HIV envelope protein gp120-induced apoptosis in lung microvascular endothelial cells by concerted upregulation of EMAP II and its receptor, CXCR3

Chronic lung diseases, such as pulmonary emphysema, are increasingly recognized complications of infection with the human immunodeficiency virus (HIV). Emphysema in HIV may occur independent of cigarette smoking, via mechanisms that are poorly understood but may involve lung endothelial cell apoptosis induced by the HIV envelope protein gp120. Recently, we have demonstrated that lung endothelial apoptosis is an important contributor to the development of experimental emphysema, via upregulation of the proinflammatory cytokine endothelial monocyte-activating polypeptide II (EMAP II) in the lung. Here we investigated the role of EMAP II and its receptor, CXCR3, in gp120-induced lung endothelial cell apoptosis. We could demonstrate that gp120 induces a rapid and robust increase in cell surface expression of EMAP II and its receptor CXCR3. This surface expression occurred via a mechanism involving gp120 signaling through its CXCR4 receptor and p38 MAPK activation. Both EMAP II and CXCR3 were essentially required for gp120-induced apoptosis and exposures to low gp120 concentrations enhanced the susceptibility of endothelial cells to undergo apoptosis when exposed to soluble cigarette smoke extract. These data indicate a novel mechanism by which HIV infection causes endothelial cell loss involved in lung emphysema formation, independent but potentially synergistic with smoking, and suggest therapeutic targets for emphysema prevention and/or treatment

Functional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation cascade from an uncultured archaeon.

The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. Although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. Encoded in operons, these components are likely representative of the progenitor apparatus that founded the modern eukaryotic ubiquitin modification systems. Here we report that these proteins from the archaeon Candidatus 'Caldiarchaeum subterraneum' operate together as a bona fide ubiquitin modification system, mediating a sequential ubiquitylation cascade reminiscent of the eukaryotic process. Our observations support the hypothesis that complex eukaryotic ubiquitylation signalling pathways have developed from compact systems originally inherited from an archaeal ancestor

A primary evaluation of Syrian forest damage since 2011: a case study of Alhamam and Alboz forest sites

Forests and trees make vital contributions to well-being, economic activities, ecosystem functioning and global system dynamics. There has been a lack of studies on the evaluation of the drivers of Syrian forest damage during the current conflict. This study estimated the damage since 2011 in the Alhamam and Alboz forest sites in Idlib province of Syria and evaluated the drivers of this damage. A multidimensional approach to damage assessment was developed which combined forest plot inventories, remotely sensed satellite image analysis, questionnaires and focus groups to enable a comparison of the forest from 2011 and 2017. The plot inventory data and remote sensing analysis provided estimates of forest damage and loss whilst focus groups and questionnaires provided vital information on the drivers of forest loss which is required for developing reforestation programmes. Overall, forest inventory data and satellite image analysis results indicated a reduction in tree cover, density and plant diversity. The results indicate a much higher loss of forest than is available from global products such as Global Forest Watch due to the prevalence in Syria of low-density Oak forests such as Alhamam not being classed as forest. The results of questionnaires and focus groups showed that the main cause of damage was an increased demand for fire-wood driven by a lack of fuel oil and increased unemployment, reduced household incomes and general price rises, making fuel more unaffordable. Respondents to surveys generally understood the importance of trees and forests and overtime the local knowledge of the importance of forest resources had not changed. This multidimensional approach indicates a reduced capacity of institutions to protect forests and will help to establish strategic plans to serve and protect the forest in the future

Towards Wind Energy-based Charging Stations: A Review of Optimization Methods

Due to the growing importance of renewable sources in sustainable energy systems, the strategic deployment of robust optimization techniques plays a crucial role in the design of Electric Vehicle Charging Stations (EVCSs). These stations need to smoothly incorporate renewable sources, ensuring optimal energy utilization. This study provides a comprehensive overview of the methodologies and approaches employed in the enhancement of wind energy based EVCSs. The aim is to discern the most efficacious techniques for optimizing charging stations. Researchers engage diverse strategies and methodologies in the realm of sizing and optimization, encompassing a spectrum of algorithmic implementations and software solutions. Evidently, each algorithm or software application bears distinctive merits and demerits. Singular reliance on a solitary algorithm or software for charging utility optimization is discerned to be potentially limiting. The investigation reveals that achieving better results in Electric Vehicle Charging Station (EVCS) optimization is facilitated by the collaborative use of multiple algorithms like GA, PSO, and ACO, among others, or software tools like Homer or RETScreen

Genotypic detection of extended spectrum beta lactamases from selected bacterial isolates in the Specialist Hospital Sokoto, Nigeria

There are numerous reported cases of extended spectrum beta lactamases (ESBLs) producing Enterobacteriaceae in Nigeria, with little effort done on the molecular detection. Epidemiological studies around the world have investigated the prevalence of ESBL-producing enterobacteriaceae and they have seen multiple mechanisms of drug-resistance. Our study was designed to detect ESBLs genes such as CTX-M, SHV, and TEM using PCR from clinical isolates in a tertiary hospital in Sokoto metropolis. Clinical isolates from the Microbiology laboratory of the tertiary hospital was collected for 3 months. These isolates were identified using standard microbiological methods. They were tested against 8 antibiotics using the modified Kirby Bauer disc diffusion method. Multidrug resistant isolates were screened for ESBL production, and further confirmed by the Double Disc Synergy Test (DDST). Genotypic confirmation was carried out using multiplex Polymerase Chain Reaction (PCR). A total of 47 isolates made up of 21 E. coli (44.6%), 13 Klebsiella spp (27.6%), 7 Salmonella spp (14.9%), 5 Proteus mirabilis (10.6%), and 1 Enterobacter spp (2.1%) were obtained from urine, stool, and wound swab. Out of the 47 isolates, (45) 95.7% were multidrug resistant. Twenty-five (53.2%) were potential ESBL producers, while only 5 (20.0%) were confirmed phenotypically using a DDST. PCR results revealed 4 out of 5 of the isolates were possessing ESBL genes. It also revealed that 3 isolates co-produce TEM and SHV at 403bp and 293bp respectively. Only 1 isolate produced CTX-M gene at 569bp. The prevalence of ESBL production in the Gram negative enterobacteriaceae in our study did not indicate a high prevalence as reported by some studies in Sokoto and Northwest Nigeria.Keywords: Molecular detection, ESBLs, Clinical isolates, PC

Inhibitory Immune Checkpoint Receptors and Ligands as Prognostic Biomarkers in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. During T-cell activation, the immune system uses different checkpoint pathways to maintain co-inhibitory and co-stimulatory signals. In COVID-19, expression of immune checkpoints (ICs) is one of the most important manifestations, in addition to lymphopenia and inflammatory cytokines, contributing to worse clinical outcomes. There is a controversy whether upregulation of ICs in COVID-19 patients might lead to T-cell exhaustion or activation. This review summarizes the available studies that investigated IC receptors and ligands in COVID-19 patients, as well as their effect on T-cell function. Several IC receptors and ligands, including CTLA-4, BTLA, TIM-3, VISTA, LAG-3, TIGIT, PD-1, CD160, 2B4, NKG2A, Galectin-9, Galectin-3, PD-L1, PD-L2, LSECtin, and CD112, were upregulated in COVID-19 patients. Based on the available studies, there is a possible relationship between disease severity and increased expression of IC receptors and ligands. Overall, the upregulation of some ICs could be used as a prognostic biomarker for disease severity. [Abstract copyright: Copyright © 2022 Al-Mterin, Alsalman and Elkord.

In Vitro Antimicrobial Activity of The Filtrate Crude Extract Produced by Aspergillus niger

Introduction: Aspergillus niger represents one of the fungi that can produce the secondary metabolites, including antimicrobial agents, industrial and biotechnological products. Methodology: A. niger was tested against Candida albicans on the same petri dish of potato dextrose agar at room temperature. A. niger was cultured in potato dextrose broth at 27 °C for 7 days. The fungal filtrate was separated from mycelia, and the filtrate was extracted for getting a crude blackish-brown extract. The GC-MS analysis used to identify the constituents of the extract. Results: The filtrate crude extract of A. niger exhibited the antimicrobial effects against Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Candida albicans.GC-MS analysis revealed that the extract contains [(5-methyl-2-phenylindolizine), (thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl-2-butenyl ester) and (22-beta.-acetoxy-3.beta.,16.alpha.-dihydroxy-13,28epoxyolean-2)].The extract had the toxic effect on a solution of the human red blood cells by using 300 µL of 10 mg/ml after 5 minutes while 100 µL and 200 µL of the same concentration did not appear the toxic effects during 1 hour of the testing time period. Conclusions: The extract of A. niger has the ability to produce the antimicrobial activity, so it very needs to separate its constituents into pure compounds for elucidating their chemical structure by using techniques of spectrometry. Then, the compounds can be separately testing against microbial pathogens, human normal cell to determine half lethal concentration (LC50)), and application of other biological tests such as test of LD50. Finally, the identified and purified compounds will be tested by volunteers in order to identify the side effects and toxicity of these compounds to be implemented as drugs for treating diseases in the hospitals

In Vitro Antimicrobial Activity of The Filtrate Crude Extract Produced by Aspergillus niger

Introduction: Aspergillus niger represents one of the fungi that can produce the secondary metabolites, including antimicrobial agents, industrial and biotechnological products. Methodology: A. niger was tested against Candida albicans on the same petri dish of potato dextrose agar at room temperature. A. niger was cultured in potato dextrose broth at 2

In vitro effects of laser beam on antifungal activity of crude chloroform extract produce from leaves of concarups spp

The current study aimed to evaluate the effects of laser irradiation on the antifungal activity of the crude chloroform extract which was produced from leaves of Conocarpus species by which DMSO concentration (50 mg / ml) of this extract was exposed to laser radiation and other concentration was not exposed. Both concentrations were tested against the growth of Cryptococcus neoformans, Microsporum canis, Trichophyton mentagrophytes, and Rhodotorula mucilaginosa. Results showed that C. neoformans was sensitive only laser- exposed chloroform extract. While, the growth of other fungal species was unaffected either from non-laser - exposed chloroform extract or laser-exposed one. GC-MS analysis resulted in a content of the laser exposed crude chloroform extract form ⁅pyrazolo [1,5-a]pyrimidine-3-carbonitrile,2-methylthio-7-(2-pyridyl), ⁅benzaldehyde,2,4-bis(trimethylsil oxy),⁅3-hydroxymandelic acid, ethyl ester, di-TMS, and ⁅ pyrimidine-4,6(3H,5H)-dione, 2-butylthio-⁆ while non-laser exposed extract had ⁅ carbamic acid, methyl-, phenyl ester ⁆, ⁅ acetic acid, phenyl ester ⁆, ⁅ phenol ⁆, ⁅ pentadecanoic acid, methyl ester ⁆, ⁅ hexadecanoic acid, methyl ester ⁆, ⁅ methyl 8-methyl-nonanoate ⁆, ⁅ phytol, acetate ⁆, ⁅3,7,11,15-tetramethyl-2-hexadecen-1-ol ⁆, ⁅ citronellyl isobutyrate ⁆, ⁅ 5H-2a,4a,7a-triaza-7b-phosphacyclopent[cd]indene-7b-thione, 1,2,3,4,6,7-hexahydro-⁆, ⁅ olean-12-en-28-oic acid, 3-oxo-, methyl ester ⁆, ⁅4-amino-5,7-dichlorobenzofurazan ⁆, ⁅ phenol, 2,4-dichloro-6-nitro ⁆, ⁅ ⁆, ⁅ cyclobarbital ⁆, ⁅ benzo[h]quinoline, 2,4-dimethyl- ⁆, ⁅ pyrido[2,3-d]pyrimidine, 4-phenyl-⁆, ⁅ 1H-indole, 5-methyl-2-phenyl-⁆, and ⁅ carbonic acid, butyl octadecyl ester ⁆

Importance of clinical practice guidelines to practicing pediatric nephrologists and IPNA survey

Clinical practice guidelines (CPGs) are systematically developed statements backed by scientific evidence to assist practitioners in management in clinical practice. An international cross-sectional survey was conducted by the IPNA to examine the perceptions of pediatric nephrologists on guidelines and their usage and to identify important diseases for future clinical practice guidelines (CPGs). The survey found that the majority of pediatric nephrologists find CPGs useful in clinical practice and admitted to using them most of the time. Developing CPGs is challenging and there are standards available to develop trustworthy guidelines. While evidence-based global guidelines are ideal, pediatric nephrologists expressed the desire that they address regional differences. Most respondents (89.2%) to the survey agreed that adult guidelines did not cover the pediatric perspective adequately and 71.4% opined that consensus-based pediatric guidelines can be developed when evidence for the pediatric population is lacking. The development of high-quality practice guidelines requires substantial resources and may not be feasible in resource-poor countries. Adaptation of an existing guideline has been suggested as an alternative and the ADAPTE collaboration provides a systematic approach to adapting guidelines. Several diseases where pediatric guidelines are needed as a priority including IgA and C3 glomerulopathy were identified in the survey. Implementation of guideline-based care is challenging and the survey found that lack of availability of guidelines (43%) and resources (22.8%) are important reasons for poor implementation in lower-middle and low-income countries. Perceived complexity of guidelines, physician attitudes, and lack of training also contribute to non-adherence to guidelines