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https://www.readbyqxmd.com/read/29353413/exploring-the-genetic-and-adaptive-diversity-of-a-pan-mediterranean-crop-wild-relative-narrow-leafed-lupin
#1
Mahsa Mousavi-Derazmahalleh, Philipp E Bayer, Bruno Nevado, Bhavna Hurgobin, Dmitry Filatov, Andrzej Kilian, Lars G Kamphuis, Karam B Singh, Jens D Berger, James K Hane, David Edwards, William Erskine, Matthew N Nelson
This first pan-Mediterranean analysis of genetic diversity in wild narrow-leafed lupin revealed strong East-West genetic differentiation of populations, an historic eastward migration, and signatures of genetic adaptation to climatic variables. Most grain crops suffer from a narrow genetic base, which limits their potential for adapting to new challenges such as increased stresses associated with climate change. Plant breeders are returning to the wild ancestors of crops and their close relatives to broaden the genetic base of their crops...
January 20, 2018: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/29353350/clinical-pharmacokinetics-and-pharmacodynamics-of-evolocumab-a-pcsk9-inhibitor
#2
REVIEW
Sreeneeranj Kasichayanula, Anita Grover, Maurice G Emery, Megan A Gibbs, Ransi Somaratne, Scott M Wasserman, John P Gibbs
Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein cholesterol (LDL-C) by decreasing expression of the LDL receptor on hepatic cells. Evolocumab is a human monoclonal immunoglobulin G2 that binds specifically to human PCSK9 to reduce LDL-C. Evolocumab exhibits nonlinear kinetics as a result of binding to PCSK9. Elimination is predominantly through saturable binding to PCSK9 at lower concentrations and a nonsaturable proteolytic pathway at higher concentrations. The effective half-life of evolocumab is 11-17 days...
January 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29353348/insulin-receptor-substrate-4-is-overexpressed-in-colorectal-cancer-and-promotes-retinoblastoma-cyclin-dependent-kinase-activation
#3
Patricia Sanmartín-Salinas, María Del Val Toledo Lobo, Fernando Noguerales-Fraguas, Miguel Toro Londoño, Antonio Jiménez-Ruiz, Luis Gonzalez Guijarro
BACKGROUND: Insulin receptor substrate 4 (IRS-4) is an adaptor protein for which new evidence suggests plays a role in tumour promotion. METHODS: We described nuclear IRS-4 in RKO colon cancer cell lines in biopsies of patients with colorectal cancer (CRC) (n = 20) and in matched adjacent normal colorectal (MANC) tissue (n = 20). RESULTS: Treatment with physiological doses of IGF-1 promoted nuclear influx of IRS-4 from cellular cytosol in RKO cells...
January 20, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29353090/investigating-the-prevalence-of-febrile-convulsion-in-kayseri-turkey-an-assessment-of-the-risk-factors-for-recurrence-of-febrile-convulsion-and-for-development-of-epilepsy
#4
Mehmet Canpolat, Huseyin Per, Hakan Gumus, Ferhan Elmali, Sefer Kumandas
PURPOSE: The purpose of this study was to investigate the prevalence and recurrence of febrile convulsion (FC) and risk factors for development of epilepsy in school children throughout in the Kayseri provincial center. METHOD: Ten thousand individuals selected using "stratified cluster sampling" from a student population of 259,428 inside the Kayseri Urban Municipality represented the study sample. Fifteen thousand questionnaires were distributed, of which 10,742 (71...
January 10, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29352860/towards-targeting-resolution-pathways-of-airway-inflammation-in-asthma
#5
REVIEW
Cindy Barnig, Nelly Frossard, Bruce D Levy
Asthma is a chronic disorder characterized by persistent inflammation of the airways with mucosal infiltration of eosinophils, T lymphocytes, and mast cells, and release of proinflammatory cytokines and lipid mediators. The natural resolution of airway inflammation is now recognized as an active host response, with highly coordinated cellular events under the control of endogenous pro-resolving mediators that enable the restoration of tissue homeostasis. Lead members of proresolving mediators are enzymatically derived from essential polyunsaturated fatty acids, including arachidonic acid-derived lipoxins, eicosapentaenoic acid-derived E-series resolvins, and docosahexaenoic acid-derived D-series resolvins, protectins, and maresins...
January 17, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29352827/political-terrorism-and-affective-polarization-in-black-and-red-terrorists-in-italy-during-the-years-1968-1988
#6
Matteo Pacini, Icro Maremmani
Psychiatric evaluations of violent political crime were mostly performed on a case-by-case basis in a forensic environment, which made them unduly dependent on categories of presumed dangerousness and legal responsibility, rather than on a clinical definition of their mental status. In referring to such "clinical" definitions, the disorder we have in mind is not limited to the major, agitated psychotic manias or mixed states. The presence of a dominant temperament, or protracted hypomania, is enough by itself to explain an individual's engagement in a wide range of activities, not necessarily sociopathic or violent...
January 21, 2018: CNS Spectrums
https://www.readbyqxmd.com/read/29352704/treatment-of-adult-chronic-indeterminate-chagas-disease-with-benznidazole-and-three-e1224-dosing-regimens-a-proof-of-concept-randomised-placebo-controlled-trial
#7
Faustino Torrico, Joaquim Gascon, Lourdes Ortiz, Cristina Alonso-Vega, María-Jesús Pinazo, Alejandro Schijman, Igor C Almeida, Fabiana Alves, Nathalie Strub-Wourgaft, Isabela Ribeiro
BACKGROUND: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. METHOD: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia...
January 15, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29352495/ultrasonographic-based-predictive-factors-influencing-successful-return-to-racing-after-superficial-digital-flexor-tendon-injuries-in-flat-racehorses-a-retrospective-cohort-study-in-469-thoroughbred-racehorses-in-hong-kong
#8
R Alzola, C Easter, C M Riggs, D S Gardner, S L Freeman
BACKGROUND: Superficial digital flexor tendon (SDFT) injury is an important health and welfare concern in racehorses. It is generally diagnosed with ultrasonography, predictive ultrasonographic features have not been reported. OBJECTIVES: To determine ultrasonographic features of forelimb SDFT injury at initial presentation in Thoroughbred racehorses, that could predict a successful return to racing (completing ≥5 races). STUDY DESIGN: Retrospective cohort study...
January 20, 2018: Equine Veterinary Journal
https://www.readbyqxmd.com/read/29352454/decreased-opioid-consumption-and-enhance-recovery-with-the-addition-of-iv-acetaminophen-in-colorectal-patients-a-prospective-multi-institutional-randomized-double-blinded-placebo-controlled-study-dociva-study
#9
Amir H Aryaie, Sepehr Lalezari, Wallace K Sergent, Yana Puckett, Christopher Juergens, Craig Ratermann, Cari Ogg
BACKGROUND: We hypothesized that administration of IV acetaminophen alone would reduce the opioid consumption in post-operative colorectal surgery and reduce the side effects of narcotics. METHODS: Patients were randomized to receive either IV acetaminophen or placebo in addition to opioid PCA. Primary endpoints evaluated were opioid consumption and pain visual analogue scale score (PVASS) during first 48 h post-operatively. Secondary endpoints evaluated were time of return of GI function (ROGIF), time to diet ordered (TTDO), length of hospital stay (LOHS), and occurrence of ileus...
January 19, 2018: Surgical Endoscopy
https://www.readbyqxmd.com/read/29352419/a-systematic-review-of-interventions-to-follow-up-test-results-pending-at-discharge
#10
Patrick J Darragh, T Bodley, A Orchanian-Cheff, K G Shojania, J L Kwan, P Cram
BACKGROUND: Patients are frequently discharged from the hospital before all test results have been finalized. Thirty to 40% of tests pending at discharge (TPADs) return potentially actionable results that could necessitate change in the patients' management, often unbeknownst to their physicians. Delayed follow-up of TPADs can lead to patient harm. We sought to synthesize the existing literature on interventions intended to improve the management of TPADs, including interventions designed to enhance documentation of TPADs, increase physician awareness when TPAD results finalize post-discharge, decrease adverse events related to missed TPADs, and increase physician satisfaction with TPAD management...
January 19, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29352238/molting-site-fidelity-accounts-for-colony-elimination-of-the-formosan-subterranean-termites-isoptera-rhinotermitidae-by-chitin-synthesis-inhibitor-baits
#11
G Kakkar, W Osbrink, N-Y Su
Site fidelity by molting termites in Formosan subterranean termite, Coptotermes formosanus Shiraki colonies is a new addition to our understanding of lower termites' behavior and biology. Our previous studies indicated that workers moved to the central nest to molt in the presence of eggs and reproductives. The current study showed that noviflumuron-affected workers also return to the central nest and died in the vicinity of reproductives and eggs. The aversion to the dead and decaying workers caused reproductives and brood to leave the original central nest site in a colony and refuge at newer sites every few days in response to newly dead workers near them...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352163/word-mode-a-crowding-free-reading-protocol-for-individuals-with-macular-disease
#12
Stuart Wallis, Yit Yang, Stephen J Anderson
Central retinal loss through macular disease markedly reduces the ability to read largely because identification of a word using peripheral vision is negatively influenced by nearby text, a phenomenon termed visual crowding. Here, we present a novel peripheral reading protocol, termed Word Mode, that eliminates crowding by presenting each word in isolation but in a position that mimics its natural position in the line of text being read, with each new word elicited using a self-paced button press. We used a gaze-contingent paradigm to simulate a central scotoma in four normally-sighted observers, and measured oral reading speed for text positioned 7...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352045/eliminating-glutamatergic-input-onto-horizontal-cells-changes-the-dynamic-range-and-receptive-field-organization-of-mouse-retinal-ganglion-cells
#13
Sebastian Ströh, Christian Puller, Sebastian Swirski, Maj-Britt Hölzel, Lea I S van der Linde, Jasmin Segelken, Konrad Schultz, Christoph Block, Hannah Monyer, Klaus Willecke, Reto Weiler, Martin Greschner, Ulrike Janssen-Bienhold, Karin Dedek
In the mammalian retina, horizontal cells receive glutamatergic inputs from many rod and cone photoreceptors and return feedback signals to them, thereby changing photoreceptor glutamate release in a light-dependent manner. Horizontal cells also provide feedforward signals to bipolar cells. It is unclear, however, how horizontal cell signals also affect the temporal, spatial and contrast tuning in retinal output neurons, the ganglion cells. To study this, we generated a genetically modified mouse line in which we eliminated the light dependency of feedback by deleting glutamate receptors from mouse horizontal cells...
January 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29352032/the-surprising-subtleties-of-changing-fear-memory-a-challenge-for-translational-science
#14
REVIEW
Merel Kindt
Current pharmacological and psychological treatments for disorders of emotional memory only dampen the affective response while leaving the original fear memory intact. Under adverse circumstances, these original memories regain prominence, causing relapses in many patients. The (re)discovery in neuroscience that after reactivation consolidated fear memories may return to a transient labile state, requiring a process of restabilization in order to persist, offers a window of opportunity for modifying fear memories with amnestic agents...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29351989/iterative-random-forests-to-discover-predictive-and-stable-high-order-interactions
#15
Sumanta Basu, Karl Kumbier, James B Brown, Bin Yu
Genomics has revolutionized biology, enabling the interrogation of whole transcriptomes, genome-wide binding sites for proteins, and many other molecular processes. However, individual genomic assays measure elements that interact in vivo as components of larger molecular machines. Understanding how these high-order interactions drive gene expression presents a substantial statistical challenge. Building on random forests (RFs) and random intersection trees (RITs) and through extensive, biologically inspired simulations, we developed the iterative random forest algorithm (iRF)...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351987/cd83-is-a-new-potential-biomarker-and-therapeutic-target-for-hodgkin-lymphoma
#16
Ziduo Li, Xinsheng Ju, Kenneth Lee, Candice Clarke, Jennifer L Hsu, Edward Abadir, Christian E Bryant, Suzanne Pears, Neroli Sunderland, Scott Heffernan, Annemarie Hennessy, Tsun-Ho Lo, Geoffrey A Pietersz, Fiona Kupresanin, Phillip D Fromm, Pablo A Silveira, Con Tsonis, Wendy A Cooper, Ilona Cunningham, Christina Brown, Georgina J Clark, Derek N J Hart
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and interestingly, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351829/inhibition-of-dynamin-related-protein-1-has-neuroprotective-effect-comparable-with-therapeutic-hypothermia-in-a-rat-model-of-cardiac-arrest
#17
Peng Wang, Yi Li, Zhengfei Yang, Tao Yu, Guanghui Zheng, Xiangshao Fang, Zitong Huang, Longyuan Jiang, Wanchun Tang
Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, it has been proven that inhibition of Drp1 by mdivi-1 improves survival and attenuates cerebral ischemic injury after cardiac arrest. In this study, we compared the effects of Drp1 inhibition with therapeutic hypothermia on post-resuscitation neurologic injury in a rat model of cardiac arrest. Rats were randomized into 4 groups: Mdivi-1 treatment group (n = 39), hypothermic group (n = 38), normothermic group (n = 41), and sham group (n = 12)...
January 8, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29351488/measurement-of-postprandial-glucose-fluxes-in-response-to-acute-and-chronic-endurance-exercise-in-healthy-humans
#18
Dale J Morrison, Greg M Kowalski, Eleonora Grespan, Andrea Mari, Clinton R Bruce, Glenn D Wadley
The effect of endurance exercise on enhancing insulin sensitivity and glucose flux has been well established with techniques such as the hyperinsulinemic clamp. Although informative, such techniques do not emulate the physiological postprandial state, and it remains unclear how exercise improves postprandial glycaemia. Accordingly, combining mixed meal tolerance testing and the triple-stable isotope glucose tracer approach, glucose fluxes (rates of meal glucose appearance (Ra), disposal (Rd) and endogenous glucose production (EGP)) were determined following acute endurance exercise (1h cycling; ~70% VO2max) and 4 weeks of endurance training (cycling 5d/wk)...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351450/cardiac-vanilloid-receptor-1-afferent-depletion-enhances-stellate-ganglion-neuronal-activity-and-efferent-sympathetic-response-to-cardiac-stress
#19
Koji Yoshie, Pradeep S Rajendran, Louis Massoud, OhJin Kwon, Vasudev Tadimeti, Siamak Salavatian, Jeffrey Laurence Ardell, Kalyanam Shivkumar, Olujimi A Ajijola
Afferent fibers expressing the vanilloid receptor 1 (VR1) channel are implicated in cardiac nociception, however, their role in modulating reflex responses to cardiac stress is not well-understood. We evaluated this role in Yorkshire pigs by percutaneous epicardial application of resiniferatoxin (RTX), a toxic activator of the VR1 channel, resulting in depletion of cardiac VR1-expressing afferents. Hemodynamics, epicardial activation recovery intervals (ARIs), and in vivo activity of stellate ganglion (SG) neurons (SGNs) were recorded in control and RTX-treated animals...
January 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351307/doxycycline-modulates-vegf-a-expression-failure-of-doxycycline-inducible-lentivirus-shrna-vector-to-knockdown-vegf-a-expression-in-transgenic-mice
#20
Mari Merentie, Riina Rissanen, Line Lottonen-Raikaslehto, Jenni Huusko, Erika Gurzeler, Mikko P Turunen, Lari Holappa, Petri Mäkinen, Seppo Ylä-Herttuala
Vascular endothelial growth factor-A (VEGF-A) is the master regulator of angiogenesis, vascular permeability and growth. However, its role in mature blood vessels is still not well understood. To better understand the role of VEGF-A in the adult vasculature, we generated a VEGF-A knockdown mouse model carrying a doxycycline (dox)-regulatable short hairpin RNA (shRNA) transgene, which silences VEGF-A. The aim was to find the critical level of VEGF-A reduction for vascular well-being in vivo. In vitro, the dox-inducible lentiviral shRNA vector decreased VEGF-A expression efficiently and dose-dependently in mouse endothelial cells and cardiomyocytes...
2018: PloS One
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