bluuebunny/crossref_metadata_2025_split huggingface dataset:
Citrate metabolism in red blood cells stored in additive solution‐3
Authors: D'Alessandro Angelo , Nemkov Travis , Yoshida Tatsuro , Bordbar Aarash , Palsson Bernhard O. , Hansen Kirk C. 
Published: November 2016

BACKGROUNDRed blood cells (RBCs) are thought to have a relatively simple metabolic network compared to other human cell types. Recent proteomics reports challenge the notion that RBCs are mere hemoglobin carriers with limited metabolic activity. Expanding our understanding of RBC metabolism has key implications in many biomedical areas, including transfusion medicine.STUDY DESIGN AND METHODSIn‐gel digestion coupled with mass spectrometric analysis proteomics approaches were combined with state‐of‐the‐art tracing experiments by incubating leukofiltered RBCs in additive solution‐3 for up to 42 days under blood bank conditions, in presence of 13C1,2,3‐glucose, 2,2,4,4‐d‐citrate, and 13C,15N‐glutamine.RESULTSResults indicate that the pentose phosphate pathway/glycolysis ratio increases during storage in additive solution‐3. While the majority of supernatant glucose is consumed to fuel glycolysis, incorporation of glucose‐derived pentose phosphate moieties was observed in nucleoside monophosphates. Incubation with deuterated citrate indicated that citrate uptake and metabolism contribute to explain the origin of up to approximately 20% to 30% lactate that could not be explained by glucose oxidation and 2,3‐diphosphoglycerate consumption alone. Incubation with 13C,15N‐glutamine showed that glutaminolysis fuels transamination reactions and accumulation of millimolar levels of 5‐oxoproline, while de novo glutathione synthesis was not significantly active during refrigerated storage.CONCLUSIONQuantitative tracing metabolic experiments revealed that mature RBCs can metabolize other substrates than glucose, such as citrate, an observation relevant to transfusion medicine (i.e., formulation of novel additives), and other research endeavors where metabolic modulation of RBCs opens potential avenues for therapeutic interventions, such as in sickle cell disease.
Draft Genome Sequence of Methylophaga muralis Bur 1, a Haloalkaliphilic (Non-Methane-Utilizing) Methylotroph Isolated from a Soda Lake
Authors: Trotsenko Yuri A. , Shmareva Maria N. , Doronina Nina V. , Tarlachkov Sergey V. , Mustakhimov Ildar I. , Vasilenko Oleg V. 
Published: November 2016

ABSTRACT

The draft genome sequence of
Methylophaga muralis
strain Bur 1 (VKM B-3046T), a non-methane-utilizing methylotroph isolated from a soda lake, is reported here. Strain Bur 1 possesses genes for methanol and methylamine (methylamine dehydrogenase and N-methylglutamate pathway) oxidation. Genes for the biosynthesis of ectoine were also found.
A diamictite dichotomy: Glacial conveyor belts and olistostromes in the Neoproterozoic of Death Valley, California, USA
Authors: Le Heron D.P. , Tofaif S. , Vandyk T. , Ali D.O. 
Published: November 2016

Abstract
Multiple intercalations of glacially derived and slope-derived diamictites testify to the drawbacks of correlating Neoproterozoic diamictites more widely, but shed new light on the close interrelationship of these processes in the Cryogenian world. In the Neoproterozoic of Death Valley, California (USA), rifting of Rodinia occurred concomitantly with a major glacial event that deposited the Kingston Peak Formation. A new sedimentologic investigation of this formation in the Silurian Hills demonstrates, for the first time, that some diamictites are ultimately of glacial origin. Abundant dropstone textures occur in interstratified heterolithic deposits, with clasts of identical composition (gneiss, schist, granite, metabasite, quartzite) to those of boulder-bearing diamictites suggesting a common source (the glacial conveyor belt). In stark contrast, megaclast-bearing diamictites, yielding clasts of carbonate and siliciclastic preglacial strata as much as 100 m across, are interpreted as olistostromes. The occurrence of syn-sedimentary faults within the succession allows glacial versus slope-derived material to be distinguished for the first time.
Conodonts in Silurian hypersaline environments: Specialized and unexpectedly diverse
Authors: Jarochowska Emilia , Viira Viive , Einasto Rein , Nawrot Rafał , Bremer Oskar , Männik Peep , Munnecke Axel 
Published: November 2016

Abstract
Hypersaline environments are commonly assumed to be barren of metazoans and therefore are avoided by paleontologists, yet a number of early Paleozoic jawless vertebrate groups specialized to live in such settings. Sampling bias against restricted settings resulted in substantial underestimation of their diversity. Rare studies venturing into such environments yielded multiple new species of conodonts, suggesting that the diversity and habitat range of these hyperdiverse predators of the early oceans are equally underestimated. We describe here autochthonous conodont fauna from evaporite-bearing horizons from the middle Silurian of Estonia that provide evidence for efficient osmoregulation in this group. Based on a global compilation of coeval conodont assemblages, we show that marginal-marine, periodically emergent environments were characterized by higher conodont diversity than open-marine shallow settings. This diversity is due to a high number of species occurring in these environments only. The high degree of specialization is also reflected by the highest within-habitat variability (β diversity) in marginal settings. Most conodont species had narrow environmental niches and, unlike in marine invertebrates, extreme environments were inhabited by the most specialized taxa. Such environments represent a large proportion of early Paleozoic tropical epicratonic basins. Our analysis allows quantification of the degree to which mid-Silurian conodont diversity is underestimated as a result of sampling bias against marginal-marine settings.
Constraining the time scales of magmatic differentiation with U-Pb zircon geochronology
Authors: Bucholz C.E. , Eddy M.P. , Jagoutz O. , Bowring S.A. , Schmidt M.W. , Sambuu O. 
Published: November 2016

Abstract
Quantifying the time scales of magmatic differentiation is critical for understanding the rate at which silicic plutonic and volcanic rocks form. Directly dating this process is difficult because locations with both clear evidence for fractional crystallization and the accessory phases necessary for radiometric dating are rare. Early zircon saturation, however, appears to be characteristic of many high-K, arc-related melts due to their generally elevated initial Zr concentrations. Thus, high-K plutonic series are ideal candidates to study the time scales of magmatic differentiation using zircon U-Pb geochronology. This study focuses on the Dariv Igneous Complex in western Mongolia where early saturation of zircon in a suite of cogenetic, upper crustal (&lt;0.5 GPa) igneous rocks ranging from ultramafic cumulates to evolved granitoids allows us to date magmatic differentiation. Crystallization ages from six samples across the sequence indicate that magmatic fractionation from a basalt to high-silica (&gt;65 wt% SiO2) melt occurred in ≤590 ± 350 k.y. This estimate is greater than modeled time scales of conductive cooling of a single intrusion and physical segregation of minerals from a melt, suggesting that continued influx of heat through magmatic activity in the complex may have prolonged cooling and thus time scales associated with the production of silica-enriched melts.
Impact of laparoscopic versus open surgery on hospital costs for colon cancer: a population-based retrospective cohort study
Authors: Laudicella Mauro , Walsh Brendan , Munasinghe Aruna , Faiz Omar 
Published: November 2016

ObjectiveLaparoscopy is increasingly being used as an alternative to open surgery in the treatment of patients with colon cancer. The study objective is to estimate the difference in hospital costs between laparoscopic and open colon cancer surgery.DesignPopulation-based retrospective cohort study.SettingsAll acute hospitals of the National Health System in England.PopulationA total of 55 358 patients aged 30 and over with a primary diagnosis of colon cancer admitted for planned (elective) open or laparoscopic major resection between April 2006 and March 2013.Primary outcomesInpatient hospital costs during index admission and after 30 and 90 days following the index admission.ResultsPropensity score matching was used to create comparable exposed and control groups. The hospital cost of an index admission was estimated to be £1933 (95% CI 1834 to 2027; p<0.01) lower among patients who underwent laparoscopic resection. After including the first unplanned readmission following index admission, laparoscopy was £2107 (95% CI 2000 to 2215; p<0.01) less expensive at 30 days and £2202 (95% CI 2092 to 2316; p<0.01) less expensive at 90 days. The difference in cost was explained by shorter hospital stay and lower readmission rates in patients undergoing minimal access surgery. The use of laparoscopic colon cancer surgery increased 4-fold between 2006 and 2012 resulting in a total cost saving in excess of £29.3 million for the National Health Service (NHS).ConclusionsLaparoscopy is associated with lower hospital costs than open surgery in elective patients with colon cancer suitable for both interventions.
Wavelet coherence analysis of cerebral oxygenation signals measured by near-infrared spectroscopy in sailors: an exploratory, experimental study
Authors: Bu Lingguo , Li Jianfeng , Li Fangyi , Liu Heshan , Li Zengyong 
Published: November 2016

ObjectiveThe objective of this study was to assess the effects of long-term offshore work on cerebral oxygenation oscillations in sailors based on the wavelet phase coherence (WPCO) of near-infrared spectroscopy (NIRS) signals.MethodsThe fatigue severity scale (FSS) was first applied to assess the fatigue level of sailors and age-matched controls. Continuous recordings of NIRS signals were then obtained from the prefrontal lobes in 30 healthy sailors and 30 age-matched controls during the resting state. WPCO between the left and right prefrontal oscillations was analysed and Pearson correlation analysis was used to study the relationship between the FSS and the wavelet amplitude (WA), and between the FSS and the WPCO level.ResultsThe periodic oscillations of Delta (HbO2) signals were identified at six frequency intervals: I (0.6–2 Hz); II (0.145–0.6 Hz); III (0.052–0.145 Hz); IV (0.021–0.052 Hz); V (0.0095–0.021 Hz); and VI (0.005–0.0095 Hz). The WA in intervals I (F=8.823, p=0.004) and III (F=4.729, p=0.034) was significantly lower in sailors than that in the controls. The WPCO values of sailor group were significantly lower in intervals III (F=4.686, p=0.039), IV (F=4.864, p=0.036) and V (F=5.195, p=0.03) than those of the control group. In the sailor group, the WA in interval I (r=−0.799, p<0.01) and in interval III (r=−0.721, p<0.01) exhibited a negative correlation with the FSS. Also, the WPCO exhibited a negative correlation with the FSS in intervals III (r=−0.839, p<0.01), IV (r=−0.765, p<0.01) and V (r=−0.775, p<0.01) in the sailor group.ConclusionsThe negative correlation between WA and FSS indicates that the lower oscillatory activities might contribute to the development of fatigue. The low WPCO in intervals III, IV and V represents a reduced phase synchronisation of myogenic, neurogenic and endothelial metabolic activities respectively and this may suggest a decline of cognitive function.
Serine Synthesis Helps Hypoxic Cancer Stem Cells Regulate Redox
Authors: Samanta Debangshu , Semenza Gregg L. 
Published: November 2016

Abstract
Phosphoglycerate dehydrogenase (PHGDH) is the metabolic enzyme responsible for shunting the glycolytic intermediate 3-phosphoglycerate to the serine synthesis pathway. In breast cancer and several other types of cancer, increased PHGDH expression is associated with patient mortality. Early studies focused on the role of PHGDH in promoting cell proliferation in the small percentage of breast cancers with PHGDH gene amplification. However, recent studies have revealed a critical role for PHGDH and downstream enzymes of the serine synthesis pathway and one carbon metabolism in NADPH production and the maintenance of redox homeostasis, which are required for enrichment of breast cancer stem cells in response to hypoxia or chemotherapy. These results provide a mechanism for PHGDH overexpression in breast cancers in which PHGDH is not amplified and have implications for improving the response of triple-negative breast cancers to cytotoxic chemotherapy. Cancer Res; 76(22); 6458–62. ©2016 AACR.
Alcohol Consumption and the Risk of Colorectal Cancer for Mismatch Repair Gene Mutation Carriers
Authors: Dashti S. Ghazaleh , Buchanan Daniel D. , Jayasekara Harindra , Ait Ouakrim Driss , Clendenning Mark , Rosty Christophe , Winship Ingrid M. , Macrae Finlay A. , Giles Graham G. , Parry Susan , Casey Graham , Haile Robert W. , Gallinger Steven , Le Marchand Loïc , Thibodeau Stephen N. , Lindor Noralane M. , Newcomb Polly A. , Potter John D. , Baron John A. , Hopper John L. , Jenkins Mark A. , Win Aung Ko 
Published: November 2016

Abstract
Background: People with germline mutation in one of the DNA mismatch repair (MMR) genes have increased colorectal cancer risk. For these high-risk people, study findings of the relationship between alcohol consumption and colorectal cancer risk have been inconclusive.
Methods: 1,925 MMR gene mutations carriers recruited into the Colon Cancer Family Registry who had completed a questionnaire on lifestyle factors were included. Weighted Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between alcohol consumption and colorectal cancer.
Results: Colorectal cancer was diagnosed in 769 carriers (40%) at a mean (SD) age of 42.6 (10.3) years. Compared with abstention, ethanol consumption from any alcoholic beverage up to 14 g/day and &gt;28 g/day was associated with increased colorectal cancer risk (HR, 1.50; 95% CI, 1.09–2.07 and 1.69; 95% CI, 1.07–2.65, respectively; Ptrend = 0.05), and colon cancer risk (HR, 1.78; 95% CI, 1.27–2.49 and 1.94; 95% CI, 1.19–3.18, respectively; Ptrend = 0.02). However, there was no clear evidence for an association with rectal cancer risk. Also, there was no evidence for associations between consumption of individual alcoholic beverage types (beer, wine, spirits) and colorectal, colon, or rectal cancer risk.
Conclusions: Our data suggest that alcohol consumption, particularly more than 28 g/day of ethanol (∼2 standard drinks of alcohol in the United States), is associated with increased colorectal cancer risk for MMR gene mutation carriers.
Impact: Although these data suggested that alcohol consumption in MMR carriers was associated with increased colorectal cancer risk, there was no evidence of a dose-response, and not all types of alcohol consumption were associated with increased risk. Cancer Epidemiol Biomarkers Prev; 26(3); 366–75. ©2016 AACR.
High Estrogen Receptor β Expression Is Prognostic among Adjuvant Chemotherapy–Treated Patients—Results from a Population-Based Breast Cancer Cohort
Authors: Elebro Karin , Borgquist Signe , Rosendahl Ann H. , Markkula Andrea , Simonsson Maria , Jirström Karin , Rose Carsten , Ingvar Christian , Jernström Helena 
Published: November 2016

Abstract
Purpose: Isoform-specific tumor estrogen receptor β (ERβ) expression may hold prognostic information in breast cancer, especially among endocrine-treated breast cancer patients. The study's purpose was to evaluate ERβ isoform 1 (ERβ1) expression in relation to tumor characteristics, ESR2 genotypes, and prognosis in different treatment groups.
Experimental Design: A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between October 2002 and June 2012 was followed until June 2014 (median 5 years). Associations between immunohistochemical ERβ1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed.
Results: Tumor ERβ1 expression was available for 911 patients (89%) and was not associated with ESR2 genotypes. ERβ1 positivity, defined as &gt;75% (ERβ175+, 72.7%), was positively associated with established favorable tumor characteristics. Overall, ERβ175+ was associated with lower risk of breast cancer events [HRadj = 0.60; 95% confidence interval (CI), 0.41–0.89]. The magnitude of the association was larger in patients with ERα− tumors (HRadj = 0.30; 95% CI, 0.12–0.76), compared with ERα+ tumors (HRadj = 0.66; 95% CI, 0.42–1.03). Among the 232 chemotherapy-treated patients, ERβ175+ tumors were associated with lower risk of breast cancer events compared with ERβ175− tumors (HRadj = 0.31; 95% CI, 0.15–0.64). Among the 671 chemonaïve patients, ERβ175 status was not associated with the outcome.
Conclusions: High ERβ1 expression was a favorable prognostic marker in this breast cancer cohort, especially in chemotherapy-treated patients, but not in endocrine therapy–treated patients. These results warrant confirmation, preferably via a biomarker study in a previously conducted randomized trial. Clin Cancer Res; 23(3); 766–77. ©2016 AACR.
Phase Ib Trial of the Toll-like Receptor 8 Agonist, Motolimod (VTX-2337), Combined with Cetuximab in Patients with Recurrent or Metastatic SCCHN
Authors: Chow Laura Q.M. , Morishima Chihiro , Eaton Keith D. , Baik Christina S. , Goulart Bernardo H. , Anderson Leslie N. , Manjarrez Kristi L. , Dietsch Gregory N. , Bryan James Kyle , Hershberg Robert M. , Disis Mary L. , Martins Renato G. 
Published: November 2016

Abstract
Purpose: As Toll-like receptors (TLR) are key mediators of immune responses, TLR agonists may be important for augmenting the efficacy of therapies for squamous cell carcinoma of the head and neck (SCCHN). Motolimod (VTX-2337), a selective small-molecule agonist of TLR8, stimulates natural killer (NK) cells, dendritic cells, and monocytes. A phase Ib clinical trial assessed the safety and antitumor activity of motolimod in combination with cetuximab in patients with SCCHN. Correlative biomarkers of immune activity were explored.
Experimental Design: Thirteen patients with recurrent or metastatic SCCHN were enrolled in this open-label, dose–escalation study using a standard 3 + 3 design. Doses of motolimod (2.5, 3.0, or 3.5 mg/m2) were given on days 1, 8, and 15, in combination with fixed weekly doses of cetuximab in 28-day cycles.
Results: There were no protocol-defined dose-limiting toxicities, drug-related deaths, or evidence of synergistic toxicities between motolimod and cetuximab. Clinical tolerability at the 3.5 mg/m2 dose level was not optimal for repeated dosing and 3.0 mg/m2 was identified as the MTD. Two patients achieved partial responses for an overall response rate of 15%. Five patients had disease stabilization equating to a disease control rate of 54%. Statistically significant increases in plasma cytokines and in the frequency and activation of circulating NK cells were observed.
Conclusions: Motolimod can be safely administered in combination with cetuximab with an acceptable toxicity profile. Encouraging antitumor activity and robust pharmacodynamic responses were observed. Motolimod is being further investigated in a phase II trial in patients with SCCHN (ClinicalTrials.gov ID: NCT01836029). Clin Cancer Res; 23(10); 2442–50. ©2016 AACR.
Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes
Authors: Bianchi Roberta , Russo Erica , Bachmann Samia B. , Proulx Steven T. , Sesartic Marko , Smaadahl Nora , Watson Steve P. , Buckley Christopher D. , Halin Cornelia , Detmar Michael 
Published: November 2016

Objective—
The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types. Therefore, we aimed to dissect the specific role of podoplanin expressed by adult lymphatic vessels.

Approach and Results—

We generated an inducible, lymphatic-specific podoplanin knockout mouse model (Pdpn
ΔLEC
) and induced gene deletion postnatally. Pdpn
ΔLEC
mice were viable, and their lymphatic vessels appeared morphologically normal with unaltered fluid drainage function. Intriguingly, Pdpn
ΔLEC
mice had blood-filled lymph nodes and vessels, most frequently in the neck and axillary region, and displayed a blood-filled thoracic duct, suggestive of retrograde filling of blood from the blood circulation into the lymphatic system. Histological and fluorescence-activated cell sorter analyses revealed normal lymph node organization with the presence of erythrocytes within lymph node lymphatic vessels but not surrounding high endothelial venules. Moreover, fluorescein isothiocyanate painting experiments revealed reduced dendritic cell migration to lymph nodes in Pdpn
ΔLEC
mice.

Conclusions—
These results reveal an important role of podoplanin expressed by lymphatic vessels in preventing postnatal blood filling of the lymphatic vascular system and in contributing to efficient dendritic cell migration to the lymph nodes.
Body growth pattern of an isolated land crab species (Johngarthia planata) (Decapoda, Gercarcinidae) from the eastern tropical Pacific: an ecological approach
Authors: Sanvicente-Añorve Laura , Lemus-Santana Elia , Solís-Weiss Vivianne 
Published: November 2016

This study examines the sexual differences in relative growth and morphometrical traits of the land crabJohngarthia planata(Stimpson, 1860). Individuals came from Clipperton, where an expedition was conducted in April 2015. A total of 275 individuals were captured manually, sexed and measured in seven dimensions from the carapace and chelae. Measurements were fitted to a power function to analyse the degree of allometry in growth. Results indicated that males had larger body and chelae sizes than females. For both sexes growth was negatively allometric for the carapace and positively allometric for the chelae. We hypothesize that stronger bodies in males confer advantages during intraspecific combats and their enlarged chelae are associated to their sexual behaviour. For each sex, measurements of both right and left chelae showed a homochelic condition. We suggest that these symmetrical features provide stability and balance to their body when feeding, fighting or excavating their burrows.