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https://www.readbyqxmd.com/read/29244195/decellularized-colorectal-cancer-matrix-as-bioactive-microenvironment-for-in-vitro-3d-cancer-research
#1
Martina Piccoli, Edoardo D'Angelo, Sara Crotti, Francesca Sensi, Luca Urbani, Edoardo Maghin, Alan Burns, Paolo De Coppi, Matteo Fassan, Massimo Rugge, Flavio Rizzolio, Antonio Giordano, Pierluigi Pilati, Enzo Mammano, Salvatore Pucciarelli, Marco Agostini
Three-dimensional (3D) cancer models are overlooking the scientific landscape with the primary goal of bridging the gaps between two-dimensional (2D) cell lines, animal models and clinical research. Here we describe an innovative tissue engineering approach applied to colorectal cancer (CRC) starting from decellularized human biopsies in order to generate an organotypic 3D-bioactive model. This in vitro 3D system recapitulates the ultrastructural environment of native tissue as demonstrated by histology, immunohistochemistry, immunofluorescence and scanning electron microscopy analyses...
December 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29244007/detecting-intermediate-protein-conformations-using-algebraic-topology
#2
Nurit Haspel, Dong Luo, Eduardo González
BACKGROUND: Understanding protein structure and dynamics is essential for understanding their function. This is a challenging task due to the high complexity of the conformational landscapes of proteins and their rugged energy levels. In particular, it is important to detect highly populated regions which could correspond to intermediate structures or local minima. RESULTS: We present a hierarchical clustering and algebraic topology based method that detects regions of interest in protein conformational space...
December 6, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29242367/subspecies-in-the-global-human-gut-microbiome
#3
Paul I Costea, Luis Pedro Coelho, Shinichi Sunagawa, Robin Munch, Jaime Huerta-Cepas, Kristoffer Forslund, Falk Hildebrand, Almagul Kushugulova, Georg Zeller, Peer Bork
Population genomics of prokaryotes has been studied in depth in only a small number of primarily pathogenic bacteria, as genome sequences of isolates of diverse origin are lacking for most species. Here, we conducted a large-scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture-independent metagenomic approach. We examined the variation landscape of 71 species in 2,144 human fecal metagenomes and found that in 44 of these, accounting for 72% of the total assigned microbial abundance, single-nucleotide variation clearly indicates the existence of sub-populations (here termed subspecies)...
December 14, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/29242347/comprehensive-computational-design-of-ordered-peptide-macrocycles
#4
Parisa Hosseinzadeh, Gaurav Bhardwaj, Vikram Khipple Mulligan, Matthew D Shortridge, Timothy W Craven, Fátima Pardo-Avila, Stephen A Rettie, David E Kim, Daniel-Adriano Silva, Yehia M Ibrahim, Ian K Webb, John R Cort, Joshua N Adkins, Gabriele Varani, David Baker
Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with l-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of l- and d-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations...
December 15, 2017: Science
https://www.readbyqxmd.com/read/29241326/the-awsem-amylometer-predicting-amyloid-propensity-and-fibril-topology-using-an-optimized-folding-landscape-model
#5
Mingchen Chen, Nicholas P Schafer, Weihua Zheng, Peter G Wolynes
Amyloids are fibrillar protein aggregates with simple repeated structural motifs in their cores, usually β-strands but sometimes α-helices. Identifying the amyloid-prone regions within protein sequences is important both for understanding the mechanisms of amyloid-associated diseases and for understanding functional amyloids. Based on the crystal structures of seven cross-β amyloidogenic peptides with different topologies and one recently solved cross-α fiber structure, we have developed a computational approach for identifying amyloidogenic segments in protein sequences using the Associative memory, Water mediated, Structure and Energy Model...
December 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29238666/preoperative-counseling-and-expectation-management-for-inflatable-penile-prosthesis-implantation
#6
REVIEW
Gopal L Narang, Bradley D Figler, Robert M Coward
The inflatable penile prosthesis (IPP) is the gold standard surgical treatment for medical refractory erectile dysfunction (ED). While the modern IPP has enjoyed high satisfaction rates as a product of its continued innovation, reliability, and performance, patient dissatisfaction can still occur. IPP implantation restores physiologic function with cosmetic and psychological consequences, both of which place inherent emphasis on preoperative counseling and expectation management. This review aims to highlight the complex nature of such counseling and provide practitioners with a roadmap to navigate the landscape...
November 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29238076/climatic-suitability-isolation-by-distance-and-river-resistance-explain-genetic-variation-in-a-brazilian-whiptail-lizard
#7
Eliana Faria Oliveira, Pablo Ariel Martinez, Vinícius Avelar São-Pedro, Marcelo Gehara, Frank Thomas Burbrink, Daniel Oliveira Mesquita, Adrian Antonio Garda, Guarino Rinaldi Colli, Gabriel Correa Costa
Spatial patterns of genetic variation can help understand how environmental factors either permit or restrict gene flow and create opportunities for regional adaptations. Organisms from harsh environments such as the Brazilian semiarid Caatinga biome may reveal how severe climate conditions may affect patterns of genetic variation. Herein we combine information from mitochondrial DNA with physical and environmental features to study the association between different aspects of the Caatinga landscape and spatial genetic variation in the whiptail lizard Ameivula ocellifera...
December 14, 2017: Heredity
https://www.readbyqxmd.com/read/29237136/biomimetic-structural-materials-inspiration-from-design-and-assembly
#8
Nicholas A Yaraghi, David Kisailus
Nature assembles weak organic and inorganic constituents into sophisticated hierarchical structures, forming structural composites that demonstrate impressive combinations of strength and toughness. Two such composites are the nacre structure forming the inner layer of many mollusk shells, whose brick-and-mortar architecture has been the gold standard for biomimetic composites, and the cuticle forming the arthropod exoskeleton, whose helicoidal fiber-reinforced architecture has only recently attracted interest for structural biomimetics...
December 13, 2017: Annual Review of Physical Chemistry
https://www.readbyqxmd.com/read/29236856/bird-diversity-along-a-gradient-of-fragmented-habitats-of-the-cerrado
#9
Shayana DE Jesus, Wagner A Pedro, Arthur A Bispo
Understanding the factors that affect biodiversity is of central interest to ecology, and essential to species conservation and ecosystems management. We sampled bird communities in 17 forest fragments in the Cerrado biome, the Central-West region of Brazil. We aimed to know the communities structure pattern and the influence of geographical distance and environmental variables on them, along a gradient of fragmented habitats at both local and landscape scales. Eight structural variables of the fragments served as an environmental distance measurement at the local scale while five metrics served as an environmental distance measurement at the landscape scale...
December 11, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29234172/influence-of-historical-land-use-and-modern-agricultural-expansion-on-the-spatial-and-ecological-divergence-of-sugarcane-borer-diatraea-saccharalis-lepidoptera-crambidae-in-brazil
#10
Vitor A C Pavinato, Andrew P Michel, Jaqueline B de Campos, Celso Omoto, Maria I Zucchi
Human-mediated changes in landscapes can facilitate niche expansion and accelerate the adaptation of insect species. The interaction between the evolutionary history of the sugarcane borer, Diatraea saccharalis Fabricius, and historical and modern agricultural activity in Brazil shaped its spatial genetic structure, facilitating ecological divergence and incipient host shifting. Based on microsatellite data, STRUCTURE analyses identified two (K = 2) and three (K = 3) significant genetic clusters that corresponded to: (a) a strong signal of spatial genetic structure and, (b) a cryptic signal of host differentiation...
January 2018: Heredity
https://www.readbyqxmd.com/read/29232962/meaning-in-hoarding-perspectives-of-people-who-hoard-on-clutter-culture-and-agency
#11
David M R Orr, Michael Preston-Shoot, Suzy Braye
Hoarding has become increasingly prominent in clinical practice and popular culture in recent years, giving rise to extensive research and commentary. Critical responses in the social sciences have criticised the cultural assumptions built in to the construct of 'hoarding disorder' and expressed fears that it may generate stigma outweighing its benefits; however, few of these studies have engaged directly with 'hoarders' themselves. This paper reports on in-depth, semi-structured interviews with 10 individuals living in England, who received assessment and intervention for hoarding from Social Services...
December 12, 2017: Anthropology & Medicine
https://www.readbyqxmd.com/read/29232711/dependence-of-prevalence-of-contiguous-pathways-in-proteins-on-structural-complexity
#12
Kelly M Thayer, Jesse C Galganov, Avram J Stein
Allostery is a regulatory mechanism in proteins where an effector molecule binds distal from an active site to modulate its activity. Allosteric signaling may occur via a continuous path of residues linking the active and allosteric sites, which has been suggested by large conformational changes evident in crystal structures. An alternate possibility is that the signal occurs in the realm of ensemble dynamics via an energy landscape change. While the latter was first proposed on theoretical grounds, increasing evidence suggests that such a control mechanism is plausible...
2017: PloS One
https://www.readbyqxmd.com/read/29232131/a-quantitative-assessment-of-the-energetics-of-dopamine-translocation-by-human-dopamine-transporter
#13
Mary Hongying Cheng, Cihan Kaya, Ivet Bahar
Computational evaluation of the energetics of substrate binding, transport and release events of neurotransmitter transporters at the molecular level is a challenge, as the structural transitions of these membrane proteins involve coupled global and local changes that span time scales of several orders of magnitude, from nanoseconds to seconds. Here, we provide a quantitative assessment of the energetics of dopamine (DA) translocation through the human DA transporter (hDAT), using a combination of molecular modeling, simulations and analysis tools...
December 12, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29231965/mapping-multi-scale-vascular-plant-richness-in-a-forest-landscape-with-integrated-lidar-and-hyperspectral-remote-sensing
#14
C R Hakkenberg, K Zhu, R K Peet, C Song
The central role of floristic diversity in maintaining habitat integrity and ecosystem function has propelled efforts to map and monitor its distribution across forest landscapes. While biodiversity studies have traditionally relied largely on ground-based observations, the immensity of the task of generating accurate, repeatable, and spatially-continuous data on biodiversity patterns at large scales has stimulated the development of remote-sensing methods for scaling up from field plot measurements. One such approach is through integrated LiDAR and hyperspectral remote-sensing...
December 12, 2017: Ecology
https://www.readbyqxmd.com/read/29228692/epigenetic-landscape-change-analysis-during-human-emt-sheds-light-on-a-key-emt-mediator-trim29
#15
Sung Kyung Choi, Kurinji Pandiyan, Jung Woo Eun, Xiaojing Yang, Seong Hwi Hong, Suk Woo Nam, Peter A Jones, Gangning Liang, Jueng Soo You
Epithelial to mesenchymal transition (EMT) is a key trans-differentiation process, which plays a critical role in physiology and pathology. Although gene expression changes in EMT have been scrutinized, study of epigenome is in its infancy. To understand epigenetic changes during TWIST-driven EMT, we used the AcceSssIble assay to study DNA methylation and chromatin accessibility in human mammary epithelial cells (HMECs). The DNA methylation changes were found to have functional significance in EMT - i.e. methylated genes were enriched for E-box motifs that can be recognized by TWIST, at the promoters suggesting a potential targeting phenomenon, whereas the demethylated regions were enriched for pro-metastatic genes, supporting the role of EMT in metastasis...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228505/a-spatio-temporal-exposure-hazard-model-for-assessing-biological-risk-and-impact
#16
Emily Walker, Melen Leclerc, Jean-François Rey, Rémy Beaudouin, Samuel Soubeyrand, Antoine Messéan
We developed a simulation model for quantifying the spatio-temporal distribution of contaminants (e.g., xenobiotics) and assessing the risk of exposed populations at the landscape level. The model is a spatio-temporal exposure-hazard model based on (i) tools of stochastic geometry (marked polygon and point processes) for structuring the landscape and describing the exposed individuals, (ii) a dispersal kernel describing the dissemination of contaminants from polygon sources, and (iii) an (eco)toxicological equation describing the toxicokinetics and dynamics of contaminants in affected individuals...
December 11, 2017: Risk Analysis: An Official Publication of the Society for Risk Analysis
https://www.readbyqxmd.com/read/29227642/x-rays-in-the-cryo-em-era-structural-biology-s-dynamic-future
#17
Susannah Shoemaker, Nozomi Ando
Over the past several years, single-particle cryo-electron microscopy (cryo-EM) has emerged as a leading method for elucidating macromolecular structures at near-atomic resolution, rivaling even the established technique of X-ray crystallography. Cryo-EM is now able to probe proteins as small as hemoglobin (64 kDa), while avoiding the crystallization bottleneck entirely. The remarkable success of cryo-EM has called into question the continuing relevance of X-ray methods, particularly crystallography. To say that the future of structural biology is either cryo-EM or crystallography, however, would be misguided...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29227476/the-molecular-landscape-of-pediatric-acute-myeloid-leukemia-reveals-recurrent-structural-alterations-and-age-specific-mutational-interactions
#18
Hamid Bolouri, Jason E Farrar, Timothy Triche, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard, Soheil Meshinchi
We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29227308/medical-bioinformatics-in-melanoma
#19
Phil F Cheng
PURPOSE OF REVIEW: Bioinformatic insights from next-generation sequencing has been integral in understanding melanoma biology, resistance to treatment and provided new avenues for melanoma treatment. Whole-genome sequencing, whole-exome sequencing and RNA sequencing has redefined the molecular classification of melanoma, revealed distinct genetic aberrations that define clinical subtypes of melanoma and uncovered the diverse heterogeneity that resides in an individual tumor. RECENT FINDINGS: In this review, we will summarize the recent whole-genome study that catalogs the genomic landscape across many melanoma subtypes, the single-cell RNA sequencing studies that interrogates tumor heterogeneity and the personalized vaccine approaches to melanoma treatment...
December 8, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29227211/babesia-occurrence-in-rodents-in-relation-to-landscapes-of-mainland-southeast-asia
#20
Anamika Karnchanabanthoeng, Serge Morand, Sathaporn Jittapalapong, Bernard Carcy
The purpose of this study is to investigate the relationships between habitat structure and Babesia spp. occurrence in rodents in mainland Southeast Asia. Of 1439 rodents and insectivores investigated, the protist Babesia was found in only 81 individuals (5.6% of the micromammals investigated) with Babesia microti U.S. type the more prevalent (4.1%), followed by the B. microti Kobe type (1.2%), and by the very rare Babesia BiCM002 (0.04%). We used georeferenced data of rodents analyzed for Babesia infection and land cover maps produced for the seven study sites in Thailand, Cambodia, and Lao PDR, where they were collected...
December 11, 2017: Vector Borne and Zoonotic Diseases
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