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https://www.readbyqxmd.com/read/28821771/thermal-acclimation-mitigates-cold-induced-paracellular-leak-from-the-drosophila-gut
#1
Heath A MacMillan, Gil Y Yerushalmi, Sima Jonusaite, Scott P Kelly, Andrew Donini
Chill susceptible insects suffer tissue damage and die at low temperatures. The mechanisms that cause chilling injury are not well understood but a growing body of evidence suggests that a cold-induced loss of ion and water homeostasis leads to hemolymph hyperkalemia that depolarizes cells, leading to cell death. The apparent root of this cascade is the net leak of osmolytes down their concentration gradients in the cold. Many insects, however, are capable of adjusting their thermal physiology, and cold-acclimated Drosophila can maintain homeostasis and avoid injury better than warm-acclimated flies...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790967/rethinking-neuroprotection-in-severe-traumatic-brain-injury-toward-bedside-neuroprotection
#2
REVIEW
Tommaso Zoerle, Marco Carbonara, Elisa R Zanier, Fabrizio Ortolano, Giulio Bertani, Sandra Magnoni, Nino Stocchetti
Neuroprotection after traumatic brain injury (TBI) is an important goal pursued strenuously in the last 30 years. The acute cerebral injury triggers a cascade of biochemical events that may worsen the integrity, function, and connectivity of the brain cells and decrease the chance of functional recovery. A number of molecules acting against this deleterious cascade have been tested in the experimental setting, often with preliminary encouraging results. Unfortunately, clinical trials using those candidate neuroprotectants molecules have consistently produced disappointing results, highlighting the necessity of improving the research standards...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28790436/three-tf-co-expression-modules-regulate-pressure-overload-cardiac-hypertrophy-in-male-mice
#3
Yao-Ming Chang, Li Ling, Ya-Ting Chang, Yu-Wang Chang, Wen-Hsiung Li, Arthur Chun-Chieh Shih, Chien-Chang Chen
Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic process are still largely unknown. In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28777506/when-patients-fail-unaids-last-90-the-failure-cascade-beyond-90-90-90-in-rural-lesotho-southern-africa-a-prospective-cohort-study
#4
Niklaus Daniel Labhardt, Isaac Ringera, Thabo Ishmael Lejone, Molisana Cheleboi, Sarah Wagner, Josephine Muhairwe, Thomas Klimkait
INTRODUCTION: HIV-infected individuals on first-line antiretroviral therapy (ART) in resource-limited settings who do not achieve the last "90" (viral suppression) enter a complex care cascade: enhanced adherence counselling (EAC), repetition of viral load (VL) and switch to second-line ART aiming to achieve resuppression. This study describes the "failure cascade" in patients in Lesotho. METHODS: Patients aged ≥16 years on first-line ART at 10 facilities in rural Lesotho received a first-time VL in June 2014...
July 19, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28772199/novel-therapeutic-targets-for-epilepsy-intervention
#5
REVIEW
Lazari Kambli, Lokesh Kumar Bhatt, Manisha Oza, Kedar Prabhavalkar
Epilepsy is a common neurological disorder involving recurrent seizures and affecting about 1% of the population worldwide. Despite several antiepileptic drugs and effective therapies available for epilepsy, about 25% of the patients show therapeutic failure. Thus there exists an unmet need for newer antiepileptic drugs targeting newer targets with different mechanisms of action. Current research in epilepsy generally focuses on mechanisms that control neuronal excitability. Recently attention has been focussed on novel targets, their various interactions, and signalling cascades relating to epilepsy...
July 25, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28756653/mir-23a-regulates-cardiomyocyte-apoptosis-by-targeting-manganese-superoxide-dismutase
#6
Bo Long, Tian-Yi Gan, Rong-Cheng Zhang, Yu-Hui Zhang
Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28754451/role-of-inflammation-and-proinflammatory-cytokines-in-cholangiocyte-pathophysiology
#7
REVIEW
Claudio, Debora Maria Giordano, Luca Maroni, Marco Marzioni
Cholangiocytes, the epithelial cells lining the bile ducts, are an important subset of liver cells. They are involved in the modification of bile volume and composition, and respond to endogenous and exogenous stimuli. Along the biliary tree, two different kinds of cholangiocytes exist: small and large cholangiocytes. Each type has different features and biological role in physiologic and pathologic conditions, and their immunobiology is important for understanding biliary diseases. Cholangiocytes provide the first line of defence against luminal microbes in the hepatobiliary system...
July 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28751931/a-review-of-the-molecular-mechanisms-underlying-the-development-and-progression-of-cardiac-remodeling
#8
REVIEW
Leonardo Schirone, Maurizio Forte, Silvia Palmerio, Derek Yee, Cristina Nocella, Francesco Angelini, Francesca Pagano, Sonia Schiavon, Antonella Bordin, Albino Carrizzo, Carmine Vecchione, Valentina Valenti, Isotta Chimenti, Elena De Falco, Sebastiano Sciarretta, Giacomo Frati
Pathological molecular mechanisms involved in myocardial remodeling contribute to alter the existing structure of the heart, leading to cardiac dysfunction. Among the complex signaling network that characterizes myocardial remodeling, the distinct processes are myocyte loss, cardiac hypertrophy, alteration of extracellular matrix homeostasis, fibrosis, defective autophagy, metabolic abnormalities, and mitochondrial dysfunction. Several pathophysiological stimuli, such as pressure and volume overload, trigger the remodeling cascade, a process that initially confers protection to the heart as a compensatory mechanism...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28750011/leptospira-interrogans-causes-quantitative-and-morphological-disturbances-in-adherens-junctions-and-other-biological-groups-of-proteins-in-human-endothelial-cells
#9
Hiromi Sato, Jenifer Coburn
Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28747166/cascade-fumarate-hydratase-mutation-screening-allows-early-detection-of-kidney-tumour-a-case-report
#10
Melanie M Y Chan, Angela Barnicoat, Faiz Mumtaz, Michael Aitchison, Lucy Side, Helen Brittain, Alan W H Bates, Daniel P Gale
BACKGROUND: Fumarate hydratase (FH) deficiency is a rare autosomal recessive disorder which results in a major defect in cellular metabolism. It presents in infancy with progressive encephalopathy, hypotonia, seizures and failure to thrive and is often fatal in childhood. It is caused by mutations in the FH gene (1q42.1) that result in deficiency of the citric acid cycle enzyme fumarate hydratase, resulting in accumulation of fumaric acid. Heterozygous germline mutations in the FH gene predispose to an aggressive autosomal dominant inherited early-onset kidney cancer syndrome: hereditary leiomyomatosis and renal cell cancer (HLRCC)...
July 26, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28727823/structural-instability-of-large-scale-functional-networks
#11
Shogo Mizutaka, Kousuke Yakubo
We study how large functional networks can grow stably under possible cascading overload failures and evaluated the maximum stable network size above which even a small-scale failure would cause a fatal breakdown of the network. Employing a model of cascading failures induced by temporally fluctuating loads, the maximum stable size nmax has been calculated as a function of the load reduction parameter r that characterizes how quickly the total load is reduced during the cascade. If we reduce the total load sufficiently fast (r ≥ rc), the network can grow infinitely...
2017: PloS One
https://www.readbyqxmd.com/read/28722141/failure-to-rescue-as-a-nurse-sensitive-indicator
#12
Jane Mushta, Kathy L Rush, Elizabeth Andersen
PROBLEM: The aim of this concept analysis was to clarify failure to rescure as a nurse-sensitive indicator. Although the concept of failure to rescue as a nurse-sensitive outcome has appeared in the nursing literature for over a decade, conceptual clarity is needed to address its variable and ambiguous use in health care. METHODS: Walker and Avant's eight-stage method of concept analysis was used to explore the concept of failure to rescue in nursing practice. Twenty-one papers were retrieved from Cumulative Index of Nursing and Allied Health Literature (CINAHL) and MEDLINE databases and selected for review and synthesis...
July 19, 2017: Nursing Forum
https://www.readbyqxmd.com/read/28711594/hepatic-mitochondrial-bioenergetics-in-aged-c57bl-6-mice-exhibit-delayed-recovery-from-severe-burn-injury
#13
Christopher Auger, Thibacg Sivayoganathan, Abdikarim Abdullahi, Alexandra Parousis, Marc G Jeschke
Severe burn injuries initiate a cascade of downstream events, culminating in multiple organ dysfunction, sepsis, and even death. The elderly are in particular vulnerable to such outcomes, due primarily to a scarcity of knowledge on trauma progression at the biomolecular level in this population. Mitochondria, the cellular powerhouses, have been increasingly scrutinized recently for their contribution to trauma outcomes. We hypothesized that elderly have a worse outcome compared to adult patients due to failed recovery of hepatic mitochondria...
July 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28698549/a-tissue-engineered-model-of-aging-interdependence-and-cooperative-effects-in-failing-tissues
#14
A Acun, D C Vural, P Zorlutuna
Aging remains a fundamental open problem in modern biology. Although there exist a number of theories on aging on the cellular scale, nearly nothing is known about how microscopic failures cascade to macroscopic failures of tissues, organs and ultimately the organism. The goal of this work is to bridge microscopic cell failure to macroscopic manifestations of aging. We use tissue engineered constructs to control the cellular-level damage and cell-cell distance in individual tissues to establish the role of complex interdependence and interactions between cells in aging tissues...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684793/differentiating-staphylococcus-aureus-from-escherichia-coli-mastitis-s-aureus-triggers-unbalanced-immune-dampening-and-host-cell-invasion-immediately-after-udder-infection
#15
Juliane Günther, Wolfram Petzl, Isabel Bauer, Siriluck Ponsuksili, Holm Zerbe, Hans-Joachim Schuberth, Ronald M Brunner, Hans-Martin Seyfert
The etiology determines quality and extent of the immune response after udder infection (mastitis). Infections with Gram negative bacteria (e.g. Escherichia coli) will quickly elicit strong inflammation of the udder, fully activate its immune defence via pathogen receptor driven activation of IκB/NF-κB signaling. This often eradicates the pathogen. In contrast, Gram-positive bacteria (e.g. Staphylococcus aureus) will slowly elicit a much weaker inflammation and immune response, frequently resulting in chronic infections...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678521/restoration-of-megalin-mediated-clearance-of-alveolar-protein-as-a-novel-therapeutic-approach-for-acute-lung-injury
#16
Christine U Vohwinkel, Yasmin Buchäckert, Hamza M Al-Tamari, Luciana C Mazzocchi, Holger K Eltzschig, Konstantin Mayer, Rory E Morty, Susanne Herold, Werner Seeger, Soni S Pullamsetti, István Vadász
Acute respiratory distress syndrome (ARDS) constitutes a significant disease burden with regard to both morbidity and mortality. Current therapies are mostly supportive and do not address the underlying pathophysiologic mechanisms. Removal of protein-rich alveolar edema - a clinical hallmark of ARDS - is critical for survival. Here, we describe a TGFβ-triggered mechanism, in which megalin, the primary mediator of alveolar protein transport, is negatively regulated by GSK3β, with protein phosphatase 1 (PP1) and nuclear inhibitor of PP1 being involved in the signaling cascade...
July 5, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28675640/characterization-of-serum-proteins-attached-to-distinct-sol-gel-hybrid-surfaces
#17
Nuno Araújo-Gomes, Francisco Romero-Gavilán, Ana M Sánchez-Pérez, Marilo Gurruchaga, Mikel Azkargorta, Felix Elortza, María Martinez-Ibañez, Ibon Iloro, Julio Suay, Isabel Goñi
The success of a dental implant depends on its osseointegration, an important feature of the implant biocompatibility. In this study, two distinct sol-gel hybrid coating formulations [50% methyltrimethoxysilane: 50% 3-glycidoxypropyl-trimethoxysilane (50M50G) and 70% methyltrimethoxysilane with 30% tetraethyl orthosilicate (70M30T)] were applied onto titanium implants. To evaluate their osseointegration, in vitro and in vivo assays were performed. Cell proliferation and differentiation in vitro did not show any differences between the coatings...
July 4, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28673566/cancer-is-an-adaptation-that-selects-in-animals-against-energy-dissipation
#18
Anthonie W J Muller
As cancer usually follows reproduction, it is generally assumed that cancer does not select. Graham has however argued that juvenile cancer, which precedes reproduction, could during evolution have implemented a "cancer selection" that resulted in novel traits that suppress this juvenile cancer; an example is protection against UV sunlight-induced cancer, required for the emergence of terrestrial animals from the sea. We modify the cancer selection mechanism to the posited "cancer adaptation" mechanism, in which juvenile mortality is enhanced through the diminished care received by juveniles from their (grand) parents when these suffer from cancer in old age...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28670735/six3-deletions-and-incomplete-penetrance-in-families-affected-by-holoprosencephaly
#19
Bethany Stokes, Seth I Berger, Beth A Hall, Karin Weiss, Donald W Hadley, David R Murdock, Subhadra Ramanathan, Robin D Clark, Erich Roessler, Paul Kruszka, Maximilian Muenke
Holoprosencephaly (HPE) is failure of the forebrain to divide completely during embryogenesis. Incomplete penetrance has not been reported previously in SIX3 whole gene deletions which are known to cause HPE. Both chromosomal microarray and whole exome sequencing (WES) were used to evaluated families with inherited HPE. Two families showed inherited deletions that contain SIX3 and were incompletely penetrant for HPE. Using WES, we ruled out parental mosaicism, a SIX3 hypomorph, and clinically significant variants in genes that are known to interact with SIX3 as causes of incomplete penetrance...
July 2, 2017: Congenital Anomalies
https://www.readbyqxmd.com/read/28670625/mechanisms-of-acetaminophen-hepatotoxicity-and-their-translation-to-the-human-pathophysiology
#20
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and mechanisms of liver injury induced by APAP overdose have been the focus of extensive investigation. Studies in the mouse model, which closely reproduces the human condition, have shown that hepatotoxicity is initiated by formation of a reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which depletes cellular glutathione and forms protein adducts on mitochondrial proteins. This leads to mitochondrial oxidative and nitrosative stress, accompanied by activation of c-jun N-terminal kinase (JNK) and its translocation to the mitochondria...
February 2017: Journal of Clinical and Translational Research
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