bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nature and origin of the J‐magnetic anomaly offshore Iberia–Newfoundland: implications for plate reconstructions
Authors: Nirrengarten Michael , Manatschal Gianreto , Tugend Julie , Kusznir Nick J. , Sauter Daniel 
Published: October 2016

AbstractThe nature and origin of the J‐magnetic anomaly along the Iberia–Newfoundland margins are controversial and its validity for plate kinematic reconstructions questioned. At present, it is interpreted as either an oceanic isochron or an edge effect of oceanic crust corresponding to lithosphere breakup. Both interpretations result in restorations that are in conflict with the current knowledge from Pyrenean and North Atlantic geology. We combine seismic interpretations and dating of magmatic additions with magnetic data to examine the nature and formation process of this anomaly and discuss its value for plate restorations. We show that the J‐anomaly is the result of polygenic and multiple magmatic events occurring during and after the formation of the first oceanic crust. Therefore, we conclude that the J‐anomaly cannot be used for plate kinematic studies and, more generally, we question the validity of using ill‐defined magnetic anomalies outside unequivocal oceanic domains for plate reconstructions.
An evaluation of sampling and full enumeration strategies for Fisher Jenks classification in big data settings
Authors: Rey Sergio J. , Stephens Philip , Laura Jason 
Published: October 2016

AbstractLarge data contexts present a number of challenges to optimal choropleth map classifiers. Application of optimal classifiers to a sample of the attribute space is one proposed solution. The properties of alternative sampling‐based classification methods are examined through a series of Monte Carlo simulations. The impacts of spatial autocorrelation, number of desired classes, and form of sampling are shown to have significant impacts on the accuracy of map classifications. Tradeoffs between improved speed of the sampling approaches and loss of accuracy are also considered. The results suggest the possibility of guiding the choice of classification scheme as a function of the properties of large data sets.
Storage characteristics of multiple‐donor pooled red blood cells compared to single‐donor red blood cell units
Authors: Mathur Aabhas , Chowdhury Raquibul , Hillyer Christopher D. , Mitchell W.Beau , Shaz Beth H. 
Published: October 2016

BACKGROUNDEach unit of blood donated is processed and stored individually resulting in variability in the amount of red blood cells (RBCs) collected, RBC properties, and the 24‐hour posttransfusion RBC survivability. As a result, each unit differs in its ability to deliver oxygen and potentially its effects on the recipient. The goal of this study was to investigate the storage of pooled RBCs from multiple donors in comparison to control standard RBC units.STUDY DESIGN AND METHODSTwo units of irradiated, leukoreduced RBCs of same ABO, D, E, C, and K antigen phenotype were collected from each of five donors using apheresis. One unit from each donor was pooled in a 2‐L bag and remaining units were used as controls. After being pooled, RBCs were separated in five bags and stored at 4°C along with the controls. Quality indexes were measured on Days 2, 14, and 28 for all the units.RESULTSAdenosine triphosphate assays for both pooled and controls showed a slight decrease from Day 2 to Day 28 (pooled/control from 5.22/5.24 to 4.35/4.33 µmol/g hemoglobin [Hb]). 2,3‐Diphosphoglycerate was successfully rejuvenated for all RBC units on Day 28 (pooled 11.46 µmol/g Hb; control 11.86 µmol/g Hb). The results showed a nonsignificant difference between pooled and control units, with a general trend of lower standard deviation for pooled units when compared to controls.CONCLUSIONPooled units have reduced unit‐to‐unit variability. Future exploration of their immunogenicity is required before using pooled units for transfusion.
Hematologic and biochemical reference intervals of free‐living Red‐Tailed Amazon parrot (Amazona brasiliensis) nestlings on Rasa Island, Paraná, Brazil
Authors: Vaz Frederico F. , Locatelli‐Dittrich Rosangela , Beltrame Olair C. , Sipinski Elenise A. B. , Abbud Maria C. , Sezerban Rafael M. 
Published: October 2016

BackgroundThe Red‐Tailed Amazon parrot (Amazona brasiliensis) is an endangered species of the Psittaciformes. There is little information about hematologic and biochemical variables of this species.ObjectivesThe purpose of this study was to determine hematologic and biochemical RIs for free‐living A brasiliensis nestlings on Rasa Island, Paraná, Brazil, and to compare the results between sexes.MethodsThirty‐seven parrots were taken from their nests and physically restrained for clinical examination and blood collection. The sex was diagnosed by PCR using the blood samples collected. Reference intervals were determined as recommended by the ASVCP guidelines in healthy nestlings. The difference between groups was analyzed using the Mann–Whitney test or Student's t‐test.ResultsSexing revealed 12 females and 25 males. The RIs for the measured variables were as follows: RBC 1.1–2.6 × 106/μL, PCV 29.1–50.3%, HGB 7.2–12.9 g/dL, MCV 152–293 fL, MCHC 22.2–28.4 g/dL, WBC 4.9–28.5 × 103/μL, 1.2–16 × 103/μL, lymphocytes 2.4–18.7 × 103/μL, monocytes 0.0–1.0 × 103/μL, eosinophils 0.0–0.9 × 103/μL, 0.0–1.3 × 103/μL, heterophil:lymphocyte ratio 0.0–2.2, plasma total solids 2.1–3.7 g/dL, uric acid 0.5–2.0 mg/dL, glucose 184.9–284.3 mg/dL, AST 100.3–226.6 U/L, LDH 178.1–927.7 U/L, CK 149.8–1144.0 U/L, cholesterol 137.5–256.9 mg/dL, total protein 1.8–3.0 g/dL, calcium 7.0–8.6 mg/dL, and phosphorus 2.9–6.1 mg/dL. Increased concentrations of cholesterol (P < .05) were observed in females.DiscussionThis is the first study to establish hematologic and biochemical RIs for free‐living A brasiliensis nestlings on Rasa Island. Hematologic and biochemical variables are important tools for evaluating the health status of free‐living birds, and also support conservation planning for endangered species.
Algorithms utilizing peripheral blood hematopoietic progenitor cell counts in lieu of some CD34+ cell counts predict successful peripheral blood stem cell collections with substantial time and cost savings
Authors: Steussy B. W. , Capper M. , Krasowski M. D. , Rosenthal N. S. , Schlueter A. J. 
Published: October 2016

Background and ObjectivesHematopoietic progenitor cell (HPC) counts from Sysmex hematology analyzers have been shown to correlate with peripheral blood (PB) CD34+ cell counts by flow cytometry. Algorithms utilizing HPC counts to guide stem cell collections have been proposed but rarely tested. This study describes the development and validation of algorithms utilizing HPC and PB CD34+ cell counts to predict adequate peripheral blood stem cell (PBSC) collections for chemomobilized and cytokine‐mobilized individuals.Materials and MethodsUtilizing a test set of 83 PB samples from chemomobilized or cytokine‐mobilized PBSC collection patients, PB CD34+ counts were correlated with HPC counts and a receiver operating characteristic curve was constructed. Cut‐offs of ≤0·5 HPC/μl and ≥7 HPC/μl were established to maximize sensitivity and specificity for using HPC to predict PB CD34+ ≥ 10 cells/μl. These cut‐offs were subsequently validated using a separate prospective validation set of 88 HPC/CD34+ cell sample pairs.ResultsUsing the algorithms, all patients in the prospective validation data set achieved adequate collections of ≥1 × 106 CD34+ cells/kg, and a 67% reduction in the number of CD34+ cell counts performed was achieved. This lead to a direct cost savings of at least $18 700 USD over a 21‐month period (88% reduction in direct costs).ConclusionUse of the algorithms provides significant time and cost savings for the laboratory while accurately predicting (i) timing of PBSC collections to obtain adequate CD34+ product yields for chemomobilized patients and (ii) when to administer plerixafor to cytokine‐mobilized patients to improve the likelihood of achieving adequate collections.
Microglia in health and pain: impact of noxious early life events
Authors: Burke Nikita N. , Fan Churmy Y. , Trang Tuan 
Published: October 2016

New Findings

What is the topic of this review?
This review discusses the origins and development of microglia, and how stress, pain or inflammation in early life disturbs microglial function during critical developmental periods, leading to altered pain sensitivity and/or increased risk of chronic pain in later life.

What advances does it highlight?
We highlight recent advances in understanding how disrupted microglial function impacts the developing nervous system and the consequences for pain processing and susceptibility for development of chronic pain in later life.

The discovery of microglia is accredited to Pío del Río‐Hortega, who recognized this ‘third element’ of CNS cells as being morphologically distinct from neurons and astrocytes. For decades after this finding, microglia were altogether ignored or relegated as simply being support cells. Emerging from virtual obscurity, microglia have now gained notoriety as immune cells that assume a leading role in the development, maintenance and protection of a healthy CNS. Pioneering studies have recently shed light on the origins of microglia, their role in the developing nervous system and the complex roles they play beyond the immune response. These studies reveal that altered microglial function can have a profoundly negative impact on the developing brain and may be a determinant in a range of neurodevelopmental disorders and neurodegenerative diseases. The realization that aberrant microglial function also critically underlies chronic pain, a debilitating disorder that afflicts over 1.5 billion people worldwide, was a major conceptual leap forward in the pain field. Adding to this advance is emerging evidence that early life noxious experiences can have a long‐lasting impact on central pain processing and adult pain sensitivity. With microglia now coming of age, in this review we examine the association between adverse early life events, such as stress, injury or inflammation, and the influence of sex differences, on the role of microglia in pain physiology in adulthood.
Respiratory gases and the regulation of transcription
Authors: Cummins Eoin P. , Keogh Ciara E. 
Published: October 2016

New Findings
What is the topic of this review?
This review highlights the transcriptional consequences for decreased cellular O2 levels (hypoxia) and increased cellular CO2 levels (hypercapnia).
What advances does it highlight?
We discuss recent advances in our understanding of the cellular response to hypoxia and consider the potential cross‐talk between O2‐ and CO2‐dependent transcriptional regulation.
Oxygen and carbon dioxide are the substrate and product of aerobic metabolism, respectively. Thus, the levels of these physiological gases are inextricably linked in physiological and pathophysiological conditions. Increased mitochondrial consumption of O2 (to produce ATP) will produce more CO2. Furthermore, in lung pathologies such as chronic obstructive pulmonary disease, sleep apnoea and central hypoventilation syndrome, hypoxia and hypercapnia are co‐incident. Acute responses to hypoxia involve carotid body‐mediated changes in the rate and depth of breathing. Chronic adaptation to hypoxia involves a multitude of changes on a transcriptional level, which simultaneously increases oxygen utilization (via hypoxia‐inducible factor and others), while suppressing superfluous energy‐demanding processes. Acute responses to CO2 affect breathing primarily via central chemoreceptors. The nature of hypercapnia‐dependent transcriptional regulation is an emerging area of research, but at present the mechanisms underpinning this response are not fully characterized and understood. Thus, given the juxtaposition of hypoxia and hypercapnia in health and disease, this manuscript reviews the current evidence for transcriptional responses to hypoxia and hypercapnia. Finally, we discuss the potential cross‐talk between hypoxia and hypercapnia on a transcriptional level.
Analysis of Repair Mechanisms following an Induced Double-Strand Break Uncovers Recessive Deleterious Alleles in the Candida albicans Diploid Genome
Authors: Feri Adeline , Loll-Krippleber Raphaël , Commere Pierre-Henri , Maufrais Corinne , Sertour Natacha , Schwartz Katja , Sherlock Gavin , Bougnoux Marie-Elisabeth , d’Enfert Christophe , Legrand Mélanie 
Published: October 2016

ABSTRACT

The diploid genome of the yeast
Candida albicans
is highly plastic, exhibiting frequent loss-of-heterozygosity (LOH) events. To provide a deeper understanding of the mechanisms leading to LOH, we investigated the repair of a unique DNA double-strand break (DSB) in the laboratory
C. albicans
SC5314 strain using the I-SceI meganuclease. Upon I-SceI induction, we detected a strong increase in the frequency of LOH events at an I-SceI target locus positioned on chromosome 4 (Chr4), including events spreading from this locus to the proximal telomere. Characterization of the repair events by single nucleotide polymorphism (SNP) typing and whole-genome sequencing revealed a predominance of gene conversions, but we also observed mitotic crossover or break-induced replication events, as well as combinations of independent events. Importantly, progeny that had undergone homozygosis of part or all of Chr4 haplotype B (Chr4B) were inviable. Mining of genome sequencing data for 155
C. albicans
isolates allowed the identification of a recessive lethal allele in the
GPI16
gene on Chr4B unique to
C. albicans
strain SC5314 which is responsible for this inviability. Additional recessive lethal or deleterious alleles were identified in the genomes of strain SC5314 and two clinical isolates. Our results demonstrate that recessive lethal alleles in the genomes of
C. albicans
isolates prevent the occurrence of specific extended LOH events. While these and other recessive lethal and deleterious alleles are likely to accumulate in
C. albicans
due to clonal reproduction, their occurrence may in turn promote the maintenance of corresponding nondeleterious alleles and, consequently, heterozygosity in the
C. albicans
species.

IMPORTANCE
Recessive lethal alleles impose significant constraints on the biology of diploid organisms. Using a combination of an I-SceI meganuclease-mediated DNA DSB, a fluorescence-activated cell sorter (FACS)-optimized reporter of LOH, and a compendium of 155 genome sequences, we were able to unmask and identify recessive lethal and deleterious alleles in isolates of
Candida albicans
, a diploid yeast and the major fungal pathogen of humans. Accumulation of recessive deleterious mutations upon clonal reproduction of
C. albicans
could contribute to the maintenance of heterozygosity despite the high frequency of LOH events in this species.
Multiple Signals Govern Utilization of a Polysaccharide in the Gut Bacterium Bacteroides thetaiotaomicron
Authors: Schwalm Nathan D. , Townsend Guy E. , Groisman Eduardo A. 
Published: October 2016

ABSTRACT

The utilization of simple sugars is widespread across all domains of life. In contrast, the breakdown of complex carbohydrates is restricted to a subset of organisms. A regulatory paradigm for integration of complex polysaccharide breakdown with simple sugar utilization was established in the mammalian gut symbiont
Bacteroides thetaiotaomicron
, whereby sensing of monomeric fructose regulates catabolism of both fructose and polymeric fructans. We now report that a different regulatory paradigm governs utilization of monomeric arabinose and the arabinose polymer arabinan. We establish that (i) arabinan utilization genes are controlled by a transcriptional activator that responds to arabinan and by a transcriptional repressor that responds to arabinose, (ii) arabinose utilization genes are regulated directly by the arabinose-responding repressor but indirectly by the arabinan-responding activator, and (iii) activation of both arabinan and arabinose utilization genes requires a pleiotropic transcriptional regulator necessary for survival in the mammalian gut. Genomic analysis predicts that this paradigm is broadly applicable to the breakdown of other polysaccharides in both
B. thetaiotaomicron
and other gut
Bacteroides
spp. The uncovered mechanism enables regulation of polysaccharide utilization genes in response to both the polysaccharide and its breakdown products.

IMPORTANCE
Breakdown of complex polysaccharides derived from “dietary fiber” is achieved by the mammalian gut microbiota. This breakdown creates a critical nutrient source for both the microbiota and its mammalian host. Because the availability of individual polysaccharides fluctuates with variations in the host diet, members of the microbiota strictly control expression of polysaccharide utilization genes. Our findings define a regulatory architecture that controls the breakdown of a polysaccharide by a gut bacterium in response to three distinct signals. This architecture integrates perception of a complex polysaccharide and its monomeric constituent as well as feedback of central metabolism. Moreover, it is broadly applicable to several prominent members of the mammalian gut microbiota. The identified regulatory strategy may contribute to the abundance of gut
Bacteroides
, despite fluctuations in the host diet.
Commensal Protection of Staphylococcus aureus against Antimicrobials by Candida albicans Biofilm Matrix
Authors: Kong Eric F. , Tsui Christina , Kucharíková Sona , Andes David , Van Dijck Patrick , Jabra-Rizk Mary Ann 
Published: October 2016

ABSTRACT

Biofilm-associated polymicrobial infections, particularly those involving fungi and bacteria, are responsible for significant morbidity and mortality and tend to be challenging to treat.
Candida albicans
and
Staphylococcus aureus
specifically are considered leading opportunistic fungal and bacterial pathogens, respectively, mainly due to their ability to form biofilms on catheters and indwelling medical devices. However, the impact of mixed-species biofilm growth on therapy remains largely understudied. In this study, we investigated the influence of
C. albicans
secreted cell wall polysaccharides on the response of
S. aureus
to antibacterial agents in biofilm. Results demonstrated significantly enhanced tolerance for
S. aureus
to drugs in the presence of
C. albicans
or its secreted cell wall polysaccharide material. Fluorescence confocal time-lapse microscopy revealed impairment of drug diffusion through the mixed biofilm matrix. Using
C. albicans
mutant strains with modulated cell wall polysaccharide expression, exogenous supplementation, and enzymatic degradation, the
C. albicans
-secreted β-1,3-glucan cell wall component was identified as the key matrix constituent providing the bacteria with enhanced drug tolerance. Further, antibody labeling demonstrated rapid coating of the bacteria by the
C. albicans
matrix material. Importantly, via its effect on the fungal biofilm matrix, the antifungal caspofungin sensitized the bacteria to the drugs. Understanding such symbiotic interactions with clinical relevance between microbial species in biofilms will greatly aid in overcoming the limitations of current therapies and in defining potential new targets for treating polymicrobial infections.

IMPORTANCE
The fungus
Candida albicans
and the bacterium
Staphylococcus aureus
are important microbial pathogens responsible for the majority of infections in hospitalized patients and are often coisolated from a host. In this study, we demonstrated that when grown together, the fungus provides the bacterium with enhanced tolerance to antimicrobial drugs. This process was mediated by polysaccharides secreted by the fungal cell into the environment. The biofilm matrix formed by these polysaccharides prevented penetration by the drugs and provided the bacteria with protection. Importantly, we show that by inhibiting the production of the fungal polysaccharides, a specific antifungal agent indirectly sensitized the bacteria to antimicrobials. Understanding the therapeutic implications of the interactions between these two diverse microbial species will aid in overcoming the limitations of current therapies and in defining new targets for treating complex polymicrobial infections.
Spatial and Temporal Shifts in Bacterial Biogeography and Gland Occupation during the Development of a Chronic Infection
Authors: Keilberg Daniela , Zavros Yana , Shepherd Benjamin , Salama Nina R. , Ottemann Karen M. 
Published: October 2016

ABSTRACT

Gland colonization may be one crucial route for bacteria to maintain chronic gastrointestinal infection. We developed a quantitative gland isolation method to allow robust bacterial population analysis and applied it to the gastric pathobiont
Helicobacter pylori
. After infections in the murine model system,
H. pylori
populations multiply both inside and outside glands in a manner that requires the bacteria to be motile and chemotactic.
H. pylori
is able to achieve gland densities averaging 25 to 40 bacteria/gland after 2 to 4 weeks of infection. After 2 to 4 weeks of infection, a primary infection leads to colonization resistance for a secondary infection. Nonetheless, about ~50% of the glands remained unoccupied, suggesting there are as-yet unappreciated parameters that prevent gastric gland colonization. During chronic infections,
H. pylori
populations collapsed to nearly exclusive gland localization, to an average of <8 bacteria/gland, and only 10% of glands occupied. We analyzed an
H. pylori
chemotaxis mutant (Che
−
) to gain mechanistic insight into gland colonization. Che
−
strains had a severe inability to spread to new glands and did not protect from a secondary infection but nonetheless achieved a chronic gland colonization state numerically similar to that of the wild type. Overall, our analysis shows that bacteria undergo substantial population dynamics on the route to chronic colonization, that bacterial gland populations are maintained at a low level during chronic infection, and that established gland populations inhibit subsequent colonization. Understanding the parameters that promote chronic colonization will allow the future successful design of beneficial microbial therapeutics that are able to maintain long-term mammalian colonization.

IMPORTANCE
Many bacteria have an impressive ability to stay in the gastrointestinal tract for decades despite ongoing flow and antimicrobial attacks. How this staying power is achieved is not fully understood, but it is important to understand as scientists plan so-called designer microbiomes. The gastrointestinal tract is lined with repeated invaginations called glands, which may provide one niche for chronic colonization. We developed a quantitative gland isolation method to allow robust and efficient bacterial population analysis and applied it to the gastric pathogen
Helicobacter pylori
. Bacterial populations increased inside and outside glands at early time points but were found exclusively within glands during late time points in the chronic state.
H. pylori
required the ability to swim to move to new glands. Last, a fit gland bacterial population leads to colonization resistance of a second one. Our approach identified previously unappreciated aspects of gland occupation, supporting the idea that glands are the desired niche for stable, chronic colonization.