Isolation and Identification of Bacillus spp. from Syrian Soils and Testing their Antifungal Activity Against Botrytis cinerea in Vitro (in vitro) في ظروف المخبر (Botrytis Cinerea)من ترب سورية واختبار فعاليتها التضادية تجاه الفطر (Bacillus) عزل وتعريف أنواع من الجنس

Three hundred seventy eight isolates of Bacillus spp. from Syrian soils were screened in vitro for their ability to inhibit the growth of Botrytis cinerea, agent of gray mold disease. The B307 isolate showed the highest antagonism activity with growth inhibition of 68%. In addition, B307 had chitinolytic activity, and the fraction from the isolate with more than 50KDa of its cell free crude extract showed the highest chitinolytic and antagonism activity against B. cinerea. This isolate was identified as Bacillus licheniformis according to the 16S DNA gene sequencing data with homology of 99%. The results of this study demonstrated that Bacillus licheniformis B307 and its free cell crude extract could be used as bio-control agent against Botrytis cinerea. تم عزل وغربلة 378 عزلة من الجنس Bacillus من ترب سورية، واختبرت قدرتها في تثبيط نمو الفطر الممرض Botrytis cinerea المسبب للعفن الرمادي، وذلك في ظروف المخبر (in vitro). أظهرت العزلة B307 أعلى فعالية تضادية في تثبيط نمو الفطر بنسبة بلغت 68 %، وأعلى فعالية في حلمهة الكيتين، وكذلك أظهر مستخلصها الخام الخالي من الخلايا والحاوي على بروتينات بأوزان جزيئية أعلى من 50 كيلو دالتون أعلى فعالية حلمهة للكيتين وتضادية تجاه الفطر Botrytis cinerea. تم تحديد هذه العزلة وفقاً لنتائج السلسلة للجينية 16S DNA على أنها Bacillus lichenformis بنسبة تشابه بلغت 99 %. أظهرت نتائج هذه الدراسة إمكانية استعمال السلالة Bacillus licheniformis B307 ومستخلصها الخام الخالي من الخلايا، والذي له فعالية في حلمهة الكيتين كعامل مكافحة حيوية للفطر Botrytis cinerea

A Biological Study of Grapevine Powdery Mildew Caused by Erysiphe necator Schwein in Sweida Province, Southern Syria, دراسة بيولوجية للفطر Erysiphe necator Schwein المسبب لمرض البياض الدقيقي على الكرمة في محافظة السويداء جنوبي سورية

Grapevine powdery mildew caused by Erysiphe necator Schwein. is one of the most important fungal diseases of the grapevine all over the world. Due to the lack of local studies about the source of primary inoculum at the beginning of the season and the progression of the disease during the season, the aims of this study were to evaluate the incidence of grapevine powdery mildew and its biology on four local varieties cultivated in Sweida province (Syria) during 2015 and 2016. The results showed that E. necator survived as mycelium in grapevine dormant buds during winter to form flag shoots at the beginning of the season. Although, cleistothecia were formed on infected leaves, but the ascospores may not have a significant role in the initiation of spring infection.The results showed also that the severity of the disease depended on the primary inoculum sources, the environmental conditions particularly frost, temperature, relative humidity, and the variety susceptibility. It was shown that Balady and Black varieties were highly susceptible to powdery mildew on the leaves and clusters. Salty variety was little susceptible, where symptoms have been observed on clusters holder only, while no symptoms were observed on Halwani variety, which seems to be the most resistant variety. يعد مرض البياض الدقيقي على الكرمة المتسبب عن الفطر Erysiphe necator Schwein واحداً من أهم الأمراض الفطرية التي تصيب الكرمة في كل أنحاء العالم، ونظراً لعدم وجود دراسات محلية حول مصدر اللقاح الأولي في بداية الموسم وتطور المرض خلال الموسم، فقد كان الهدف من الدراسة متابعة تطور مرض البياض الدقيقي عل أربعة أصناف محلية مزروعة في بعض بساتين الكرمة في محافظة السويداء جنوبي سورية، وذلك خلال عامي 2015 و2016. أظهرت النتائج أن الفطر E. necator يمضي فصل الشتاء على شكل مشيجة في البراعم الساكنة على طرود مصابة من العام السابق، والتي تشكل في بداية الموسم ما يدعى بطرود العلم Flag shoots . وعلى الرغم من تشكل الثمار الزقية على الأوراق المصابة، إلا أنها لم تسهم في حدوث الإصابة في بدية الموسم، كما أظهرت النتائج أن شدة الإصابة ترتبط بمصدر اللقاح الأولي(مشيجة ساكنة في البراعم المصابة أو أبواغ كونيدية محمولة بالتيارات الهوائية)، والظروف البيئية من صقيع ودرجة حرارة ورطوبة جوية، وطبيعة الصنف، إذ تبين أن الصنفين بلدي وأسود كانا شديدي القابلية للإصابة بالبياض الدقيقي على الأوراق والعناقيد، بينما الصنف سلطي قليل القابلية، إذ لوحظت الأعراض على حامل العناقيد فقط، في حين لم تلحظ أية إصابة على الصنف حلواني الذي يبدو مقاوماً لإصابة بالمرض

Investigating the role of loop c hydrophilic residue 'T244' in the binding site of ρ1 GABAC receptors via site mutation and partial agonism

The loop C hydrophilic residue, threonine 244 lines the orthosteric binding site of ρ1 GABAC receptors was studied by point mutation into serine, alanine and cysteine, and tested with GABA, some representative partial agonists and antagonists. Thr244 has a hydroxyl group essential for GABA activity that is constrained by the threonine methyl group, orienting it toward the binding site. Significant decreases in activation effects of the studied ligands at ρ1 T244S mutant receptors, suggests a critical role for this residue. Results of aliphatic and heteroaromatic partial agonists demonstrate different pharmacological effects at ρ1 T244S mutant receptors when co-applied with GABA EC50 responses. ρ1 T244A and ρ1 T244C mutant receptors have minimal sensitivity to GABA at high mM concentrations, whereas, the ρ1 WT partial agonists, β-alanine and MTSEA demonstrate more efficacy and potency, respectively, than GABA at these mutant receptors. This study explores the role of Thr244 in the binding of agonists as an initial step during channel gating by moving loop C towards the ligand

Omental infarction in the postpartum period: a case report and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Omental infarction is a rare and often misdiagnosed clinical event with unspecific symptoms. It affects predominantly young and middle aged women.</p> <p>Case presentation</p> <p>This is a case report of a 26-year-old Caucasian woman with spontaneous omental infarction two weeks after normal vaginal delivery.</p> <p>Conclusion</p> <p>Omental infarction is a differential diagnosis in the postpartum acute abdomen. As some cases of omental infarction, which are caused by torsion, can be adequately diagnosed via computed tomography, a conservative treatment strategy for patients without complications should be considered in order to avoid any unnecessary surgical intervention.</p

Age-dependent alterations in the inflammatory response to pulmonary challenge

The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 months or greater than 18 months (approximating humans of 20 and 55-65 years), were challenged, intratracheally, with lipoteichoic acid and peptidoglycan. Cellular and cytokine evaluations were performed on both bronchoalveolar lavage fluid (BAL) and plasma, 24 h post-challenge. The plasma concentration of free thyroxine, a marker of severity in non-thyroidal illness, was also evaluated. The older animals had an increased chemotactic gradient in favor of the airspaces, which was associated with a greater accumulation of neutrophils and protein. Furthermore, macrophage migration inhibitory factor (MIF), an inflammatory mediator and putative biomarker in acute lung injury, was increased in both the plasma and BAL of the older, but not young animals. Conversely, plasma free thyroxine, a natural inhibitor of MIF, was decreased in the older animals. These findings identify age-associated inflammatory/metabolic changes following pulmonary challenge that it may be possible to manipulate to improve outcome in the older, critically ill patient

Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination

Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none

Neurotoxicity of endocrine disruptors : evaluation of the impact of bisphenol A on myelination by a global lipidomics approach

Au cours du développement, le cerveau est exposé à une myriade de perturbateurs endocriniens (EDC) qui, même à faible dose, peuvent interférer avec de nombreuses voies de signalisation et, de ce fait, contribuer au développement de troubles neurodéveloppementaux. Peu d'études ont exploré l'incidence des EDC sur les oligodendrocytes, alors même qu'ils assurent la myélinisation, une étape fondamentale du développement du SNC (Smirnova et al., ALTEX, 2014). Les lipides, constituants très majoritaires de la myéline, peuvent être considérés comme des indicateurs essentiels des perturbations pathologiques ou toxiques dont elle est la cible. Notre étude visait à étudier l'effet du bisphénol A (BPA), EDC de référence, sur la différenciation des oligodendrocytes et la myélinisation au travers des perturbations du lipidome. Nous nous sommes appuyés sur deux modèles expérimentaux : un modèle in vivo reposant sur l'exposition de souris au BPA pendant la gestation et la lactation, du jour de gestation (G) 7 au jour post-natal (P) 22, et un modèle in vitro d'oligodendrocytes en cours de différenciation, la lignée Oli-neu. Nous avons également fondé notre étude sur une caractérisation exhaustive des modifications lipidiques dans ces deux modèles, à l'aide d'analyses lipidomiques par chromatographie liquide ultra-performance couplée à la spectrométrie de masse. En prérequis à l'étude des effets du BPA, les modifications lipidiques associées à la différenciation des oligodendrocytes et à la myélinisation ont tout abord été caractérisées. Chez la souris femelle, entre un stade précoce peu myélinisé (P15) et un stade tardif myélinisé (P30/P40/P60), la myélinisation s'est accompagnée par un enrichissement en lipides caractéristiques de la myéline tels que les sulfatides (ST), les hexosylcéramides, les plasmalogènes phosphatidyléthanolamine (ePE) et le cholestérol. La myélinisation s'est également accompagnée d'une diminution de la teneur en phosphatidylcholines (PC) et une augmentation de la teneur en phosphatidyléthanolamines (PE), phosphatidylsérines (PS) et phosphatidylinositols (PI), concomitante à une proportion accrue d'acides gras monoinsaturés (AGMI) dans ces sous-classes. Ces résultats ont été étayés par une expression augmentée des gènes impliqués dans la synthèse des PE, PI, PS et AGMI dans les oligodendrocytes O4+ au cours du développement post-natal. La plupart de ces changements ont également été observés chez les mâles mais avec une amplitude plus faible en raison d'une myélinisation plus avancée à P15 par rapport aux femelles. De façon similaire à la myélinisation in vivo, la différentiation des Oli-neu s'est accompagnée d'une augmentation des teneurs en ST, ePE, PE, et PI et une diminution du taux de PC. In vivo, l'exposition précoce au BPA (40 µg.kg-1.j-1) a provoqué des modifications transitoires du lipidome de la myéline à P15, disparaissant à P30 et à P60. Ces modifications, observées uniquement chez la femelle, incluaient une diminution de la teneur en PC concomitante à une augmentation des PS, PE, ePE, PI, et de leur contenu en AGMI, corroborés par l'augmentation de l'expression du gène codant ETNK1 dans le cerveau, enzyme impliquée dans la biosynthèse des PE. Ces modifications suggèrent que l'exposition au BPA accélère le processus de myélinisation chez la femelle au cours des deux premières semaines postnatales. A l'inverse, in vitro, le BPA (10 µM) a légèrement freiné la différenciation des Oli-neu en ciblant le métabolisme des ST. En conclusion, en s'intéressant au processus de myélinisation et à sa perturbation par le BPA par l'exploration exhaustive du lipidome, cette étude pourrait contribuer à clarifier le rôle de cet EDC dans les troubles neurodéveloppementaux.During development, the brain is exposed to a myriad of endocrine disruptors (EDCs) which, even at low doses, can interfere with many signaling pathways and thereby contribute to the development of neurodevelopmental disorders. Few studies have explored the impact of EDCs on oligodendrocytes, even as they provide myelination, a fundamental step in CNS development (Smirnova et al., ALTEX, 2014). Lipids, the very majority constituents of myelin, can be considered as essential indicators of the pathological or toxic disturbances of which it is the target. Our study aimed to investigate the effect of bisphenol A (BPA), a reference EDC, on oligodendrocyte differentiation and myelination through lipidome disturbances. We relied on two experimental models: an in vivo model based on the exposure of mice to BPA during gestation and lactation, from gestational day (G) 7 to postnatal day (P) 22, and an in vitro model of oligodendrocytes in the process of differentiation, the Oli-neu line. We also based our study on an exhaustive characterization of the lipid modifications in these two models, using lipidomic analyzes by ultra-performance liquid chromatography coupled with mass spectrometry. As a prerequisite for studying the effects of BPA, the lipid changes associated with oligodendrocyte differentiation and myelination were first characterized. In female mice, between a poorly myelinated early stage (P15) and a late myelinated stage (P30/P40/P60), myelination was accompanied by an enrichment in lipids characteristic of myelin such as sulfatides (ST), hexosylceramides, phosphatidylethanolamine (ePE) plasmalogens and cholesterol. Myelination was also accompanied by a decrease in the content of phosphatidylcholines (PC) and an increase in the content of phosphatidylethanolamines (PE), phosphatidylserines (PS) and phosphatidylinositols (PI), concomitant with an increased proportion of fatty acids monounsaturated (MUFA) in these subclasses. These results were supported by an increased expression of genes involved in the synthesis of PE, PI, PS and MUFA in O4+ oligodendrocytes during postnatal development. Most of these changes were also observed in males but with a lower amplitude due to more advanced myelination at P15 compared to females. Similarly, the differentiation of Oli-neu was accompanied by an increase in the contents of ST, ePE, PE, and PI and a decrease in the level of PC. In vivo, early exposure to BPA (40 µg.kg-1.d-1) caused transient changes in the myelin lipidome at P15, disappearing at P30 and P60. These changes, observed only in females, included a decrease in PC content concomitant with an increase in PS, PE, ePE, PI, and their MUFA content, corroborated by the increase in the expression of the gene encoding ETNK1 in the brain, an enzyme involved in the biosynthesis of PEs. These changes suggest that exposure to BPA accelerates the process of myelination in the female during the first two postnatal weeks. Conversely, in vitro, BPA (10 µM) slightly slowed down Oli-neu differentiation by targeting ST metabolism. In conclusion, by focusing on the process of myelination and its disruption by BPA through the exhaustive exploration of the lipidome, this study could contribute to clarifying the role of this EDC in neurodevelopmental disorders

Bisphenol A Impairs Lipid Remodeling Accompanying Cell Differentiation in the Oligodendroglial Cell Line Oli-Neu

In the central nervous system, the process of myelination involves oligodendrocytes that wrap myelin around axons. Myelin sheaths are mainly composed of lipids and ensure efficient conduction of action potentials. Oligodendrocyte differentiation is an essential preliminary step to myelination which, in turn, is a key event of neurodevelopment. Bisphenol A (BPA), a ubiquitous endocrine disruptor, is suspected to disrupt this developmental process and may, thus, contribute to several neurodevelopmental disorders. In this study, we assessed the effect of BPA on oligodendrocyte differentiation through a comprehensive analysis of cell lipidome by UHPLC-HRMS. For this purpose, we exposed the oligodendroglial cell line Oli-neu to several BPA concentrations for 72 h of proliferation and another 72 h of differentiation. In unexposed cells, significant changes occurred in lipid distribution during Oli-neu differentiation, including an increase in characteristic myelin lipids, sulfatides, and ethanolamine plasmalogens, and a marked remodeling of phospholipid subclasses and fatty acid contents. Moreover, BPA induced a decrease in sulfatide and phosphatidylinositol plasmalogen contents and modified monounsaturated/polyunsaturated fatty acid relative contents in phospholipids. These effects counteracted the lipid remodeling accompanying differentiation and were confirmed by gene expression changes. Altogether, our results suggest that BPA disrupts lipid remodeling accompanying early oligodendrocyte differentiation