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Pre-integration complex

Joanna Shepherd, Matthew Fisher, Abigail Welford, Donald M McDonald, Chryso Kanthou, Gillian M Tozer
Solid tumours vary in sensitivity to the vascular disrupting agent combretastatin A-4 3-O-phosphate (CA4P), but underlying factors are poorly understood. The signaling sphingolipid, sphingosine-1-phosphate (S1P), promotes vascular barrier integrity by promoting assembly of VE-cadherin/β-catenin complexes. We tested the hypothesis that tumour pre-treatment with S1P would render tumours less susceptible to CA4P. S1P (1μM) pretreatment attenuated an increase in endothelial cell (HUVEC) monolayer permeability induced by 10μM CA4P...
November 10, 2017: Oncotarget
Sneha Rao, Gregory W Kirschen, Joanna Szczurkowska, Adrian Di Antonio, Jia Wang, Shaoyu Ge, Maya Shelly
New dentate granule cells are continuously generated, and integrate into the pre-existing hippocampal network in the adult brain. How an adult-born neuron with initially simple spindle-like morphology develops into a complex dentate granule cell (DGC), consisting of a single apical dendrite with further branches, remains largely unknown. Here, using retroviruses to birth-date and manipulate newborn neurons, we examined initial dendritic formation, and possible underlying mechanisms. We found that GFP-expressing newborn cells began to establish a DGC-like morphology at around 7 days after birth, with a primary dendrite pointing to the molecular layer, but at this stage, with several neurites in the neurogenic zone...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ingibjörg Bjartmarz, Helga Jónsdóttir, Thóra B Hafsteinsdóttir
Background: Nurses often have difficulties with using interdisciplinary stroke guidelines for patients with stroke as they do not focus sufficiently on nursing. Therefore, the Stroke Nursing Guideline (SNG) was developed and implemented. The aim of this study was to determine the implementation and feasibility of the SNG in terms of changes in documentation and use of the guideline in the care of stroke patients on Neurological and Rehabilitation wards, barriers and facilitators, and nurses' and auxiliary nurses' view of the implementation...
2017: BMC Nursing
Chao Gu, J Andrew Pruszynski, Paul L Gribble, Brian D Corneil
A core assumption underlying mental chronometry is that more complex tasks increase cortical processing, prolonging reaction times. Here we show that increases in task complexity alter the magnitude, rather than the latency, of the output for a circuit that rapidly transforms visual information into motor actions. We quantified visual stimulus-locked responses (SLRs), which are changes in upper limb muscle recruitment that evolve at a fixed latency ~100 ms after novel visual stimulus onset. First, we studied the underlying reference frame of the SLR, by dissociating initial eye and hand position...
December 6, 2017: Journal of Neurophysiology
T Richard Nichols
This review is an update on the role of force feedback from Golgi tendon organs in the regulation of limb mechanics during voluntary movement. Some current ideas about the role of force feedback are based on circuit motifs linking idealized systems of agonists, synergists and antagonistic muscles. Force feedback is widely distributed across the muscles of a limb and cannot be understood based on these circuit motifs. Muscle architecture similarly cannot be understood in terms of idealized systems. It is hypothesized that distributed force feedback better represents the complex mechanical interactions of muscles, including viscoelastic coupling and inertial coupling across joints and axes of rotation...
December 6, 2017: Journal of Neurophysiology
Davide Crivelli, Michela Balconi
According to philosophy of mind and neuroscientific models, the sense of agency can be defined as the sense that I am the one that is generating an action and causing its effects. Such ability to sense ourselves as causal agents is critical for the definition of intentional behavior and is a primary root for human interaction skills. The present mini-review aims at discussing evidences from non-invasive brain stimulation (NIBS) studies targeting functional correlates of different aspects of agency and evidences on the way stimulation techniques affect such core feature of human subjective experience...
2017: Frontiers in Behavioral Neuroscience
Mehmet G Badur, Christian M Metallo
Metabolic dysfunction has reemerged as an essential hallmark of tumorigenesis, and metabolic phenotypes are increasingly being integrated into pre-clinical models of disease. The complexity of these metabolic networks requires systems-level interrogation, and metabolic flux analysis (MFA) with stable isotope tracing present a suitable conceptual framework for such systems. Here we review efforts to elucidate mechanisms through which metabolism influences tumor growth and survival, with an emphasis on applications using stable isotope tracing and MFA...
November 30, 2017: Metabolic Engineering
Kai Cheng, Zhibin Ning, Xu Zhang, Leyuan Li, Bo Liao, Janice Mayne, Alain Stintzi, Daniel Figeys
BACKGROUND: Research involving microbial ecosystems has drawn increasing attention in recent years. Studying microbe-microbe, host-microbe, and environment-microbe interactions are essential for the understanding of microbial ecosystems. Currently, metaproteomics provide qualitative and quantitative information of proteins, providing insights into the functional changes of microbial communities. However, computational analysis of large-scale data generated in metaproteomic studies remains a challenge...
December 2, 2017: Microbiome
Wonmo Kang, Adnan Ashfaq, Thomas O'Shaughnessy, Amit Bagchi
Dynamic cavitation in soft materials is becoming increasingly relevant due to emerging medical implications such as the potential of cavitation-induced brain injury or cavitation created by therapeutic medical devices. However, the current understanding of dynamic cavitation in soft materials is still very limited, mainly due to lack of robust experimental techniques. To experimentally characterize cavitation nucleation under dynamic loading, we utilize a recently developed experimental instrument, the integrated drop tower system...
December 2, 2017: Acta Biomaterialia
Brandy Deffenbacher, Shannon Langner, Morteza Khodaee
BACKGROUND AND OBJECTIVES: A family medicine residency is a unique training environment where residents are exposed to care in multiple settings, across all ages. Procedures are an integral part of family medicine practice. Family medicine residency (FMR) programs are tasked with the job of teaching these skills at a level of intensity and frequency that allows a resident to achieve competency of such skills. In an environment that is limited by work hour restrictions, self-study teaching methods are one way to ensure all residents receive the fundamental knowledge of how to perform procedures...
November 2017: Family Medicine
Ahmad Hafez, João B Buçard, Rukoya Tanikawa
BACKGROUND: Several intracranial pathologies require opening the Sylvian fissure to be approached, and they are traditionally accessed through the frontal side of the superficial Sylvian veins. The integrated multimaneuver dissecting technique (IMMDT) interchanges the steps with the veins still secured for safe dissection, but the Sylvian fissure is approached from the optimal, safe side with integrated techniques. OBJECTIVE: To determine whether the 1-way dissection of the Sylvian fissure converts to the more favorable and flexible IMMDT...
December 1, 2017: Operative Neurosurgery (Hagerstown, Md.)
Julia Martín, Enrique Jacobo Díaz Montaña, Agustin G Asuero
Anthocyanins are naturally occurring polyphenolic compounds and give many flowers, fruits and vegetable their orange, red, purple, and blue colors. Besides their color attributes, anthocyanins have received much attention in recent years due to the growing evidence of their antioxidant capacity and health benefits on humans. However, these compounds usually occur in low concentrations in mixtures of complex matrices, and therefore large-scale harvesting is needed to obtain sufficient amounts for their practical usage...
November 29, 2017: Critical Reviews in Analytical Chemistry
Chuanlai Shen, Tao Xu, You Wu, Xiaoe Li, Lingzhi Xia, Wei Wang, Khawar Ali Shahzad, Lei Zhang, Xin Wan, Jie Qiu
Conventional peptide-major histocompatibility complex (pMHC) multimer staining, intracellular cytokine staining, and enzyme-linked immunospot (ELISPOT) assay cannot concurrently determine the frequency and reactivity of antigen-specific T cells (AST) in a single assay. In this report, pMHC multimer, magnetic-activated cell sorting (MACS), and ELISPOT techniques have been integrated into a micro well by coupling pMHC multimers onto cell-sized magnetic beads to characterize AST cell populations in a 96-well microplate which pre-coated with cytokine-capture antibodies...
November 27, 2017: Scientific Reports
Yi-Yu Wei, Hung-Ta Chen
Rpc34 is a subunit of the Rpc82/34/31 subcomplex residing on the DNA-binding cleft of RNA polymerase (pol) III. Rpc34 contains a structurally flexible N-terminal tandem winged-helix (tWH) domain related to the transcription factor TFIIE. While the second WH (WH2) fold of the tWH domain is known to function in DNA melting activity during transcription initiation, the functional role of the WH1 fold is unknown. In this study, we generated a series of new Rpc34 tWH mutants conferring a cold-sensitive growth phenotype...
November 27, 2017: Molecular and Cellular Biology
Di Wu, Chun-Jie Huang, Xiao-Fei Jiao, Zhi-Ming Ding, Jia-Yu Zhang, Fan Chen, Yong-Sheng Wang, Xiang Li, Li-Jun Huo
Sertoli cells, by creating an immune-privileged and nutrition supporting environment, maintain mammalian spermatogenesis and thereby holds the heart of male fertility. Olaquindox, an effective feed additive in livestock industry, could potentially expose human into the risk of biological hazards due to its genotoxicity and cytotoxicity, highlighting the significance of determining its bio-safety regarding human reproduction. Herein, we deciphered the detrimental effects of olaquindox on male fertility by mechanistically unraveling how olaquindox intervenes blood-testis barrier in mouse...
October 24, 2017: Oncotarget
Lisa Fromm, Sebastian Falk, Dirk Flemming, Jan Michael Schuller, Matthias Thoms, Elena Conti, Ed Hurt
Removal of internal transcribed spacer 2 (ITS2) from pre-ribosomal RNA is essential to make functional ribosomes. This complicated processing reaction begins with a single endonucleolytic cleavage followed by exonucleolytic trimming at both new cleavage sites to generate mature 5.8S and 25S rRNA. We reconstituted the 7S→5.8S processing branch within ITS2 using purified exosome and its nuclear cofactors. We find that both Rrp44's ribonuclease activities are required for initial RNA shortening followed by hand over to the exonuclease Rrp6...
November 27, 2017: Nature Communications
Thijs Vandenryt, Bart van Grinsven, Kasper Eersels, Peter Cornelis, Safira Kholwadia, Thomas J Cleij, Ronald Thoelen, Ward De Ceuninck, Marloes Peeters, Patrick Wagner
Serotonin is an important neurotransmitter that plays a major role in the pathogenesis of a variety of conditions, including psychiatric disorders. The detection of serotonin typically relies on high-performance liquid chromatography (HPLC), an expensive technique that requires sophisticated equipment and trained personnel, and is not suitable for point-of-care applications. In this contribution, we introduce a novel sensor platform that can measure spiked neurotransmitter concentrations in whole blood samples in a fast and low-cost manner by combining synthetic receptors with a thermal readout technique-the heat-transfer method...
November 23, 2017: Sensors
Geul Bang, Young Hwan Kim, Junghyo Yoon, Yeong Jun Yu, Seok Chung, Jeong Ah Kim
Pre-treatment of samples is the one of most important steps in analytical methods for efficient and accurate results. Typically, an extraction method used for lipid analysis with mass spectrometry is accompanied by complex liquid-liquid extraction. We have devised a simple, rapid, and efficient lipid extraction method using super absorbent polymers (SAPs) and developed a high-throughput lipid extraction platform based on a microfluidic system. Since SAPs can rapidly absorb an aqueous solution from a raw sample and convert it into the gel, the lipid extraction process can be remarkably simplified...
November 22, 2017: Analytical Chemistry
Omri Malik, Hadeel Khamis, Sergei Rudnizky, Ariel Kaplan
Retroviral reverse transcriptase catalyses the synthesis of an integration-competent dsDNA molecule, using as a substrate the viral RNA. Using optical tweezers, we follow the Murine Leukemia Virus reverse transcriptase as it performs strand-displacement polymerization on a template under mechanical force. Our results indicate that reverse transcriptase functions as a Brownian ratchet, with dNTP binding as the rectifying reaction of the ratchet. We also found that reverse transcriptase is a relatively passive enzyme, able to polymerize on structured templates by exploiting their thermal breathing...
November 20, 2017: Nucleic Acids Research
Kornelius Zeth, Enea Sancho-Vaello
Mammals protect themselves from inflammation triggered by microorganisms through secretion of antimicrobial peptides (AMPs). One mechanism by which AMPs kill bacterial cells is perforating their membranes. Membrane interactions and pore formation were investigated for α-helical AMPs leading to the formulation of three basic mechanistic models: the barrel stave, toroidal, and carpet model. One major drawback of these models is their simplicity. They do not reflect the real in vitro and in vivo conditions. To challenge and refine these models using a structure-based approach we set out to investigate how human cathelicidin (LL-37) and dermcidin (DCD) interact with membranes...
2017: Frontiers in Chemistry
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