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https://www.readbyqxmd.com/read/28346491/a-genetic-switch-controls-the-production-of-flagella-and-toxins-in-clostridium-difficile
#1
Brandon R Anjuwon-Foster, Rita Tamayo
In the human intestinal pathogen Clostridium difficile, flagella promote adherence to intestinal epithelial cells. Flagellar gene expression also indirectly impacts production of the glucosylating toxins, which are essential to diarrheal disease development. Thus, factors that regulate the expression of the flgB operon will likely impact toxin production in addition to flagellar motility. Here, we report the identification a "flagellar switch" that controls the phase variable production of flagella and glucosylating toxins...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346089/a-chemogenomic-screening-platform-used-to-identify-chemotypes-perturbing-hsp90-pathways
#2
Fiona M Thomas, Kourtney M Goode, Bartek Rajwa, Andrew B Bieberich, Larisa V Avramova, Tony R Hazbun, V Jo Davisson
Compounds that modulate the heat shock protein (HSP) network have potential in a broad range of research applications and diseases. A yeast-based liquid culture assay that measured time-dependent turbidity enabled the high-throughput screening of different Saccharomyces cerevisae strains to identify HSP modulators with unique molecular mechanisms. A focused set of four strains, with differing sensitivities to Hsp90 inhibitors, was used to screen a compound library of 3680 compounds. Computed turbidity curve functions were used to classify strain responses and sensitivity to chemical effects across the compound library...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345861/identification-of-gene-transcription-start-sites-and-enhancers-responding-to-pulmonary-carbon-nanotube-exposure-in-vivo
#3
Jette Bornholdt, Anne Thoustrup Saber, Berit Lilje, Mette Boyd, Mette Jørgensen, Yun Chen, Morana Vitezic, Nicklas Raun Jacobsen, Sarah Søs Poulsen, Trine Berthing, Simon Bressendorff, Kristoffer Vitting-Seerup, Robin Andersson, Karin Sørig Hougaard, Carole L Yauk, Sabina Halappanavar, Håkan Wallin, Ulla Vogel, Albin Sandelin
Increased use of nanomaterials in industry, medicine and consumer products has raised concerns over their toxicity. To ensure safe use of nanomaterials, understanding their biological effects at the molecular level is crucial. In particular, the regulatory mechanisms responsible for the cascade of genes activated by nanomaterial exposure are not well characterized. To this end, we profiled the genome-wide usage of gene transcription start sites and linked active enhancer regions in lungs of C57BL/6 mice 24h after intratracheal instillation of a single dose of the multiwalled carbon nanotube Mitsui-7...
March 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28345451/the-impact-of-advanced-proteomics-in-the-search-for-markers-and-therapeutic-targets-of-bladder-cancer
#4
Hongshuo Zhang, Yue Fan, Lingling Xia, Chunhui Gao, Xin Tong, Hanfu Wang, Lili Sun, Tuo Ji, Mingyu Jin, Bing Gu, Bo Fan
Bladder cancer is the most common cancer of the urinary tract and can be avoided through proper surveillance and monitoring. Several genetic factors are known to contribute to the progression of bladder cancer, many of which produce molecules that serve as cancer biomarkers. Blood, urine, and tissue are commonly analyzed for the presence of biomarkers, which can be derived from either the nucleus or the mitochondria. Recent advances in proteomics have facilitated the high-throughput profiling of data generated from bladder cancer-related proteins or peptides in parallel with high sensitivity and specificity, providing a wealth of information for biomarker discovery and validation...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344933/precision-medicine-the-golden-gate-for-detection-treatment-and-prevention-of-alzheimer-s-disease
#5
H Hampel, S E O'Bryant, J I Castrillo, C Ritchie, K Rojkova, K Broich, N Benda, R Nisticò, R A Frank, B Dubois, V Escott-Price, S Lista
During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy...
December 2016: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/28344885/pappalysin-1-t-cell-receptor-transgenic-allo-restricted-t-cells-kill-ewing-sarcoma-in-vitro-and-in-vivo
#6
Andreas Kirschner, Melanie Thiede, Thomas G P Grünewald, Rebeca Alba Rubio, Günther H S Richter, Thomas Kirchner, Dirk H Busch, Stefan Burdach, Uwe Thiel
Pregnancy-associated plasma protein-A (PAPPA), also known as pappalysin, is a member of the insulin-like growth factor (IGF) family. PAPPA acts as a protease, cleaving IGF inhibitors, i.e., IGF binding proteins (IGFBPs), thereby setting free IGFs. The insulin/IGF-axis is involved in cancer in general and in Ewing sarcoma (ES) in particular. ES is a highly malignant bone tumor characterized by early metastatic spread. PAPPA is associated with various cancers. It is overexpressed and required for proliferation in ES...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344651/identification-of-a-novel-dmd-duplication-identified-by-a-combination-of-mlpa-and-targeted-exome-sequencing
#7
Beibei Wu, Liying Wang, Ting Dong, Jiahui Jin, Yili Lu, Huiping Wu, Yue Luo, Xiaoou Shan
BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle-wasting disease caused by a mutation in the DMD gene. The aim of this study was to identify a de novo mutation of the DMD gene in the family of a 9-month-old Chinese male patient, as well as to describe the phenotypic characteristics of this patient. RESULTS: The patient was suspected to suffer from DMD according to physical examination, biochemical analyses, and electromyogram. We identified a duplication of exons 4-42 in DMD gene with targeted exome sequencing and multiplex ligation-dependent probe amplification (MLPA)...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28344541/olfm4-kng1-and-sec24c-identified-by-proteomics-and-immunohistochemistry-as-potential-markers-of-early-colorectal-cancer-stages
#8
Florence Quesada-Calvo, Charlotte Massot, Virginie Bertrand, Rémi Longuespée, Noëlla Blétard, Joan Somja, Gabriel Mazzucchelli, Nicolas Smargiasso, Dominique Baiwir, Marie-Claire De Pauw-Gillet, Philippe Delvenne, Michel Malaise, Carla Coimbra Marques, Marc Polus, Edwin De Pauw, Marie-Alice Meuwis, Edouard Louis
BACKGROUND: Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for reducing CRC incidence and increasing patient's survival. METHODS: We analysed 76 colorectal tissue samples originated from early CRC stages, normal or inflamed mucosa by label-free proteomics. The characterisation of three selected biomarker candidates was performed by immunohistochemistry on an independent set of precancerous and cancerous lesions harbouring increasing CRC stages...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28344169/the-identification-characterization-and-function-of-two-trems-genes-in-chinese-yangzhou-goose-anas-cygnoides
#9
Huanxi Zhu, Xiaoqian Liu, Jie Du, Mingming Lei, Shijia Ying, Junshu Yan, Jianning Yu, Zhendan Shi, Hui Li
Triggering receptor expressed on myeloid cells (TREM) is a cell-surface receptor primarily expressed on macrophages. Here, two novel TREM genes, AcTREM1 and AcTREM2, were identified from Anas cygnoides. AcTREM1 cDNA contained a putative signal peptide, two IG domains, and a transmembrane domain. The deduced AcTREM2 sequence also contained a signal peptide, an IG domain, and a transmembrane domain. qRT-PCR, fluorescence in situ hybridization, and immunofluorescence experiments showed that AcTREM1 and AcTREM2 were mainly expressed in the liver and spleen, and both genes and proteins were mainly distributed in cytoplasm...
March 23, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28344004/identification-of-three-early-phases-of-cell-fate-determination-during-osteogenic-and-adipogenic-differentiation-by-transcription-factor-dynamics
#10
Jeroen van de Peppel, Tanja Strini, Julia Tilburg, Hans Westerhoff, Andre J van Wijnen, Johannes P van Leeuwen
Age-related skeletal degeneration in patients with osteoporosis is characterized by decreased bone mass and occurs concomitant with an increase in bone marrow adipocytes. Using microarray expression profiling with high temporal resolution, we identified gene regulatory events in early stages of osteogenic and adipogenic lineage commitment of human mesenchymal stromal cells (hMSCs). Data analysis revealed three distinct phases when cells adopt a committed expression phenotype: initiation of differentiation (0-3 hr, phase I), lineage acquisition (6-24 hr, phase II), and early lineage progression (48-96 hr, phase III)...
March 16, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28343983/comprehensive-cell-surface-protein-profiling-identifies-specific-markers-of-human-naive-and-primed-pluripotent-states
#11
Amanda J Collier, Sarita P Panula, John Paul Schell, Peter Chovanec, Alvaro Plaza Reyes, Sophie Petropoulos, Anne E Corcoran, Rachael Walker, Iyadh Douagi, Fredrik Lanner, Peter J Rugg-Gunn
Human pluripotent stem cells (PSCs) exist in naive and primed states and provide important models to investigate the earliest stages of human development. Naive cells can be obtained through primed-to-naive resetting, but there are no reliable methods to prospectively isolate unmodified naive cells during this process. Here we report comprehensive profiling of cell surface proteins by flow cytometry in naive and primed human PSCs. Several naive-specific, but not primed-specific, proteins were also expressed by pluripotent cells in the human preimplantation embryo...
March 21, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28343909/pneumonia
#12
REVIEW
Thomas A Hooven, Richard A Polin
Neonatal pneumonia may occur in isolation or as one component of a larger infectious process. Bacteria, viruses, fungi, and parasites are all potential causes of neonatal pneumonia, and may be transmitted vertically from the mother or acquired from the postnatal environment. The patient's age at the time of disease onset may help narrow the differential diagnosis, as different pathogens are associated with congenital, early-onset, and late-onset pneumonia. Supportive care and rationally selected antimicrobial therapy are the mainstays of treatment for neonatal pneumonia...
March 23, 2017: Seminars in Fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28343764/channelopathies-genetic-testing-and-risk-stratification
#13
Arthur A M Wilde, Ahmad Amin
The cardiac channelopathies are a group of diseases with (disease-) specific electrocardiographic (ECG) characteristics and a disease-specific risk of sudden cardiac death (SCD). This group includes the Long QT Syndromes (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Brugada Syndrome (BrS), Short QT Syndromes (SQTS), and Early Repolarization Syndrome (ERS). In the past 2 decades the genetic basis for these disease entities has largely been unraveled and that, together with the identification of the genetic basis of the cardiomyopathies, has paved the way for the complete new field of Cardiogenetics...
March 18, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28343750/academic-remediation-why-early-identification-and-intervention-matters
#14
REVIEW
Carol M Rumack, Jeannette Guerrasio, Alicia Christensen, Eva M Aagaard
At our institution, we have developed a remediation team of strong, focused experts who help us with struggling learners in making the diagnosis and then coaching on their milestone deficits. It is key for all program directors to recognize struggling residents because early recognition and intervention gives the resident the best chance of success.
March 23, 2017: Academic Radiology
https://www.readbyqxmd.com/read/28343453/a-trans-diagnostic-perspective-on-obsessive-compulsive-disorder
#15
C M Gillan, N A Fineberg, T W Robbins
Progress in understanding the underlying neurobiology of obsessive-compulsive disorder (OCD) has stalled in part because of the considerable problem of heterogeneity within this diagnostic category, and homogeneity across other putatively discrete, diagnostic categories. As psychiatry begins to recognize the shortcomings of a purely symptom-based psychiatric nosology, new data-driven approaches have begun to be utilized with the goal of solving these problems: specifically, identifying trans-diagnostic aspects of clinical phenomenology based on their association with neurobiological processes...
March 27, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28343323/post-traumatic-sleep-wake-disorders
#16
REVIEW
Tatyana Mollayeva, Andrea D'Souza, Shirin Mollayeva, Angela Colantonio
All living organisms that face a traumatic life event are susceptible to sleep-wake disturbances. Stress, which can result in trauma, evokes a high level of physiological arousal associated with sympathetic nervous system activation, during both sleep and wakefulness. Heredity, sex hormones, early losses, developmental factors and intra- and interpersonal conflicts, contribute to the level of baseline physiological arousal, producing either subclinical, clinical or complex clinical traits, acutely and at any time after exposure to a traumatic event...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28343321/a-risk-score-based-on-admission-characteristics-to-predict-progressive-hemorrhagic-injury-from-traumatic-brain-injury-in-children
#17
Guo-Wen Hu, Hai-Li Lang, Hua Guo, Lei Wu, Pei Zhang, Wei Kuang, Xin-Gen Zhu
Traumatic brain injury (TBI) is one of the leading causes of death and disability in children, and progressive hemorrhagic injury (PHI) post TBI is associated with poor outcomes. Therefore, the objective of this study was to develop and validate a prognostic model that uses the information available at admission to determine the likelihood of PHI occurrence after TBI in children. The identified demographic data, cause of injury, clinical predictors on admission, computed tomography scan characteristics, and routine laboratory parameters were collected and used to develop a PHI prognostic model with logistic regression analysis, and the prediction model was validated in 68 children...
March 25, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28342162/brief-report-estimated-prevalence-of-a-community-diagnosis-of-autism-spectrum-disorder-by-age-4-years-in-children-from-selected-areas-in-the-united-states-in-2010-evaluation-of-birth-cohort-effects
#18
Gnakub N Soke, M J Maenner, D Christensen, M Kurzius-Spencer, L A Schieve
We compared early-diagnosed autism spectrum disorder (ASD) (defined as diagnosis by age 4 years) between the 2002 and 2006 birth cohorts, in five sites of the Autism and Developmental Disabilities Monitoring Network. In the 2002 cohort, the prevalence/1000 of early-diagnosed ASD was half the 8-year-old prevalence (7.2 vs. 14.7, prevalence ratio [PR] 0.5 [0.4-0.6]). Overall, the prevalence of early-diagnosed ASD did not differ between birth cohorts (PR 1.1 [0.9-1.3]). However, in three sites with complete case ascertainment, the prevalence of early-diagnosed ASD was higher for those born in 2006 versus 2002 (PR 1...
March 24, 2017: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/28341674/interbacterial-adhesion-networks-within-the-early-oral-biofilm-of-individual-human-hosts
#19
Robert J Palmer, Nehal Shah, Alex Valm, Bruce Paster, Floyd Dewhirst, Taichi Inui, John O Cisar
Specific interbacterial adhesion, termed coaggregation, is well established for three early colonizers of the plaque biofilm: streptococci, actinomyces, and veillonellae. However, little is known about interactions of other early colonizers, and about the extent of interactions within the bacterial community from a single host. To address these gaps, subject-specific culture collections from two individuals were established using an intra-oral biofilm retrieval device. Molecular taxonomy (Human Oral Microbe Identification Microarray: HOMIM) of biofilm samples corroborated integrity and completeness of the collections...
March 24, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28341579/beware-the-looping-vas-deferens-in-orchidopexy
#20
Thomas P Cundy, Day Way Goh
A looping vas deferens may be present in up to 20% of undescended testes located within or proximal to the inguinal canal. This associated abnormality is vulnerable to transection during orchidopexy. We present an example of a very long looping vas to emphasize the importance of inspection for this anomaly, and demonstrate the extreme extent that a looping vas may extend. Identification of the vas amongst cord structures may provide false reassurance of normal ductal anatomy. Examination for a looping vas by inspecting structures caudal to the testis should occur at an early opportunity during orchidopexy to avoid inadvertent transection...
March 21, 2017: Urology
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