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Self destructive

Jennifer Sarah Maria Loose, Magnus Øverlie Arntzen, Bastien Bissaro, Roland Ludwig, Vincent G H Eijsink, Gustav Vaaje-Kolstad
Lytic polysaccharide monooxygenases (LPMOs) play a crucial role in the degradation of polysaccharides in biomass by catalyzing powerful oxidative chemistry using only a single copper ion as co-factor. Despite the natural abundance and importance of these powerful mono-copper enzymes, the structural determinants of their functionality have remained largely unknown. We have used site-directed mutagenesis to probe the roles of 13 conserved amino acids located on the flat substrate-binding surface of CBP21, a chitin-active family AA10 LPMO from Serratia marcescens, also known as SmLPMO10A...
June 14, 2018: Biochemistry
Yanxi Zhang, Gang Ye, Saurabh Soni, Xinkai Qiu, Theodorus L Krijger, Harry T Jonkman, Marco Carlotti, Eric Sauter, Michael Zharnikov, Ryan C Chiechi
Quantum interference effects (QI) are of interest in nano-scale devices based on molecular tunneling junctions because they can affect conductance exponentially through minor structural changes. However, their utilization requires the prediction and deterministic control over the position and magnitude of QI features, which remains a significant challenge. In this context, we designed and synthesized three benzodithiophenes based molecular wires; one linearly-conjugated, one cross-conjugated and one cross-conjugated quinone...
May 21, 2018: Chemical Science
Yonghua Bi, Hongmei Chen, Yahua Li, Zepeng Yu, Xinwei Han, Jianzhuang Ren
The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group...
2018: PloS One
Lary C Walker
Senile plaques and neurofibrillary tangles are the principal histopathologic hallmarks of Alzheimer disease. The essential constituents of these lesions are structurally abnormal variants of normally generated proteins: Aβ protein in plaques and tau protein in tangles. At the molecular level, both proteins in a pathogenic state share key properties with classic prions, i.e., they consist of alternatively folded, β-sheet-rich forms of the proteins that autopropagate by the seeded corruption and self-assembly of like proteins...
2018: Handbook of Clinical Neurology
Ignacio Colomer, Sarah M Morrow, Stephen P Fletcher
Developing physical models of complex dynamic systems showing emergent behaviour is key to informing on persistence and replication in biology, how living matter emerges from chemistry, and how to design systems with new properties. Herein we report a fully synthetic small molecule system in which a surfactant replicator is formed from two phase-separated reactants using an alkene metathesis catalyst. The replicator self-assembles into aggregates, which catalyse their own formation, and is thermodynamically unstable...
June 8, 2018: Nature Communications
C Braaksma, D Vermeulen, A M van Leeuwen, M J G M Speth, T M Piscaer
Rapidly progressive hip disease (RDHD) is a rare condition of the hip joint, causing destruction of the femoral head. The pathogenesis is unknown. The disease is self-limiting, there is no treatment to stop the disease. Hip arthroplasty is a successful way to relieve pain and restore function. We present a case where both hips were involved and analysed. A favourable result was obtained by bilateral total hip arthroplasty.
June 2018: Journal of Orthopaedics
Claire O'Dwyer, Philip McCallion, Éilish Burke, Rachael Carroll, Máire O'Dwyer, Mary McCarron
A growing number of adults with intellectual disabilities (ID) are reaching old age, however, little is known about epidemiology of problem behaviours (PBs) in this population. The aim was to identify the prevalence and associated factors of PBs among older adults with ID in Ireland. Data was generated from Wave 2 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a nationally representative sample of adults with ID aged ≥40. Data on PBs was available for 683 (98...
June 5, 2018: Research in Developmental Disabilities
Jia-Jye Lee, Satish Rao, Gaurav Kaushik, Evren U Azeloglu, Kevin D Costa
Atomic force microscopy (AFM) is used to study mechanical properties of biological materials at submicron length scales. However, such samples are often structurally heterogeneous even at the local level, with different regions having distinct mechanical properties. Physical or chemical disruption can isolate individual structural elements but may alter the properties being measured. Therefore, to determine the micromechanical properties of intact heterogeneous multilayered samples indented by AFM, we propose the Hybrid Eshelby Decomposition (HED) analysis, which combines a modified homogenization theory and finite element modeling to extract layer-specific elastic moduli of composite structures from single indentations, utilizing knowledge of the component distribution to achieve solution uniqueness...
June 5, 2018: Biophysical Journal
Alessandra di Masi, Loris Leboffe, Fabio Polticelli, Federica Tonon, Cristina Zennaro, Marianna Caterino, Pasquale Stano, Stephan Fischer, Marlen Hägele, Martin Müller, Alexander Kleger, Panagiotis Papatheodorou, Giuseppina Nocca, Alessandro Arcovito, Andrea Gori, Margherita Ruoppolo, Holger Barth, Nicola Petrosillo, Paolo Ascenzi, Stefano Di Bella
The pathogenic effects of Clostridium difficile are primarily attributable to the production of the large protein toxins A (TcdA) and B (TcdB). These toxins monoglucosylate Rho GTPases in the cytosol of host cells, causing destruction of the actin cytoskeleton with cytotoxic effects. Low human serum albumin (HSA) levels indicate a higher risk of acquiring and developing a severe C. difficile infection (CDI) and are associated with recurrent and fatal disease. Our results show that HSA at physiological concentrations rescues human epithelial colorectal adenocarcinoma cells and protects stem cell-derived human intestinal organoids from intoxication by a TcdA:TcdB mixture...
June 2, 2018: Journal of Infectious Diseases
Julia Ruskin, Rehana Rasul, Samantha Schneider, Kristin Bevilacqua, Emanuela Taioli, Rebecca M Schwartz
Destruction caused by natural disasters compromises medical providers' and hospitals' abilities to administer care. Hurricane Sandy was particularly devastating, resulting in massive disruptions of medical care in the region. This study aimed to determine whether a lack of access to medical care during Hurricane Sandy was associated with posttraumatic stress disorder (PTSD) symptoms and other mental health/substance abuse outcomes. A secondary aim was to examine whether having a chronic illness moderates those associations...
June 2018: Preventive Medicine Reports
Takayuki Katsuyama, George C Tsokos, Vaishali R Moulton
Systemic lupus erythematosus (SLE) is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result in the breakdown of immune tolerance to "self" leading to damage and destruction of multiple organs, such as the skin, joints, kidneys, heart and brain. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Dendritic cells, neutrophils, and innate lymphoid cells are important in initiating antigen presentation and propagating inflammation at lymphoid and peripheral tissue sites...
2018: Frontiers in Immunology
Nicolas Benoot, Pierre Marcasuzaa, Laurence Pessoni, Sirikorn Chasvised, Stéphanie Reynaud, Antoine Bousquet, Laurent Billon
Hierarchically organized polymer films are produced with a high level of order from the combination of block copolymer nanophase segregation, "breath figure" methodology and microwave irradiation. A block copolymer based on poly(methyl methacrylate) and poly(n-butylacrylate) featuring cylindrical nanopatterns is involved in the "breath figure" process to create a microporous honeycomb structure. These films are submitted to microwave annealing to enhance the degree of ordering of the nano-segregation without the destruction of the honeycomb microstructure, which is not possible by classical thermal or solvent annealing...
May 31, 2018: Soft Matter
Linda B Thompson, Stephen L Powell
Trigeminal trophic syndrome is a rare condition that develops from trigeminal nerve damage causing dysesthesias that result in self-mutilation. Facial and nasal destruction develops from self-destructive behavior (repetitive picking or scratching) secondary to the altered skin sensation created by the damaged trigeminal nerve. Early recognition of this condition is crucial to the prevention of the detrimental complications of facial ulceration and nasal tissue necrosis that can lead to corneal ulcerations, full-thickness eyelid defect, and canthal lesions...
May 2018: Clinical practice and cases in emergency medicine
Kevin C Osum, Adam L Burrack, Tijana Martinov, Nathanael L Sahli, Jason S Mitchell, Christopher G Tucker, Kristen E Pauken, Klearchos Papas, Balamurugan Appakalai, Justin A Spanier, Brian T Fife
Type 1 diabetes is caused by autoreactive T cell-mediated β cell destruction. Even though co-inhibitory receptor programmed death-1 (PD-1) restrains autoimmunity, the expression and regulation of its cognate ligands on β cell remains unknown. Here, we interrogated β cell-intrinsic programmed death ligand-1 (PD-L1) expression in mouse and human islets. We measured a significant increase in the level of PD-L1 surface expression and the frequency of PD-L1+ β cells as non-obese diabetic (NOD) mice aged and developed diabetes...
May 29, 2018: Scientific Reports
A A A van der Linde, A E van Herwaarden, J D Oosting, H L Claahsen-van der Grinten, E P L M de Grouw
BACKGROUND: We describe a 6-year old boy with central diabetes insipidus (CDI) caused by destruction of the pituitary gland due to treatment of an optical pathway glioma. He has been treated with chemotherapy and has had several debulking operations over the past years and consequently developed central hypocortisolism, hypothyroidism and CDI. The treatment of CDI was gravely complicated by an impaired thirst perception and compulsive drinking behavior. He was frequently seen at the ER or admitted due to dysregulation of fluid balance...
April 2018: Pediatric Endocrinology Reviews: PER
Yalei Miao, Yudian Qiu, Wenjing Yang, Yuqi Guo, Hongwei Hou, Zhongyi Liu, Xubo Zhao
Dual pH-/reduction-sensitive biodegradable poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine)/chitosan/dimethylmaleic anhydride-modified chitosan (PMAABACy /CS/CS-DMMA) nanoparticles with PMAABACy cores as carriers and dimethylmaleic anhydride-modified chitosan as charge reversible shells were rationally designed. PMAABACy cores using N,N-Bis(acryloyl)cystamine (BACy) as a crosslinker and methacrylic acid (MAA) as a monomer were fabricated via a mild and facile one-pot distillation-precipitation polymerization...
May 17, 2018: Colloids and Surfaces. B, Biointerfaces
Nicholas Borcherding, Ryan Kolb, Jodi Gullicksrud, Praveen Vikas, Yuwen Zhu, Weizhou Zhang
Immune checkpoints are a diverse set of inhibitory signals to the immune system that play a functional role in adaptive immune response and self-tolerance. Dysregulation of these pathways are a vital mechanism in the avoidance of immune destruction by tumor cells. Immune checkpoint blockade (ICB) refers to targeted strategies to disrupt the tumor co-opted immune suppression to enhance anti-tumor immunity. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) are two immune checkpoints that have the widest range of antibody-based therapies...
May 22, 2018: Journal of Molecular Biology
John G Gunderson, Sabine C Herpertz, Andrew E Skodol, Svenn Torgersen, Mary C Zanarini
Caretakers are often intimidated or alienated by patients with borderline personality disorder (BPD), compounding the clinical challenges posed by the severe morbidity, high social costs and substantial prevalence of this disorder in many health-care settings. BPD is found in ∼1.7% of the general population but in 15-28% of patients in psychiatric clinics or hospitals and in a large proportion of individuals seeking help for psychological problems in general health facilities. BPD is characterized by extreme sensitivity to perceived interpersonal slights, an unstable sense of self, intense and volatile emotionality and impulsive behaviours that are often self-destructive...
May 24, 2018: Nature Reviews. Disease Primers
Tianhui Zhou, Ye Sun, Ming Li, Yongsen Ding, Rongkun Yin, Ziqiang Li, Qing Xie, Shisan Bao, Wei Cai
Acute-on-chronic liver failure is mainly due to host immunity self-destruction. The histone H3 lysine 27 (H3K27) trimethylating enzyme, enhancer of zeste homolog 2 (EZH2) mediates epigenetic silencing of gene expression and regulates immunity, also involves pathogenesis of several liver diseases. The current study was to determine the role of methyltransferase EZH2 and its catalysed H3K27 trimethylation (H3K27me3) in liver failure, and to further investigate the potential target for liver failure treatment...
May 22, 2018: Cell Death & Disease
Wenjun Shan, Ronghe Chen, Qiang Zhang, Jie Zhao, Binbin Chen, Xi Zhou, Shefang Ye, Shengli Bi, Liming Nie, Lei Ren
In recent years, hepatitis B core protein virus-like particle (HBc VLP) is an impressive biomaterial, which has attracted considerable attention due to favorable properties such as structural stability, high uptake efficiency, and biocompatibility in biomedical applications. Heretofore, only a few attempts have been made to apply it in physical, chemical, and biological therapy for cancer. In this study, a tumor-targeting RGD-HBc VLP is first fabricated through genetic engineering. For image-guided cancer phototherapy, indocyanine green (ICG) is loaded into RGD-HBc VLP via a disassembly/reassembly pathway and electrostatic attraction with high efficiency...
May 22, 2018: Advanced Materials
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