bluuebunny/crossref_metadata_2025 huggingface dataset:
Pectin Penta‐Oligogalacturonide Suppresses Intestinal Bile Acids Absorption and Downregulates the FXR‐FGF15 Axis in High‐Cholesterol Fed Mice
Authors: Zhu Rugang , Hou Yuting , Sun Yandi , Li Tuoping , Fan Jungang , Chen Gang , Wei Junxiu
Published: May 2017

Haw pectin penta‐oligogalacturonide (HPPS), purified from the hydrolysates of haw pectin, has important role in decreasing hepatic cholesterol accumulation and promoting bile acids (BA) excretion in the feces of mice fed a high‐cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on BA reabsorption in ileum and biosynthesis in liver of mice. Results showed that HPPS increased fecal BA output by approximately 110%, but decreased ileal BA and the total BA pool size by approximately 47 and 36%, respectively, compared to HCD. Studies of molecular mechanism revealed that HPPS significantly decreased the mRNA and protein levels of farnesoid X receptor (FXR) in the small intestine of mice and inactivated the fibroblast growth factor 15 (FXR‐FGF15) axis, which increased the mRNA and protein levels of CYP7A1 by approximately 204 and 104%, respectively, compared to HCD. Interestingly, the mRNA and protein levels of apical sodium‐dependent bile acid transporter (ASBT) in the small intestine were approximately 128 and 73% higher in HPPS‐fed mice than those in HCD‐fed mice, respectively. However, no significant difference was detected for ASBT expression between HCD group and BA sequestrant cholestyramine group. These findings indicate that HPPS can suppress intestinal BA reabsorption and promoting hepatic BA biosynthesis. We speculated that HPPS could be ASBT competitive inhibitor rather than BA sequestrant in inhibiting BA reabsorption in ileum and improving cholesterol metabolism.
The structure of PTSD symptoms according to DSM-5 and IDC-11 proposal: A multi-sample analysis
Authors: Cyniak-Cieciura M. , Staniaszek K. , Popiel A. , Pragłowska E. , Zawadzki B.
Published: May 2017

Posttraumatic stress disorder (PTSD) symptoms structure is a subject of ongoing debate since its inclusion in DSM-III classification in 1980. Different research on PTSD symptoms structure proved the better fit of four-factor and five-factor models comparing to the one proposed by DSM-IV. With the publication of DSM-5 classification, which introduced significant changes to PTSD diagnosis, the question arises about the adequacy of the proposed criteria to the real structure of disorder symptoms. Recent analyses suggest that seven-factor hybrid model is the best reflection of symptoms structure proposed to date. At the same time, some researchers and ICD-11 classification postulate a simplification of PTSD diagnosis restricting it to only three core criteria and adding additional diagnostic unit of complex-PTSD. This research aimed at checking symptoms’ structure according to well-known and supported four-, five-, six- and seven-factor models based on DSM-5 symptoms and the conceptualization proposed by the ICD-11 as well as examining the relation between PTSD symptoms categories with borderline personality disorder. Four different trauma populations were examined with self-reported Posttraumatic Diagnostic Scale for DSM-5 (PDS-5) measure. The results suggest that six- and seven-factor hybrid model as well as three-factor ICD-11 concept fits the data better than other models. The core PTSD symptoms were less related to borderline personality disorder than other, broader, symptoms categories only in one sample. Combination of ICD-11 simplified PTSD diagnosis with the more complex approach (e.g. basing on a seven-factor model) may be an attractive proposal for both scientists and practitioners, however does not necessarily lower its comorbidity with borderline personality disorder.
Prophylactic Acetaminophen or Ibuprofen Result in Equivalent Acute Mountain Sickness Incidence at High Altitude: A Prospective Randomized Trial
Authors: Kanaan Nicholas C. , Peterson Alicia L. , Pun Matiram , Holck Peter S. , Starling Jennifer , Basyal Bikash , Freeman Thomas F. , Gehner Jessica R. , Keyes Linda , Levin Dana R. , O’Leary Catherine J. , Stuart Katherine E. , Thapa Ghan B. , Tiwari Aditya , Velgersdyk Jared L. , Zafren Ken , Basnyat Buddha
Published: May 2017

Objective

Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen’s mechanism of possible symptom reduction by predominantly mediating nociception in the brain.

Methods

A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score.

Results

Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS ( P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS.

Conclusions

We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed.
Product set phenomena for measured groups
Authors: BJÖRKLUND MICHAEL
Published: May 2017

We strengthen and extend in this paper some recent results by Di Nasso, Goldbring, Jin, Leth, Lupini and Mahlburg on piecewise syndeticity of product sets in countableamenablegroups to general countable measured groups. We also address several fundamental differences between the behavior of products of ‘large’ sets in Liouville and non-Liouville measured groups. As a (very) special case of our main results, we show that if$G$is a free group of finite rank, and$A$and$B$are ‘spherically large’ subsets of$G$, then there exists a finite set$F\subset G$such that$AFB$is thick. The position of the set$F$is curious, but seems to be necessary; in fact, we can produceleft thicksets$A,B\subset G$such that$B$is ‘spherically large’, but$AB$isnotpiecewise syndetic. On the other hand, if$A$is spherically large, then$AA^{-1}$is always piecewise syndeticandpiecewise left syndetic. However, contrary to what happens for amenable groups,$AA^{-1}$may fail to be syndetic. The same phenomena occur for many other (even amenable, but non-Liouville) measured groups. Our proofs are based on some ergodic-theoretical results concerning stationary actions which should be of independent interest.
Lyapunov-maximizing measures for pairs of weighted shift operators
Authors: MORRIS IAN D.
Published: May 2017

Motivated by recent investigations of ergodic optimization for matrix cocycles, we study the measures of the maximum top Lyapunov exponent for pairs of bounded weighted shift operators on a separable Hilbert space. We prove that, for generic pairs of weighted shift operators, the Lyapunov-maximizing measure is unique, and show that there exist pairs of operators whose unique Lyapunov-maximizing measure takes any prescribed value less than $\log 2$ for its metric entropy. We also show that, in contrast to the matrix case, the Lyapunov-maximizing measures of pairs of bounded operators are, in general, not characterized by their supports: we construct explicitly a pair of operators and a pair of ergodic measures on the 2-shift with identical supports, such that one of the two measures is Lyapunov-maximizing for the pair of operators and the other measure is not. Our proofs make use of the Ornstein $\overline{d}$-metric to estimate differences in the top Lyapunov exponent of a pair of weighted shift operators as the underlying measure is varied.
Smale solenoid attractors and affine Hirsch foliations
Authors: YU BIN
Published: May 2017

The main purpose of this paper is to study north–south Smale solenoid diffeomorphisms on$3$-manifolds by using affine Hirsch foliations. A north–south Smale solenoid diffeomorphism$f$on a closed$3$-manifold$M$is a diffeomorphism whose non-wandering set is composed of a Smale solenoid attractor$\unicode[STIX]{x1D6EC}_{a}$and a Smale solenoid repeller$\unicode[STIX]{x1D6EC}_{r}$. The key observation is that a north–south Smale solenoid diffeomorphism$f$automatically induces two non-isotopically leaf-conjugate affine Hirsch foliations${\mathcal{H}}^{s}$and${\mathcal{H}}^{u}$on the orbit space of the wandering set of$f$(abbreviated to thewandering orbit spaceof$f$) by the stable and unstable manifolds of$\unicode[STIX]{x1D6EC}_{a}$and$\unicode[STIX]{x1D6EC}_{r}$, respectively. Under this viewpoint, we build some close relationships between north–south Smale solenoid diffeomorphisms and Hirsch manifolds (the closed$3$-manifolds admitting two non-isotopically leaf-conjugate affine Hirsch foliations).

∙

On the one hand, the union of the wandering orbit spaces is nearly in one-to-one correspondence with the union of Hirsch manifolds.

∙

On the other hand, surprisingly, the topology of the wandering orbit space (Hirsch manifold) is nearly a complete invariant of north–south Smale solenoid diffeomorphisms up to semi-global conjugacy.

Moreover, as applications, we consider several more concrete questions. For instance, we prove that every diffeomorphism in many semi-global conjugacy classes of north–south Smale solenoid diffeomorphisms are not structurally stable.
A sticky situation
Authors: Brun P.-T.
Published: May 2017

The whirling helical structure obtained when pouring honey onto toast may seem like an easy enough problem to solve at breakfast. Specifically, one would hope that a quick back-of-the-envelope scaling argument would help rationalize the observed behaviour and predict the coiling frequency. Not quite: multiple forces come into play, both in the part of the flow stretched by gravity and in the coil itself, which buckles and bends like a rope. In fact, the resulting abundance of regimes requires the careful numerical continuation method reported by Ribe (J. Fluid Mech., vol. 812, 2017, R2) to build a complete phase diagram of the problem and untangle this sticky situation.
Negative polarity items in Ewe
Authors: COLLINS CHRIS , POSTAL PAUL M. , YEVUDEY ELVIS
Published: May 2017

Collins & Postal (2014) argue that English NPIs have two distinct syntactic structures: a unary NEG structure and a binary NEG structure. They suggest that this distinction is generally valid for natural languages. This formal difference was taken to reconstruct the common distinction in NPI studies between strong and weak NPIs. The present analysis of Ewe NPIs seeks to provide cross-linguistic support for this dual conception of NPIs by showing that theke-NPIs in this language are all properly analyzed exclusively as unary NEG structures.
Ethnic inequality in retirement income: a comparative analysis of immigrant–native gaps in Western Europe
Authors: HEISIG JAN PAUL , LANCEE BRAM , RADL JONAS
Published: May 2017

Previous research unequivocally shows that immigrants are less successful in the labour market than the native-born population. However, little is known about whether ethnic inequality persists after retirement. We use data on 16 Western European countries from the European Union Statistics on Income and Living Conditions (EU-SILC, 2004–2013) to provide the first comparative study of ethnic inequalities among the population aged 65 and older. We focus on the retirement income gap (RIG) between immigrants from non-European Union countries and relate its magnitude to country differences in welfare state arrangements. Ethnic inequality after retirement is substantial: after adjusting for key characteristics including age, education and occupational status, the average immigrant penalty across the 16 countries is 28 per cent for men and 29 per cent for women. Country-level regressions show that income gaps are smaller in countries where the pension system is more redistributive. We also find that easy access to long-term residence is associated with larger RIGs, at least for men. There is no clear evidence that immigrants’ access to social security programmes, welfare state transfers to working-age households or the strictness of employment protection legislation affect the size of the RIG.
Polynomial chaos assessment of design tolerances for vortex-induced vibrations of two cylinders in tandem
Authors: Geraci Gianluca , De Tullio Marco Donato , Iaccarino Gianluca
Published: May 2017

The presence of aerodynamics loadings makes the design of some classes of elastic structures, as, for instance, marine structures and risers, very challenging. Moreover, capturing the complex physical interaction between the structure and the fluid is challenging for both theoretical and numerical models. One of the most important phenomena that appear in these situations is vortex-induced vibrations. The picture is even more complicated when multiple elastic elements are close enough to interact by modifying the fluid flow pattern. In the present work, we show how the common design practice for these structures, which is entirely based on deterministic simulations, needs to be complemented by the uncertainty quantification analysis. The model problem is a structure constituted by two elastically mounted cylinders exposed to a two-dimensional uniform flow at Reynolds number 200. The presence of a manufacturing tolerance in the relative position of the two cylinders, which we consider to be a source of uncertainty, is addressed. The overall numerical procedure is based on a Navier–Stokes immersed boundary solver that uses a flexible moving least squares approach to compute the aerodynamics loadings on the structure, whereas the uncertainty quantification propagation is obtained by means of a nonintrusive polynomial chaos technique. A range of reduced velocities is considered, and the quantification, in a probabilistic sense, of the difference in the performances of this structure with respect to the case of an isolated cylinder is provided. The numerical investigation is also complemented by a global sensitivity analysis based on the analysis of variance.
Change mode and effects analysis by enhanced grey relational analysis under subjective environments
Authors: Zhu Guo-Niu , Hu Jie , Qi Jin , He Tao , Peng Ying-Hong
Published: May 2017

Change mode and effects analysis (CMEA) is a powerful technique for measuring product flexibility toward future changes and diminishing the cost of redesign as well as shortening time to market. As a systematic methodology, it provides an in-depth view for the investigation of potential changes, causes, and effects in designs, products, and processes. Traditional CMEA determines the risk priorities of change modes by using change potential number, which requires the risk factors of design flexibility, occurrence, and readiness to be precisely evaluated. However, this is not always possible in real applications due to the uncertainty and subjectivity involved in the early design stages. It has been criticized much for its deficiencies in criteria weighting of the risk factors, change potential number calculation, and risk priorities determination of the change modes. This paper presents a systematic evaluation approach for determining a more rational rank of change modes by combining with the entropy weight method, rough number, and grey relational analysis. In this study, the entropy weight method is adopted to calculate the relative importance of risk factors. Rough number is presented to aggregate individual weights and preferences, and to manipulate the vagueness in the evaluation process. Then a rough number enhanced grey relational analysis is proposed to evaluate the risk ranking of change modes. Finally, a practical example is put forward to validate the performance of the proposed method. The result shows that the proposed change mode evaluation method can effectively overcome the shortcomings of traditional CMEA and strengthen the objectivity of product flexibility measurement.
Connectedness with things. Animated objects of Viking Age Scandinavia and early medieval Europe
Authors: Lund Julie
Published: May 2017

This article examines a small group of artefacts of the Viking Age that may have been perceived as animated objects. These specific weapons and pieces of jewellery appear in narratives in the Old Norse sources as named, as having a will of their own, as possessing personhood. In archaeological contexts the same types of artefact are handled categorically differently than the rest of the material culture. Further, the possible links between these perspectives and the role of animated objects in early medieval Christianity of the Carolingian Empire are examined through studies of the reopening of Reihengräber and the phenomenon offurta sacra. By linking studies of the social biographies of objects with studies of animism, the article aims to identify aspects of Viking Age ontology and its similarities to Carolingian Christianity.
The automated patient discharge summary: improving communication at transfers of care after completion of radiotherapy
Authors: Rozanec Natalie , Chan Edwin , Malam Shaziya , Loudon James
Published: May 2017

Aim

To develop an auto-generated patient discharge summary for all patients being treated in the Radiation Therapy Department.

Materials and methods

A patient discharge summary was developed using auto-generated data for all patients being treated in the Radiation Therapy Department. This ensures information relevant to the care of the patient is communicated effectively during transitions of care following radiation treatment, and provides a record of the treatment site(s), dose delivered, start/completion dates and contact information for Radiation Oncologists. The eScribe feature in MosaiQTM is utilised to auto-generate the patient discharge summary in less than one minute, and then printed and given to patients on the last day of treatment. This was piloted with palliative radiotherapy patients (n=22), who also completed a telephone survey.

Results

Results revealed patients had passed this document onto other healthcare providers and appreciated having a record of their treatments. Feedback was obtained from radiation therapy staff and the Patient and Family Advisory Committee. Subsequently, the language of the patient discharge summary was simplified and a disclaimer was added, indicating the document is not a complete radiation therapy treatment record. This initiative was then rolled out to all radiotherapy patients.

Findings

Overall, the patient discharge summary allows for a quick, automated and standardised approach for transfer of information during care transitions without significant impact to the Radiation Therapy Departmental workflow.
A stochastic Expectation–Maximisation (EM) algorithm for construction of mortality tables
Authors: Esparza Luz Judith R. , Baltazar-Larios Fernando
Published: May 2017

In this paper, we present an extension of the model proposed by Lin & Liu that uses the concept of physiological age to model the ageing process by using phase-type distributions to calculate the probability of death. We propose a finite-state Markov jump process to model the hypothetical ageing process in which it is possible the transition rates between non-consecutive physiological ages. Since the Markov process has only a single absorbing state, the death time follows a phase-type distribution. Thus, to build a mortality table the challenge is to estimate this matrix based on the records of the ageing process. Considering the nature of the data, we consider two cases: having continuous time information of the ageing process, and the more interesting and realistic case, having reports of the process just in determined times. If the ageing process is only observed at discrete time points we have a missing data problem, thus, we use a stochastic Expectation–Maximisation (SEM) algorithm to find the maximum likelihood estimator of the intensity matrix. And in order to do that, we build Markov bridges which are sampled using the Bisection method. The theory is illustrated by a simulation study and used to fit real data.
Stealth democracy and the support for new and challenger parties
Authors: Lavezzolo Sebastián , Ramiro Luis
Published: May 2017

In the wake of the 2008 Great Recession, new and challenger parties have enjoyed electoral gains in some European countries. Political and economic disaffection have been pointed out as the main drivers of their electoral support. This article proposes voter’s stealth democracy attitudes, as defined by Hibbing and Theiss-Morse, as an additional driving force to account for this electoral change. We examine the case of Spain with a survey conducted after the far-reaching transformation of the party system, which has led to the emergence of two new parties:Ciudadanos(on the center-right) andPodemos(on the radical-left). We find that stealth democracy attitudes are positively related to the support for the former and negatively related to the support for the latter. Additionally, we provide evidence of this relationship being conditional on voters’ ideology. The study illustrates how an unexplored attitudinal dimension contributes to party system change, and how the relevance of these attitudes might go beyond the temporary political discontent caused by the economic crisis.
Expanding Suicide Crisis Services to Text and Chat
Authors: Predmore Zachary , Ramchand Rajeev , Ayer Lynsay , Kotzias Virginia , Engel Charles , Ebener Patricia , Kemp Janet E. , Karras Elizabeth , Haas Gretchen L.
Published: May 2017

Abstract. Background: Crisis support services have historically been offered by phone-based suicide prevention hotlines, but are increasingly becoming available through alternative modalities, including Internet chat and text messaging. Aims: To better understand differences in the use of phone and chat/text services. Method: We conducted semistructured interviews with call responders at the Veterans Crisis Line who utilize multimodal methods to respond to veterans in crisis. Results: Responders indicated that veterans may access the chat/text service primarily for reasons that included a desire for anonymity and possible inability to use the phone. Responders were divided on whether callers and chatters presented with different issues or risk of suicide; however, they suggested that veterans frequently use chat/text to make their first contact with mental health services. Limitations: We spoke with call responders, not the veterans themselves. Additionally, as this is qualitative research, applicability to other settings may be limited. Conclusion: While new platforms offer promise, participants also indicated that chat services can supplement phone lines, but not replace them.
Loss of miR-514a-3p regulation of PEG3 activates the NF-kappa B pathway in human testicular germ cell tumors
Authors: Özata Deniz Mahmut , Li Xidan , Lee Linkiat , Liu Jikai , Warsito Dudi , Hajeri Praveensingh , Hultman Isabell , Fotouhi Omid , Marklund Stefan , Ährlund-Richter Lars , Juhlin Carl Christofer , Larsson Catharina , Lui Weng-Onn
Published: May 2017

Deregulation of microRNAs (miRNAs) contributes to the development and progression of many cancer types; however, their functions in the pathogenesis of testicular germ cell tumor (TGCT) remain unclear. Here, we determined miRNA expression profiles of TGCTs and normal testes using small RNA sequencing, and identified several deregulated miRNAs in TGCTs, including the miR-506~514 cluster. In functional studies in vitro we demonstrated that miR-514a-3p induced apoptosis through direct regulation of the paternally expressed gene 3 (PEG3), and ectopically expressed PEG3 could rescue the apoptotic effect of miR-514a-3p overexpression. Silencing of PEG3 or miR-514a-3p overexpression reduced nuclear accumulation of p50 and NF-κB reporter activity. Furthermore, PEG3 was co-immunoprecipitated with tumor necrosis factor receptor-associated factor 2 (TRAF2) in TGCT cell lysates. We propose a model of PEG3-mediated activation of NF-κB in TGCT. Loss of miR-514a-3p expression in TGCT increases PEG3 expression that recruits TRAF2 and activates the NF-kappa B pathway, which protects germ cells from apoptosis. Importantly, we observed strong expression of PEG3 and nuclear p50 in the majority of TGCTs (83% and 78%, respectively). In conclusion, our study describes a novel function for miR-514a-3p in TGCT and highlights an unrecognized mechanism of PEG3 regulation and NF-κB activation in TGCT.
Erratum: Amino-acid transporters in T-cell activation and differentiation
Authors: Ren Wenkai , Liu Gang , Yin Jie , Tan Bie , Wu Guoyao , Bazer Fuller W , Peng Yuanyi , Yin Yulong
Published: May 2017

Correction to: Cell Death and Disease (2017) 8, e2655; doi:10.1038/cddis.2016.222; published online 2 March 2017. It has been noticed since publication of this article that the full names of the authors were omitted. The correct author list is as follows: Wenkai Ren, Gang Liu, Jie Yin, Bie Tan, Guoyao Wu, Fuller W Bazer, Yuanyi Peng, Yulong Yin
MiR-1 suppresses tumor cell proliferation in colorectal cancer by inhibition of Smad3-mediated tumor glycolysis
Authors: Xu Wanfu , Zhang Zijing , Zou Kejian , Cheng Yang , Yang Min , Chen Huan , Wang Hongli , Zhao Junhong , Chen Peiyu , He Liying , Chen Xinwen , Geng Lanlan , Gong Sitang
Published: May 2017

Aberrant expression of microRNA (miR)-1 has been observed in many human malignancies. However, the function and underlying mechanism of miR-1 remains elusive. To address the specific role of miR-1 in tumor glycolysis using the gain- or loss-of-function studies. Metabolic studies combined with gene expression analysis were performed in vitro and in vivo. We demonstrated aberrant expression of miR-1 in aerobic glycolysis, the Warburg effect, in cancer cells. MiR-1 suppressed aerobic glycolysis and tumor cell proliferation via inactivation of Smad3 and targeting HIF-1α, leading to reduce HK2 and MCT4 expression, which illustrated a novel pathway to mediate aerobic glycolysis in cancer cells. Overexpression of miR-1 mimics significantly decreased tumor glycolysis, including lactate production and glucose uptake, and cell proliferation, and these effects were reversed by ectopic expression of Smad3. Importantly, endogenous Smad3 regulated and interacted with HIF-1α, resulting in increasing activity of Smad3, and this interaction was dramatically abolished by addition of miR-1. We further demonstrated that Smad3 was central to the effects of miR-1 in colorectal cancer cells, establishing a previously unappreciated mechanism by which the miR-1/Smad3/HIF-1α axis facilitates the Warburg effect to promote cancer progression in vitro and in vivo. The results indicate that miR-1 may have an essential role as a tumor suppressor, suggesting its potential role in molecular therapy of patients with advanced colorectal cancer.
Automated multiplex genome-scale engineering in yeast
Authors: Si Tong , Chao Ran , Min Yuhao , Wu Yuying , Ren Wen , Zhao Huimin
Published: May 2017

Genome-scale engineering is indispensable in understanding and engineering microorganisms, but the current tools are mainly limited to bacterial systems. Here we report an automated platform for multiplex genome-scale engineering in Saccharomyces cerevisiae, an important eukaryotic model and widely used microbial cell factory. Standardized genetic parts encoding overexpression and knockdown mutations of >90% yeast genes are created in a single step from a full-length cDNA library. With the aid of CRISPR-Cas, these genetic parts are iteratively integrated into the repetitive genomic sequences in a modular manner using robotic automation. This system allows functional mapping and multiplex optimization on a genome scale for diverse phenotypes including cellulase expression, isobutanol production, glycerol utilization and acetic acid tolerance, and may greatly accelerate future genome-scale engineering endeavours in yeast.
Biosynthesis of the antibiotic nonribosomal peptide penicillin in baker’s yeast
Authors: Awan Ali R. , Blount Benjamin A. , Bell David J. , Shaw William M. , Ho Jack C.H. , McKiernan Robert M. , Ellis Tom
Published: May 2017

Fungi are a valuable source of enzymatic diversity and therapeutic natural products including antibiotics. Here we engineer the baker’s yeast Saccharomyces cerevisiae to produce and secrete the antibiotic penicillin, a beta-lactam nonribosomal peptide, by taking genes from a filamentous fungus and directing their efficient expression and subcellular localization. Using synthetic biology tools combined with long-read DNA sequencing, we optimize productivity by 50-fold to produce bioactive yields that allow spent S. cerevisiae growth media to have antibacterial action against Streptococcus bacteria. This work demonstrates that S. cerevisiae can be engineered to perform the complex biosynthesis of multicellular fungi, opening up the possibility of using yeast to accelerate rational engineering of nonribosomal peptide antibiotics.
Artificial gravity field, astrophysical analogues, and topological phase transitions in strained topological semimetals
Authors: Guan Shan , Yu Zhi-Ming , Liu Ying , Liu Gui-Bin , Dong Liang , Lu Yunhao , Yao Yugui , Yang Shengyuan A.
Published: May 2017

Effective gravity and gauge fields are emergent properties intrinsic for low-energy quasiparticles in topological semimetals. Here, taking two Dirac semimetals as examples, we demonstrate that applied lattice strain can generate warped spacetime, with fascinating analogues in astrophysics. Particularly, we study the possibility of simulating black-hole/white-hole event horizons and gravitational lensing effect. Furthermore, we discover strain-induced topological phase transitions, both in the bulk materials and in their thin films. Especially in thin films, the transition between the quantum spin Hall and the trivial insulating phases can be achieved by a small strain, naturally leading to the proposition of a novel piezo-topological transistor device. Possible experimental realizations and analogue of Hawking radiation effect are discussed. Our result bridges multiple disciplines, revealing topological semimetals as a unique table-top platform for exploring interesting phenomena in astrophysics and general relativity; it also suggests realistic materials and methods to achieve controlled topological phase transitions with great potential for device applications.
Nexus fermions in topological symmorphic crystalline metals
Authors: Chang Guoqing , Xu Su-Yang , Huang Shin-Ming , Sanchez Daniel S. , Hsu Chuang-Han , Bian Guang , Yu Zhi-Ming , Belopolski Ilya , Alidoust Nasser , Zheng Hao , Chang Tay-Rong , Jeng Horng-Tay , Yang Shengyuan A. , Neupert Titus , Lin Hsin , Hasan M. Zahid
Published: May 2017

Topological metals and semimetals (TMs) have recently drawn significant interest. These materials give rise to condensed matter realizations of many important concepts in high-energy physics, leading to wide-ranging protected properties in transport and spectroscopic experiments. It has been well-established that the known TMs can be classified by the dimensionality of the topologically protected band degeneracies. While Weyl and Dirac semimetals feature zero-dimensional points, the band crossing of nodal-line semimetals forms a one-dimensional closed loop. In this paper, we identify a TM that goes beyond the above paradigms. It shows an exotic configuration of degeneracies without a well-defined dimensionality. Specifically, it consists of 0D nexus with triple-degeneracy that interconnects 1D lines with double-degeneracy. We show that, because of the novel form of band crossing, the new TM cannot be described by the established results that characterize the topology of the Dirac and Weyl nodes. Moreover, triply-degenerate nodes realize emergent fermionic quasiparticles not present in relativistic quantum field theory. We present materials candidates. Our results open the door for realizing new topological phenomena and fermions including transport anomalies and spectroscopic responses in metallic crystals with nontrivial topology beyond the Weyl/Dirac paradigm.
Establishment of induced pluripotent stem cells from normal B cells and inducing AID expression in their differentiation into hematopoietic progenitor cells
Authors: Kawamura Fumihiko , Inaki Makoto , Katafuchi Atsushi , Abe Yu , Tsuyama Naohiro , Kurosu Yumiko , Yanagi Aki , Higuchi Mitsunori , Muto Satoshi , Yamaura Takumi , Suzuki Hiroyuki , Noji Hideyoshi , Suzuki Shinichi , Yoshida Mitsuaki A. , Sasatani Megumi , Kamiya Kenji , Onodera Masafumi , Sakai Akira
Published: May 2017

B cell derived induced pluripotent stem cells (BiPSCs) were recently established from peripheral blood B cells by the simultaneous transfection of Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) and C/EBPα using a Sendai virus vector. Here, using a different method, we established BiPSCs with immunoglobulin heavy chain (IgH) gene rearrangement from normal B cells purified from lymph nodes. The critical points of our method are pre-stimulation of B cells with IL-21 and CD40-ligand (CD40L), followed by consecutive transfection of highly concentrated Yamanaka factors using a retroviral vector. Following each transfection the cells were centrifuged onto a retronectin coated plate and the activated by IL-4, IL-2, and CD40L. Furthermore, we established BiPSCs (BiPSC-A) in which activation-induced cytidine deaminase (AID) could be induced using the doxycycline-controlled. Both the parental BiPSC and BiPSC-A showed the capability of differentiating into hematopoietic progenitor cells (HPCs) based on confirmation of CD34 expression and colony-formation from CD34-positive cells. The findings that BiPSC-A can differentiate into HPCs suggest that there is a possibility that induction of AID expression would result in chromosomal translocations in the process of differentiation from BiPSCs, and therefore that these BiPSCs could be useful in elucidating the tumor origin of abnormal B cells in myelomagenesis.
Nanoscale Brownian heating by interacting magnetic dipolar particles
Authors: Chalopin Yann , Bacri Jean-Claude , Gazeau Florence , Devaud Martin
Published: May 2017

Clusters of magnetic nanoparticles have received considerable interest in various research fields. Their capacity to generate heat under an alternating magnetic field has recently opened the way to applications such as cancer therapy by hyperthermia. This work is an attempt to investigate the collective effects of interacting dipoles embedded in magnetic nano-particles (MNP) to predict their thermal dissipation with a liquid. We first present a general approach, based on the tracking of the microscopic dipole fluctuations, to access to the dissipation spectra of any spatial distribution of MNPs. Without any other assumption that the linear response regime, it is shown that increasing the particle concentration (dipolar interactions) dramatically diminishes and blueshifts the dissipation processes. This effect originates in a predominance of the coupling energy over the Brownian torques, which create a long-range ordering that saturates the response of the system to an external field. Consequently, the particle density is of fundamental importance to the control of the absorption of electromagnetic energy and its subsequent dissipation in the form of heat.
An Aqueous-Based Approach for Fabrication of PVDF/MWCNT Porous Composites
Authors: Rezvantalab Hossein , Ghazi Nastaran , Ambrusch Matthew J. , Infante Jeffrey , Shojaei-Zadeh Shahab
Published: May 2017

In this paper, we demonstrate the fabrication of conductive porous polymers based on foaming of an aqueous dispersion of polymeric particles and multi-walled carbon nanotubes (CNT). By tuning the surface energy of the constituents, we direct their preferential adsorption at the air-liquid (bubble) interface or within the liquid film between the bubbles. Sintering this bi-constituent foam yields solid closed-cell porous structure which can be electrically conductive if CNT are able to form a conductive path. We measure transport (electrical and thermal), mechanical, and morphological properties of such porous structures as a function of CNT loading and the method used for their surface functionalization. For a fixed polymer volume fraction, we demonstrate the limit in which increasing CNT results in decreasing the mechanical strength of the sample due to lack of adequate polymer-CNT bond. Such lightweight conductive porous composites are considered in applications including EMI shielding, electrostatic discharge protection, and electrets.
Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action
Authors: Yu Yi , Wan Pin , Cao Yanhua , Zhang Wei , Chen Junbo , Tan Li , Wang Yan , Sun Zhichen , Zhang Qi , Wan Yushun , Zhu Ying , Liu Fang , Wu Kailang , Liu Yingle , Wu Jianguo
Published: May 2017

Hepatitis B virus (HBV) infection causes acute hepatitis B (AHB), chronic hepatitis B (CHB), liver cirrhosis (LC), and eventually hepatocellular carcinoma (HCC). The presence of hepatitis B e antigen (HBeAg) in the serum generally indicates ongoing viral replication and disease progression. However, the mechanism by which HBeAg regulates HBV infection remains unclear. Interferons (IFNs) are pleiotropic cytokines that participate in host innate immunity. After binding to receptors, IFNs activate the JAK/STAT pathway to stimulate expression of IFN-stimulated genes (ISGs), leading to induction of antiviral responses. Here, we revealed that HBeAg represses IFN/JAK/STAT signaling to facilitate HBV replication. Initially, HBeAg stimulates the expression of suppressor of cytokine signaling 2 (SOCS2). Subsequently, SOCS2 impairs IFN/JAK/STAT signaling through reducing the stability of tyrosine kinase 2 (TYK2), downregulating the expression of type I and III IFN receptors, attenuating the phosphorylation and nucleus translocation of STAT1. Finally, SOCS2 inhibits the expression of ISGs, which leads to the repression of IFN action and facilitation of viral replication. These results demonstrate an important role of HBeAg in the regulation of IFN action, and provide a possible molecular mechanism by which HBV resists the IFN therapy and maintains persistent infection.
The association between psychological stress and miscarriage: A systematic review and meta-analysis
Authors: Qu Fan , Wu Yan , Zhu Yu-Hang , Barry John , Ding Tao , Baio Gianluca , Muscat Ruth , Todd Brenda K. , Wang Fang-Fang , Hardiman Paul J
Published: May 2017

This systematic review and meta-analysis was designed to investigate whether maternal psychological stress and recent life events are associated with an increased risk of miscarriage. A literature search was conducted to identify studies reporting miscarriage in women with and without history of exposure to psychological stress (the only exposure considered). The search produced 1978 studies; 8 studies were suitable for analysis. A meta-analysis was performed using a random-effects model with effect sizes weighted by the sampling variance. The risk of miscarriage was significantly higher in women with a history of exposure to psychological stress (OR 1.42, 95% CI 1.19–1.70). These findings remained after controlling for study type (cohort and nested case-control study OR 1.33 95% CI 1.14–1.54), exposure types (work stress OR 1.27, 95% CI 1.10–1.47), types of controls included (live birth OR 2.82 95% CI: 1.64–4.86). We found no evidence that publication bias or study heterogeneity significantly influenced the results. Our finding provides the most robust evidence to date, that prior psychological stress is harmful to women in early pregnancy.
Hormonal pleiotropy helps maintain queen signal honesty in a highly eusocial wasp
Authors: Oliveira Ricardo Caliari , Vollet-Neto Ayrton , Akemi Oi Cintia , van Zweden Jelle S. , Nascimento Fabio , Sullivan Brent Colin , Wenseleers Tom
Published: May 2017

In insect societies, both queens and workers produce chemicals that reliably signal caste membership and reproductive status. The mechanisms that help to maintain the honesty of such queen and fertility signals, however, remain poorly studied. Here we test if queen signal honesty could be based on the shared endocrine control of queen fertility and the production of specific signals. In support of this “hormonal pleiotropy” hypothesis, we find that in the common wasp, application of methoprene (a juveline hormone analogue) caused workers to acquire a queen-like cuticular hydrocarbon profile, resulting in the overproduction of known queen pheromones as well as some compounds typically linked to worker fertility. By contrast, administration of precocene-I (a JH inhibitor) had a tendency to have the opposite effect. Furthermore, a clear gonadotropic effect of JH in queens was suggested by the fact that circulating levels of JH were ca. 2 orders of magnitude higher in queens than those in workers and virgin, non-egg-laying queens, even if methoprene or precocene treatment did not affect the ovary development of workers. Overall, these results suggest that queen signal honesty in this system is maintained by queen fertility and queen signal production being under shared endocrine control.
Exploring the link between cadmium and psoriasis in a nationally representative sample
Authors: Liaw Fang-Yih , Chen Wei-Liang , Kao Tung-Wei , Chang Yaw-Wen , Huang Ching-Fu
Published: May 2017

Psoriasis, a skin inflammatory disease, originates from dysregulated interactions of the immune system. Cadmium, an environment pollutant, increases the levels of inflammation markers and influences the immune system. To clarify the relationship between cadmium and psoriasis, 5,927 participants, ≥20 years, in the National Health and Nutrition Examination Survey (NHANES) 2003–2006 were studied. Psoriasis severity was assessed using self-reported dermatology questionnaires. Cadmium was measured using blood chemistry. Three adjusted models were applied for the interaction between serum cadmium and severity of psoriasis. Psoriasis patients had significantly higher blood cadmium (0.67 vs. 0.52 μg/L,p = 0.006). There was a strong linear increase in predicted blood cadmium values with an increase in severity of psoriasis (pfor trend = 0.002). The β coefficient of the predicted serum cadmium in the “few patches to extensive psoriasis” group was 0.234 (p = 0.002) after adjusting covariates. Participants with severe psoriasis have higher blood cadmium. Environmental exposure to cadmium can predispose to the worsening of psoriasis. Although there are still limitations in this study, such as not included treatment data, these results have substantial public health implications for the general population, as they demonstrate the importance of cadmium exposure prevention, particularly among psoriasis patients.
Unexpected Efficacy of a Novel Sodium Channel Modulator in Dravet Syndrome
Authors: Anderson Lyndsey L. , Hawkins Nicole A. , Thompson Christopher H. , Kearney Jennifer A. , George Alfred L.
Published: May 2017

Dravet syndrome, an epileptic encephalopathy affecting children, largely results from heterozygous loss-of-function mutations in the brain voltage-gated sodium channel gene SCN1A. Heterozygous Scn1a knockout (Scn1a+/−) mice recapitulate the severe epilepsy phenotype of Dravet syndrome and are an accepted animal model. Because clinical observations suggest conventional sodium channel blocking antiepileptic drugs may worsen the disease, we predicted the phenotype of Scn1a+/− mice would be exacerbated by GS967, a potent, unconventional sodium channel blocker. Unexpectedly, GS967 significantly improved survival of Scn1a+/− mice and suppressed spontaneous seizures. By contrast, lamotrigine exacerbated the seizure phenotype. Electrophysiological recordings of acutely dissociated neurons revealed that chronic GS967-treatment had no impact on evoked action potential firing frequency of interneurons, but did suppress aberrant spontaneous firing of pyramidal neurons and was associated with significantly lower sodium current density. Lamotrigine had no effects on neuronal excitability of either neuron subtype. Additionally, chronically GS967-treated Scn1a+/− mice exhibited normalized pyramidal neuron sodium current density and reduced hippocampal NaV1.6 protein levels, whereas lamotrigine treatment had no effect on either pyramidal neuron sodium current or hippocampal NaV1.6 levels. Our findings demonstrate unexpected efficacy of a novel sodium channel blocker in Dravet syndrome and suggest a potential mechanism involving a secondary change in NaV1.6.
Structural Basis for Importin-α Binding of the Human Immunodeficiency Virus Tat
Authors: Smith K. M. , Himiari Z. , Tsimbalyuk S. , Forwood J. K.
Published: May 2017

HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning 48GRKKRR, and a cell penetrating peptide (CPP) signal spanning 48GRKKRRQRRRAPQN. However, the mechanism by which this NLS/CPP region mediates interaction with the nuclear import receptors remains to be resolved structurally. Here, we establish that the HIV-1 Tat:NLS/CPP is able to form a stable and direct interaction with the classical nuclear import receptor importin-α and using x-ray crystallography, we have determined the molecular interface and binding determinants to a resolution of 2.0 Å. We show for the first time that the interface is the same as host factors such as Ku70 and Ku80, rather than other virus proteins such as Ebola VP24 that bind on the outer surface of importin-α.
Rapid face adaptation distributes representation in inferior-temporal cortex across time and neuronal dimensions
Authors: Vahabie Abdol-Hossein , Dehaqani Mohammad-Reza A. , Ahmadabadi Majid Nili , Araabi Babak Nadjar , Esteky Hossein
Published: May 2017

Neuronal networks of the brain adapt their information processing according to the history of stimuli. Whereas most studies have linked adaptation to repetition suppression, recurrent connections within a network and disinhibition due to adaptation predict more complex response patterns. The main questions of this study are as follows: what is the effect of the selectivity of neurons on suppression/enhancement of neural responses? What are the consequences of adaptation on information representation in neural population and the temporal structure of response patterns? We studied rapid face adaptation using spiking activities of neurons in the inferior-temporal (IT) cortex. Investigating the responses of neurons, within a wide range from negative to positive face selectivity, showed that despite the peak amplitude suppression in highly positive selective neurons, responses were enhanced in most other neurons. This enhancement can be attributed to disinhibition due to adaptation. Delayed and distributed responses were observed for positive selective neurons. Principal component analysis of the IT population responses over time revealed that repetition of face stimuli resulted in temporal decorrelation of the network activity. The contributions of the main and higher neuronal dimensions were changed under an adaptation condition, where more neuronal dimensions were used to encode repeated face stimuli.