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https://www.readbyqxmd.com/read/28640984/is-it-right-to-ignore-learning-curve-patients-laparoscopic-colorectal-trials
#1
Alan P Meagher, Shi Yang, Shuyuan Li
BACKGROUND: Increasingly complex, technically demanding surgical procedures utilizing emerging technologies have developed over recent decades and are recognized as having long 'learning curves'. This raises significant new issues. Ethically and scientifically, the outcome of a patient in the learning curve is as important as the outcome of a patient outside the learning curve. The aim of this study is to highlight just one aspect of our approach to learning-curve patients that should change...
June 22, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28640968/the-impact-of-andean-patagonian-mycoflora-in-the-search-for-new-lead-molecules
#2
REVIEW
Pedro M Aqueveque, Carlos L Cespedes, Isao Kubo, David S Seigler, Olov Sterner
Secondary metabolites from fungi have become a major source of chemical innovation in programs searching for lead molecules with bioactivities, especially over the last 50 years. In this review, we discuss the fundamental considerations in the discovery of molecules for agricultural and medicinal uses. This group of organisms possesses a strong potential for scientific and industrial communities. Recently, the incorporation of new technologies for the artificial cultivation of fungi and the use of better equipment to isolate and identify active metabolites has allowed the discovery of leading molecules for the design of new and safer drugs and pesticides...
June 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28640705/genomic-analysis-of-childhood-brain-tumors-methods-for-genome-wide-discovery-and-precision-medicine-become-mainstream
#3
Stephen C Mack, Paul A Northcott
Recent breakthroughs in next-generation sequencing technology and complementary genomic platforms have transformed our capacity to interrogate the molecular landscapes of human cancers, including childhood brain tumors. Numerous high-throughput genomic studies have been reported for the major histologic brain tumor entities diagnosed in children, including interrogations at the level of the genome, epigenome, and transcriptome, many of which have yielded essential new insights into disease biology. The nature of these discoveries has been largely platform dependent, exemplifying the usefulness of applying different genomic and computational strategies, or integrative approaches, to address specific biologic and/or clinical questions...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28635333/molecular-biomarkers-to-guide-precision-medicine-in-localized-prostate-cancer
#4
Minke Smits, Niven Mehra, Michiel Sedelaar, Winald Gerritsen, Jack A Schalken
Major advances through tumor profiling technologies, that include next-generation sequencing, epigenetic, proteomic and transcriptomic methods, have been made in primary prostate cancer, providing novel biomarkers that may guide precision medicine in the near future. Areas covered: The authors provided an overview of novel molecular biomarkers in tissue, blood and urine that may be used as clinical tools to assess prognosis, improve selection criteria for active surveillance programs, and detect disease relapse early in localized prostate cancer...
June 21, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28634607/a-high-throughput-microfluidic-platform-for-size-selective-enrichment-of-cell-populations-in-tissue-and-blood-samples
#5
Nivedita Nivedita, Neha Garg, Abraham P Lee, Ian Papautsky
Numerous applications in biology and medicine require the efficient and reliable separation of cells for disease diagnosis, genetic analysis, drug screening, and therapeutics. In this work, we demonstrate a novel technology that integrates a passive and an active device to separate, enrich and release cells on-demand from a complex blood sample, or cancer cells derived from a tissue biopsy. We exploit the high throughput (>1 mL min(-1)), size-based sorting capability of the passive spiral inertial microfluidic (iMF) device to focus particles/cells towards an active lateral cavity acoustic transducer (LCAT) device for size-selective enrichment...
June 21, 2017: Analyst
https://www.readbyqxmd.com/read/28633563/mammalian-synthetic-biology-engineering-biological-systems
#6
Joshua B Black, Pablo Perez-Pinera, Charles A Gersbach
The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution...
June 21, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#7
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28630964/an-insertion-self-fusion-mechanism-for-cell-membrane-immobilization-on-porous-silica-beads-to-fabricate-biomimic-carriers
#8
Xu Wang, Liang Xu, Ruizhi Mao, Xinchao Zhao, Bei Xu, Cheng Tang, Jiahui He, Yanwen Zhang
Immobilization of membrane proteins on solid supports with high stability, favorable reusability and prevention of contamination is of great interest in nanobiology and medicine. Cell membrane coating technology enables the membrane proteins associated with their surrounding membranes to co-immobilize onto the solid matrix, largely enhancing the loading efficiency and conserving the bioactivity of the membrane proteins. Herein, we systematically illustrate the mechanism of cell membrane immobilization on porous silica beads, facilitating the fabricated biomimic carriers applied for chromatography...
June 20, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28630164/single-molecule-nanopore-enzymology
#9
REVIEW
Kherim Willems, Veerle Van Meervelt, Carsten Wloka, Giovanni Maglia
Biological nanopores are a class of membrane proteins that open nanoscale water conduits in biological membranes. When they are reconstituted in artificial membranes and a bias voltage is applied across the membrane, the ionic current passing through individual nanopores can be used to monitor chemical reactions, to recognize individual molecules and, of most interest, to sequence DNA. In addition, a more recent nanopore application is the analysis of single proteins and enzymes. Monitoring enzymatic reactions with nanopores, i...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630163/measuring-the-potential-energy-barrier-to-lipid-bilayer-electroporation
#10
Jason T Sengel, Mark I Wallace
Electroporation is a common tool for gene transfection, tumour ablation, sterilization and drug delivery. Using experimental methods, we explore the temperature dependence of electropore formation in a model membrane system (droplet-interface bilayers), using optical single-channel recording to image the real-time gating of individual electropores. We investigate the influence of the agarose substrate on electropores formed in this system. Furthermore, by examining the temperature-dependent kinetics of pore opening and closure we are able to estimate a barrier to pore opening in 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) membranes to be 25...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630162/real-time-dynamics-of-carbon-nanotube-porins-in-supported-lipid-membranes-visualized-by-high-speed-atomic-force-microscopy
#11
Yuliang Zhang, Ramya H Tunuguntla, Pyung-On Choi, Aleksandr Noy
In-plane mobility of proteins in lipid membranes is one of the fundamental mechanisms supporting biological functionality. Here we use high-speed atomic force microscopy (HS-AFM) to show that a novel type of biomimetic channel-carbon nanotube porins (CNTPs)-is also laterally mobile in supported lipid membranes, mimicking biological protein behaviour. HS-AFM can capture real-time dynamics of CNTP motion in the supported lipid bilayer membrane, build long-term trajectories of the CNTP motion and determine the diffusion coefficients associated with this motion...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630161/insertion-of-proteins-and-lipopolysaccharide-into-the-bacterial-outer-membrane
#12
REVIEW
Istvan Botos, Nicholas Noinaj, Susan K Buchanan
The bacterial outer membrane contains phospholipids in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet. Both proteins and LPS must be frequently inserted into the outer membrane to preserve its integrity. The protein complex that inserts LPS into the outer membrane is called LptDE, and consists of an integral membrane protein, LptD, with a separate globular lipoprotein, LptE, inserted in the barrel lumen. The protein complex that inserts newly synthesized outer-membrane proteins (OMPs) into the outer membrane is called the BAM complex, and consists of an integral membrane protein, BamA, plus four lipoproteins, BamB, C, D and E...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630160/listeriolysin-o-from-bazooka-to-swiss-army-knife
#13
REVIEW
Suzanne E Osborne, John H Brumell
Listeria monocytogenes (Lm) is a Gram-positive facultative intracellular pathogen. Infections in humans can lead to listeriosis, a systemic disease with a high mortality rate. One important mechanism of Lm dissemination involves cell-to-cell spread after bacteria have entered the cytosol of host cells. Listeriolysin O (LLO; encoded by the hly gene) is a virulence factor present in Lm that plays a central role in the cell-to-cell spread process. LLO is a member of the cholesterol-dependent cytolysin (CDC) family of toxins that were initially thought to promote disease largely by inducing cell death and tissue destruction-essentially acting like a 'bazooka'...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630159/the-mystery-behind-membrane-insertion-a-review-of-the-complement-membrane-attack-complex
#14
REVIEW
Charles Bayly-Jones, Doryen Bubeck, Michelle A Dunstone
The membrane attack complex (MAC) is an important innate immune effector of the complement terminal pathway that forms cytotoxic pores on the surface of microbes. Despite many years of research, MAC structure and mechanism of action have remained elusive, relying heavily on modelling and inference from biochemical experiments. Recent advances in structural biology, specifically cryo-electron microscopy, have provided new insights into the molecular mechanism of MAC assembly. Its unique 'split-washer' shape, coupled with an irregular giant β-barrel architecture, enable an atypical mechanism of hole punching and represent a novel system for which to study pore formation...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630158/computational-studies-of-peptide-induced-membrane-pore-formation
#15
REVIEW
Richard Lipkin, Themis Lazaridis
A variety of peptides induce pores in biological membranes; the most common ones are naturally produced antimicrobial peptides (AMPs), which are small, usually cationic, and defend diverse organisms against biological threats. Because it is not possible to observe these pores directly on a molecular scale, the structure of AMP-induced pores and the exact sequence of steps leading to their formation remain uncertain. Hence, these questions have been investigated via molecular modelling. In this article, we review computational studies of AMP pore formation using all-atom, coarse-grained, and implicit solvent models; evaluate the results obtained and suggest future research directions to further elucidate the pore formation mechanism of AMPs...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630157/pore-formation-by-dimeric-bak-and-bax-an-unusual-pore
#16
REVIEW
Rachel T Uren, Sweta Iyer, Ruth M Kluck
Apoptotic cell death via the mitochondrial pathway occurs in all vertebrate cells and requires the formation of pores in the mitochondrial outer membrane. Two Bcl-2 protein family members, Bak and Bax, form these pores during apoptosis, and how they do so has been investigated for the last two decades. Many of the conformation changes that occur during their transition to pore-forming proteins have now been delineated. Notably, biochemical, biophysical and structural studies indicate that symmetric homodimers are the basic unit of pore formation...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630156/apoptotic-foci-at-mitochondria-in-and-around-bax-pores
#17
REVIEW
Begoña Ugarte-Uribe, Ana J García-Sáez
The permeabilization of the mitochondrial outer membrane by Bax and Bak during apoptosis is considered a key step and a point of no return in the signalling pathway. It is always closely related to the reorganization of mitochondrial cristae that frees cytochrome c to the intermembrane space and to massive mitochondrial fragmentation mediated by the dynamin-like protein Drp1. Despite multiple evidence in favour of a functional link between these processes, the molecular mechanisms that connect them and their relevance for efficient apoptosis signalling remain obscure...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630155/haemolytic-actinoporins-interact-with-carbohydrates-using-their-lipid-binding-module
#18
Koji Tanaka, Jose M M Caaveiro, Koldo Morante, Kouhei Tsumoto
Pore-forming toxins (PFTs) are proteins endowed with metamorphic properties that enable them to stably fold in water solutions as well as in cellular membranes. PFTs produce lytic pores on the plasma membranes of target cells conducive to lesions, playing key roles in the defensive and offensive molecular systems of living organisms. Actinoporins are a family of potent haemolytic toxins produced by sea anemones vigorously studied as a paradigm of α-helical PFTs, in the context of lipid-protein interactions, and in connection with nanopore technologies...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630153/membrane-spanning-%C3%AE-helical-barrels-as-tractable-protein-design-targets
#19
REVIEW
Ai Niitsu, Jack W Heal, Kerstin Fauland, Andrew R Thomson, Derek N Woolfson
The rational (de novo) design of membrane-spanning proteins lags behind that for water-soluble globular proteins. This is due to gaps in our knowledge of membrane-protein structure, and experimental difficulties in studying such proteins compared to water-soluble counterparts. One limiting factor is the small number of experimentally determined three-dimensional structures for transmembrane proteins. By contrast, many tens of thousands of globular protein structures provide a rich source of 'scaffolds' for protein design, and the means to garner sequence-to-structure relationships to guide the design process...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630152/repurposing-a-pore-highly-conserved-perforin-like-proteins-with-alternative-mechanisms
#20
REVIEW
Tao Ni, Robert J C Gilbert
Pore-forming proteins play critical roles in pathogenic attack and immunological defence. The membrane attack complex/perforin (MACPF) group of homologues represents, with cholesterol-dependent cytolysins, the largest family of such proteins. In this review, we begin by describing briefly the structure of MACPF proteins, outlining their common mechanism of pore formation. We subsequently discuss some examples of MACPF proteins likely implicated in pore formation or other membrane-remodelling processes. Finally, we focus on astrotactin and bone morphogenetic protein and retinoic acid-induced neural-specific proteins, highly conserved MACPF family members involved in developmental processes, which have not been well studied to date or observed to form a pore-and which data suggest may act by alternative mechanisms...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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