bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic variants in the PIWI‐piRNA pathway gene DCP1A predict melanoma disease‐specific survival
Authors: Zhang Weikang , Liu Hongliang , Yin Jieyun , Wu Wenting , Zhu Dakai , Amos Christopher I. , Fang Shenying , Lee Jeffrey E. , Li Yi , Han Jiali , Wei Qingyi
Published: September 2016

The Piwi‐piRNA pathway is important for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control and thus may be involved in cancer development. In this study, we comprehensively analyzed prognostic roles of 3,116 common SNPs in PIWI‐piRNA pathway genes in melanoma disease‐specific survival. A published genome‐wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used to identify associated SNPs, which were later validated by another GWAS from the Harvard Nurses' Health Study and Health Professionals Follow‐up Study. After multiple testing correction, we found that there were 27 common SNPs in two genes (PIWIL4 and DCP1A) with false discovery rate < 0.2 in the discovery dataset. Three tagSNPs (i.e., rs7933369 and rs508485 in PIWIL4; rs11551405 in DCP1A) were replicated. The rs11551405 A allele, located at the 3' UTR microRNA binding site of DCP1A, was associated with an increased risk of melanoma disease‐specific death in both discovery dataset [adjusted Hazards ratio (HR) = 1.66, 95% confidence interval (CI) = 1.21–2.27, p =1.50 × 10−3] and validation dataset (HR = 1.55, 95% CI = 1.03–2.34, p = 0.038), compared with the C allele, and their meta‐analysis showed an HR of 1.62 (95% CI, 1.26–2.08, p =1.55 × 10−4). Using RNA‐seq data from the 1000 Genomes Project, we found that DCP1A mRNA expression levels increased significantly with the A allele number of rs11551405. Additional large, prospective studies are needed to validate these findings.
Snus use, smoking and survival among prostate cancer patients
Authors: Wilson Kathryn M. , Markt Sarah C. , Fang Fang , Nordenvall Caroline , Rider Jennifer R. , Ye Weimin , Adami Hans‐Olov , Stattin Pär , Nyrén Olof , Mucci Lorelei A.
Published: September 2016

Smoking is associated with prostate cancer mortality. The Scandinavian smokeless tobacco product snus is a source of nicotine but not the combustion products of smoke and has not been studied with respect to prostate cancer survival. The study is nested among 9,582 men with incident prostate cancer within a prospective cohort of 336,381 Swedish construction workers. Information on tobacco use was collected at study entry between 1971 and 1992, and categorized into (i) never users of any tobacco, (ii) exclusive snus: ever users of snus only, (iii) exclusive smokers: ever smokers (cigarette, cigar and/or pipe) only and (iv) ever users of both snus and smoking. Hazard ratios for prostate cancer‐specific and total mortality for smoking and snus use based on Cox proportional hazards models adjusted for age, calendar period at diagnosis and body mass index at baseline. During 36 years of follow‐up, 4,758 patients died—2,489 due to prostate cancer. Compared to never users of tobacco, exclusive smokers were at increased risk of prostate cancer mortality (HR 1.15, 95% CI: 1.05–1.27) and total mortality (HR 1.17, 95% CI: 1.09–1.26). Exclusive snus users also had increased risks for prostate cancer mortality (HR 1.24, 95% CI: 1.03–1.49) and total mortality (HR 1.19, 95% CI: 1.04–1.37). Among men diagnosed with nonmetastatic disease, the HR for prostate cancer death among exclusive snus users was 3.17 (95% CI: 1.66–6.06). The study is limited by a single assessment of tobacco use prior to diagnosis. Snus use was associated with increased risks of prostate cancer and total mortality among prostate cancer patients. This suggests that tobacco‐related components such as nicotine or tobacco‐specific carcinogens may promote cancer progression independent of tobacco's combustion products.
Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β1 and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells
Authors: Hara Takato , Yoshida Eiko , Shinkai Yasuhiro , Yamamoto Chika , Fujiwara Yasuyuki , Kumagai Yoshito , Kaji Toshiyuki
Published: September 2016

Proteoglycans are macromolecules that consist of a core protein and one or more glycosaminoglycan side chains. A small leucine‐rich dermatan sulfate proteoglycan, biglycan, is one of the predominant types of proteoglycans synthesized by vascular endothelial cells; however, the physiological functions of biglycan are not completely understood. In the present study, bovine aortic endothelial cells in culture were transfected with small interfering RNAs for biglycan, and the expression of other proteoglycans was examined. Transforming growth factor‐β1 signaling was also investigated, because the interaction of biglycan with cytokines has been reported. Biglycan was found to form a complex with either transforming growth factor‐β1 or the transforming growth factor‐β1 type I receptor, ALK5, and to intensify the phosphorylation of Smad2/3, resulting in a lower expression of the transmembrane heparan sulfate proteoglycan, syndecan‐4. This is the first report to clarify the function of biglycan as a regulatory molecule of the ALK5–Smad2/3 TGF‐β1 signaling pathway that mediates the suppression of syndecan‐4 expression in vascular endothelial cells. J. Cell. Biochem. 118: 1087–1096, 2017. © 2016 Wiley Periodicals, Inc.
Knowledge, Skills, and Attributes of Graduate Student and Postdoctoral Mentors in Undergraduate Research Settings
Authors: Ahn Benjamin , Cox Monica F.
Published: September 2016

Background

Many undergraduate research (UR) students are mentored by graduate students or postdoctoral researchers, yet few studies have examined the mentoring knowledge, skills, and attributes (KSAs) of mentors in UR settings or assessed their beliefs about their mentoring KSAs.

Purpose

The purpose of this study was to identify important mentoring KSAs for graduate students and postdoctoral researchers who serve as mentors in engineering and science UR settings and to use these KSAs to develop a survey that mentors can use to assess their beliefs about their mentoring KSAs.

Design/Method

In Phase I of the study, semistructured interviews were conducted with one postdoctoral researcher and 16 graduate students who were recognized by their students as outstanding mentors. In Phase II, survey items were created from the results of Phase I for assessing the beliefs of graduate students and postdoctoral researchers about their mentoring KSAs.

Results

The study identified important mentoring KSAs and produced a 30‐item survey that assesses the beliefs of mentors about their mentoring KSAs; the items are grouped into four factors: building a positive working relationship, recognizing individual student needs and personalizing the mentoring approach, monitoring students' daily tasks, and building a personal relationship with students.

Conclusions

The study findings can help graduate students and postdoctoral researchers to become better mentors in UR settings by identifying important mentoring KSAs and by enabling them to assess their beliefs about their mentoring KSAs.
MALDI‐TOF mass spectrometry analysis of proteins and lipids in Escherichia coli exposed to copper ions and nanoparticles
Authors: Calvano C.D. , Picca R.A. , Bonerba E. , Tantillo G. , Cioffi N. , Palmisano F.
Published: September 2016

Escherichia coli (E. coli) is one of the most important foodborne pathogens to the food industry responsible for diseases as bloody diarrhea, hemorrhagic colitis and life‐threatening hemolytic–uremic syndrome. For controlling and eliminating E. coli, metal nano‐antimicrobials (NAMs) are frequently used as bioactive systems for applications in food treatments. Most NAMs provide controlled release of metal ions, eventually slowing down or completely inhibiting the growth of undesired microorganisms. Nonetheless, their antimicrobial action is not totally unraveled and is strongly dependent on metal properties and environmental conditions.

In this work, we propose the use of matrix‐assisted laser desorption ionization time‐of‐flight (MALDI TOF) mass spectrometry as a powerful tool for direct, time efficient, plausible identification of the cell membrane damage in bacterial strains exposed to copper‐based antimicrobial agents, such as soluble salts (chosen as simplified AM material) and copper nanoparticles. E. coli ATCC 25922 strain was selected as ‘training bacterium’ to set up some critical experimental parameters (i.e. cell concentration, selection of the MALDI matrix, optimal solvent composition, sample preparation method) for the MS analyses. The resulting procedure was then used to attain both protein and lipid fingerprints from E. coli after exposure to different loadings of Cu salts and NPs. Interestingly, bacteria exposed to copper showed over‐expression of copper binding proteins and degradation of lipids when treated with soluble salt. These findings were completed with other investigations, such as microbiological experiments. Copyright © 2016 John Wiley & Sons, Ltd.
Adding Career Biographies and Career Narratives to Career Interest Inventories
Authors: Burns Stephanie T. , Garcia Gayle L. , Smith Danielle M. , Goodman Stephanie R.
Published: September 2016

This study with 20 adults explored adding career biographies and career narrative writing to the career interest assessment report process. Participants reported that biographies and narratives helped them identify themes to consider how their career plans fit their personal lifestyle, meaning making, and values. This study offers 1 way to incorporate narratives and story to explore the self and self‐in‐context to activate meaning‐making processes in career interest assessment reports. Until career interest assessment reports include career biographies and a process for writing career narratives, only career counselors can offer this type of service to clients.
Outplacement Adequacy and Benefits: The Mediating Role of Overall Justice
Authors: Marzucco Laurence , Hansez Isabelle
Published: September 2016

Despite a rapid growth and an ongoing need for outplacement services, little is known about the perceived adequacy and benefits of these services for the redundant employees using them. The authors surveyed 360 Belgian redundant employees (i.e., clients) who were using outplacement services provided by a public employment agency. Results indicated that an outplacement experience that is perceived as adequate by clients fosters their overall impressions of justice toward the dismissing organization. Perceived outplacement adequacy, in turn, led to benefits for the redundant employees—namely, a reduction of negative emotions and an enhancement of their perceived well‐being, future perspectives, and job‐seeking activities—thus confirming the mediating role of overall justice.
Metabolic variations in normal and fibrotic human laryngotracheal‐derived fibroblasts: A Warburg‐like effect
Authors: Ma Garret , Samad Idris , Motz Kevin , Yin Linda X. , Duvvuri Madhavi V. , Ding Dacheng , Namba Daryan R. , Elisseeff Jennifer H. , Horton Maureen R. , Hillel Alexander T.
Published: September 2016

Objectives/Hypothesis

Laryngotracheal stenosis (LTS) is a chronic fibrotic disease characterized by fibroblast proliferation, collagen deposition, and matrix remodeling in the lamina propria of the larynx and/or trachea. Current medical therapies are limited by a poor understanding of the effector cell's (fibroblasts) cellular biology and metabolism. The purpose of this study was to compare cellular proliferation, function, and metabolism between normal and LTS‐derived fibroblasts in vitro. We hypothesize that LTS‐derived fibroblasts will demonstrate aberrant behavior with faster proliferation, increased collagen production, and altered metabolic allocation compared with normal fibroblasts.

Study Design

In vitro comparative analysis.

Methods

Human biopsies of normal and iatrogenic LTS tissue (n = 7) were obtained, and fibroblasts were isolated and cultured in vitro. Cellular proliferation, cellular histology, gene expression, and metabolic analyses were performed. Statistical analyses comparing normal and scar‐derived fibroblasts were performed.

Results

LTS fibroblast proliferation rate, cellular surface area, and collagen‐1 expression were increased compared to normal fibroblasts. Cellular metabolic analysis of LTS‐derived fibroblasts demonstrated reduced oxidative phosphorylation and increased glycolysis/oxidative phosphorylation ratio compared with normal fibroblasts.

Conclusions

Human iatrogenic LTS‐derived fibroblasts demonstrated aberrant behavior when compared with normal fibroblasts. A Warburg‐like effect was revealed, suggesting human iatrogenic LTS fibroblasts drive their proliferation with aerobic glycolysis. The distinct metabolism suggests metabolic inhibitors could reduce fibroblast hyperplasia and hypertrophy in LTS and fibrosis in general.

Level of Evidence

NA Laryngoscope, 127:E107–E113, 2017
Industrial Fiber Beam Delivery System for Ultrafast Lasers
Authors: Wedel Björn , Funck Max
Published: September 2016

Fiber optic beam delivery has been the key enabler for the wide industrial application of high power solid state cw lasers. Up until recently, fiber optic beam delivery could not be used with ultrafast lasers. Micro‐structured hollow core fibers now make it possible to confine the laser light inside a small hollow core and transmit pico‐ and femtosecond pulses of high energy with excellent beam quality. Packaged into a rugged laser light cable, this is likely the start of a new era in laser beam delivery.
Protective effect of metformin in an aberrant crypt foci model induced by 1,2‐dimethylhydrazine: Modulation of oxidative stress and inflammatory process
Authors: Bordini Heloíza Paranzini , Kremer Jean Lucas , Fagundes Tatiane Renata , Melo Gabriella Pasqual , Conchon‐Costa Ivete , da Silva Suelen Santos , Cecchini Alessandra Lourenço , Panis Carolina , Luiz Rodrigo Cabral
Published: September 2016

Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET—an anti‐hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2‐dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. © 2016 Wiley Periodicals, Inc.
Trends in adult overweight and obesity prevalence in Mongolia, 2005‐2013
Authors: Chimeddamba Oyun , Gearon Emma , Stevenson Christopher , Liviya Ng Winda , Baasai Bulganchimeg , Peeters Anna
Published: September 2016

Objective

To analyze trends in the prevalence of overweight and obesity among Mongolian adults during the past decade as measured by body mass index (BMI) and waist circumference (WC).

Methods

Data from the repeated cross‐sectional surveys on the prevalence of noncommunicable disease risk factors conducted in 2005, 2009, and 2013 in Mongolia were used. Linear regression was used to quantify trends in mean BMI and WC, adjusted for age group, sex, and survey year.

Results

The age‐standardized prevalence of obesity, denoted by the international BMI cutoff values, in men and women between 2005 and 2013 increased from 10.8% to 17.6% and from 18.9% to 26.4%, respectively. Using Asian‐specific BMI cutoff values for men and women, the age‐standardized prevalence of obesity between 2005 and 2013 increased from 20.0% to 32.8% and 33.4% to 43.7%, respectively.

Conclusions

The prevalence of overweight and obesity has increased markedly between 2005 and 2013 similarly across all age groups and sexes. It is important to consider the use of Asian‐specific cut‐offs as the burden of obesity is twice as high as when using international BMI cutoffs. These data demonstrate the urgent need for obesity treatment, prevention, and monitoring in Mongolia.
Maternal diet, gestational weight gain, and inflammatory markers during pregnancy
Authors: Hrolfsdottir Laufey , Schalkwijk Casper G. , Birgisdottir Bryndis E. , Gunnarsdottir Ingibjorg , Maslova Ekaterina , Granström Charlotta , Strøm Marin , Olsen Sjurdur F. , Halldorsson Thorhallur I.
Published: September 2016

Objective

To examine the associations of gestational weight gain (GWG) and diet with low‐grade inflammation in pregnancy.

Methods

A cross‐sectional analysis of 671 pregnant women was performed, and diet was assessed in gestational week 30. GWG was recorded in weeks 30 and ∼37 (difference between the weight recorded at these time points and pre‐pregnancy weight). Markers of inflammation, high‐sensitivity C‐reactive protein (hsCRP), serum amyloid A (SAA), interleukin (IL)−6, IL‐8, IL‐1β, and tumor necrosis factor‐α were quantified in serum from week 30.

Results

After adjusting for age, pre‐pregnancy BMI, parity, smoking status, and education, each 1 kg increase in GWG was associated with 3% (95% CI: 1–5) higher hsCRP and 3% (95% CI: 1–4) higher SAA concentrations, which corresponded to ∼18% to 25% increase in these biomarkers among those with excessive weight gain. GWG was inversely associated with IL‐8 while no associations were found for the other inflammatory markers. With respect to diet, women in the highest compared with lowest quintile of protein intake had 26% (95% CI: 3–54) higher hsCRP concentrations. This increase appeared to be driven by intake of animal protein. A similar pattern was observed for SAA.

Conclusions

Excessive GWG, as well as high intake of animal protein, was associated with higher concentrations of inflammatory factors.
Novel association of familial testicular germ cell tumor and autosomal dominant polycystic kidney disease with PKD1 mutation
Authors: Truscott Laurel , Gell Joanna , Chang Vivian Y. , Lee Hane , Strom Samuel P. , Pillai Rex , Sisk Anthony , Martinez‐Agosto Julian A. , Anderson Martin , Federman Noah
Published: September 2016

Adolescent brothers were diagnosed with testicular germ cell tumors within the same month. Both were found to have multiple renal cysts on pretreatment imaging done for staging. The proband, his brother, and their mother, were all found to have a novel splice variant in intron 8 of the PKD1 gene by clinical exome sequencing. This is the second family reported with both familial testicular germ cell tumor (FTGCT) and autosomal dominant polycystic kidney disease (ADPKD), and the first described association of FTGCT with a splice variant in PKD1. We suggest that this novel variant in PKD1 may convey increased risk for FTGCT in addition to causing ADPKD.
Genetic variation and bone mineral density in long‐term adult survivors of childhood cancer
Authors: den Hoed Marissa A. H. , Pluijm Saskia M. F. , Stolk Lisette , Uitterlinden André G. , Pieters Rob , van den Heuvel‐Eibrink Marry M.
Published: September 2016

Purpose

Despite similarities in upfront treatment of childhood cancer, not every adult survivor of childhood cancer (CCS) has an impaired bone mineral density (BMD). No data are available on the role of genetic variation on impairment of BMD in CCS.

Methods

This cross‐sectional single‐center cohort study included 334 adult CCSs (median follow‐up time after cessation of treatment: 15 years; median age at follow‐up: 26 years). Total body BMD (BMDTB) and lumbar spine BMD (BMDLS) were measured by dual x‐ray absorptiometry. We selected 12 candidate single‐nucleotide polymorphisms (SNPs) in 11 genes (COL1A1, TNFSF11, TNFRSF11, TNRFSA11B, VDR, ESR1, WLS, LRP5, MTHFR, MTRR, IL‐6).

Results

Multivariate analyses revealed that lower BMD was associated with lower weight and height at follow‐up, male sex, and previously administered radiotherapy. Survivors with the homozygous minor allele (GG) genotype of rs2504063 (ESR1: estrogen receptor type 1) had a lower BMDTB values (–1.16 vs. –0.82; P = 0.01) than those with the AG/AA genotype; however, BMDLS was not different. Carriers of two minor alleles (GG) of rs599083 (LRP5: low‐density lipoprotein receptor) revealed lower BMDTB (–1.20 vs. –0.78; P = 0.02) and lower BMDLS (–0.95 vs. –0.46; P = 0.01) values than those with the TT/TG genotype.

Conclusion

CCSs who are carriers of candidate SNPs in the ESR1 or LRP5 genes seem to have an impaired bone mass at an early adult age. Information on genetic variation, in addition to patient‐ and treatment‐related factors, may be helpful in identifying survivors who are at risk for low bone density after childhood cancer treatment.
Management of Dabigatran‐Associated Bleeding with Two Doses of Idarucizumab Plus Hemodialysis
Authors: Marino Kaylee K. , Santiago Raul A. , Dew Richard B. , Berliner Nancy , Connors Jean M. , Connell Nathan T. , Tucker John Kevin
Published: September 2016

Vitamin K antagonists have been a mainstay of treatment for patients requiring anticoagulation for atrial fibrillation, but direct oral anticoagulants, such as dabigatran, have become increasingly prescribed. Compared with warfarin, dabigatran has a significantly lower risk of life‐threatening bleeding; however, bleeding events can still occur, supporting the need for effective reversal strategies. Idarucizumab was recently approved by the U.S. Food and Drug Administration to reverse the anticoagulant effects of dabigatran when life‐threatening bleeding occurs or an urgent need for an invasive medical procedure exists. Before idarucizumab's approval, reversal strategies included hemodialysis, coagulation factor replacement, and, in the setting of acute ingestion, activated charcoal. We describe the case of a 58‐year‐old, obese woman with a history of atrial fibrillation who developed acute kidney injury while taking dabigatran 150 mg twice/day, resulting in coagulopathy. Despite receiving idarucizumab 5 g and hemodialysis, there was a rebound increase in prothrombin time (PT) and activated partial thromboplastin time (aPTT) values, prompting administration of an additional 5‐g dose of idarucizumab and continued hemodialysis, with subsequent PT and aPTT values remaining within their appropriate ranges. To our knowledge, this is the first case report to describe the successful use of repeat dosing of idarucizumab with hemodialysis to reverse the anticoagulant effects of dabigatran. Although two doses of idarucizumab were given to our patient, this dosing regimen is not the current standard of practice. Administration of idarucizumab and the use of additional reversal strategies should involve an assessment of each individual patient's severity of bleeding and subsequent risk of thrombosis. Due to the recent availability of idarucizumab and varying success with alternative reversal strategies, additional knowledge is needed for the optimal reversal of anticoagulation from dabigatran.
A Quantitative Analysis of FDA Adverse Event Reports with Oral Bisphosphonates and Clostridium difficile
Authors: McConeghy Kevin W. , Soriano Melinda M. , Danziger Larry H.
Published: September 2016

Background

Studies have shown associations between Clostridium difficile infection (CDI) and non‐antimicrobial medications including proton pump inhibitors, osteoporosis medications, and antidepressants.

Objectives

Our primary objective was to evaluate oral bisphosphonates and reported CDI adverse drug reactions in the United States using the Food and Drug Administration Adverse Event Reporting System data (FAERS).

Methods

We performed a disproportionality analysis evaluating the proportion of reports with bisphosphonates and CDI compared with other adverse drug reactions in the database. A relatively increased number of reports for a given adverse drug reaction (ADR) is termed a “signal.” Four major measures of association are used to describe reports: reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean. Drugs with statistically significant safety signals were stratified by age (18–40, 41–65, and 65+ years) and gender.

Results

Alendronate had 0.4% (103/23,603) reports with CDI. There were 0.4% (16/3672) and 0.2% (17/7945) of reports for risedronate and ibandronate, respectively. Alendronate (Fosamax) was the only drug with a significant signal using all four calculation methods. For reports with gender available, alendronate CDI ADRs were more common for women (0.45% [93/20,586]) versus men (0.25% [4/1568]), and a signal was detected with all four methods. For reports with age available, there were limited alendronate reports for those 18–39 years of age, and CDI reports were present in 0.50% (27/5350) of cases of 40–64 years and 0.49% (42/8525) of cases aged 65 or older.

Conclusion

Alendronate was associated with a high number of CDI ADRs relative to other drugs in FAERS. This signal was strongest for women and those 40 years or older. This interesting finding should be interpreted with caution, and further research is warranted.
Die Machsche Pfeife
Authors: Mathelitsch Leopold , Verovnik Ivo
Published: September 2016

Die von Ernst Mach entwickelte Pfeife ist kein Musikinstrument. Es ist ein Experiment, das die Existenz des Doppler‐Effekts ohne großen Aufwand nachweisen konnte. Aufwendigere Experimente hatte zuvor zum Beispiel Trompeter auf vorbeifahrenden Zügen eingesetzt. Machs handlicher Aufbau bestand im Kern aus einer drehbaren Röhre mit einer Pfeife an einem Ende und konnte so den Doppler‐Effekt deutlich vernehmbar produzieren. Er schrieb damit Physikgeschichte.
Astronomie unter dem Meer
Authors: Feige Jenny
Published: September 2016

Ein von Wissenschaftlern der TU München entdecktes 60Fe‐Signal wurde auf der gesamten Erde und in Mondproben nachgewiesen. Die Breite des Signals von über 1, 5 Millionen Jahren in einem Zeitbereich zwischen 1, 7 und 3, 2 Millionen Jahren lässt auf mehrere Sternexplosionen in Erdnähe schließen, die das Radionuklid zur Erde transportierten. Modellrechnungen bestätigen diese Annahme und bringen das Signal mit der Lokalen Superblase in Verbindung, deren Entstehung durch eine Reihe von Supernovae vor etwa 13 Millionen Jahren ihren Anfang nahm.
Gelatine im Eis: Physik auf allen Skalen
Authors: Vilgis Thomas
Published: September 2016

Viele Eishersteller nützen “Stabilisatoren”, zum Beispiel Gelatine, ein langes, kettenförmiges Molekül, dessen Grundbausteine, die Aminosäuren, sowohl wasserlöslich als auch wasserunlöslich sind. Dabei sind die hydrophilen Aminosäuren polar, positiv und negativ geladen. Damit bindet Gelatine viel Wasser und verleiht dem Eis einen formidablen Stand.
Key regulators of galectin–glycan interactions
Authors: Kamili Nourine A. , Arthur Connie M. , Gerner‐Smidt Christian , Tafesse Eden , Blenda Anna , Dias‐Baruffi Marcelo , Stowell Sean R.
Published: September 2016

Protein–ligand interactions serve as fundamental regulators of numerous biological processes. Among protein–ligand pairs, glycan binding proteins (GBPs) and the glycans they recognize represent unique and highly complex interactions implicated in a broad range of regulatory activities. With few exceptions, cell surface receptors and secreted proteins are heavily glycosylated. As these glycans often represent highly regulatable post‐translational modifications, alterations in glycosylation can fundamentally impact GBP recognition. Among GBPs, galectins in particular appear to engage a diverse set of glycan determinants to impact a broad range of biological processes. In this review, we will explore factors that impact galectin activity, including the effect of glycan modification on galectin–glycan interactions.
Halobenzene activation by heterofullerenes: computational investigation of oxidative addition activity
Authors: Padole Manjusha C. , Deshpande Parag A.
Published: September 2016

Potential of Pd‐ and Ni‐substituted fullerenes for oxidative addition of halobenzenes was investigated using density functional theory. The metal centers in the catalysts were found to be the potential reaction sites. Adsorption of halobenzenes was mildly exergonic over both the compounds. Activation of all halobenzenes was observed over both the compounds. Oxidative addition of C6H5I was found to be the least energy intensive process with a free energy requirement that was 3 times smaller than that for C6H5F over C59Pd. Activities of both the catalysts were found to be comparable with the end products differing in the coordination of phenyl ring with the heterofullerenes.
Interaction mode between catalytic and regulatory subunits in glucosidase II involved in ER glycoprotein quality control
Authors: Satoh Tadashi , Toshimori Takayasu , Noda Masanori , Uchiyama Susumu , Kato Koichi
Published: September 2016

The glycoside hydrolase family 31 (GH31) α‐glucosidases play vital roles in catabolic and regulated degradation, including the α‐subunit of glucosidase II (GIIα), which catalyzes trimming of the terminal glucose residues of N‐glycan in glycoprotein processing coupled with quality control in the endoplasmic reticulum (ER). Among the known GH31 enzymes, only GIIα functions with its binding partner, regulatory β‐subunit (GIIβ), which harbors a lectin domain for substrate recognition. Although the structural data have been reported for GIIα and the GIIβ lectin domain, the interaction mode between GIIα and GIIβ remains unknown. Here, we determined the structure of a complex formed between GIIα and the GIIα‐binding domain of GIIβ, thereby providing a structural basis underlying the functional extension of this unique GH31 enzyme.
Towards carbon nanotube growth into superconducting microwave resonator geometries
Authors: Blien S. , Götz K. J. G. , Stiller P. L. , Mayer T. , Huber T. , Vavra O. , Hüttel A. K.
Published: September 2016

The in‐place growth of suspended carbon nanotubes facilitates the observation of both unperturbed electronic transport spectra and high‐Q vibrational modes. For complex structures integrating, e.g., superconducting rf elements on‐chip, selection of a chemically and physically resistant material that survives the chemical vapor deposition (CVD) process provides a challenge. We demonstrate the implementation of molybdenum–rhenium coplanar waveguide resonators that exhibit clear resonant behavior at cryogenic temperatures even after having been exposed to nanotube growth conditions. The properties of the MoRe devices before and after CVD are compared to a reference niobium device.

(a) Schematic of the CVD growth environment; a metal thin film is exposed to a CH4 /H2 atmosphere at 850 °C. (b) MoRe coplanar waveguides still display superconductivity after this treatment, with clear resonant behavior of a structure.
Effect of correlation on covariate selection in linear and nonlinear mixed effect models
Authors: Bonate Peter L.
Published: September 2016

The effect of correlation among covariates on covariate selection was examined with linear and nonlinear mixed effect models. Demographic covariates were extracted from the National Health and Nutrition Examination Survey III database. Concentration‐time profiles were Monte Carlo simulated where only one covariate affected apparent oral clearance (CL/F). A series of univariate covariate population pharmacokinetic models was fit to the data and compared with the reduced model without covariate. The “best” covariate was identified using either the likelihood ratio test statistic or AIC. Weight and body surface area (calculated using Gehan and George equation, 1970) were highly correlated (r = 0.98). Body surface area was often selected as a better covariate than weight, sometimes as high as 1 in 5 times, when weight was the covariate used in the data generating mechanism. In a second simulation, parent drug concentration and three metabolites were simulated from a thorough QT study and used as covariates in a series of univariate linear mixed effects models of ddQTc interval prolongation. The covariate with the largest significant LRT statistic was deemed the “best” predictor. When the metabolite was formation‐rate limited and only parent concentrations affected ddQTc intervals the metabolite was chosen as a better predictor as often as 1 in 5 times depending on the slope of the relationship between parent concentrations and ddQTc intervals. A correlated covariate can be chosen as being a better predictor than another covariate in a linear or nonlinear population analysis by sheer correlation These results explain why for the same drug different covariates may be identified in different analyses. Copyright © 2016 John Wiley & Sons, Ltd.
A Systematic Review of the Research on Vocabulary Instruction That Impacts Text Comprehension
Authors: Wright Tanya S. , Cervetti Gina N.
Published: September 2016

Although numerous studies have identified a correlational relationship between vocabulary and comprehension, we know less about vocabulary interventions that impact reading comprehension. Therefore, this study is a systematic review of vocabulary interventions with comprehension outcomes. Analyses of 36 studies that met criteria are organized around (a) type of comprehension measure (i.e., comprehension of passages that included taught words or more generalized comprehension measures) and (b) type of intervention (i.e., direct teaching of word meanings or word‐learning strategies). The authors looked for patterns in characteristics of vocabulary instruction within these analyses. Their findings led to four major themes: (1) Teaching of word meanings supported comprehension of text containing the target words in almost all cases; (2) instruction that focused on some active processing was typically more impactful than a definition or a dictionary method for supporting comprehension of text containing the target words, but we do not know how much instruction is sufficient; (3) there is very limited evidence that direct teaching of word meanings, even long‐term, multifaceted interventions of large numbers of words, can improve generalized comprehension; and (4) there is currently no empirical evidence that instruction in one or two strategies for solving word meanings will impact generalized comprehension. However, studies that actively teach students to monitor their understanding of vocabulary and to use multiple, flexible strategies for solving word meanings are a promising area for future research. The authors discuss the implications of these themes, as well as critical avenues for future vocabulary research.
From imagery to ecology: leveraging time series of all available Landsat observations to map and monitor ecosystem state and dynamics
Authors: Pasquarella Valerie J. , Holden Christopher E. , Kaufman Les , Woodcock Curtis E.
Published: September 2016

With over 30 years of directly comparable Landsat satellite observations now freely available, and new imagery being added to the Landsat archive every day, Landsat time series analysis affords novel opportunities for ecosystem mapping, environmental monitoring and comparative ecology. This study presents a series of data‐driven examples that illustrate the potential of using Landsat time series to further the study of land cover characterization, vegetation phenology and landscape dynamics. Our goal is to showcase how ecosystem properties and dynamics manifest in the Landsat data record, laying the foundation for better integration of remote sensing and ecology using Landsat time series. Our results suggest that time series provide valuable information on ecosystem cover, use and condition that could advance understanding of ecosystem function, resilience and dynamics. We have only just begun to understand how to use the complete record of Landsat observations for the study of ecology, and we hope this work will encourage future studies on quantifying and analyzing relationships between time series data, ecosystems and ecological processes.
A marginal structural model for recurrent events in the presence of time‐dependent confounding: non‐specific effects of vaccines on child hospitalisations
Authors: Jensen Aksel K. G. , Ravn Henrik , Sørup Signe , Andersen Per
Published: September 2016

Using a Danish register‐based study on childhood vaccination and hospitalisation as motivation, a marginal structural model for recurrent events is studied. The model addresses a number of challenges which may be seen more generally in large register‐based cohort studies. One is to adjust for a time‐dependent confounder when studying the effect of a time‐varying exposure on a recurrent event based on an analysis in continuous time. Another is to report results via a measure which is easy to interpret and communicate even though quite elaborate treatment regimes are considered. Lastly, the implementation of continuously updated weights implies a substantial computationally demanding workload. Copyright © 2016 John Wiley & Sons, Ltd.
Organic–inorganic interface simulation for new material discoveries
Authors: Ramakrishnan Sathish Kumar , Zhu Jie , Gergely Csilla
Published: September 2016

Organic–inorganic interactions are of high importance in several biological processes and in modern nanobiotechnological applications. Despite its significance in interface sciences, the basic mechanism of biomolecules’ specific binding to a surface is still not well understood. Current experimental methods have not reached the level either to follow the dynamics of interactions at the picosecond scale or to observe the surface morphology at the nanoscale level. The increasing interest in bio‐interfaces particularly for engineering applications demands proteins or peptides to be designed to recognize the inorganic surface with high specificity. Molecular simulation has been well adopted in the past couple of decades to decipher the protein–surface interactions at different levels of time and length scales. Several molecular simulation methods such as quantum mechanics, atomistic, and coarse grain simulations were employed in this domain of research, but the continuous improvements in interfacial force field (FF) development, availability of experimental data and new sampling methods make the atomistic simulation more attractive due to the offered accurate representation of protein adsorption behavior at the atomic level. However, the exactitude of such simulations entirely depends on the appliedFFparameters, conformational sampling, and the solvation effects. In this overview, we briefly summarize the applicability of different simulation methods and of interfaceFFs. We also present the recent advances in the simulation of protein–surface interactions, and the challenges posed by the current simulation methods to reproduce the exact phenomenon. Future directions in this research field are also discussed.WIREs Comput Mol Sci2017, 7:e1277. doi: 10.1002/wcms.1277

This article is categorized under:

Structure and Mechanism > Computational Biochemistry and Biophysics

Structure and Mechanism > Computational Materials Science

Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods
Building and maintaining joints by exquisite local control of cell fate
Authors: Smeeton Joanna , Askary Amjad , Crump J. Gage
Published: September 2016

We owe the flexibility of our bodies to sophisticated articulations between bones. Establishment of these joints requires the integration of multiple tissue types: permanent cartilage that cushions the articulating bones, synovial membranes that enclose a lubricating fluid‐filled cavity, and a fibrous capsule and ligaments that provide structural support. Positioning the prospective joint region involves establishment of an “interzone” region of joint progenitor cells within a nascent cartilage condensation, which is achieved through the interplay of activators and inhibitors of multiple developmental signaling pathways. Within the interzone, tight regulation of BMP and TGFβ signaling prevents the hypertrophic maturation of joint chondrocytes, in part through downstream transcriptional repressors and epigenetic modulators. Synovial cells then acquire further specializations through expression of genes that promote lubrication, as well as the formation of complex structures such as cavities and entheses. Whereas genetic investigations in mice and humans have uncovered a number of regulators of joint development and homeostasis, recent work in zebrafish offers a complementary reductionist approach toward understanding joint positioning and the regulation of chondrocyte fate at joints. The complexity of building and maintaining joints may help explain why there are still few treatments for osteoarthritis, one of the most common diseases in the human population. A major challenge will be to understand how developmental abnormalities in joint structure, as well as postnatal roles for developmental genes in joint homeostasis, contribute to birth defects and degenerative diseases of joints. WIREs Dev Biol 2017, 6:e245. doi: 10.1002/wdev.245

This article is categorized under:

Gene Expression and Transcriptional Hierarchies > Cellular Differentiation

Signaling Pathways > Cell Fate Signaling

Vertebrate Organogenesis > Musculoskeletal and Vascular
Changes in the diagnosis of congenital cardiovascular malformations during the 1st year of life: impacts on epidemiological risk factor associations
Authors: Firl Kevin C. , King Jacquie S. , Makambi Kepher H. , Loffredo Christopher A.
Published: September 2016

Many epidemiological studies base their classification of congenital cardiovascular malformations in newborns upon a single, initial diagnosis. This study aimed to evaluate the effect of subsequent diagnostic investigations on the results of epidemiological studies. We used diagnostic codes from the Baltimore-Washington Infant Study from the time of birth and at ~1 year of age. Odds ratios and 95% confidence intervals were used to identify associations between changes in diagnoses and infant characteristics, time period, that is, before and after introduction of color flow Doppler imaging, and diagnostic variables. Of the 3054 patients with data at both time points, 400 (13.1%) had diagnostic changes. For congenital cardiovascular malformations of early cardiogenesis, such as laterality and looping defects, conotruncal malformations, and atrioventricular septal defects, significant associations were observed between diagnostic change and case infants large for gestational age (odds ratio=0.22, p=0.01), diagnosed initially by echocardiography only (odds ratio=2.05, p=0.001), or with non-cardiac malformations (odds ratio=0.60, p=0.03). For all other congenital cardiovascular malformations, significant associations were observed with echocardiography-only diagnosis (odds ratio=1.43, p=0.04) and non-cardiac malformations (odds ratio=0.57, p<0.001). We found no statistically significant differences between risk factor odds ratios calculated using initial diagnoses versus those calculated using 1-year update diagnoses. Changes in congenital cardiovascular malformation diagnoses from birth to year 1 interval were significantly associated with infant characteristics and diagnostic modality but did not materially affect the outcome of risk factor associations.
Tremors Reveal the Structure of Deep Glacial Shafts
Authors: Stanley Sarah
Published: September 2016

Seismic waves produced by free-falling meltwater could improve understanding of glacial drainage processes.
HSV-1-induced activation of NF-κB protects U937 monocytic cells against both virus replication and apoptosis
Authors: Marino-Merlo Francesca , Papaianni Emanuela , Medici Maria Antonietta , Macchi Beatrice , Grelli Sandro , Mosca Claudia , Borner Christoph , Mastino Antonio
Published: September 2016

The transcription factor nuclear factor-kappa B (NF-κB) is a crucial player of the antiviral innate response. Intriguingly, however, NF-κB activation is assumed to favour herpes simplex virus (HSV) infection rather than restrict it. Apoptosis, a form of innate response to viruses, is completely inhibited by HSV in fully permissive cells, but not in cells incapable to fully sustain HSV replication, such as immunocompetent cells. To resolve the intricate interplay among NF-κB signalling, apoptosis and permissiveness to HSV-1 in monocytic cells, we utilized U937 monocytic cells in which NF-κB activation was inhibited by expressing a dominant-negative IκBα. Surprisingly, viral production was increased in monocytic cells in which NF-κB was inhibited. Moreover, inhibition of NF-κB led to increased apoptosis following HSV-1 infection, associated with lysosomal membrane permeabilization. High expression of late viral proteins and induction of apoptosis occurred in distinct cells. Transcriptional analysis of known innate response genes by real-time quantitative reverse transcription-PCR excluded a contribution of the assayed genes to the observed phenomena. Thus, in monocytic cells NF-κB activation simultaneously serves as an innate process to restrict viral replication as well as a mechanism to limit the damage of an excessive apoptotic response to HSV-1 infection. This finding may clarify mechanisms controlling HSV-1 infection in monocytic cells.
RBM24 suppresses cancer progression by upregulating miR-25 to target MALAT1 in nasopharyngeal carcinoma
Authors: Hua Wen-Feng , Zhong Qian , Xia Tian-Liang , Chen Qi , Zhang Mei-Yin , Zhou Ai-Jun , Tu Zi-Wei , Qu Chen , Li Man-Zhi , Xia Yun-Fei , Wang Hui-Yun , Xie Dan , Claret Francois-Xavier , Song Er-Wei , Zeng Mu-Sheng
Published: September 2016

Abnormal interaction between non-coding RNAs has been demonstrated to be a common molecular event in various human cancers, but its significance and underlying mechanisms have not been well documented. RNA-binding proteins (RBPs) are key regulators of RNA transcription and post-transcriptional processing. In this study, we found that RNA-binding protein 24 (RBM24) was frequently downregulated in nasopharyngeal carcinoma (NPC). The restoration of RBM24 expression suppressed NPC cellular proliferation, migration and invasion and impeded metastatic colonization in mouse models. Microarray analyses revealed that miR-25 expression was upregulated by RBM24 expression in NPC cells. Similarly, ectopic miR-25 expression suppressed NPC cellular growth and motility by targeting the pro-oncogenic lncRNA MALAT1, and the knockdown of MALAT1 expression exhibited similar effects as RBM24 restoration in NPC cells. Overall, these findings suggest a novel role of RBM24 as a tumor suppressor. Mechanistically, RBM24 acts at least in part through upregulating the expression of miR-25, which in turn targets MALAT1 for degradation.