bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective pressures on human cancer genes along the evolution of mammals
Authors: Vicens Alberto , Posada David 
Published: August 2018

AbstractCancer is a disease of the genome caused by somatic mutation and subsequent clonal selection. Several genes associated to cancer in humans, hereafter cancer genes, also show evidence of (germline) positive selection among species. Taking advantage of a large collection of mammalian genomes, we systematically looked for statistically significant signatures of positive selection using dN/dS models in a list of 430 cancer genes. Among these, we identified 63 genes under putative positive selection in mammals, which are significantly enriched in processes like crosslinking DNA repair. We also found evidence of a higher incidence of positive selection in cancer genes bearing germline mutations, like BRCA2, where positively selected residues are physically linked with known pathogenic variants, suggesting a potential association between germline positive selection and risk of hereditary cancer. Overall, our results suggest that genes associated with hereditary cancer have less selective constraints than genes related to sporadic cancer. Also, that the adaptive evolution of human cancer genes in mammals has been most likely driven by adaptive changes in important traits not directly related to cancer.
Evidence for phospholipid export from the gram-negative inner membrane: time to rethink the Mla pathway?
Authors: Hughes Gareth W. , Hall Stephen C. L. , Laxton Claire S. , Sridhar Pooja , Mahadi Amirul H. , Hatton Caitlin , Piggot Thomas J. , Jamshad Mohammed , Spana Vaclav , Ian Cadby T. , Harding Christopher , Isom Georgia L. , Bryant Jack , Parr Rebecca J. , Yakub Yasin , Jeeves Mark , Huber Damon , Ian Henderson R. , Clifton Luke A. , Andrew Lovering L. , Knowles Timothy J. 
Published: August 2018

AbstractThe Mla pathway is believed to be involved in maintaining the asymmetrical Gram-negative outer membrane via retrograde phospholipid transport. The pathway is composed of 3 components: the outer membrane MlaA-OmpC/F complex, a soluble periplasmic protein, MlaC, and the inner membrane ATPase, MlaFEDB complex. Here we solve the crystal structure of MlaC in its phospholipid free closed apo conformation, revealing a novel pivoting β-sheet mechanism which functions to open and close the phospholipid-binding pocket. Using the apo form of MlaC we provide evidence that the Mla pathway functions in an anterograde rather than a retrograde direction by showing the inner membrane MlaFEDB machinery exports phospholipids and transfers them to MlaC in the periplasm. We confirm that the lipid export process occurs through the MlaD component of the MlaFEDB complex. This lipid export process is shown to be independent of ATP. Our data provides, for the first time, evidence of an apparatus for lipid export to the outer membrane.
Loss of Frrs1l disrupts synaptic AMPA receptor function, and results in neurodevelopmental, motor, cognitive and electrographical abnormalities
Authors: Stewart Michelle , Lau Petrina , Banks Gareth , Bains Rasneer Sonia , Castroflorio Enrico , Oliver Peter L. , Dixon Christine L. , Kruer Michael C. , Kullmann Dimitri M. , Acevedo-Arozena Abraham , Wells Sara E. , Corrochano Silvia , Nolan Patrick M. 
Published: August 2018

Summary statementIn this study, we show that the loss of the epilepsy-related gene Frrs1l in mice causes a dramatic reduction in AMPA receptor levels at the synapse. This change elicits severe motor and coordination disabilities, hyperactivity, cognitive defects, behavioural seizures and abnormal electroencephalographic (EEG) patterns.AbstractLoss of function mutations in the human AMPA receptor-associated protein, ferric chelate reductase 1-like (FRRS1L), are associated with a devastating neurological condition incorporating choreoathetosis, cognitive deficits and epileptic encephalopathies. Furthermore, evidence from overexpression and ex vivo studies have implicated FRRS1L in AMPA receptor biogenesis and assembly, suggesting that changes in glutamatergic signalling might underlie the disorder. Here, we investigated the neurological and neurobehavioural correlates of the disorder using a mouse Frrs1l null mutant. The study revealed several neurological defects that mirrored those seen in human patients. We established that mice lacking Frrs1l suffered from a broad spectrum of early-onset motor deficits with no progressive, age-related deterioration. Moreover, Frrs1l-/- mice were hyperactive irrespective of test environment, exhibited working memory deficits and displayed significant sleep fragmentation. Longitudinal electroencephalographic recordings also revealed abnormal EEG in Frrs1l-/- mice. Parallel investigations into disease aetiology identified a specific deficiency in AMPA receptor levels in the brain of Frrs1l-/- mice, while the general levels of several other synaptic components remained unchanged with no obvious alterations in the number of synapses. Furthermore, we established that Frrsl1 deletion results in glycosylation deficits in GLUA2 and GLUA4 AMPA receptor proteins, leading to cytoplasmic retention and a reduction of those specific AMPA receptor levels in the postsynaptic membrane. Overall, this study determines, for the first time in vivo, how loss of FRRS1L function can affect glutamatergic signalling and provides mechanistic insight into the development and progression of a human hyperkinetic disorder.
Variations in neonatal age segments mortality in Kenya’s malaria epidemiological zones by community uptake of iron-supplements and anti-malaria drugs during pregnancy: Analysis based on 2014 Kenya demographic and health survey
Authors: K’Oyugi Boniface O. 
Published: August 2018

AbstractIntroductionAlthough past studies have established that iron-supplements and anti-malaria drugs taken by mothers during pregnancy reduce the risk of neonatal deaths in high prone malaria areas, little is known about their impact on mortality risks in neonatal age segments in Kenya. The study objective was to analyse variations in neonatal age segments mortality rates by uptake of these two antenatal care services and determine their effects on the age segments mortality in Kenya’s malaria zones.Data and methodsThis study used data from the 2014 Kenya Demographic and Health Survey (KDHS). Survival status information for 20,794 children born less than 60 months prior to interview date and reported mothers’ uptake of iron-supplements and anti-malaria drugs during last pregnancy was analysed. Life table method was used to estimate mortality rates and Poisson multivariate regression models were fitted to determine relative risks of death for the study variables.ResultsThe results show that variations in neonatal age segments mortality in Kenya’s malaria zones are statistically insignificant. The contributions of early neonatal (0 to 7 days) to neonatal mortality rate are 80% and 100% in low and high malaria zones, respectively. Combined high community uptake of iron-supplements and anti-malaria drugs during pregnancy reduce significantly mortality risk in late neonatal (8 days to less than one month) in all malaria zones when effects of other risk factors are controlled for.ConclusionsThe findings suggest that future decline in neonatal mortality in all Kenya’s malaria zones depend mainly on reduction of early neonatal mortality. High community uptake of iron-supplements and anti-malaria drugs during pregnancy has significant reduction effect on late neonatal mortality in all malaria zones. This study recommends improvement of future KDHS data quality, especially on care for small and sick neonates.
The single mitochondrion of the kinetoplastid parasite Crithidia fasciculata is a dynamic network
Authors: DiMaio John , Ruthel Gordon , Cannon Joshua J. , Malfara Madeline F. , Povelones Megan L. 
Published: August 2018

AbstractMitochondria are central organelles in cellular metabolism. Their structure is highly dynamic, allowing them to adapt to different energy requirements, to be partitioned during cell division, and to maintain functionality. Mitochondrial dynamics, including membrane fusion and fission reactions, are well studied in yeast and mammals but it is not known if these processes are conserved throughout eukaryotic evolution. Kinetoplastid parasites are some of the earliest-diverging eukaryotes to retain a mitochondrion. Each cell has only a single mitochondrial organelle, making them an interesting model for the role of dynamics in controlling mitochondrial architecture. We have investigated the mitochondrial division cycle in the kinetoplastid Crithidia fasciculata. The majority of mitochondrial biogenesis occurs during the G1 phase of the cell cycle, and the mitochondrion is divided symmetrically in a process coincident with cytokinesis. Mitochondrial division was not inhibited by the putative dynamin inhibitor mdivi-1, although mitochondrial membrane potential and cell size were affected. Live cell imaging revealed that the mitochondrion is highly dynamic, with frequent changes in the topology of the branched network. These remodeling reactions include tubule fission, fusion, and sliding, as well as new tubule formation. We hypothesize that the function of this dynamic remodeling is to homogenize mitochondrial contents and to facilitate rapid transport of mitochondria-encoded gene products from the area containing the mitochondrial nucleoid to other parts of the organelle.
Measuring researcher independence using bibliometric data: A proposal for a new performance indicator
Authors: van den Besselaar Peter , Sandström Ulf 
Published: August 2018

AbstractBibliometric indicators are increasingly used at the individual level – as is exemplified by the popularity of the H-index and many other publication and citation based indicators used in evaluation. The issue isn’t whether these indicators can be considered useful, as they do provide a description of a researcher’s oeuvre. However, at the same time, they are not enough to assess the quality of a researcher and his/her oeuvre: Quality has more dimensions than productivity and impact alone. In this paper, we argue that independence is an equally important characteristic that however lacks validated indicators for measuring it at the individual level. We propose two indicators to measure different dimensions of independence: one assessing whether a researcher has developed an own collaboration network, and another assessing the level of thematic independence. We illustrate how these indicators distinguish between researchers that are equally productive and have similar impact. The independence indicator is a step forward in evaluating individual scholarly quality: in cases where citations and publications do not distinguish, the indicators for independence may do.
Microorganism adhesion experimental study using silicon dioxide
Authors: Lozins Roberts , Ozoliņš Dzintars 
Published: August 2018

AbstractIn this study, yeast, Gram positive and Gram negative bacteria were attached to silicon dioxide microparticles or silica in order to measure their absorbance, also known as physical absorption of light, changes using spectrophotometry. The goal of the study was to determine if spectrophotometry is an effective way to distinguish microorganisms and if microorganisms have an affinity for silicon dioxide since it is a suitable material for the production of prostheses. The experiment was done by examining the light absorption properties of yeast, Gram positive and Gram negative bacteria in a spectrophotometer with and without silicon dioxide microparticles. During the experiment there have been several promising results. First of all, the spectrophotometers presented graphs of yeast were noticeably different from the graphs of both Gram positive and Gram negative bacteria. Secondly, the absorption of light in both Gram positive and Gram negative bacteria at near infrared (700-1500 nm) wavelengths increased when silicon dioxide microparticles were added to the suspension, unlike yeast. When silicon dioxide microparticles were added to yeast, the absorption of light decreased during the whole wavelength interval of the spectrophotometer measurement. The results indicate that spectrophotometry could be used to distinguish yeast from bacteria and possibly bacteria from each other. The results also suggest that silicon dioxide should not be used in the production of prostheses since it could be a favourable material for the development of biofilms.
Landscape structure influences avian species diversity in tropical urban mosaics
Authors: Muderere Trymore , Murwira Amon , Tagwireyi Paradzayi , Chiweshe Ngoni 
Published: August 2018

AbstractIn this study, we tested whether urban landscape structure influences avian species diversity using data for Harare, Zimbabwe. Initially, we quantified landscape structure using fragmentation indices derived from a 5m resolution SPOT 5 imagery. We collected bird species data through field-based observations of birds at 35 locations occurring in five land use/land cover types. We quantified avian species diversity using Barger-Parker, Menhinick and Simpson’s Indices. Regression analysis was used to determine the nature and strength of the relationships between avian species diversity and fragmentation indices. Results indicated that woodland specialist avian species are negatively associated with landscape fragmentation, while grassland specialist and generalist avian species positively responded to patch edge density, habitat patch size and shape complexity. Overall, our results suggest that changes in landscape structure due to expansion of built-up areas in tropical urban areas may influence avian species diversity.
A Pentatricopeptide Repeat Protein in the Plasmodium apicoplast is essential and shows sequence-specific RNA binding
Authors: Hicks Joanna L. , Lassadi Imen , Carpenter Emma , Eno Madeleine , Vardakis Alexandros , Waller Ross F. , Howe Christopher J. , Nisbet R. Ellen R. 
Published: August 2018

ABSTRACTThe malaria parasite Plasmodium and other apicomplexans such as Toxoplasma evolved from photosynthetic organisms and contain an essential, remnant plastid termed the apicoplast. Transcription of the apicoplast genome is polycistronic with extensive RNA processing. Little is known about the mechanism of post-transcriptional processing. In plant chloroplasts, post-transcriptional RNA processing is controlled by multiple pentatricopeptide repeat (PPR) proteins. Here, we present the biochemical characterisation of the single apicoplast-targeted PPR protein. Apicoplast PPR1 is essential, and binds specific RNA sequences corresponding with previously characterized RNA processing sites. We identify the specific binding motif of PPR1. In RNAse protection assays, PPR1 shields apicoplast transcripts from ribonuclease degradation. Our results show that apicoplast RNA processing is under the control of a single protein, thus presenting an Achilles’ heel for the development of new anti-malarial drugs.
Very high-density platelets determine reactivity and activity of circulating platelets
Authors: Järemo P. 
Published: August 2018

AbstractBackgroundFor many decades, platelets have been known to display a substantial density heterogeneity. Knowledge about the origins and functions of specific platelet density subpopulations is scarce. This study investigates if very high-density (1.09 kg/L) platelets impact upon the reactivity and activity of all platelets.MethodsSubjects (n=52) were recruited in conjunction with a nurse-guided blood pressure control. Platelet reactivity in citrate anticoagulated whole blood, i.e. surface-bound P-selectin after provocation, was analysed using a flow cytometry technique. ADP (8.5 μmol/L) was employed as an agonist. Subsequently, the entire population was separated according to density into 17 subpopulations, with fraction 1 containing the densest platelets (1.09 kg/L). In each subfraction surface P-selectin expression was determined. Subjects were then divided according to the number of very high-density platelets in 1.09high(n=17) and 1.09low(n=35) demonstrating >8×109/L and ≤8×109/L 1.09 kg/L fraction 1 platelets, respectively.ResultsSurface-attached P-selectin after provocation reveals that 1.09highassociates with increased whole blood reactivity of the entire platelet population. The level of significance wasp≤0.01 (8.5 μmol/L ADP). Furthermore, 1.09highrelates to increased spontaneous activity of density populations, as evidenced by membrane-bound P-selectin. For the fractionsnos. 2, 4-7, 9, 10 the differences were significant, withp-values ranging fromp≤0.05 top≤0.01.ConclusionThe number of very high-density (1.09 kg/L) platelets reflects the reactivity of the entire population. It is also closely related to subfraction P-selectin activity. It is unlikely that platelets gain density when circulating. Therefore, evidence suggests that very dense cells are created for this purpose at thrombopoiesis. It is tenable that such platelets regulate the reactivity of the entire population.
Identification of dysregulation of atrial proteins in rats with chronic obstructive apnea using twodimensional polyacrylamide gel electrophoresis and mass spectrometry
Authors: Lux Jacob C. , Channaveerappa Devika , Aslebagh Roshanak , Heintz Timothy A. , McLerie Meredith , Panama Brian K. , Darie Costel C. 
Published: August 2018

AbstractObstructive sleep apnea (OSA) affects an estimated 20% of adults worldwide with up to 80% of patients remaining undiagnosed. OSA has been associated with electrical and structural abnormalities of the atria, although the molecular mechanisms are not well understood. We have implemented a rat model of OSA involving the surgical implantation of a tracheal obstructive device. Rats were divided into severe and moderate apnea groups, receiving 23 seconds (severe) or 13 seconds (moderate) apneas per minute, 60 apneas per minute for 8 hours a day over 2 weeks. We recently performed a pilot study using onedimensional polyacrylamide gel electrophoresis (1D PAGE) and nanoliquid chromatography-tandem mass spectrometry (NanoLC-MS/MS) to investigate the protein dysregulations in rat atria which was induced with OSA using the rat model we developed. We found, among others, that some aerobic and anaerobic glycolytic enzymes and Krebs cycle enzymes were downregulated, suggesting that apnea may be a result of paucity of oxygen and production of ATP and reducing equivalents. Here, we used twodimensional polyacrylamide gel electrophoresis (2D PAGE) coupled with nanoLC-MS/MS as a complementary approach to investigate the proteins that are dysregulated in the atria from severe and moderate apnea when compared to control. We not only found that the entire glycolytic pathway and Krebs cycle are downregulated, but also found evidence that additional enzymes involved in the beta-oxidation, electron transport chain and Krebs cycle anaplerotic reactions were also downregulated. Other protein dysregulations identified are involved in metabolic, structural, or inflammatory pathways, suggesting that these proteins may play a role in atrial pathology developing via chronic obstructive apnea and hypoxia.
Heterodimerization of UNC-13/RIM regulates synaptic vesicle release probability but not priming
Authors: Liu Haowen , Li Lei , Nedelcu Daniel , Hall Qi , Zhou Lijun , Wang Wei , Yu Yi , Kaplan Joshua M. , Hu Zhitao 
Published: August 2018

AbstractUNC-13 proteins play an essential role in synaptic transmission by recruiting synaptic vesicles (SVs) to become available for release, which is termed SV priming. Here we show that the C2A domain of UNC-13L, like the corresponding domain in mammalian Munc13-1, displays two conserved binding modes: forming C2A/C2A homodimers, or forming a heterodimer with the zinc finger domain of UNC-10/RIM (C2A/RIM). Functional analysis revealed that UNC-13L’s C2A promotes synaptic transmission by regulating a post-priming process. Stimulus-evoked release but not SV priming, was impaired in unc-10 mutants deficient for C2A/RIM heterodimerization, leading to decreased release probability. Disrupting C2A/C2A homodimerization in UNC-13L-rescued animals had no effect on synaptic transmission, but fully restored the evoked release and the release probability of unc-10/RIM mutants deficient for C2A/RIM heterodimerization. Thus, our results support the model that RIM binding C2A releases UNC-13L from an autoinhibitory homodimeric complex to become fusion-competent by functioning as a switch only.
Intracellular mass density increase is accompanying but not sufficient for stiffening and growth arrest of yeast cells
Authors: Abuhattum Shada , Kim Kyoohyun , Franzmann Titus M. , Eßlinger Anne , Midtvedt Daniel , Schlüßler Raimund , Möllmert Stephanie , Kuan Hui-Shun , Alberti Simon , Zaburdaev Vasily , Guck Jochen 
Published: August 2018

AbstractMany organisms, including yeast cells, bacteria, nematodes and tardigrades, endure harsh environmental conditions, such as nutrient scarcity, or lack of water and energy for a remarkably long time. The rescue programs that these organisms launch upon encountering these adverse conditions include reprogramming their metabolism in order to enter a quiescent or dormant state in a controlled fashion. Reprogramming coincides with changes in the macromolecular architecture and changes in the physical and mechanical properties of the cells. However, the cellular mechanisms underlying the physical-mechanical changes remain enigmatic. Here, we induce metabolic arrest of yeast cells by lowering their intracellular pH. We then determine the differences in the intracellular mass density and stiffness of active and metabolically arrested cells using optical diffraction tomography and atomic force microscopy. We show that an increased intracellular mass density is associated with an increase in stiffness when the growth of yeast is arrested. However, increasing the intracellular mass density alone is not sufficient for maintenance of the growth-arrested state in yeast cells. Our data suggest that the cytoplasm of metabolically arrested yeast displays characteristics of solid. Our findings constitute a bridge between the mechanical behavior of the cytoplasm and the physical and chemical mechanisms of metabolically arrested cells with the ultimate aim of understanding dormant organisms.
Adaptor protein Bbc1 regulates localization of Wsp1 and Vrp1 during endocytic actin patch assembly
Authors: MacQuarrie Cameron , Mangione MariaSanta , Carroll Robert , James Michael , Gould Kathleen L. , Sirotkin Vladimir 
Published: August 2018

ABSTRACTArp2/3 complex-nucleated branched actin networks provide the force necessary for endocytosis. The Arp2/3 complex is activated by Nucleation Promoting Factors (NPFs) including theSchizosaccharomyces pombeproteins WASp Wsp1 and myosin-1 Myo1. There are >40 known yeast endocytic proteins with distinct spatial and temporal localizations and functions; however, it is still unclear how these proteins work together to drive endocytosis. We used quantitative live cell imaging to determine the function of the uncharacterizedS. pombeprotein Bbc1. We discovered Myo1 interacts with and recruits Bbc1 to sites of endocytosis. Bbc1 competes with verprolin Vrp1 for Myo1 binding, thus releasing Vrp1 and its binding partner Wsp1 from Myo1. Normally Myo1 remains at the base of the endocytic invagination and Vrp1-Wsp1 internalize with the endocytic vesicle; however, in the absence of Bbc1, a portion of Vrp1-Wsp1 remains with Myo1 at the base of the invagination and endocytic invaginations are twice as long. We propose that Bbc1 disrupts a transient Myo1-Vrp1-Wsp1 interaction and limits Arp2/3 complex-nucleation of actin branches at the plasma membrane.