Centrally concentrated molecular gas driving galactic-scale ionized gas outflows in star-forming galaxies

We perform a joint analysis of high spatial resolution molecular gas and star-formation rate (SFR) maps in main-sequence star-forming galaxies experiencing galactic-scale outflows of ionized gas. Our aim is to understand the mechanism that determines which galaxies are able to launch these intense winds. We observed CO(1→0) at 1-arcsec resolution with ALMA in 16 edge-on galaxies, which also have 2-arcsec spatial-resolution optical integral field observations from the SAMI Galaxy Survey. Half the galaxies in the sample were previously identified as harbouring intense and large-scale outflows of ionized gas (‘outflow types’) and the rest serve as control galaxies. The data set is complemented by integrated CO(1→0) observations from the IRAM 30-m telescope to probe the total molecular gas reservoirs. We find that the galaxies powering outflows do not possess significantly different global gas fractions or star-formation efficiencies when compared with a control sample. However, the ALMA maps reveal that the molecular gas in the outflow-type galaxies is distributed more centrally than in the control galaxies. For our outflow-type objects, molecular gas and star-formation are largely confined within their inner effective radius (reff), whereas in the control sample, the distribution is more diffuse, extending far beyond reff. We infer that outflows in normal star-forming galaxies may be caused by dynamical mechanisms that drive molecular gas into their central regions, which can result in locally enhanced gas surface density and star-formation

Genotyping of single nucleotide polymorphisms related to attention-deficit hyperactivity disorder

Pharmacological treatment of several diseases, such as attention-deficit hyperactivity disorder (ADHD), presents marked variability in efficiency and its adverse effects. The genotyping of specific single nucleotide polymorphisms (SNPs) can support the prediction of responses to drugs and the genetic risk of presenting comorbidities associated with ADHD. This study presents two rapid and affordable microarray-based strategies to discriminate three clinically important SNPs in genes ADRA2A, SL6CA2, and OPRM1 (rs1800544, rs5569, and rs1799971, respectively). These approaches are allele-specific oligonucleotide hybridization (ASO) and a combination of allele-specific amplification (ASA) and solid-phase hybridization. Buccal swab and blood samples taken from ADHD patients and controls were analyzed by ASO, ASA, and a gold-reference method. The results indicated that ASA is superior in genotyping capability and analytical performance.This research has been funded through projects FEDER MINECO INNPACTO IPT-2011-1132-010000, CTQ/2013/45875R, and PrometeoII/2014/040 (GVA).Tortajada-Genaro, LA.; Mena-Mollá, S.; Niñoles Rodenes, R.; Puigmule, M.; Viladevall, L.; Maquieira Catala, Á. (2016). Genotyping of single nucleotide polymorphisms related to attention-deficit hyperactivity disorder. Analytical and Bioanalytical Chemistry. 408(9):2339-2345. https://doi.org/10.1007/s00216-016-9332-3S233923454089Cortese S. The neurobiology and genetics of Attention-Deficit/Hyperactivity Disorder (ADHD): what every clinician should know. Eur J Paediatr Neurol. 2012;16:422–33.Contini V, Rovaris DL, Victor MM, Grevet EH, Rohde LA, Bau CH. Pharmacogenetics of response to methylphenidate in adult patients with attention-deficit/hyperactivity disorder (ADHD): a systematic review. Eur Neuropsychopharmacol. 2013;23:555–60.Gardiner SJ, Begg EJ. Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev. 2006;58(3):521–90.Abul-Husn NS, Obeng AO, Sanderson SC, Gottesman O, Scott SA. Implementation and utilization of genetic testing in personalized medicine. Pharmacogenomics Pers Med. 2014;7:227.Altman RB, Flockhart D, Goldstein DB, editors. Principles of pharmacogenetics and pharmacogenomics. Cambridge: Cambridge University Press; 2012.Hawi Z, Cummins TDR, Tong J, Johnson B, Lau R, Samarrai W, et al. The molecular genetic architecture of attention deficit hyperactivity disorder. Mol Psychiatry. 2015;20:289–97.Limaye N. Pharmacogenomics, Theranostics and Personalized Medicine-the complexities of clinical trials: challenges in the developing world. Appl Transl Genomics. 2013;2:17–21.Manolio TA, Chisholm RL, Ozenberger B, Roden DM, Williams MS, Wilson R, et al. Implementing genomic medicine in the clinic: the future is here. Genet Med. 2013;15:258–67.Kim S, Misra A. PharmGKB: the Pharmacogenomics Knowledge Base. Annu Rev Biomed Eng. 2007;9:289–320.Lucarelli F, Tombelli S, Minunni M, Marrazza G, Mascini M. Electrochemical and piezoelectric DNA biosensors for hybridisation detection. Anal Chim Acta. 2008;609:139–59.Knez K, Spasic D, Janssen KP, Lammertyn J. Emerging technologies for hybridization based single nucleotide polymorphism detection. Analyst. 2014;139:353–70.Choi JY, Kim YT, Byun JY, Ahn J, Chung S, Gweon DG, et al. Integrated allele-specific polymerase chain reaction–capillary electrophoresis microdevice for single nucleotide polymorphism genotyping. Lab Chip. 2012;12:5146–54.Ragoussis J. Genotyping Technologies for Genetic Research. Annu Rev Genomics Hum Genet. 2009;10:117–33.Sethi D, Gandhi RP, Kuma P, Gupta KC. Chemical strategies for immobilization of oligonucleotides. Biotechnol J. 2009;4:1513–29.Bañuls MJ, Morais SB, Tortajada-Genaro LA, Maquieira A. Microarray Developed on Plastic Substrates. Microarray Technology: Methods and Applications, 2016; 37-51.Tortajada-Genaro LA, Rodrigo A, Hevia E, Mena S, Niñoles R, Maquieira A. Microarray on digital versatile disc for identification and genotyping of Salmonella and Campylobacter in meat products. Anal Bioanal Chem. 2015;407:7285–94.Kieling C, Genro JP, Hutz MH, Rohde LA. A current update on ADHD pharmacogenomics. Pharmacogenomics. 2010;11:407–19.Kim BN, Kim JW, Cummins TD, Bellgrove MA, Hawi Z, Hong SB, et al. Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder. J Clin Psychopharmacol. 2013;33:356–62.Carpentier PJ, Arias Vasquez A, Hoogman M, Onnink M, Kan CC, Kooij JJS, et al. Shared and unique genetic contributions to attention deficit/hyperactivity disorder and substance use disorders: A pilot study of six candidate genes. Eur Neuropsychopharmacol. 2013;23:448–57.Zhang Y, Haraksingh R, Grubert F, Abyzov A, Gerstein M, Weissman S, et al. Child development and structural variation in the human genome. Child Dev. 2013;84:34–48.Asari M, Watanabe S, Matsubara K, Shiono H, Shimizu K. Single nucleotide polymorphism genotyping by mini-primer allele-specific amplification with universal reporter primers for identification of degraded DNA. Anal Biochem. 2009;386:85–90.Choi JY, Kim YT, Ahn J, Kim KS, Gweon DG, Seo TS. Integrated allele-specific polymerase chain reaction–capillary electrophoresis microdevice for single nucleotide polymorphism genotyping. Biosens Bioelectron. 2012;35:327–34.Konstantou JK, Ioannou PC, Christopoulos TK. Dual-allele dipstick assay for genotyping single nucleotide polymorphisms by primer extension reaction. Eur J Hum Genet. 2009;17:105–11.Sebastian T, Cooney CG, Parker J, Qu P, Perov A, Golova JB, et al. Integrated amplification microarray system in a lateral flow cell for warfarin genotyping from saliva. Clin Chim Acta. 2014;429:198–205

Skin friction blistering: computer model

BACKGROUND/PURPOSE: Friction blisters, a common injury in sports and military operations, can adversely effect or even halt performance. Given its frequency and hazardous nature, recent research efforts appear limited. Blistering can be treated as a delamination phenomenon; similar issues in materials science have been extensively investigated in theory and experiment. An obstacle in studying blistering is the difficulty of conducting experiment on humans and animals. Computer modeling thus becomes a preferred tool. METHOD: This paper used a dynamic non-linear finite-element model with a blister-characterized structure and contact algorithm for outer materials and blister roof to investigate the effects on deformation and stress of an existing blister by changing the friction coefficient and elastic modulus of the material in contact with the blister. RESULTS: Through the dynamics mode and harmonic frequency approach, we demonstrated that the loading frequency leads to dramatic changes of displacement and stress in spite of otherwise similar loading. Our simulations show that an increased friction coefficient does not necessarily result in an increase in either the stress on the hot spot or blister deformation; local maximum friction stress and Von Mises stress exist for some friction coefficients over the wide range examined here. In addition, the stiffness of contact material on blistering is also investigated, and no significant effects on deformation and Von Mises stress are found, again at the range used. The model and method provided here may be useful for evaluating loading environments and contact materials in reducing blistering incidents. CONCLUSION: The coupling finite-element model can predict the effects of friction coefficient and contacting materials' stiffness on blister deformation and hot spot stress

Bacillus subtilis MreB Orthologs Self-Organize into Filamentous Structures underneath the Cell Membrane in a Heterologous Cell System

Actin-like bacterial cytoskeletal element MreB has been shown to be essential for the maintenance of rod cell shape in many bacteria. MreB forms rapidly remodelling helical filaments underneath the cell membrane in Bacillus subtilis and in other bacterial cells, and co-localizes with its two paralogs, Mbl and MreBH. We show that MreB localizes as dynamic bundles of filaments underneath the cell membrane in Drosophila S2 Schneider cells, which become highly stable when the ATPase motif in MreB is modified. In agreement with ATP-dependent filament formation, the depletion of ATP in the cells lead to rapid dissociation of MreB filaments. Extended induction of MreB resulted in the formation of membrane protrusions, showing that like actin, MreB can exert force against the cell membrane. Mbl also formed membrane associated filaments, while MreBH formed filaments within the cytosol. When co-expressed, MreB, Mbl and MreBH built up mixed filaments underneath the cell membrane. Membrane protein RodZ localized to endosomes in S2 cells, but localized to the cell membrane when co-expressed with Mbl, showing that bacterial MreB/Mbl structures can recruit a protein to the cell membrane. Thus, MreB paralogs form a self-organizing and dynamic filamentous scaffold underneath the membrane that is able to recruit other proteins to the cell surface

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is the most frequent inherited neuromuscular disorder. The juvenile form has been associated with cognitive and psychiatric dysfunction, but the phenotype remains unclear. We reviewed the literature to examine the psychiatric phenotype of juvenile DM1 and performed an admixture analysis of the IQ distribution of our own patients, as we hypothesised a bimodal distribution. Two-thirds of the patients had at least one DSM-IV diagnosis, mainly attention deficit/ hyperactivity disorder and anxiety disorder. Two-thirds had learning disabilities comorbid with mental retardation on one hand, but also attention deficit, low cognitive speed and visual spatial impairment on the other. IQ showed a bi-modal distribution and was associated with parental transmission. The psychiatric phenotype in juvenile DM1 is complex. We distinguished two different phenotypic subtypes: one group characterised by mental retardation, severe developmental delay and maternal transmission; and another group characterised by borderline full scale IQ, subnormal development and paternal transmission

Elucidating the mechanism of ferrocytochrome c heme disruption by peroxidized cardiolipin

The interaction of peroxidized cardiolipin with ferrocytochrome c induces two kinetically and chemically distinct processes. The first is a rapid oxidation of ferrocytochrome c, followed by a slower, irreversible disruption of heme c. The oxidation of ferrocytochrome c by peroxidized cardiolipin is explained by a Fenton-type reaction. Heme scission is a consequence of the radical-mediated reactions initiated by the interaction of ferric heme iron with peroxidized cardiolipin. Simultaneously with the heme c disruption, generation of hydroxyl radical is detected by EPR spectroscopy using the spin trapping technique. The resulting apocytochrome c sediments as a heterogeneous mixture of high aggregates, as judged by sedimentation analysis. Both the oxidative process and the destructive process were suppressed by nonionic detergents and/or high ionic strength. The mechanism for generating radicals and heme rupture is presented

Wing pathology of white-nose syndrome in bats suggests life-threatening disruption of physiology

White-nose syndrome (WNS) is causing unprecedented declines in several species of North American bats. The characteristic lesions of WNS are caused by the fungus Geomyces destructans, which erodes and replaces the living skin of bats while they hibernate. It is unknown how this infection kills the bats. We review here the unique physiological importance of wings to hibernating bats in relation to the damage caused by G. destructans and propose that mortality is caused by catastrophic disruption of wing-dependent physiological functions. Mechanisms of disease associated with G. destructans seem specific to hibernating bats and are most analogous to disease caused by chytrid fungus in amphibians

Inhibition of Nipah Virus Infection In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses

Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse