Higginsmontoya0006
Coxsackievirus B3 (CVB3) belongs to the genus Enterovirus of the family Picornaviridae and can cause acute acinar pancreatitis in adults. However, the molecular mechanisms of pathogenesis underlying CVB3-induced acute pancreatitis have remained unclear. In this study, we discovered that CVB3 capsid protein VP1 inhibited pancreatic cell proliferation and exerted strong cytopathic effects on HPAC cells. Through yeast two-hybrid, co-immunoprecipitation, and confocal microscopy, we show that Menage a trois 1 (MAT1), a subunit of the Cdk-Activating Kinase (CAK) complex involved in cell proliferation and transcription, is a novel interaction protein with CVB3 VP1. Moreover, CVB3 VP1 inhibited MAT1 accumulation and localization, thus interfering with its interaction with CDK7. Furthermore, CVB3 VP1 could suppress CAK complex enzymic phosphorylation activity towards RNA Pol II and CDK4/6, direct substrates of CAK. VP1 also suppresses phosphorylation of retinoblastoma protein (pRb), an indirect CAK substrate, especially at phospho-pRb Ser780 and phospho-pRb Ser807/811 residues, which are associated with cell proliferation. Finally, we present evidence using deletion mutants that the C-terminal domain (VP1-D8, 768-859aa) is the minimal VP1 region required for its interaction with MAT1, and furthermore, VP1-D8 alone was sufficient to arrest cells in G1/S phase as observed during CVB3 infection. Taken together, we demonstrate that CVB3 VP1 can inhibit CAK complex assembly and activity through direct interaction with MAT1, to block MAT1-mediated CAK-CDK4/6-Rb signaling, and ultimately suppress cell proliferation in pancreatic cells. These findings substantially extend our basic understanding of CVB3-mediated pancreatitis, providing strong candidates for strategic therapeutic targeting.Vesicular trafficking defects, particularly those in the autophagolysosomal system, have been strongly implicated in the pathogenesis of Parkinson's disease and related α-synucleinopathies. However, mechanisms mediating dysfunction of membrane trafficking remain incompletely understood. Using a Drosophila model of α-synuclein neurotoxicity with widespread and robust pathology, we find that human α-synuclein expression impairs autophagic flux in aging adult neurons. Genetic destabilization of the actin cytoskeleton rescues F-actin accumulation, promotes autophagosome clearance, normalizes the autophagolysosomal system, and rescues neurotoxicity in α-synuclein transgenic animals through an Arp2/3 dependent mechanism. Similarly, mitophagosomes accumulate in human α-synuclein-expressing neurons, and reversal of excessive actin stabilization promotes both clearance of these abnormal mitochondria-containing organelles and rescue of mitochondrial dysfunction. These results suggest that Arp2/3 dependent actin cytoskeleton stabilization mediates autophagic and mitophagic dysfunction and implicate failure of autophagosome maturation as a pathological mechanism in Parkinson's disease and related α-synucleinopathies.This study aims to understand tourists' willingness to pay a price premium for a local green hotel certification, and is one of only a few in the literature for small-island tourism destinations in emerging economies with their unique and pressing sustainability challenges. In a survey of 535 tourists visiting Gili Trawangan, Indonesia, facing numerous waste management and coral reef conservation issues, the willingness to pay extra for sustainable hotel services was elicited. There were five discrete pricing levels across the surveys that ranged from $0.75 USD to $7.50 USD extra per night. We examined the relationship of the respondents' payment choice to their socio-demographic attributes and attitudes regarding environmental issues such as climate change. The main findings and practical implications of the study are (1) to demonstrate the broad willingness to pay for sustainable hotel services. Findings indicate at all price levels (between $0.75 USD and $7.50 USD), more than 50% of tourists are willing to pay. (2) To estimate a lower bound mean willingness to pay per night for a local green hotel certificate of $1.55USD and 1.34€ EUR, and (3) To identify individual attributes that influence willingness to pay. Findings indicate environmental knowledge and preferences play a role. Apamin These results can be used generally to incorporate evidence-based practices into the development of a green hotel marketing strategy, and to help define the target market for small-scale green hotel certification. Additionally, we propose a finance strategy for funding local and sustainable initiatives that support the hotel industry and the island's infrastructure through the premiums collected from the 'Gili Green Award' certificate.In this study, based on the regional land-use risk space division (regional ecological risk source/receptor space identification) using production-living-ecology analysis, three spatial function indexes, i.e., production, living, and ecology function indexes, were proposed for regional ecological risk assessment (RERA) with respect to human disturbance. The first two indexes can be regarded as regional ecological risk source indexes, whereas the final index can be regarded as a regional ecological risk receptor index. Using an artificial assignment method based on the land-use types and Defense Meteorological Program Operational Line-Scan System (DMSP/OLS) nighttime light intensity data, these three spatial function indexes were effectively manifested. By incorporating these indexes with eco-environmental vulnerability proxies, an RERA framework was established and applied in the Poyang Lake Eco-economic Zone (PLEZ), which is an ecological-protection and economic-development coordination-oriented region in Cht results can provide a scientific basis for regional ecological risk management within the PLEZ.Anopheles stephensi with three different biotypes is a major vector of malaria in Asia. It breeds in a wide range of habitats. Therefore, safer and more sustainable methods are needed to control its immature stages rather than chemical pesticides. The larvicidal and antibacterial properties of the Pelargonium roseum essential oil (PREO) formulations were investigated against mysorensis and intermediate forms of An. stephensi in laboratory conditions. A series of nanoemulsions containing different amounts of PREO, equivalent to the calculated LC50 values for each An. stephensi form, and various quantities of surfactants and co-surfactants were developed. The physical and morphological properties of the most lethal formulations were also determined. PREO and its major components, i.e. citronellol (21.34%), L-menthone (6.41%), linalool (4.214%), and geraniol (2.19%), showed potent larvicidal activity against the studied mosquitoes. The LC50/90 values for mysorensis and intermediate forms were computed as 11.44/4. stephensi.Winter turnip rape (Brassica rapa L.) is an important overwintering oil crop that is widely planted in northwestern China. It considered to be a good genetic resource for cold-tolerant research because its roots can survive harsh winter conditions. Here, we performed comparative transcriptomics analysis of the roots of two winter turnip rape varieties, Longyou7 (L7, strong cold tolerance) and Tianyou2 (T2, low cold tolerance), under normal condition (CK) and cold stress (CT) condition. A total of 8,366 differentially expressed genes (DEGs) were detected between the two L7 root groups (L7CK_VS_L7CT), and 8,106 DEGs were detected for T2CK_VS_T2CT. Among the DEGs, two ω-3 fatty acid desaturase (FAD3), two delta-9 acyl-lipid desaturase 2 (ADS2), one diacylglycerol kinase (DGK), and one 3-ketoacyl-CoA synthase 2 (KCS2) were differentially expressed in the two varieties and identified to be related to fatty acid synthesis. Four glutamine synthetase cytosolic isozymes (GLN), serine acetyltransferase 1 (SAT1), and ses during cold treatment.
To determine if the presence of microorganisms in follicular fluid of women undergoing in vitro fertilization-embryo transfer (IVF-ET) adversely affects the outcome of the treatment cycles.
Follicular fluid was collected from 86 women enrolled for IVF-ET at the National Hospital, Abuja from June 1, 2018 to December 1, 2018. Microscopy imaging and cultures were performed to identify bacteria and fungi in the follicular fluid and the vagina. Women with follicular fluid microorganisms were the test group while the controls were those without follicular fluid microorganisms. Fertilization and pregnancy rates were subsequently determined and their association with the presence of follicular fluid microorganisms was assessed using univariable and multivariable logistic regression modelling.
The mean age and mean Body Mass Index (BMI) of the participants were 35(± 3.5) years and 28(± 4.9) kg/m2 respectively. Bacteria and fungi were isolated in 17% of the follicular fluid samples collected (n = 15/86). Most common isolates were Streptococcus spp. (n = 4/15), Staphylococcus aureus (n = 7/15), Enterococcus spp. (n = 4/15), Lactobacillus species (n = 2/15) and Candida albicans (n = 2/15). There was no statistically significant difference in the fertilization rates (adjusted odds ratio [AdjOR] 0.55, 95% confidence interval [CI] 0.04-7.34; P = 0.10) and pregnancy rates (AdjOR 4.02, 95% CI 0.56-28.92; P = 0.19) between the group of women with positive follicular fluid bacterial /fungal colonization as compared against those with negative follicular fluid colonization.
Isolation of microorganisms from follicular fluid did not adversely affect fertilization and pregnancy rates following IVF-ET treatment cycles at the fertility centre of National Hospital, Abuja.
Isolation of microorganisms from follicular fluid did not adversely affect fertilization and pregnancy rates following IVF-ET treatment cycles at the fertility centre of National Hospital, Abuja.
To assess the feasibility of radiologic measurements and find out whether hearing outcome could be predicted based on computer tomography (CT) scan evaluation in patients with temporal bone fractures and suspected ossicular joint dislocation.
We assessed 4002 temporal bone CT scans and identified 34 patients with reported ossicular joint dislocation due to trauma. We excluded those with no proven traumatic ossicular dislocation in CT scan and patients with bilateral temporal bone fractures. We measured four parameters such as malleus-incus axis distance, malleus-incus angle at midpoints, malleus- incus axis angle and ossicular joint space. The contralateral healthy side served as its own control. Hearing outcome 1-3 months after the index visit was analyzed. We assessed diagnostic accuracy and performed a logistic regression using radiologic measurement parameters for outcome prediction of conductive hearing loss (defined as >20dB air-bone gap).
We found excellent inter-rater agreement on the measures and the malleus were strongly predictive for poor hearing outcome in terms of air conduction 1-3 months after trauma. We propose a 3-level classification system for hearing outcome prediction based on radiologic measures.Tick-borne encephalitis (TBE) is a widespread viral infection of the central nervous system with increasing incidence in Europe and northern Asia. Post-infectious sequelae are frequent, and patients with TBE commonly experience long-term fatigue and subjective sleep disturbances. Obstructive sleep apnea (OSA) may be a contributing factor, and objective sleep studies with polysomnography (PSG) are lacking. Forty-two adults, 22 TBE patients (cases), diagnosed in Region Västra Götaland, Sweden, between 2012 and 2015, and 20 controls without a known TBE history, underwent an overnight PSG, respectively. All participants responded to questionnaires. The cases and controls were similar regarding age, sex, obesity, concomitant diseases, smoking, and alcohol habits. Despite similar PSG characteristics such as total sleep time and OSA severity indices, the TBE cases reported statistically more sleep-related functional impairment on the Functional Outcome of Sleep Questionnaire (FOSQ) compared with the controls (median scores 18.