bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells
Authors: D'Alessandro Angelo , Reisz Julie A. , Culp‐Hill Rachel , Korsten Herbert , van Bruggen Robin , de Korte Dirk 
Published: April 2018

BACKGROUNDOver a century of advancements in the field of additive solutions for red blood cell (RBC) storage has made transfusion therapy a safe and effective practice for millions of recipients worldwide. Still, storage in the blood bank results in the progressive accumulation of metabolic alterations, a phenomenon that is mitigated by storage in novel storage additives, such as alkaline additive solutions. While novel alkaline additive formulations have been proposed, no metabolomics characterization has been performed to date.STUDY DESIGN AND METHODSWe performed UHPLC‐MS metabolomics analyses of red blood cells stored in SAGM (standard additive in Europe), (PAGGSM), or alkaline additives SOLX, E‐SOL 5 and PAG3M for either 1, 21, 35 (end of shelf‐life in the Netherlands), or 56 days.RESULTSAlkaline additives (especially PAG3M) better preserved 2,3‐diphosphoglycerate and adenosine triphosphate (ATP). Deaminated purines such as hypoxanthine were predictive of hemolysis and morphological alterations. Guanosine supplementation in PAGGSM and PAG3M fueled ATP generation by feeding into the nonoxidative pentose phosphate pathway via phosphoribolysis. Decreased urate to hypoxanthine ratios were observed in alkaline additives, suggestive of decreased generation of urate and hydrogen peroxide. Despite the many benefits observed in purine and redox metabolism, alkaline additives did not prevent accumulation of free fatty acids and oxidized byproducts, opening a window for future alkaline formulations including (lipophilic) antioxidants.CONCLUSIONAlkalinization via different strategies (replacement of chloride anions with either high bicarbonate, high citrate/phosphate, or membrane impermeant gluconate) results in different metabolic outcomes, which are superior to current canonical additives in all cases.
Plasma biochemistry RIs and age effect in European Strigiformes
Authors: Agusti Montolio Susana , Cuenca Valera Rafaela , Lavín González Santiago , Cray Carolyn , Molina López Rafael , Ferron Emmanuel Serrano , Francisco Olga Nicolás , Marco Sánchez Ignasi , Casas‐Díaz Encarna 
Published: April 2018

BackgroundBlood biochemistry and hematology are essential in the laboratory diagnosis of disease. In Strigiformes, little information regarding reference values and influence of different preanalytic factors is available, while age is known to have an effect on some biochemistry analytes, especially in early life characterized by a rapid growth rate and increase in body mass.ObjectiveThe objective of this study was to determine baseline data for 29 blood biochemistry variables in 5 species of Iberian Strigiformes assigned to different age classes.MethodsHealthy nocturnal birds living in wildlife health centers of Catalonia, Northeastern Spain were assigned to different age classes (chicks, juveniles, adults where possible and available) and their blood was collected and analyzed for different standard biochemistry variables. Species included Tawny owls, Little owls, Long‐eared owls, Scop owls, and Barn owls.ResultsA total of 276 clinically healthy animals were sampled, including between 179 chicks, 52 juveniles, and 45 adults. The RIs of cholesterol, albumin, and osmolality were the only variables that did not show interspecific variability. Common trends between age class groups were observed in 4 species. Phosphorus and calcium concentrations and ALP activities decreased with increasing age, while concentrations of sodium and γ‐globulins tended to increase in the Strigidae family. Differences were concentrated in chicks and no differences were observed between juveniles and adults in any variable.ConclusionsOur results demonstrate the importance of defining biochemical RIs specific for certain age classes
Diagnosis of pneumocystis pneumonia in a 2‐year‐old King Charles Cavalier Spaniel using the polymerase chain reaction
Authors: Okine Ayeley A. K. , Chapman Seth , Hostutler Roger A. , Livingston Robert 
Published: April 2018

AbstractA 2‐year‐old, female spayed, King Charles Cavalier Spaniel was presented for evaluation of dyspnea, inappetence, and lethargy. Thoracic radiographs revealed a moderate diffuse interstitial lung pattern affecting the perihilar and caudodorsal lung fields, and an echocardiogram revealed severe pulmonary hypertension. A bronchoalveolar lavage (BAL) was performed, and cytology revealed mixed inflammation with cysts and trophozoites consistent with Pneumocystis. Pneumocystis infection was later confirmed with PCR. To the author's knowledge, this report represents the first case of canine pneumocystis pneumonia diagnosed antemortem with PCR from a BAL sample. Pneumocystis represents an important, but uncommon cause of afebrile pneumonia in immunosuppressed dogs.
Water harvesting from fog using building envelopes: part II
Authors: Caldas Luisa , Andaloro Annalisa , Calafiore Giuseppe , Munechika Keiko , Taube Benjamin , Oliveira Manuel , Cabrini Stefano 
Published: April 2018

AbstractFog harvesting stands out as a simple and inexpensive form to produce drinkable water from alternative sources, when compared to other available techniques. This paper presents results from a set of experiments performed on radiative condensers, deemed as a promising system to be integrated in building envelopes, following a literature review on fog condensers presented in a previous work. An analysis of condensation potential obtained using high emissivity substrates and titanium dioxide nanocoatings is presented, as well as the influence of sample position and orientation, and impact of climatic variables. Finally, the role of nanotechnology in overcoming limitations of radiative systems is discussed as a means to increase harvesting efficiency with functionalized, engineered nano‐patterns on collector surface. Based on biomimicry principles, nanocoatings including nanoscale 3D optimal geometries are discussed, and the use of nanoimprint technology (NIL) is proposed to massively produce nano‐patterned panels with biomimetic fog capturing features.
Acontecimiento, efectuación y sentido en la filosofía  de Gilles Deleuze
Authors: Esperón Juan Pablo 
Published: April 2018

<p>Este artículo tiene dos objetivos: por un lado, aclarar qué designan las nociones de acontecimiento, efectuación y sentido en la filosofía de Deleuze; y, por otro, mostrar cómo estas nociones permiten pensar la singularidad sin que resulte explicada a partir de un fundamento trascendente y sus problemas derivados.</p><p> </p>
Importance of Proteasome Gene Expression during Model Dough Fermentation after Preservation of Baker's Yeast Cells by Freezing
Authors: Watanabe Daisuke , Sekiguchi Hiroshi , Sugimoto Yukiko , Nagasawa Atsushi , Kida Naotaka , Takagi Hiroshi 
Published: April 2018

ABSTRACT

Freeze-thaw stress causes various types of cellular damage, survival and/or proliferation defects, and metabolic alterations. However, the mechanisms underlying how cells cope with freeze-thaw stress are poorly understood. Here, model dough fermentations using two baker's yeast strains, 45 and YF, of
Saccharomyces cerevisiae
were compared after 2 weeks of cell preservation in a refrigerator or freezer. YF exhibited slow fermentation after exposure to freeze-thaw stress due to low cell viability. A DNA microarray analysis of the YF cells during fermentation revealed that the genes involved in oxidative phosphorylation were relatively strongly expressed, suggesting a decrease in the glycolytic capacity. Furthermore, we found that mRNA levels of the genes that encode the components of the proteasome complex were commonly low, and ubiquitinated proteins were accumulated by freeze-thaw stress in the YF strain. In the cells with a laboratory strain background, treatment with the proteasome inhibitor MG132 or the deletion of each transcriptional activator gene for the proteasome genes (
RPN4
,
PDR1
, or
PDR3
) led to marked impairment of model dough fermentation using the frozen cells. Based on these data, proteasomal degradation of freeze-thaw-damaged proteins may guarantee high cell viability and fermentation performance. We also found that the freeze-thaw stress-sensitive YF strain was heterozygous at the
PDR3
locus, and one of the alleles (A148T/A229V/H336R/L541P) was shown to possess a dominant negative phenotype of slow fermentation. Removal of such responsible mutations could improve the freeze-thaw stress tolerance and the fermentation performance of baker's yeast strains, as well as other industrial
S. cerevisiae
strains.

IMPORTANCE
The development of freezing technology has enabled the long-term preservation and long-distance transport of foods and other agricultural products. Fresh yeast, however, is usually not frozen because the fermentation performance and/or the viability of individual cells is severely affected after thawing. Here, we demonstrate that proteasomal degradation of ubiquitinated proteins is an essential process in the freeze-thaw stress responses of
S. cerevisiae
. Upstream transcriptional activator genes for the proteasome components are responsible for the fermentation performance after freezing preservation. Thus, this study provides a potential linkage between freeze-thaw stress inputs and the transcriptional regulatory network that might be functionally conserved in higher eukaryotes. Elucidation of the molecular targets of freeze-thaw stress will contribute to advances in cryobiology, such as freezing preservation of human cells, tissues, and embryos for medical purposes and breeding of industrial microorganisms and agricultural crops that adapt well to low temperatures.
Survival of the Enveloped Virus Phi6 in Droplets as a Function of Relative Humidity, Absolute Humidity, and Temperature
Authors: Prussin Aaron J. , Schwake David Otto , Lin Kaisen , Gallagher Daniel L. , Buttling Lauren , Marr Linsey C. 
Published: April 2018

ABSTRACT

Infectious diseases caused by enveloped viruses, such as influenza, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), cause thousands of deaths and billions of dollars of economic losses per year. Studies have found a relationship among temperature, humidity, and influenza virus incidence, transmission, or survival; however, there are contradictory claims about whether absolute humidity (AH) or relative humidity (RH) is most important in mediating virus infectivity. Using the enveloped bacteriophage Phi6, which has been suggested as a surrogate for influenza viruses and coronaviruses, we designed a study to discern whether AH, RH, or temperature is a better predictor of virus survival in droplets. Our results show that Phi6 survived best at high (>85%) and low (<60%) RHs, with a significant decrease in infectivity at mid-range RHs (∼60 to 85%). At an AH of less than 22 g · m
−3
, the loss in infectivity was less than 2 orders of magnitude; however, when the AH was greater than 22 g · m
−3
, the loss in infectivity was typically greater than 6 orders of magnitude. At a fixed RH of 75%, infectivity was very sensitive to temperature, decreasing two orders of magnitude between 19°C and 25°C. We used random forest modeling to identify the best environmental predictors for modulating virus infectivity. The model explained 83% of variation in Phi6 infectivity and suggested that RH is the most important factor in controlling virus infectivity in droplets. This research provides novel information about the complex interplay between temperature, humidity, and the survival of viruses in droplets.

IMPORTANCE
Enveloped viruses are responsible for a number of infectious diseases resulting in thousands of deaths and billions of dollars of economic losses per year in the United States. There has been a lively debate in the literature over whether absolute humidity (AH) or relative humidity (RH) modulates virus infectivity. We designed a controlled study and used advanced statistical modeling techniques specifically to address this question. By providing an improved understanding of the relationship between environmental conditions and virus infectivity, our work will ultimately lead to improved strategies for predicting and controlling disease transmission.
Salt-Induced Stress Stimulates a Lipoteichoic Acid-Specific Three-Component Glycosylation System in Staphylococcus aureus
Authors: Kho Kelvin , Meredith Timothy C. 
Published: April 2018

ABSTRACT

Lipoteichoic acid (LTA) in
Staphylococcus aureus
is a poly-glycerophosphate polymer anchored to the outer surface of the cell membrane. LTA has numerous roles in cell envelope physiology, including regulating cell autolysis, coordinating cell division, and adapting to environmental growth conditions. LTA is often further modified with substituents, including
d
-alanine and glycosyl groups, to alter cellular function. While the genetic determinants of
d
-alanylation have been largely defined, the route of LTA glycosylation and its role in cell envelope physiology have remained unknown, in part due to the low levels of basal LTA glycosylation in
S. aureus
. We demonstrate here that
S. aureus
utilizes a membrane-associated three-component glycosylation system composed of an undecaprenol (Und)
N
-acetylglucosamine (GlcNAc) charging enzyme (CsbB; SAOUHSC_00713), a putative flippase to transport loaded substrate to the outside surface of the cell (GtcA; SAOUHSC_02722), and finally an LTA-specific glycosyltransferase that adds α-GlcNAc moieties to LTA (YfhO; SAOUHSC_01213). We demonstrate that this system is specific for LTA with no cross recognition of the structurally similar polyribitol phosphate containing wall teichoic acids. We show that while wild-type
S. aureus
LTA has only a trace of GlcNAcylated LTA under normal growth conditions, amounts are raised upon either overexpressing CsbB, reducing endogenous
d
-alanylation activity, expressing the cell envelope stress responsive alternative sigma factor SigB, or by exposure to environmental stress-inducing culture conditions, including growth media containing high levels of sodium chloride.

IMPORTANCE
The role of glycosylation in the structure and function of
Staphylococcus aureus
lipoteichoic acid (LTA) is largely unknown. By defining key components of the LTA three-component glycosylation pathway and uncovering stress-induced regulation by the alternative sigma factor SigB, the role of
N
-acetylglucosamine tailoring during adaptation to environmental stresses can now be elucidated. As the
dlt
and glycosylation pathways compete for the same sites on LTA and induction of glycosylation results in decreased
d
-alanylation, the interplay between the two modification systems holds implications for resistance to antibiotics and antimicrobial peptides.
Convergence of PASTA Kinase and Two-Component Signaling in Response to Cell Wall Stress in Enterococcus faecalis
Authors: Kellogg Stephanie L. , Kristich Christopher J. 
Published: April 2018

ABSTRACT

Two common signal transduction mechanisms used by bacteria to sense and respond to changing environments are two-component systems (TCSs) and eukaryote-like Ser/Thr kinases and phosphatases (eSTK/Ps).
Enterococcus faecalis
is a Gram-positive bacterium and a serious opportunistic pathogen that relies on both a TCS and an eSTK/P pathway for intrinsic resistance to cell wall-targeting antibiotics. The TCS consists of a histidine kinase (CroS) and a response regulator (CroR) that become activated upon exposure of cells to cell wall-targeting antibiotics, leading to a modulation of gene expression. The eSTK/P pathway consists of a transmembrane kinase (IreK) and its cognate phosphatase (IreP), which act antagonistically to mediate antibiotic resistance through an unknown mechanism. Because both CroS/R and IreK/P contribute to enterococcal resistance toward cell wall-targeting antibiotics, we hypothesized that these signaling systems are intertwined. To test this hypothesis, we analyzed CroR phosphorylation and CroS/R-dependent gene expression to probe the influence of IreK and IreP on CroS/R signaling. In addition, we analyzed the phosphorylation state of CroS, which revealed the IreK-dependent phosphorylation of a Thr residue important for CroS function. Our results are consistent with a model in which IreK positively influences CroR-dependent gene expression through the phosphorylation of CroS to promote antimicrobial resistance in
E. faecalis
.

IMPORTANCE
Two-component signaling systems (TCSs) and eukaryote-like Ser/Thr kinases (eSTKs) are used by bacteria to sense and adapt to changing environments. Understanding how these pathways are regulated to promote bacterial survival is critical for a more complete understanding of bacterial stress responses and physiology. The opportunistic pathogen
Enterococcus faecalis
relies on both a TCS (CroS/R) and an eSTK (IreK) for intrinsic resistance to cell wall-targeting antibiotics. We probed the relationship between CroS/R and IreK, revealing the convergence of IreK and the sensor kinase CroS to enhance signaling through CroS/R and increase antimicrobial resistance in
E. faecalis
. This newly described example of eSTK/TCS convergence adds to our understanding of the signaling networks mediating antimicrobial resistance in
E. faecalis
.
Association of ω with the C-Terminal Region of the β′ Subunit Is Essential for Assembly of RNA Polymerase in Mycobacterium tuberculosis
Authors: Mao Chunyou , Zhu Yan , Lu Pei , Feng Lipeng , Chen Shiyun , Hu Yangbo 
Published: April 2018

ABSTRACT

The ω subunit is the smallest subunit of bacterial RNA polymerase (RNAP). Although homologs of ω are essential in both eukaryotes and archaea, this subunit has been known to be dispensable for RNAP in
Escherichia coli
and in other bacteria. In this study, we characterized an indispensable role of the ω subunit in
Mycobacterium tuberculosis
. Unlike the well-studied
E. coli
RNAP, the
M. tuberculosis
RNAP core enzyme cannot be functionally assembled in the absence of the ω subunit. Importantly, substitution of
M. tuberculosis
ω with ω subunits from
E. coli
or
Thermus thermophilus
cannot restore the assembly of
M. tuberculosis
RNAP. Furthermore, by replacing different regions in
M. tuberculosis
ω with the corresponding regions from
E. coli
ω, we found a nonconserved loop region in
M. tuberculosis
ω essential for its function in RNAP assembly. From RNAP structures, we noticed that the location of the C-terminal region of the β′ subunit (β′CTD) in
M. tuberculosis
RNAP but not in
E. coli
or
T. thermophilus
RNAP is close to the ω loop region. Deletion of this β′CTD in
M. tuberculosis
RNAP destabilized the binding of
M. tuberculosis
ω on RNAP and compromised
M. tuberculosis
core assembly, suggesting that these two regions may function together to play a role in ω-dependent RNAP assembly in
M. tuberculosis
. Sequence alignment of the ω loop and the β′CTD regions suggests that the essential role of ω is probably restricted to mycobacteria. Together, our study characterized an essential role of
M. tuberculosis
ω and highlighted the importance of the ω loop region in
M. tuberculosis
RNAP assembly.

IMPORTANCE
DNA-dependent RNA polymerase (RNAP), which consists of a multisubunit core enzyme (α
2
ββ′ω) and a dissociable σ subunit, is the only enzyme in charge of transcription in bacteria. As the smallest subunit, the roles of ω remain the least well studied. In
Escherichia coli
and some other bacteria, the ω subunit is known to be nonessential for RNAP. In this study, we revealed an essential role of the ω subunit for RNAP assembly in the human pathogen
Mycobacterium tuberculosis
, and a mycobacterium-specific ω loop that plays a role in this function was also characterized. Our study provides fresh insights for further characterizing the roles of bacterial ω subunit.
Developing and Evaluating Inhibitors against the RNase H Active Site of HIV-1 Reverse Transcriptase
Authors: Boyer Paul L. , Smith Steven J. , Zhao Xue Zhi , Das Kalyan , Gruber Kevin , Arnold Eddy , Burke Terrence R. , Hughes Stephen H. 
Published: April 2018

ABSTRACT

We tested three compounds for their ability to inhibit the RNase H (RH) and polymerase activities of HIV-1 reverse transcriptase (RT). A high-resolution crystal structure (2.2 Å) of one of the compounds showed that it chelates the two magnesium ions at the RH active site; this prevents the RH active site from interacting with, and cleaving, the RNA strand of an RNA-DNA heteroduplex. The compounds were tested using a variety of substrates: all three compounds inhibited the polymerase-independent RH activity of HIV-1 RT. Time-of-addition experiments showed that the compounds were more potent if they were bound to RT before the nucleic acid substrate was added. The compounds significantly inhibited the site-specific cleavage required to generate the polypurine tract (PPT) RNA primer that initiates the second strand of viral DNA synthesis. The compounds also reduced the polymerase activity of RT; this ability was a result of the compounds binding to the RH active site. These compounds appear to be relatively specific; they do not inhibit either
Escherichia coli
RNase HI or human RNase H2. The compounds inhibit the replication of an HIV-1-based vector in a one-round assay, and their potencies were only modestly decreased by mutations that confer resistance to integrase strand transfer inhibitors (INSTIs), nucleoside analogs, or nonnucleoside RT inhibitors (NNRTIs), suggesting that their ability to block HIV replication is related to their ability to block RH cleavage. These compounds appear to be useful leads that can be used to develop more potent and specific compounds.

IMPORTANCE
Despite advances in HIV-1 treatment, drug resistance is still a problem. Of the four enzymatic activities found in HIV-1 proteins (protease, RT polymerase, RT RNase H, and integrase), only RNase H has no approved therapeutics directed against it. This new target could be used to design and develop new classes of inhibitors that would suppress the replication of the drug-resistant variants that have been selected by the current therapeutics.
Antimicrobial Resistance in
Campylobacter
spp
Authors: Shen Zhangqi , Wang Yang , Zhang Qijing , Shen Jianzhong 
Published: April 2018

ABSTRACT

Campylobacter
is a major foodborne pathogen and has become increasingly resistant to clinically important antimicrobials. To cope with the selection pressure from antimicrobial use in both veterinary and human medicine,
Campylobacter
has developed multiple mechanisms for antibiotic resistance, including modification or mutation of antimicrobial targets, modification or inactivation of antibiotics, and reduced drug accumulation by drug efflux pumps. Some of these mechanisms confer resistance to a specific class of antimicrobials, while others give rise to multidrug resistance. Notably, new antibiotic resistance mechanisms continuously emerge in
Campylobacter
, and some examples include the recently discovered multidrug resistance genomic islands harboring multiple genes involved in the resistance to aminoglycosides and macrolides, a novel Cfr(C) conferring resistance to phenicols and other drugs, and a potent multidrug efflux pump CmeABC variant (RE-CmeABC) that shows a significantly enhanced function in multidrug resistance and is associated with exceedingly high-level resistance to fluoroquinolones. These newly emerged resistance mechanisms are horizontally transferable and greatly facilitate the adaptation of
Campylobacter
in the food-producing environments where antibiotics are frequently used. In this article, we will discuss how
Campylobacter
resists the action of various classes of antimicrobials, with an emphasis on newly discovered mechanisms.