keyword
https://read.qxmd.com/read/38076825/short-term-evolution-of-antibiotic-responses-in-highly-dynamic-environments-favors-loss-of-regulation
#21
John Crow, Hao Geng, Daniel Schultz
Microbes inhabit natural environments that are remarkably dynamic, with sudden environmental shifts that require immediate action by the cell. To cope with changing environments, microbes are equipped with regulated response mechanisms that are only activated when needed. However, when exposed to extreme environments such as clinical antibiotic treatments, complete loss of regulation is frequently observed. Although recent studies suggest that the initial evolution of microbes in new environments tends to favor mutations in regulatory pathways, it is not clear how this evolution is affected by how quickly conditions change (i...
November 30, 2023: bioRxiv
https://read.qxmd.com/read/38066041/high-resolution-simulation-of-basilar-artery-infarct-and-flow-within-the-circle-of-willis
#22
JOURNAL ARTICLE
Jon W S McCullough, Peter V Coveney
On a global scale, cerebro- and cardiovascular diseases have long been one of the leading causes of death and disability and their prevalence appears to be increasing in recent times. Understanding potential biomarkers and risk factors will help to identify individuals potentially at risk of suffering an ischemic stroke. However, the widely variable construction of the cerebral vasculature makes it difficult to provide a specific assessment without the knowledge of a patient's physiology. In this paper we use the 3D blood flow simulator HemeLB to study flow within three common structural variations of the circle of Willis during and in the moments after a blockage of the basilar artery...
December 8, 2023: Scientific Reports
https://read.qxmd.com/read/38057295/a-novel-dsp-zebrafish-model-reveals-training-and-drug-induced-modulation-of-arrhythmogenic-cardiomyopathy-phenotypes
#23
JOURNAL ARTICLE
Rudy Celeghin, Giovanni Risato, Giorgia Beffagna, Marco Cason, Maria Bueno Marinas, Mila Della Barbera, Nicola Facchinello, Alice Giuliodori, Raquel Brañas Casas, Micol Caichiolo, Andrea Vettori, Enrico Grisan, Stefania Rizzo, Luisa Dalla Valle, Francesco Argenton, Gaetano Thiene, Natascia Tiso, Kalliopi Pilichou, Cristina Basso
Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested...
December 6, 2023: Cell Death Discovery
https://read.qxmd.com/read/37988834/ischemic-stroke-with-positive-antiphospholipid-antibodies-in-bloom-syndrome-a-case-report
#24
Jing Zhang, Chenming Wei, Jian Wu
OBJECTIVE: Bloom syndrome is a chromosomal breakage disorder associated with immune deficiency, characterized by short stature, predisposition to early-onset cancer, and immune defects. Currently, there have been no reports of acute cerebral infarction in patients with Bloom syndrome. Here, we report a case of Bloom syndrome complicated by elevated antiphospholipid antibodies and acute cerebral infarction. MATERIALS AND METHODS: A 23-year-old male with a known genetic diagnosis of Bloom syndrome was admitted to the Respiratory Department due to pulmonary aspergillosis...
January 2024: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://read.qxmd.com/read/37980911/short-oral-regimens-for-pulmonary-rifampicin-resistant-tuberculosis-tb-practecal-an-open-label-randomised-controlled-phase-2b-3-multi-arm-multicentre-non-inferiority-trial
#25
RANDOMIZED CONTROLLED TRIAL
Bern-Thomas Nyang'wa, Catherine Berry, Emil Kazounis, Ilaria Motta, Nargiza Parpieva, Zinaida Tigay, Ronelle Moodliar, Matthew Dodd, Varvara Solodovnikova, Irina Liverko, Shakira Rajaram, Mohammed Rassool, Timothy McHugh, Melvin Spigelman, David A Moore, Koert Ritmeijer, Philipp du Cros, Katherine Fielding
BACKGROUND: Around 500 000 people worldwide develop rifampicin-resistant tuberculosis each year. The proportion of successful treatment outcomes remains low and new treatments are needed. Following an interim analysis, we report the final safety and efficacy outcomes of the TB-PRACTECAL trial, evaluating the safety and efficacy of oral regimens for the treatment of rifampicin-resistant tuberculosis. METHODS: This open-label, randomised, controlled, multi-arm, multicentre, non-inferiority trial was conducted at seven hospital and community sites in Uzbekistan, Belarus, and South Africa, and enrolled participants aged 15 years and older with pulmonary rifampicin-resistant tuberculosis...
February 2024: Lancet Respiratory Medicine
https://read.qxmd.com/read/37950157/actinomyces-meyeri-induced-brain-abscess-in-pregnancy-a-case-report
#26
JOURNAL ARTICLE
Yaping Zhang, Zhinan Ye, Qianqian Miao, Hao Xu, Wenyang Pang
BACKGROUND: Brain abscesses can occur when suppurative, bacterial or protozoan infections spread to the brain. Here, we report a rare case of Actinomyces meyeri-induced brain abscess in a pregnant woman. CASE PRESENTATION: We present the case of a 38-years-old primipara admitted to the emergency department at our hospital with a 4-day history of fever and vomiting. The symptoms worsened rapidly during the 8 h prior to admission, and the patient experienced a sudden loss of consciousness 4 h before arrival to the unit...
November 11, 2023: BMC Neurology
https://read.qxmd.com/read/37893308/orange-carotenoid-protein-in-mesoporous-silica-a-new-system-towards-the-development-of-colorimetric-and-fluorescent-sensors-for-ph-and-temperature
#27
JOURNAL ARTICLE
Silvia Leccese, Andrea Calcinoni, Adjélé Wilson, Diana Kirilovsky, Donatella Carbonera, Thomas Onfroy, Claude Jolivalt, Alberto Mezzetti
Orange carotenoid protein (OCP) is a photochromic carotenoprotein involved in the photoprotection of cyanobacteria. It is activated by blue-green light to a red form OCPR capable of dissipating the excess of energy of the cyanobacterial photosynthetic light-harvesting systems. Activation to OCPR can also be achieved in the dark. In the present work, activation by pH changes of two different OCPs-containing echinenone or canthaxanthin as carotenoids-is investigated in different conditions. A particular emphasis is put on OCP encapsulated in SBA-15 mesoporous silica nanoparticles...
September 29, 2023: Micromachines
https://read.qxmd.com/read/37891008/pgr5-is-required-to-avoid-photosynthetic-oscillations-during-light-transitions
#28
JOURNAL ARTICLE
Gustaf E Degen, Federica Pastorelli, Matthew P Johnson
The production of ATP and NADPH by the light reactions of photosynthesis and their consumption by the Calvin-Benson-Bassham (CBB) cycle and other downstream metabolic reactions requires careful regulation. Environmental shifts perturb this careful balance, leading to photo-oxidative stress and losses in CO2 assimilation. Imbalances in the production and consumption of ATP and NADPH manifest themselves as transient instability in the chlorophyll fluorescence, P700, electrochromic shift and CO2 uptake signals recorded on leaves...
October 28, 2023: Journal of Experimental Botany
https://read.qxmd.com/read/37850910/desolvation-processes-in-channel-solvates-of-niclosamide
#29
JOURNAL ARTICLE
Jen E Mann, Renee Gao, Shae S London, Jennifer A Swift
The antiparasitic drug niclosamide (NCL) is notable for its ability to crystallize in multiple 1:1 channel solvate forms, none of which are isostructural. Here, using a combination of time-resolved synchrotron powder X-ray diffraction and thermogravimetry, the process-induced desolvation mechanisms of methanol and acetonitrile solvates are investigated. Structural changes in both solvates follow a complicated molecular-level trajectory characterized by a sudden shift in lattice parameters several degrees below the temperature where the desolvated phase first appears...
October 18, 2023: Molecular Pharmaceutics
https://read.qxmd.com/read/37820026/unraveling-propylene-oxide-formation-in-alkali-metal-batteries
#30
JOURNAL ARTICLE
Daniel Stottmeister, Leonie Wildersinn, Julia Maibach, Andreas Hofmann, Fabian Jeschull, Axel Groß
The increasing need for electrochemical energy storage drives the development of post-lithium battery systems. Among the most promising battery types are sodium-based battery systems. However, like its lithium predecessor, sodium batteries suffer from various issues like parasitic side reactions, which lead to a loss of active sodium inventory, thus reducing the capacity over time. Some problems in sodium batteries arise from an unstable solid electrolyte interphase (SEI) reducing its protective power. While it is known that the electrolyte affects the SEI structure, the exact formation mechanism of the SEI is not yet fully understood...
October 11, 2023: ChemSusChem
https://read.qxmd.com/read/37809206/double-trouble-eales-disease-in-a-background-of-paradoxical-embolism
#31
David Horvath, Usama Aljameey, Elizabeth Douglas
Eales disease is an idiopathic retinal vasculitis that mainly affects the periphery of the retina. The disease commonly manifests as peripheral retinal perivasculitis, peripheral retinal capillary nonperfusion, neovascularization, and recurrent vitreous hemorrhage. Here, we present the case of a 36-year-old male who was diagnosed with Eales disease after presenting with sudden onset flashes of light, reduced visual acuity, and a black spot in his left eye. Upon examination, his left eye exhibited a superior non-foveal branch retinal artery occlusion (BRAO) with a sludged blood column, an old extramacular branch retinal vein occlusion (BRVO) with hemorrhage, and vascular sheathing...
September 2023: Curēus
https://read.qxmd.com/read/37809125/skull-base-collision-tumors-giant-non-functioning-pituitary-adenoma-and-olfactory-groove-meningioma
#32
Mehmet V Aydin, Kivanc Yangi, Ezgi Toptas, Seckin Aydin
A collision tumor complex is composed of at least two different tumors, benign or malignant, with at least two different histopathological features located adjacent to each other in the exact anatomical localization. Pathologies such as meningiomas, pituitary adenomas, gliomas, and schwannomas may be involved in a collision tumor complex. However, co-occurrence of pituitary adenomas and meningiomas as skull base collision tumors is rare. Here, we present a 65-year-old male patient who presented with olfactory groove meningioma and non-functioning pituitary adenoma as a collision tumor...
September 2023: Curēus
https://read.qxmd.com/read/37808493/acute-spinal-cord-infarction-secondary-to-ankylosing-spondylitis-a-case-report-and-literature-review
#33
Wenjuan Li, Jia Guo, Lei Wang, Tinghua Zhang, Tian Li
INTRODUCTION: Spinal cord infarction secondary to ankylosing spondylitis is a rare but severe disorder. CASE PRESENTATION: Here we present a case of acute spinal cord infarction in a 54 years-old man with a medical history of ankylosing spondylitis, scoliosis, and hypotension. The patient complained of a sudden onset of lower limb weakness. A physical examination showed that he suffered from a dissociative sensory disorder, paralysis, and concomitant sphincter disturbances...
2023: Frontiers in Neurology
https://read.qxmd.com/read/37808472/human-blood-labyrinth-barrier-model-to-study-the-effects-of-cytokines-and-inflammation
#34
JOURNAL ARTICLE
Marijana Sekulic, Raoul Puche, Daniel Bodmer, Vesna Petkovic
Hearing loss is one of the 10 leading causes of disability worldwide. No drug therapies are currently available to protect or restore hearing. Inner ear auditory hair cells and the blood-labyrinth barrier (BLB) are critical for normal hearing, and the BLB between the systemic circulation and stria vascularis is crucial for maintaining cochlear and vestibular homeostasis. BLB defects are associated with inner ear diseases that lead to hearing loss, including vascular malformations, inflammation, and Meniere's disease (MD)...
2023: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/37798525/experimental-study-on-the-seepage-mutation-of-natural-karst-collapse-pillar-kcp-fillings-over-mass-outflow
#35
JOURNAL ARTICLE
Boyang Zhang, Gang Liu, Yingchun Li, Zhibin Lin
Conduction between the unique geological formation karst collapse pillar (KCP) and the fractures caused by mining in the coal seam floor can lead to catastrophic water inrush disasters in many coalmines in Northern China. It is widely recognized that seepage mutation induced by the migration/loss of KCP fillings (highly broken rocks filling the fractured rocks) happens during occurrence of the KCP-related water inrush. However, roles of fluid path (mining-induced fracture) scale and KCP filling porosity in seepage mutation evolution remain unclear...
October 6, 2023: Environmental Science and Pollution Research International
https://read.qxmd.com/read/37793168/proline-rich-transmembrane-protein-2-knock-in-mice-present-dopamine-dependent-motor-deficits
#36
JOURNAL ARTICLE
Daisuke Hatta, Kaito Kanamoto, Shiho Makiya, Kaori Watanabe, Tatsuya Kishino, Akira Kinoshita, Koh-Ichiro Yoshiura, Naohiro Kurotaki, Keiro Shirotani, Nobuhisa Iwata
Mutations of proline-rich transmembrane protein 2 (PRRT2) lead to dyskinetic disorders such as paroxysmal kinesigenic dyskinesia (PKD), which is characterized by attacks of involuntary movements precipitated by suddenly initiated motion, and some convulsive disorders. Although previous studies have shown that PKD might be caused by cerebellar dysfunction, PRRT2 has not been sufficiently analyzed in some motor-related regions including the basal ganglia, where dopaminergic neurons are most abundant in the brain...
October 4, 2023: Journal of Biochemistry
https://read.qxmd.com/read/37786311/human-kidney-proximal-tubule-microvascular-model-facilitates-high-throughput-analyses-of-structural-and-functional-effects-of-ischemia-reperfusion-injury
#37
JOURNAL ARTICLE
Erin M Shaughnessey, Samuel H Kann, Joseph L Charest, Else M Vedula
Kidney ischemia reperfusion injury (IRI) poses a major global healthcare burden, but effective treatments remain elusive. IRI involves a complex interplay of tissue-level structural and functional changes caused by interruptions in blood and filtrate flow and reduced oxygenation. Existing in vitro models poorly replicate the in vivo injury environment and lack means of monitoring tissue function during the injury process. Here, a high-throughput human primary kidney proximal tubule (PT)-microvascular model is described, which facilitates in-depth structural and rapid functional characterization of IRI-induced changes in the tissue barrier...
October 2, 2023: Advanced biology
https://read.qxmd.com/read/37740238/personalized-medicine-in-the-dish-to-prevent-calcium-leak-associated-with-short-coupled-polymorphic-ventricular-tachycardia-in-patient-derived-cardiomyocytes
#38
JOURNAL ARTICLE
Yvonne Sleiman, Steven Reiken, Azzouz Charrabi, Fabrice Jaffré, Leah R Sittenfeld, Jean-Luc Pasquié, Sarah Colombani, Bruce B Lerman, Shuibing Chen, Andrew R Marks, Jim W Cheung, Todd Evans, Alain Lacampagne, Albano C Meli
BACKGROUND: Polymorphic ventricular tachycardia (PMVT) is a rare genetic disease associated with structurally normal hearts which in 8% of cases can lead to sudden cardiac death, typically exercise-induced. We previously showed a link between the RyR2-H29D mutation and a clinical phenotype of short-coupled PMVT at rest using patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs). In the present study, we evaluated the effects of clinical and experimental anti-arrhythmic drugs on the intracellular Ca2+ handling, contractile and molecular properties in PMVT hiPSC-CMs in order to model a personalized medicine approach in vitro...
September 23, 2023: Stem Cell Research & Therapy
https://read.qxmd.com/read/37707495/a-generic-binding-pocket-for-small-molecule-i-ks-activators-at-the-extracellular-inter-subunit-interface-of-kcnq1-and-kcne1-channel-complexes
#39
JOURNAL ARTICLE
Magnus Chan, Harutyun Sahakyan, Jodene Eldstrom, Daniel Sastre, Yundi Wang, Ying Dou, Marc Pourrier, Vitya Vardanyan, David Fedida
The cardiac IKs ion channel comprises KCNQ1, calmodulin, and KCNE1 in a dodecameric complex which provides a repolarizing current reserve at higher heart rates and protects from arrhythmia syndromes that cause fainting and sudden death. Pharmacological activators of I Ks are therefore of interest both scientifically and therapeutically for treatment of I Ks loss-of-function disorders. One group of chemical activators are only active in the presence of the accessory KCNE1 subunit and here we investigate this phenomenon using molecular modeling techniques and mutagenesis scanning in mammalian cells...
September 14, 2023: ELife
https://read.qxmd.com/read/37672386/loss-of-ptpmt1-limits-mitochondrial-utilization-of-carbohydrates-and-leads-to-muscle-atrophy-and-heart-failure-in-tissue-specific-knockout-mice
#40
JOURNAL ARTICLE
Hong Zheng, Qianjin Li, Shanhu Li, Zhiguo Li, Marco Brotto, Daiana Weiss, Domenick Prosdocimo, Chunhui Xu, Ashruth Reddy, Michelle Puchowicz, Xinyang Zhao, M Neale Weitzmann, Mukesh K Jain, Cheng-Kui Qu
While mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here, we report that the deletion of Ptpmt1 , a mitochondria-based phosphatase, critically alters mitochondrial fuel selection - the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced...
September 6, 2023: ELife
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