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Yiwen Ouyang, Jingyi Li, Doris M Haverstick, James P Landers
We recently defined a magnetic bead-based assay that exploited an agglutination-like response for DNA and applied it to DNA-containing cell enumeration using inexpensive benchtop hardware [ J. Am. Chem. Soc. 2012 , 134 ( 12 ), 5689 - 96 ]. Although cost-efficient, the open-well format assay required numerous manual steps, and the magnetic field actuation scheme was not readily adaptable for integration. Here, we demonstrate a low-cost (<$2 in-lab), higher-throughput "pinwheel assay" platform that relies on a combination of a disposable rotation-driven microdisc (RDM), and a simple bidirectional rotating magnetic field (bi-RMF)...
October 25, 2016: Analytical Chemistry
Yan Qu, Qiu Gen Zhang, Faizal Soyekwo, Run Sheng Gao, Rui Xue Lv, Chen Xiao Lin, Meng Meng Chen, Ai Mei Zhu, Qing Lin Liu
Two-dimensional nanosheets of late show great promise as novel materials for size-selective separation membranes of high efficiency. Herein, we demonstrate a novel laminated nanofiltration membrane for fast water purification and organic solvent nanofiltration using the 1 nm-thick and 50 nm-wide nickel hydroxide nanosheets that are facilely prepared by a green chemistry method. The resulting membranes exhibit uniform and flectional two-dimensional laminated structure. With about 1 nm high laminated channels, they allow super-fast transport of water and organic solvents...
October 24, 2016: Nanoscale
Shaoling Jiang, Hanchang He, Lishan Tan, Liangliang Wang, Zhengxiu Su, Yufeng Liu, Hongguo Zhu, Menghuan Zhang, Fan Fan Hou, Aiqing Li
Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex...
October 24, 2016: Scientific Reports
Kathleen M Clark, Jermaine L Jenkins, Nadia Fedoriw, Mark E Dumont
The function and localization of proteins and peptides containing C-terminal "CaaX" (Cys-aliphatic-aliphatic-anything) sequence motifs are modulated by post-translational attachment of isoprenyl groups to the cysteine sulfhydryl, followed by proteolytic cleavage of the aaX amino acids. The zinc metalloprotease ZMPSTE24 is one of two enzymes known to catalyze this cleavage. The only identified target of mammalian ZMPSTE24 is prelamin A, the precursor to the nuclear scaffold protein lamin A. ZMPSTE24 also cleaves prelamin A at a second site 15 residues upstream from the CaaX site...
October 24, 2016: Protein Science: a Publication of the Protein Society
D Digles, B Zdrazil, J-M Neefs, H Van Vlijmen, C Herhaus, A Caracoti, J Brea, B Roibás, M I Loza, N Queralt-Rosinach, L I Furlong, A Gaulton, L Bartek, S Senger, C Chichester, O Engkvist, C T Evelo, N I Franklin, D Marren, G F Ecker, E Jacoby
Phenotypic screening is in a renaissance phase and is expected by many academic and industry leaders to accelerate the discovery of new drugs for new biology. Given that phenotypic screening is per definition target agnostic, the emphasis of in silico and in vitro follow-up work is on the exploration of possible molecular mechanisms and efficacy targets underlying the biological processes interrogated by the phenotypic screening experiments. Herein, we present six exemplar computational protocols for the interpretation of cellular phenotypic screens based on the integration of compound, target, pathway, and disease data established by the IMI Open PHACTS project...
June 1, 2016: MedChemComm
Nataliya Di Donato, Ying Y Jean, A Murat Maga, Briana D Krewson, Alison B Shupp, Maria I Avrutsky, Achira Roy, Sarah Collins, Carissa Olds, Rebecca A Willert, Agnieszka M Czaja, Rachel Johnson, Jessi A Stover, Steven Gottlieb, Deborah Bartholdi, Anita Rauch, Amy Goldstein, Victoria Boyd-Kyle, Kimberly A Aldinger, Ghayda M Mirzaa, Anke Nissen, Karlla W Brigatti, Erik G Puffenberger, Kathleen J Millen, Kevin A Strauss, William B Dobyns, Carol M Troy, Robert N Jinks
Lissencephaly is a malformation of cortical development typically caused by deficient neuronal migration resulting in cortical thickening and reduced gyration. Here we describe a "thin" lissencephaly (TLIS) variant characterized by megalencephaly, frontal predominant pachygyria, intellectual disability, and seizures. Trio-based whole-exome sequencing and targeted re-sequencing identified recessive mutations of CRADD in six individuals with TLIS from four unrelated families of diverse ethnic backgrounds. CRADD (also known as RAIDD) is a death-domain-containing adaptor protein that oligomerizes with PIDD and caspase-2 to initiate apoptosis...
October 18, 2016: American Journal of Human Genetics
Louise Hetherington, Elena Schneider, Caroline Scott, David DeKretser, Charles H Muller, Hubert Hondermarck, Tony Velkov, Mark A Baker
Globally, approximately 1 in 15 men of reproductive age are infertile, yet the precise mechanisms underlying their gamete failure are unknown. Although a semen-analysis is performed to determine fertilizing potential, the diagnostic suitability of this analysis has been questioned in several reports, as many men, classified as "infertile" according to their semen analysis, subsequently turn out to be fertile. Herein, we have used a quantitative (phospho)-proteomic analysis, using enrichment on titanium dioxide followed by ion-trap mass spectrometry (LC-MS/MS), to compare the semen of infertile versus fertile males...
October 21, 2016: Molecular & Cellular Proteomics: MCP
Zhanzhan Du, Fang Shi, Dong Liu, Hongling Ye, Maheen Mahwish Surhio, Jinglei Li, Ming Ye
A sulfated polysaccharide, designated as SLEP-1, was obtained after sulfation of the exopolysaccharide (LEP-1) which was isolated from Lachnum. The degree of substitution (DS) of sulfate group of SLEP-1 was 1.97. SEM images of SLEP-1 revealed laminated structure in mesh. UV, FT-IR and (13)C NMR spectra indicated that the LEP-1 was sulfated successfully. The result of the anticoagulant activity in vitro showed that both of LEP-1 and SLEP-1 could effectively prolong activated partial thromboplastin time (APTT) and thrombin time (TT) of the normal mice plasma, in which SLEP-1 was more effectively than those of LEP-1, and dose-effect relationships were found...
October 1, 2016: Bioorganic & Medicinal Chemistry Letters
Rasmus B Jensen, Signe H Danielsen, Anne-Helene Tauson
BACKGROUND: Obesity is related to the development of several diseases like insulin resistance and laminitis in horses. The prevalence of obesity among mature Icelandic horses in Denmark has not been investigated previously. This study aimed to find the prevalence of obesity, to compare body condition score (BCS) based on owner perception with that of an experienced person and to correlate the BCS to body weight (BW) and morphometric measures in a group of mature Icelandic horses in Denmark...
October 20, 2016: Acta Veterinaria Scandinavica
Brandon L Thompson, Christopher Birch, Daniel A Nelson, Jingyi Li, Jacquelyn A DuVall, Delphine Le Roux, An-Chi Tsuei, Daniel L Mills, Brian E Root, James P Landers
Current conventional methods utilized for forensic DNA analysis are time consuming and labor-intensive requiring large and expensive equipment and instrumentation. While more portable Rapid DNA systems have been developed, introducing them to a working laboratory still necessitates a high cost of initiation followed by the recurrent cost of the devices. This has highlighted the need for an inexpensive, rapid and portable DNA analysis tool for human identification in a forensic setting. In order for an integrated DNA analysis system such as this to be realized, device operations must always be concluded by a rapid separation of short-tandem repeat (STR) DNA fragments...
October 21, 2016: Lab on a Chip
Jillian Iafrati, Arnaud Malvache, Cecilia Gonzalez Campo, M Juliana Orejarena, Olivier Lassalle, Lamine Bouamrane, Pascale Chavis
The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiological mechanisms contributing to these disorders, we revisited the endophenotype approach from a developmental viewpoint. The extracellular matrix protein reelin which contributes to cellular and network plasticity, is a risk factor for several psychiatric diseases. We mapped the aggregate effect of the RELN risk allele on postnatal development of PFC functions by cross-sectional synaptic and behavioral analysis of reelin-haploinsufficient mice...
October 21, 2016: Scientific Reports
Karina Beatriz Acosta, Melina Noelia Lorenzini Campos, Susana Beatriz Etcheverry, Pedro Dario Zapata
The α6β4 integrin is composed of the α6 and β4 subunits that are encoded by the ITGα6 and the ITGβ4 genes, respectively. The α6β4 main function is to intervene in lamination and epithelia integrity maintenance by cell-matrix interactions. This integrin appears to have importance in breast cancer malignancy, as well as other epithelial carcinomas. The aim of this work was to investigate the potential role of ITGα6 (A380T) and ITGβ4 (R1281W) genetic variations in breast cancer susceptibility, in a female population from the northeast region of Argentina (Misiones)...
October 18, 2016: International Journal of Molecular Sciences
Angelyn V Nguyen, Kendra D Nyberg, Michael B Scott, Alia M Welsh, Andrew H Nguyen, Nanping Wu, Sophia V Hohlbauch, Nicholas A Geisse, Ewan A Gibb, A Gordon Robertson, Timothy R Donahue, Amy C Rowat
Metastasis is a fundamentally physical process in which cells are required to deform through narrow gaps as they invade surrounding tissues and transit to distant sites. In many cancers, more invasive cells are more deformable than less invasive cells, but the extent to which mechanical phenotype, or mechanotype, can predict disease aggressiveness in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here we investigate the invasive potential and mechanical properties of immortalized PDAC cell lines derived from primary tumors and a secondary metastatic site, as well as noncancerous pancreatic ductal cells...
October 20, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Emilie Lukasova, Aleš Kovařík, Alena Bačíková, Martin Falk, Stanislav Kozubek
The cellular transition to senescence is associated with extensive chromatin reorganization and gene expression changes. Recent studies appeared implying an association of lamin B1 (LB1) reduction with chromatin rearrangement in human fibroblasts promoted to senescence, while the mechanisms and structural features of these relations were not yet clarified. In this work we examined the functions of LB1 and lamin B receptor (LBR) in human cancer cells. We found that both LB1 and LBR tend to deplete during cancer cells transfer to senescence by γ-irradiation...
October 19, 2016: Biochemical Journal
Richard F Spaide
PURPOSE: To investigate the structural optical coherence tomography and related microvascular flow characteristics in eyes with retinal vasculitis. METHODS: Regions involved with perivascular infiltration in eyes with retinal vasculitis, but no evidence of large vessel occlusion were evaluated with optical coherence tomography (OCT), OCT angiography, and fluorescein angiography. RESULTS: Ten eyes of 5 patients with a variety of etiologies of retinal vasculitis were evaluated...
October 18, 2016: Retina
Bhaskar Dudem, Yeong Hwan Ko, Jung Woo Leem, Joo Ho Lim, Jae Su Yu
We report the hierarchical nano/micro architectured (HNMA)-polydimethylsiloxane (PDMS) film-based hybrid energy cells with multi-functionality to simultaneously harvest mechanical, solar, and wind energies. These films consist of nano/micro dual-scale architectures (i.e., nanonipples on inverted micro pyramidal arrays) on the PDMS surface. The HNMA-PDMS is replicable by a facile and cost-effective soft imprint lithography (SIL) using a nanoporous anodic alumina oxide (AAO) film formed on the micro-pyramidal (MP) structured silicon substrate...
October 19, 2016: ACS Applied Materials & Interfaces
Subarna Dutta, Maitree Bhattacharyya, Kaushik Sengupta
Lamins are mechanosensitive and elastic components of the nuclear lamina that respond to external mechanical cues by altering gene regulation in a feedback mechanism. Numerous mutations in A-type lamins cause a plethora of diverse diseases collectively termed as laminopathies, the majority of which are characterized by irregularly shaped, fragile, and plastic nuclei. These nuclei are challenged to normal mechanotransduction and lead to disease phenotypes. Here, we review our current understanding of the nucleocytoskeleton coupling in mechanotransduction mediated by lamins...
October 14, 2016: Cells
Xia Zhang, Jingyu Hu, Yan Chen
Betulinic acid (BA), a lupane-type pentacyclic triterpenoid saponin from tree bark, has the potential to induce the apoptosis of cancer cells without toxicity towards normal cells in vitro and in vivo. The antitumor pharmacological effects of BA consist of triggering apoptosis via the mitochondrial pathway, regulating the cell cycle and the angiogenic pathway via factors, including specificity protein transcription factors, cyclin D1 and epidermal growth factor receptor, inhibiting the signal transducer and activator of transcription 3 and nuclear factor‑κB signaling pathways, preventing the invasion and metastasis of tumor cells, and affecting the expression of topoisomerase I, p53 and lamin B1...
October 4, 2016: Molecular Medicine Reports
Subha Ghosh, Rahul Renapurkar, Subha V Raman
BACKGROUND: The objective of this study was to evaluate patients with known hereditary cardiac conduction and myocardial disease (HCCMD) caused by a lamin A/C gene mutation for skeletal muscle involvement using magnetic resonance imaging (MRI) computed tomography (CT). METHODS: Twenty-one patients with the diagnosis of HCCMD were available for study. Of these 21, 11 had MRI scans of the lower legs. The 11 that had an MRI were compared to a control group of 17 healthy controls...
October 2016: Cardiovascular Diagnosis and Therapy
Sandra Murcia, Ellen Lavoie, Tim Linley, Arun Devaraj, E Alex Ossa, D Arola
Fish scales exhibit a unique balance of flexibility, strength and toughness, which is essential to provide protection without encumbering locomotion. Although the mechanical behavior and structure of this natural armor are of recent interest, a comparison of these qualities from scales of different fish species has not been reported. In this investigation the armor of fish with different locomotion, size and protection needs were analyzed. Scales from the Arapaima gigas, the tarpon (Megalops atlanticus) and the carp (Cyprinus carpio) were compared in terms of the stacking sequence of individual plies and their microstructure...
September 20, 2016: Journal of the Mechanical Behavior of Biomedical Materials
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