bluuebunny/crossref_metadata_2025_split huggingface dataset:
The distinct PhoPR mediated responses to phosphate limitation in Bacillus subtilis subspecies subtilis and spizizenii stem from differences in wall teichoic acid composition and metabolism
Authors: Prunty Michael P. , Noone David , Devine Kevin M. 
Published: April 2018

SummaryThe PhoPR‐mediated response to phosphate limitation (PHO response) in Bacillus subtilis subsp subtilis is amplified and maintained by reducing the level of Lipid VG composed of poly(glycerol phosphate), a wall teichoic acid (WTA) biosynthetic intermediate that inhibits PhoR autokinase activity. However, the reduction in Lipid VG level is effected by activated PhoP∼P, raising the question of how the PHO response is first initiated. Furthermore, that WTA is composed of poly(ribitol phosphate) in Bacillus subtilis subsp spizizenii prompted an investigation of how the PHO response is regulated in that bacterium. We report that the PHO responses of B. subtilis subsp subtilis and subsp spizizenii are distinct. The PhoR kinases of the two B. subtilis subspecies are functionally equivalent and are activated either by the TagA/TarA or TagB/TarB enzyme product. However, they are inhibited by Lipid VG composed of poly(glycerol phosphate) but not by Lipid VR composed of poly(ribitol phosphate). Therefore, the distinctive PHO responses of these B. subtilis subspecies stem from the differential sensitivity of PhoR kinases to the polyol composition of Lipid V and from the genomic organization of WTA biosynthetic genes and the regulation of their expression.
MLCK‐mediated intestinal permeability promotes immune activation and visceral hypersensitivity in PI‐IBS mice
Authors: Long Y. , Du L. , Kim J. J. , Chen B. , Zhu Y. , Zhang Y. , Yao S. , He H. , Zheng X. , Huang Z. , Dai N. 
Published: April 2018

AbstractBackgroundAlterations in intestinal permeability regulated by tight junctions (TJs) are associated with immune activation and visceral hypersensitivity in irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important mediator of epithelial TJ. The aim of this study is to investigate the role of MLCK in the pathogenesis of IBS using a post infectious IBS (PI‐IBS) mouse model.MethodsTrichinella spiralis‐infected PI‐IBS mouse model was used. Urine lactulose/mannitol ratio was measured to assess intestinal epithelial permeability. Western blotting was used to evaluate intestinal TJ protein (zonula occludens‐1) and MLCK‐associated protein expressions. Immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distension.ResultsEight weeks after inoculation with T. spiralis, PI‐IBS mice developed decreased pain and volume thresholds during colorectal distention, increased urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and decreased zonula occludens‐1 expression compared to the control mice. MLCK expression was dramatically elevated in the colonic mucosa of PI‐IBS mice compared to the control mice, alongside increased pMLC/MLC and decreased MLCP expression. Administration of MLCK inhibitor and TJ blocker both reversed the increased intestinal permeability, visceral hypersensitivity, and Th1‐dominant immune profile in PI‐IBS mice.ConclusionMLCK is a pivotal step in inducing increased intestinal permeability promoting low‐grade intestinal immune activation and visceral hypersensitivity in PI‐IBS mice. MLCK inhibitor may provide a potential therapeutic option in the treatment of IBS.
Colchicine may be of therapeutic benefit in prurigo pigmentosa
Authors: An Isa , Ucmak Derya , Ibiloglu Ibrahim , Demir Vasfiye , Akdeniz Sedat 
Published: April 2018

AbstractPrurigo pigmentosa (PP) is a rare inflammatory skin disease. Neutrophil‐mediated inflammation is considered to be responsible for the etiopathogenesis of PP. We consider that colchicine may be an effective agent in the treatment of PP since it exerts an antiinflammatory effect by inhibiting neutrophil chemotaxis. Further studies are required to verify whether colchicine is an effective treatment option for PP.
Zircon U–Pb and Wolframite Sm–Nd Dating of the Bayinsukhtu Tungsten Deposit in Southern Mongolia and its Geological Significance
Authors: Guo Zhihua , Zhang Baolin , Guo Bowei , Dang Yongqi , Hou Jinliang 
Published: April 2018

AbstractThe Bayinsukhtu tungsten deposit is a newly discovered quartz‐vein tungsten deposit in the Xing'an–Mongolia Orogenic Belt (XMOB) in southern Mongolia, hosted by the Bayinsukhtu granite porphyry. The granite porphyry is located mainly south of the study area, over 3 km2. The rock consists of quartz and feldspar phenocrysts in a fine‐grained matrix, also mainly composed of feldspar and quartz. The granite porphyry samples demonstrate high SiO2 and high alkalinity. All samples also straddle the high‐potassium calc‐alkaline series. In a plot of the molar ratios of A/NK versus A/CNK, the granites are metaluminous. The chondrite‐normalized REE patterns are characterized by large negative Eu anomalies and fractionated LREEs. The U–Pb age of zircons from the granite porphyry is 298.8 ± 1.8 Ma, and the Sm–Nd age of the five wolframite samples from the tungsten deposit is 303 ± 19 Ma. The cooling age of the granite porphyry and tungsten mineralization is within the error of measurement and is of the Late Carboniferous age. Geological and geochronological evidence shows that the tungsten mineralization and the granite porphyry at Bayinsukhtu are genetically closely related and that they are results of Carboniferous magmatism. Their tectonic setting is related to the accretion of the Central Asian Orogenic Belt during the late Paleozoic era.
A Single Amino Acid in the Polymerase Acidic Protein Determines the Pathogenicity of Influenza B Viruses
Authors: Bae Joon-Yong , Lee Ilseob , Kim Jin Il , Park Sehee , Yoo Kirim , Park Miso , Kim Gayeong , Park Mee Sook , Lee Joo-Yeon , Kang Chun , Kim Kisoon , Park Man-Seong 
Published: April 2018

ABSTRACT
Influenza B virus (IBV) is one of the human respiratory viruses and one of the targets of seasonal vaccination. However, the bifurcation of two antigenically distinct lineages of IBVs makes it difficult to arrange proper medical countermeasures. Moreover, compared with pathogenicity-related molecular markers known for influenza A virus, little has been known for IBVs. To understand pathogenicity caused by IBVs, we investigated the molecular determinants of IBV pathogenicity in animal models. After serial lung-to-lung passages of Victoria lineage B/Brisbane/60/2008 (Vc_BR60) and Yamagata lineage B/Wisconsin/01/2010 (Ym_WI01) viruses in BALB/c mice, we identified the mouse-adapted Vc_BR60 (maVc_BR60) and Ym_WI01 (maYm_WI01) viruses, respectively. To find a molecular clue(s) to the increased pathogenicity of maVc_BR60 and maYm_WI01, we determined their genetic sequences. Several amino acid mutations were identified in the PB2, PB1, PA, BM2, and/or NS1 protein-coding regions, and one concurrent lysine (K)-to-arginine (R) mutation in PA residue 338 (PA K338R) was found in both maVc_BR60 and maYm_WI01 viruses. When analyzed using viruses rescued through reverse genetics, it was shown that PA K338R alone could increase the pathogenicity of both IBVs in mice and viral replication in the respiratory tracts of ferrets. In a subsequent minireplicon assay, the effect of PA K338R was highlighted by the enhancement of viral polymerase complex activity of both Vc_BR60 and Ym_WI01 viruses. These results suggest that the PA K338R mutation may be a molecular determinant of IBV pathogenicity via modulating the viral polymerase function of IBVs.

IMPORTANCE
To investigate molecular pathogenic determinants of IBVs, which are one of the targets of seasonal influenza vaccines, we adapted both Victoria and Yamagata lineage IBVs independently in mice. The recovered mouse-adapted viruses exhibited increased virulence, and of the various mutations identified from both mouse-adapted viruses, a concurrent amino acid mutation was found in the PA protein-coding region. When analyzed using viruses rescued through reverse genetics, the PA mutation alone appeared to contribute to viral pathogenicity in mice within the compatible genetic constellation between the IBV lineages and to the replication of IBVs in ferrets. Regarding the potential mechanism of increased viral pathogenicity, it was shown that the PA mutation could upregulate the viral polymerase complex activity of both IBV lineages. These results indicate that the PA mutation could be a newly defined molecular pathogenic determinant of IBVs that substantiates our understanding of the viral pathogenicity and public health risks of IBVs.
Geology and vertebrate paleontology of Tule Springs Fossil Beds National Monument, Nevada, USA
Authors: Springer Kathleen B. , Pigati Jeffrey S. , Scott Eric 
Published: April 2018

ABSTRACT
Tule Springs Fossil Beds National Monument (TUSK) preserves 22,650 acres of the upper Las Vegas Wash in the northern Las Vegas Valley, Nevada, USA. TUSK is home to extensive and stratigraphically complex groundwater discharge (GWD) deposits, called the Las Vegas Formation, which represent springs and desert wetlands that covered much of the valley during the late Quaternary. The GWD deposits record hydrologic changes that occurred here in a dynamic and temporally congruent response to abrupt climatic oscillations over the last ~300 ka (thousands of years). The deposits also entomb the Tule Springs Local Fauna (TSLF), one of the most significant late Pleistocene (Rancholabrean) vertebrate assemblages in the American Southwest. The TSLF is both prolific and diverse, and includes a large mammal assemblage dominated by Mammuthus columbiandCamelops hesternus.Two and possibly three distinct species ofEquus,two species ofBison, Panthera atrox, Smilodon fatalis, Canis dirus, Megalonyx jeffersonii,andNothrotheriops shastensis are also present, and newly recognized faunal components include micromammals, amphibians, snakes, and birds. Invertebrates, plant macrofossils, and pollen also occur in the deposits and provide important and complementary paleoenvironmental information. This field compendium highlights some of the classic stratigraphic sequences of the Las Vegas Formation within TUSK, emphasizes the significant hydrologic changes that occurred in the area during the recent geologic past, and examines the subsequent and repeated effect of rapid climate change on the local desert wetland ecosystem.
Glutamate dehydrogenase: role in regulating metabolism and insulin release in pancreatic β-cells
Authors: Wilson David F. , Cember Abigail T. J. , Matschinsky Franz M. 
Published: April 2018

Regulation of insulin release and glucose homeostasis by pancreatic β-cells is dependent on the metabolism of glucose by glucokinase (GK) and the influence of that activity on oxidative phosphorylation. Genetic alterations that result in hyperactivity of mitochondrial glutamate dehydrogenase (GDH-1) can cause hypoglycemia-hyperammonemia following high protein meals, but the role of GDH-1 remains poorly understood. GDH-1 activity is strongly inhibited by GTP, to near zero in the absence of ADP, and cooperatively activated ( n = 2.3) by ADP. The dissociation constant for ADP is near 200 µM in vivo, but leucine and its nonmetabolized analog 2-amino-2-norbornane-carboxylic acid (BCH) can activate GDH-1 by increasing the affinity for ADP. Under physiological conditions, as [ADP] increases GDH-1 activity remains very low until ~35 µM (threshold) and then increases rapidly. A model for GDH-1 and its regulation has been combined with a previously published model for glucose sensing that coupled GK activity and oxidative phosphorylation. The combined model (GK-GDH-core) shows that GK activity determines the energy state ([ATP]/[ADP][Pi]) in β-cells for glucose concentrations > 5 mM ([ADP] < 35 µM). As glucose falls < 5 mM the [ADP]-dependent increase in GDH-1 activity prevents [ADP] from rising above ~70 µM. Thus, GDH-1 dynamically buffers β-cell energy metabolism during hypoglycemia, maintaining the energy state and the basal rate of insulin release. GDH-1 hyperactivity suppresses the normal increase in [ADP] in hypoglycemia. This leads to hypoglycemia following a high protein meal by increasing the basal rate of insulin release (β-cells) and decreasing glucagon release (α-cells).NEW & NOTEWORTHY A model of β-cell metabolism and regulation of insulin release is presented. The model integrates regulation of oxidative phosphorylation, glucokinase (GK), and glutamate dehydrogenase (GDH-1). GDH-1 is near equilibrium under physiological conditions, but the activity is inhibited by GTP. In hypoglycemia, however, GK activity is low and [ADP], a potent activator of GDH-1, increases. Reducing equivalents from GDH dynamically buffers the intramitochondrial [NADH]/[NAD+], and thereby the energy state, preventing hypoglycemia-induced substrate deprivation.
Outcomes of Peripheral Vascular Interventions in Select Patients With Lower Extremity Acute Limb Ischemia
Authors: Inagaki Elica , Farber Alik , Kalish Jeffrey A. , Eslami Mohammad H. , Siracuse Jeffrey J. , Eberhardt Robert T. , Rybin Denis V. , Doros Gheorghe , Hamburg Naomi M. ,   the Vascular Study Group of New England
Published: April 2018

Background

Contemporary data on patients presenting with acute limb ischemia (
ALI
), who are selected for treatment with endovascular peripheral vascular interventions (
PVI
), are limited. Our study examined outcomes following endovascular
PVI
in patients with
ALI
by comparing with patients treated for chronic critical limb ischemia using a regional quality improvement registry.

Methods and Results

Of the 11 035 patients in the Vascular Study Group of New England
PVI
database (2010–2014), we identified 365 patients treated for lower extremity
ALI
who were 5:1 frequency matched (by procedure year and arterial segments treated) to 1808 patients treated for critical limb ischemia.
ALI
patients treated with
PVI
had high burden of atherosclerotic risk factors and were more likely to have had prior ipsilateral revascularizations.
ALI
patients were less likely to be treated with self‐expanding stents and more likely to undergo thrombolysis than patients with critical limb ischemia. In multivariable analysis,
ALI
was associated with higher technical failure (odds ratio 1.7, 95% confidence interval, 1.1%–2.5%), increased rate of distal embolization (odds ratio 2.7, 95% confidence interval, 1.5%–4.9%), longer length of stay (means ratio 1.6, 95% confidence interval, 1.4%–1.8%), and higher in‐hospital mortality (odds ratio 2.8, 95% confidence interval, 1.3%–5.9%).
ALI
was not associated with risk of major amputation or mortality at 1 year.

Conclusions

In a multicenter cohort of patients treated with
PVI
, we found that
ALI
patients selected for treatment with endovascular techniques experienced greater short‐term adverse events but similar long‐term outcomes as their critical limb ischemia counterparts. Further studies are needed to refine the selection of
ALI
patients who are best served by
PVI
.
Pro‐Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction
Authors: Abernethy Abraham , Raza Sadi , Sun Jie‐Lena , Anstrom Kevin J. , Tracy Russell , Steiner Johannes , VanBuren Peter , LeWinter Martin M. 
Published: April 2018

Background

Underlying inflammation has been increasingly recognized in heart failure with a preserved ejection fraction (
HF
p
EF
). In this study we tested the hypothesis that pro‐inflammatory biomarkers are elevated in patients with acutely decompensated
HF
p
EF
(
AD
‐
HF
p
EF
) compared with patients with stable
HF
p
EF
(S‐
HF
p
EF
).

Methods and Results

Using a post hoc analysis the serum biomarkers tumor necrosis factor‐alpha, high‐sensitivity C‐reactive protein interleukin 6 and pentraxin 3 (
PTX
3) and clinical, demographic, echocardiographic‐Doppler and clinical outcomes data were analyzed in
HF
p
EF
patients enrolled in
NHLBI
Heart Failure Research Network clinical trials which enrolled patients with either
AD
‐
HF
p
EF
or S‐
HF
p
EF
. Compared to S‐
HF
p
EF
,
AD
‐
HF
p
EF
patients had higher levels of
PTX
3 (3.08 ng/
mL
versus 1.27 ng/
mL
,
P
<0.0001),
interleukin
‐6 (4.14 pg/
mL
versus 1.71 pg/
mL
,
P
<0.0001),
tumor necrosis factor‐alpha
(11.54 pg/
mL
versus 8.62 pg/
mL
,
P
=0.0015), and high‐sensitivity C‐reactive protein (11.90 mg/
dL
versus 3.42 mg/
dL
,
P
<0.0001). Moreover, high‐sensitivity C‐reactive protein,
interleukin
‐6 and
PTX
3 levels were significantly higher in
AD
‐
HF
p
EF
compared with S‐
HF
p
EF
patients admitted for decompensated
HF
within the previous year.
PTX
3 was positively correlated with left atrial volume index (
r
=0.41,
P
=0.0017) and left ventricular mass (
r
=0.26,
P
=0.0415), while tumor necrosis factor‐alpha was inversely correlated with E/A ratio (
r
=−0.31,
P
=0.0395).

Conclusions

Levels of pro‐inflammatory biomarkers are strikingly higher in
AD
‐
HF
p
EF
compared with S‐
HF
p
EF
patients.
PTX
3 and tumor necrosis factor‐alpha are correlated with echocardiographic‐Doppler evidence of diastolic dysfunction. Taken together these data support the concept that a heightened pro‐inflammatory state has a pathophysiologic role in the development of
AD
‐
HF
p
EF
.
Outcomes in Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction Undergoing Rest and Treadmill Stress Echocardiography
Authors: Huded Chetan P. , Masri Ahmad , Kusunose Kenya , Goodman Andrew L. , Grimm Richard A. , Gillinov A. Marc , Johnston Douglas R. , Rodriguez L. Leonardo , Popovic Zoran B. , Svensson Lars G. , Griffin Brian P. , Desai Milind Y. 
Published: April 2018

Background

In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess the incremental prognostic value of resting valvuloarterial impedence (Zva) and left ventricular global longitudinal strain (
LV
‐
GLS
) to treadmill stress echocardiography.

Methods and Results

We studied 504 such patients (66±12 years, 78% men, 32% with coronary artery disease who underwent treadmill stress echocardiography between 2001 and 2012. Clinical and exercise variables (% of age‐sex predicted metabolic equivalents [%
AGP
‐
MET
s]) were recorded. Resting Zva ([systolic arterial pressure+mean aortic valve gradient]/[
LV
‐stroke volume index]) and
LV
‐
GLS
(measured offline using Velocity Vector Imaging, Siemens) were obtained from the baseline resting echocardiogram. Death was the primary outcome. There were no major adverse cardiac events during treadmill stress echocardiography. Indexed aortic valve area, Zva, and
LV
‐
GLS
were 0.46±0.1 cm
2
/m
2
, 4.5±0.9 mm Hg/mL per m
2
and −16±4%, respectively; only 50% achieved >100%
AGP
‐
MET
s. Sixty‐four percent underwent aortic valve replacement. Death occurred in 164 (33%) patients over 8.9±3.6 years (2 within 30 days of aortic valve replacement). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio or
HR
1.06), lower %
AGP
‐
METS
(
HR
1.16), higher Zva (
HR
1.25) and lower
LV
‐
GLS
(
HR
1.12) were associated with higher longer‐term mortality, while aortic valve replacement (
HR
0.45) was associated with improved survival (all
P
<0.01). Sequential addition of
ZV
a and
LV
‐
GLS
to clinical model (Society of Thoracic Surgeons score and %
AGP
‐
MET
s) increased the c‐statistic from 0.65 to 0.69 and 0.75, respectively, both
P
<0.001); findings were similar in the subgroup of patients who underwent aortic valve replacement.

Conclusions

In asymptomatic patients with severe aortic stenosis undergoing treadmill stress echocardiography,
LV
‐
GLS
and
ZV
a offer incremental prognostic value.
Outcome Prediction in Acute Stroke Patients by Continuous Glucose Monitoring
Authors: Wada Shinichi , Yoshimura Sohei , Inoue Manabu , Matsuki Takayuki , Arihiro Shoji , Koga Masatoshi , Kitazono Takanari , Makino Hisashi , Hosoda Kiminori , Ihara Masafumi , Toyoda Kazunori 
Published: April 2018

Background
The purpose of this study was to examine the relationships between glucose parameters obtained by continuous glucose monitoring and clinical outcomes in acute stroke patients.

Methods and Results

Consecutive patients with acute ischemic stroke or intracerebral hemorrhage within 24 hours after onset were included. A
continuous glucose monitoring
device (
iP
ro2) was attached for the initial 72 hours after emergent admission. Eight glucose parameters were obtained from
continuous glucose monitoring
: maximum, minimum, mean, and SD of blood glucose levels, as well as area under the curve more than 8 mmol/L of blood glucose, distribution time more than 8 mmol/L of blood glucose, coefficient of variation (%
CV
), and presence of time less than 4 mmol/L over 72 hours. The primary outcome measure was death or dependency at 3 months (
modified Rankin Scale
score ≥3). One hundred patients with acute ischemic stroke (n=58) or intracerebral hemorrhage (n=42) were included. Blood glucose levels varied between 5.2±1.4 and 11.4±3.2 mmol/L over 72 hours, with area under the curve more than 8 mmol/L of blood glucose of 0.7±1.4 min×mmol/L, distribution time more than 8 mmol/L of blood glucose of 31.7±32.7%, coefficient of variation of 15.5±5.4%, and presence of hypoglycemia in 20% of overall patients. Mean glucose level (adjusted odds ratio, 1.60, 95% confidence interval, 1.12–2.28/1 mmol/L), area under the curve more than 8 mmol/L of blood glucose (2.13, 1.12–4.02/1 min×mmol/L), and distribution time more than 8 mmol/L of blood glucose (1.25, 1.05–1.50/10%) were related to death or dependency for overall patients, as well as for acute ischemic stroke patients (2.05, 1.15–3.65; 2.38, 1.04–5.44; 1.85, 1.10–3.10, respectively).

Conclusions
High mean glucose levels, distribution time more than 8 mmol/L of blood glucose, and areas under the curve more than 8 mmol/L of blood glucose during the initial 72 hours of acute stroke were associated with death or dependency at 3 months.
An Evaluation of a Diabetes Self-Management Education (DSME) Intervention Delivered Using Avatar-Based Technology: Certified Diabetes Educators’ Ratings and Perceptions
Authors: Duncan-Carnesciali Joanne , Wallace Barbara C. , Odlum Michelle 
Published: April 2018

Purpose The purpose of this study was to evaluate the perceptions that certified diabetes educators (CDEs), of diverse health professions, have of a culturally appropriate e-health intervention that used avatar-based technology. Methods Cross-sectional, survey-based design using quantitative and qualitative paradigms. A logic model framed the study, which centered on the broad and general concepts leading to study outcomes. In total, 198 CDEs participated in the evaluation. Participants were mostly female and represented an age range of 26 to 76 years. The profession representative of the sample was registered nurses. Study setting and data collection occurred at https://www.surveymonkey.com/r/AvatarVideoSurvey-for-Certified_Diabetes_Educators . Study instruments used were the Basic Demographics Survey (BD-13), Educational Material Use and Rating of Quality Scale (EMU-ROQ-9), Marlowe-Crowne Social Desirability Survey (MS-SOC-DES-CDE-13), Quality of Avatar Video Rating Scale (QAVRS-7), Recommend Avatar to Patients Scale (RAVTPS-3), Recommend Avatar Video to Health Professionals Scale (RAVTHP-3), and Avatar Video Applications Scale (AVAPP-1). Statistical analysis used included t tests, Pearson product moment correlations, backward stepwise regression, and content/thematic analysis. Results Age, ethnicity, Arab/Middle Eastern, Asian, and white/European descents were significant predictors of a high-quality rating of the video. Thematic and content analysis of the data revealed an overall positive perception of the video. Conclusions An e-health intervention grounded in evidence-based health behavior theories has potential to increase access to diabetes self-management education as evidenced in the ratings and perceptions of the video by CDEs.