bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondria-associated ER membranes (MAMs) and lysosomal storage diseases
Authors: Annunziata Ida , Sano Renata , d’Azzo Alessandra 
Published: February 2018

AbstractLysosomal storage diseases (LSDs) comprise a large group of disorders of catabolism, mostly due to deficiency of a single glycan-cleaving hydrolase. The consequent endo-lysosomal accumulation of undigested or partially digested substrates in cells of virtually all organs, including the nervous system, is diagnostic of these diseases and underlies pathogenesis. A subgroup of LSDs, the glycosphingolipidoses, are caused by deficiency of glycosidases that process/degrade sphingolipids and glycosphingolipids (GSLs). GSLs are among the lipid constituents of mammalian membranes, where they orderly distribute and, together with a plethora of membrane proteins, contribute to the formation of discrete membrane microdomains or lipid rafts. The composition of intracellular membranes enclosing organelles reflects that at the plasma membrane (PM). Organelles have the tendencies to tether to one another and to the PM at specific membrane contact sites that, owing to their lipid and protein content, resemble PM lipid rafts. The focus of this review is on the MAMs, mitochondria associated ER membranes, sites of juxtaposition between ER and mitochondria that function as biological hubs for the exchange of molecules and ions, and control the functional status of the reciprocal organelles. We will focus on the lipid components of the MAMs, and highlight how failure to digest or process the sialylated GSL, GM1 ganglioside, in lysosomes alters the lipid conformation and functional properties of the MAMs and leads to neuronal cell death and neurodegeneration.
Mitochondria-associated membranes (MAMs) and inflammation
Authors: Missiroli Sonia , Patergnani Simone , Caroccia Natascia , Pedriali Gaia , Perrone Mariasole , Previati Maurizio , Wieckowski Mariusz R. , Giorgi Carlotta 
Published: February 2018

AbstractThe endoplasmic reticulum (ER) and mitochondria are tightly associated with very dynamic platforms termed mitochondria-associated membranes (MAMs). MAMs provide an excellent scaffold for crosstalk between the ER and mitochondria and play a pivotal role in different signaling pathways that allow rapid exchange of biological molecules to maintain cellular health. However, dysfunctions in the ER–mitochondria architecture are associated with pathological conditions and human diseases. Inflammation has emerged as one of the various pathways that MAMs control. Inflammasome components and other inflammatory factors promote the release of pro-inflammatory cytokines that sustain pathological conditions. In this review, we summarize the critical role of MAMs in initiating inflammation in the cellular defense against pathogenic infections and the association of MAMs with inflammation-mediated diseases.
Redox crosstalk at endoplasmic reticulum (ER) membrane contact sites (MCS) uses toxic waste to deliver messages
Authors: Yoboue Edgar Djaha , Sitia Roberto , Simmen Thomas 
Published: February 2018

AbstractMany cellular redox reactions housed within mitochondria, peroxisomes and the endoplasmic reticulum (ER) generate hydrogen peroxide (H2O2) and other reactive oxygen species (ROS). The contribution of each organelle to the total cellular ROS production is considerable, but varies between cell types and also over time. Redox-regulatory enzymes are thought to assemble at a “redox triangle” formed by mitochondria, peroxisomes and the ER, assembling “redoxosomes” that sense ROS accumulations and redox imbalances. The redoxosome enzymes use ROS, potentially toxic by-products made by some redoxosome members themselves, to transmit inter-compartmental signals via chemical modifications of downstream proteins and lipids. Interestingly, important components of the redoxosome are ER chaperones and oxidoreductases, identifying ER oxidative protein folding as a key ROS producer and controller of the tri-organellar membrane contact sites (MCS) formed at the redox triangle. At these MCS, ROS accumulations could directly facilitate inter-organellar signal transmission, using ROS transporters. In addition, ROS influence the flux of Ca2+ ions, since many Ca2+ handling proteins, including inositol 1,4,5 trisphosphate receptors (IP3Rs), SERCA pumps or regulators of the mitochondrial Ca2+ uniporter (MCU) are redox-sensitive. Fine-tuning of these redox and ion signaling pathways might be difficult in older organisms, suggesting a dysfunctional redox triangle may accompany the aging process.
Direct observation of orbital hybridisation in a cuprate superconductor
Authors: Matt C. E. , Sutter D. , Cook A. M. , Sassa Y. , Månsson M. , Tjernberg O. , Das L. , Horio M. , Destraz D. , Fatuzzo C. G. , Hauser K. , Shi M. , Kobayashi M. , Strocov V. N. , Schmitt T. , Dudin P. , Hoesch M. , Pyon S. , Takayama T. , Takagi H. , Lipscombe O. J. , Hayden S. M. , Kurosawa T. , Momono N. , Oda M. , Neupert T. , Chang J. 
Published: February 2018

AbstractThe minimal ingredients to explain the essential physics of layered copper-oxide (cuprates) materials remains heavily debated. Effective low-energy single-band models of the copper–oxygen orbitals are widely used because there exists no strong experimental evidence supporting multi-band structures. Here, we report angle-resolved photoelectron spectroscopy experiments on La-based cuprates that provide direct observation of a two-band structure. This electronic structure, qualitatively consistent with density functional theory, is parametrised by a two-orbital ($$d_{x^2 - y^2}$$

d

x

2

-

y

2

and $$d_{z^2}$$

d

z

2

) tight-binding model. We quantify the orbital hybridisation which provides an explanation for the Fermi surface topology and the proximity of the van-Hove singularity to the Fermi level. Our analysis leads to a unification of electronic hopping parameters for single-layer cuprates and we conclude that hybridisation, restraining d-wave pairing, is an important optimisation element for superconductivity.
Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer
Authors: Denby Charles M. , Li Rachel A. , Vu Van T. , Costello Zak , Lin Weiyin , Chan Leanne Jade G. , Williams Joseph , Donaldson Bryan , Bamforth Charles W. , Petzold Christopher J. , Scheller Henrik V. , Martin Hector Garcia , Keasling Jay D. 
Published: February 2018

AbstractFlowers of the hop plant provide both bitterness and “hoppy” flavor to beer. Hops are, however, both a water and energy intensive crop and vary considerably in essential oil content, making it challenging to achieve a consistent hoppy taste in beer. Here, we report that brewer’s yeast can be engineered to biosynthesize aromatic monoterpene molecules that impart hoppy flavor to beer by incorporating recombinant DNA derived from yeast, mint, and basil. Whereas metabolic engineering of biosynthetic pathways is commonly enlisted to maximize product titers, tuning expression of pathway enzymes to affect target production levels of multiple commercially important metabolites without major collateral metabolic changes represents a unique challenge. By applying state-of-the-art engineering techniques and a framework to guide iterative improvement, strains are generated with target performance characteristics. Beers produced using these strains are perceived as hoppier than traditionally hopped beers by a sensory panel in a double-blind tasting.
Characterization of gene regulation and protein interaction networks for Matrin 3 encoding mutations linked to amyotrophic lateral sclerosis and myopathy
Authors: Iradi M. Carolina Gallego , Triplett Judy C. , Thomas James D. , Davila Rachel , Crown Anthony M. , Brown Hilda , Lewis Jada , Swanson Maurice S. , Xu Guilian , Rodriguez-Lebron Edgardo , Borchelt David R. 
Published: February 2018

AbstractTo understand how mutations in Matrin 3 (MATR3) cause amyotrophic lateral sclerosis (ALS) and distal myopathy, we used transcriptome and interactome analysis, coupled with microscopy. Over-expression of wild-type (WT) or F115C mutant MATR3 had little impact on gene expression in neuroglia cells. Only 23 genes, expressed at levels of >100 transcripts showed ≥1.6-fold changes in expression by transfection with WT or mutant MATR3:YFP vectors. We identified ~123 proteins that bound MATR3, with proteins associated with stress granules and RNA processing/splicing being prominent. The interactome of myopathic S85C and ALS-variant F115C MATR3 were virtually identical to WT protein. Deletion of RNA recognition motif (RRM1) or Zn finger motifs (ZnF1 or ZnF2) diminished the binding of a subset of MATR3 interacting proteins. Remarkably, deletion of the RRM2 motif caused enhanced binding of >100 hundred proteins. In live cells, MATR3 lacking RRM2 (ΔRRM2) formed intranuclear spherical structures that fused over time into large structures. Our findings in the cell models used here suggest that MATR3 with disease-causing mutations is not dramatically different from WT protein in modulating gene regulation or in binding to normal interacting partners. The intra-nuclear localization and interaction network of MATR3 is strongly modulated by its RRM2 domain.
Direct Detection of Unamplified Pathogen RNA in Blood Lysate using an Integrated Lab-in-a-Stick Device and Ultrabright SERS Nanorattles
Authors: Ngo Hoan T. , Freedman Elizabeth , Odion Ren Abelard , Strobbia Pietro , De Silva Indrasekara Agampodi Swarnapali , Vohra Priya , Taylor Steve M. , Vo-Dinh Tuan 
Published: February 2018

AbstractDirect detection of genetic biomarkers in body fluid lysate without target amplification will revolutionize nucleic acid-based diagnostics. However, the low concentration of target sequences makes this goal challenging. We report a method for direct detection of pathogen RNA in blood lysate using a bioassay using surface-enhanced Raman spectroscopy (SERS)-based detection integrated in a “lab-in-a-stick” portable device. Two levels of signal enhancement were employed to achieve the sensitivity required for direct detection. Each target sequence was tagged with an ultrabright SERS-encoded nanorattle with ultrahigh SERS signals, and these tagged target sequences were concentrated into a focused spot for detection using hybridization sandwiches with magnetic microbeads. Furthermore, the washing process was automated by integration into a “lab-in-a-stick” portable device. We could directly detect synthetic target with a limit of detection of 200 fM. More importantly, we detected plasmodium falciparum malaria parasite RNA directly in infected red blood cells lysate. To our knowledge, this is the first report of SERS-based direct detection of pathogen nucleic acid in blood lysate without nucleic acid extraction or target amplification. The results show the potential of our integrated bioassay for field use and point-of-care diagnostics.
Increased Glutamine Consumption in Cisplatin-Resistant Cells Has a Negative Impact on Cell Growth
Authors: Duan Guihua , Shi Mengyue , Xie Lijuan , Xu Mingcui , Wang Yun , Yan Hongli , Zhuge Yuzheng , Zou Xiaoping 
Published: February 2018

AbstractThe emergence of drug-resistant subclones remains the primary reason for tumor treatment failure. Some theories suggest that drug-resistant cell growth can be suppressed by drug-sensitive cells because resistant cells are less fit than sensitive cells in the absence of drug. We investigated fitness differences and their underlying mechanisms in cisplatin (ddp)-resistant cells and parental cells. We found that glutamine (Gln) consumption was substantially higher in ddp-resistant cells than that in sensitive cells, indicating that significantly fewer ddp-resistant cells than sensitive cells could be generated under the same Gln conditions. Interestingly, the antioxidant capacity of ddp-resistant cells was also significantly enhanced and was directly related to the presence of Gln. Then, we found that enhanced antioxidant capacity was sustained by accelerated Gln catabolism in resistant cells through oncogenic KRAS. Further analysis indicated that rapid Gln catabolism directly mediated ddp resistance through enhanced antioxidant capacity, but the maximum number of resistant cells that could be produced with the same amount of Gln was significantly reduced due to increased Gln catabolism. Collectively, our study revealed that rapid Gln catabolism provided ddp-resistant cells with the ability to tolerate cytotoxic treatment but also hindered the growth of ddp-resistant cells due to excessive Gln consumption.
The pharmacokinetic advantage of 5-methyltetrahydrofolate for minimization of the risk for birth defects
Authors: Bailey Steven W. , Ayling June E. 
Published: February 2018

AbstractDespite efforts to increase folic acid (FA) intake, even within countries mandating FA fortification, there remain pregnant women with folate levels inadequate to minimize congenital disorders (e.g., of the neural tube, heart, and lip/palate). The pharmacokinetics of FA and [6S]-5-methyltetrahydrofolate (5-MTHF) were examined to find a reliable and minimal dose for rapidly rescuing folate status prior to critical periods of embryonic development. Serum total folate increased much more rapidly over the first four days in insufficient women given 7.5 mg doses of 5-MTHF than the same regimen of FA (P for trend <0.0001). Nearly all women given 7.5 mg 5-MTHF (every 12 hours, five doses total) almost immediately reached 50 nM serum total folate. Moreover, this level could be maintained by subsequent administration of 0.4 mg/d of folic acid. Thus, 5-MTHF enables repletion of folate stores more quickly and uniformly than FA and without exposure to unmetabolized FA.
Tunable Dielectric Properties of Poly(vinylidenefluoride-co-hexafluoropropylene) Films with Embedded Fluorinated Barium Strontium Titanate Nanoparticles
Authors: Han Wooje , Kim Taehee , Yoo Byungwook , Park Hyung-Ho 
Published: February 2018

AbstractFluoropolymer nanocomposites of poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP) were prepared using fluorinated barium strontium titanate (Ba1−xSrxTiO3, BSTO) nanoparticles (NPs) by low-temperature synthesis using a modified liquid–solid solution process. The exact stoichiometry of as-synthesized BSTO NPs was confirmed by X-ray diffraction analysis along with lattice parameter calculations. The synthesized BSTO NPs were fluorinated using 2,2,2-trifluoroacetic acid as a fluorous ligand. The BSTO NPs showed high solubility in the fluorous system (polymer and solvent) on account of their modified surface. The root-mean-square roughness of the fluorinated BSTO/PVdF-HFP nanocomposite was 76 times lower than that of the nonfluorinated BSTO/PVdF-HFP nanocomposite. The dielectric constant of the fluorinated BSTO/PVdF-HFP nanocomposite exhibited Curie temperature behavior. The dielectric constant of the nanocomposite predicted using the modified Kerner model at room temperature agreed well with the experimental values.
Comparison of non-insulin antidiabetic agents as an add-on drug to insulin therapy in type 2 diabetes: a network meta-analysis
Authors: Yoon Jeong-Hwa , Min Se Hee , Ahn Chang Ho , Cho Young Min , Hahn Seokyung 
Published: February 2018

AbstractWe aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and ClinicalTrials.gov through April 2016. Bayesian network meta-analyses were performed with covariate adjustment. The primary outcome was the change in glycated hemoglobin A1c (HbA1c) from baseline. Fifty randomized controlled trials covering 15,494 patients were included. GLP-1RA showed the greatest HbA1c-lowering effect compared to the control (−0.84%; 95% credible interval, −1.00% to −0.69%), followed by TZD (−0.73%; −0.93 to −0.52%), SGLT2i (−0.66%; −0.84% to −0.48%), and DPP4i (−0.54%; −0.68% to −0.39%). SGLT2i showed the greatest fasting plasma glucose reduction. GLP-1RA and SGLT2i showed greater body weight reduction, whereas TZD increased body weight. TZD was ranked the highest in terms of insulin dose reduction. The risk of hypoglycemia was increased with TZD or GLP-1RA. The study provides the best available evidence on the comparative efficacy and safety of non-insulin anti-diabetic agents on top of pre-existing insulin therapy for inadequately controlled T2DM patients.
Isolation of levoglucosan-utilizing thermophilic bacteria
Authors: Iwazaki Shintaro , Hirai Hirokazu , Hamaguchi Norihisa , Yoshida Nobuyuki 
Published: February 2018

AbstractWe previously developed an industrial production process for novel water-soluble indigestible polysaccharides (resistant glucan mixture, RGM). During the process, an anhydrosugar—levoglucosan —is formed as a by-product and needs to be removed to manufacture a complete non-calorie product. Here, we attempted to isolate thermophilic bacteria that utilize levoglucosan as a sole carbon source, to establish a removing process for levoglucosan at higher temperature. Approximately 800 natural samples were used to isolate levoglucosan-utilizing microorganisms. Interestingly, levoglucosan-utilizing microorganisms—most of which were filamentous fungi or yeasts—could be isolated from almost all samples at 25°C. We isolated three thermophilic bacteria that grew well on levoglucosan medium at 60°C. Two of them and the other were identified as Bacillus smithii and Parageobacillus thermoglucosidasius, respectively, by 16S rDNA sequence analysis. Using B. smithii S-2701M, which showed best growth on levoglucosan, glucose and levoglucosan in 5% (wt/vol) RGM were completely diminished at 50°C for 144 h. These bacteria are known to have a biotechnological potential, given that they can ferment a range of carbon sources. This is the first report in the utilization of levoglucosan by these thermophiles, suggesting that our results expand their biotechnological potential for the unutilized carbon resources.
Understanding type Ia supernovae through their U-band spectra
Authors: Nordin J. , Aldering G. , Antilogus P. , Aragon C. , Bailey S. , Baltay C. , Barbary K. , Bongard S. , Boone K. , Brinnel V. , Buton C. , Childress M. , Chotard N. , Copin Y. , Dixon S. , Fagrelius P. , Feindt U. , Fouchez D. , Gangler E. , Hayden B. , Hillebrandt W. , Kim A. , Kowalski M. , Kuesters D. , Leget P.-F. , Lombardo S. , Lin Q. , Pain R. , Pecontal E. , Pereira R. , Perlmutter S. , Rabinowitz D. , Rigault M. , Runge K. , Rubin D. , Saunders C. , Smadja G. , Sofiatti C. , Suzuki N. , Taubenberger S. , Tao C. , Thomas R. C. ,   The Nearby Supernova Factory
Published: February 2018

Context. Observations of type Ia supernovae (SNe Ia) can be used to derive accurate cosmological distances through empirical standardization techniques. Despite this success neither the progenitors of SNe Ia nor the explosion process are fully understood. The U-band region has been less well observed for nearby SNe, due to technical challenges, but is the most readily accessible band for high-redshift SNe.
Aims. Using spectrophotometry from the Nearby Supernova Factory, we study the origin and extent of U-band spectroscopic variations in SNe Ia and explore consequences for their standardization and the potential for providing new insights into the explosion process.
Methods. We divide the U-band spectrum into four wavelength regions λ(uNi), λ(uTi), λ(uSi) and λ(uCa). Two of these span the Ca H&K λλ 3934, 3969 complex. We employ spectral synthesis using SYNAPPS to associate the two bluer regions with Ni/Co and Ti.
Results. The flux of the uTi feature is an extremely sensitive temperature/luminosity indicator, standardizing the SN peak luminosity to 0.116 ± 0.011 mag root mean square (RMS). A traditional SALT2.4 fit on the same sample yields a 0.135 mag RMS. Standardization using uTi also reduces the difference in corrected magnitude between SNe originating from different host galaxy environments. Early U-band spectra can be used to probe the Ni+Co distribution in the ejecta, thus offering a rare window into the source of light curve power. The uCa flux further improves standardization, yielding a 0.086 ± 0.010 mag RMS without the need to include an additional intrinsic dispersion to reach χ2∕dof ~ 1. This reduction in RMS is partially driven by an improved standardization of Shallow Silicon and 91T-like SNe.
Detailed chemical compositions of the wide binary HD 80606/80607: revised stellar properties and constraints on planet formation
Authors: Liu F. , Yong D. , Asplund M. , Feltzing S. , Mustill A. J. , Meléndez J. , Ramírez I. , Lin J. 
Published: February 2018

Differences in the elemental abundances of planet-hosting stars in binary systems can give important clues and constraints about planet formation and evolution. In this study we performed a high-precision, differential elemental abundance analysis of a wide binary system, HD 80606/80607, based on high-resolution spectra with high signal-to-noise ratio obtained with Keck/HIRES. HD 80606 is known to host a giant planet with the mass of four Jupiters, but no planet has been detected around HD 80607 so far. We determined stellar parameters as well as abundances for 23 elements for these two stars with extremely high precision. Our main results are that (i) we confirmed that the two components share very similar chemical compositions, but HD 80606 is marginally more metal-rich than HD 80607, with an average difference of +0.013 ± 0.002 dex (σ = 0.009 dex); and (ii) there is no obvious trend between abundance differences and condensation temperature. Assuming that this binary formed from material with the same chemical composition, it is difficult to understand how giant planet formation could produce the present-day photospheric abundances of the elements we measure. We cannot exclude the possibility that HD 80606 might have accreted about 2.5 to 5 MEarth material onto its surface, possibly from a planet destabilised by the known highly eccentric giant.
Mikrobielle Keratitis – Teil 2: mykotische und Akanthamöbenkeratitiden
Authors: Schmack Ingo , Müller Michael , Kohnen Thomas 
Published: February 2018

ZusammenfassungPilze und Akanthamöben stellen neben Bakterien wesentliche Ursachen für die Entstehung infektiöser Hornhauterkrankungen (mikrobielle Keratitis) und möglicher nachfolgender Erblindung des betroffenen Auges dar. Aufgrund weitgehend unspezifischer Gewebereaktionen, vor allem in den Frühstadien der Entzündung, wird die Diagnose infektiöser Hornhauterkrankungen oftmals erst verspätet gestellt. Insbesondere bei Akanthamöben sind Verwechslungen mit viralen (herpetischen) Keratitiden leicht möglich. Der behandelnde Augenarzt ist daher vor hohe diagnostische Herausforderungen gestellt.