bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high‐fat diet
Authors: Leontieva Olga V. , Paszkiewicz Geraldine M. , Blagosklonny Mikhail V. 
Published: March 2014

SummaryRecent discoveries have revealed the key role of mTOR (target of rapamycin) in aging. Furthermore, rapamycin extends lifespan in mice, especially in female mice. Here, we treated obese male mice on high‐fat diet with rapamycin given intermittently: either weekly (once a week) or alternating bi‐weekly (three injections every other week). While only marginally reducing obesity, intermittent administration of rapamycin significantly extended lifespan. Significance was achieved for weekly treated group and for the three rapamycin‐received groups combined. In weekly treatment group, 100% mice were alive by the age of 2 years, whereas 60% of mice died in untreated group by this age. The effect of weekly treatment on survival was highly significant and cannot be fully explained by partial reduction in obesity. Alternating bi‐weekly treatments seem to be less effective than weekly treatment, although effects of additional factors (see ) may not be excluded. After one year of treatment, all survived mice were sacrificed 8 days after the last administration of rapamycin to avoid its direct interference with parameters examined. Fasting levels of cardiac and hepatic p‐S6, a marker of mTORC1 activity, were lower in weekly treatment group compared with control mice. In contrast, levels of p‐Akt (S473), glucose, triglycerides and insulin were unchanged, whereas leptin and IGF‐1 tended to be lower. Thus, weekly treatment with rapamycin may slow down aging in obese male mice on high‐fat diet.
The diversity of young adult wheeze: a cluster analysis in a longitudinal birth cohort
Authors: Kurukulaaratchy R. J. , Zhang H. , Raza A. , Patil V. , Karmaus W. , Ewart S. , Arshad S. H. 
Published: March 2014

SummaryBackgroundCluster analyses have enhanced understanding of the heterogeneity of both paediatric and adult wheezing. However, while adolescence represents an important transitional phase, the nature of young adult wheeze has yet to be clearly characterised.ObjectivesTo use cluster analysis to define, for the first time, clinically relevant young adult wheeze clusters in a longitudinal birth cohort.MethodsK‐means cluster analysis was undertaken among 309 currently wheezing subjects at 18 years in the Isle of Wight birth cohort (N = 1456). Thirteen disease‐characterising clustering variables at 18 years were used. Resulting clusters were then further characterised by severity indices plus potential risk factors for wheeze development throughout the 1st 18 years of life.ResultsSix wheeze clusters were identified. Cluster 1 (12.3%) male‐early‐childhood‐onset‐atopic‐wheeze‐with‐normal‐lung‐function had male predominance, normal spirometry, low bronchodilator reversibility (BDR), intermediate bronchial hyper‐responsiveness (BHR), high atopy prevalence and more admissions. Cluster 2 (24.2%) early‐childhood‐onset‐wheeze‐with‐intermediate‐lung‐function had no specific sex association, intermediate spirometry, BDR, BHR, more significant BTS step therapy and admissions. Cluster 3 (9.7%) female‐early‐childhood‐onset‐atopic‐wheeze‐with‐impaired‐lung‐function showed female predominance, high allergic disease comorbidity, more severe BDR and BHR, greatest airflow obstruction, high smoking prevalence, higher symptom severity and admissions. Cluster 4 (19.4%) female‐undiagnosed‐wheezers had adolescent‐onset non‐atopic wheeze, low BDR and BHR, impaired but non‐obstructed spirometry, high symptom frequency and highest smoking prevalence. Cluster 5 (24.6%) female‐late‐childhood‐onset‐wheeze‐with‐normal‐lung‐function showed no specific atopy association, normal spirometry, low BDR, BHR and symptom severity. Cluster 6 (9.7%) male‐late‐childhood‐onset‐atopic‐wheeze‐with‐impaired‐lung‐function had high atopy and rhinitis prevalence, increased BDR and BHR, moderately impaired spirometry, high symptom severity and higher BTS step therapy.Conclusions and Clinical RelevanceYoung adult wheeze is diverse and can be classified into distinct clusters. More severe clusters merit attention and are associated with childhood onset, atopy, impaired lung function and in some, smoking. Smoking‐associated undiagnosed wheezers also merit recognition. Better understanding of young adult wheeze could facilitate better later adult respiratory health.
Procollagen type I N‐terminal peptide in preterm infants is associated with growth during the first six months post‐term
Authors: van de Lagemaat Monique , van der Veer Eveline , van Weissenbruch Mirjam M. , Lafeber Harrie N. , Rotteveel Joost 
Published: March 2014

SummaryObjectiveTo identify growth‐related collagen and bone parameters in small‐for‐gestational‐age (SGA) and appropriate‐for‐gestational‐age (AGA) preterm infants during the first six months post‐term. In SGA preterm infants, increased growth and decreased bone acquisition, which we demonstrated previously, may be reflected by these markers.DesignObservational study within a randomized controlled trial.PatientsThirty‐three SGA (weight, length or both at birth <‐2 SDS) and 98 AGA preterm infants (gestational age [median (IQR)]: 31·1 (1·6) vs 30·3 (2·0) weeks; 72·7% vs 42·9% boys).MeasurementsWeight (g), length (cm), procollagen type I N‐terminal peptide (PINP; μg/l), urinary helical peptide (UHP; μg/mmol creatinine) and alkaline phosphatase (ALP; U/l) expressed as standard deviation scores (SDS) at term age, three and six months post‐term.ResultsWeight and length gain during the first six months post‐term and PINP SDS at term age, three months and six months post‐term were higher in SGA compared with AGA infants. UHP SDS and ALP SDS were similar in SGA and AGA infants. PINP SDS and UHP SDS at term age and PINP SDS at three months were associated with subsequent weight and length gain until six months post‐term.ConclusionsIncreased growth in SGA compared with AGA preterm infants is reflected by increased collagen type I synthesis during the first six months post‐term, suggesting that PINP and UHP correspond with growth in preterm infants. An explanation for decreased bone acquisition of SGA preterm infants may be that increased collagen type I synthesis is not directly followed by increased bone mineralization.
The incidence, management, and evolution of rapamycin‐related side effects in kidney transplant recipients
Authors: Verhave Jacobien , Boucher Anne , Dandavino Raymond , Collette Suzon , Senécal Lynne , Hebert Marie‐Josée , Girardin Catherine , Cardinal Héloïse 
Published: March 2014

AbstractConversion from a calcineurin‐inhibitor‐based immunosuppression to a rapamycin‐based immunosuppression may preserve kidney graft function. The side effects of rapamycin can limit its usefulness, but their management and evolution are rarely reported in clinical trials. We performed a retrospective cohort study in patients transplanted before December 31, 2008 and who received rapamycin to replace calcineurin inhibitors. In 219 patients studied, 98% presented ≥1 side effects after starting rapamycin. Side effects occurring in ≥10% of patients were dyslipidemia (52%, 95% confidence interval (CI): 45–59%), peripheral edema (37%, 95%CI: 31–43%), cytopenia (36%, 95% CI: 30–42%), acne (29%, 95% CI: 23–35%), proteinuria (23%, 95% CI: 17–29%), and oral ulcers 14% (95% CI: 10–18%). Proteinuria, ulcers, and edema were difficult to manage and were more likely to cause cessation of rapamycin. Rapamycin was discontinued in 46% of patients (95% CI: 40–52%). Age (odds ratio [OR] per 10‐yr increase: 1.29, 95% CI: 1.05–1.59) and obesity (OR: 2.57, 95% CI: 1.10–6.01) were independently associated with cessation of rapamycin. We conclude that successful control of dyslipidemia and cytopenia can be achieved without discontinuing rapamycin. Most other side effects are harder to manage. Leaner and younger patients are less likely to discontinue rapamycin due to side effects.
Renal retransplantation after kidney and pancreas transplantation using the renal vessels of the failed allograft: pitfalls and pearls
Authors: Chedid Marcio F. , Moreno Gonzales Manuel , Raghavaiah Suresh , Chauhan Ashutosh , Taner Timucin , Nedredal Geir I. , Park Walter D. , Stegall Mark D. 
Published: March 2014

AbstractRenal retransplantation after a failed prior kidney and pancreas transplant is being increasingly performed. In these complex cases, both iliac fossae have been used for prior transplants, and the placement of the new allograft can be problematic. We describe our experience with an alternative technique for renal retransplantation (RRTx) in the setting of severe bilateral aortoiliac atherosclerosis or scarring and fibrosis on the iliac vessels. Nephrectomy of the failed allograft is performed, and the renal vessels of the failed allograft (RVFA) are preserved. The new kidney is implanted on RVFA at the same operative time. This technique was attempted and successfully accomplished in a total of six patients (mean operative time = 240 ± 63 min). One postoperative complication occurred: poor arterial inflow to the allograft, being corrected reoperatively. Hospitalizations ranged from five to eight d. Five of the six patients were alive with a functioning allograft at last follow‐up (a single graft failure occurred 21 months postoperatively in the setting of post‐transplant lymphoproliferative disease that also led to patient death). Renal vessels of the failed allograft seem to be suitable alternative vascular conduits for renal retransplantation after prior kidney and pancreas transplants.
Improved survival outcomes in patients with non‐alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002–2012 United Network for Organ Sharing data
Authors: Wong Robert J. , Chou Christina , Bonham Clark A. , Concepcion Waldo , Esquivel Carlos O. , Ahmed Aijaz 
Published: March 2014

AbstractThere is an increasing trend of patients with hepatocellular carcinoma (HCC) and non‐alcoholic fatty liver disease undergoing liver transplantation in the US. Our study utilized data from the 2002 to 2012 United Network for Organ Sharing registry to evaluate model for end‐stage liver disease era trends in US liver transplantations focused on patients with non‐alcoholic steatohepatitis (NASH), hepatitis C (HCV), alcoholic liver disease (ALD), and HCC. Survival outcomes were stratified by liver disease etiology and compared across time periods using Kaplan–Meier and Cox proportional hazards models. Patients with NASH were more likely to be women, had higher body mass index (BMI), and had higher prevalence of diabetes and cardiac disease. However, overall long‐term survival was significantly higher in patients with NASH and ALD (p < 0.001). Compared to HCV, patients with NASH had significantly higher post‐transplantation survival (HR 0.69, 95% CI 0.63–0.77), and lower risk of graft failure (HR 0.76, 95% CI 0.69–0.83). Despite having higher BMI and higher prevalence of diabetes and cardiac disease, patients with NASH had better post‐liver transplantation survival compared to patients with HCV or HCC. Patients with ALD also had superior survival outcomes. However, these survival differences were limited to patients without HCC that underwent liver transplantation.
Correlation between CT‐based measured renal volumes and nuclear‐renography‐based split renal function in living kidney donors. Clinical diagnostic utility and practice patterns
Authors: Diez Alejandro , Powelson John , Sundaram Chandru P. , Taber Tim E. , Mujtaba Muhammad A. , Yaqub Muhammad S. , Mishler Dennis P. , Goggins William C. , Sharfuddin Asif A. 
Published: March 2014

AbstractIntroductionLiving donor evaluation involves imaging to determine the choice of kidney for nephrectomy. Our aim was to study the diagnostic accuracy and correlation between CT‐based volume measurements and split renal function (SRF) as measured by nuclear renography in potential living donors and its impact on kidney selection decision.MethodsWe analyzed 190 CT‐based volume measurements in healthy donors, of which 65 donors had a radionuclide study performed to determine SRF.ResultsThere were no differences in demographics, anthropometric measurements, total volumes, eGFR, creatinine clearances between those who required a nuclear scan and those who did not. There was a significant correlation between CT‐volume‐measurement‐based SRF and nuclear‐scan‐based SRF (Pearson coefficient r 0.59; p < 0.001). Furthermore, selective nuclear‐based SRF allowed careful selection of donor nephrectomy, leaving the donor with the higher functioning kidney in most cases. There was also a significantly higher number of right‐sided nephrectomies selected after nuclear‐based SRF studies.ConclusionCT‐based volume measurements in living donor imaging have sufficient correlation with nuclear‐based SRF. Selective use of nuclear‐scan‐based SRF allows careful selection for donor nephrectomy.
SPAK mediates KCC3‐enhanced cervical cancer tumorigenesis
Authors: Chiu Min‐Hsi , Liu Hsiao‐Sheng , Wu Yi‐Hui , Shen Meng‐Ru , Chou Cheng‐Yang 
Published: March 2014

Ste20‐related proline/alanine‐rich kinase (SPAK) plays a role in regulating many biological activities, and interacts with K‐Cl co‐transporter 3 (KCC3); however, the importance of SPAK for KCC3 function has not been demonstrated. Here, we investigated the role of SPAK in KCC3‐regulated cell invasiveness and tumor formation. We show that induction of KCC3 expression triggers activation of the NF‐κB and SPAK signaling cascades, leading to activation of p38 mitogen‐activated protein kinase (MAPK) and matrix metalloproteinase‐2 (MMP2). A small interference RNA‐mediated reduction in SPAK protein levels suppressed the invasive ability and oncogenic potential of cervical cancer cells, and decreased tumor formation in mouse xenografts. A combination of experimental approaches, including RT‐PCR and real‐time RT‐PCR, gelatin zymography, NF‐κB luciferase activity and chromatin immunoprecipitation assays, showed that the induction of KCC3 over‐expression increased MMP2 expression and augmented binding of NF‐κB to its putative SPAK promoter binding site, suggesting that the SPAK/MMP2 axis is up‐regulated by NF‐κB. Pharmacological inhibition of NF‐κB or MMP2 abrogated KCC3‐triggered, SPAK‐dependent cell invasiveness. Furthermore, p38 MAPK was identified as the upstream regulator of KCC3‐dependent MMP2 activation. We conclude that SPAK may promote KCC3‐mediated tumor aggressiveness via the NF‐κB/p38 MAPK/MMP2 axis.Structured digital abstractKCC3 physically interacts with SPAK by anti-bait co-immunoprecipitation (view interaction)
Structure of a novel farnesylated bilin from an insect – formation by α‐cleavage of heme A of mitochondrial cytochrome c oxidases?
Authors: Kayser Hartmut , Wray Victor , Nimtz Manfred 
Published: March 2014

Biliproteins are present in almost all forms of life, and many of them play vital roles in photobiology. The bilin ligand of a recently characterized 500‐kDa biliprotein from an insect has been isolated and its structure elucidated with chemical and spectroscopic techniques (UV–visible, IR, MS, NMR, and CD). This blue pigment, named CV‐bilin, represents a unique high molecular mass derivative of biliverdin IXα, with an unusual 10E‐configuration and a molecular mass of 852 Da, corresponding to C48H60N4O10. The high mass of this open‐chain tetrapyrrole results from the presence of an epoxi‐dihydroxyethylfarnesyl substituent at C‐18 and a hydroxymethyl substituent at C‐13. This substitution pattern exactly reflects that of heme A of mitochondrial cytochrome c oxidases with a hydroxyethylfarnesyl chain and a formyl group at corresponding positions of the cyclic tetrapyrrole. As no other natural product is known to show these structural features (heme O, the precursor of heme A, has a methyl group at C‐13), this bilin is presumed to be derived from heme A by cleavage of the α‐methine bridge and oxidative modifications at C‐13 and the hydroxyethylfarnesyl chain. Possibly, a bilin structurally related to this insect bilin is also produced in other organisms as a result of mitochondrial turnover or degradation. As CV‐bilin in complex with a specific protein is accumulated at the end of larval life, stored in the pupa, and finally transferred to the oocytes, a possible role of the free or protein‐bound pigment in egg or embryonic development is discussed.
Basaltic diversity at the Apollo 12 landing site: Inferences from petrologic examinations of the soil sample 12003
Authors: Snape Joshua F. , Joy Katherine H. , Crawford Ian A. , Alexander Louise 
Published: March 2014

AbstractA detailed petrologic survey has been made of 17 basaltic chips (sized between 1 and 10 mm) from the 12003 soil sample as part of an ongoing study of basaltic diversity at the Apollo 12 landing site. An attempt has been made to classify these samples according to the well‐established grouping of olivine, pigeonite, ilmenite, and feldspathic basalts. Particular attention has been paid to variations in major, minor, and trace element mineral chemistry (determined by electron microprobe analysis and laser ablation ICP‐MS), which may be indicative of particular basaltic suites and less susceptible to sampling bias than bulk sample characteristics. Examples of all three main (olivine, pigeonite, and ilmenite) basaltic suites have been identified within the 12003 soil. One sample is identified as a possible new addition to the feldspathic suite, which currently consists of only one other confirmed sample. Identification of additional feldspathic basalts strengthens the argument that they represent a poorly sampled basaltic flow local to the Apollo 12 site, rather than exotic material introduced to the site by impact mixing processes. Three samples are identified as representing members of one or two previously unrecognized basaltic suites.
VEGF‐C Induces Lymphangiogenesis and Angiogenesis in the Rat Mesentery Culture Model
Authors: Sweat Richard S. , Sloas David C. , Murfee Walter L. 
Published: March 2014

AbstractObjectiveLymphatic and blood microvascular systems are critical for tissue function. Insights into the coordination of both systems can be gained by investigating the relationships between lymphangiogenesis and angiogenesis. Recently, our laboratory established the rat mesentery culture model as a novel tool to investigate multicellular interactions during angiogenesis in an intact microvascular network scenario. The objective of this study was to determine whether the rat mesentery culture model can be used to study lymphangiogenesis.MethodsMesenteric tissue windows were harvested from adult male Wistar rats and cultured for three or five days in either serum‐free MEM or MEM supplemented with VEGF‐C. Tissues were immunolabeled for PECAM and LYVE‐1 to identify blood and lymphatic endothelial cells, respectively. Tissues selected randomly from those containing vascular networks were quantified for angiogenesis and lymphangiogenesis.ResultsVEGF‐C treatment resulted in an increase in the density of blood vessel sprouting compared to controls by day 3. By day 5, lymphatic sprouting was increased compared to controls.ConclusionsThese results are consistent with in vivo findings that lymphangiogenesis lags angiogenesis after chronic stimulation and establish a tool for investigating the interrelationships between lymphangiogenesis and angiogenesis in a multisystem microvascular environment.
Identification and suppression of the p‐coumaroyl CoA:hydroxycinnamyl alcohol transferase in Zea mays L.
Authors: Marita Jane M. , Hatfield Ronald D. , Rancour David M. , Frost Kenneth E. 
Published: March 2014

SummaryGrasses, such as Zea mays L. (maize), contain relatively high levels of p‐coumarates (pCA) within their cell walls. Incorporation of pCA into cell walls is believed to be due to a hydroxycinnamyl transferase that couples pCA to monolignols. To understand the role of pCA in maize development, the p‐coumaroyl CoA:hydroxycinnamyl alcohol transferase (pCAT) was isolated and purified from maize stems. Purified pCAT was subjected to partial trypsin digestion, and peptides were sequenced by tandem mass spectrometry. TBLASTN analysis of the acquired peptide sequences identified a single full‐length maize cDNA clone encoding all the peptide sequences obtained from the purified enzyme. The cDNA clone was obtained and used to generate an RNAi construct for suppressing pCAT expression in maize. Here we describe the effects of suppression of pCAT in maize. Primary screening of transgenic maize seedling leaves using a new rapid analytical platform was used to identify plants with decreased amounts of pCA. Using this screening method, mature leaves from fully developed plants were analyzed, confirming reduced pCA levels throughout plant development. Complete analysis of isolated cell walls from mature transgenic stems and leaves revealed that lignin levels did not change, but pCA levels decreased and the lignin composition was altered. Transgenic plants with the lowest levels of pCA had decreased levels of syringyl units in the lignin. Thus, altering the levels of pCAT expression in maize leads to altered lignin composition, but does not appear to alter the total amount of lignin present in the cell walls.
OsNIP3;1, a rice boric acid channel, regulates boron distribution and is essential for growth under boron‐deficient conditions
Authors: Hanaoka Hideki , Uraguchi Shimpei , Takano Junpei , Tanaka Mayuki , Fujiwara Toru 
Published: March 2014

SummaryBoron is an essential micronutrient for higher plants. Boron deficiency is an important agricultural issue because it results in loss of yield quality and/or quantity in cereals and other crops. To understand boron transport mechanisms in cereals, we characterized OsNIP3;1, a member of the major intrinsic protein family in rice (Oryza sativa L.), because OsNIP3;1 is the most similar rice gene to the Arabidopsis thaliana boric acid channel genes AtNIP5;1 and AtNIP6;1. Yeast cells expressing OsNIP3;1 imported more boric acid than control cells. GFP‐tagged OsNIP3;1 expressed in tobacco BY2 cells was localized to the plasma membrane. The accumulation of OsNIP3;1 transcript increased fivefold in roots within 6 h of the onset of boron starvation, but not in shoots. Promoter–GUS analysis suggested that OsNIP3;1 is expressed mainly in exodermal cells and steles in roots, as well as in cells around the vascular bundles in leaf sheaths and pericycle cells around the xylem in leaf blades. The growth of OsNIP3;1 RNAi plants was impaired under boron limitation. These results indicate that OsNIP3;1 functions as a boric acid channel, and is required for acclimation to boron limitation. Boron distribution among shoot tissues was altered in OsNIP3;1 knockdown plants, especially under boron‐deficient conditions. This result demonstrates that OsNIP3;1 regulates boron distribution among shoot tissues, and that the correct boron distribution is crucial for plant growth.