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Aaron J Martin, Matthew Clark, Gregory Gojanovich, Fatima Manzoor, Keith Miller, Douglas E Kline, Y Maurice Morillon, Bo Wang, Roland Tisch
There continues to be a need for immunotherapies to treat type 1 diabetes in the clinic. We previously reported that nondepleting anti-CD4 and -CD8 Ab treatment effectively reverses diabetes in new-onset NOD mice. A key feature of the induction of remission is the egress of the majority of islet-resident T cells. How this occurs is undefined. Herein, the effects of coreceptor therapy on islet T cell retention were investigated. Bivalent Ab binding to CD4 and CD8 blocked TCR signaling and T cell cytokine production, while indirectly downregulating islet chemokine expression...
October 20, 2016: JCI Insight
Micah Allen, Darya Frank, D Samuel Schwarzkopf, Francesca Fardo, Joel S Winston, Tobias U Hauser, Geraint Rees
Human perception is invariably accompanied by a graded feeling of confidence that guides metacognitive awareness and decision-making. It is often assumed that this arises solely from the feed-forward encoding of the strength or precision of sensory inputs. In contrast, interoceptive inference models suggest that confidence reflects a weighted integration of sensory precision and expectations about internal states, such as arousal. Here we test this hypothesis using a novel psychophysical paradigm, in which unseen disgust-cues induced unexpected, unconscious arousal just before participants discriminated motion signals of variable precision...
October 25, 2016: ELife
Ebrahim Alipanahpour Dil, Mehrorang Ghaedi, Arash Asfaram, Shaaker Hajati, Fatemeh Mehrabi, Alireza Goudarzi
Copper oxide nanoparticle-loaded activated carbon (CuO-NP-AC) was synthesized and characterized using different techniques such as FE-SEM, XRD and FT-IR. It was successfully applied for the ultrasound-assisted simultaneous removal of Pb(2+) ions and malachite green (MG) dye in binary system from aqueous solution. The effect of important parameters was modeled and optimized by artificial neural network (ANN) and response surface methodology (RSM). Maximum simultaneous removal percentages (>99.0%) were found at 25mgL(-1), 20mgL(-1), 0...
January 2017: Ultrasonics Sonochemistry
Soraya Sajadimajd, Razieh Yazdanparast
Trastuzumab (Herceptin) monoclonal antibody directed against HER2 receptor has been administered as a treatment for metastatic HER2 positive breast cancer. The problematic issue in treatment of HER2 positive breast cancer cells is commonly the induction of resistance to trastuzumab which might be due to modulation of some vital signaling elements such as Notch1 and Pin1. In this study, we were aimed to investigate whether the cross talk between pin1 and Notch1 has a role in this event. Our results indicated that the expression level of Pin1 in resistant SKBR3 cells increased by about twofold relative to sensitive SKBR3 cells...
October 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
Abdul Akbar, Ananya Kuanar, Raj K Joshi, I S Sandeep, Sujata Mohanty, Pradeep K Naik, Antaryami Mishra, Sanghamitra Nayak
The drug yielding potential of turmeric (Curcuma longa L.) is largely due to the presence of phyto-constituent 'curcumin.' Curcumin has been found to possess a myriad of therapeutic activities ranging from anti-inflammatory to neuroprotective. Lack of requisite high curcumin containing genotypes and variation in the curcumin content of turmeric at different agro climatic regions are the major stumbling blocks in commercial production of turmeric. Curcumin content of turmeric is greatly influenced by environmental factors...
2016: Frontiers in Plant Science
Terezinha M Souza, Linda Rieswijk, Twan van den Beucken, Jos Kleinjans, Danyel Jennen
Chemical carcinogenesis, albeit complex, often relies on modulation of transcription through activation or repression of key transcription factors. While analyzing extensive networks may hinder the biological interpretation, one may focus on dynamic network motifs, among which persistent feed-forward loops (FFLs) are known to chronically influence transcriptional programming. Here, to investigate the relevance a FFL-oriented approach in depth, we have focused on aflatoxin B1-induced transcriptomic alterations during distinct states of exposure (daily administration during 5 days followed by a non-exposed period) of human hepatocytes, by exploring known interactions in human transcription...
October 17, 2016: Toxicology
Cosima Engerer, Pascal O Berberat, Andreas Dinkel, Baerbel Rudolph, Heribert Sattel, Alexander Wuensch
BACKGROUND: Feedback is considered a key didactic element in medical education, especially for teaching of communication skills. This study investigates the impact of a best evidence-based practice feedback concept within the context of communication skills training (CST). We evaluate this concept for acceptance and changes in students self-ratings of communication competence. METHODS: Our CST integrating feedback process comprises a short theoretical introduction presenting standards for good communication and a constructive 360° feedback from three perspectives: feedback from peers, from standardized patients (SPs), and from a trainer...
October 18, 2016: BMC Medical Education
Shazia Nafis, Kalaiarasan Ponnusamy, Mohammad Husain, R K Brojen Singh, Rameshwar N K Bamezai
An experimentally validated set of apoptosis-regulatory proteins was subjected to network analysis, depicting a scale-free hierarchical fractal network. The power-law distribution of the various topological properties of the network revealed the fractal nature of the network, a signature of self-organization of the network where the network maintained the democratic constitution of nodes at various levels and showed the absence of the centrality-lethality control system. Even though network breakdown under the absence of the centrality-lethality rule of hub removal did not happen, the change in the topological properties of the network could be observed...
October 18, 2016: Molecular BioSystems
Qiang Zhang, Nebojsa Stojanovic, Cristian Prodaniuc, Changsong Xie, Michael Koenigsmann, Piotr Laskowski
We experimentally demonstrate the generation and transmission of a single-lane 180  Gbit/s (90 GBaud) four-level pulse-amplitude modulation (PAM-4) signal in an intensity-modulation direct-detection system with a 7.5 GHz 3 dB bandwidth. The generated signal is transmitted over a 2 km standard single-mode fiber with, to the best of our knowledge, the highest reported net data rate in the C-band: 150  Gbit/s. A net data rate of 168  Gbit/s is also reachable with 1 km reach. The PAM-4 and duobinary (DB) PAM-4 modulation schemes are compared; the obtained results show that DB-PAM-4 significantly outperforms PAM-4 in the considered strong bandwidth-constrained system...
October 1, 2016: Optics Letters
Alyne O Lavinsky, Kelly C Detmann, Josimar V Reis, Rodrigo T Ávila, Matheus L Sanglard, Lucas F Pereira, Lílian M V P Sanglard, Fabrício A Rodrigues, Wagner L Araújo, Fábio M DaMatta
Silicon (Si) has been recognized as a beneficial element to improve rice (Oryza sativa L.) grain yield. Despite some evidence suggesting that this positive effect is observed when Si is supplied along the reproductive growth stage (from panicle initiation to heading), it remains unclear whether its supplementation during distinct growth phases can differentially impact physiological aspects of rice and its yield and the underlying mechanisms. Here, we investigated the effects of additions/removals of Si at different growth stages and their impacts on rice yield components, photosynthetic performance, and expression of genes (Lsi1, Lsi2 and Lsi6) involved in Si distribution within rice shoots...
October 5, 2016: Journal of Plant Physiology
Jyun-Yuan Huang, Hung-Lin Chen, Chiaho Shih
Hepatitis B virus (HBV) is a major human pathogen. In this study, we found that miR-204 and miR-1236 were down-regulated in HBV-producing cells, and each could suppress HBV replication. Using a bioinformatic approach and a reporter assay, we identified miR-1236, which can reduce HBV replication and protein production by directly targeting at HBV specific mRNA. In contrast, miR-204 was identified by a microarray approach, and had no effect on HBV RNA and protein production. Surprisingly, miR-204 could inhibit HBV pregenomic RNA encapsidation and capsid assembly...
October 13, 2016: Scientific Reports
Lindsey Fay, Allison Carll-White, James Harrell
PURPOSE: This article illustrates a collaborative, full cycle diagnostic postoccupancy evaluation (POE) conducted in an emergency department (ED) to demonstrate methods of planning a POE, conducting research to capture meaningful data, and applying outcomes through the use of a design charrette. BACKGROUND: POEs often end with the reporting of findings rather than suggesting how this knowledge feeds forward. A design charrette presents an opportunity to engage with POE evidence and integrate research into practice...
October 12, 2016: HERD
Darko Ivanović, Aleksandar Kupusinac, Edita Stokić, Rade Doroslovački, Dragan Ivetić
The diagnosis of metabolic syndrome (MetS) has a leading role in the early prevention of chronic disease, such as cardiovascular disease, type 2 diabetes, cancers and chronic kidney disease. It would be very greatful that MetS diagnosis can be predicted in everyday clinical practice. This paper presents artificial neural network (ANN) prediction of the diagnosis of MetS that includes solely non-invasive, low-cost and easily-obtained diagnostic methods. This solution can extract the risky persons and suggests complete tests only on them by saving money and time...
December 2016: Journal of Medical Systems
F Javier Bernardo-Garcia, Tim-Henning Humberg, Cornelia Fritsch, Simon G Sprecher
Development of the insect compound eye requires a highly controlled interplay between transcription factors. However, the genetic mechanisms that link early eye field specification to photoreceptor terminal differentiation and fate maintenance remain largely unknown. Here, we decipher the function of two transcription factors, Glass and Hazy, which play a central role during photoreceptor development. The regulatory interactions between Glass and Hazy suggest that they function together in a coherent feed-forward loop in all types of Drosophila photoreceptors...
October 10, 2016: Fly
Nadia Kafui Adotevi, Beulah Leitch
Absence seizures arise from disturbances within the corticothalamocortical network, however the precise cellular and molecular mechanisms underlying seizure generation arising from different genetic backgrounds are not fully understood. While recent experimental evidence suggests that changes in inhibitory microcircuits in the cortex may contribute to generation of the hallmark spike-wave discharges, it is still unclear if altered cortical inhibition is a result of interneuron dysfunction due to compromised glutamatergic excitation and/or changes in cortical interneuron number...
October 4, 2016: Neuroscience
Daniela Liebsch, Olivier Keech
563 I. 563 II. 564 III. 564 IV. 565 V. 565 VI. 567 VII. 567 568 References 568 SUMMARY: Leaf senescence - the coordinated, active process leading to the organized dismantling of cellular components to remobilize resources - is a fundamental aspect of plant life. Its tight regulation is essential for plant fitness and has crucial implications for the optimization of plant productivity and storage properties. Various investigations have shown light deprivation and light perception via phytochromes as key elements modulating senescence...
November 2016: New Phytologist
Ashley N Nilson, Kelsey C English, Julia E Gerson, T Barton Whittle, C Nicolas Crain, Judy Xue, Urmi Sengupta, Diana L Castillo-Carranza, Wenbo Zhang, Praveena Gupta, Rakez Kayed
It is well-established that inflammation plays an important role in Alzheimer's disease (AD) and frontotemporal lobar dementia (FTLD). Inflammation and synapse loss occur in disease prior to the formation of larger aggregates, but the contribution of tau to inflammation has not yet been thoroughly investigated. Tau pathologically aggregates to form large fibrillar structures known as tangles. However, evidence suggests that smaller soluble aggregates, called oligomers, are the most toxic species and form prior to tangles...
October 1, 2016: Journal of Alzheimer's Disease: JAD
Hang Jin Jo, Daniela Mattos, Elisabeth B Lucassen, Xuemei Huang, Mark L Latash
The authors explored the changes in multidigit synergies in patients with multiple sclerosis (MS) within the framework of the uncontrolled manifold hypothesis. The specific hypotheses were that both synergy indices and anticipatory synergy adjustments prior to the initiation of a self-paced quick action would be diminished in the patients compared to age-matched controls. The MS patients and age-matched controls (n = 13 in both groups) performed one-finger and multifinger force production tasks involving both accurate steady-state force production and quick force pulses...
August 11, 2016: Journal of Motor Behavior
Janine Toggweiler, Maria Willecke, Konrad Basler
Tumorigenesis is driven by genetic alterations that perturb the signaling networks regulating proliferation or cell death. In order to block tumor growth, one has to precisely know how these signaling pathways function and interplay. Here, we identified the transcription factor Ets21C as a pivotal regulator of tumor growth and propose a new model of how Ets21C could affect this process. We demonstrate that a depletion of Ets21C strongly suppressed tumor growth while ectopic expression of Ets21C further increased tumor size...
October 7, 2016: Scientific Reports
Melissa Lever, Hong-Sheng Lim, Philipp Kruger, John Nguyen, Nicola Trendel, Enas Abu-Shah, Philip Kumar Maini, Philip Anton van der Merwe, Omer Dushek
T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-cell responses to 1 million-fold variations in both pMHC affinity and dose produced bell-shaped dose-response curves and different optimal pMHC affinities at different pMHC doses. Using sequential model rejection/identification algorithms, we identified a unique, minimal model of cellular signaling incorporating kinetic proofreading with limited signaling coupled to an incoherent feed-forward loop (KPL-IFF) that reproduces these observations...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
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