rate of Cryptosporidium spp. was 4.5% (57/1254), including 5.5% (17/307) in suckling piglets, 2.7% (8/299) in weaned piglets, 7.4% (7/95) in fattening pigs and 4.5% (25/553) in sows, respectively. In addition, two human-pathogenic species Cryptosporidium scrofarum (80.7%, 46/57) and Cryptosporidium suis (19.3%, 11/57) were identified. C. scrofarum and C. suis were observed in pigs tested in all age groups. Interestingly, a high colonization incidence of C. scrofarum (16/57) was observed in suckling piglets. This study revealed the prevalence and species of Cryptosporidium spp. in diarrheic pigs in three provinces of southern China, which suggested that diarrhea maybe not a direct factor affecting the prevalence of Cryptosporidium spp. in pigs. More prevention and control of this parasite in pigs should receive greater attention from farmers in investigated provinces.Human papillomavirus (HPV) represents the most prevalent sexually transmitted infectious agent worldwide. Vaccination has been an approach successfully used as a prophylactic measure against this infectious agent in patients without previous contact with the genotypes present in the vaccine. In this work, we use a computational approach to predict CD8 T cell epitopes from HPV proteins to promote cell-mediated immunity. We evaluated immunogenicity, conservation, toxicity, stability and population coverage of epitopes. Finally, a molecular docking analysis was performed to confirm the stability of the complexes formed. NVP-BSK805 research buy We identified 17 epitopes with affinity for several HLA alleles, covering 5 binding supermotifs (A2, A3, A24, B62 and B57). The analyses showed that these epitopes have a high population coverage and are highly conserved among several HPV genotypes. Seven of them (NWKNFFSTTWE1594-603, KVSAFQYRVFRVL163-74, LQFIFQLCKL1372-380, RVFRVQLPDPNKL170-81, FNKPYWLHRL1307-315, FITCVDTTRL1330-338 and HLRREQIFARL1248-257) were 100% conserved. Finally, molecular docking confirmed the stability of the complexes by means of a large network of hydrogen bonds formed and the calculated low bonding energy. The epitopes identified in this study are potential candidates as components of therapeutic vaccines and we suggest that these epitopes can be used in future studies aiming to activate antigen-specific CD8 T cells.The neuronal microtubule-associated protein tau undergoes multiple post-translational modifications, which dynamically modulate its molecular functions and biochemical features in space and time. Among them, we have recently reported that a conserved lysine residue mapping to the microtubule-binding domain of the protein (K306 in mouse and K317 in human) is differentially methylated in a model of chronic autoimmune demyelination. In contrast with other well-studied tau post-translational modifications such as phosphorylation, lysine methylation is far less investigated and its specific impact on tau biology is not fully understood. Here we performed a comprehensive analysis of the effects of K317 methylation on key tau features. By combining in silico simulations with in vitro biochemical assays and live-cell imaging, we show that methylated tau is more prone to self-assembly into insoluble structures. Moreover, we demonstrate that K317 methylation affects the stabilization activity of tau on microtubule dynamics. Lastly, we highlight a role for K317 methylation in regulating both neuronal differentiation and cell proliferation. Altogether, these findings shed light on the biology of an overlooked tau post-translational modification as well as on the fine tuning of tau functionality in health and disease.

In the United States and the United Kingdom, the roles of nurses in antimicrobial stewardship (AS) have been described in guidelines. However, in Japan, no previous studies have clarified nurses' recognition of the role of AS. Moreover, how the AS roles were implemented among nurses in Japan has not been fully clarified. The objectives of this study were to determine the perceptions of infection control nurses (ICNs) in Japan regarding the AS role of nurses and the extent of nurses' practice.

A questionnaire survey of ICNs was conducted.

Four hundred responses (response rate, 30.8%) were analyzed. Some of the items that have already gained consensus as the AS role of nurses were not recognized as the AS role of nurses by ICNs or had low implementation rates in Japan. Meanwhile, both recognition and implementation rates were high for the 5 types of care proposed.

The reason the ICNs agreed that these 5 types of care are AS roles for nurses is that they know that such care can prevent infection and thereby obviate the need for antimicrobial administration. However, whether nurses themselves understand that these are roles for nurses in AS is unclear. To promote AS in Japan, communicating the fact that nurses already contribute to AS, strengthening nurse education, and improving staffing are desirable.

The reason the ICNs agreed that these 5 types of care are AS roles for nurses is that they know that such care can prevent infection and thereby obviate the need for antimicrobial administration. However, whether nurses themselves understand that these are roles for nurses in AS is unclear. To promote AS in Japan, communicating the fact that nurses already contribute to AS, strengthening nurse education, and improving staffing are desirable.

Reminding health care workers, especially senior students, of the critical role they play in preventing COVID-19 transmission is more important than ever, therefore it is vital to reinforce graduate students' intrinsic motivation to implement infection prevention and control guidelines. Serious games are an interesting intervention that could improve adherence to COVID-19 safe behaviors to lower the high prevalence of nosocomial infections. These games, as a type of technology-enhanced simulation, can increase student satisfaction and engagement while still conveying vital ideas. For this reason, this study aimed to develop a serious game and evaluate its effectiveness to prevent the spread of infection and develop safe behaviors during the COVID-19 pandemic.

In total, 62 nursing students completed a socio-demographic questionnaire, COVID-19 information form, and game usability form, with the students' responses analyzed pre-test and post-test.

Serious game implementation significantly increased senior students' knowledge of infection and safe behaviors concerning COVID-19.