bluuebunny/crossref_metadata_2025 huggingface dataset:
Starting and Stopping Points: A Response to Stavros Gadinis
Authors: Johns Fleur
Published: June 2017

Open the website of the Financial Action Task Force (or FATF) and find your way to the “FATF Presidency” page. Up until the end of June 2015, you would have encountered a headshot of a dapper fellow with smiling eyes and a pink bowtie: Roger Wilkins OA, President of FATF between July 2014 and June 2015. A one time “mandarin” of the public service in Australia (former Secretary of the federal Attorney-General’s Department in that country), Mr. Wilkins seems an apt embodiment of those qualities that Stavros Gadinis would have us see in the FATF, as a “ministry executives” network. It seems entirely plausible to cast Wilkins as a vehicle of such networks’ “key motivation”—to pursue “broad societal goals.” From his record, he seems well suited to the role of guardian of “states’ interests” in a “secure environment,” deft at deploying his “longstanding connections” and “power relations” in order to “strike deals” and, where necessary, unleash “sanctions’ firepower.” In short, Mr. Wilkins seems to “fit neatly within the three types—private, regulator, ministry” around which Stavros Gadinis’ thought-provoking article revolves.
Foreign Official Immunity in the International Law Commission: The Meanings of “Official Capacity”
Authors: Dodge William S.
Published: June 2017

Of all the issues facing the International Law Commission (ILC) in its work on the topic of “Immunity of State Officials from Foreign Criminal Jurisdiction,” how to define “act performed in an official capacity” is certainly one of the most difficult and important. If serious international crimes, like torture, are considered acts performed in an official capacity, then foreign officials responsible for such crimes may (unless an exception applies) be immune from criminal jurisdiction in other states for such acts even after they leave office.
Advancing Doctrine through Devil’s Advocacy: A Response to Alan O. Sykes
Authors: Alvarez-Jimenez Alberto
Published: June 2017

Alan Sykes’ editorial comment, Economic “Necessity” in International Law, provides a multi-layered analysis of the defense of “necessity” in international investment disputes. Sykes’ main proposition is that the obligation to compensate investors for government measures prejudicing their investments during economic emergencies mitigates the risk of moral hazard and incentivizes States to “select the least expensive way to protect their interests (the optimal policy instrument).” Otherwise, he contends, “actors will take risks that imperil them to an excessive degree if they can save themselves by imposing costs on others.” Sykes nonetheless argues that payment of the compensation could be deferred in light of the emergency, and not be subject to market interest rates.
Criminalizing Sexual Violence Against Women in Intimate Relationships: State Obligations Under Human Rights Law
Authors: Randall Melanie , Venkatesh Vasanthi
Published: June 2017

Criminalization of sexual violence against women in intimate relationships must form a central part of the human rights agenda for achieving gender equality. According to a study by the United Nations Secretary-General, “[t]he most common form of violence experienced by women globally is intimate partner violence” including “a range of sexually, psychologically and physically coercive acts.” The World Health Organization reports that nearly one in four women in some countries may experience sexual violence perpetrated against them by an intimate partner. Other research suggests that approximately 40% of all assaulted women are forced into sex at one time or another by their male partners.
Self-Referring to the International Criminal Court: A Continuation of War by Other Means
Authors: Menon Parvathi
Published: June 2017

Weak sub-Saharan African states use international law and its institutions to legitimate their actions and delegitimate their internal enemies. In this essay, I argue that during internal armed conflicts, African states use international criminal law to redefine the conflict as international and thereby rebrand domestic political opponents as international criminals/enemies who are a threat to the entire community. This in turn sets the stage for invoking belligerent privileges under international humanitarian law (IHL).
Islamic Contributions to International Humanitarian Law: Recalibrating TWAIL Approaches for Existing Contributions and Legacies
Authors: Zoli Corri
Published: June 2017

This short essay focuses on the involvement of Muslim-majority state leadership in the pre-World War II development of international humanitarian law (IHL), including their appeals to Islamic norms. This historical snapshot reveals how national leaders joined debates during conferences leading up to the revised 1949 Geneva Conventions, the heart of modern IHL. Such accounts complicate our assumptions about the cultural and national composition of public international law as “Western,” and shed light on global hierarchies involving modern Arab and Muslim states and their investment in such norms. The essay argues by example that, ultimately, in Third World Approaches to International Law (TWAIL) more emphasis is needed on history, traditions of governance, and states’ distinctive responses to macrostructural pressures—rather than on static notions of identity, resistant narratives, and presumed shared ideologies. TWAIL seeks alternatives to international law’s presumed oppressive role in Western-non-Western power dynamics, and new ideas and opportunities for a “third-world” legal scholarship beyond current global underdevelopment dynamics.
“If You Buy a Cup, Why Would You Not Use It?” Marital Rape: The Acceptable Face of Gender Based Violence
Authors: Banda Fareda
Published: June 2017

There are cases that one never forgets. DPP v. Morgan is one of those for me. I read it as an eighteen-year-old in my first year of law school. It was in the criminal law class where we were being taught about rape. The facts left me shocked and outraged. Morgan went out drinking with his friends. At the end of the night, he invited the friends back to his house. He told them that they could have sex with his wife and added that they should not worry if she appeared to resist, because she liked it that way. The friends duly came over and helped themselves to his wife as per his instructions. Morgan also forced her to have sex with him despite her protestations. She experienced injuries which necessitated medical treatment. His friends were convicted of rape, but he was convicted of indecent assault. This seemed strange. Had they all not forced her to have sex with them despite her clearly expressed refusal? Why was he charged with a lesser crime? The reason was simple: he was her husband. Under the law as it then operated in England, there was no recognition of marital rape. Her consent to lifelong sex on demand, even if it was against her will, was taken as part of the contract of marriage. The words “I do” spoken at the time of the marriage, were taken to mean free access for the husband for as long as they both lived, or until the marriage was legally dissolved or a formal separation was in place.
Zero-Tolerance Comes to International Law
Authors: Gruber Aya
Published: June 2017

It is difficult to engage from a theoretical perspective an advocacy piece that largely reads like a brief in favor of particular claim of law, namely, that a state’s failure to (vigorously) criminalize marital rape violates international human rights law. In a brief, the litigant pulls together various sources to prove the legal claim is correct. Opponents typically respond by cobbling together their own sources to undermine that claim. In their essay, Criminalizing Sexual Violence Against Women in Intimate Relationships, Randall and Venkatesh set out to prove that international human rights law, in fact, requires states to criminalize marital rape. I suspect there are international lawyers who can persuasively argue that international human rights law does not, in fact, require such criminalization.
Genomics and metagenomics of trimethylamine-utilizing Archaea in the human gut microbiome
Authors: Borrel Guillaume , McCann Angela , Deane Jennifer , Neto Marta C , Lynch Denise B , Brugère Jean- François , O’Toole Paul W
Published: June 2017

The biological significance of Archaea in the human gut microbiota is largely unclear. We recently reported genomic and biochemical analyses of the Methanomassiliicoccales, a novel order of methanogenic Archaea dwelling in soil and the animal digestive tract. We now show that these Methanomassiliicoccales are present in published microbiome data sets from eight countries. They are represented by five Operational Taxonomic Units present in at least four cohorts and phylogenetically distributed into two clades. Genes for utilizing trimethylamine (TMA), a bacterial precursor to an atherosclerogenic human metabolite, were present in four of the six novel Methanomassiliicoccales genomes assembled from ELDERMET metagenomes. In addition to increased microbiota TMA production capacity in long-term residential care subjects, abundance of TMA-utilizing Methanomassiliicoccales correlated positively with bacterial gene count for TMA production and negatively with fecal TMA concentrations. The two large Methanomassiliicoccales clades have opposite correlations with host health status in the ELDERMET cohort and putative distinct genomic signatures for gut adaptation.
Loss of function CHCHD10 mutations in cytoplasmic TDP-43 accumulation and synaptic integrity
Authors: Woo Jung-A. A. , Liu Tian , Trotter Courtney , Fang Cenxiao C. , De Narvaez Emillio , LePochat Patrick , Maslar Drew , Bukhari Anusha , Zhao Xingyu , Deonarine Andrew , Westerheide Sandy D. , Kang David E.
Published: June 2017

Although multiple CHCHD10 mutations are associated with the spectrum of familial and sporadic frontotemporal dementia–amyotrophic lateral sclerosis (FTD–ALS) diseases, neither the normal function of endogenous CHCHD10 nor its role in the pathological milieu (that is, TDP-43 pathology) of FTD/ALS have been investigated. In this study, we made a series of observations utilizing Caenorhabditis elegans models, mammalian cell lines, primary neurons and mouse brains, demonstrating that CHCHD10 normally exerts a protective role in mitochondrial and synaptic integrity as well as in the retention of nuclear TDP-43, whereas FTD/ALS-associated mutations (R15L and S59L) exhibit loss of function phenotypes in C. elegans genetic complementation assays and dominant negative activities in mammalian systems, resulting in mitochondrial/synaptic damage and cytoplasmic TDP-43 accumulation. As such, our results provide a pathological link between CHCHD10-associated mitochondrial/synaptic dysfunction and cytoplasmic TDP-43 inclusions.
Chirality and energy transfer amplified circularly polarized luminescence in composite nanohelix
Authors: Yang Dong , Duan Pengfei , Zhang Li , Liu Minghua
Published: June 2017

Transfer of both chirality and energy information plays an important role in biological systems. Here we show a chiral donor π-gelator and assembled it with an achiral π-acceptor to see how chirality and energy can be transferred in a composite donor–acceptor system. It is found that the individual chiral gelator can self-assemble into nanohelix. In the presence of the achiral acceptor, the self-assembly can also proceed and lead to the formation of the composite nanohelix. In the composite nanohelix, an energy transfer is realized. Interestingly, in the composite nanohelix, the achiral acceptor can both capture the supramolecular chirality and collect the circularly polarized energy from the chiral donor, showing both supramolecular chirality and energy transfer amplified circularly polarized luminescence (ETACPL).
Treating tobacco dependence: guidance for primary care on life-saving interventions. Position statement of the IPCRG
Authors: Van Schayck O. C. P. , Williams S. , Barchilon V. , Baxter N. , Jawad M. , Katsaounou P. A. , Kirenga B. J. , Panaitescu C. , Tsiligianni I. G. , Zwar N. , Ostrem A.
Published: June 2017

Tobacco smoking is the world’s leading cause of premature death and disability. Global targets to reduce premature deaths by 25% by 2025 will require a substantial increase in the number of smokers making a quit attempt, and a significant improvement in the success rates of those attempts in low, middle and high income countries. In many countries the only place where the majority of smokers can access support to quit is primary care. There is strong evidence of cost-effective interventions in primary care yet many opportunities to put these into practice are missed. This paper revises the approach proposed by the International Primary Care Respiratory Group published in 2008 in this journal to reflect important new evidence and the global variation in primary-care experience and knowledge of smoking cessation. Specific for primary care, that advocates for a holistic, bio-psycho-social approach to most problems, the starting point is to approach tobacco dependence as an eminently treatable condition. We offer a hierarchy of interventions depending on time and available resources. We present an equitable approach to behavioural and drug interventions. This includes an update to the evidence on behaviour change, gender difference, comparative information on numbers needed to treat, drug safety and availability of drugs, including the relatively cheap drug cytisine, and a summary of new approaches such as harm reduction. This paper also extends the guidance on special populations such as people with long-term conditions including tuberculosis, human immunodeficiency virus, cardiovascular disease and respiratory disease, pregnant women, children and adolescents, and people with serious mental illness. We use expert clinical opinion where the research evidence is insufficient or inconclusive. The paper describes trends in the use of waterpipes and cannabis smoking and offers guidance to primary-care clinicians on what to do faced with uncertain evidence. Throughout, it recognises that clinical decisions should be tailored to the individual’s circumstances and attitudes and be influenced by the availability and affordability of drugs and specialist services. Finally it argues that the role of the International Primary Care Respiratory Group is to improve the confidence as well as the competence of primary care and, therefore, makes recommendations about clinical education and evaluation. We also advocate for an update to the WHO Model List of Essential Medicines to optimise each primary-care intervention. This International Primary Care Respiratory Group statement has been endorsed by the Member Organisations of World Organization of Family Doctors Europe.
Knee Symptomatic Osteoarthritis, Walking Disability, NSAIDs Use and All-cause Mortality: Population-based Wuchuan Osteoarthritis Study
Authors: Liu Qiang , Niu Jingbo , Li Hu , Ke Yan , Li Rujun , Zhang Yuqing , Lin Jianhao
Published: June 2017

Knee symptomatic osteoarthritis (SxOA) was associated with all-cause mortality. Walking disability and NSAIDs use have been postulated as potential mechanisms linking knee SxOA to all-cause mortality. Data were collected on ability of walking for 1 kilometer and use of NSAIDs at baseline and death information at follow-up. Subjects with knee SxOA were identified if at least one knee had both radiographic OA and pain. We first fitted a Cox proportional hazards model to examine the relation of knee SxOA to the risk of all-cause mortality. We then used marginal structural models to decompose total effect of knee SxOA on all-cause mortality into indirect and direct effects via walking disability and use of NSAIDs, respectively. Among 1025 subjects, 99 died over 8 years of follow-up. A multivariable adjusted hazard ratio of mortality for SxOA was 1.98 (95% CI: 1.09–3.62). The indirect effect of knee SxOA on all-cause mortality through either a walking disability or NSAIDs use was 1.92 (95% CI: 0.86–4.26) and 1.45 (95% CI: 0.72–2.92), respectively. The corresponding direct effect was 1.08 (95% CI: 0.55–1.12) and 1.35 (95% CI: 0.75–2.44). In this population-based cohort study, high all-cause mortality from knee SxOA was mediated mainly through a walking disability.
Nuclear TRADD prevents DNA damage-mediated death by facilitating non-homologous end-joining repair
Authors: Koo Gi-Bang , Ji Jae-Hoon , Cho Hyeseong , Morgan Michael J. , Kim You-Sun
Published: June 2017

TNF receptor-associated death domain (TRADD) is an essential mediator of TNF receptor signaling, and serves as an adaptor to recruit other effectors. TRADD has been shown to cycle between the cytoplasm and nucleus due to its nuclear localization (NLS) and export sequences (NES). However, the underlying function of nuclear TRADD is poorly understood. Here we demonstrate that cytoplasmic TRADD translocates to DNA double-strand break sites (DSBs) during the DNA damage response (DDR). Deficiency of TRADD or its sequestration in cytosol leads to accumulation of γH2AX-positive foci in response to DNA damage, which is reversed by nuclear TRADD expression. TRADD facilitates non-homologous end-joining (NHEJ) by recruiting NHEJ repair factors 53BP1 and Ku70/80 complex, whereas TRADD is dispensable for homologous recombination (HR) repair. Finally, an impaired nuclear localization of TRADD triggers cell death through the persistent activation of JNK and accumulation of reactive oxygen species (ROS). Thus, our findings suggest that translocation of TRADD to DSBs into the nucleus contributes to cell survival in response to DNA damage through an activation of DNA damage repair.
Neuropilin-1 Associated Molecules in the Blood Distinguish Poor Prognosis Breast Cancer: A Cross-Sectional Study
Authors: Naik Adviti , Al-Zeheimi Noura , Bakheit Charles Saki , Al Riyami Marwa , Al Jarrah Adil , Al Moundhri Mansour S. , Al Habsi Zamzam , Basheer Maysoon , Adham Sirin A.
Published: June 2017

Circulating plasma and peripheral blood mononuclear (PBMCs) cells provide an informative snapshot of the systemic physiological state. Moreover, they provide a non-invasively accessible compartment to identify biomarkers for personalized medicine in advanced breast cancer. The role of Neuropilin-1 (NRP-1) and its interacting molecules in breast tumor tissue was correlated with cancer progression; however, the clinical impact of their systemic levels was not extensively evaluated. In this cross-sectional study, we found that circulating and tumor tissue expression of NRP-1 and circulating placental growth factor (PlGF) increase in advanced nodal and metastatic breast cancer compared with locally advanced disease. Tumor tissue expression of NRP-1 and PlGF is also upregulated in triple negative breast cancer (TNBC) compared to other subtypes. Conversely, in PBMCs, NRP-1 and its interacting molecules SEMA4A and SNAI1 are significantly downregulated in breast cancer patients compared to healthy controls, indicating a protective role. Moreover, we report differential PBMC expression profiles that correlate inversely with disease stage (SEMA4A, SNAI1, PLXNA1 and VEGFR3) and can differentiate between the TNBC and non-TNBC tumor subtypes (VEGFR3 and PLXNA1). This work supports the importance of NRP-1-associated molecules in circulation to characterize poor prognosis breast cancer and emphasizes on their role as favorable drug targets.
Robust water repellent ZnO nanorod array by Swift Heavy Ion Irradiation: Effect of Electronic Excitation Induced Local Chemical State Modification
Authors: Ranjith Kugalur Shanmugam , Nivedita Lalitha Raveendran , Asokan Kandasami , Krishnamurthy Satheesh , Pandian Ramanathaswamy , Kamruddin Mohammed , Avasthi Devesh Kumar , Rajendra Kumar Ramasamy Thangavelu
Published: June 2017

Tailoring the surface properties by varying the chemistry and roughness could be of interest for self-cleaning applications. We demonstrate the transformation of hydrophobic ZnO Nano rod (NR) array into superhydrophobic nature by changing the local chemical state and without altering the surface roughness by swift heavy ion (SHI) irradiation. The aligned ZnO NR arrays were irradiated using 150 MeV Ag ions with different fluences from 5E10 to 3E12 ions/cm2. The observed static water contact angles of ZnO NRs samples were 103° ± 3°, 152° ± 4°,161° ± 3°, 164° ± 2°, 167° ± 2°,154 ± 3° and 151° ± 2° for the pristine, ion fluencies of 1E11, 3E11, 5E11, 7E11, 1E12 and 3E12 ions cm−2, respectively. The change in local surface chemistry via formation of surface oxygen related defects due to electronic excitations induced by ion irradiation determine the water dewetting properties. It is found that surface oxygen related defects could be tuned by varying the fluence of the SHIs. Durability tests show that the SHI induced surface oxygen-deficient ZnO NRs have the stable superhydrophobic behavior for more than a year.
Exploring a Role for Regulatory miRNAs In Wound Healing during Ageing:Involvement of miR-200c in wound repair
Authors: Aunin Eerik , Broadley David , Ahmed Mohammed I. , Mardaryev Andrei N. , Botchkareva Natalia V.
Published: June 2017

Multiple factors and conditions can lead to impaired wound healing. Chronic non-healing wounds are a common problem among the elderly. To identify microRNAs negatively impacting the wound repair, global miRNA profiling of wounds collected from young and old mice was performed. A subset of miRNAs that exhibited an age-dependent expression pattern during wound closure was identified, including miR-31 and miR-200c. The expression of miR-200 family members was markedly downregulated upon wounding in both young and aged mice, with an exception of acute upregulation of miR-200c at the early phase of wound healing in aged skin. In unwounded aged skin (versus unwounded younger skin), the level of miR-200c was also found elevated in both human and mice. Overexpression of miR-200c in human ex vivo wounds delayed re-epithelialisation and inhibited cell proliferation in the wound epithelium. Modulation of miR-200c expression in both human and mouse keratinocytes in vitro revealed inhibitory effects of miR-200c on migration, but not proliferation. Accelerated wound closure in vitro induced by anti-miR-200c was associated with upregulation of genes controlling cell migration. Thus, our study identified miR-200c as a critical determinant that inhibits cell migration during skin repair after injury and may contribute to age-associated alterations in wound repair.
RIM1/2 in retinal ganglion cells are required for the refinement of ipsilateral axons and eye-specific segregation
Authors: Assali Ahlem , Le Magueresse Corentin , Bennis Mohamed , Nicol Xavier , Gaspar Patricia , Rebsam Alexandra
Published: June 2017

Neural activity is crucial for the refinement of neuronal connections during development, but the contribution of synaptic release mechanisms is not known. In the mammalian retina, spontaneous neural activity controls the refinement of retinal projections to the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC) to form appropriate topographic and eye-specific maps. To evaluate the role of synaptic release, the rab-interacting molecules (RIMs), a family of active zone proteins that play a central role in calcium-triggered release, were conditionally ablated in a subset of retinal ganglion cells (RGCs). We found that this deletion is sufficient to reduce presynaptic release probability onto dLGN neurons. Furthermore, eye-specific segregation in the dLGN and topographic refinement of ipsilateral axons in the SC and the dLGN, are impaired in RIM1/2 conditional knock-out (Rim-cDKO) mice. These defects are similar to those found when retinal activity is globally disturbed. However, reduction in synaptic release had no effect on eye-specific lamination in the SC nor on the retinotopic refinement of contralateral axons in the SC. This study highlights a potential distinction between synaptic and non-synaptic roles of neuronal activity for different mapping rules operating in visual system development.
Yield-phenology relations and water use efficiency of maize (Zea mays L.) in ridge-furrow mulching system in semiarid east African Plateau
Authors: Mo Fei , Wang Jian-Yong , Li Feng-Min , Nguluu Simon N. , Ren Hong-Xu , Zhou Hong , Zhang Jian , Kariuki Charles W. , Gicheru Patrick , Kavagi Levis , Cheruiyot Wesly K. , Xiong You-Cai
Published: June 2017

Yield-phenology relation is a critical issue affecting rainfed maize field productivity in semiarid east African Plateau (EAP). We first introduced Chinese ridge-furrow mulching (RFM) system to EAP, using three maize cultivars with early-, mid- and late-maturing traits as test materials. A two-year field experiment was conducted in a semiarid farm of Kenya from 2012 to 2013. Three treatments were designed: alternative ridge and furrow with transparent plastic mulching (FT), with black plastic mulching (FB) and without mulching (CK). We found that FT and FB significantly increased soil moisture and accelerated crop maturity across two growing seasons. Leaf area and shoot biomass were increased by 30.2% and 67.5% in FT, 35.2% and 73.5% in FB, respectively, compared with CK. Grain yield, water use efficiency and economic output were increased by 55.6%, 57.5% and 26.7% in FT, and 50.8%, 53.3% and 19.8% in FB, respectively. Optimal yield and economic benefit were observed in late-maturing cultivar due to increased topsoil temperature in FT in 2012 (cool), and in early-maturing cultivar owing to cooling effect in FB in 2013 (warm). Our study suggested RFM system, combined with crop phenology selection, be a promising strategy to boost maize productivity and profitability in semiarid EAP.
Experimental demonstration of quantum digital signatures over 43 dB channel loss using differential phase shift quantum key distribution
Authors: Collins Robert J. , Amiri Ryan , Fujiwara Mikio , Honjo Toshimori , Shimizu Kaoru , Tamaki Kiyoshi , Takeoka Masahiro , Sasaki Masahide , Andersson Erika , Buller Gerald S.
Published: June 2017

Ensuring the integrity and transferability of digital messages is an important challenge in modern communications. Although purely mathematical approaches exist, they usually rely on the computational complexity of certain functions, in which case there is no guarantee of long-term security. Alternatively, quantum digital signatures offer security guaranteed by the physical laws of quantum mechanics. Prior experimental demonstrations of quantum digital signatures in optical fiber have typically been limited to operation over short distances and/or operated in a laboratory environment. Here we report the experimental transmission of quantum digital signatures over channel losses of up to 42.8 ± 1.2 dB in a link comprised of 90 km of installed fiber with additional optical attenuation introduced to simulate longer distances. The channel loss of 42.8 ± 1.2 dB corresponds to an equivalent distance of 134.2 ± 3.8 km and this represents the longest effective distance and highest channel loss that quantum digital signatures have been shown to operate over to date. Our theoretical model indicates that this represents close to the maximum possible channel attenuation for this quantum digital signature protocol, defined as the loss for which the signal rate is comparable to the dark count rate of the detectors.
Recombinant Thrombomodulin Exerts Anti-autophagic Action in Endothelial Cells and Provides Anti-atherosclerosis Effect in Apolipoprotein E Deficient Mice
Authors: Chen Po-Sheng , Wang Kuan-Chieh , Chao Ting-Hsing , Chung Hsing-Chun , Tseng Shi-Ya , Luo Chawn-Yau , Shi Guey-Yueh , Wu Hua-Lin , Li Yi-Heng
Published: June 2017

Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway. In addition, treatment of rTM decreased SS-induced EC apoptosis, but this effect of rTM could not be recapitulated by co-treatment with a potent autophagy inducer, rapamycin and in ECs with ATG5 knockdown. In human atherosclerosis specimens, expression of autophagy markers, ATG13 and LC3, were more abundant in aortic intimal ECs with severe atherosclerosis than those without atherosclerosis. Moreover, compared to saline treatment group, administration of rTM reduced LC3 and ATG13 expression, intimal EC apoptosis, and atherosclerotic lesion severity in the aorta of apolipoprotein E deficient mice. In conclusion, treatment with rTM suppressed stress-induced autophagy overactivation in ECs, provided ECs protective effects, and decreased atherosclerosis in apolipoprotein E deficient mice.
Preferential suppression of Anopheles gambiae host sequences allows detection of the mosquito eukaryotic microbiome
Authors: Belda Eugeni , Coulibaly Boubacar , Fofana Abdrahamane , Beavogui Abdoul H. , Traore Sekou F. , Gohl Daryl M. , Vernick Kenneth D. , Riehle Michelle M.
Published: June 2017

Anopheles mosquitoes are vectors of the human malaria parasite, Plasmodium falciparum. The vector microbiota is a likely factor influencing parasite transmission. The prokaryotic microbiota of mosquitoes is efficiently surveyed by sequencing of hypervariable regions of the 16s ribosomal RNA (rRNA) gene. However, identification of the eukaryotic microbiota by targeting the 18s rRNA gene is challenging due to simultaneous amplification of the abundant 18s rRNA gene target in the mosquito host. Consequently, the eukaryotic microbial diversity of mosquitoes is vastly underexplored. An efficient methodology is needed to identify this component of the microbiota, expected to include relatives of Plasmodium. Here, we use defined panels of Anopheles samples from West Africa to test two experimental PCR clamp approaches to maximize the specific amplification of 18s rRNA gene hypervariable regions from eukaryotic microbes: anneal-inhibiting blocking primers and peptide-nucleic acid (PNA) oligonucleotide blockers. Of the two, PNA blockers were the only efficient blocking strategy, allowing a reduction of mosquito 18s rRNA gene sequences by more than 80% for the V4 hypervariable region. These PNA blockers will facilitate taxonomic profiling of the eukaryotic microbiota of the A. gambiae species complex, and contribute to a better understanding of microbial influence upon immunity and pathogen infection.
Quantification of within-sample genetic heterogeneity from SNP-array data
Authors: Martinez Pierre , Kimberley Christopher , BirkBak Nicolai J. , Marquard Andrea , Szallasi Zoltan , Graham Trevor A.
Published: June 2017

Intra-tumour genetic heterogeneity (ITH) fosters drug resistance and is a critical hurdle to clinical treatment. ITH can be well-measured using multi-region sampling but this is costly and challenging to implement. There is therefore a need for tools to estimate ITH in individual samples, using standard genomic data such as SNP-arrays, that could be implemented routinely. We designed two novel scores S and R, respectively based on the Shannon diversity index and Ripley’s L statistic of spatial homogeneity, to quantify ITH in single SNP-array samples. We created in-silico and in-vitro mixtures of tumour clones, in which diversity was known for benchmarking purposes. We found significant but highly-variable associations of our scores with diversity in-silico (p < 0.001) and moderate associations in–vitro (p = 0.015 and p = 0.085). Our scores were also correlated to previous ITH estimates from sequencing data but heterogeneity in the fraction of tumour cells present across samples hampered accurate quantification. The prognostic potential of both scores was moderate but significantly predictive of survival in several tumour types (corrected p = 0.03). Our work thus shows how individual SNP-arrays reveal intra-sample clonal diversity with moderate accuracy.
Cooperative Micromanipulation Using the Independent Actuation of Fifty Microrobots in Parallel
Authors: Rahman M. Arifur , Cheng Julian , Wang Zhidong , Ohta Aaron T.
Published: June 2017

Micromanipulation for applications in areas such as tissue engineering can require mesoscale structures to be assembled with microscale resolution. One method for achieving such manipulation is the parallel actuation of many microrobots in parallel. However, current microrobot systems lack the independent actuation of many entities in parallel. Here, the independent actuation of fifty opto-thermocapillary flow-addressed bubble (OFB) microrobots in parallel is demonstrated. Individual microrobots and groups of microrobots were moved along linear, circular, and arbitrary 2D trajectories. The independent addressing of many microrobots enables higher-throughput microassembly of micro-objects, and cooperative manipulation using multiple microrobots. Demonstrations of manipulation with multiple OFB microrobots include the transportation of microstructures using a pair or team of microrobots, and the cooperative manipulation of multiple micro-objects. The results presented here represent an order of magnitude increase in the number of independently actuated microrobots in parallel as compared to other magnetically or electrostatically actuated microrobots, and a factor of two increase as compared to previous demonstrations of OFB microrobots.
Predictors of chronic kidney disease in type 1 diabetes: a longitudinal study from the AMD Annals initiative
Authors: Piscitelli Pamela , Viazzi Francesca , Fioretto Paola , Giorda Carlo , Ceriello Antonio , Genovese Stefano , Russo Giuseppina , Guida Pietro , Pontremoli Roberto , De Cosmo Salvatore
Published: June 2017

We evaluated 2,656 patients with type 1 diabetes mellitus and preserved renal function from the database of the Italian Association of Clinical Diabetologists network to identify clinical predictors for the development of chronic kidney disease. We measured estimated glomerular filtration rate (eGFR), urinary albumin excretion, HbA1c, lipids, blood pressure. Over a 5-year period 4.3% (n = 115) developed reduced eGFR (<60 ml/min/1.73 m2), 18.0% (n = 477) albuminuria, and 21.0% (n = 559) either one of the renal endpoints (CKD). Odds ratios for eGFR below 90 mL/min/1.73 m2 (1.48, P < 0.001), HbA1c (1.13, P = 0.002), triglycerides (1.04, P = 0.021 by 20 mg/dL), low density lipoprotein cholesterol (LDL-c) (0.95, P = 0.002 by 10 mg/dL) were independently related to the onset of CKD. Known duration of diabetes (1.15, P = 0.014 by 10 years), HbA1c (1.16, P = 0.001), triglycerides (1.05, P = 0.005 by 20 mg/dL), LDL-c (0.95, P = 0.003 by 10 mg/dL), antihypertensive treatment (2.28, P = 0.018) were related to the onset of albuminuria while age and presence of baseline eGFR values between 90 and 60 mL/min/1.73 m2, independently affected the developing of reduced eGFR (OR 1.95, P < 0.001 by 10 years and 2.92, P < 0.001). Patients with type 1 diabetes mellitus and unfavorable CV risk profile are at high risk of developing CKD. The two main traits of CKD share several determinants, although with some specificities.
A new look at risk patterns related to coronary heart disease incidence using survival tree analysis: 12 Years Longitudinal Study
Authors: Ramezankhani Azra , Bagherzadeh-Khiabani Farideh , Khalili Davood , Azizi Fereidoun , Hadaegh Farzad
Published: June 2017

We identified risk patterns associated with incident coronary heart disease (CHD) using survival tree, and compared performance of survival tree versus Cox proportional hazards (Cox PH) in a cohort of Iranian adults. Data on 8,279 participants (3,741 men) aged ≥30 yr were used to analysis. Survival trees identified seven subgroups with different risk patterns using four [(age, non-HDL-C, fasting plasma glucose (FPG) and family history of diabetes] and five [(age, systolic blood pressure (SBP), non-HDL-C, FPG and family history of CVD] predictors in women and men, respectively. Additional risk factors were identified by Cox models which included: family history of CVD and waist circumference (in both genders); hip circumference, former smoking and using aspirin among men; diastolic blood pressure and lipid lowering drug among women. Survival trees and multivariate Cox models yielded comparable performance, as measured by integrated Brier score (IBS) and Harrell’s C-index on validation datasets; however, survival trees produced more parsimonious models with a minimum number of well recognized risk factors of CHD incidence, and identified important interactions between these factors which have important implications for intervention programs and improve clinical decision making.
Genetic mapping with testcrossing associations and F2:3 populations reveals the importance of heterosis in chilling tolerance at maize seedling stage
Authors: Yan Jinbo , Wu Yu , Li Wenming , Qin Xiner , Wang Yi , Yue Bing
Published: June 2017

Maize seedlings are sensitive to low temperatures, and genetic mapping for chilling tolerance at the seedling stage with genetically diverse populations would facilitate the genetic improvement of this important trait. In this study, quantitative trait loci (QTL) mapping for four chilling tolerance-related traits at the seedling stage was conducted via a genome-wide association study (GWAS) with 338 testcrosses. A total of 32 significant loci and 36 stress tolerance-related candidate genes were identified, though none of them have been revealed by QTL mapping using maize inbred lines in previous reports. Moreover, expression of ten of the candidate genes was induced by chilling stress in a maize hybrid, though only a few of these genes were upregulated in its tolerant parent. These implied that heterosis might be involved in maize chilling tolerance. To further evaluate the importance of heterosis in chilling tolerance at the seedling stage, genetic mapping for chilling tolerance was conducted using an F2:3 population derived from the two inbred lines used for the gene expression assay. Of the seven QTL revealed, six loci showed partial dominance or over-dominance effects. Results from this study demonstrate that heterosis plays an important role in chilling tolerance in maize seedlings.
The role of touch in regulating inter-partner physiological coupling during empathy for pain
Authors: Goldstein Pavel , Weissman-Fogel Irit , Shamay-Tsoory Simone G.
Published: June 2017

The human ability to synchronize with other individuals is critical for the development of social behavior. Recent research has shown that physiological inter-personal synchronization may underlie behavioral synchrony. Nevertheless, the factors that modulate physiological coupling are still largely unknown. Here we suggest that social touch and empathy for pain may enhance interpersonal physiological coupling. Twenty-two romantic couples were assigned the roles of target (pain receiver) and observer (pain observer) under pain/no-pain and touch/no-touch conditions, and their ECG and respiration rates were recorded. The results indicate that the partner touch increased interpersonal respiration coupling under both pain and no-pain conditions and increased heart rate coupling under pain conditions. In addition, physiological coupling was diminished by pain in the absence of the partner’s touch. Critically, we found that high partner’s empathy and high levels of analgesia enhanced coupling during the partner’s touch. Collectively, the evidence indicates that social touch increases interpersonal physiological coupling during pain. Furthermore, the effects of touch on cardio-respiratory inter-partner coupling may contribute to the analgesic effects of touch via the autonomic nervous system.
Development of a root canal treatment model in the rat
Authors: Yoneda Naomichi , Noiri Yuichiro , Matsui Saori , Kuremoto Katsutaka , Maezono Hazuki , Ishimoto Takuya , Nakano Takayoshi , Ebisu Shigeyuki , Hayashi Mikako
Published: June 2017

Root canal treatment is performed to treat apical periodontitis, and various procedures and techniques are currently used. Although animal models have been used in the developmental research of root canal treatment, little of this research has used small animals such as rats, because of their small size. In this study, root canal treatment was performed on the rat mandibular first molar, which had four root canals, using a microscope, and the therapeutic effect was evaluated bacteriologically, radiologically and histopathologically. By performing root canal treatment, the level of bacteria in the mesial root of the treated teeth was reduced by 75% compared with the control. Additionally, the volume of the periapical lesions of the treated teeth as measured by micro-computed tomography decreased significantly 2 weeks after the root canal treatment when compared with the control. Histological evidence of healing was observed in the treatment group 8 weeks after root canal treatment. These results suggest that a root canal treatment model using rats can be used in developmental research for novel methods of root canal treatment.
FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC
Authors: Kim Kyoung Min , Park See-Hyoung , Bae Jun Sang , Noh Sang Jae , Tao Guo-Zhong , Kim Jung Ryul , Kwon Keun Sang , Park Ho Sung , Park Byung-Hyun , Lee Ho , Chung Myoung Ja , Moon Woo Sung , Sylvester Karl G. , Jang Kyu Yun
Published: June 2017

Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients. In HLE and HepG2 HCC cells, knock-down of FAM83H inhibited proliferation and invasive activity of HCC cells. FAM83H induced expression of cyclin-D1, cyclin-E1, snail and MMP2 and inhibited the expression of P53 and P27. In hepatic tumor cells derived from Tet-O-MYC mice, the expression of mRNA and protein of FAM83H were dependent on MYC expression. Moreover, a chromatin immunoprecipitation assay demonstrated that MYC binds to the promotor of FAM83H and that MYC promotes the transcription of FAM83H, which was supported by the results of a dual-luciferase reporter assay. In conclusion, we present an oncogenic role of FAM83H in liver cancer, which is closely associated with the oncogene MYC. In addition, our results suggest FAM83H expression as a poor prognostic indicator of HCC patients.
IGF-1 mediated Neurogenesis Involves a Novel RIT1/Akt/Sox2 Cascade
Authors: Mir Sajad , Cai Weikang , Carlson Shaun W. , Saatman Kathryn E. , Andres Douglas A.
Published: June 2017

Insulin-like growth factor 1 (IGF-1) is known to have diverse effects on brain structure and function, including the promotion of stem cell proliferation and neurogenesis in the adult dentate gyrus. However, the intracellular pathways downstream of the IGF-1 receptor that contribute to these diverse physiological actions remain relatively uncharacterized. Here, we demonstrate that the Ras-related GTPase, RIT1, plays a critical role in IGF-1-dependent neurogenesis. Studies in hippocampal neuronal precursor cells (HNPCs) demonstrate that IGF-1 stimulates a RIT1-dependent increase in Sox2 levels, resulting in pro-neural gene expression and increased cellular proliferation. In this novel cascade, RIT1 stimulates Akt-dependent phosphorylation of Sox2 at T118, leading to its stabilization and transcriptional activation. When compared to wild-type HNPCs, RIT1
−/−
HNPCs show deficient IGF-1-dependent Akt signaling and neuronal differentiation, and accordingly, Sox2-dependent hippocampal neurogenesis is significantly blunted following IGF-1 infusion in knockout (RIT1
−/−
) mice. Consistent with a role for RIT1 function in the modulation of activity-dependent plasticity, exercise-mediated potentiation of hippocampal neurogenesis is also diminished in RIT1
−/−
mice. Taken together, these data identify the previously uncharacterized IGF1-RIT1-Akt-Sox2 signaling pathway as a key component of neurogenic niche sensing, contributing to the regulation of neural stem cell homeostasis.
The potentially neglected culprit of DC surface flashover: electron migration under temperature gradients
Authors: Li Chuanyang , Hu Jun , Lin Chuanjie , He Jinliang
Published: June 2017

This report intends to reveal the role of electron migration and its effects in triggering direct current (DC) surface flashover under temperature gradient conditions when using epoxy-based insulating composites. The surface potential and the surface flashover voltage are both measured using insulators that are bridged between two thermo-regulated electrodes. The space charge injection and migration properties under different temperature are detected. The results show that the surface potential rises significantly because of electron migration near the high voltage (HV) electrode under high temperature conditions, thus creating an “analogous ineffective region”. The expansion of this “analogous ineffective region” results in most of the voltage drop occurring near the ground electrode, which serves as an important factor triggering positive streamers across the insulation surface. This work is helpful in understanding of DC surface flashover mechanism from a new perspective and also has important significance in design of a suitable DC insulator to avoid surface flashover problem.
Spiraling elliptic Hermite-Gaussian solitons in nonlocal nonlinear media without anisotropy
Authors: Liang Guo , Dai Zhiping
Published: June 2017

We introduce a kind of the spiraling elliptic Hermite-Gaussian solitons in nonlocal nonlinear media without anisotropy, which carries the orbital angular momentum and can rotate in the transverse. The n–th mode of the spiraling elliptic Hermite-Gaussian solitons has n holes nested in the elliptic profile. The analytical spiraling elliptic Hermite-Gaussian solitons solutions are obtained based on the variational approach, which agree well with the numerical simulations. It is found that the critical power and the critical angular velocity for the spiraling elliptic Hermite-Gaussian solitons are the same as the counterpart of the ground mode.
Evolution of Complex Maillard Chemical Reactions, Resolved in Time
Authors: Hemmler Daniel , Roullier-Gall Chloé , Marshall James W. , Rychlik Michael , Taylor Andrew J. , Schmitt-Kopplin Philippe
Published: June 2017

In this study, we monitored the thermal formation of early ribose-glycine Maillard reaction products over time by ion cyclotron resonance mass spectrometry. Here, we considered sugar decomposition (caramelization) apart from compounds that could only be produced in the presence of the amino acid. More than 300 intermediates as a result of the two initial reactants were found after ten hours (100 °C) to participate in the interplay of the Maillard reaction cascade. Despite the large numerical variety the majority of intermediates follow simple and repetitive reaction patterns. Dehydration, carbonyl cleavage, and redox reactions turned out to have a large impact on the diversity the Maillard reaction causes. Although the Amadori breakdown is considered as the main Maillard reaction pathway, other reactive intermediates, often of higher molecular weight than the Amadori rearrangement product, contribute to a large extent to the multitude of intermediates we observed.