bluuebunny/crossref_metadata_2025 huggingface dataset:
Body Mass Index and Stump Morphology Predict an Increased Incidence of Pancreatic Fistula After Pancreaticoduodenectomy
Authors: Fang Chi‐hua , Chen Qing‐shan , Yang Jian , Xiang Fei , Fang Zhao‐shan , Zhu Wen
Published: January 2016

Background

A majority of factors associated with the occurrence of clinical relevant postoperative pancreatic fistula (CR‐POPF) after pancreaticoduodenectomy (PD) can only be identified intra‐ or postoperatively. There are no reports for assessing the morphological features of pancreatic stump and analyzing its influence on CR‐POPF risk after PD preoperatively.

Method

A total of 90 patients underwent PD between April 2012 and May 2014 in our hospital were included. Preoperative computed tomographic (CT) images were imported into the Medical Image Three‐Dimensional Visualization System (MI‐3DVS) for acquiring the morphological features of pancreatic stump. The demographics, laboratory test and morphological features of pancreatic stump were recorded prospectively. The clinical course was evaluated focusing on the occurrence of pancreatic fistula as defined by the International Study Group on Pancreatic Fistula (ISGPF). Logistic regression analysis was used to identify independent predictors of CR‐POPF.

Results

CR‐POPF occurred in 18 patients (14 grade B, 4 grade C). In univariate analysis, male gender (P = 0.026), body mass index (BMI) ≥ 25.3 kg/m2 (P = 0.002), main pancreas duct diameter (MPDD) < 3.1 mm (P = 0.005), remnant pancreatic parenchymal volume (RPPV) > 27.8 mL (P < 0.001), and area of cut surface (AOCS) > 222.3 mm2 (P < 0.001) were associated with an increased risk of CR‐POPF. In multivariate analysis, BMI ≥ 25.3 kg/m2 (OR 12.238, 95 % CI 1.822–82.215, P = 0.010) and RPPV > 27.8 mL (OR 12.907, 95 % CI 1.602–104.004, P = 0.016) were the only independent risk factors associated with CR‐POPF. A cut‐off value of 27.8 mL for RPPV established based on the receiver operating characteristic (ROC) curve, which was the strongest single predictive factor for CR‐POPF, with a sensitivity and specificity of 77.8 and 86.1 %, respectively. The area under the ROC curve of RPPV was 0.770 (95 % CI 0.629–0.911, P < 0.001).

Conclusions

Our study demonstrated that CR‐POPF is correlated with BMI and RRPV. MI‐3DVS provides us a novel and convenient method for measuring the RPPV. Preoperative acquisition of RPPV and BMI may help the surgeons in fitting postoperative management to patient’s individual risk after PD.
Optimization of growth medium for Sporosarcina pasteurii in bio-based cement pastes to mitigate delay in hydration kinetics
Authors: Williams Sarah L , Kirisits Mary Jo , Ferron Raissa Douglas
Published: January 2016

Microbial-induced calcium carbonate precipitation has been identified as a novel method to improve durability and remediate cracks in concrete. One way to introduce microorganisms to concrete is by replacing the mixing water with a bacterial culture in nutrient medium. In the literature, yeast extract often has been used as a carbon source for this application; however, severe retardation of hydration kinetics has been observed when yeast extract is added to cement. This study investigates the suitability of alternative carbon sources to replace yeast extract for microbial-induced calcium carbonate precipitation in cement-based materials. A combination of meat extract and sodium acetate was identified as a suitable replacement in growth medium for Sporosarcina pasteurii; this alternative growth medium reduced retardation by 75 % (as compared to yeast extract) without compromising bacterial growth, urea hydrolysis, cell zeta potential, and ability to promote calcium carbonate formation.
Mouse Strain Impacts Fatty Acid Uptake and Trafficking in Liver, Heart, and Brain: A Comparison of C57BL/6 and Swiss Webster Mice
Authors: Seeger D. R. , Murphy E. J.
Published: January 2016

C57BL/6 and Swiss Webster mice are used to study lipid metabolism, although differences in fatty acid uptake between these strains have not been reported. Using a steady state kinetic model, [1‐14C]16:0, [1‐14C]20:4n‐6, or [1‐14C]22:6n‐3 was infused into awake, adult male mice and uptake into liver, heart, and brain determined. The integrated area of [1‐14C]20:4n‐6 in plasma was significantly increased in C57BL/6 mice, but [1‐14C]16:0 and [1‐14C]22:6n‐3 were not different between groups. In heart, uptake of [1‐14C]20:4n‐6 was increased 1.7‐fold in C57BL/6 mice. However, trafficking of [1‐14C]22:6n‐3 into the organic fraction of heart was significantly decreased 33 % in C57BL/6 mice. Although there were limited differences in fatty acid tracer trafficking in liver or brain, [1‐14C]16:0 incorporation into liver neutral lipids was decreased 18 % in C57BL/6 mice. In heart, the amount of [1‐14C]16:0 and [1‐14C]22:6n‐3 incorporated into total phospholipids were decreased 45 and 49 %, respectively, in C57BL/6 mice. This was accounted for by a 53 and 37 % decrease in [1‐14C]16:0 and 44 and 52 % decrease in [1‐14C]22:6n‐3 entering ethanolamine glycerophospholipids and choline glycerophospholipids, respectively. In contrast, there was a significant increase in [1‐14C]20:4n‐6 esterification into all heart phospholipids of C57BL/6 mice. Although changes in uptake were limited to heart, several significant differences were found in fatty acid trafficking into heart, liver, and brain phospholipids. In summary, our data demonstrates differences in tissue fatty acid uptake and trafficking between mouse strains is an important consideration when carrying out fatty acid metabolic studies.
The role of simulation in the development of endovascular surgical skills
Authors: Nesbitt Craig Iain , Birdi Nikhil , Mafeld Sebastian , Stansby Gerrard
Published: January 2016

Endovascular trainees in the National Health Service still largely rely on the apprentice-apprenticeship model from the late 19th century. As the scope for endovascular therapy increases, due to the rapid innovation, evolution and refinement of technology, so too do patients’ therapeutic options. This climate has also opened the door for more novel training adjuncts, to address the gaps that exist in our current endovascular training curriculum. The aim of this paper is to present a succinct overview of endovascular simulation, synthesizing the trials and research behind this rapidly evolving training as well as highlighting areas where further research is required. The authors searched MEDLINE and EMBASE for relevant manuscripts on all aspects of endovascular simulation training. A comprehensive Google search was also undertaken to look for any relevant information on endovascular training courses available and any unpublished work that had been presented at relevant scientific meetings. Papers were categorized into the four models: synthetic, animal, virtual reality and human cadaver, and separate searches for evidence of skill transfer were also undertaken. Authors of novel research projects were contacted for further details of unpublished work and permission granted to report such findings in this manuscript.
An online intervention using information on the mental health-mental illness continuum to reduce stigma
Authors: Schomerus G. , Angermeyer M.C. , Baumeister S.E. , Stolzenburg S. , Link B.G. , Phelan J.C.
Published: January 2016

Background

A core component of stigma is being set apart as a distinct, dichotomously different kind of person. We examine whether information on a continuum from mental health to mental illness reduces stigma.

Method

Online survey experiment in a quota sample matching the German population for age, gender and region (n = 1679). Participants randomly received information on either (1) a continuum, (2) a strict dichotomy of mental health and mental illness, or (3) no information. We elicited continuity beliefs and stigma toward a person with schizophrenia or depression.

Results

The continuum intervention decreased perceived difference by 0.19 standard deviations (SD, P < 0.001) and increased social acceptance by 0.18 SD (P = 0.003) compared to the no-text condition. These effects were partially mediated by continuity beliefs (proportion mediated, 25% and 26%), which increased by 0.19 SD (P < 0.001). The dichotomy intervention, in turn, decreased continuity beliefs and increased notions of difference, but did not affect social acceptance.

Conclusion

Attitudes towards a person with mental illness can be improved by providing information on a mental health-mental illness continuum.
Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt‐Jakob disease
Authors: Podlesniy Petar , Llorens Franc , Golanska Ewa , Sikorska Beata , Liberski Pawel , Zerr Inga , Trullas Ramon
Published: January 2016

Introduction

Low content of cell‐free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker of early stage Alzheimer's disease (AD), but whether mtDNA is altered in a rapid neurodegenerative dementia such as Creutzfeldt‐Jakob disease is unknown.

Methods

CSF mtDNA was measured using digital polymerase chain reaction (dPCR) in two independent cohorts comprising a total of 112 patients diagnosed with sporadic Creutzfeldt‐Jakob disease (sCJD), probable AD, or non‐Alzheimer's type dementia.

Results

Patients with AD exhibit low mtDNA content in CSF compared with patients diagnosed with sCJD or with non‐Alzheimer's type dementias. The CSF concentration of mtDNA does not correlate with Aβ, t‐tau, p‐tau, and 14‐3‐3 protein levels in CSF.

Discussion

Low‐CSF mtDNA is not a consequence of brain damage and allows the differential diagnosis of AD from sCJD and other dementias. These results support the hypothesis that mtDNA in CSF is a pathophysiological biomarker of AD.
Percutaneous Tibial Nerve Stimulation Improves Female Sexual Function in Women with Overactive Bladder Syndrome
Authors: Musco Stefania , Serati Maurizio , Lombardi Giuseppe , Lumi Ermal , Parisi Annunziata Isabella , Del Popolo Giulio , Finazzi Agrò Enrico
Published: January 2016

Introduction

Percutaneous tibial nerve stimulation (PTNS) is an established treatment for overactive bladder (OAB), especially in women with other concomitant pelvic disorders, such as sexual impairment.

Aim

To evaluate the impact of PTNS on female sexual dysfunction (FSD) in women undergoing PTNS for OAB and analyze the results.

Methods

An observational prospective study was conducted in two Italian centers. Consecutive women undergoing PTNS for dry OAB were enrolled from May 2013 to June 2014. All patients were asked to complete the Female Sexual Function Index (FSFI), the OAB short-form questionnaire, and a 24-hour bladder diary at baseline and 3 months later, at the end of the PTNS course. Patients with an FSFI total score no higher than 26.55 at inclusion were considered as presenting with FSD. Patients with an FSFI total score higher than 26.55 after treatment (if the increase in FSFI score was ≥20%) were considered FSD objective responders.

Main Outcome Measures

Sexuality was assessed using the FSFI. The 24-hour bladder diary and completed OAB short-form questionnaire were assessed before and after PTNS to evaluate OAB symptoms.

Results

Forty-one women were evaluable. Twenty-one of 41 women (51%; mean age = 51 ± 10.67 years) were considered affected by FSD at inclusion. All FSFI domains showed statistically significant improvement in women with FSD (P < .05). In particular, 9 of 21 patients with FSD (43%) objectively responded (before treatment: mean FSFI total score = 18.11, range 10.8–26.3; after treatment: mean FSFI total score = 31.04, range 27.6–35). Also, women without FSD at baseline reported statistically significant improvement in their sexual function based on FSFI scores (P < .05). No significant correlations were seen between data questionnaires.

Conclusion

PTNS improves sexual function in women with dry OAB. This amelioration is independent of urinary symptoms. Further studies are needed to confirm a possible role of PTNS in treating FSD.
Circulating free xeno‐microRNAs – The new kids on the block
Authors: Fabris Linda , Calin George Adrian
Published: January 2016

The role of circulating free microRNAs (cfmiRNAs) as promising tools for cancer screening, prognosis and monitoring of anticancer therapies has been widely studied in the past decades. cfmiRNAs have all the characteristics of the perfect biomarkers owing high stability under storage and handling conditions and being detectable not only in plasma, but in almost all body fluids. Moreover, their levels in plasma are likely to resemble ones in the primary tumor. Recently, viral and plant miRNAs have been found in plasma of healthy individuals through deep sequencing technique, and subsequently the same ones were deregulated in patients. Growing body of literature is recently focusing on understanding the potential cross‐kingdom regulation of human mRNAs by miRNAs most likely absorbed with food ingestion. In this article we will review the literature concerning the xenomiRs detected in plasma and their role in influencing cancer onset and progression. XenomiRs could potentially be used not only as early screening tool, but also for patients' prognosis.
Social Anxiety, Pain Catastrophizing and Return-To-Work Self-Efficacy in chronic pain: a cross-sectional study
Authors: Thomtén Johanna , Boersma Katja , Flink Ida , Tillfors Maria
Published: January 2016

Background and aims

Returning to work after periods of sick-leave due to chronic pain problems, involve a number of situations of interpersonal nature (e.g. meeting supervisors/insurance companies to adapt work setting to present functional level, receive help from colleagues, express pain, etc.). Since chronic pain has shown co-morbidity with social anxiety, it is of interest to investigate restraining factors in return to work among chronic pain sufferers from a social perspective. Catastrophizing is identified in both pain and social anxiety as a mechanism that might fuel a continuous bias in how situations are perceived (threat) and by hindering the development of functional behavior strategies. The presence of social anxiety in chronic pain patients might be seen as a stressor that limits the individuals’ ability to effectively communicate pain-related needs to colleagues, and/or employers and therefore act as a hindering factor in return-to-work. Hence, the overall aim of this study was to examine the relationship between social anxiety, pain catastrophizing, and perceived ability to communicate pain-related needs to the work environment in a clinical pain population.

Methods

The study employed a cross-sectional design and involved 247 individuals with chronic pain (82.3% women; M
age = 44 years). Measures included the Pain catastrophizing Scale, the Social Phobia Screening Questionnaire and the communication of pain-related needs-subscale of the Return-To-Work Self-efficacy Questionnaire. Analyzes were run to examine whether social anxiety moderated the relation between pain catastrophizing, and perceived ability to communicate pain-related needs while controlling for pain severity/interference and sick leave.

Results

Social anxiety and pain catastrophizing correlated positively with each other and negatively with perceived ability to communicate pain-related needs. No support was obtained for a moderating effect of social anxiety. However, social anxiety and pain interference were each significant predictors of the individual’s confidence in being able to communicate pain-related needs to the work environment.

Conclusions

In the context of pain and work-related communication, symptoms of social anxiety was identified as being of similar importance to the outcome as pain interference, while pain severity was not associated with the individual’s confidence in communicating one’s pain-related needs.

Implications

The results implicate that fears relating to pain-related social situations at work might be central in the process of return-to-work and rehabilitation in chronic pain.
The Mysterious Ethics of High-Frequency Trading
Authors: Cooper Ricky , Davis Michael , Van Vliet Ben
Published: January 2016

The ethics of high frequency trading are obscure, due in part to the complexity of the practice. This article contributes to the existing literature of ethics in financial markets by examining a recent trend in regulation in high frequency trading, the prohibition of deception. We argue that in the financial markets almost any regulation, other than the most basic, tends to create a moral hazard and increase information asymmetry. Since the market’s job is, at least in part, price discovery, we argue that simplicity of regulation and restraint in regulation are virtues to a greater extent than in other areas of finance. This article proposes criteria for determining which high-frequency trading strategies should be regulated.
Historical Reconstruction of Submarine Earthquakes Using210Pb,137Cs, and241Am Turbidite Chronology and Radiocarbon Reservoir Age Estimation off East Taiwan
Authors: Dezileau L , Lehu R , Lallemand S , Hsu S-K , Babonneau N , Ratzov G , Lin A T , Dominguez S
Published: January 2016

Taiwan is a young and seismically active mountain belt, where a series of strong earthquakes (M>7) have occurred over the past hundred years. Identifying historical earthquakes around Taiwan is a key to better constrain the geodynamic of this active region. Sedimentological and geochemical analyses of surface sediments from one station offshore east Taiwan revealed the presence of coarse-grained layers interpreted as turbidites. The age of these layers have been determined by210Pb,137Cs, and241Am chronology. Dating of the three most recent turbidites provides ages of AD 2001±3, AD 1950±5, and AD 1928±10. The results show striking temporal correspondence of turbidite layers to large (M≥6.8) earthquakes recorded in the region since the 20th century. The chronologies of sediment layers lead us to believe that turbidites resulted from the 2003 Taitung earthquake (M 6.8), the 1951 Chengkong earthquake (M 7.1), and the 1935 Lutao earthquake (M 7.0), respectively. Such a good correlation between turbidites and high-magnitude (M≥6.8) historical and instrumental seismic events suggests that turbidite paleoseismology constitutes a valuable tool for earthquake assessment in the eastern Taiwan margin. Moreover, the modern reservoir radiocarbon age and the regional marine reservoir correction (ΔR) of the Kuroshio Current off Taiwan were estimated by comparing accelerator mass spectrometry (AMS)14C ages with ages derived from corrected210Pb profiles and historical accounts of identifiable seismic events. Such a determination is important to calibrate the14C ages of marine materials for accurate comparison of marine and continental geological records. Our calculated mean ΔR value of 232±5414C yr (n=2) is higher than its modern value of 86±4014C yr. This high value can be explained by the presence of local upwelling cells and turbulence in the Kuroshio Current, north of Green Island. These upwelling cells bring14C-depleted water to the surface, resulting in an increase of the modern ΔR value in this portion of the Kuroshio Current.
Malayalam (Namboodiri Dialect)
Authors: Namboodiripad Savithry , Garellek Marc
Published: January 2016

Malayalam ( /malajaːɭam/; ISO 639) is a Dravidian language (Southern branch) spoken by over 33 million people in India, predominantly in Kerala (Lewis, Simmons & Fenning 2013). The language is diglossic, with the formal register used in written media and orally in formal settings. Colloquial Malayalam, for which there is no standard orthography, varies by region and social community (Asher & Kumari 1997). The speech illustrated below is representative of the variety spoken by the Namboodiri subcaste of Brahmins in and around Kochi, a city in central Kerala. The Namboodiri subcaste was traditionally a land-owning priestly class, and until relatively recently, the community was very insular. Consequently, the dialect differed from standard Malayalam as it is spoken today; this is discussed in some detail in U. Namboodiripad (1989, personal communication).
Mesenchymal stem cells and immunomodulation: current status and future prospects
Authors: Gao F , Chiu S M , Motan D A L , Zhang Z , Chen L , Ji H-L , Tse H-F , Fu Q-L , Lian Q
Published: January 2016

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy.
Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response
Authors: Deuel J W , Schaer C A , Boretti F S , Opitz L , Garcia-Rubio I , Baek J H , Spahn D R , Buehler P W , Schaer D J
Published: January 2016

Intravascular hemolysis can result in hemoglobinuria with acute kidney injury. In this study we systematically explored two in vivo animal models and a related cell culture system to identify hemoglobinuria-triggered damage pathways. In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs we found that hemoglobinuria led to intrarenal conversion of ferrous Hb(Fe2+) to ferric Hb(Fe3+), accumulation of free heme and Hb-cross-linking products, enhanced 4-hydroxynonenal reactivity in renal tissue, and acute tubule injury. These changes were associated in guinea pigs with activation of a renal cortex gene expression signature indicative of oxidative stress and activation of the unfolded protein response (UPR). Tubule cells of hemolytic animals demonstrated enhanced protein expression of heme oxygenase and heat shock protein and enhanced expression of acute kidney injury-related neutrophil gelatinase-associated lipocalin. These adverse changes were completely prevented by haptoglobin treatment. The in vivo findings were extrapolated to a MS-based proteome analysis of SILAC-labeled renal epithelial cells that were exposed to free heme within a concentration range estimate of renal tubule heme exposure. These experiments confirmed that free heme is a likely trigger of tubule barrier deregulation and oxidative cell damage and reinforced the hypothesis that uncontrolled free heme could trigger the UPR as an important pathway of renal injury during hemoglobinuria.
Engineered Mott ground state in a LaTiO3+δ/LaNiO3 heterostructure
Authors: Cao Yanwei , Liu Xiaoran , Kareev M. , Choudhury D. , Middey S. , Meyers D. , Kim J.-W. , Ryan P. J. , Freeland J.W. , Chakhalian J.
Published: January 2016

In pursuit of creating cuprate-like electronic and orbital structures, artificial heterostructures based on LaNiO3 have inspired a wealth of exciting experimental and theoretical results. However, to date there is a very limited experimental understanding of the electronic and orbital states emerging from interfacial charge transfer and their connections to the modified band structure at the interface. Towards this goal, we have synthesized a prototypical superlattice composed of a correlated metal LaNiO3 and a doped Mott insulator LaTiO3+δ, and investigated its electronic structure by resonant X-ray absorption spectroscopy combined with X-ray photoemission spectroscopy, electrical transport and theory calculations. The heterostructure exhibits interfacial charge transfer from Ti to Ni sites, giving rise to an insulating ground state with orbital polarization and eg orbital band splitting. Our findings demonstrate how the control over charge at the interface can be effectively used to create exotic electronic, orbital and spin states.
Pin1At regulates PIN1 polar localization and root gravitropism
Authors: Xi Wanyan , Gong Ximing , Yang Qiaoyun , Yu Hao , Liou Yih-Cherng
Published: January 2016

Root gravitropism allows plants to establish root systems and its regulation depends on polar auxin transport mediated by PIN-FORMED (PIN) auxin transporters. PINOID (PID) and PROTEIN PHOSPHATASE 2A (PP2A) act antagonistically on reversible phosphorylation of PINs. This regulates polar PIN distribution and auxin transport. Here we show that a peptidyl-prolyl cis/trans isomerase Pin1At regulates root gravitropism. Downregulation of Pin1At suppresses root agravitropic phenotypes of pp2aa and 35S:PID, while overexpression of Pin1At affects root gravitropic responses and enhances the pp2aa agravitropic phenotype. Pin1At also affects auxin transport and polar localization of PIN1 in stele cells, which is mediated by PID and PP2A. Furthermore, Pin1At catalyses the conformational change of the phosphorylated Ser/Thr-Pro motifs of PIN1. Thus, Pin1At mediates the conformational dynamics of PIN1 and affects PID- and PP2A-mediated regulation of PIN1 polar localization, which correlates with the regulation of root gravitropism.
Erratum: Ankyrin-mediated self-protection during cell invasion by the bacterial predator Bdellovibrio bacteriovorus
Authors: Lambert Carey , Cadby Ian T. , Till Rob , Bui Nhat Khai , Lerner Thomas R. , Hughes William S. , Lee David J. , Alderwick Luke J. , Vollmer Waldemar , Sockett R. Elizabeth , Lovering Andrew L.
Published: January 2016

Nature Communications 6: Article number: 8884 (2015); Published: 2 December 2015; Updated: 21 January 2016. The original HTML version of this Article contained an error in the spelling of the author R. Elizabeth Sockett, which was incorrectly given as Elizabeth R. Sockett. This has now been corrected in the HTML.
Correction: Corrigendum: Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases
Authors: Niehues Sven , Bussmann Julia , Steffes Georg , Erdmann Ines , Köhrer Caroline , Sun Litao , Wagner Marina , Schäfer Kerstin , Wang Guangxia , Koerdt Sophia N. , Stum Morgane , Jaiswal Sumit , RajBhandary Uttam L. , Thomas Ulrich , Aberle Hermann , Burgess Robert W. , Yang Xiang-Lei , Dieterich Daniela , Storkebaum Erik
Published: January 2016

Nature Communications 6: Article number: 7520 (2015); Published: 3 July 2015; Updated: 21 January 2016. The authors inadvertently omitted Sumit Jaiswal, who was originally included in the Acknowledgements section of this Article and contributed to the cloning of transgenic constructs and the balancing of transgenic flies, from the author list.
Scaling-up Fermentation of Pichia pastoris to demonstration-scale using new methanol-feeding strategy and increased air pressure instead of pure oxygen supplement
Authors: Liu Wan-Cang , Gong Ting , Wang Qing-Hua , Liang Xiao , Chen Jing-Jing , Zhu Ping
Published: January 2016

Scaling-up of high-cell-density fermentation (HCDF) of Pichia pastoris from the lab or pilot scale to the demonstration scale possesses great significance because the latter is the final technological hurdle in the decision to go commercial. However, related investigations have rarely been reported. In this paper, we study the scaling-up processes of a recombinant P. pastoris from the pilot (10 to 100-L) to the demonstration (1,000-L) scales, which can be used to convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol by the β-xylosidase for semi-synthesis of Taxol. We demonstrated that a pure oxygen supplement can be omitted from the HCDF if the super atmospheric pressure was increased from 0.05 to 0.10 ± 0.05 MPa and we developed a new methanol feeding biomass-stat strategy (0.035 mL/g/h) with 1% dissolved oxygen and 100 g/L initial induction biomass (dry cell weight). The scaling-up was reproducible and the best results were obtained from the 1,000-L scale, featuring a shorter induction time and the highest enzyme activities and productions, respectively. The specific growth and specific production rates were also determined. This study lays a solid foundation for the commercial preparation of 10-deacetyltaxol through the recombinant yeast. It also provides a successful paradigm for scaling-up HCDF of P. pastoris to the demonstration scale.
Predicting chemotherapeutic drug combinations through gene network profiling
Authors: Nguyen Thi Thuy Trang , Chua Jacqueline Kia Kee , Seah Kwi Shan , Koo Seok Hwee , Yee Jie Yin , Yang Eugene Guorong , Lim Kim Kiat , Pang Shermaine Yu Wen , Yuen Audrey , Zhang Louxin , Ang Wee Han , Dymock Brian , Lee Edmund Jon Deoon , Chen Ee Sin
Published: January 2016

Contemporary chemotherapeutic treatments incorporate the use of several agents in combination. However, selecting the most appropriate drugs for such therapy is not necessarily an easy or straightforward task. Here, we describe a targeted approach that can facilitate the reliable selection of chemotherapeutic drug combinations through the interrogation of drug-resistance gene networks. Our method employed single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as a model of proliferating cells to delineate a drug resistance gene network using a synthetic lethality workflow. Using the results of a previous unbiased screen, we assessed the genetic overlap of doxorubicin with six other drugs harboring varied mechanisms of action. Using this fission yeast model, drug-specific ontological sub-classifications were identified through the computation of relative hypersensitivities. We found that human gastric adenocarcinoma cells can be sensitized to doxorubicin by concomitant treatment with cisplatin, an intra-DNA strand crosslinking agent and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor. Our findings point to the utility of fission yeast as a model and the differential targeting of a conserved gene interaction network when screening for successful chemotherapeutic drug combinations for human cells.
On-chip Microfluidic Multimodal Swimmer toward 3D Navigation
Authors: Barbot Antoine , Decanini Dominique , Hwang Gilgueng
Published: January 2016

Mobile microrobots have a promising future in various applications. These include targeted drug delivery, local measurement, biopsy or microassembly. Studying mobile microrobots inside microfluidics is an essential step towards such applications. But in this environment that was not designed for the robot, integration process and propulsion robustness still pose technological challenges. In this paper, we present a helical microrobot with three different motions, designed to achieve these goals. These motions are rolling, spintop motion and swimming. Through these multiple motions, microrobots are able to selectively integrate a chip through a microfluidic channel. This enables them to perform propulsion characterizations, 3D (Three Dimensional) maneuverability, particle cargo transport manipulation and exit from the chip. The microrobot selective integration inside microfluidics could lead to various in-vitro biologic or in-vivo biomedical applications.
Correction: Corrigendum: Thermal invisibility based on scattering cancellation and mantle cloaking
Authors: Farhat M. , Chen P.-Y. , Bagci H. , Amra C. , Guenneau S. , Alù A.
Published: January 2016

We theoretically and numerically analyze thermal invisibility based on the concept of scattering cancellation and mantle cloaking. We show that a small object can be made completely invisible to heat diffusion waves, by tailoring the heat conductivity of the spherical shell enclosing the object. This means that the thermal scattering from the object is suppressed, and the heat flow outside the object and the cloak made of these spherical shells behaves as if the object is not present. Thermal invisibility may open new vistas in hiding hot spots in infrared thermography, military furtivity, and electronics heating reduction.
Rational steering of insulin binding specificity by intra-chain chemical crosslinking
Authors: Viková Jitka , Collinsová Michaela , Kletvíková Emília , Buděšínský Miloš , Kaplan Vojtěch , Žáková Lenka , Veverka Václav , Hexnerová Rozálie , Aviñó Roberto J. Tarazona , Straková Jana , Selicharová Irena , Vaněk Václav , Wright Daniel W. , Watson Christopher J. , Turkenburg Johan P. , Brzozowski Andrzej M. , Jiráček Jiří
Published: January 2016

Insulin is a key hormone of human metabolism with major therapeutic importance for both types of diabetes. New insulin analogues with more physiological profiles and better glycemic control are needed, especially analogues that preferentially bind to the metabolic B-isoform of insulin receptor (IR-B). Here, we aimed to stabilize and modulate the receptor-compatible conformation of insulin by covalent intra-chain crosslinking within its B22–B30 segment, using the CuI-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of azides and alkynes. This approach resulted in 14 new, systematically crosslinked insulin analogues whose structures and functions were extensively characterized and correlated. One of the analogues, containing a B26–B29 triazole bridge, was highly active in binding to both IR isoforms, with a significant preference for IR-B. Our results demonstrate the potential of chemistry-driven modulation of insulin function, also shedding new light on the functional importance of hormone’s B-chain C-terminus for its IR-B specificity.
Cd(II) Sorption on Montmorillonite-Humic acid-Bacteria Composites
Authors: Du Huihui , Chen Wenli , Cai Peng , Rong Xingmin , Dai Ke , Peacock Caroline L. , Huang Qiaoyun
Published: January 2016

Soil components (e.g., clays, bacteria and humic substances) are known to produce mineral-organic composites in natural systems. Herein, batch sorption isotherms, isothermal titration calorimetry (ITC) and Cd K-edge EXAFS spectroscopy were applied to investigate the binding characteristics of Cd on montmorillonite(Mont)-humic acid(HA)-bacteria composites. Additive sorption and non-additive Cd(II) sorption behaviour is observed for the binary Mont-bacteria and ternary Mont-HA-bacteria composite, respectively. Specifically, in the ternary composite, the coexistence of HA and bacteria inhibits Cd adsorption, suggesting a “blocking effect” between humic acid and bacterial cells. Large positive entropies (68.1 ~ 114.4 J/mol/K) and linear combination fitting of the EXAFS spectra for Cd adsorbed onto Mont-bacteria and Mont-HA-bacteria composites, demonstrate that Cd is mostly bound to bacterial surface functional groups by forming inner-sphere complexes. All our results together support the assertion that there is a degree of site masking in the ternary clay mineral-humic acid-bacteria composite. Because of this, in the ternary composite, Cd preferentially binds to the higher affinity components-i.e., the bacteria.
Development of a conditional liver tumor model by mifepristone-inducible Cre recombination to control oncogenic krasV12 expression in transgenic zebrafish
Authors: Nguyen Anh Tuan , Koh Vivien , Spitsbergen Jan M. , Gong Zhiyuan
Published: January 2016

Here we report a new transgenic expression system by combination of liver-specific expression, mifepristone induction and Cre-loxP recombination to conditionally control the expression of oncogenic krasV12. This transgenic system allowed expression of krasV12 specifically in the liver by a brief exposure of mifepristone to induce permanent genomic recombination mediated by the Cre-loxP system. We found that liver tumors were generally induced from multiple foci due to incomplete Cre-loxP recombination, thus mimicking naturally occurring human tumors resulting from one or a few mutated cells and clonal proliferation to form nodules. Similar to our earlier studies by both constitutive and inducible expression of the krasV12 oncogene, hepatocellular carcinoma (HCC) is the main type of liver tumor induced by krasV12 expression. Moreover, mixed tumors with hepatocellular adenoma and hepatoblastoma (HB) were also frequently observed. Molecular analyses also indicated similar increase of phosphorylated ERK1/2 in all types of liver tumors, but nuclear localization of β–catenin, a sign of malignant transformation, was found only in HCC and HB. Taken together, our new transgenic system reported in this study allows transgenic krasV12 expression specifically in the zebrafish liver only by a brief exposure of mifepristone to induce permanent genomic recombination mediated by the Cre-loxP system.
Turn on the super-elastic collision nature of coronal mass ejections through low approaching speed
Authors: Shen Fang , Wang Yuming , Shen Chenglong , Feng Xueshang
Published: January 2016

It has been proved from the observations and numerical simulations that the collision between solar coronal mass ejections (CMEs), the largest plasmoids in the heliosphere, could be super-elastic. This finding suggests that the CMEs’ magnetic energy and thermal energy could be converted into kinetic energy through a more efficient way. However CME collisions are not always super-elastic, which means that this distinct property of plasmoids is probably excited conditionally. As the first attempt, we carry out a series of three-dimensional numerical experiments and establish a diagram showing the dependence of the collision nature on the CME speed and k-number, the ratio of the CME’s kinetic energy to the CME’s total energy. It is found that the super-elastic nature of CMEs appears at the relatively low approaching speed and most of the previous case studies are in agreement with this diagram. Our study firmly advances the understanding of the super-elastic property of plasmoids and does give us new clues to deeply understand why and how the magnetic energy and/or thermal energy of the colliding plasmoids can be converted into kinetic energy in such an efficient way.
Increasing aridity, temperature and soil pH induce soil C-N-P imbalance in grasslands
Authors: Jiao Feng , Shi Xin-Rong , Han Feng-Peng , Yuan Zhi-You
Published: January 2016

Due to the different degrees of controls exerted by biological and geochemical processes, climate changes are suggested to uncouple biogeochemical C, N and P cycles, influencing biomass accumulation, decomposition and storage in terrestrial ecosystems. However, the possible extent of such disruption in grassland ecosystems remains unclear, especially in China’s steppes which have undergone rapid climate changes with increasing drought and warming predicted moving forward in these dryland ecosystems. Here, we assess how soil C-N-P stoichiometry is affected by climatic change along a 3500-km temperate climate transect in Inner Mongolia, China. Our results reveal that the soil from more arid and warmer sites are associated with lower soil organic C, total N and P. The ratios of both soil C:P and N:P decrease, but soil C:N increases with increasing aridity and temperature, indicating the predicted decreases in precipitation and warming for most of the temperate grassland region could lead to a soil C-N-P decoupling that may reduce plant growth and production in arid ecosystems. Soil pH, mainly reflecting long-term climate change in our sites, also contributes to the changing soil C-N-P stoichiometry, indicating the collective influences of climate and soil type on the shape of soil C-N-P balance.
c.A2456C-substitution in Pck1 changes the enzyme kinetic and functional properties modifying fat distribution in pigs
Authors: Latorre Pedro , Burgos Carmen , Hidalgo Jorge , Varona Luis , Carrodeguas José Alberto , López-Buesa Pascual
Published: January 2016

Cytosolic phosphoenolpyruvate carboxykinase, PCK1, is one of the main regulatory enzymes of gluconeogenesis and glyceroneogenesis. The substitution of a single amino acid (Met139Leu) in PCK1 as a consequence of a single nucleotide polymorphism (SNP), c.A2456C, is associated in the pig to a negative phenotype characterized by reduced intramuscular fat content, enhanced backfat thickness and lower meat quality. The p.139L enzyme shows reduced kcat values in the glyceroneogenic direction and enhanced ones in the anaplerotic direction. Accordingly, the expression of the p.139L isoform results in about 30% lower glucose and 9% lower lipid production in cell cultures. Moreover, the ability of this isoform to be acetylated is also compromised, what would increase its susceptibility to be degraded in vivo by the ubiquitin-proteasome system. The high frequency of the c.2456C allele in modern pig breeds implies that the benefits of including c.A2456C SNP in selection programs could be considerable.
Tubastatin A, an HDAC6 inhibitor, alleviates stroke-induced brain infarction and functional deficits: potential roles of α-tubulin acetylation and FGF-21 up-regulation
Authors: Wang Zhifei , Leng Yan , Wang Junyu , Liao Hsiao-Mei , Bergman Joel , Leeds Peter , Kozikowski Alan , Chuang De-Maw
Published: January 2016

Histone deacetylase (HDAC) 6 exists exclusively in cytoplasm and deacetylates cytoplasmic proteins such as α-tubulin. HDAC6 dysfunction is associated with several pathological conditions in the central nervous system. This study investigated the beneficial effects of tubastatin A (TubA), a novel specific HDAC6 inhibitor, in a rat model of transient middle cerebral artery occlusion (MCAO) and an in vitro model of excitotoxicity. Post-ischemic TubA treatment robustly improved functional outcomes, reduced brain infarction and ameliorated neuronal cell death in MCAO rats. These beneficial effects lasted at least three days after MCAO. Notably, when given at 24 hours after MCAO, TubA still exhibited significant protection. Levels of acetylated α-tubulin were decreased in the ischemic hemisphere on Days 1 and 3 after MCAO and were significantly restored by TubA. MCAO markedly downregulated fibroblast growth factor-21 (FGF-21) and TubA significantly reversed this downregulation. TubA also mitigated impaired FGF-21 signaling in the ischemic hemisphere, including up-regulating β-Klotho and activating ERK and Akt/GSK-3β signaling pathways. In addition, both TubA and exogenous FGF-21 conferred neuroprotection and restored mitochondrial trafficking in rat cortical neurons against glutamate-induced excitotoxicity. Our findings suggest that the neuroprotective effects of TubA likely involve HDAC6 inhibition and the subsequent up-regulation of acetylated α-tubulin and FGF-21.
Hair cortisol varies with season and lifestyle and relates to human interactions in German shepherd dogs
Authors: Roth Lina S. V. , Faresjö Åshild , Theodorsson Elvar , Jensen Per
Published: January 2016

It is challenging to measure long-term endocrine stress responses in animals. We investigated whether cortisol extracted from dog hair reflected the levels of activity and stress long-term, during weeks and months. Hair samples from in total 59 German shepherds were analysed. Samples for measuring cortisol concentrations were collected at three occasions and we complemented the data with individual scores from the Canine Behavioural Assessment and Research Questionnaire (C-BARQ). Generalised linear mixed model (GLMM) results showed that hair cortisol varied with season and lifestyle: competition dogs had higher levels than companion and professional working dogs and levels were higher in January than in May and September. In addition, a positive correlation was found between the cortisol levels and the C-BARQ score for stranger-directed aggression (r = 0.31, P = 0.036). Interestingly, the factor “playing often with the dog” (r = −0.34, P = 0.019) and “reward with a treat/toy when the dog behaves correctly” (r = −0.37, P = 0.010) correlated negatively with cortisol levels, suggesting that positive human interactions reduce stress. In conclusion, hair cortisol is a promising method for revealing the activity of the HPA-axis over a longer period of time and human interactions influence the cortisol level in dogs.
Proteomics Profiling Reveals Carbohydrate Metabolic Enzymes and 14-3-3 Proteins Play Important Roles for Starch Accumulation during Cassava Root Tuberization
Authors: Wang Xuchu , Chang Lili , Tong Zheng , Wang Dongyang , Yin Qi , Wang Dan , Jin Xiang , Yang Qian , Wang Liming , Sun Yong , Huang Qixing , Guo Anping , Peng Ming
Published: January 2016

Cassava is one of the most important root crops as a reliable source of food and carbohydrates. Carbohydrate metabolism and starch accumulation in cassava storage root is a cascade process that includes large amounts of proteins and cofactors. Here, comparative proteomics were conducted in cassava root at nine developmental stages. A total of 154 identified proteins were found to be differentially expressed during starch accumulation and root tuberization. Many enzymes involved in starch and sucrose metabolism were significantly up-regulated and functional classification of the differentially expressed proteins demonstrated that the majority were binding-related enzymes. Many proteins were took part in carbohydrate metabolism to produce energy. Among them, three 14-3-3 isoforms were induced to be clearly phosphorylated during storage root enlargement. Overexpression of a cassava 14-3-3 gene inArabidopsis thalianaconfirmed that the older leaves of these transgenic plants contained higher sugar and starch contents than the wild-type leaves. The 14-3-3 proteins and their binding enzymes may play important roles in carbohydrate metabolism and starch accumulation during cassava root tuberization. These results not only deepened our understanding of the tuberous root proteome, but also uncovered new insights into carbohydrate metabolism and starch accumulation during cassava root enlargement.
Secure Multiparty Quantum Computation for Summation and Multiplication
Authors: Shi Run-hua , Mu Yi , Zhong Hong , Cui Jie , Zhang Shun
Published: January 2016

As a fundamental primitive, Secure Multiparty Summation and Multiplication can be used to build complex secure protocols for other multiparty computations, specially, numerical computations. However, there is still lack of systematical and efficient quantum methods to compute Secure Multiparty Summation and Multiplication. In this paper, we present a novel and efficient quantum approach to securely compute the summation and multiplication of multiparty private inputs, respectively. Compared to classical solutions, our proposed approach can ensure the unconditional security and the perfect privacy protection based on the physical principle of quantum mechanics.
Urinary Kininogen-1 and Retinol binding protein-4 respond to Acute Kidney Injury: predictors of patient prognosis?
Authors: Gonzalez-Calero Laura , Martin-Lorenzo Marta , Ramos-Barron Angeles , Ruiz-Criado Jorge , Maroto Aroa S. , Ortiz Alberto , Gomez-Alamillo Carlos , Arias Manuel , Vivanco Fernando , Alvarez-Llamas Gloria
Published: January 2016

Implementation of therapy for acute kidney injury (AKI) depends on successful prediction of individual patient prognosis. Clinical markers as serum creatinine (sCr) have limitations in sensitivity and early response. The aim of the study was to identify novel molecules in urine which show altered levels in response to AKI and investigate their value as predictors of recovery. Changes in the urinary proteome were here investigated in a cohort of 88 subjects (55 AKI patients and 33 healthy donors) grouped in discovery and validation independent cohorts. Patients’ urine was collected at three time points: within the first 48 h after diagnosis(T1), at 7 days of follow-up(T2) and at discharge of Nephrology(T3). Differential gel electrophoresis was performed and data were confirmed by Western blot (WB), liquid chromatography/mass spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). Retinol binding protein 4 (RBP4) and kininogen-1 (KNG1) were found significantly altered following AKI. RBP4 increased at T1 and progressively decreased towards normalization. Maintained decrease was observed for KNG1 from T1. Individual patient response along time revealed RBP4 responds to recovery earlier than sCr. In conclusion, KNG1 and RBP4 respond to AKI. By monitoring RBP4, patient’s recovery can be anticipated pointing to a role of RBP4 in prognosis evaluation.