bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals
Authors: Fisher James P. , Hartwich Doreen , Seifert Thomas , Olesen Niels D. , McNulty Clare L. , Nielsen Henning B. , van Lieshout Johannes J. , Secher Niels H. 
Published: December 2012

Key points
The influence of normative ageing on cerebral perfusion, oxygenation and metabolism during exercise is not well known.
This study assessed cerebral perfusion and concentration differences for oxygen, glucose and lactate across the brain, in young and elderly individuals at rest and during incremental exercise to exhaustion.
We observed that during submaximal exercise (at matched relative intensities) and during maximal exercise, cerebral perfusion was reduced in older individuals compared with young individuals, while the cerebral metabolic rate for oxygen and uptake of glucose and lactate were similar.
The results indicate that the age‐related reduction in cerebral perfusion during exercise does not affect brain uptake of lactate and glucose.
Abstract  We evaluated cerebral perfusion, oxygenation and metabolism in 11 young (22 ± 1 years) and nine older (66 ± 2 years) individuals at rest and during cycling exercise at low (25%Wmax), moderate (50%Wmax), high (75%Wmax) and exhaustive (100%Wmax) workloads. Mean middle cerebral artery blood velocity (MCA Vmean), mean arterial pressure (MAP), cardiac output (CO) and partial pressure of arterial carbon dioxide () were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O2), glucose and lactate across the brain. The molar ratio between cerebral uptake of O2 versus carbohydrate (O2–carbohydrate index; O2/[glucose +1/2 lactate]; OCI), the cerebral metabolic rate of O2 (CMRO2) and changes in mitochondrial O2 tension () were calculated. 100%Wmax was ∼33% lower in the older group. Exercise increased MAP and CO in both groups (P < 0.05 vs. rest), but at each intensity MAP was higher and CO lower in the older group (P < 0.05). MCA Vmean, and cerebral vascular conductance index (MCA Vmean/MAP) were lower in the older group at each exercise intensity (P < 0.05). In contrast, young and older individuals exhibited similar increases in CMRO2 (by ∼30 μmol (100 g−1) min−1), and decreases in OCI (by ∼1.5) and (by ∼10 mmHg) during exercise at ≥75%Wmax. Thus, despite the older group having reduced cerebral perfusion and maximal exercise capacity, cerebral oxygenation and uptake of lactate and glucose are similar during exercise in young and older individuals.
Different NMDA receptor subtypes mediate induction of long‐term potentiation and two forms of short‐term potentiation at CA1 synapses in rat hippocampus in vitro
Authors: Volianskis Arturas , Bannister Neil , Collett Valerie J. , Irvine Mark W. , Monaghan Daniel T. , Fitzjohn Stephen M. , Jensen Morten S. , Jane David E. , Collingridge Graham L. 
Published: December 2012

Key points
N‐Methyl‐d‐aspartate receptor (NMDAR)‐dependent potentiation of synaptic transmission is widely accepted as a cellular model of learning and memory.
It is most often studied in the CA1 area of rat hippocampal slices where it comprises a decremental and a sustained phase, which are commonly referred to as short‐term potentiation (STP) and long‐term potentiation (LTP), respectively.
In this study we show for the first time that STP and LTP are triggered by the activation of different classes of NMDARs and that STP itself comprises two pharmacologically and kinetically distinct components.
We suggest that the mechanistic separation of STP and LTP is likely to have important functional implications in that these two forms of synaptic plasticity can subserve unique physiological functions in a behaving animal.
Abstract  Potentiation at synapses between CA3 and the CA1 pyramidal neurons comprises both transient and sustained phases, commonly referred to as short‐term potentiation (STP or transient LTP) and long‐term potentiation (LTP), respectively. Here, we utilized four subtype‐selective N‐methyl‐d‐aspartate receptor (NMDAR) antagonists to investigate whether the induction of STP and LTP is dependent on the activation of different NMDAR subtypes. We find that the induction of LTP involves the activation of NMDARs containing both the GluN2A and the GluN2B subunits. Surprisingly, however, we find that STP can be separated into two components, the major form of which involves activation of NMDARs containing both GluN2B and GluN2D subunits. These data demonstrate that synaptic potentiation at CA1 synapses is more complex than is commonly thought, an observation that has major implications for understanding the role of NMDARs in cognition.
Quantitative Screening for Anticestode Drugs Based on Changes in Baseline Enzyme Secretion by Taenia crassiceps
Authors: Mahanty Siddhartha , Madrid Elise M. , Nash Theodore E. 
Published: December 2012

ABSTRACT

Neurocysticercosis (NCC), an infection of the brain with the larval stage of the
Taenia solium
tapeworm, is responsible for an estimated one-third of adult-onset epilepsy cases in regions of the world where it is endemic. Currently, anthelmintic drugs used for treatment of NCC are only partially effective, and there is, therefore, a pressing need for new therapeutic agents. Discovery of new anthelmintics with activity against
T. solium
has been limited by the lack of suitable sensitive assays that allow high-throughput screening. Using an
in vitro
culture system with
Taenia crassiceps
metacestodes, we demonstrate that changes in secretion of parasite-associated alkaline phosphatase (AP) and phosphoglucose isomerase (PGI) can be used to detect and quantify anthelmintic effects of praziquantel (PZQ), a drug with activity against
T. solium
. We applied two enzyme release assays to screen for anti-
T. crassiceps
activity in nonconventional antiparasitic drugs and demonstrate that nitazoxanide and artesunate induced release of both AP and PGI in differing time- and dose-related patterns. Furthermore, imatinib, a tyrosine kinase inhibitor previously reported to have parasiticidal activity against
Schistosoma mansoni
, also induced release of both AP and PGI in a dose-dependent manner, similar in pattern to that observed with the other anthelmintics. We also evaluated release of ATP into cyst supernatants as an indicator of drug effects but did not see any differences between treated and untreated cysts. These data provide the basis for rapid and quantitative screening assays for testing for anthelmintic activity in candidate anticestode agents.
In Vitro
Activity of a New Oral Glucan Synthase Inhibitor (MK-3118) Tested against Aspergillus spp. by CLSI and EUCAST Broth Microdilution Methods
Authors: Pfaller Michael A. , Messer Shawn A. , Motyl Mary R. , Jones Ronald N. , Castanheira Mariana 
Published: December 2012

ABSTRACT

MK-3118, a glucan synthase inhibitor derived from enfumafungin, and comparator agents were tested against 71
Aspergillus
spp., including itraconazole-resistant strains (MIC, ≥4 μg/ml), using CLSI and EUCAST reference broth microdilution methods. The CLSI 90% minimum effective concentration (MEC
90
)/MIC
90
values (μg/ml) for MK-3118, amphotericin B, and caspofungin, respectively, were as follows: 0.12, 2, and 0.03 for
Aspergillus flavus
species complex (SC); 0.25, 2, and 0.06 for
Aspergillus fumigatus
SC; 0.12, 2, and 0.06 for
Aspergillus terreus
SC; and 0.06, 1, and 0.03 for
Aspergillus niger
SC. Essential agreement between the values found by CLSI and EUCAST (±2 log
2
dilution steps) was 94.3%. MK-3118 was determined to be a potent agent regardless of the
in vitro
method applied, with excellent activity against contemporary wild-type and itraconazole-resistant strains of
Aspergillus
spp.
Exposure of Salmonella enterica Serovar Typhimurium to a Protective Monoclonal IgA Triggers Exopolysaccharide Production via a Diguanylate Cyclase-Dependent Pathway
Authors: Amarasinghe Jayaleka J. , D'Hondt Rebecca E. , Waters Christopher M. , Mantis Nicholas J. 
Published: December 2012

ABSTRACT

Sal4 is a monoclonal polymeric IgA antibody directed against the O antigen (O-Ag) of
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium), which is sufficient to protect mice against intestinal infections from
S
. Typhimurium. We recently reported that the exposure of
S
. Typhimurium to Sal4 results in the immediate loss of flagellum-based motility, in alterations to the outer membrane (OM) integrity, and in the concomitant appearance of a mucoid phenotype that is reminiscent of cells in the earliest stages of biofilm formation. We demonstrate here that prolonged (>4 h) exposure of
S
. Typhimurium to Sal4 at 37°C (but not at ambient temperature [25°C]) results in measurable exopolysaccharide (EPS) accumulation and biofilm formation on both borosilicate glass surfaces and polystyrene microtiter plates. The polysaccharide produced by
S
. Typhimurium in response to Sal4 contains cellulose, in addition to O-Ag capsule and colanic acid. EPS production was dependent on YeaJ, a proposed inner membrane-localized diguanylate cyclase (DGC) and a known regulator of cellulose biosynthesis. An
S
. Typhimurium Δ
yeaJ
strain was unable to produce cellulose or form a biofilm in response to Sal4. Conversely, the overexpression of
yeaJ
in
S
. Typhimurium enhanced Sal4-induced biofilm formation and resulted in increased intracellular levels of cyclic dimeric guanosine monophosphate (c-di-GMP) compared to that of a wild-type control; this strongly suggests that YeaJ is indeed a functional DGC. Based on these data, we speculate that Sal4, by virtue of its ability to associate with the O-Ag and to induce OM stress, renders
S
. Typhimurium avirulent by triggering a c-di-GMP-dependent signaling pathway via YeaJ that leads to the suppression of bacterial motility while simultaneously stimulating EPS production.
Helicobacter pylori Stores Nickel To Aid Its Host Colonization
Authors: Benoit Stéphane L. , Miller Erica F. , Maier Robert J. 
Published: December 2012

ABSTRACT

The transition metal nickel (Ni) is critical for the pathogenicity of
Helicobacter pylori
. Indeed the element is a required component of two enzymes, hydrogenase and urease, that have been shown to be important for
in vivo
colonization of the host gastric mucosa. Urease accounts for up to 10% of the total cellular
H. pylori
protein content, and therefore the bacterial Ni demand is very high.
H. pylori
possess two small and abundant histidine-rich, Ni-binding proteins, Hpn and Hpn-like, whose physiological role in the host have not been investigated. In this study, special husbandry conditions were used to control Ni levels in the host (mouse), including the use of Ni-free versus Ni-supplemented food. The efficacy of each diet was confirmed by measuring the Ni concentrations in sera of mice fed with either diet. Colonization levels (based on rank tests) of the
Δhpn Δhpn
-like double mutants isolated from the mice provided Ni-deficient chow were statistically lower than those for mice given Ni in their diet. In contrast,
H. pylori
wild-type colonization levels were similar in both host groups (e.g., regardless of Ni levels). Our results indicate that the gastric pathogen
H. pylori
can utilize stored Ni via defined histidine-rich proteins to aid colonization of the host.
Activation of the Nlrp1b Inflammasome by Reduction of Cytosolic ATP
Authors: Liao Kuo-Chieh , Mogridge Jeremy 
Published: December 2012

ABSTRACT
The efficacy of the innate immune system depends on its ability to mount an appropriate response to diverse infections and damaging agents. Key components of this system are pattern recognition receptors that detect pathogen-associated and damage-associated molecular patterns (PAMPs and DAMPs). Nlrp1b is a pattern recognition receptor that forms a caspase-1 activation platform, known as an inflammasome, upon sensing the proteolytic activity of anthrax lethal toxin. The activation of caspase-1 leads to the release of proinflammatory cytokines that aid in the clearance of the anthrax infection. Here, we demonstrate that Nlrp1b also becomes activated in cells that are subjected to energy stress caused by metabolic inhibitors or by nutrient deprivation. Glucose starvation and hypoxia were used to correlate the level of cytosolic ATP to the degree of inflammasome activation. Because lowering the ratio of cytosolic ATP to AMP activates the main cellular energy sensor, AMP-activated protein kinase (AMPK), we assessed whether AMPK promoted inflammasome activity by using a combination of small interfering RNA (siRNA) and transfection of a dominant negative AMPK subunit. We found that AMPK promoted inflammasome activity, but activation of AMPK in the absence of ATP depletion was not sufficient for caspase-1-mediated pro-interleukin 1β (pro-IL-1β) processing. Finally, we found that mutation of the ATP-binding motif of Nlrp1b caused constitutive activation, suggesting that ATP might inhibit the Nlrp1b inflammasome instead of being required for its assembly.
Controls on bud activation and tiller initiation in C3and C4tallgrass prairie grasses: the role of light and nitrogen
Authors: Williamson Melinda M. , Wilson Gail W.T. , Hartnett David C. 
Published: December 2012

Population dynamics of perennial grasses in tallgrass prairie ecosystems are strongly influenced by vegetative outgrowth from their belowground bud banks. We examined the role of light and nitrogen in regulating tiller initiation and tested an integrated model of controls on bud dormancy and activation in several C3and C4grasses. In addition, we assessed the interaction of nitrogen and light quantity and red – far red spectral composition on tiller initiation. Belowground perennating organs of three C3and three C4species were grown under full light or dark conditions, amended with one of four nitrogen concentrations (0 to 350 ppm N). Dormant buds were also subjected to full light under different spectral compositions or to continuous darkness. Our results among C3grasses support the integrated model as light and nitrogen played important and interacting roles in the regulation of bud banks. However, differences in responses among C4grasses and a lack of light × nitrogen interactions suggest that an alternative model may be necessary for this functional group. Our results provide predictions of responses to nitrogen enrichment or light imitations in prairie ecosystems due to interacting disturbances such as reduction in fire frequencies, alterations in grazing intensities, or climate change.
Detection and localization of the endophyteUndifilum oxytropisin locoweed tissues
Authors: Reyna Roxanna , Cooke Peter , Grum Daniel , Cook Daniel , Creamer Rebecca 
Published: December 2012

Poisoning of livestock owing to grazing on locoweeds results in significant economic losses in the western United States. Some Oxytropis spp. locoweeds contain a seed-transmitted endophytic fungus, Undifilum oxytropis, which produces the toxic alkaloid swainsonine. We sought to localize and characterize growth patterns of the fungus within leaves and petioles of Oxytropis lambertii Pursh and Oxytropis sericea Nutt. to help define the types of interactions between the fungus and its hosts. Vegetative hyphae were observed within locoweed tissues using integrated imaging. Topographical images from scanning electron microscopy revealed the presence of the endophyte in the pith tissue of petioles. The fungus was identified between plant cells but did not appear to penetrate host cells. Transmission electron microscopy images of thin sections revealed that hyphae were closely associated with host cell walls. Oxytropis sericea was innoculated with green fluorescent protein-transformed U. oxytropis and observed by confocal microscopy, confirming the presence of the endophyte hyphae in leaves and petioles. The fungus was identified only in the pith of petioles using fluorescence and in the vascular bundle throughout extracellular spaces in leaves. These results revealed no signs of a pathogenic interaction between plant and fungus and support the hypothesis of a mutualistic or commensal relationship.
American chestnut (Castanea dentata) to northern red oak (Quercus rubra): forest dynamics of an old-growth forest in the Blue Ridge Mountains, USA
Authors: van de Gevel Saskia L. , Hart Justin L. , Spond Mark D. , White Philip B. , Sutton Megan N. , Grissino-Mayer Henri D. 
Published: December 2012

We analyzed tree species composition and age structure in a rare, old-growth Quercus rubra L. (northern red oak) forest at Bluff Mountain Preserve, North Carolina, to assess potential changes associated with Cryphonectria parasitica (Murrill) M.E. Barr (chestnut blight), selective logging, livestock grazing, ice storms, wind events, and fire history. We established forest inventory plots to determine the forest composition, vertical structure, and age of the high-elevation Q. rubra dominated forest. We developed the longest Q. rubra dendroecological history (1671–2009) in North America. Several living Q. rubra individuals were more than 250 years old. The frequency, magnitude, and spatial extent of canopy disturbance events were shown in radial growth trends in Q. rubra samples. We also examined Q. rubra climate – radial growth relationships to compare high-elevation Q. rubra climate response patterns with results from lower elevation Quercus dendroclimatological studies. Stand-wide release events corresponded with the loss of Castanea dentata (Marsh.) Borkh. (American chestnut) during the 1930s and frequent ice storms or wind events. Although we observed fire scars on living hardwood trees, we did not find fire scars on the remnant logs. The lack of fire scars on the remnant logs indicates that the observed fires likely occurred during the second half of the 20th century. Quercus rubra were most climatically sensitive to cool March temperatures. Quercus rubra sampled at higher elevations were more sensitive to temperature than lower elevation Quercus spp. trees, which may indicate higher sensitivity to March frosts. Quercus rubra has been a dominant species at Bluff Mountain for the past 300 years; however, our data indicate that the forest will transition to support a much stronger Acer saccharum Marsh. (sugar maple) component during the next 50 years. This study provides a multicentury perspective to guide conservation efforts and forest management in high-elevation Quercus spp. forests in the southern Appalachian Mountains.
A chronsequential approach to investigating microbial community shifts following clearcutting in Boreal Plain forest soils
Authors: Hynes Holly M. , Germida James J. 
Published: December 2012

Impacts of forest harvesting are often assessed in short-term studies that ignore the longer term changes associated with the disturbance. A chronosequence approach was taken to investigate changes in microbial community size and composition over ∼20 years post-harvest in lodgepole pine ( Pinus contorta Douglas ex Loudon) stands of the Boreal Plain. The LFH and mineral Ae horizons of Orthic Gray Luvisolic soils were sampled in six cutblocks, aged 1–19 years since harvest, in 2009 and 2010. Changes in microbial communities were assessed using phospholipid fatty acid analysis (PLFA) and 16S rDNA analysis. Physical and chemical soil parameters were measured to delineate microsite changes impacting microbial community shifts. Total microbial biomass (PLFA) was unaffected by harvesting disturbance, although fungal biomass was significantly larger in the oldest cutblock of the chronosequence. Microbial community composition did, however, differ between younger and older cutblocks as indicated by both lipid PLFA and 16S rDNA fingerprinting techniques. Forest soil microbial communities subject to clearcutting were observed to shift in overall community composition while remaining consistent in overall community size. The shift in community composition, which occurred in concert with the maintenance of biomass, indicated that the microbial community adapted sufficiently to the new post-harvest microsite conditions.
Recent advances in the synthesis of colloidal nanowires
Authors: Repko Anton , Cademartiri Ludovico 
Published: December 2012

We review critically the advances in the synthesis of colloidal nanowires that have occurred over the past three years, with a focus on those that produced very thin (or “ultrathin”) nanowires (∼2–3 nm in diameter or less). We discuss the importance of these ultrathin nanowires, especially in light of the emerging evidence of their topological properties and their potential similarities with polymers.
Fire-injured ponderosa pine provide a pulsed resource for bark beetles
Authors: Davis Ryan S. , Hood Sharon , Bentz Barbara J. 
Published: December 2012

Bark beetles can cause substantial mortality of trees that would otherwise survive fire injuries. Resin response of fire-injured northern Rocky Mountain ponderosa pine ( Pinus ponderosa Douglas ex P. Lawson & C. Lawson) and specific injuries that contribute to increased bark beetle attack susceptibility and brood production are unknown. We monitored ponderosa pine mortality and resin flow and bark beetle colonization and reproduction following a prescribed fire in Idaho and a wildfire in Montana. The level of fire-caused tree injury differed between the two sites, and the level of tree injury most susceptible to bark beetle attack and colonization also differed. Strip-attacked trees alive 3 years post-fire had lower levels of bole and crown injury than trees mass attacked and killed by bark beetles, suggesting that fire-injured trees were less well defended. Brood production of western pine beetle ( Dendroctonus brevicomis LeConte) did not differ between fire-injured and uninjured trees, although mountain pine beetle ( Dendroctonus ponderosae Hopkins) brood production was low in both tree types, potentially due to competition with faster developing bark beetle species that also colonized trees. Despite a large number of live trees remaining at both sites, bark beetle response to fire-injured trees pulsed and receded within 2 years post-fire, potentially due to a limited number of trees that could be easily colonized.
Supervised patient similarity measure of heterogeneous patient records
Authors: Sun Jimeng , Wang Fei , Hu Jianying , Edabollahi Shahram 
Published: December 2012

Patient similarity assessment is an important task in the context of patient cohort identif cation for comparative effectiveness studies and clinical decision support applications. The goal is to derive clinically meaningful distance metric to measure the similarity between patients represented by their key clinical indicators. How to incorporate physician feedback with regard to the retrieval results? How to interactively update the underlying similarity measure based on the feedback? Moreover, often different physicians have different understandings of patient similarity based on their patient cohorts. The distance metric learned for each individual physician often leads to a limited view of the true underlying distance metric. How to integrate the individual distance metrics from each physician into a globally consistent unif ed metric?
We describe a suite of supervised metric learning approaches that answer the above questions. In particular, we present Locally Supervised Metric Learning (LSML) to learn a generalized Mahalanobis distance that is tailored toward physician feedback. Then we describe the interactive metric learning (iMet) method that can incrementally update an existing metric based on physician feedback in an online fashion. To combine multiple similarity measures from multiple physicians, we present Composite Distance Integration (Comdi) method. In this approach we f rst construct discriminative neighborhoods from each individual metrics, then combine them into a single optimal distance metric. Finally, we present a clinical decision support prototype system powered by the proposed patient similarity methods, and evaluate the proposed methods using real EHR data against several baselines.