bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal‐Catalyzed Alkene Functionalization Reactions Towards Production of Detergent and Surfactant Feedstocks
Authors: Alam Mohd. Gulfam , Tshabalala Thandeka A. , Ojwach Stephen O.
Published: September 2016

Metal complexes have been used as catalysts in alkene transformation reactions to produce alcohols, esters, and organic acids as potential raw materials for the manufacture of detergents, perfumes, and other fine chemicals. Herein, we report the use of palladium(II) and ruthenium complexes as efficient catalyst precursors for the methoxycarbonylation, hydrogenolysis, and ethoxylation reactions of higher alkenes. The palladium catalysts showed high chemoselectivity (>98 %) and regioselectivities of about 40 % towards the formation of esters and branched isomers, respectively. Subsequent hydrogenolysis of the esters to the corresponding alcohols was achieved using ruthenium catalysts. Reactions of the esters and alcohols with ethylene oxide using calcinated aluminum oxide catalysts produced the corresponding alcohol and methyl ester ethoxylates, respectively. The identity of the phosphine derivatives, catalyst loading, reaction time, temperature, and pressure were found to influence the catalytic activity and regioselectivity of the complexes.
Productivity, Rank, and Returns in Polygamy
Authors: Matz Julia Anna
Published: September 2016

This study sheds light on the development of family structures in a polygamous context with a particular emphasis on wife order, and offers an explanation for the association between outcomes of children and the status of their mothers among wives based on observable maternal characteristics. In a simple framework, I propose that selection into rank among wives with respect to female productivity takes place: highly productive women are more strongly demanded in the marriage market than less productive women, giving them a higher chance of becoming first wives. Furthermore, productivity is positively associated with a wife’s bargained share of family income to be spent on consumption and investment for herself and her offspring because of greater contributions to family income and larger outside options. The findings are empirically supported by a positive relationship between indicators of female productivity and women’s levels of seniority among wives, and by a concise replication of existing evidence relating wife order to children’s educational outcomes in household survey data from rural Ethiopia.
Patient Discussion About Sexual Health with Health Care Providers After Cancer—A National Survey
Authors: Ben Charif Ali , Bouhnik Anne-Déborah , Courbiere Blandine , Rey Dominique , Préau Marie , Bendiane Marc-Karim , Peretti-Watel Patrick , Mancini Julien
Published: September 2016

Introduction

A discussion about sexuality should become a routine part of the personalized care pathway for patients with cancer.

Aim

To assess rates of patient discussion about sexuality with health care providers after cancer.

Methods

We used data from the representative French nationwide 2012 VICAN survey, which included 4,349 adults 18 to 82 years old who were still alive 2 years after diagnosis at 12 cancer sites.

Main Outcome Measures

Self-reported rates of discussion about sexuality with health care providers were assessed, and associated factors were tested after systematic adjustment for a sexual health indicator (created from six items of the Relationship and Sexuality Scale).

Results

Of 4,181 respondents to the question on a discussion about sexuality, 54.7% reported that nobody had proposed a discussion to them, 21.9% did not want any discussion, and 23.4% had had a discussion. Women had less discussion about sexuality with health care providers (11.1% vs 36.7% of men, P < .001) and were more likely to request a discussion at their own initiative (62.9% vs 48.0% of men, P < .001). Discussion about sexuality was more frequent with patients with prostate (56.3%) and cervical (39.6%) cancer, but increasing age was associated with a greater reluctance to discuss this issue (odds ratio = 1.17, 95% CI = 1.04–1.2). The likelihood of discussion increased with severe sexual problems, radiotherapy, general sequelae, having an information-seeker profile, previous professional psychological help, and initial treatment in private centers. Patients initially wishing for psychological help were more likely to desire a discussion about sexuality.

Conclusion

Sexuality receives little attention in French patients with cancer. Inequalities in the discussion about sexuality were observed in relation to the type of care center where the patient was initially managed. Information on supportive interventions, including more systematic referral for professional psychological help, should be developed to facilitate discussion and should be offered to all patients, irrespective of severity of sexual problems, age, sex, cancer site, and care center.
Reperfusion treatment delays amongst patients with painless ST segment elevation myocardial infarction
Authors: Pek Pin Pin , Loy En Yun , Wah Win , Ho Andrew Fu Wah , Zheng Huili , Fook-Chong Stephanie Man Chung , Chua Terrance Siang Jin , Koh Tian Hai , Chow Khuan Yew , Liu Nan , Ong Marcus Eng Hock
Published: September 2016

Objective

Early reperfusion therapy in the treatment of ST segment elevation myocardial infarction (STEMI) patients can improve outcomes. Silent myocardial infarction is associated with poor prognosis, but little is known about its effect on treatment delays. We aimed to characterize STEMI patients presenting without complaints of pain to the emergency departments (EDs) in Singapore.

Methods

Retrospective data were requested from the Singapore Myocardial Infarction Registry (SMIR), a national level registry in Singapore. Painless STEMI was defined as the absence of pain (chest, back, shoulder, jaw, and epigastric pain) during ED presentation. The primary outcome was door-to-balloon (D2B) time, defined as the earliest time a patient arrived in the ED to balloon inflation. Secondary outcomes were 1-month and 1-year mortality and occurrence of adverse events.

Results

From January 2010 to December 2012, the SMIR collected 6412 cases; 10.9% of patients presented without any pain. These patients were older (median age =75 v. 58 years old), more likely to be females (39.9% v. 16.1%), Chinese (74.9% v. 62.7%), obese (median body mass index [BMI] =24.5 v. 22.1), and with history of hypertension (71.1% v. 54.6%), diabetes mellitus (48.6% v. 37.0%), and acute myocardial infarction (20.0% v. 12.3%). They had a longer median D2B (80.5 v. 63 minutes, p<0.001) and a higher occurrence of 30-day (38.4% v. 5.7%) and 1-year mortality rates (47.3% v. 8.5%).

Conclusion

A small proportion of STEMI patients presented without any pain to the ED. They tended to have a higher D2B and risks of mortality. Targeted effort is required to improve diagnostic and treatment efficiency in this group.
ZHOU FENGWU 周鳳五 (1947–2015)
Authors: Huang Kuan-yun
Published: September 2016

Zhou Fengwu, renowned scholar and Taiwan's foremost paleographer, passed away at the age of sixty-nine.
ASSESSMENT OF NUTRIENT MANAGEMENT TECHNOLOGIES FOR EGGPLANT PRODUCTION UNDER SUBTROPICAL CONDITIONS: A COMPREHENSIVE APPROACH
Authors: BATABYAL K. , MANDAL B. , SARKAR D. , MURMU S.
Published: September 2016

We developed a protocol for comprehensive evaluation of nutrient management (NM) technologies for production of eggplant taking its yield, produce quality, profitability, energy balance and environmental sustainability in terms of upkeeping soil quality as the goal variables. Fifteen NM technologies comprising of three sources of nutrients viz., organics [vermicompost (VC), farmyard manure (FYM) and mustard oil cake (MOC)], inorganic fertilizations [recommended N–P–K at the rate of 100–22–42 kg ha−1and 150% of recommended N–P–K (NPK^)] and their selected combinations were tested for growing the plants. Integrated NM technology was proved to be socio-economically sound and environment-friendly practice. It helped to upkeep soil quality by improving soil organic carbon stock, microbial biomass carbon, bulk density and available nutrients in soils. Combining all the parameters by employing non-parametric evaluation of regression factor scores through principal component analysis, the NM technology of VC3 Mg ha−1+NPK^ was found to be the best when considering the marketable fruits (12.27 Mg ha−1), economic return (benefit-cost ratio 3.3; marginal rate of return 8.7), energy conserving efficiency (net energy 113.8 GJ ha−1), soil and crop quality for human welfare. Only organics were less productive and profitable, and energetically less efficient than the integrated and inorganic NM systems and as such may not be sustainable for eggplant production in subtropical India.
Effects of dam parity and pre-weaning average daily gain of Holstein calves on future milk production
Authors: Hoseyni Fatemeh , Mahjoubi Ehsan , Zahmatkesh Davood , Yazdi Mehdi Hossein
Published: September 2016

This research communication describes relationships between pre-weaning average daily gain (ADG) and dam parity with future productivity of dairy calves. Higher ADG before weaning has been shown to be related to greater milk production in the first lactation of Holstein calves fed milk replacer. However, data is limited on the relationship between pre-weaning ADG and first lactation performance of Holstein calves fed whole milk. Data of three hundred and thirty-two Holstein calves from 35 primiparous and 297 multiparous cows was investigated to evaluate the relationship between the dam parity and pre-weaning ADG with the first lactation performance. Results indicated that birth (P < 0·01), and weaning body weight (P < 0·001) were greater in calves born from multiparous cows. Neither 305 d milk production nor pre-weaning ADG differed significantly between calves born to primiparous or multiparous cows, although milk yield tended to be higher in the former and ADG higher in the latter. Correlations between 305 d milk yield and pre-weaning ADG, dam parity and birth body weight were low and non-significant, although there was a tendency for a positive correlation between ADG and milk yield.
Seroprevalence of Trichinella infections in domestic dogs from Slovakia
Authors: Miterpáková M. , Antolová D. , Hurníková Z. , Březinová N. , Čabanová V. , Reiterová K.
Published: September 2016

Trichinellosis is constantly present in the sylvatic cycle in Slovakia, with several sporadic human outbreaks registered since the 1960s. The largest outbreak of trichinellosis occurred in 1998 and was related to the consumption of dog meat that had been added to smoked pork sausages. The aim of this study was to estimate the seroprevalence of Trichinella infection in domestic dogs in various regions of Slovakia. Out of 439 dogs tested, 56 (12.8%) were classified as a seropositive based on the enzyme-linked immunosorbent assay (ELISA), with confirmation by Western blotting. The highest seropositivity was recorded among dogs from the eastern part of Slovakia, in the Prešov (22.9%) and Košice (17.1%) regions, long considered to be highly endemic for Trichinella occurrence and where the prevalence of infection in the vulpine population is also the highest in Slovakia. Trichinella-seropositive animals were detected significantly more often in dogs kept in rural areas (21.1%) when compared with animals living in towns or suburban localities (7.7%). On the other hand, neither age, nor gender and size of the dogs were shown to be a significant factor for Trichinella infection (P > 0.05). The present results indicate that the dog population in Slovakia is at high risk of exposure to Trichinella parasites and could potentially represent a suitable host group for serological monitoring of Trichinella infection as convenient sentinel animals.
The impact of postpartum post-traumatic stress disorder symptoms on child development: a population-based, 2-year follow-up study
Authors: Garthus-Niegel S. , Ayers S. , Martini J. , von Soest T. , Eberhard-Gran M.
Published: September 2016

Background

Against the background of very limited evidence, the present study aimed to prospectively examine the impact of maternal postpartum post-traumatic stress disorder (PTSD) symptoms on four important areas of child development, i.e. gross motor, fine motor, communication and social–emotional development.

Method

This study is part of the large, population-based Akershus Birth Cohort. Data from the hospital's birth record as well as questionnaire data from 8 weeks and 2 years postpartum were used (n= 1472). The domains of child development that were significantly correlated with PTSD symptoms were entered into regression analyses. Interaction analyses were run to test whether the influence of postpartum PTSD symptoms on child development was moderated by child sex or infant temperament.

Results

Postpartum PTSD symptoms had a prospective relationship with poor child social–emotional development 2 years later. This relationship remained significant even when adjusting for confounders such as maternal depression and anxiety or infant temperament. Both child sex and infant temperament moderated the association between maternal PTSD symptoms and child social–emotional development, i.e. with increasing maternal PTSD symptom load, boys and children with a difficult temperament were shown to have comparatively higher levels of social–emotional problems.

Conclusions

Examining four different domains of child development, we found a prospective impact of postpartum PTSD symptoms on children's social–emotional development at 2 years of age. Our findings suggest that both boys and children with an early difficult temperament may be particularly susceptible to the adverse impact of postpartum PTSD symptoms. Additional studies are needed to further investigate the mechanisms at work.
Effects of early life stress on depression, cognitive performance and brain morphology
Authors: Saleh A. , Potter G. G. , McQuoid D. R. , Boyd B. , Turner R. , MacFall J. R. , Taylor W. D.
Published: September 2016

Background

Childhood early life stress (ELS) increases risk of adulthood major depressive disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure.

Method

This cross-sectional study included 64 antidepressant-free depressed and 65 never-depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T magnetic resonance imaging (MRI). Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on the cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus.

Results

Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in non-depressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects.

Conclusions

Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression.
LAST RESORT OR KEY RESOURCE? WOMEN WORKERS FROM THE NAZI-OCCUPIED SOVIET TERRITORIES, THE REICH LABOUR ADMINISTRATION AND THE GERMAN WAR EFFORT
Authors: Harvey Elizabeth
Published: September 2016

Foreign labour was an essential resource for the Nazi war economy: by September 1944, around six million civilian labourers from across Europe were working in the Reich. Any initial readiness on the part of the peoples of Nazi-occupied Europe to volunteer for work in the Reich had quickly dissipated as the harsh and often vicious treatment of foreign workers became known. The abuse and exploitation of foreign forced labourers by the Nazi regime is well documented. Less well understood is why women formed such a substantial proportion of the labour recruited or forcibly deported from occupied eastern Europe: in September 1944, a third of Polish forced labourers and just over over half of Soviet civilian forced labourers were women. This article explores the factors influencing the demand for and the supply of female labour from the Nazi-occupied territories of the Soviet Union, particularly after the appointment of Fritz Sauckel as Plenipotentiary for Labour in March 1942. It explores the attitudes of labour officials towards these women workers and shows how Nazi gender politics and the Nazi hierarchy of race intersected in the way they were treated.
Proper Emotion Recognition, Dysfunctional Emotion Regulation
Authors: Legenbauer Tanja , Hübner Jan , Pinnow Marlies , Ball Anna , Pniewski Benjamin , Holtmann Martin
Published: September 2016

Abstract. Objective: A considerable number of adolescents exhibit severe self-regulation deficits in affect and behavior, which are referred to as affective dysregulation (AD). AD may be conceptualized as a dimensional trait that, in its extreme form, resembles the diagnostic categories of severe mood dysregulation (SMD) or disruptive mood dysregulation disorder (DMDD). Assuming a shared pathway of psychopathology in AD and SMD, similar underlying dysfunctional mechanisms in emotion processing, particularly emotion recognition (RECOG) and regulation (REGUL), may be postulated. Method: Adolescent inpatients with AD (CAD, N = 35), without AD (CCG, N = 28), and nonclinical controls (NCG; N = 28) were administered a morphed facial recognition task (RECOG). REGUL abilities, levels of irritability as well as depressive symptoms were also assessed. Results: We found no significant group differences in accuracy and thresholds for RECOG abilities. Patients with AD reported more dysfunctional REGUL strategies than did CCG and NCG. Both depression and AD, but not irritability, influenced the overall degree of maladaptive REGUL. Conclusion: The broad phenotype of AD does not involve the deficits in RECOG reported for adolescents with a narrow phenotype (SMD); regarding REGUL strategies, AD seems to be associated with specific impairments.
Mesenchymal stem cells stimulate intestinal stem cells to repair radiation-induced intestinal injury
Authors: Gong Wei , Guo Mengzheng , Han Zhibo , Wang Yan , Yang Ping , Xu Chang , Wang Qin , Du Liqing , Li Qian , Zhao Hui , Fan Feiyue , Liu Qiang
Published: September 2016

The loss of stem cells residing in the base of the intestinal crypt has a key role in radiation-induced intestinal injury. In particular, Lgr5+ intestinal stem cells (ISCs) are indispensable for intestinal regeneration following exposure to radiation. Mesenchymal stem cells (MSCs) have previously been shown to improve intestinal epithelial repair in a mouse model of radiation injury, and, therefore, it was hypothesized that this protective effect is related to Lgr5+ ISCs. In this study, it was found that, following exposure to radiation, transplantation of MSCs improved the survival of the mice, ameliorated intestinal injury and increased the number of regenerating crypts. Furthermore, there was a significant increase in Lgr5+ ISCs and their daughter cells, including Ki67+ transient amplifying cells, Vil1+ enterocytes and lysozyme+ Paneth cells, in response to treatment with MSCs. Crypts isolated from mice treated with MSCs formed a higher number of and larger enteroids than those from the PBS group. MSC transplantation also reduced the number of apoptotic cells within the small intestine at 6 h post-radiation. Interestingly, Wnt3a and active β-catenin protein levels were increased in the small intestines of MSC-treated mice. In addition, intravenous delivery of recombinant mouse Wnt3a after radiation reduced damage in the small intestine and was radioprotective, although not to the same degree as MSC treatment. Our results show that MSCs support the growth of endogenous Lgr5+ ISCs, thus promoting repair of the small intestine following exposure to radiation. The molecular mechanism of action mediating this was found to be related to increased activation of the Wnt/β-catenin signaling pathway.
Pharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis
Authors: Livne-Bar Izhar , Lam Susy , Chan Darren , Guo Xiaoxin , Askar Idil , Nahirnyj Adrian , Flanagan John G , Sivak Jeremy M
Published: September 2016

Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and increased polymerization of type III intermediate filaments (IFs), particularly glial fibrillary acidic protein and vimentin. However, the consequences of IF dynamics in the adult CNS remains unclear, and no pharmacologic tools have been available to target this mechanism in vivo. The mammalian retina is an accessible model to study the regulation of astrocyte stress responses, and their influence on retinal neuronal homeostasis. In particular, our work and others have implicated p38 mitogen-activated protein kinase (MAPK) signaling as a key regulator of glutamate recycling, antioxidant activity and cytokine secretion by astrocytes and related Müller glia, with potent influences on neighboring neurons. Here we report experiments with the small molecule inhibitor, withaferin A (WFA), to specifically block type III IF dynamics in vivo. WFA was administered in a model of metabolic retinal injury induced by kainic acid, and in combination with a recent model of debridement-induced astrocyte reactivity. We show that WFA specifically targets IFs and reduces astrocyte and Müller glial reactivity in vivo. Inhibition of glial IF polymerization blocked p38 MAPK-dependent secretion of TNF-α, resulting in markedly reduced neuronal apoptosis. To our knowledge this is the first study to demonstrate that pharmacologic inhibition of IF dynamics in reactive glia protects neurons in vivo.
Posttranslational arginylation enzyme Ate1 affects DNA mutagenesis by regulating stress response
Authors: Kumar Akhilesh , Birnbaum Michael D , Patel Devang M , Morgan William M , Singh Jayanti , Barrientos Antoni , Zhang Fangliang
Published: September 2016

Arginyltransferase 1 (Ate1) mediates protein arginylation, a poorly understood protein posttranslational modification (PTM) in eukaryotic cells. Previous evidence suggest a potential involvement of arginylation in stress response and this PTM was traditionally considered anti-apoptotic based on the studies of individual substrates. However, here we found that arginylation promotes cell death and/or growth arrest, depending on the nature and intensity of the stressing factor. Specifically, in yeast, mouse and human cells, deletion or downregulation of the ATE1 gene disrupts typical stress responses by bypassing growth arrest and suppressing cell death events in the presence of disease-related stressing factors, including oxidative, heat, and osmotic stresses, as well as the exposure to heavy metals or radiation. Conversely, in wild-type cells responding to stress, there is an increase of cellular Ate1 protein level and arginylation activity. Furthermore, the increase of Ate1 protein directly promotes cell death in a manner dependent on its arginylation activity. Finally, we found Ate1 to be required to suppress mutation frequency in yeast and mammalian cells during DNA-damaging conditions such as ultraviolet irradiation. Our study clarifies the role of Ate1/arginylation in stress response and provides a new mechanism to explain the link between Ate1 and a variety of diseases including cancer. This is also the first example that the modulation of the global level of a PTM is capable of affecting DNA mutagenesis.
miRNA-558 promotes gastric cancer progression through attenuating Smad4-mediated repression of heparanase expression
Authors: Zheng Liduan , Jiao Wanju , Song Huajie , Qu Hongxia , Li Dan , Mei Hong , Chen Yajun , Yang Feng , Li Huanhuan , Huang Kai , Tong Qiangsong
Published: September 2016

Previous studies have indicated that as the only mammalian endo-β-D-glucuronidase, heparanase (HPSE) is up-regulated and associated with poor prognosis in gastric cancer, while the underlying mechanisms still remain to be determined. Herein, through integrative analysis of public datasets, we found microRNA-558 (miR-558) and SMAD family member 4 (Smad4) as the crucial transcription regulators of HPSE expression in gastric cancer, with their adjacent target sites within the promoter of HPSE. We identified that endogenous miR-558 activated the transcription and expression of HPSE in gastric cancer cell lines. In contrast, Smad4 suppressed the nascent transcription and expression of HPSE via directly binding to its promoter. Mechanistically, miR-558 recognized its complementary site within HPSE promoter to decrease the binding of Smad4 in an Argonaute 1-dependent manner. Ectopic expression or knockdown experiments indicated that miR-558 promoted the in vitro and in vivo tumorigenesis and aggressiveness of gastric cancer cell lines via attenuating Smad4-mediated repression of HPSE expression. In clinical gastric cancer specimens, up-regulation of miR-558 and down-regulation of Smad4 were positively correlated with HPSE expression. Kaplan–Meier survival analysis revealed that miR-558 and Smad4 were associated with unfavourable and favourable outcome of gastric cancer patients, respectively. Therefore, these findings demonstrate that miR-558 facilitates the progression of gastric cancer through directly targeting the HPSE promoter to attenuate Smad4-mediated repression of HPSE expression.
Quantized conductance doubling and hard gap in a two-dimensional semiconductor–superconductor heterostructure
Authors: Kjaergaard M. , Nichele F. , Suominen H. J. , Nowak M. P. , Wimmer M. , Akhmerov A. R. , Folk J. A. , Flensberg K. , Shabani J. , Palmstrøm C. J. , Marcus C. M.
Published: September 2016

Coupling a two-dimensional (2D) semiconductor heterostructure to a superconductor opens new research and technology opportunities, including fundamental problems in mesoscopic superconductivity, scalable superconducting electronics, and new topological states of matter. One route towards topological matter is by coupling a 2D electron gas with strong spin–orbit interaction to an s-wave superconductor. Previous efforts along these lines have been adversely affected by interface disorder and unstable gating. Here we show measurements on a gateable InGaAs/InAs 2DEG with patterned epitaxial Al, yielding devices with atomically pristine interfaces between semiconductor and superconductor. Using surface gates to form a quantum point contact (QPC), we find a hard superconducting gap in the tunnelling regime. When the QPC is in the open regime, we observe a first conductance plateau at 4e2/h, consistent with theory. The hard-gap semiconductor–superconductor system demonstrated here is amenable to top-down processing and provides a new avenue towards low-dissipation electronics and topological quantum systems.
Young asteroidal fluid activity revealed by absolute age from apatite in carbonaceous chondrite
Authors: Zhang Ai-Cheng , Li Qiu-Li , Yurimoto Hisayoshi , Sakamoto Naoya , Li Xian-Hua , Hu Sen , Lin Yang-Ting , Wang Ru-Cheng
Published: September 2016

Chondritic meteorites, consisting of the materials that have formed in the early solar system (ESS), have been affected by late thermal events and fluid activity to various degrees. Determining the timing of fluid activity in ESS is of fundamental importance for understanding the nature, formation, evolution and significance of fluid activity in ESS. Previous investigations have determined the relative ages of fluid activity with short-lived isotope systematics. Here we report an absolute207Pb/206Pb isochron age (4,450±50 Ma) of apatite from Dar al Gani (DaG) 978, a type ∼3.5, ungrouped carbonaceous chondrite. The petrographic, mineralogical and geochemical features suggest that the apatite in DaG 978 should have formed during metamorphism in the presence of a fluid. Therefore, the apatite age represents an absolute age for fluid activity in an asteroidal setting. An impact event could have provided the heat to activate this young fluid activity in ESS.
Aromatic thiol-mediated cleavage of N–O bonds enables chemical ubiquitylation of folded proteins
Authors: Weller Caroline E. , Dhall Abhinav , Ding Feizhi , Linares Edlaine , Whedon Samuel D. , Senger Nicholas A. , Tyson Elizabeth L. , Bagert John D. , Li Xiaosong , Augusto Ohara , Chatterjee Champak
Published: September 2016

Access to protein substrates homogenously modified by ubiquitin (Ub) is critical for biophysical and biochemical investigations aimed at deconvoluting the myriad biological roles for Ub. Current chemical strategies for protein ubiquitylation, however, employ temporary ligation auxiliaries that are removed under harsh denaturing conditions and have limited applicability. We report an unprecedented aromatic thiol-mediated N–O bond cleavage and its application towards native chemical ubiquitylation with the ligation auxiliary 2-aminooxyethanethiol. Our interrogation of the reaction mechanism suggests a disulfide radical anion as the active species capable of cleaving the N–O bond. The successful semisynthesis of full-length histone H2B modified by the small ubiquitin-like modifier-3 (SUMO-3) protein further demonstrates the generalizability and compatibility of our strategy with folded proteins.
ICER is requisite for Th17 differentiation
Authors: Yoshida Nobuya , Comte Denis , Mizui Masayuki , Otomo Kotaro , Rosetti Florencia , Mayadas Tanya N. , Crispín José C. , Bradley Sean J. , Koga Tomohiro , Kono Michihito , Karampetsou Maria P. , Kyttaris Vasileios C. , Tenbrock Klaus , Tsokos George C.
Published: September 2016

Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6–STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4+ T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane-induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4+ T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17-dependent manner.
Should the diagnosis of COPD be based on a single spirometry test?
Authors: Schermer Tjard R , Robberts Bas , Crockett Alan J , Thoonen Bart P , Lucas Annelies , Grootens Joke , Smeele Ivo J , Thamrin Cindy , Reddel Helen K
Published: September 2016

Clinical guidelines indicate that a chronic obstructive pulmonary disease (COPD) diagnosis is made from a single spirometry test. However, long-term stability of diagnosis based on forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) ratio has not been reported. In primary care subjects at risk for COPD, we investigated shifts in diagnostic category (obstructed/non-obstructed). The data were from symptomatic 40+ years (ex-)smokers referred for diagnostic spirometry, with three spirometry tests, each 12±2 months apart. The obstruction was based on post-bronchodilator FEV1/FVC < lower limit of normal (LLN) and <0.70 (fixed ratio). A total of 2,352 subjects (54% male, post-bronchodilator FEV1 76.5% predicted) were studied. By LLN definition, 32.2% were obstructed at baseline, but 32.2% of them were no longer obstructed at years 1 and/or 2. By fixed ratio, these figures were 46.6 and 23.8%, respectively. Overall, 14.3% of subjects changed diagnostic category by 1 year and 15.4% by 2 years when applying the LLN cut-off, and 15.1 and 14.6% by fixed ratio. Change from obstructed to non-obstructed was more likely for patients with higher body mass index (BMI) and baseline short-acting bronchodilator (SABA) users, and less likely for older subjects, those with lower FEV1% predicted, baseline inhaled steroid users, and current smokers or SABA users at year 1. Change from non-obstructed to obstructed was more likely for males, older subjects, current smokers and patients with lower baseline FEV1% predicted, and less likely for those with higher baseline BMI. Up to one-third of symptomatic (ex-)smokers with baseline obstruction on diagnostic spirometry had shifted to non-obstructed when routinely re-tested after 1 or 2 years. Given the implications for patients and health systems of a diagnosis of COPD, it should not be based on a single spirometry test.
Interplay between cell cycle and autophagy induced by boswellic acid analog
Authors: Pathania Anup S. , Guru Santosh K. , Kumar Suresh , Kumar Ashok , Ahmad Masroor , Bhushan Shashi , Sharma Parduman R. , Mahajan Priya , Shah Bhahwal A. , Sharma Simmi , Nargotra Amit , Vishwakarma Ram , Korkaya Hasan , Malik Fayaz
Published: September 2016

In this study, we investigated the role of autophagy induced by boswellic acid analog BA145 on cell cycle progression in pancreatic cancer cells. BA145 induced robust autophagy in pancreatic cancer cell line PANC-1 and exhibited cell proliferation inhibition by inducing cells to undergo G2/M arrest. Inhibition of G2/M progression was associated with decreased expression of cyclin A, cyclin B, cyclin E, cdc2, cdc25c and CDK-1. Pre-treatment of cells with autophagy inhibitors or silencing the expression of key autophagy genes abrogated BA145 induced G2/M arrest and downregulation of cell cycle regulatory proteins. It was further observed that BA145 induced autophagy by targeting mTOR kinase (IC50 1 μM), leading to reduced expression of p-mTOR, p-p70S6K (T389), p-4EBP (T37/46) and p-S6 (S240/244). Notably, inhibition of mTOR signalling by BA145 was followed by attendant activation of AKT and its membrane translocation. Inhibition of Akt through pharmacological inhibitors or siRNAs enhanced BA145 mediated autophagy, G2/M arrest and reduced expression of G2/M regulators. Further studies revealed that BA145 arbitrated inhibition of mTOR led to the activation of Akt through IGFR/PI3k/Akt feedback loop. Intervention in IGFR/PI3k/Akt loop further depreciated Akt phosphorylation and its membrane translocation that culminates in augmented autophagy with concomitant G2/M arrest and cell death.
Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels
Authors: Haque Amranul , Gheibi Pantea , Gao Yandong , Foster Elena , Son Kyung Jin , You Jungmok , Stybayeva Gulnaz , Patel Dipali , Revzin Alexander
Published: September 2016

The approaches for maintaining hepatocytes in vitro are aimed at recapitulating aspects of the native liver microenvironment through the use of co-cultures, surface coatings and 3D spheroids. This study highlights the effects of spatial confinement-a less studied component of the in vivo microenvironment. We demonstrate that hepatocytes cultured in low-volume microfluidic channels (microchambers) retain differentiated hepatic phenotype for 21 days whereas cells cultured in regular culture plates under identical conditions de-differentiate after 7 days. Careful consideration of nutrient delivery and oxygen tension suggested that these factors could not solely account for enhanced cell function in microchambers. Through a series of experiments involving microfluidic chambers of various heights and inhibition of key molecular pathways, we confirmed that phenotype of hepatocytes in small volumes was shaped by endogenous signals, both hepato-inductive growth factors (GFs) such as hepatocyte growth factor (HGF) and hepato-disruptive GFs such as transforming growth factor (TGF)-β1. Hepatocytes are not generally thought of as significant producers of GFs–this role is typically assigned to nonparenchymal cells of the liver. Our study demonstrates that, in an appropriate microenvironment, hepatocytes produce hepato-inductive and pro-fibrogenic signals at the levels sufficient to shape their phenotype and function.
Genomic Selection Improves Heat Tolerance in Dairy Cattle
Authors: Garner J. B. , Douglas M. L. , Williams S. R. O , Wales W. J. , Marett L. C. , Nguyen T. T. T. , Reich C. M. , Hayes B. J.
Published: September 2016

Dairy products are a key source of valuable proteins and fats for many millions of people worldwide. Dairy cattle are highly susceptible to heat-stress induced decline in milk production, and as the frequency and duration of heat-stress events increases, the long term security of nutrition from dairy products is threatened. Identification of dairy cattle more tolerant of heat stress conditions would be an important progression towards breeding better adapted dairy herds to future climates. Breeding for heat tolerance could be accelerated with genomic selection, using genome wide DNA markers that predict tolerance to heat stress. Here we demonstrate the value of genomic predictions for heat tolerance in cohorts of Holstein cows predicted to be heat tolerant and heat susceptible using controlled-climate chambers simulating a moderate heatwave event. Not only was the heat challenge stimulated decline in milk production less in cows genomically predicted to be heat-tolerant, physiological indicators such as rectal and intra-vaginal temperatures had reduced increases over the 4 day heat challenge. This demonstrates that genomic selection for heat tolerance in dairy cattle is a step towards securing a valuable source of nutrition and improving animal welfare facing a future with predicted increases in heat stress events.
A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force
Authors: Bano Fouzia , Banerji Suneale , Howarth Mark , Jackson David G. , Richter Ralf P.
Published: September 2016

Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.
Band Gap Engineering of Two-Dimensional Nitrogene
Authors: Li Jie-Sen , Wang Wei-Liang , Yao Dao-Xin
Published: September 2016

In our previous study, we have predicted the novel two-dimensional honeycomb monolayers of pnictogen. In particular, the structure and properties of the honeycomb monolayer of nitrogen, which we call nitrogene, are very unusual. In this paper, we make an in-depth investigation of its electronic structure. We find that the band structure of nitrogene can be engineered in several ways: controlling the stacking of monolayers, application of biaxial tensile strain, and application of perpendicular electric field. The band gap of nitrogene is found to decrease with the increasing number of layers. The perpendicular electric field can also reduce the band gap when it is larger than 0.18 V/Å, and the gap closes at 0.35 V/Å. A nearly linear dependence of the gap on the electric field is found during the process. Application of biaxial strain can decrease the band gap as well, and eventually closes the gap. After the gap-closing, we find six inequivalent Dirac points in the Brillouin zone under the strain between 17% and 28%, and the nitrogene monolayer becomes a Dirac semimetal. These findings suggest that the electronic structure of nitrogene can be modified by several techniques, which makes it a promising candidate for electronic devices.
Large low field magnetocaloric effect in first-order phase transition compound TlFe3Te3 with low-level hysteresis
Authors: Mao Qianhui , Yang Jinhu , Wang Hangdong , Khan Rajwali , Du Jianhua , Zhou Yuxing , Xu Binjie , Chen Qin , Fang Minghu
Published: September 2016

Magnetic refrigeration based on the magnetocaloric effect (MCE) is an environment-friendly, high-efficiency technology. It has been believed that a large MCE can be realized in the materials with a first-order magnetic transition (FOMT). Here, we found that TlFe3Te3 is a ferromagnetic metal with a first-order magnetic transition occurring at Curie temperature TC = 220 K. The maximum values of magnetic entropy change (Δ"Equation missing") along the crystallographic c-axis, estimated from the magnetization data, reach to 5.9 J kg−1K−1 and 7.0 J kg−1 K−1 for the magnetic field changes, ΔH = 0–1 T and 0–2 T, respectively, which is significantly larger than that of MCE materials with a second-order magnetic transition (SOMT). Besides the large ΔSM, the low-level both thermal and field hysteresis make TlFe3Te3 compound an attractive candidate for magnetic refrigeration. Our findings should inspire the exploration of high performance new MCE materials.
Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury
Authors: Chen Yu-Li , Hwang Tsong-Long , Yu Huang-Ping , Fang Jia-You , Chong Kowit Yu , Chang Yao-Wen , Chen Chun-Yu , Yang Hsuan-Wu , Chang Wen-Yi , Hsieh Pei-Wen
Published: September 2016

Acute lung injury (ALI) is a severe respiratory disease with high mortality rates worldwide. Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy. In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs). Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC50, 11.37 ± 1.59 μg/mL). Using bioactivity-guided fractionation, one new compound and 23 known compounds were identified. Compound 6 (identified as 3,5-dicaffeoylquinic acid; 3,5-DCQA) exerted the most potent and selective inhibitory effect on HNE activity (IC50, 1.86 ± 0.06 μM). In a cell-based assay, 3,5-DCQA not only directly reduced superoxide generation and elastase activity but also attenuated the Src family kinase (SRKs)/Vav signaling pathway in N-formyl-L-Met-L-Leu-L-Phe (fMLF)-stimulated human neutrophils. In an animal disease model, both 3,5-DCQA and standardized IKWE protected against lipopolysaccharide-induced ALI in mice, which provides support for their potential as candidates in the development of new therapeutic agents for neutrophilic inflammatory diseases.
Identity information content depends on the type of facial movement
Authors: Dobs Katharina , Bülthoff Isabelle , Schultz Johannes
Published: September 2016

Facial movements convey information about many social cues, including identity. However, how much information about a person’s identity is conveyed by different kinds of facial movements is unknown. We addressed this question using a recent motion capture and animation system, with which we animated one avatar head with facial movements of three types: (1) emotional, (2) emotional in social interaction and (3) conversational, all recorded from several actors. In a delayed match-to-sample task, observers were best at matching actor identity across conversational movements, worse with emotional movements in social interactions, and at chance level with emotional facial expressions. Model observers performing this task showed similar performance profiles, indicating that performance variation was due to differences in information content, rather than processing. Our results suggest that conversational facial movements transmit more dynamic identity information than emotional facial expressions, thus suggesting different functional roles and processing mechanisms for different types of facial motion.
Formation of droplet interface bilayers in a Teflon tube
Authors: Walsh Edmond , Feuerborn Alexander , Cook Peter R.
Published: September 2016

Droplet-interface bilayers (DIBs) have applications in disciplines ranging from biology to computing. We present a method for forming them manually using a Teflon tube attached to a syringe pump; this method is simple enough it should be accessible to those without expertise in microfluidics. It exploits the properties of interfaces between three immiscible liquids and uses fluid flow through the tube to pack together drops coated with lipid monolayers to create bilayers at points of contact. It is used to create functional nanopores in DIBs composed of phosphocholine using the protein α-hemolysin (αHL), to demonstrate osmotically-driven mass transfer of fluid across surfactant-based DIBs and to create arrays of DIBs. The approach is scalable and thousands of DIBs can be prepared using a robot in one hour; therefore, it is feasible to use it for high throughput applications.
Detecting individual extracellular vesicles using a multicolor in situ proximity ligation assay with flow cytometric readout
Authors: Löf Liza , Ebai Tonge , Dubois Louise , Wik Lotta , Ronquist K. Göran , Nolander Olivia , Lundin Emma , Söderberg Ola , Landegren Ulf , Kamali-Moghaddam Masood
Published: September 2016

Flow cytometry is a powerful method for quantitative and qualitative analysis of individual cells. However, flow cytometric analysis of extracellular vesicles (EVs) and the proteins present on their surfaces has been hampered by the small size of the EVs – in particular for the smallest EVs, which can be as little as 40 nm in diameter, the limited number of antigens present and their low refractive index. We addressed these limitations for detection and characterization of EV by flow cytometry through the use of multiplex and multicolor in situ proximity ligation assays (in situ PLA), allowing each detected EV to be easily recorded over background noise using a conventional flow cytometer. By targeting sets of proteins on the surface that are specific for distinct classes of EVs, the method allows for selective recognition of populations of EVs in samples containing more than one type of EVs. The method presented herein opens up for analyses of EVs using flow cytometry for their characterization and quantification.