bluuebunny/crossref_metadata_2025 huggingface dataset:
In silico binding of 4,4'‐bisphenols predicts in vitro estrogenic and antiandrogenic activity
Authors: Conroy‐Ben Otakuye , Garcia Isabel , Teske Sondra S.
Published: February 2018

Bisphenols, anthropogenic pollutants, leach from consumer products and have potential to be ingested and are excreted in waste. The endocrine disrupting effects of highly manufactured bisphenols (BPA, BPS, and BPF) are known, however the activities of others are not. Here, the estrogenic and androgenic activities of a series of 4,4'‐bisphenols that vary at the inter‐connecting bisphenol bridge were determined (BPA, BPB, BPBP, BPC2, BPE, BPF, BPS, and BPZ) and compared to in silico binding to estrogen receptor‐alpha and the androgen receptor. Bioassay results showed the order of estrogenicity (BPC2 (strongest) > BPBP > BPB > BPZ > BPE > BPF > BPA > BPS, r2 = 0.995) and anti‐androgenicity (BPC2 (strongest) > BPE, BPB, BPA, BPF, and BPS, r2 = 0.996) correlated to nuclear receptor binding affinities. Like testosterone and the anti‐androgen hydroxyflutamide, bisphenol fit in the ligand‐binding domain through hydrogen‐bonding at residues Thr877 and Asn705, but also interacted at either Cys784/Ser778 or Gln711 through the other phenol ring. This suggests the 4,4'‐bisphenols, like hydroxyflutamide, are androgen receptor antagonists. Hydrogen‐bond trends between ERα and the 4,4'‐bisphenols were limited to residue Glu353, which interacted with the –OH of one phenol and the –OH of the A ring of 17β‐estradiol; hydrogen‐bonding varied at the –OH of ring D of 17β‐estradiol and the second phenol –OH group. While both estrogen and androgen bioassays correlated to in silico results, conservation of hydrogen‐bonding residues in the androgen receptor provides a convincing picture of direct antagonist binding by 4,4'‐bisphenols.
Ionic Ferrocenyl Coordination Compounds Derived from Imidazole and 1,2,4‐Triazole Ligands and Their Catalytic Effects During Combustion
Authors: Zhang Na , Zhang Guofang , Li Jizhen , Zhang Weiqiang , Gao Ziwei
Published: February 2018

Alkylferrocene‐based burning‐rate catalysts (BRCs) show conspicuous migration tendency and volatility during prolonged storage and fabrication process of a composite solid propellant. To enhance anti‐migration ability of the BRCs, forty novel ionic coordination compounds, [M(L)4(H2O)2]mXn (M = Mn2+, Co2+, Cu2+, Ni2+, Zn2+, Fe2+, Pb2+, Cr3+, Bi3+, or Cd2+; L = ferrocenylmethyl imidazole or ferrocenylmethyl‐1,2,4‐triazole; X = picrate or trinitroresorcinolate), were synthesized and characterized by FT‐IR, UV/Vis, and elementary analysis. Additionally, the crystal structures of six compounds were confirmed by single‐crystal X‐ray diffraction. The TG analyses revealed that the new compounds show high thermal stability. Cyclic voltammetry studies suggested that theyare irreversible redox systems. Their catalytic activities in the thermal degradation of ammonium perchlorate (AP), 1,3,5‐trinitro‐1,3,5‐triazacyclo‐hexane (RDX) and 1,2,5,7‐tetranitro‐1,3,5,7‐tetraazacyclooctane (HMX) were examined by DSC technique. The results indicated that all the new compounds exert great effects on the thermal decomposition of AP and RDX, among them some compounds are more active than catocene. Compound 26 has good catalytic ability in the thermal decomposition of HMX, representing a rare example of the reported ferrocene‐based BRCs which show catalytic activity during combustion of HMX.
Personalized risk prediction of postoperative cognitive impairment – rationale for the EU-funded BioCog project
Authors: Winterer G. , Androsova G. , Bender O. , Boraschi D. , Borchers F. , Dschietzig T.B. , Feinkohl I. , Fletcher P. , Gallinat J. , Hadzidiakos D. , Haynes J.D. , Heppner F. , Hetzer S. , Hendrikse J. , Ittermann B. , Kant I.M.J. , Kraft A. , Krannich A. , Krause R. , Kühn S. , Lachmann G. , van Montfort S.J.T. , Müller A. , Nürnberg P. , Ofosu K. , Pietsch M. , Pischon T. , Preller J. , Renzulli E. , Scheurer K. , Schneider R. , Slooter A.J.C. , Spies C. , Stamatakis E. , Volk H.D. , Weber S. , Wolf A. , Yürek F. , Zacharias N. ,   BioCog consortium
Published: February 2018

Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions – particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost–benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.
Neonatal systemic inflammation and the risk of low scores on measures of reading and mathematics achievement at age 10 years among children born extremely preterm
Authors: Leviton Alan , Dammann Olaf , Allred Elizabeth N. , Joseph Robert M. , Fichorova Raina N. , O'Shea T. Michael , Kuban Karl C.K.
Published: February 2018

Background

Difficulties with reading and math occur more commonly among children born extremely preterm than among children born at term. Reasons for this are unclear.

Methods

We measured the concentrations of 27 inflammatory‐related and neurotrophic/angiogenic proteins (angio‐neurotrophic proteins) in multiple blood specimens collected a week apart during the first postnatal month from 660 children born before the 28th week of gestation who at age 10 years had an IQ ≥ 70 and a Wechsler Individual Achievement Test 3rd edition (WIAT‐III) assessment. We identified four groups of children, those who had a Z‐score ≤ −1 on the Word Reading assessment only, on the Numerical Operations assessment only, on both of these assessments, and on neither, which served as the referent group. We then modeled the risk of each learning limitation associated with a top quartile concentration of each protein, and with high and lower concentrations of multiple proteins.

Results

The protein profile of low reading scores was confined to the third and fourth postnatal weeks when increased risks were associated with high concentrations of IL‐8 and ICAM‐1 in the presence of low concentrations of angio‐neurotrophic proteins. The profile of low math scores was very similar, except it did not include ICAM‐1. In contrast, the profile of low scores on both assessments was present in each of the first four postnatal weeks. The increased risks associated with high concentrations of TNF‐α in the first two weeks and of IL‐8 and ICAM‐1 in the next two weeks were modulated down by high concentrations of angio‐neurotrophic proteins.

Conclusions

High concentrations of angio‐neurotrophic proteins appear to reduce/moderate the risk of each learning limitation associated with systemic inflammation. The three categories of limitations have protein profiles with some similarities, and yet some differences, too.
Prevalência da deficiência de vitamina D em pacientes com fraturas ocasionadas por trauma de baixa energia
Authors: Devigili Júnior Nilo , Botega Luiza , Back Simony , Stipp Willian , Netto Martins
Published: February 2018

Avaliar os níveis séricos da 25–hidroxivitamina D [25(OH)D] em pacientes internados com fraturas causadas por traumas de baixa energia e analisar o perfil desses pacientes e os principais tipos de fraturas.

Estudo transversal observacional em que foram obtidas amostras séricas de 25(OH)D de 40 pacientes internados com fraturas resultantes de trauma de baixa energia. As seguintes variáveis foram analisadas: tipo da fratura, idade, sexo, uso de vitamina D, tabagismo, atividade física e uso de protetor solar.

Apresentaram níveis deficientes de 25(OH)D 29 (72,5%) pacientes, dez (25%) apresentaram níveis insuficientes e apenas um (2,5%) apresentou níveis suficientes. Os pacientes que faziam uso de vitamina D obtiveram níveis de 25(OH)D (24,8 ± 12,75) estatisticamente significantes (p = 0,048) em relação aos que não usavam (16,47 ± 6,28). Além disso, aqueles que praticavam exercícios físicos duas a três vezes por semana obtiveram uma concentração média de 25(OH)D (22,5 ± 6,08 ng/mL) estatisticamente significante (p = 0,042) em comparação com o grupo que referiu não fazer atividade física (15,5 ± 7,25 ng/mL).

A prevalência da deficiência de 25(OH)D foi de 72,5%, indivíduos que praticavam atividade física duas a três vezes por semana, bem como aqueles que faziam uso de vitamina D, apresentaram um nível maior de vitamina D.
Neuroprotective effect of a new photobiomodulation technique against Aβ25–35 peptide–induced toxicity in mice: Novel hypothesis for therapeutic approach of Alzheimer's disease suggested
Authors: Blivet Guillaume , Meunier Johann , Roman Francois J. , Touchon Jacques
Published: February 2018

Introduction

Photobiomodulation was assessed as a novel treatment of Alzheimer's disease (AD) by the use of a new device RGn500 combining photonic and magnetic emissions in a mouse model of AD.

Methods

Following the injection of amyloid β 25‐35 peptide in male Swiss mice, RGn500 was applied once a day for 7 days either on the top of the head or the center of abdomen or both.

Results

RGn500 daily application for 10 min produced a neuroprotective effect on the neurotoxic effects of amyloid β 25‐35 peptide injection when this type of photobiomodulation was applied both on the head and on the abdomen. Protection was demonstrated by memory restoration and on the normalization of key markers of AD (amyloid β 1‐42, pTau), oxidative stress (lipid peroxidation), apoptosis (Bax/Bcl2) and neuroinflammation.

Discussion

RGn500 displays therapeutic efficacy similar to other pharmacological approaches evaluated in this model of AD.
Expert Failure
Authors: Koppl Roger
Published: February 2018

The humble idea that experts are ordinary human beings leads to surprising conclusions about how to get the best possible expert advice. All too often, experts have monopoly power because of licensing restrictions or because they are government bureaucrats protected from both competition and the consequences of their decisions. This book argues that, in the market for expert opinion, we need real competition in which rival experts may have different opinions and new experts are free to enter. But the idea of breaking up expert monopolies has far-reaching implications for public administration, forensic science, research science, economics, America's military-industrial complex, and all domains of expert knowledge. Roger Koppl develops a theory of experts and expert failure, and uses a wide range of examples - from forensic science to fashion - to explain the applications of his theory, including state regulation of economic activity.
The Transition from Hospital to Home: Protocol for a Longitudinal Study of Australian Aboriginal and Torres Strait Islander Traumatic Brain Injury (TBI)
Authors: Bohanna India , Fitts Michelle S. , Bird Katrina , Fleming Jennifer , Gilroy John , Esterman Adrian , Maruff Paul , Clough Alan R.
Published: February 2018

Background: Traumatic brain injury (TBI) is a leading cause of disability in Australia. Evidence shows that multidisciplinary rehabilitation and support in the six months following TBI is important for successful independent living and social re-integration. Despite this, access to services and supports during this period is often limited by environmental, socio-economic, geographic and cultural factors. Australian studies on outcomes after brain injury have reported primarily on non-Indigenous people. This study will investigate key sentinel events during the transition from hospital to home after a TBI in the first longitudinal study with Indigenous Australians.

Method: Indigenous Australians admitted to one of three major trauma hospitals in northern Australia with a TBI, and their care givers, will be recruited. Clinical and brain injury risk factor information, along with measures of cognitive function, transition events, mental health and community re-integration will be collected at three time points prior to hospital discharge, and at three and six months post-discharge. Qualitative interviews will also be conducted. Data will be analysed using regression methods for the quantitative component, and situational analysis for the qualitative component. Annual rates of brain injury will be calculated for patients admitted to tertiary hospital facilities in the study region with a diagnosis of TBI.

Discussion: Understanding the experience and events which shape the transition period is critical to determining the services and supports that may enhance transition outcomes, and ensure that such services are culturally appropriate and endorsed by Indigenous families and communities.
Between Local and Global: the ‘Ndrangheta’s Drug Trafficking Route
Authors: Calandra Francesca
Published: February 2018

According to the last United Nations Office on Drugs and Crime report (2016), 247 million people aged between 15 and 64 years used drugs at least once in the past year, with cocaine being the best-selling of the goods from the ‘Ndrangheta. In this case, the drugs trade is 60% of the systemic gain due to illicit trafficking that allowed the spreading of the Calabrian criminal organization across five continents. Nevertheless, this sometimes little-known apparently harmless organization, which comes from the Aspromonte heartland in Calabria, was included by the United States in the blacklist of the 75 most dangerous drug-trafficking organizations only in 2008. Therefore, this investigative study, based on reference literature, aims to analyse what are the aspects that make the Calabrian criminal organization “local” and “global” at the same time as well as the strengths and weaknesses in combating ‘Ndrangheta’s drug trafficking.
Psychological Assessment of Adolescent Offenders: Validity of the Brazilian Jesness Inventory–Revised
Authors: Costa Rafaelle Carolynne Santos , Komatsu André Vilela , Bazon Marina Rezende
Published: February 2018

This work presents validation of the Jesness Inventory, particularly its revised version, to the Brazilian reality. It was developed by Carl Jesness, based on his clinical experience and research programs for juvenile offenders, to assess juvenile offenders, particularly to understand the functioning of their personality, offering clues to customize psychosocial intervention, and verification of results from this, in terms of changes in adolescents’ beliefs/values and attitudes. Regarding the psychometric properties, the revised version showed an adequate internal consistency and temporal stability. For the evidence of validity, the results of the concurrent criterion and simultaneous validity were in agreement with those found in other studies, emphasizing the specific capacities of this instrument to distinguish adolescent offenders from non-offenders and properly classify them, denoting its quality in helping the diagnostic process. Research to verify predictive and construct validity is being carried out.
IMPROVED INEQUALITIES FOR THE NUMERICAL RADIUS: WHEN INVERSE COMMUTES WITH THE NORM
Authors: CAIN BRYAN E.
Published: February 2018

New inequalities relating the norm $n(X)$ and the numerical radius $w(X)$ of invertible bounded linear Hilbert space operators were announced by Hosseini and Omidvar [‘Some inequalities for the numerical radius for Hilbert space operators’, Bull. Aust. Math. Soc.94 (2016), 489–496]. For example, they asserted that $w(AB)\leq$$2w(A)w(B)$ for invertible bounded linear Hilbert space operators $A$ and $B$. We identify implicit hypotheses used in their discovery. The inequalities and their proofs can be made good by adding the extra hypotheses which take the form $n(X^{-1})=n(X)^{-1}$. We give counterexamples in the absence of such additional hypotheses. Finally, we show that these hypotheses yield even stronger conclusions, for example, $w(AB)=w(A)w(B)$.
Orientations to negotiated language and task rules in online L2 interaction
Authors: Sert Olcay , Balaman Ufuk
Published: February 2018

Recent research shows that negotiation of meaning in online task-oriented interactions can be a catalyst for L2 (second/foreign/additional language) development. However, how learners undertake such negotiation work and what kind of an impact it has on interactional development in an L2 are still largely unknown mainly due to a lack of focus on task engagement processes. A conversation analytic investigation into negotiation of meaning (NoM) in task-oriented interactions can bring evidence to such development, as conversation analysis (CA), given its analytic tools, allows us to see how participant orientations in interaction evolve over time. Based on an examination of screen-recorded multiparty online task-oriented interactions, this study aimed to describe how users (n=8) of an L2 (1) negotiate and co-construct language and task rules and (2) later show orientations to these rules both in the short term (50 minutes) and in the long term (8 weeks). The findings showed that in addition to negotiating existing rules, the learners co-constructed new rules around an action called policing, which occurred when the learners attended to the breach of language and task rules. Furthermore, even after the negotiation work was completed, they oriented to negotiated rules through policing their own utterances (i.e. self-policing). Overall, this interactional continuum (from other-repairs to self-repairs) brought longitudinal evidence to bear on the role of NoM in the development of L2 interactional competence. These findings bring new insights into NoM, technology-mediated task-based language teaching (TBLT), and CA for second language acquisition (SLA).
Clinorotation-induced autophagy via HDM2-p53-mTOR pathway enhances cell migration in vascular endothelial cells
Authors: Li Cheng-Fei , Sun Jia-Xing , Gao Yuan , Shi Fei , Pan Yi-Kai , Wang Yong-Chun , Sun Xi-Qing
Published: February 2018

Individuals exposed to long-term spaceflight often experience cardiovascular dysfunctions characterized by orthostatic intolerance, disability on physical exercise, and even frank syncope. Recent studies have showed that the alterations of cardiovascular system are closely related to the functional changes of endothelial cells. We have shown previously that autophagy can be induced by simulated microgravity in human umbilical vein endothelial cells (HUVECs). However, the mechanism of enhanced autophagy induced by simulated microgravity and its role in the regulation of endothelial function still remain unclear. We report here that 48 h clinorotation promoted cell migration in HUVECs by induction of autophagy. Furthermore, clinorotation enhanced autophagy by the mechanism of human murine double minute 2 (HDM2)-dependent degradation of cytoplasmic p53 at 26S proteasome, which results in the suppression of mechanistic target of rapamycin (mTOR), but not via activation of AMPK in HUVECs. These results support the key role of HDM2–p53 in direct downregulation of mTOR, but not through AMPK in microgravity-induced autophagy in HUVECs.
Inactivation of ribosomal protein S27-like confers radiosensitivity via the Mdm2-p53 and Mdm2–MRN–ATM axes
Authors: Zhao Yongchao , Tan Mingjia , Liu Xia , Xiong Xiufang , Sun Yi
Published: February 2018

RPS27L (ribosomal protein S27-like) is an evolutionarily conserved ribosomal protein and a direct p53 target. We recently reported that Rps27l disruption triggers ribosomal stress to induce p53, causing postnatal death, which can be rescued by Trp53
+/−
. Whether and how Rps27l modulates radiosensitivity is unknown. Here we report that Rps27l
−/−
; Trp53
+/−
mice are extremely sensitive to radiation due to reduced proliferation and massive induction of apoptosis in radiation-sensitive organs. Mechanistically, the radiation sensitivity is mediated by two signaling pathways: (1) activated p53 pathway due to imbalanced Mdm2/Mdm4 levels and reduced E3 ligase activity; and (2) reduced DNA damage response due to reduced MRN/Atm signal as a result of elevated Mdm2 binding of Nbs1 to inhibit Nbs1–Atm binding and subsequent Atm activation. Indeed, heterozygous deletion of Mdm2 restores the MRN/Atm signal. Collectively, our study revealed a physiological condition under which Rps27l regulates the Mdm2/p53 and MRN/Atm axes to maintain DNA damage response and to confer radioprotection in vivo.
SMAD4 feedback regulates the canonical TGF-β signaling pathway to control granulosa cell apoptosis
Authors: Du Xing , Pan Zengxiang , Li Qiqi , Liu Honglin , Li Qifa
Published: February 2018

Canonical TGF-β signals are transduced from the cell surface to the cytoplasm, and then translocated into the nucleus, a process that involves ligands (TGF-β1), receptors (TGFBR2/1), receptor-activated SMADs (SMAD2/3), and the common SMAD (SMAD4). Here we provide evidence that SMAD4, a core component of the canonical TGF-β signaling pathway, regulates the canonical TGF-β signaling pathway in porcine granulosa cells (GCs) through a feedback mechanism. Genome-wide analysis and qRT-PCR revealed that SMAD4 affected miRNA biogenesis in GCs. Interestingly, TGFBR2, the type II receptor of the canonical TGF-β signaling pathway, was downregulated in SMAD4-silenced GCs and found to be a common target of SMAD4-inhibited miRNAs. miR-425, the most significantly elevated miRNA in SMAD4-silenced GCs, mediated the SMAD4 feedback regulation of the TGF-β signaling pathway. This was accomplished through a direct interaction between the transcription factor SMAD4 and the miR-425 promoter, and a direct interaction between miR-425 and the TGFBR2 3′-UTR. Furthermore, miR-425 enhanced GC apoptosis by targeting TGFBR2 and the canonical TGF-β signaling pathway, which was rescued by SMAD4 and TGF-β1. Overall, our findings demonstrate that a positive feedback mechanism exists within the canonical TGF-β signaling pathway. This study also provides new insights into mechanism underlying the canonical TGF-β signaling pathway, which regulates GC function and follicular development.
Nicotine associated breast cancer in smokers is mediated through high level of EZH2 expression which can be reversed by methyltransferase inhibitor DZNepA
Authors: Kumari Kanchan , Das Biswajit , Adhya Amit , Chaudhary Sanjib , Senapati Shantibhusan , Mishra Sandip K.
Published: February 2018

Recent studies show substantial growth-promoting properties of nicotine (NIC) in cancer, which is a combined outcome of genetic and epigenetic alterations. However, the role of epigenetic modifiers in response to NIC in breast cancer is less studied. In the present study, for the first time we have shown NIC-induced enhanced EZH2 expression. Six pairs of smoking-associated breast cancer patient tissues were analyzed. Samples from smoking breast cancer patients showed distinguished enhanced EZH2 expression in comparison to non-smoking ones. The upregulation in EZH2, which is due to NIC, was further confirmed in breast carcinoma cell lines using 10 µM NIC, 1 µM DZNepA, and EZH2si. The upregulation of EZH2 was concomitant with upregulation in Myc and α9-nAChR. The xenograft of breast cancer cells in BALB/c nude mice in the presence or absence of NIC showed significantly higher tumor uptake in the NIC injected group, which clearly demonstrates the effect of NIC in breast cancer progression. Interestingly, DZNepA considerably suppressed the NIC-mediated tumor growth. CHIP-qPCR assay confirmed the increased Myc enrichment on EZH2 promoter upon NIC treatment, thereby strengthening our findings that there exists an association between NIC, Myc, and EZH2. Overall, the present study identifies a strong association between NIC and EZH2 particularly in the progression of breast cancer in smokers through a novel axis involving nAChR and Myc. Moreover, the findings provide preliminary evidence suggesting potential of high level of EZH2 expression as a prognostic marker in smoking-associated breast cancer.
Optimal compressed representation of high throughput sequence data via light assembly
Authors: Ginart Antonio A. , Hui Joseph , Zhu Kaiyuan , Numanagić Ibrahim , Courtade Thomas A. , Sahinalp S. Cenk , Tse David N.
Published: February 2018

The most effective genomic data compression methods either assemble reads into contigs, or replace them with their alignment positions on a reference genome. Such methods require significant computational resources, but faster alternatives that avoid using explicit or de novo-constructed references fail to match their performance. Here, we introduce a new reference-free compressed representation for genomic data based on light de novo assembly of reads, where each read is represented as a node in a (compact) trie. We show how to efficiently build such tries to compactly represent reads and demonstrate that among all methods using this representation (including all de novo assembly based methods), our method achieves the shortest possible output. We also provide an lower bound on the compression rate achievable on uniformly sampled genomic read data, which is approximated by our method well. Our method significantly improves the compression performance of alternatives without compromising speed.
Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity
Authors: Stone Will J. R. , Campo Joseph J. , Ouédraogo André Lin , Meerstein-Kessel Lisette , Morlais Isabelle , Da Dari , Cohuet Anna , Nsango Sandrine , Sutherland Colin J. , van de Vegte-Bolmer Marga , Siebelink-Stoter Rianne , van Gemert Geert-Jan , Graumans Wouter , Lanke Kjerstin , Shandling Adam D. , Pablo Jozelyn V. , Teng Andy A. , Jones Sophie , de Jong Roos M. , Fabra-García Amanda , Bradley John , Roeffen Will , Lasonder Edwin , Gremo Giuliana , Schwarzer Evelin , Janse Chris J. , Singh Susheel K. , Theisen Michael , Felgner Phil , Marti Matthias , Drakeley Chris , Sauerwein Robert , Bousema Teun , Jore Matthijs M.
Published: February 2018

Infection withPlasmodiumcan elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes.
Stimuli-responsive hydroxyapatite liquid crystal with macroscopically controllable ordering and magneto-optical functions
Authors: Nakayama Masanari , Kajiyama Satoshi , Kumamoto Akihito , Nishimura Tatsuya , Ikuhara Yuichi , Yamato Masafumi , Kato Takashi
Published: February 2018

Liquid crystals are mostly formed by self-assembly of organic molecules. In contrast, inorganic materials available as liquid crystals are limited. Here we report the development of liquid-crystalline (LC) hydroxyapatite (HAp), which is an environmentally friendly and biocompatible biomineral. Its alignment behavior, magneto-optical properties, and atomic-scale structures are described. We successfully induce LC properties into aqueous colloidal dispersions of rod-shaped HAp by controlling the morphology of the material using acidic macromolecules. These LC HAp nanorod materials are macroscopically oriented in response to external magnetic fields and mechanical forces. We achieve magnetic modulation of the optical transmission by dynamic control of the LC order. Atomic-scale observations using transmission electron microscopy show the self-organized inorganic/organic hybrid structures of mesogenic nanorods. HAp liquid crystals have potential as bio-friendly functional materials because of their facile preparation, the bio-friendliness of HAp, and the stimuli-responsive properties of these colloidal ordered fluids.
Ultrafast ion sieving using nanoporous polymeric membranes
Authors: Wang Pengfei , Wang Mao , Liu Feng , Ding Siyuan , Wang Xue , Du Guanghua , Liu Jie , Apel Pavel , Kluth Patrick , Trautmann Christina , Wang Yugang
Published: February 2018

The great potential of nanoporous membranes for water filtration and chemical separation has been challenged by the trade-off between selectivity and permeability. Here we report on nanoporous polymer membranes with an excellent balance between selectivity and permeability of ions. Our membranes are fabricated by irradiating 2-μm-thick polyethylene terephthalate Lumirror® films with GeV heavy ions followed by ultraviolet exposure. These membranes show a high transport rate of K+ ions of up to 14 mol h−1 m−2 and a selectivity of alkali metal ions over heavy metal ions of >500. Combining transport experiments and molecular dynamics simulations with a polymeric nanopore model, we demonstrate that the high permeability is attributable to the presence of nanopores with a radius of ~0.5 nm and a density of up to 5 × 1010 cm−2, and the selectivity is ascribed to the interaction between the partially dehydrated ions and the negatively charged nanopore wall.
Extreme rejuvenation and softening in a bulk metallic glass
Authors: Pan J. , Wang Y. X. , Guo Q. , Zhang D. , Greer A. L. , Li Y.
Published: February 2018

Rejuvenation of metallic glasses, bringing them to higher-energy states, is of interest in improving their plasticity. The mechanisms of rejuvenation are poorly understood, and its limits remain unexplored. We use constrained loading in compression to impose substantial plastic flow on a zirconium-based bulk metallic glass. The maximum measured effects are that the hardness of the glass decreases by 36%, and its excess enthalpy (above the relaxed state) increases to 41% of the enthalpy of melting. Comparably high degrees of rejuvenation have been reported only on microscopic scales at the centre of shear bands confined to low volume fractions. This extreme rejuvenation of a bulk glass gives a state equivalent to that obtainable by quenching the liquid at ~1010 K s–1, many orders of magnitude faster than is possible for bulk specimens. The contrast with earlier results showing relaxation in similar tests under tension emphasizes the importance of hydrostatic stress.
Transformable masks for colloidal nanosynthesis
Authors: Wang Zhenxing , He Bowen , Xu Gefei , Wang Guojing , Wang Jiayi , Feng Yuhua , Su Dongmeng , Chen Bo , Li Hai , Wu Zhonghua , Zhang Hua , Shao Lu , Chen Hongyu
Published: February 2018

Synthetic skills are the prerequisite and foundation for the modern chemical and pharmaceutical industry. The same is true for nanotechnology, whose development has been hindered by the sluggish advance of its synthetic toolbox, i.e., the emerging field of nanosynthesis. Unlike organic chemistry, where the variety of functional groups provides numerous handles for designing chemical selectivity, colloidal particles have only facets and ligands. Such handles are similar in reactivity to each other, limited in type, symmetrically positioned, and difficult to control. In this work, we demonstrate the use of polymer shells as adjustable masks for nanosynthesis, where the different modes of shell transformation allow unconventional designs beyond facet control. In contrast to ligands, which bind dynamically and individually, the polymer masks are firmly attached as sizeable patches but at the same time are easy to manipulate, allowing versatile and multi-step functionalization of colloidal particles at selective locations.
Evolution and stabilization of subnanometric metal species in confined space by in situ TEM
Authors: Liu Lichen , Zakharov Dmitri N. , Arenal Raul , Concepcion Patricia , Stach Eric A. , Corma Avelino
Published: February 2018

Understanding the behavior and dynamic structural transformation of subnanometric metal species under reaction conditions will be helpful for understanding catalytic phenomena and for developing more efficient and stable catalysts based on single atoms and clusters. In this work, the evolution and stabilization of subnanometric Pt species confined in MCM-22 zeolite has been studied by in situ transmission electron microscopy (TEM). By correlating the results from in situ TEM studies and the results obtained in a continuous fix-bed reactor, it has been possible to delimitate the factors that control the dynamic agglomeration and redispersion behavior of metal species under reaction conditions. The dynamic reversible transformation between atomically dispersed Pt species and clusters/nanoparticles during CO oxidation at different temperatures has been elucidated. It has also been confirmed that subnanometric Pt clusters can be stabilized in MCM-22 crystallites during NO reduction with CO and H2.
Site-specific phosphorylation of TRANSPARENT TESTA GLABRA1 mediates carbon partitioning in Arabidopsis seeds
Authors: Li Chengxiang , Zhang Bin , Chen Bin , Ji Lianghui , Yu Hao
Published: February 2018

Seed development is dependent on nutrients, such as a source of carbon, supplied by the parent plant. It remains largely unknown how these nutrients are distributed to zygotic and maternal tissues to coordinate storage of reserve compounds and development of protective tissues like seed coat. Here we show that phosphorylation of TRANSPARENT TESTA GLABRA1 (TTG1) is regulated by SHAGGY-like kinases 11/12 (SK11/12) and that this mediates carbon flow to fatty acid synthesis and seed coat traits in Arabidopsis seeds. SK11/12 phosphorylate TTG1 at serine 215, thus preventing TTG1 interaction with TRANSPARENT TESTA2. This compromises recruitment of TTG1 to the GLABRA2 locus and downregulates GLABRA2 expression, which enhances biosynthesis of fatty acids in the embryo, but reduces production of mucilage and flavonoid pigments in the seed coat. Therefore, site-specific phosphorylation of TTG1 by SK11/SK12 regulates carbon partitioning between zygotic and maternal sinks in seeds.
Regulation of mutant TERT by BRAF V600E/MAP kinase pathway through FOS/GABP in human cancer
Authors: Liu Rengyun , Zhang Tao , Zhu Guangwu , Xing Mingzhao
Published: February 2018

The unique oncogene duet of coexisting BRAF V600E and TERT promoter mutations are widely found to be a robust genetic background promoting human cancer aggressiveness, but the mechanism is unclear. Here, we demonstrate that the BRAF V600E/MAP kinase pathway phosphorylates and activates FOS, which in turn acts as a transcription factor to bind and activate the GABPB promoter, increasing GABPB expression and driving formation of GABPA-GABPB complex; the latter selectively binds and activates mutant TERT promoter, upregulating TERT expression. Elevated TERT functions as a strong oncoprotein, robustly promoting aggressive behaviors of cancer cells and tumor development. We thus identify a molecular mechanism for the activation of mutant TERT by the BRAF V600E/MAP kinase pathway, in which FOS as a transcriptional factor of GABPB promoter plays a key role in functionally bridging the two oncogenes in cooperatively promoting oncogenesis, providing important cancer biological and clinical implications.
Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α
Authors: Wang Qirui , He Zhenqiang , Huang Menggui , Liu Tianrun , Wang Yanling , Xu Haineng , Duan Hao , Ma Peihong , Zhang Lin , Zamvil Scott S. , Hidalgo Juan , Zhang Zhenfeng , O’Rourke Donald M. , Dahmane Nadia , Brem Steven , Mou Yonggao , Gong Yanqing , Fan Yi
Published: February 2018

Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-γ-dependent transcriptional activation of hypoxia-inducible factor-2α. Finally, utilizing a genetic murine GBM model, we show that EC-specific knockout of IL-6 inhibits macrophage alternative activation and improves survival in the GBM-bearing mice. These findings illustrate a vascular niche-dependent mechanism for alternative macrophage activation and cancer progression, and suggest that targeting endothelial IL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors.
SOD3 improves the tumor response to chemotherapy by stabilizing endothelial HIF-2α
Authors: Mira Emilia , Carmona-Rodríguez Lorena , Pérez-Villamil Beatriz , Casas Josefina , Fernández-Aceñero María Jesús , Martínez-Rey Diego , Martín-González Paula , Heras-Murillo Ignacio , Paz-Cabezas Mateo , Tardáguila Manuel , Oury Tim D. , Martín-Puig Silvia , Lacalle Rosa Ana , Fabriás Gemma , Díaz-Rubio Eduardo , Mañes Santos
Published: February 2018

One drawback of chemotherapy is poor drug delivery to tumor cells, due in part to hyperpermeability of the tumor vasculature. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme usually repressed in the tumor milieu. Here we show that specific SOD3 re-expression in tumor-associated endothelial cells (ECs) increases doxorubicin (Doxo) delivery into and chemotherapeutic effect on tumors. Enhanced SOD3 activity fostered perivascular nitric oxide accumulation and reduced vessel leakage by inducing vascular endothelial cadherin (VEC) transcription. SOD3 reduced HIF prolyl hydroxylase domain protein activity, which increased hypoxia-inducible factor-2α (HIF-2α) stability and enhanced its binding to a specific VEC promoter region. EC-specific HIF-2α ablation prevented both the SOD3-mediated increase in VEC transcription and the enhanced Doxo effect. SOD3, VEC, and HIF-2α levels correlated positively in primary colorectal cancers, which suggests a similar interconnection of these proteins in human malignancy.
Hemimetabolous genomes reveal molecular basis of termite eusociality
Authors: Harrison Mark C. , Jongepier Evelien , Robertson Hugh M. , Arning Nicolas , Bitard-Feildel Tristan , Chao Hsu , Childers Christopher P. , Dinh Huyen , Doddapaneni Harshavardhan , Dugan Shannon , Gowin Johannes , Greiner Carolin , Han Yi , Hu Haofu , Hughes Daniel S. T. , Huylmans Ann-Kathrin , Kemena Carsten , Kremer Lukas P. M. , Lee Sandra L. , Lopez-Ezquerra Alberto , Mallet Ludovic , Monroy-Kuhn Jose M. , Moser Annabell , Murali Shwetha C. , Muzny Donna M. , Otani Saria , Piulachs Maria-Dolors , Poelchau Monica , Qu Jiaxin , Schaub Florentine , Wada-Katsumata Ayako , Worley Kim C. , Xie Qiaolin , Ylla Guillem , Poulsen Michael , Gibbs Richard A. , Schal Coby , Richards Stephen , Belles Xavier , Korb Judith , Bornberg-Bauer Erich
Published: February 2018

Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the 2-Gb genome of the German cockroach, Blattella germanica, and the 1.3-Gb genome of the drywood termite Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.
Clonal genome evolution and rapid invasive spread of the marbled crayfish
Authors: Gutekunst Julian , Andriantsoa Ranja , Falckenhayn Cassandra , Hanna Katharina , Stein Wolfgang , Rasamy Jeanne , Lyko Frank
Published: February 2018

The marbled crayfish Procambarus virginalis is a unique freshwater crayfish characterized by very recent speciation and parthenogenetic reproduction. Marbled crayfish also represent an emerging invasive species and have formed wild populations in diverse freshwater habitats. However, our understanding of marbled crayfish biology, evolution and invasive spread has been hampered by the lack of freshwater crayfish genome sequences. We have now established a de novo draft assembly of the marbled crayfish genome. We determined the genome size at approximately 3.5 gigabase pairs and identified >21,000 genes. Further analysis confirmed the close relationship to the genome of the slough crayfish, Procambarusfallax, and also established a triploid AA’B genotype with a high level of heterozygosity. Systematic fieldwork and genotyping demonstrated the rapid expansion of marbled crayfish on Madagascar and established the marbled crayfish as a potent invader of freshwater ecosystems. Furthermore, comparative whole-genome sequencing demonstrated the clonality of the population and their genetic identity with the oldest known stock from the German aquarium trade. Our study closes an important gap in the phylogenetic analysis of animal genomes and uncovers the unique evolutionary history of an emerging invasive species.
Anisotropic Friedel oscillations in graphene-like materials: The Dirac point approximation in wave-number dependent quantities revisited
Authors: Farajollahpour Tohid , Khamouei Shirin , Shateri Shabnam Safari , Phirouznia Arash
Published: February 2018

Friedel oscillations of the graphene-like materials are investigated theoretically for low and intermediate Fermi energies. Numerical calculations have been performed within the random phase approximation. It was demonstrated that for intra-valley transitions the contribution of the different Dirac points in the wave-number dependent quantities is determined by the orientation of the wave-number in k-space. Therefore, identical contribution of the different Dirac points is not automatically guaranteed by the degeneracy of the Hamiltonian at these points. Meanwhile, it was shown that the contribution of the inter-valley transitions is always anisotropic even when the Dirac points coincide with the Fermi level (E
F
= 0). This means that the Dirac point approximation based studies could give the correct physics only at long wave length limit. The anisotropy of the static dielectric function reveals different contribution of the each Dirac point. Additionally, the anisotropic k-space dielectric function results in anisotropic Friedel oscillations in graphene-like materials. Increasing the Rashba interaction strength slightly modifies the Friedel oscillations in this family of materials. Anisotropy of the dielectric function in k-space is the clear manifestation of band anisotropy in the graphene-like systems.
Independent estimates of marine population connectivity are more concordant when accounting for uncertainties in larval origins
Authors: Nolasco R. , Gomes I. , Peteiro L. , Albuquerque R. , Luna T. , Dubert J. , Swearer S. E. , Queiroga H.
Published: February 2018

Marine larval dispersal is a complex biophysical process that depends on the effects of species biology and oceanography, leading to logistical difficulties in estimating connectivity among populations of marine animals with biphasic life cycles. To address this challenge, the application of multiple methodological approaches has been advocated, in order to increase confidence in estimates of population connectivity. However, studies seldom account for sources of uncertainty associated with each method, which undermines a direct comparative approach. In the present study we explicitly account for the statistical uncertainty in observed connectivity matrices derived from elemental chemistry of larval mussel shells, and compare these to predictions from a biophysical model of dispersal. To do this we manipulate the observed connectivity matrix by applying different confidence levels to the assignment of recruits to source populations, while concurrently modelling the intrinsic misclassification rate of larvae to known sources. We demonstrate that the correlation between the observed and modelled matrices increases as the number of observed recruits classified as unknowns approximates the observed larval misclassification rate. Using this approach, we show that unprecedented levels of concordance in connectivity estimates (r = 0.96) can be achieved, and at spatial scales (20–40 km) that are ecologically relevant.
Phenotyping field-state wheat root system architecture for root foraging traits in response to environment×management interactions
Authors: Chen Xinxin , Li Yinian , He Ruiyin , Ding Qishuo
Published: February 2018

An important aspect of below-ground crop physiology is its root foraging performance, which is inherently related to root system architecture (RSA). A 2-yr field experiment was conducted and the field-state wheat RSA was phenotyped for root foraging trait (RFT). Four RSA-derived traits, i.e. Root horizontal angle (RHA), axial root expansion volume (AREV), RSA convex hull volume (CHV) and effective volume per unit root length (EVURL), were analyzed for RFTs in response to environment × management interactions. Results showed a dynamical RHA process but without statistical difference both within crop seasons and tillage treatments. AREV increased with root developmental stages, revealing an overall better root performance in the first year. However, tillage treatments did not induce observed difference within both crop seasons. CHV varied drastically from year to year and between tillage treatments, correlating well to the root length, but not with RHA. EVURL was both sensitive to tillage treatments and crop seasons, being a potential indicator for RFT. Above all, tillage effect on RFT was statistically far less than that induced by crop seasons. Pro/E assisted modeling can be used as an effective means for phenotyping integrated, RSA-derived, RFTs for root foraging response to induced environment × management interactions.