bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Topical Atorvastatin (2 %) on Posthemorrhoidectomy Pain and Wound Healing: A Randomized Double‐Blind Placebo‐Controlled Clinical Trial
Authors: Ala Shahram , Alvandipour Mina , Saeedi Majid , Hamidian Maliheh , Shiva Afshin , Rahmani Nasrin , Faramarzi Fatemeh
Published: October 2016

Background

Atorvastatin is a 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase inhibitor widely used in treatment of hypercholesterolemia and prevention of coronary heart disease and has various pleiotropic effects. In this study, the efficacy of atorvastatin emulgel (2 %) in reducing postoperative pain at rest, pain during defecation and analgesic requirement after open hemorrhoidectomy was investigated.

Methods

A total of 66 patients with third‐ and fourth‐degree hemorrhoids undergoing open hemorrhoidectomy were included in this prospective, double‐blind, randomized controlled trial. The patients were randomly assigned to either atorvastatin emulgel or placebo immediately after surgery and then every 12 h for 14 days. The primary outcomes were intensity of pain at rest and during defecation, measured with a visual analog scale, and the analgesic requirement, measured by amount of pethidine and acetaminophen consumption, and percent of wound healing.

Results

There was no significant difference in the average postoperative pain scores in the first 48 h (P12h = 1, P24h = 0.128 and P48h = 0.079) after the surgery between the two groups, but at the week 1 the pain scores during defecation were considerably lower in the atorvastatin group than in placebo group (P = 0.004), which also was the same at the week 2 (P = 0.03). There was no significant difference in the average pethidine and acetaminophen (mg) administration at 12 h and 24 h between the two groups after surgery. Regarding the data about wound healing, at the week two the healing was much better in the treatment group than it was in control group and the difference was statistically significant (P = 0.04).

Conclusions

Compared with placebo, atorvastatin emulgel reduced postoperative pain at rest and on defecation and could improve the healing process after open hemorrhoidectomy.

Trial registration number

IRCT201404013014N8.
Role of Drain Placement in Major Hepatectomy: A NSQIP Analysis of Procedure‐Targeted Hepatectomy Cases
Authors: Shwaartz Chaya , Fields Adam C. , Aalberg Jeffrey J. , Divino Celia M.
Published: October 2016

Background

The value of drain placement in hepatic surgery has not been conclusive. The aim of this study was to determine whether drain placement during major hepatectomy was associated with negative postoperative outcomes and whether its placement reduced the need for secondary procedures.

Methods

The American College of Surgeons National Surgical Quality Improvement Program Procedure‐Targeted Hepatectomy Database was used to identify patients who underwent major hepatectomy. Patients were divided into two groups based on the placement of a drain during the procedure. Propensity score‐matched cohorts of patients who underwent major hepatic resection with or without drain placement were created accounting for patient characteristics. The primary outcomes were 30‐day postoperative complications including bile leak, post‐hepatectomy liver failure, and invasive intervention as well as mortality and readmission.

Results

A total of 1005 patients underwent major hepatectomy; 500 patients (49.8 %) had prophylactic drains placed at the conclusion of the procedure. Drain placement was associated with any complication (p < 0.001), blood transfusion (p < 0.001), renal insufficiency (p = 0.02), bile leak (p < 0.001), invasive intervention (p = 0.02), length of stay (p = 0.001), and readmission (p < 0.001). In the matched cohort, drain placement was associated with any complication (p < 0.001), blood transfusion (p < 0.001), superficial surgical site infection (SSI) (p = 0.028), bile leak (p < 0.001), and longer length of stay (0.03). In addition, placement of a prophylactic drain did not decrease the rate of postoperative bile leaks requiring therapeutic intervention (p = 0.21) (Table 2). In multivariate analysis, drain placement was independently associated with any complication (p < 0.001), blood transfusion (p = 0.02), bile leak (p < 0.001), invasive intervention (p = 0.011), superficial surgical site infection (SSI) (p = 0.039), and hospital readmission (p = 0.005) (Table 3). Placement of a prophylactic drain did not decrease the rate of postoperative bile leaks requiring therapeutic intervention (p = 0.15).

Conclusion

Drain placement after major hepatectomy may lead to increased postoperative complications including bile leak, superficial surgical site infection, and hospital length of stay and does not decrease the need for secondary procedures in patients with bile leaks.
Functional genomics analysis of free fatty acid production under continuous phosphate limiting conditions
Authors: Youngquist J Tyler , Korosh Travis C , Pfleger Brian F
Published: October 2016

Free fatty acids (FFA) are an attractive platform chemical that serves as a functional intermediate in metabolic pathways for producing oleochemicals. Many groups have established strains of Escherichia coli capable of producing various chain-length mixtures of FFA by heterologous expression of acyl-ACP thioesterases. For example, high levels of dodecanoic acid are produced by an E. coli strain expressing the Umbellularia californica FatB2 thioesterase, BTE. Prior studies achieved high dodecanoic acid yields and productivities under phosphate-limiting media conditions. In an effort to understand the metabolic and physiological changes that led to increased FFA production, the transcriptome of this strain was assessed as a function of nutrient limitation and growth rate. FFA generation under phosphate limitation led to consistent changes in transporter expression, osmoregulation, and central metabolism. Guided by these results, targeted knockouts led to a further ~11 % in yield in FFA.
Modelling Conditional Dependence Between Response Time and Accuracy
Authors: Bolsinova Maria , de Boeck Paul , Tijmstra Jesper
Published: October 2016

The assumption of conditional independence between response time and accuracy given speed and ability is commonly made in response time modelling. However, this assumption might be violated in some cases, meaning that the relationship between the response time and the response accuracy of the same item cannot be fully explained by the correlation between the overall speed and ability. We propose to explicitly model the residual dependence between time and accuracy by incorporating the effects of the residual response time on the intercept and the slope parameter of the IRT model for response accuracy. We present an empirical example of a violation of conditional independence from a low-stakes educational test and show that our new model reveals interesting phenomena about the dependence of the item properties on whether the response is relatively fast or slow. For more difficult items responding slowly is associated with a higher probability of a correct response, whereas for the easier items responding slower is associated with a lower probability of a correct response. Moreover, for many of the items slower responses were less informative for the ability because their discrimination parameters decrease with residual response time.
Locking Plate Arthrodesis Compares Favorably with LRTI for Thumb Trapeziometacarpal Arthrosis: Early Outcomes from a Longitudinal Cohort Study
Authors: Kazmers Nikolas H. , Hippensteel K. J. , Calfee Ryan P. , Wall Lindley B. , Boyer Martin I. , Goldfarb Charles A. , Gelberman Richard H. , Osei Daniel A.
Published: October 2016

Background

Trapeziometacarpal arthrodesis (TMA) has been complicated by nonunion and hardware failure.

Questions/Purposes

We hypothesized that modification of the TMA technique with a locking cage plate construct would afford reliable bony union while producing greater hand function than trapeziectomy with ligament reconstruction and tendon interposition (LRTI) at early follow-up.

Methods

We enrolled 36 consecutive patients with trapeziometacapal osteoarthritis (14 TMA patients (15 thumbs), 22 LRTI patients (22 thumbs)). The study was powered to detect a minimal clinically important difference on the QuickDASH questionnaire between groups. Secondary outcomes included Michigan Hand Questionnaire (MHQ), VAS-pain, and EQ-5D-3L scores. Patients were examined to evaluate thumb motion and strength. TMA patients were evaluated clinically and radiographically for union.

Results

Mean follow-up was 15.6 months, and the mean age was 59.2 years. Union was achieved in 14/15 (93%) of TMA thumbs. Improvement in QuickDASH scores was similar after TMA and LRTI (49 to 28 and 50 to 18, respectively). Postoperative patient-rated upper extremity function, health status, and pain were similar between groups. Pinch strength was significantly greater after TMA (5.9 vs 4.7 kg). No differences in thumb or wrist range of motion were observed postoperatively with the exception of greater total metacarpophalangeal joint motion after TMA. Complications after TMA included nonunion (7%), development of symptomatic scaphotrapezotrapezoidal (STT) arthrosis (7%), symptomatic hardware (7%), and superficial branch of the radial nerve (SBRN) paresthesia (7%). Complications after LRTI included subsidence (5%), MP hyperextension deformity (5%), and SBRN paresthesias (5%).

Conclusions

At early follow-up, patient-rated function was similar among patients undergoing TMA and LRTI. TMA produced 25% greater pinch strength compared with LRTI. Despite historical concerns regarding global loss of ROM with arthrodesis, motion was similar between groups. Our observed TMA nonunion rate of 7% is low relative to historically reported nonunion rates (7–16%). Locking cage plate technology affords rigid fixation for TMA with promising early results noting reliable bony union while minimizing complications.
Simulating power of economic experiments: the powerBBK package
Authors: Bellemare Charles , Bissonnette Luc , Kröger Sabine
Published: October 2016

In this article, we highlight how simulation methods can be used to analyze power of economic experiments. We provide the powerBBK package programmed for experimental economists, that can be used to perform simulations in STATA. Power can be simulated using a single command line for various statistical tests (nonparametric and parametric), estimation methods (linear, binary, and censored regression models), treatment variables (binary, continuous, time-invariant or time varying), sample sizes, experimental periods, and other design features (within or between-subjects design). The package can be used to predict minimum sample sizes required to reach a user-specific level of power, to maximize power of a design given the researcher supplied a budget constraint, or to compute power to detect a user-specified treatment order effect in within-subjects designs. The package can also be used to compute the probability of sign errors—the probability of rejecting the null hypothesis in the wrong direction as well as the share of rejections pointing in the wrong direction. The powerBBK package is provided as an .ado file along with a help file, both of which can be downloaded here (http://www.bbktools.org).
A metabolic synthetic lethal strategy with arginine deprivation and chloroquine leads to cell death in ASS1-deficient sarcomas
Authors: Bean Gregory R , Kremer Jeff C , Prudner Bethany C , Schenone Aaron D , Yao Juo-Chin , Schultze Matthew B , Chen David Y , Tanas Munir R , Adkins Douglas R , Bomalaski John , Rubin Brian P , Michel Loren S , Van Tine Brian A
Published: October 2016

Sarcomas comprise a large heterogeneous group of mesenchymal cancers with limited therapeutic options. When treated with standard cytotoxic chemotherapies, many sarcomas fail to respond completely and rapidly become treatment resistant. A major problem in the investigation and treatment of sarcomas is the fact that no single gene mutation or alteration has been identified among the diverse histologic subtypes. We searched for therapeutically druggable targets that are common to a wide range of histologies and hence could provide alternatives to the conventional chemotherapy. Seven hundred samples comprising 45 separate histologies were examined. We found that almost 90% were arginine auxotrophs, as the expression of argininosuccinate synthetase 1 was lost or significantly reduced. Arginine auxotrophy confers sensitivity to arginine deprivation, leading temporarily to starvation and ultimately to cell survival or death under different circumstances. We showed that, in sarcoma, arginine deprivation therapy with pegylated arginine deiminase (ADI-PEG20) maintains a prolonged state of arginine starvation without causing cell death. However, when starvation was simultaneously prolonged by ADI-PEG20 while inhibited by the clinically available drug chloroquine, sarcoma cells died via necroptosis and apoptosis. These results have revealed a novel metabolic vulnerability in sarcomas and provided the basis for a well-tolerated alternative treatment strategy, potentially applicable to up to 90% of the tumors, regardless of histology.
Effects of YM155 on survivin levels and viability in neuroblastoma cells with acquired drug resistance
Authors: Voges Yvonne , Michaelis Martin , Rothweiler Florian , Schaller Torsten , Schneider Constanze , Politt Katharina , Mernberger Marco , Nist Andrea , Stiewe Thorsten , Wass Mark N , Rödel Franz , Cinatl Jindrich
Published: October 2016

Resistance formation after initial therapy response (acquired resistance) is common in high-risk neuroblastoma patients. YM155 is a drug candidate that was introduced as a survivin suppressant. This mechanism was later challenged, and DNA damage induction and Mcl-1 depletion were suggested instead. Here we investigated the efficacy and mechanism of action of YM155 in neuroblastoma cells with acquired drug resistance. The efficacy of YM155 was determined in neuroblastoma cell lines and their sublines with acquired resistance to clinically relevant drugs. Survivin levels, Mcl-1 levels, and DNA damage formation were determined in response to YM155. RNAi-mediated depletion of survivin, Mcl-1, and p53 was performed to investigate their roles during YM155 treatment. Clinical YM155 concentrations affected the viability of drug-resistant neuroblastoma cells through survivin depletion and p53 activation. MDM2 inhibitor-induced p53 activation further enhanced YM155 activity. Loss of p53 function generally affected anti-neuroblastoma approaches targeting survivin. Upregulation of ABCB1 (causes YM155 efflux) and downregulation of SLC35F2 (causes YM155 uptake) mediated YM155-specific resistance. YM155-adapted cells displayed increased ABCB1 levels, decreased SLC35F2 levels, and a p53 mutation. YM155-adapted neuroblastoma cells were also characterized by decreased sensitivity to RNAi-mediated survivin depletion, further confirming survivin as a critical YM155 target in neuroblastoma. In conclusion, YM155 targets survivin in neuroblastoma. Furthermore, survivin is a promising therapeutic target for p53 wild-type neuroblastomas after resistance acquisition (neuroblastomas are rarely p53-mutated), potentially in combination with p53 activators. In addition, we show that the adaptation of cancer cells to molecular-targeted anticancer drugs is an effective strategy to elucidate a drug’s mechanism of action.
Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats
Authors: Zhang Xiang-Sheng , Wu Qi , Wu Ling-Yun , Ye Zhen-Nan , Jiang Tian-Wei , Li Wei , Zhuang Zong , Zhou Meng-Liang , Zhang Xin , Hang Chun-Hua
Published: October 2016

Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced early brain injury (EBI). In the first set of experiments, rats were randomly divided into sham group and SAH groups at 2, 6, 12, 24, 48 and 72 h. The expression of SIRT1 was evaluated by western blot analysis, immunohistochemistry and immunofluorescence. In another set of experiments, SIRT1-specific inhibitor (sirtinol) and activator (activator 3) were exploited to study the role of SIRT1 in SAH-induced EBI. It showed that the protein level of SIRT1 was markedly elevated at the early stage of SAH and peaked at 24 h after SAH. The expression of SIRT1 could be observed in neurons and microglia, and the enhanced SIRT1 was mainly located in neurons after SAH. Administration of sirtinol inhibited the expression and activation of SIRT1 pathways after SAH, while activator 3 enhanced the expression and activation of SIRT1 pathways after SAH. In addition, inhibition of SIRT1 could exacerbate forkhead transcription factors of the O class-, nuclear factor-kappa B- and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis, leading to aggravated brain injury after SAH. In contrast, activator 3 treatment could reduce forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis to protect against EBI. These results suggest that SIRT1 plays an important role in neuroprotection against EBI after SAH by deacetylation and subsequent inhibition of forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative, inflammatory and apoptotic pathways. SIRT1 might be a new promising molecular target for SAH.
CDK5 functions as a tumor promoter in human colorectal cancer via modulating the ERK5–AP-1 axis
Authors: Zhuang Kangmin , Zhang Juchang , Xiong Man , Wang Xianfei , Luo Xiaobei , Han Lu , Meng Yan , Zhang Yali , Liao Wenting , Liu Side
Published: October 2016

Abnormal expression of cyclin-dependent kinase 5 (CDK5) has been found in several human cancers, whereas the role of CDK5 in the malignant development of colorectal cancer (CRC) has not been well characterized. Here we investigated the role of CDK5 in CRC and found that its expression was much higher in CRC tissues than that in normal tissues with a higher expression level of CDK5 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size and poor prognosis of CRC. Biological function experiments showed that CDK5 regulated CRC cell proliferation and metastasis ability. Whole-genome microarray analysis, co-immunoprecipitation,in vitrokinase assay, western blotting, luciferase reporter assays and electrophoretic mobility shift assay (EMSA) showed that CDK5 could directly phosphorylate ERK5 at threonine (Thr) 732 and finally modulate the oncogenic ERK5–AP-1 axis. Further researches showed that CDK5–ERK5–AP-1 axis could promote progression of CRC carcinogenesis and had a significant correlation in human CRC samples. In summary, this study revealed the functional and mechanistic links between CDK5 and the oncogenic ERK5–AP-1 signaling pathway in the pathogenesis of CRC. These findings suggest that CDK5 has an important role in CRC development and may serve as a potential therapeutic target for CRC.
Flexible ferroelectric organic crystals
Authors: Owczarek Magdalena , Hujsak Karl A. , Ferris Daniel P. , Prokofjevs Aleksandrs , Majerz Irena , Szklarz Przemysław , Zhang Huacheng , Sarjeant Amy A. , Stern Charlotte L. , Jakubas Ryszard , Hong Seungbum , Dravid Vinayak P. , Stoddart J. Fraser
Published: October 2016

Flexible organic materials possessing useful electrical properties, such as ferroelectricity, are of crucial importance in the engineering of electronic devices. Up until now, however, only ferroelectric polymers have intrinsically met this flexibility requirement, leaving small-molecule organic ferroelectrics with room for improvement. Since both flexibility and ferroelectricity are rare properties on their own, combining them in one crystalline organic material is challenging. Herein, we report that trisubstituted haloimidazoles not only display ferroelectricity and piezoelectricity—the properties that originate from their non-centrosymmetric crystal lattice—but also lend their crystalline mechanical properties to fine-tuning in a controllable manner by disrupting the weak halogen bonds between the molecules. This element of control makes it possible to deliver another unique and highly desirable property, namely crystal flexibility. Moreover, the electrical properties are maintained in the flexible crystals.
Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer’s disease
Authors: Beck Michael W. , Derrick Jeffrey S. , Kerr Richard A. , Oh Shin Bi , Cho Woo Jong , Lee Shin Jung C. , Ji Yonghwan , Han Jiyeon , Tehrani Zahra Aliakbar , Suh Nayoung , Kim Sujeong , Larsen Scott D. , Kim Kwang S. , Lee Joo-Yong , Ruotolo Brandon T. , Lim Mi Hee
Published: October 2016

The absence of effective therapeutics against Alzheimer’s disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal–Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets’ reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.
Chiral optical response of planar and symmetric nanotrimers enabled by heteromaterial selection
Authors: Banzer Peter , Woźniak Paweł , Mick Uwe , De Leon Israel , Boyd Robert W.
Published: October 2016

Chirality is an intriguing property of certain molecules, materials or artificial nanostructures, which allows them to interact with the spin angular momentum of the impinging light field. Due to their chiral geometry, they can distinguish between left- and right-hand circular polarization states or convert them into each other. Here we introduce an approach towards optical chirality, which is observed in individual two-dimensional and geometrically mirror-symmetric nanostructures. In this scheme, the chiral optical response is induced by the chosen heterogeneous material composition of a particle assembly and the corresponding resonance behaviour of the constituents it is built from, which breaks the symmetry of the system. As a proof of principle, we investigate such a structure composed of individual silicon and gold nanoparticles both experimentally, as well as numerically. Our proposed concept constitutes an approach for designing two-dimensional chiral media tailored at the nanoscale, allowing for high tunability of their optical response.
Immunisation of two rodent species with new live-attenuated mutants of Yersinia pestis CO92 induces protective long-term humoral- and cell-mediated immunity against pneumonic plague
Authors: Tiner Bethany L , Sha Jian , Cong Yingzi , Kirtley Michelle L , Andersson Jourdan A , Chopra Ashok K
Published: October 2016

We showed recently that the live-attenuated Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants of Yersinia pestis CO92 provided short-term protection to mice against developing subsequent lethal pneumonic plague. These mutants were either deleted for genes encoding Braun lipoprotein (Lpp), an acetyltransferase (MsbB) and the attachment invasion locus (Ail) (Δlpp ΔmsbB Δail) or contained a modified version of the ail gene with diminished virulence (Δlpp ΔmsbB::ailL2). Here, long-term immune responses were first examined after intramuscular immunisation of mice with the above-mentioned mutants, as well as the newly constructed Δlpp ΔmsbB Δpla mutant, deleted for the plasminogen-activator protease (pla) gene instead of ail. Y. pestis-specific IgG levels peaked between day 35 and 56 in the mutant-immunised mice and were sustained until the last tested day 112. Splenic memory B cells peaked earlier (day 42) before declining in the Δlpp ΔmsbB::ailL2 mutant-immunised mice while being sustained for 63 days in the Δlpp ΔmsbB Δail and Δlpp ΔmsbB Δpla mutant-immunised mice. Splenic CD4+ T cells increased in all immunised mice by day 42 with differential cytokine production among the immunised groups. On day 120, immunised mice were exposed intranasally to wild-type (WT) CO92, and 80–100% survived pneumonic challenge. Mice immunised with the above-mentioned three mutants had increased innate as well as CD4+ responses immediately after WT CO92 exposure, and coupled with sustained antibody production, indicated the role of both arms of the immune response in protection. Likewise, rats vaccinated with either Δlpp ΔmsbB Δail or the Δlpp ΔmsbB Δpla mutant also developed long-term humoral and cell-mediated immune responses to provide 100% protection against developing pneumonic plague. On the basis of the attenuated phenotype, the Δlpp ΔmsbB Δail mutant was recently excluded from the Centers for Disease Control and Prevention select agent list.
Structural phase transitions and photoluminescence properties of oxonitridosilicate phosphors under high hydrostatic pressure
Authors: Lazarowska Agata , Mahlik Sebastian , Grinberg Marek , Li Guogang , Liu Ru-Shi
Published: October 2016

Spectroscopic properties of a series of (Sr0.98-xBaxEu0.02)Si2O2N2 (0 ≤ x ≤ 0.98) compounds has been studied under high hydrostatic pressure applied in a diamond anvil cell up to 200 kbar. At ambient pressure the crystal structures of (Sr0.98-xBaxEu0.02)Si2O2N2 (0 ≤ x ≤ 0.98) are related to the ratio of strontium to barium and three different phases exists: orthorhombic Pbcn(0.78 ≤ x ≤ 0.98), triclinic P1 (0 < x ≤ 0.65) and triclinic P1 (0.65 < x < 0.78). It was found that Eu2+ luminescence reveals abrupt changes under pressure (decay time, energy and shape) which indicate the variation of the local symmetry and crystal field strength in Eu2+ sites. These changes are attributed to the reversible pressure-induced structural phase transitions of triclinic (Sr0.98-xBaxEu0.02)Si2O2N2 into orthorhombic structure. Pressure in which phase transition occurs decreases linearly with increasing of Ba composition in (Sr0.98-xBaxEu0.02)Si2O2N2 series. Additionally, very different pressure shifts of the Eu2+ luminescence in different phases of (Sr0.98-xBaxEu0.02)Si2O2N2:Eu from −40 cm−1/kbar to 0 cm−1/kbar have been observed. This effect is explained by different interaction of the Eu2+ 5d electron with the second coordination sphere around the impurity cations.
3Disease Browser: A Web server for integrating 3D genome and disease-associated chromosome rearrangement data
Authors: Li Ruifeng , Liu Yifang , Li Tingting , Li Cheng
Published: October 2016

Chromosomal rearrangement (CR) events have been implicated in many tumor and non-tumor human diseases. CR events lead to their associated diseases by disrupting gene and protein structures. Also, they can lead to diseases through changes in chromosomal 3D structure and gene expression. In this study, we search for CR-associated diseases potentially caused by chromosomal 3D structure alteration by integrating Hi-C and ChIP-seq data. Our algorithm rediscovers experimentally verified disease-associated CRs (polydactyly diseases) that alter gene expression by disrupting chromosome 3D structure. Interestingly, we find that intellectual disability may be a candidate disease caused by 3D chromosome structure alteration. We also develop a Web server (3Disease Browser, http://3dgb.cbi.pku.edu.cn/disease/) for integrating and visualizing disease-associated CR events and chromosomal 3D structure.
MicroRNA miR-204 and miR-1236 inhibit hepatitis B virus replication via two different mechanisms
Authors: Huang Jyun-Yuan , Chen Hung-Lin , Shih Chiaho
Published: October 2016

Hepatitis B virus (HBV) is a major human pathogen. In this study, we found that miR-204 and miR-1236 were down-regulated in HBV-producing cells, and each could suppress HBV replication. Using a bioinformatic approach and a reporter assay, we identified miR-1236, which can reduce HBV replication and protein production by directly targeting at HBV specific mRNA. In contrast, miR-204 was identified by a microarray approach, and had no effect on HBV RNA and protein production. Surprisingly, miR-204 could inhibit HBV pregenomic RNA encapsidation and capsid assembly. We further demonstrated that HBV suppressed miR-204 expression via activating a host transcription factor STAT3. We established a positive feed-forward loop between HBV, miR-204 and STAT3. Interestingly, miR-204 has been considered as a tumor suppressor in some literature. Since the risk for hepatocellular carcinoma (HCC) is significantly increased in chronic HBV patients, it is possible that chronic suppression of miR-204 by HBV contributes to HCC incidence. Both miR-204 and miR-1236 might be useful for developing new therapeutics against HBV.
Electrochemical deposition of layered copper thin films based on the diffusion limited aggregation
Authors: Wei Chenhuinan , Wu Guoxing , Yang Sanjun , Liu Qiming
Published: October 2016

In this work layered copper films with smooth surface were successfully fabricated onto ITO substrate by electrochemical deposition (ECD) and the thickness of the films was nearly 60 nm. The resulting films were characterized by SEM, TEM, AFM, XPS, and XRD. We have investigated the effects of potential and the concentration of additives and found that 2D dendritic-like growth process leaded the formation of films. A suitable growth mechanism based on diffusion limited aggregation (DLA) mechanism for the copper films formation is presented, which are meaningful for further designing homogeneous and functional films.
Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding
Authors: Danilov Sergei M. , Lünsdorf Heinrich , Akinbi Henry T. , Nesterovitch Andrew B. , Epshtein Yuliya , Letsiou Eleftheria , Kryukova Olga V. , Piegeler Tobias , Golukhova Elena Z. , Schwartz David E. , Dull Randal O. , Minshall Richard D. , Kost Olga A. , Garcia Joe G. N.
Published: October 2016

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.
Characterizing the residual glass in a MgO/Al2O3/SiO2/ZrO2/Y2O3 glass-ceramic
Authors: Seidel Sabrina , Patzig Christian , Wisniewski Wolfgang , Gawronski Antje , Hu Yongfeng , Höche Thomas , Rüssel Christian
Published: October 2016

The non-isochemical crystallization of glasses leads to glass-ceramics in which the chemical composition of the amorphous matrix differs from that of the parent glass. It is challenging to solely analyse the properties of these residual glassy phases because they frequently contain finely dispersed crystals. In this study, the composition of the residual glass matrix after the crystallization of a glass with the mol% composition 50.6 SiO2 · 20.7 MgO · 20.7 Al2O3 · 5.6 ZrO2 · 2.4 Y2O3 is analysed by scanning transmission electron microscopy (STEM) including energy dispersive X-ray analysis (EDXS). A batch of the residual glass with the determined composition is subsequently melted and selected properties are analysed. Furthermore, the crystallization behaviour of this residual glass is studied by X-ray diffraction, scanning electron microscopy including electron backscatter diffraction and STEM-EDXS analyses. The residual glass shows sole surface crystallization of indialite and multiple yttrium silicates while bulk nucleation does not occur. This is in contrast to the crystallization behaviour of the parent glass, in which a predominant bulk nucleation of spinel and ZrO2 is observed. The crystallization of the residual glass probably leads to different crystalline phases when it is in contact to air, rather than when it is enclosed within the microstructure of the parent glass-ceramics.
Haemocoel injection of PirA1B1 to Galleria mellonella larvae leads to disruption of the haemocyte immune functions
Authors: Wu Gongqing , Yi Yunhong
Published: October 2016

The bacterium Photorhabdus luminescens produces a number of insecticidal proteins to kill its larval prey. In this study, we cloned the gene coding for a binary toxin PirA1B1 and purified the recombinant protein using affinity chromatography combined with desalination technology. Furthermore, the cytotoxicity of the recombinant protein against the haemocytes of Galleria mellonella larvae was investigated. We found that the protein had haemocoel insecticidal activity against G. mellonella with an LD50 of 131.5 ng/larva. Intrahaemocoelic injection of PirA1B1 into G. mellonella resulted in significant decreases in haemocyte number and phagocytic ability. In in vitro experiments, PirA1B1 inhibited the spreading behaviour of the haemocytes of G. mellonella larvae and even caused haemocyte degeneration. Fluorescence microscope analysis and visualization of haemocyte F-actin stained with phalloidin-FITC showed that the PirA1B1 toxin disrupted the organization of the haemocyte cytoskeleton. Our results demonstrated that the PirA1B1 toxin disarmed the insect cellular immune system.
Chytrid parasitism facilitates trophic transfer between bloom-forming cyanobacteria and zooplankton (Daphnia)
Authors: Agha Ramsy , Saebelfeld Manja , Manthey Christin , Rohrlack Thomas , Wolinska Justyna
Published: October 2016

Parasites are rarely included in food web studies, although they can strongly alter trophic interactions. In aquatic ecosystems, poorly grazed cyanobacteria often dominate phytoplankton communities, leading to the decoupling of primary and secondary production. Here, we addressed the interface between predator-prey and host-parasite interactions by conducting a life-table experiment, in which fourDaphnia galeatagenotypes were maintained on quantitatively comparable diets consisting of healthy cyanobacteria or cyanobacteria infected by a fungal (chytrid) parasite. In four out of five fitness parameters, at least oneDaphniagenotype performed better on parasitised cyanobacteria than in the absence of infection. Further treatments consisting of purified chytrid zoospores and heterotrophic bacteria suspensions established the causes of improved fitness. First,Daphniafeed on chytrid zoospores which trophically upgrade cyanobacterial carbon. Second, an increase in heterotrophic bacterial biomass, promoted by cyanobacterial decay, provides an additional food source forDaphnia. In addition, chytrid infection induces fragmentation of cyanobacterial filaments, which could render cyanobacteria more edible. Our results demonstrate that chytrid parasitism can sustain zooplankton under cyanobacterial bloom conditions, and exemplify the potential of parasites to alter interactions between trophic levels.
Structural basis for ligand recognition by a Cache chemosensory domain that mediates carboxylate sensing in Pseudomonas syringae
Authors: Brewster Jodi L. , McKellar James L. O. , Finn Thomas J. , Newman Janet , Peat Thomas S. , Gerth Monica L.
Published: October 2016

Chemoreceptors enable bacteria to detect chemical signals in the environment and navigate towards niches that are favourable for survival. The sensor domains of chemoreceptors function as the input modules for chemotaxis systems, and provide sensory specificity by binding specific ligands. Cache-like domains are the most common extracellular sensor module in prokaryotes, however only a handful have been functionally or structurally characterised. Here, we have characterised a chemoreceptor Cache-like sensor domain (PscD-SD) from the plant pathogen Pseudomonas syringae pv. actinidiae (Psa). High-throughput fluorescence thermal shift assays, combined with isothermal thermal titration calorimetry, revealed that PscD-SD binds specifically to C2 (glycolate and acetate) and C3 (propionate and pyruvate) carboxylates. We solved the structure of PscD-SD in complex with propionate using X-ray crystallography. The structure reveals the key residues that comprise the ligand binding pocket and dictate the specificity of this sensor domain for C2 and C3 carboxylates. We also demonstrate that all four carboxylate ligands are chemoattractants for Psa, but only two of these (acetate and pyruvate) are utilisable carbon sources. This result suggests that in addition to guiding the bacteria towards nutrients, another possible role for carboxylate sensing is in locating potential sites of entry into the host plant.
Study of corneal epithelial progenitor origin and the Yap1 requirement using keratin 12 lineage tracing transgenic mice
Authors: Kasetti Ramesh Babu , Gaddipati Subhash , Tian Shifu , Xue Lei , Kao Winston W.-Y. , Lu Qingxian , Li Qiutang
Published: October 2016

Key issues in corneal epithelium biology are the mechanism for corneal epithelium stem cells to maintain the corneal epithelial homeostasis and wound healing responses, and what are the regulatory molecular pathways involved. There are apparent discrepancies about the locations of the progenitor populations responsible for corneal epithelial self-renewal. We have developed a genetic mouse model to trace the corneal epithelial progenitor lineages during adult corneal epithelial homeostasis and wound healing response. Our data revealed that the early corneal epithelial progenitor cells expressing keratin-12 originated from limbus, and gave rise to the transit amplifying cells that migrated centripetally to differentiate into corneal epithelial cells. Our results support a model that both corneal epithelial homeostasis and wound healing are mainly maintained by the activated limbal stem cells originating form limbus, but not from the corneal basal epithelial layer. In the present study, we further demonstrated the nuclear expression of transcriptional coactivator YAP1 in the limbal and corneal basal epithelial cells and its essential role for maintaining the high proliferative potential of those corneal epithelial progenitor cells in vivo.
Language/Culture Modulates Brain and Gaze Processes in Audiovisual Speech Perception
Authors: Hisanaga Satoko , Sekiyama Kaoru , Igasaki Tomohiko , Murayama Nobuki
Published: October 2016

Several behavioural studies have shown that the interplay between voice and face information in audiovisual speech perception is not universal. Native English speakers (ESs) are influenced by visual mouth movement to a greater degree than native Japanese speakers (JSs) when listening to speech. However, the biological basis of these group differences is unknown. Here, we demonstrate the time-varying processes of group differences in terms of event-related brain potentials (ERP) and eye gaze for audiovisual and audio-only speech perception. On a behavioural level, while congruent mouth movement shortened the ESs’ response time for speech perception, the opposite effect was observed in JSs. Eye-tracking data revealed a gaze bias to the mouth for the ESs but not the JSs, especially before the audio onset. Additionally, the ERP P2 amplitude indicated that ESs processed multisensory speech more efficiently than auditory-only speech; however, the JSs exhibited the opposite pattern. Taken together, the ESs’ early visual attention to the mouth was likely to promote phonetic anticipation, which was not the case for the JSs. These results clearly indicate the impact of language and/or culture on multisensory speech processing, suggesting that linguistic/cultural experiences lead to the development of unique neural systems for audiovisual speech perception.
Molecular evolution of a widely-adopted taxonomic marker (COI) across the animal tree of life
Authors: Pentinsaari Mikko , Salmela Heli , Mutanen Marko , Roslin Tomas
Published: October 2016

DNA barcodes are widely used for identification and discovery of species. While such use draws on information at the DNA level, the current amassment of ca. 4.7 million COI barcodes also offers a unique resource for exploring functional constraints on DNA evolution. Here, we explore amino acid variation in a crosscut of the entire animal kingdom. Patterns of DNA variation were linked to functional constraints at the level of the amino acid sequence in functionally important parts of the enzyme. Six amino acid sites show variation with possible effects on enzyme function. Overall, patterns of amino acid variation suggest convergent or parallel evolution at the protein level connected to the transition into a parasitic life style. Denser sampling of two diverse insect taxa revealed that the beetles (Coleoptera) show more amino acid variation than the butterflies and moths (Lepidoptera), indicating fundamental difference in patterns of molecular evolution in COI. Several amino acid sites were found to be under notably strong purifying selection in Lepidoptera as compared to Coleoptera. Overall, these findings demonstrate the utility of the global DNA barcode library to extend far beyond identification and taxonomy, and will hopefully be followed by a multitude of work.
High-resolution crystal structure of the therapeutic antibody pembrolizumab bound to the human PD-1
Authors: Horita Shoichiro , Nomura Yayoi , Sato Yumi , Shimamura Tatsuro , Iwata So , Nomura Norimichi
Published: October 2016

Pembrolizumab is an FDA-approved therapeutic antibody that targets the programmed cell death-1 (PD-1) to block the immune checkpoint pathway for the treatment of various types of cancer. It receives remarkable attention due to the high degree of efficacy. Very recently, the crystal structure of the Fab fragment of pembrolizumab (PemFab) in complex with the extracellular domain of human PD-1 (PD-1ECD) was reported at a resolution of 2.9 Å. However, this relatively low-resolution structural data fails to provide sufficient information on interfacial water molecules at the binding interface that substantially contribute to affinity and specificity between the therapeutic antibody and target. Here, we present the independently determined crystal structure of the Fv fragment of pembrolizumab (PemFv) in complex with the PD-1ECD at a resolution of 2.15 Å. This high-resolution structure allows the accurate mapping of the interaction including water-mediated hydrogen bonds and provides, for the first time, a coherent explanation of PD-1 antagonism by pembrolizumab. Our structural data also provides new insights into the rational design of improved anti-PD-1 therapeutics.
Hexagonal 2H-MoSe2 broad spectrum active photocatalyst for Cr(VI) reduction
Authors: Chu Haipeng , Liu Xinjuan , Liu Baibai , Zhu Guang , Lei Wenyan , Du Huigang , Liu Junying , Li Jianwei , Li Can , Sun Changqing
Published: October 2016

To make full use of the solar energy, exploring broad spectrum active photocatalysts has become one of the core issues for photocatalysis. Here we report a novel hexagonal 2H-MoSe2 photocatalyst with ultraviolet (UV)-visible-near infrared (NIR) light response for the first time. The results indicate that the MoSe2 displays excellent photo-absorption and photocatalytic activity in the reduction of Cr(VI) under UV and visible even NIR light irradiation. MoSe2 synthesized at pH value of 2 achieves the highest Cr(VI) reduction rates of 99%, 91% and 100% under UV, visible and NIR light irradiation, respectively, which should be attributed to its comparatively higher light absorption, efficient charge separation and transfer as well as relatively large number of surface active sites. The excellent broad spectrum active photocatalytic activity makes the MoSe2 to be a promising photocatalyst for the effective utilization of solar energy.
Evaluation of five microbial and four mitochondrial DNA markers for tracking human and pig fecal pollution in freshwater
Authors: He Xiwei , Liu Peng , Zheng Guolu , Chen Huimei , Shi Wei , Cui Yibin , Ren Hongqiang , Zhang Xu-Xiang
Published: October 2016

This study systematically evaluated five microbial and four mitochondrial DNA (mtDNA) markers, including sensitivities and specificities under PCR method, and fecal concentrations and decay rates in water under qPCR method. The microbial DNA markers were the three human-associated (BacH, HF183 and B.adolescentis) and two pig-associated (Pig-2-Bac and L.amylovorus), while the mtDNA ones were two human- (H-ND6 and H-ND5) and two pig-associated (P-CytB and P-ND5). All the mtDNA markers showed higher sensitivity (100%) than the microbial ones (84.0–88.8%) except Pig-2-Bac (100%). Specificities of the human mtDNA markers (99.1 and 98.1%) were higher than those of the human-associated microbial ones (57.0–88.8%). But this pattern was not observed in the pig-associated markers where Pig-2-Bac had 100% specificity. The reliability of H-ND6 and H-ND5 was further evidenced to identify locations of the most polluted within the Taihu Lake watershed of China. In general, the microbial DNA markers demonstrated a higher fecal concentration than the mtDNA ones; increasing temperature and sunlight exposure accelerated significantly the decay of all the DNA markers. Results of this study suggest that DNA markers H-ND6, H-ND5, and Pig-2-Bac may be among the best for fecal source tracking in water.