bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in nutritional status and nutrient intakes and correlates of overweight/obesity among rural adult women (≥18–60 years) in India: National Nutrition Monitoring Bureau (NNMB) national surveys
Authors: Meshram II , Balakrishna N , Sreeramakrishna K , Rao K Mallikharjun , Kumar R Hari , Arlappa N , Manohar G , Reddy Ch Gal , Ravindranath M , Kumar S Sharad , Brahmam GNV , Laxmaiah A
Published: August 2015

Objective

To assess trends in nutrient intakes and nutritional status of rural adult women (≥18–60 years) and the association of sociodemographic characteristics with overweight/obesity.

Design

Community-based cross-sectional studies carried out during 1975–79 to 2011–12 by the National Nutrition Monitoring Bureau (NNMB) were used. Anthropometric measurements such as height, weight and waist circumference, carried out during the surveys, were used. Association and logistic regression analyses between sociodemographic characteristics and overweight/obesity and abdominal obesity were conducted using a complex samples procedure.

Setting

Ten NNMB states of India.

Subjects

Non-pregnant and non-lactating rural women aged ≥18–60 years covered during the above periods from ten states in India.

Results

The prevalence of chronic energy deficiency has declined from 52 % during 1975–79 to 34 % during 2011–12, while that of overweight/obesity has increased from 7 % to 24 % during the same period. Median intakes of most of the nutrients have increased over the same period, although they were below recommended levels. The chance of overweight/obesity and abdominal obesity was significantly (P<0·01) higher among women aged 40–60 years, those belonging to Christian religion and other backward communities, women living in pucca houses, literate women, women engaged in service and business, and those having higher per capita income.

Conclusions

Prevalence of chronic energy deficiency has declined significantly; however, overweight/obesity has increased during the same period. This increase in overweight/obesity may be attributed to increased consumption of fatty foods, sedentary lifestyle and improved socio-economic status. There is a need to educate the community about regular physical exercise, low intakes of fats and oils, and a balanced diet.
Polymeric composites on the basis of Martian ground for building future mars stations
Authors: Mukbaniani O. V. , Aneli J. N. , Markarashvili E. G. , Tarasashvili M. V. , Aleksidze N. D.
Published: August 2015

The colonization of Mars will require obtaining building materials which can be put in place and processed into buildings via various constructive technologies. We tried to use artificial Martian ground – AMG (GEO PAT 11-234 (2015)) and special resins for the preparation of building block prototypes. The composite material has been obtained based on the AMG as filler, epoxy resin (type ED-20) and tetraethoxysilane – TEOS. We have studied strengthening – softening temperatures and water absorption of the AMG polymer composites that are determined by epoxy resin and TEOS modification. Comparison of the experimental results shows that composites containing modified filler have higher values of the maximum ultimate strength, resistance and flexibility parameters than unmodified composites with definite loading. Modified composites also have a higher softening temperature and lower water absorption.
TO THE MOUNTAINTOP AGAIN: THE EARLY RAWLS AND POST-PROTESTANT ETHICS IN POSTWAR AMERICA
Authors: BOK P. MACKENZIE
Published: August 2015

This article draws on archival sources to offer the first thoroughgoing account of how John Rawls moved from his undergraduate Christian ethics to the mature moral theory that undergirdedA Theory of Justice. Identifying the liberal Protestant (rather than neo-orthodox) convictions at the heart of Rawls's senior thesis, it shows how he found an alternative postwar grounding for these views by applying Wittgenstein's later arguments about concepts, criteria, and inductive reasoning to ethics. The article places Rawls in the context of a whole community of mid-century American ethical theorists drawing upon Wittgenstein and trumpeting forms of moral “naturalism,” many of whom shared Rawls's Protestant heritage. It suggests that we can only make sense of the reliance of Rawls's moral theory on personal recognition, emotion, and a universal vision if we sideline the traditional dichotomies of the secularization debate and regard the postwar ethics of Rawls and his cohort as “post-Protestant.”
Corporate social responsibility, juridification and globalisation: ‘inventive interventionism’ for a ‘paradox’
Authors: Osuji Onyeka K.
Published: August 2015

This paper proposes ‘inventive interventionism’ as a regulatory approach to incorporate substantive outcomes, stakeholder empowerment, effective disclosure and a global multi-stakeholder and multidimensional view of corporate social responsibility (CSR) and social disclosure. Inventive interventionism also applies new paradigms of regulation that recognise CSR as one of the proximate engineers of efficient public governance and ultimate sources of socio-economic development. The paper adopts a transnational and comparative approach to regulatory CSR and situates the voluntary and prescriptive approaches in the wider regulation debate. It draws on reflexive law, responsive regulation, institutional and other theories to demonstrate that existing CSR regulations in several jurisdictions are not representative of the law's multidimensional and multidirectional nature. Inventive interventionism reflects a functional approach to the law–CSR dialectic relationship and contributes to the development of an analytical framework for CSR and reforming its national and global regulatory environment.
Unearthing bureaucratic legal consciousness: government officials’ legal identification and moral ideals
Authors: Richards Zach
Published: August 2015

The legal consciousness of citizens receiving the law has been extensively explored but little attention has been paid to the legal consciousness of individuals applying the law. This paper draws on interviews with forty government officials in the Refugee Review Tribunal of Australia to address this concern, analysing how government bureaucrats think about law. In doing so, it identifies a series of underlying ideals informing the officials’ legal identification narratives. It presents a heuristic that positions bureaucratic legal identification in relation to broader moral ideals, demonstrating that as government officials’ identification with law increases so too does their idealisation of intellect and information processing. Conversely, as the officials’ identification with law decreases, their idealisation of experience and truth verification increases. These findings provide new insights into how law works in government, revealing bureaucratic legal identification as structured according to broader moral values, and thereby unearthing legal consciousness’ latent metacognitive dimension.
Analysis of Israelis [Jews and Arab–Palestinians]: exploring law in society and society in law
Authors: Barzilai Gad
Published: August 2015

Attributing a great deal of attention to global and local knowledge, this paper is focused on law and society scholarship that has been published by Israelis, both Jewish and Arab-Palestinians. It attempts to unveil and to map some of the major issues that have characterised the scholarly debates and intellectual discourse, primarily critical questions on law and political power, the nation-state, legal rights discourse and equality. More specifically, the paper analyses socio-legal research on various local issues, such as multiculturalism and national rifts on the backdrop of the 1967 military occupation alongside the emergence of a neoliberal capitalist economy. The protracted Arab-Palestinian–Israeli conflict and the fragmentation of the political partisan map in Israel have incited more emphasis on the place of the Israeli Supreme Court, primarily sitting as a High Court of Justice, in public life as an important regulatory institution. This focus on the judicial power of the Court has resulted in an even more frantic controversy on whether the Court has become too engaged in political affairs. In all the law and society debates, local concepts and global knowledge have been intertwined. Hence, the paper enables scholars around the world to closely examine law and society scholarship on the convergence of local and global knowledge.
Nonsuicidal Self-Injury in Adolescents
Authors: In-Albon Tina
Published: August 2015

Abstract. Nonsuicidal self-injury (NSSI) is a prevalent, pervasive, clinically significant behavior in adolescents, frequently associated with serious social, physical, and psychological consequences. It is characterized by high comorbidity with various disorders. Therefore, NSSI has been included as a research diagnosis in the Diagnostic and statistical manual of mental disorders (5th ed., American Psychiatric Association (APA; 2013) ; DSM-5; Section 3), as a condition requiring further study for possible future official adoption. This is a positive step toward providing researchers with a uniform definition and criteria. This state-of-the-art article gives an overview of prevalence rates, comorbidity, clinical correlates, functions, and risk factors as well as treatment and dealing with adolescents with NSSI and their Internet activities. Furthermore, the association and differences between NSSI and suicidality as well as borderline personality disorder are reviewed. The article concludes with future directions for research, for example, the dimensional approach to classification of the Research Domain Criteria project.
MicroRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by regulating PPP2R1B expression in colorectal cancer
Authors: Zhang Y , Talmon G , Wang J
Published: August 2015

Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-587 modulates drug resistance through downregulation of expression of PPP2R1B, a regulatory subunit of the PP2A complex, which negatively regulates AKT activation. Knockdown of PPP2R1B expression increases AKT phosphorylation, which leads to elevated XIAP expression and enhanced 5-FU resistance; whereas rescue of PPP2R1B expression in miR-587-expressing cells decreases AKT phosphorylation/XIAP expression, re-sensitizing colon cancer cells to 5-FU-induced apoptosis. Moreover, a specific and potent AKT inhibitor, MK2206, reverses miR-587-conferred 5-FU resistance. Importantly, studies of colorectal cancer specimens indicate that the expression of miR-587 and PPP2R1B positively and inversely correlates with chemoresistance, respectively, in colorectal cancer. These findings indicate that the miR-587/PPP2R1B/pAKT/XIAP signaling axis has an important role in mediating response to chemotherapy in colorectal cancer. A major implication of our study is that inhibition of miR-587 or restoration of PPP2R1B expression may have significant therapeutic potential to overcome drug resistance in colorectal cancer patients and that the combined use of an AKT inhibitor with 5-FU may increase efficacy in colorectal cancer treatment.
Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview
Authors: Nardacci R , Perfettini J-L , Grieco L , Thieffry D , Kroemer G , Piacentini M
Published: August 2015

Infection by human immunodeficiency virus-1 (HIV-1) is associated with a progressive decrease in CD4 T-cell numbers and the consequent collapse of host immune defenses. The major pathogenic mechanism of AIDS is the massive apoptotic destruction of the immunocompetent cells, including uninfected cells. The latter process, also known as by-stander killing, operates by various mechanisms one of which involves the formation of syncytia which undergo cell death by following a complex pathway. We present here a detailed and curated map of the syncytial apoptosis signaling network, aimed at simplifying the whole mechanism that we have characterized at the molecular level in the last 15 years. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner software and encompasses 36 components (proteins/genes) and 54 interactions. The simplification of this complex network paves the way for the development of novel therapeutic strategies to eradicate HIV-1 infection. Agents that induce the selective death of HIV-1-elicited syncytia might lead to the elimination of viral reservoirs and hence constitute an important complement to current antiretroviral therapies.
Chop deficiency prevents UUO-induced renal fibrosis by attenuating fibrotic signals originated from Hmgb1/TLR4/NFκB/IL-1β signaling
Authors: Zhang M , Guo Y , Fu H , Hu S , Pan J , Wang Y , Cheng J , Song J , Yu Q , Zhang S , Xu J-F , Pei G , Xiang X , Yang P , Wang C-Y
Published: August 2015

Renal fibrosis, particularly tubulointerstitial fibrosis is considered to be the final manifestation of almost all chronic kidney diseases (CKDs). Herein we demonstrated evidence that CHOP-related ER stress is associated with the development of renal fibrosis in both CKD patients and unilateral ureteral obstruction (UUO)-induced animals, and specifically, mice deficient in Chop were protected from UUO-induced renal fibrosis. Mechanistic studies revealed that loss of Chop protected tubular cells from UUO-induced apoptosis and secondary necrosis along with attenuated Hmgb1 passive release and active secretion. As a result, Chop deficiency suppressed Hmgb1/TLR4/NFκB signaling, which then repressed UUO-induced IL-1β production. Consequently, the IL-1β downstream Erk1/2 activity and its related c-Jun transcriptional activity were reduced, leading to attenuated production of TGF-β1 following UUO insult. It was further noted that reduced IL-1β production also inhibited UUO-induced PI3K/AKT signaling, and both of which ultimately protected mice from UUO-induced renal fibrosis. Together, our data support that suppression of CHOP expression could be a viable therapeutic strategy to prevent renal fibrosis in patients with CKDs.
Protein tyrosine kinase 6 promotes ERBB2-induced mammary gland tumorigenesis in the mouse
Authors: Peng M , Ball-Kell S M , Tyner A L
Published: August 2015

Protein tyrosine kinase 6 (PTK6) expression, activation, and amplification of thePTK6gene have been reported in ERBB2/HER2-positive mammary gland cancers. To explore contributions of PTK6 to mammary gland tumorigenesis promoted by activated ERBB2, we crossedPtk6−/−mice with the mouse mammary tumor virus-ERBB2 transgenic mouse line expressing activated ERBB2 and characterized tumor development and progression. ERBB2-induced tumorigenesis was significantly delayed and diminished in mice lacking PTK6. PTK6 expression was induced in the mammary glands of ERBB2 transgenic mice before tumor development and correlated with activation of signal transducer and activator of transcription 3 (STAT3) and increased proliferation. Disruption of PTK6 impaired STAT3 activation and proliferation. Phosphorylation of the PTK6 substrates focal adhesion kinase (FAK) and breast cancer anti-estrogen resistance 1 (BCAR1; p130CAS) was decreased inPtk6−/−mammary gland tumors. Reduced numbers of metastases were detected in the lungs ofPtk6−/−mice expressing activated ERBB2, compared with wild-type ERBB2 transgenic mice. PTK6 activation was detected at the edges of ERBB2-positive tumors. These data support roles for PTK6 in both ERBB2-induced mammary gland tumor initiation and metastasis, and identify STAT3, FAK, and BCAR1 as physiologically relevant PTK6 substrates in breast cancer. Including PTK6 inhibitors as part of a treatment regimen could have distinct benefits in ERBB2/HER2-positive breast cancers.
Scaffolding protein Homer1a protects against NMDA-induced neuronal injury
Authors: Wang Y , Rao W , Zhang C , Zhang C , Liu M-d , Han F , Yao L-b , Han H , Luo P , Su N , Fei Z
Published: August 2015

Excessive N-methyl-D-aspartate receptor (NMDAR) activation and the resulting activation of neuronal nitric oxide synthase (nNOS) cause neuronal injury. Homer1b/c facilitates NMDAR-PSD95-nNOS complex interactions, and Homer1a is a negative competitor of Homer1b/c. We report that Homer1a was both upregulated by and protected against NMDA-induced neuronal injury in vitro and in vivo. The neuroprotective activity of Homer1a was associated with NMDA-induced Ca2+ influx, oxidative stress and the resultant downstream signaling activation. Additionally, we found that Homer1a functionally regulated NMDAR channel properties in neurons, but did not regulate recombinant NR1/NR2B receptors in HEK293 cells. Furthermore, we found that Homer1a detached the physical links among NR2B, PSD95 and nNOS and reduced the membrane distribution of NMDAR. NMDA-induced neuronal injury was more severe in Homer1a homozygous knockout mice (KO, Homer1a−/−) when compared with NMDA-induced neuronal injury in wild-type mice (WT, Homer1a+/+). Additionally, Homer1a overexpression in the cortex of Homer1a−/− mice alleviated NMDA-induced neuronal injury. These findings suggest that Homer1a may be a key neuroprotective endogenous molecule that protects against NMDA-induced neuronal injury by disassembling NR2B-PSD95-nNOS complexes and reducing the membrane distribution of NMDARs.
Tyr1068-phosphorylated epidermal growth factor receptor (EGFR) predicts cancer stem cell targeting by erlotinib in preclinical models of wild-type EGFR lung cancer
Authors: Sette G , Salvati V , Mottolese M , Visca P , Gallo E , Fecchi K , Pilozzi E , Duranti E , Policicchio E , Tartaglia M , Milella M , De Maria R , Eramo A
Published: August 2015

Tyrosine kinase inhibitors (TKIs) have shown strong activity against non-small-cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations. However, a fraction of EGFR wild-type (WT) patients may have an improvement in terms of response rate and progression-free survival when treated with erlotinib, suggesting that factors other than EGFR mutation may lead to TKI sensitivity. However, at present, no sufficiently robust clinical or biological parameters have been defined to identify WT-EGFR patients with greater chances of response. Therapeutics validation has necessarily to focus on lung cancer stem cells (LCSCs) as they are more difficult to eradicate and represent the tumor-maintaining cell population. Here, we investigated erlotinib response of lung CSCs with WT-EGFR and identified EGFR phosphorylation at tyrosine1068 (EGFRtyr1068) as a powerful biomarker associated with erlotinib sensitivity both in vitro and in preclinical CSC-generated xenografts. In contrast to the preferential cytotoxicity of chemotherapy against the more differentiated cells, in EGFRtyr1068 cells, erlotinib was even more active against the LCSCs compared with their differentiated counterpart, acquiring potential value as CSC-directed therapeutics in the context of WT-EGFR lung cancer. Although tumor growth was inhibited to a similar extent during erlotinib or chemotherapy administration to responsive tumors, erlotinib proved superior to chemotherapy in terms of higher tolerability and reduced tumor aggressiveness after treatment suspension, substantiating the possibility of preferential LCSC targeting, both in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) tumors. We conclude that EGFRtyr1068 may represent a potential candidate biomarker predicting erlotinib response at CSC-level in EGFR-WT lung cancer patients. Finally, besides its invariable association with erlotinib sensitivity in EGFR-WT lung CSCs, EGFRtyr1068 was associated with EGFR-sensitizing mutations in cell lines and patient tumors, with relevant diagnostic, clinical and therapeutic implications.
Assessment of p53 and ATM functionality in chronic lymphocytic leukemia by multiplex ligation-dependent probe amplification
Authors: te Raa G D , Moerland P D , Leeksma A C , Derks I A , Yigittop H , Laddach N , Loden-van Straaten M , Navrkalova V , Trbusek M , Luijks D M , Zenz T , Skowronska A , Hoogendoorn M , Stankovic T , van Oers M H , Eldering E , Kater A P
Published: August 2015

The ATM-p53 DNA-damage response (DDR) pathway has a crucial role in chemoresistance in CLL, as indicated by the adverse prognostic impact of genetic aberrations of TP53 and ATM. Identifying and distinguishing TP53 and ATM functional defects has become relevant as epigenetic and posttranscriptional dysregulation of the ATM/p53 axis is increasingly being recognized as the underlying cause of chemoresistance. Also, specific treatments sensitizing TP53- or ATM-deficient CLL cells are emerging. We therefore developed a new ATM-p53 functional assay with the aim to (i) identify and (ii) distinguish abnormalities of TP53versusATM and (iii) enable the identification of additional defects in the ATM-p53 pathway. Reversed transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) was used to measure ATM and/or p53-dependent genes at the RNA level following DNA damage using irradiation. Here, we showed that this assay is able to identify and distinguish three subgroups of CLL tumors (i.e., TP53-defective, ATM-defective and WT) and is also able to detect additional samples with a defective DDR, without molecular aberrations in TP53 and/or ATM. These findings make the ATM-p53 RT-MLPA functional assay a promising prognostic tool for predicting treatment responses in CLL.
Destructive tsunami-like wave generated by surf beat over a coral reef during Typhoon Haiyan
Authors: Roeber Volker , Bricker Jeremy D.
Published: August 2015

Storm surges cause coastal inundation due to setup of the water surface resulting from atmospheric pressure, surface winds and breaking waves. Here we show that during Typhoon Haiyan, the setup generated by breaking waves near the fringing-reef-protected town of Hernani, the Philippines, oscillated with the incidence of large and small wave groups, and steepened into a tsunami-like wave that caused extensive damage and casualties. Though fringing reefs usually protect coastal communities from moderate storms, they can exacerbate flooding during strong events with energetic waves. Typical for reef-type bathymetries, a very short wave-breaking zone over the steep reef face facilitates the freeing of infragravity-period fluctuations (surf beat) with little energy loss. Since coastal flood planning relies on phase-averaged wave modelling, infragravity surges are not being accounted for. This highlights the necessity for a policy change and the adoption of phase-resolving wave models for hazard assessment in regions with fringing reefs.
Design of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription
Authors: Jang Mihue , Kim Jong Hwan , Nam Hae Yun , Kwon Ick Chan , Ahn Hyung Jun
Published: August 2015

For therapeutic applications of siRNA, there are technical challenges with respect to targeted and systemic delivery. We here report a new siRNA carrier, RNAtr NPs, in a way that multiple tandem copies of RNA hairpins as a result of rolling circle transcription (RCT) can be readily adapted in tumour-targeted and systemic siRNA delivery. RNAtr NPs provide a means of condensing large amounts of multimeric RNA transcripts into the compact nanoparticles, especially without the aid of polycationic agents, and thus reduce the risk of immunogenicity and cytotoxicity by avoiding the use of synthetic polycationic reagents. This strategy allows the design of a platform technology for systemic delivery of siRNA to tumour sites, because RCT reaction, which enzymatically generates RNA polymers in multiple copy numbers at low cost, can lead to directly accessible routes to targeted and systemic delivery. Therefore, RNAtr NPs suggest great potentials as the siRNA therapeutics for cancer treatment.
Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant
Authors: Yuchi Zhiguang , Yuen Siobhan M. Wong King , Lau Kelvin , Underhill Ainsley Q. , Cornea Razvan L. , Fessenden James D. , Van Petegem Filip
Published: August 2015

Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca2+-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we describe the crystal structures of the SPRY1 and tandem-repeat domains at 1.2–1.5 Å resolution, which reveal several structural elements not detected in recent cryo-EM reconstructions of RyRs. The cryo-EM studies disagree on the position of SPRY domains, which had been proposed based on homology modelling. Computational docking of the crystal structures, combined with FRET studies, show that the SPRY1 domain is located next to FK506-binding protein (FKBP). Molecular dynamics flexible fitting and mutagenesis experiments suggest a hydrophobic cluster within SPRY1 that is crucial for FKBP binding. A RyR1 disease mutation, N760D, appears to directly impact FKBP binding through interfering with SPRY1 folding.
MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation
Authors: Pon Julia R. , Wong Jackson , Saberi Saeed , Alder Olivia , Moksa Michelle , Grace Cheng S. -W. , Morin Gregg B. , Hoodless Pamela A. , Hirst Martin , Marra Marco A.
Published: August 2015

Myocyte enhancer factor 2B (MEF2B) is a transcription factor with mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL). To provide insight into the regulatory network of MEF2B, in this study, we analyse global gene expression and DNA-binding patterns. We find that candidate MEF2B direct target genes include RHOB, RHOD, CDH13, ITGA5 and CAV1, and that indirect target genes of MEF2B include MYC, TGFB1, CARD11, MEF2C, NDRG1 and FN1. MEF2B overexpression increases HEK293A cell migration and epithelial–mesenchymal transition, and decreases DLBCL cell chemotaxis. K4E, Y69H and D83V MEF2B mutations decrease the capacity of MEF2B to activate transcription and decrease its’ effects on cell migration. The K4E and D83V mutations decrease MEF2B DNA binding. In conclusion, our map of the MEF2B regulome connects MEF2B to drivers of oncogenesis.
Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity
Authors: Winkelmann Donald A. , Forgacs Eva , Miller Matthew T. , Stock Ann M.
Published: August 2015

Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin that is in clinical trials for treatment of systolic heart failure. A detailed kinetic analysis of cardiac myosin has shown that the drug accelerates phosphate release by shifting the equilibrium of the hydrolysis step towards products, leading to a faster transition from weak to strong actin-bound states. The structure of the human β-cardiac motor domain (cMD) with OM bound reveals a single OM-binding site nestled in a narrow cleft separating two domains of the human cMD where it interacts with the key residues that couple lever arm movement to the nucleotide state. In addition, OM induces allosteric changes in three strands of the β-sheet that provides the communication link between the actin-binding interface and the nucleotide pocket. The OM-binding interactions and allosteric changes form the structural basis for the kinetic and mechanical tuning of cardiac myosin.
Museum samples reveal rapid evolution by wild honey bees exposed to a novel parasite
Authors: Mikheyev Alexander S. , Tin Mandy M. Y. , Arora Jatin , Seeley Thomas D.
Published: August 2015

Understanding genetic changes caused by novel pathogens and parasites can reveal mechanisms of adaptation and genetic robustness. Using whole-genome sequencing of museum and modern specimens, we describe the genomic changes in a wild population of honey bees in North America following the introduction of the ectoparasitic mite,Varroa destructor. Even though colony density in the study population is the same today as in the past, a major loss of haplotypic diversity occurred, indicative of a drastic mitochondrial bottleneck, caused by massive colony mortality. In contrast, nuclear genetic diversity did not change, though hundreds of genes show signs of selection. The genetic diversity within each bee colony, particularly as a consequence of polyandry by queens, may enable preservation of genetic diversity even during population bottlenecks. These findings suggest that genetically diverse honey bee populations can recover from introduced diseases by evolving rapid tolerance, while maintaining much of the standing genetic variation.
Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications
Authors: Liu Fuyao , He Xiuxia , Chen Hongda , Zhang Junping , Zhang Huimao , Wang Zhenxin
Published: August 2015

An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe3+, gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3 nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging.
The burden of ambient temperature on years of life lost in Guangzhou, China
Authors: Yang Jun , Ou Chun-Quan , Guo Yuming , Li Li , Guo Cui , Chen Ping-Yan , Lin Hua-Liang , Liu Qi-Yong
Published: August 2015

Limited evidence is available on the association between temperature and years of life lost (YLL). We applied distributed lag non-linear model to assess the nonlinear and delayed effects of temperature on YLL due to cause-/age-/education-specific mortality in Guangzhou, China. We found that hot effects appeared immediately, while cold effects were more delayed and lasted for 14 days. On average, 1 °C decrease from 25th to 1st percentile of temperature was associated with an increase of 31.15 (95%CI: 20.57, 41.74), 12.86 (8.05, 17.68) and 6.64 (3.68, 9.61) YLL along lag 0–14 days for non-accidental, cardiovascular and respiratory diseases, respectively. The corresponding estimate of cumulative hot effects (1 °C increase from 75th to 99th percentile of temperature) was 12.71 (−2.80, 28.23), 4.81 (−2.25, 11.88) and 2.81 (−1.54, 7.16). Effect estimates of cold and hot temperatures-related YLL were higher in people aged up to 75 years and persons with low education level than the elderly and those with high education level, respectively. The mortality risks associated with cold and hot temperatures were greater on the elderly and persons with low education level. This study highlights that YLL provides a complementary method for assessing the death burden of temperature.
Critical anatomic region of nasopalatine canal based on tridimensional analysis: cone beam computed tomography
Authors: Fernández-Alonso Ana , Antonio Suárez-Quintanilla Juan , Muinelo-Lorenzo Juan , Varela-Mallou Jesús , Smyth Chamosa Ernesto , Mercedes Suárez-Cunqueiro María
Published: August 2015

The study aim of this was to define the critical anatomic region of the premaxilla by evaluating dimensions of nasopalatine canal, buccal bone plate (BBP) and palatal bone plate (PBP). 230 CBCTs were selected with both, one or no upper central incisors present (+/+, −/+, −/−) and periodontal condition was evaluated. T-student test, ANOVA, Pearson´s correlation and a multivariant-linear regression model (MLRM) were used. Regarding gender, significant differences at level 1 (lower NC) were found for: buccal-palatal, transversal and sagittal NC diameters and NC length (NCL). Regarding dental status, significant differences were found for: total BBP length (tBL) and PBP width (PW2) at level 2 (NCL midpoint). NCL was correlated with PW2, tBL and PBP length at level 3 (foramina of Stenson level). An MLRM had a high prediction value for NCL (69.3%). Gender is related to NC dimensions. Dental status has an influence on BBP dimensions, but does not influence on NC and PBP. Periodontal condition should be evaluated for precise premaxillae analysis NC diameters at the three anatomical planes are related to each other, while NCL is related to BBP and PBP lengths. A third of premaxilla is taken up by NC, thus, establishing the critical anatomic region.
Tumor necrosis factor (TNF)-receptor 1 and 2 mediate homeostatic synaptic plasticity of denervated mouse dentate granule cells
Authors: Becker Denise , Deller Thomas , Vlachos Andreas
Published: August 2015

Neurological diseases are often accompanied by neuronal cell death and subsequent deafferentation of connected brain regions. To study functional changes after denervation we generated entorhino-hippocampal slice cultures, transected the entorhinal pathway and denervated dentate granule cells in vitro. Our previous work revealed that partially denervated neurons respond to the loss of input with a compensatory, i.e., homeostatic, increase in their excitatory synaptic strength. TNFα maintains this denervation-induced homeostatic strengthening of excitatory synapses. Here, we used pharmacological approaches and mouse genetics to assess the role of TNF-receptor 1 and 2 in lesion-induced excitatory synaptic strengthening. Our experiments disclose that both TNF-receptors are involved in the regulation of denervation-induced synaptic plasticity. In line with this result TNF-receptor 1 and 2 mRNA-levels were upregulated after deafferentation in vitro. These findings implicate TNF-receptor signaling cascades in the regulation of homeostatic plasticity of denervated networks and suggest an important role for TNFα-signaling in the course of neurological diseases accompanied by deafferentation.
Latency of auditory evoked potential monitoring the effects of general anesthetics on nerve fibers and synapses
Authors: Huang Bowan , Liang Feixue , Zhong Lei , Lin Minlin , Yang Juan , Yan Linqing , Xiao Jinfan , Xiao Zhongju
Published: August 2015

Auditory evoked potential (AEP) is an effective index for the effects of general anesthetics. However, it’s unknown if AEP can differentiate the effects of general anesthetics on nerve fibers and synapses. Presently, we investigated AEP latency and amplitude changes to different acoustic intensities during pentobarbital anesthesia. Latency more regularly changed than amplitude during anesthesia. AEP Latency monotonically decreased with acoustic intensity increase (i.e., latency-intensity curve) and could be fitted to an exponential decay equation, which showed two components, the theoretical minimum latency and stimulus-dependent delay. From the latency-intensity curves, the changes of these two components (∆L and ∆I) were extracted during anesthesia. ∆L and ∆I monitored the effect of pentobarbital on nerve fibers and synapses. Pentobarbital can induce anesthesia and two side effects, hypoxemia and hypothermia. The hypoxemia was not related with ∆L and ∆I. However, ∆L was changed by the hypothermia, whereas ∆I was changed by the hypothermia and anesthesia. Therefore, we conclude that, AEP latency is superior to amplitude for the effects of general anesthetics, ∆L monitors the effect of hypothermia on nerve fibers and ∆I monitors a combined effect of anesthesia and hypothermia on synapses. When eliminating the temperature factor, ∆I monitors the anesthesia effect on synapses.
Highly Efficient Processing of Multi-photon States
Authors: Lin Qing , He Bing
Published: August 2015

How to implement multi-qubit gates is an important problem in quantum information processing. Based on cross phase modulation, we present an approach to realizing a family of multi-qubit gates that deterministically operate on single photons as the qubits. A general n-qubit unitary operation is a typical example of these gates. The approach greatly relax the requirement on the resources, such as the ancilla photons and coherent beams, as well as the number of operations on the qubits. The improvement in this framework may facilitate large scale quantum information processing.
Caustics and Rogue Waves in an Optical Sea
Authors: Mathis Amaury , Froehly Luc , Toenger Shanti , Dias Frédéric , Genty Goëry , Dudley John M.
Published: August 2015

There are many examples in physics of systems showing rogue wave behaviour, the generation of high amplitude events at low probability. Although initially studied in oceanography, rogue waves have now been seen in many other domains, with particular recent interest in optics. Although most studies in optics have focussed on how nonlinearity can drive rogue wave emergence, purely linear effects have also been shown to induce extreme wave amplitudes. In this paper, we report a detailed experimental study of linear rogue waves in an optical system, using a spatial light modulator to impose random phase structure on a coherent optical field. After free space propagation, different random intensity patterns are generated, including partially-developed speckle, a broadband caustic network and an intermediate pattern with characteristics of both speckle and caustic structures. Intensity peaks satisfying statistical criteria for rogue waves are seen especially in the case of the caustic network and are associated with broader spatial spectra. In addition, the electric field statistics of the intermediate pattern shows properties of an “optical sea” with near-Gaussian statistics in elevation amplitude and trough-to-crest statistics that are near-Rayleigh distributed but with an extended tail where a number of rogue wave events are observed.
Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors
Authors: Lindenberger Jared J. , Kumar Veleti Sri , Wilson Brittney N. , Sucheck Steven J. , Ronning Donald R.
Published: August 2015

GlgE is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched α-glucan. In Mycobacterium tuberculosis (M. tb), inactivation of GlgE (Mtb GlgE) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design. In this study, the crystal structures of the Mtb GlgE in a binary complex with maltose and a ternary complex with maltose and a maltosyl-acceptor molecule, maltohexaose, were solved to 3.3 Å and 4.0 Å, respectively. The maltohexaose structure reveals a dominant site for α-glucan binding. To obtain more detailed interactions between first generation, non-covalent inhibitors and GlgE, a variant Streptomyces coelicolor GlgEI (Sco GlgEI-V279S) was made to better emulate the Mtb GlgE M1P binding site. The structure of Sco GlgEI-V279S complexed with α-maltose-C-phosphonate (MCP), a non-hydrolyzable substrate analogue, was solved to 1.9 Å resolution and the structure of Sco GlgEI-V279S complexed with 2,5-dideoxy-3-O-α-D-glucopyranosyl-2,5-imino-D-mannitol (DDGIM), an oxocarbenium mimic, was solved to 2.5 Å resolution. These structures detail important interactions that contribute to the inhibitory activity of these compounds and provide information on future designs that may be exploited to improve upon these first generation GlgE inhibitors.
The thorax morphology of Epiophlebia (Insecta: Odonata) nymphs – including remarks on ontogenesis and evolution
Authors: Büsse Sebastian , Helmker Benjamin , Hörnschemeyer Thomas
Published: August 2015

The species of Epiophlebia are unique among the recent Odonata in showing a mixture of morphological characters of dragonflies (Anisoptera) and damselflies (Zygoptera). The status of the four described extant species of Epiophlebia is disputable from a genetic as well as from a morphological point of view. Here we present an analysis of the thoracic musculature of different nymphal instars of Epiophlebia laidlawi and Epiophlebia superstes to elucidate their morphology and ontogenetic development. In total, 75 muscles have been identified in the thorax of Epiophlebia. This represents the highest number of thoracic muscles ever found in any odonate. It includes six muscles that are reported for the first time for Odonata and three of these are even new for Pterygota. In total, our results indicate that Epiophlebia has the most ancestral thoracic morphology among Odonata.
Ultrafast excited-state dynamics and fluorescence deactivation of near-infrared fluorescent proteins engineered from bacteriophytochromes
Authors: Zhu Jingyi , Shcherbakova Daria M. , Hontani Yusaku , Verkhusha Vladislav V. , Kennis John T. M.
Published: August 2015

Near-infrared fluorescent proteins, iRFPs, are recently developed genetically encoded fluorescent probes for deep-tissue in vivo imaging. Their functions depend on the corresponding fluorescence efficiencies and electronic excited state properties. Here we report the electronic excited state deactivation dynamics of the most red-shifted iRFPs: iRFP702, iRFP713 and iRFP720. Complementary measurements by ultrafast broadband fluorescence and absorption spectroscopy show that single exponential decays of the excited state with 600 ~ 700 ps dominate in all three iRFPs, while photoinduced isomerization was completely inhibited. Significant kinetic isotope effects (KIE) were observed with a factor of ~1.8 in D2O and are interpreted in terms of an excited-state proton transfer (ESPT) process that deactivates the excited state in competition with fluorescence and chromophore mobility. On this basis, new approaches for rational molecular engineering may be applied to iRFPs to improve their fluorescence.
Climate changes and solar cycles recorded at the Holocene Paraná Delta and their impact on human population
Authors: Milana Juan Pablo , Kröhling Daniela
Published: August 2015

The Paraná delta, growing at a rate of c. 2 km2 yr−1 since 6,000 yrs, is one of the most complete records of the Late Holocene in southern South America. The evolution of this 17,400 km2 delta enclosed in Plata estuary, can be tracked by a series of 343 successive coastal-ridges showing a c.11 years period, in coincidence with sunspot cycle, also found in some North Hemisphere coastal-ridge successions. The Paraná delta shifted from fluvial, to wave-dominated and back to the present fluvial-dominated delta, in response to climate changes associated with wind activity correlating with South American glacial cycles. The wave-dominated windy period coincides with the activation of the Pampean Sand Sea, suggesting desert conditions prevailed on the Pampas between 5,300 and 1,700 yrs, in coincidence with scarce or absent pre-historic aborigine remains (“archeological silence”). Further warmer and less windy conditions allowed human repopulation. Results suggest that aside the solar forcing, both short and medium term climate changes controlled delta evolution. An important learning is that a slight cooling would turn the highly productive pampas, into that unproductive desert and, given the lack of artificial irrigation systems, changing present-day warmhouse into a cooling cycle might be economically catastrophic for the region.
Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo
Authors: Yuan Xing , Chen Hao , Li Xia , Dai Ming , Zeng Huawu , Shan Lei , Sun Qingyan , Zhang Weidong
Published: August 2015

Targeted inhibition of protein kinase C (PKC) inhibits hepatocellular carcinoma (HCC) proliferation and metastasis. We previously reported the cytotoxicity of a series of synthetic phenyl-substituted polyoxygenated xanthone derivatives against human HCC. In the current study, the most potent natural product, isojacareubin (ISJ), was synthesized and its cellular-level antihepatoma activities were evaluated. ISJ significantly inhibited cell proliferation and was highly selective for HCC cells in comparison to nonmalignant QSG-7701 hepatocytes. Moreover, ISJ exhibited pro-apoptotic effects on HepG2 hepatoma cells, as well as impaired HepG2 cell migration and invasion. Furthermore, ISJ was a potent inhibitor of PKC, with differential actions against various PKC isotypes. ISJ selectively inhibited the expression of aPKC (PKCζ) in the cytosol and the translocation of cytosolic PKCζ to membrane site. ISJ also directly interacted with cPKC (PKCα) and nPKC (PKCδ, PKCε and PKCμ) and thereby inhibited the early response of major MAPK phosphorylation and the late response of HCC cell invasion and proliferation. In a hepatoma xenograft model, ISJ pretreatment resulted in significant antihepatoma activity in vivo. These findings identify ISJ as a promising lead compound for the development of new antihepatoma agents and may guide the search for additional selective PKC inhibitors.
Rational Design of Photonic Dust from Nanoporous Anodic Alumina Films: A Versatile Photonic Nanotool for Visual Sensing
Authors: Chen Yuting , Santos Abel , Wang Ye , Kumeria Tushar , Ho Daena , Li Junsheng , Wang Changhai , Losic Dusan
Published: August 2015

Herein, we present a systematic study on the development, optimisation and applicability of interferometrically coloured distributed Bragg reflectors based on nanoporous anodic alumina (NAA-DBRs) in the form of films and nanoporous microparticles as visual/colorimetric analytical tools. Firstly, we synthesise a complete palette of NAA-DBRs by galvanostatic pulse anodisation approach, in which the current density is altered in a periodic fashion in order to engineer the effective medium of the resulting photonic films in depth. NAA-DBR photonic films feature vivid colours that can be tuned across the UV-visible-NIR spectrum by structural engineering. Secondly, the effective medium of the resulting photonic films is assessed systematically by visual analysis and reflectometric interference spectroscopy (RIfS) in order to establish the most optimal nanoporous platforms to develop visual/colorimetric tools. Then, we demonstrate the applicability of NAA-DBR photonic films as a chemically selective sensing platform for visual detection of mercury(II) ions. Finally, we generate a new nanomaterial, so-called photonic dust, by breaking down NAA-DBRs films into nanoporous microparticles. The resulting microparticles (μP-NAA-DBRs) display vivid colours and are sensitive towards changes in their effective medium, opening new opportunities for developing advanced photonic nanotools for a broad range of applications.