bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of cumulative illness severity on hippocampal gray matter volume in major depression: a voxel-based morphometry study
Authors: Zaremba Dario , Enneking Verena , Meinert Susanne , Förster Katharina , Bürger Christian , Dohm Katharina , Grotegerd Dominik , Redlich Ronny , Dietsche Bruno , Krug Axel , Kircher Tilo , Kugel Harald , Heindel Walter , Baune Bernhard T , Arolt Volker , Dannlowski Udo
Published: February 2018

Background

Patients with major depression show reduced hippocampal volume compared to healthy controls. However, the contribution of patients’ cumulative illness severity to hippocampal volume has rarely been investigated. It was the aim of our study to find a composite score of cumulative illness severity that is associated with hippocampal volume in depression.

Methods

We estimated hippocampal gray matter volume using 3-tesla brain magnetic resonance imaging in 213 inpatients with acute major depression according to DSM-IV criteria (employing the SCID interview) and 213 healthy controls. Patients’ cumulative illness severity was ascertained by six clinical variables via structured clinical interviews. A principal component analysis was conducted to identify components reflecting cumulative illness severity. Regression analyses and a voxel-based morphometry approach were used to investigate the influence of patients’ individual component scores on hippocampal volume.

Results

Principal component analysis yielded two main components of cumulative illness severity: Hospitalization and Duration of Illness. While the component Hospitalization incorporated information from the intensity of inpatient treatment, the component Duration of Illness was based on the duration and frequency of illness episodes. We could demonstrate a significant inverse association of patients’ Hospitalization component scores with bilateral hippocampal gray matter volume. This relationship was not found for Duration of Illness component scores.

Conclusions

Variables associated with patients’ history of psychiatric hospitalization seem to be accurate predictors of hippocampal volume in major depression and reliable estimators of patients’ cumulative illness severity. Future studies should pay attention to these measures when investigating hippocampal volume changes in major depression.
A Critical Investigation of English Language Teaching in Bangladesh
Authors: Rahman Mohammad Mosiur , Pandian Ambigapathy
Published: February 2018

The 2016 World Bank report on worldwide per capita Gross Domestic Product (GDP) identified Bangladesh as a lower middle-income country based on its consistent GDP growth throughout last decade (World Bank, 2016). To maintain this growth rate and meet the radical demand for human resources in increasingly globalised world markets, the country needs to communicate more effectively with the outside world. Inevitably, this means improving the quality of English teaching and learning. The significance of English, as the globallingua franca, to Bangladeshi learners is at its zenith. In this developing country, however, economic constraints mean that funds allocated to education are limited compared to many other Southeast Asian countries (Habib & Adhikary, 2016). Even given the generally low level of educational standards in Bangladesh (Islam, 2015), the standard of English language teaching and learning has decreased alarmingly in recent years (Hamid, 2011). English language education in Bangladesh has always been problematic, despite various attempts to initiate curriculum reform. As Hamid & Baldauf (2008) point out, the first of these major shifts in the ELT curriculum took place in the mid-1990s, when the traditional Grammar-Translation Method (GTM) was replaced with a curriculum based on a Communicative Language Teaching (CLT) model. The principal objective of this article is to review the major problems associated with ELT in Bangladesh that have hindered the implementation of the new CLT curriculum from the perspective of teachers, and eventually to make recommendations for more effective ELT curriculum reform.
Prestige Asymmetry in American Physics: Aspirations, Applications, and the Purloined Letter Effect
Authors: Martin Joseph D.
Published: February 2018

Argument

Why do similar scientific enterprises garner unequal public approbation? High energy physics attracted considerable attention in the late-twentieth-century United States, whereas condensed matter physics – which occupied the greater proportion of US physicists – remained little known to the public, despite its relevance to ubiquitous consumer technologies. This paper supplements existing accounts of this much remarked-upon prestige asymmetry by showing that popular emphasis on the mundane technological offshoots of condensed matter physics and its focus on human-scale phenomena have rendered it more recondite than its better-known sibling field. News reports about high energy physics emphasize intellectual achievement; reporting on condensed matter physics focuses on technology. And whereas frontier-oriented rhetoric of high energy physics communicates ideals of human potential, discoveries that smack of the mundane highlight human limitations and fail to resonate with the widespread aspirational vision of science – a consequence I call “the purloined letter effect.”
Subsistence, Environment and Mesolithic Landscape Archaeology
Authors: Taylor Barry
Published: February 2018

Since the 1970s, research into Mesolithic landscapes has been heavily influenced by economic models of human activity where patterns of settlement and mobility result from the relationship between subsistence practices and the environment. However, in reconstructing these patterns we have tended to generalize both the modes of subsistence and the temporal and spatial variability of the environment, and ignored the role that cultural practices played in the way subsistence tasks were organized. While more recent research has emphasized the importance that cultural practices played in the way landscapes were perceived and understood, these have tended to underplay the role of subsistence and have continued to consider the environment in a very generalized manner. This paper argues that we can only develop detailed accounts of Mesolithic landscapes by looking at the specific forms of subsistence practice and the complex relationships they created with the environment. It will also show that the inhabitation of Mesolithic landscapes was structured around cultural attitudes to particular places and to the environment, and that this can be seen archaeologically through practices of deposition and recursive patterns of occupation at certain sites.
GROWTH AND WELFARE EFFECTS OF MACROPRUDENTIAL REGULATION
Authors: Agénor Pierre-Richard
Published: February 2018

This paper studies the growth and welfare effects of macroprudential regulation in an overlapping generations model of endogenous growth with banking and agency costs. Indivisible investment projects combine with informational imperfections to create a double moral hazard problem à la Holmström–Tirole and a role for bank monitoring. When the optimal monitoring intensity is endogenously determined, an increase in the required reserve ratio (motivated by systemic risk considerations) has conflicting effects on investment and growth. On one hand, requiring banks to put away a fraction of the deposits that they receive reduces the supply of loanable funds. On the other, a higher required ratio raises incentives to save and mitigates banks' incentives to monitor, thereby lowering monitoring costs and freeing up resources to increase lending. In addition, it may mitigate the systemic risk externality associated with excessive leverage. This trade-off can be internalized by choosing the required reserve ratio that maximizes growth and welfare. However, the risk of disintermediation means that in practice financial supervision may also need to be strengthened, and the perimeter of regulation broadened, if the optimal ratio is relatively high.
THE DISPOSITIONS OF CRITICAL THINKERS
Authors: Dunne Gerry
Published: February 2018

Most theorists agree that the ability to think critically is distinct from the disposition to do so. Many of us may have the ability to be critical thinkers, but unless we are consistently and internally motivated to think and reason this way, these abilities are effectively redundant. Such dispositions are both intellectual character traits, and dispositions to behave in certain ways. As such, the first step to understanding critical thinking requires us to develop an operationalized taxonomy of critical thinking dispositions. To avoid explicating these dispositions in abstracto, this article draws upon a murder trial in order to demonstrate the central role dispositions play in critical thinking.
PCSK9 inhibition for LDL lowering and beyond – implications for patients with peripheral artery disease
Authors: Gebauer Katrin , Reinecke Holger
Published: February 2018

Abstract. Low-density lipoprotein cholesterol (LDL-C) has been proven to be a causal factor of atherosclerosis and, along with other triggers like inflammation, the most frequent reason for peripheral arterial disease. Moreover, a linear correlation between LDL-C concentration and cardiovascular outcome in high-risk patients could be established during the past century. After the development of statins, numerous randomized trials have shown the superiority for LDL-C reduction and hence the decrease in cardiovascular outcomes including mortality. Over the past decades it became evident that more intense LDL-C lowering, by either the use of highly potent statin supplements or by additional cholesterol absorption inhibitor application, accounted for an even more profound cardiovascular risk reduction. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a serin protease with effect on the LDL receptor cycle leading to its degradation and therefore preventing continuing LDL-C clearance from the blood, is the target of a newly developed monoclonal antibody facilitating astounding LDL-C reduction far below to what has been set as target level by recent ESC/EAS guidelines in management of dyslipidaemias. Large randomized outcome trials including subjects with PAD so far have been able to prove significant and even more intense cardiovascular risk reduction via further LDL-C debasement on top of high-intensity statin medication. Another approach for LDL-C reduction is a silencing interfering RNA muting the translation of PCSK9 intracellularly. Moreover, PCSK9 concentrations are elevated in cells involved in plaque composition, so the potency of intracellular PCSK9 inhibition and therefore prevention or reversal of plaques may provide this mechanism of action on PCSK9 with additional beneficial effects on cells involved in plaque formation. Thus, simultaneous application of statins and PCSK9 inhibitors promise to reduce cardiovascular event burden by both LDL-C reduction and pleiotropic effects of both agents.
Damage Assessment by Laser Could Focus Postearthquake Response
Authors: Shields Laura
Published: February 2018

Airborne lidar surveys taken before and after a powerful 2016 earthquake in Japan revealed the potential for such surveys to identify hard-hit buildings quickly.
Alterations of specific chromatin conformation affect ATRA-induced leukemia cell differentiation
Authors: Li Yanjian , He Yi , Liang Zhengyu , Wang Yang , Chen Fengling , Djekidel Mohamed Nadhir , Li Guipeng , Zhang Xu , Xiang Shuqin , Wang Zejun , Gao Juntao , Zhang Michael Q. , Chen Yang
Published: February 2018

Chromatin conformation plays a key role in regulating gene expression and controlling cell differentiation. However, the whole-genome chromatin conformation changes that occur during leukemia cell differentiation are poorly understood. Here, we characterized the changes in chromatin conformation, histone states, chromatin accessibility, and gene expression using an all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation model. The results showed that the boundaries of topological associated domains (TADs) were stable during differentiation; however, the chromatin conformations within several specific TADs were obviously changed. By combining H3K4me3, H3K27ac, and Hi-C signals, we annotated the differential gene-regulatory chromatin interactions upon ATRA induction. The gains and losses of the gene-regulatory chromatin interactions are significantly correlated with gene expression and chromatin accessibility. Finally, we found that the loss of GATA2 expression and DNA binding are crucial for the differentiation process, and changes in the chromatin structure around the GATA2 regulate its expression upon ATRA induction. This study provided both statistical insights and experimental details regarding the relationship between chromatin conformation changes and transcription regulation during leukemia cell differentiation, and the results suggested that the chromatin conformation is a new type of potential drug target for cancer therapy.
Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II
Authors: Ma Yiqiong , Yang Qian , Zhong Zhentong , Liang Wei , Zhang Lu , Yang Yingjie , Ding Guohua
Published: February 2018

Our previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies showed that nephrin was required for cytoskeletal remodeling in glomerular podocytes. But its specific mechanisms remain incompletely understood. As a nonreceptor tyrosine kinase involved in cytoskeletal regulation, c-Abl may be a candidate of signaling proteins interacting with Src homology 2/3 (SH2/SH3) domains of nephrin. Therefore, it is proposed that c-Abl contributes to nephrin-dependent cytoskeletal remodeling of podocytes. Herein, we observed that nephrin-c-Abl colocalization were suppressed in glomeruli of patients with proteinuria. Next, CD16/7-nephrin and c-Abl vectors were constructed to investigate the nephrin-c-Abl signaling pathway in podocyte actin-cytoskeletal remodeling. The disorganized cytoskeleton stimulated by cytochalasin D in COS7 cells was dramatically restored by co-transfection with phosphorylated CD16/7-nephrin and c-Abl full-length constructs. Further, co-immunoprecipitation showed that phosphorylated CD16/7-nephrin interacted with wild-type c-Abl, but not with SH2/SH3-defective c-Abl. These findings suggest that phosphorylated nephrin is able to recruit c-Abl in a SH2/SH3-dependent manner and detached c-Abl from dephosphorylated nephrin contributes to cytoskeletal remodeling in podocytes.
Regenerative potential of tonsil mesenchymal stem cells on surgical cutaneous defect
Authors: Shin Sung-Chan , Seo Yoojin , Park Hee Young , Jung Da-Woon , Shin Tae-Hoon , Son Haejin , Kim Young Keum , Lee Jin-Choon , Sung Eui-Suk , Jang Jeon Yeob , Kim Hyung-Sik , Lee Byung-Joo
Published: February 2018

As tissue engineering and regenerative medicine have evolved recently, stem cell therapy has been investigated in the field of impaired wound healing. Several studies have reported that mesenchymal stem cells derived from various tissues including bone marrow and adipose tissue can exert the regenerative efficacy in the wound healing. Previously, we have demonstrated the isolation and characterization of tonsil-derived mesenchymal stem cells (TMSCs) with excellent proliferative property. In the present study, we aimed to evaluate the regenerative efficacy of TMSCs in the wound healing process. Two distinct cutaneous surgical defects were generated in the dorsum of mice. Each wound was treated with TMSCs or phosphate-buffered saline (PBS), respectively. After sacrifice, the skin and subcutaneous tissues around the surgical defect were harvested and assessed for inflammation, re-epithelialization, dermal regeneration, and granulation tissue formation. The administration of TMSCs into wound beds significantly promoted the repair of surgical defects in mice. Especially, TMSCs efficiently contributed to the attenuation of excessive inflammation in the surgical lesion, as well as the augmentation of epidermal and dermal regeneration. To elucidate the underlying mechanisms, TMSCs were analyzed for their potency in immunomodulatory ability on immune cells, stimulatory effect on the proliferation of keratinocytes, and fibroblasts, as well as the regulation of fibroblast differentiation. TMSCs inhibited the non-specific or T-cell-specific proliferation of peripheral blood mononuclear cells, as well as the M1 polarization of macrophage-like cells. Moreover, TMSCs augmented the proliferation of skin-constituting fibroblasts and keratinocytes while they suppressed the differentiation of fibroblasts into myofibroblasts. Taken together, our findings demonstrate the regenerative potential of TMSCs in wound healing process through the regulation on inflammation, proliferation, and remodeling of various skin cells, implying that TMSCs can be a promising alternative for wound repair.
Dynamics of starvation and recovery predict extinction risk and both Damuth’s law and Cope’s rule
Authors: Yeakel Justin D. , Kempes Christopher P. , Redner Sidney
Published: February 2018

The eco-evolutionary dynamics of species are fundamentally linked to the energetic constraints of their constituent individuals. Of particular importance is the interplay between reproduction and the dynamics of starvation and recovery. To elucidate this interplay, here we introduce a nutritional state-structured model that incorporates two classes of consumers: nutritionally replete, reproducing consumers, and undernourished, nonreproducing consumers. We obtain strong constraints on starvation and recovery rates by deriving allometric scaling relationships and find that population dynamics are typically driven to a steady state. Moreover, these rates fall within a “refuge” in parameter space, where the probability of population extinction is minimized. We also show that our model provides a natural framework to predict steady state population abundances known as Damuth's law, and maximum mammalian body size. By determining the relative stability of an otherwise homogeneous population to a competing population with altered percent body fat, this framework provides a principled mechanism for a selective driver of Cope’s rule.
Nanobody-triggered lockdown of VSRs reveals ligand reloading in the Golgi
Authors: Früholz Simone , Fäßler Florian , Kolukisaoglu Üner , Pimpl Peter
Published: February 2018

Protein degradation in lytic compartments is crucial for eukaryotic cells. At the heart of this process, vacuolar sorting receptors (VSRs) bind soluble hydrolases in the secretory pathway and release them into the vacuolar route. Sorting efficiency is suggested to result from receptor recycling. However, how and to where plant VSRs recycle remains controversial. Here we present a nanobody–epitope interaction-based protein labeling and tracking approach to dissect their anterograde and retrograde transport routes in vivo. We simultaneously employ two different nanobody–epitope pairs: one for the location-specific post-translational fluorescence labeling of receptors and the other pair to trigger their compartment-specific lockdown via an endocytosed dual-epitope linker protein. We demonstrate VSR recycling from the TGN/EE, thereby identifying the cis-Golgi as the recycling target and show that recycled VSRs reload ligands. This is evidence that bidirectional VSR-mediated sorting of vacuolar proteins exists and occurs between the Golgi and the TGN/EE.
3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection
Authors: Ortega-Prieto A. M. , Skelton J. K. , Wai S. N. , Large E. , Lussignol M. , Vizcay-Barrena G. , Hughes D. , Fleck R. A. , Thursz M. , Catanese M. T. , Dorner M.
Published: February 2018

With more than 240 million people infected, hepatitis B virus (HBV) is a major health concern. The inability to mimic the complexity of the liver using cell lines and regular primary human hepatocyte (PHH) cultures pose significant limitations for studying host/pathogen interactions. Here, we describe a 3D microfluidic PHH system permissive to HBV infection, which can be maintained for at least 40 days. This system enables the recapitulation of all steps of the HBV life cycle, including the replication of patient-derived HBV and the maintenance of HBV cccDNA. We show that innate immune and cytokine responses following infection with HBV mimic those observed in HBV-infected patients, thus allowing the dissection of pathways important for immune evasion and validation of biomarkers. Additionally, we demonstrate that the co-culture of PHH with other non-parenchymal cells enables the identification of the cellular origin of immune effectors, thus providing a valuable preclinical platform for HBV research.
Publisher Correction: Role of outer surface probes for regulating ion gating of nanochannels
Authors: Li Xinchun , Zhai Tianyou , Gao Pengcheng , Cheng Hongli , Hou Ruizuo , Lou Xiaoding , Xia Fan
Published: February 2018

The original version of this Article contained an error in Fig. 3. The scale bars in Figs 3c and 3d were incorrectly labelled as 50 μA. In the correct version, the scale bars are labelled as 0.5 μA. This has now been corrected in both the PDF and HTML versions of the Article.
High enthalpy storage thermoset network with giant stress and energy output in rubbery state
Authors: Fan Jizhou , Li Guoqiang
Published: February 2018

Low output in stress and energy in rubbery state has been a bottleneck for wide-spread applications of thermoset shape memory polymers (SMPs). Traditionally, stress or energy storage in thermoset network is through entropy reduction by mechanical deformation or programming. We here report another mechanism for energy storage, which stores energy primarily through enthalpy increase by stretched bonds during programming. As compared to entropy-driven counterparts, which usually have a stable recovery stress from tenths to several MPa and energy output of several tenths MJ/m3, our rubbery network achieved a recovery stress of 17.0 MPa and energy output of 2.12 MJ/m3 in bulk form. The giant stress and energy release in the rubbery state will enhance applications of thermoset SMPs in engineering structures and devices.
Interventions to enhance the adoption of asthma self-management behaviour in the South Asian and African American population: a systematic review
Authors: Ahmed Salina , Steed Liz , Harris Katherine , Taylor Stephanie J. C. , Pinnock Hilary
Published: February 2018

South Asian and other minority communities suffer poorer asthma outcomes, have a higher rate of unscheduled care and benefit less from most existing self-management interventions when compared to the majority population. Possible reasons for these differences include failure to implement asthma self-management strategies, or that strategies implemented were inappropriate for their needs; alternatively, they may relate to the minority and/or lower socioeconomic status of these populations. We aimed to synthesise evidence from randomised controlled trials for asthma self-management in South Asian and Black populations from different sociocultural contexts, and identify barriers and facilitators to implementing self-management. We systematically searched eight electronic databases, and research registers, and manually searched relevant journals and reference lists of reviews. Seventeen trials met the inclusion criteria and were analysed narratively. We found two culturally targeted interventions compared to fifteen culturally modified interventions. Interventions used diverse self-management strategies; education formed a central component. Interventions in South Asian and African-American minority communities were less effective than interventions delivered in indigenous populations in South Asia, though the latter trials were at higher risk of bias. Education, with continuous professional support, was common to most interventions. Facilitators to asthma self-management included: ensuring culturally/linguistically appropriate education, adapting to learning styles, addressing daily stressors/social support and generic self-management strategies. In conclusion, when developing and evaluating self-management interventions aimed at different cultures, the influence of sociocultural contexts (including whether patients are from a minority or indigenous population) can be important for the conceptualisation of culture and customisation of self-management strategies.
Expression, Purification and Characterization of the Human Cannabinoid 1 Receptor
Authors: Mallipeddi Srikrishnan , Zvonok Nikolai , Makriyannis Alexandros
Published: February 2018

The human cannabinoid 1 receptor (hCB1) is involved in numerous physiological processes and therefore provides a wide scope of potential therapeutic opportunities to treat maladies such as obesity, cardio-metabolic disorders, substance abuse, neuropathic pain, and multiple sclerosis. Structure-based drug design using the current knowledge of the hCB1 receptor binding site is limited and requires purified active protein. Heterologous expression and purification of functional hCB1 has been the bottleneck for ligand binding structural studies using biophysical methods such as mass spectrometry, x-ray crystallography and NMR. We constructed several plasmids for in-cell or in vitro Escherichia coli (E. coli) based expression of truncated and stabilized hCB1 receptor (hΔCB1 and hΔCB1T4L) variants and evaluated their competency to bind the CP-55,940 ligand. MALDI-TOF MS analysis of in vitro expressed and purified hΔCB1T4Lhis6 variants, following trypsin digestion, generated ~80% of the receptor sequence coverage. Our data demonstrate the feasibility of a cell-free expression system as a promising part of the strategy for the elucidation of ligand binding sites of the hCB1 receptor using a “Ligand Assisted Protein Structure” (LAPS) approach.
Being slightly overweight is associated with a better quality of life in breast cancer survivors
Authors: Xia Juan , Tang Zheng , Deng Qinglong , Wang Jiwei , Yu Jinming
Published: February 2018

To examine the association between BMI and QOL in breast cancer survivors in China, we conducted a cross-sectional survey and recruited 10708 breast cancer survivors. Survivors self-reported QOL was measured using the EORTC QLQ-C30 and the QLQ-BR23. The impact of BMI on QOL was examined through standard least squares regression. Normal weight and overweight survivors were more likely to have a better QOL than underweight and obese survivors and the results were similar to survivors diagnosed as having chronic diseases. After adjustment for clinical and sociodemographic factors, the QOL increased with increasing BMI in breast cancer survivors ranged from underweight to overweight with no chronic diseases, especially in the scales of emotional function and fatigue. Obese breast cancer survivors reported a significantly worse QOL compared to normal weight and overweight breast cancer survivors. Within breast cancer survivors with one or more chronic diseases, it was more obvious that overweight ones had a significantly better QOL with clear evidence of a dose relationship across underweight to overweight in almost all scales. Unlike obese breast cancer survivors without chronic diseases, the ones with chronic disease(s) had a similar QOL compared to normal weight breast cancer survivors in all scales except in the domain of fatigue.
Daily circadian misalignment impairs human cognitive performance task-dependently
Authors: Chellappa Sarah L. , Morris Christopher J. , Scheer Frank A. J. L.
Published: February 2018

Shift work increases the risk for human errors, such that drowsiness due to shift work has contributed to major industrial disasters, including Space Shuttle Challenger, Chernobyl and Alaska Oil Spill disasters, with extraordinary socio-economical costs. Overnight operations pose a challenge because our circadian biology inhibits cognitive performance at night. Yet how the circadian system modulates cognition over multiple days under realistic shift work conditions remains to be established. Importantly, because task-specific cognitive brain regions show different 24-h circadian dynamics, we hypothesize that circadian misalignment impacts cognition task-dependently. Using a biologically-driven paradigm mimicking night shift work, with a randomized, cross-over design, we show that misalignment between the circadian pacemaker and behavioral/environmental cycles increases cognitive vulnerability on sustained attention, cognitive throughput, information processing and visual-motor performance over multiple days, compared to circadian alignment (day shifts). Circadian misalignment effects are task-dependent: while they acutely impair sustained attention with recovery after 3-days, they progressively hinder daily learning. Individuals felt sleepier during circadian misalignment, but they did not rate their performance as worse. Furthermore, circadian misalignment effects on sustained attention depended on prior sleep history. Collectively, daily circadian misalignment may provide an important biological framework for developing countermeasures against adverse cognitive effects in shift workers.
Molecular determinants of Guanylate Cyclase Activating Protein subcellular distribution in photoreceptor cells of the retina
Authors: López-Begines Santiago , Plana-Bonamaisó Anna , Méndez Ana
Published: February 2018

Retinal guanylate cyclase (RetGC) and guanylate cyclase activating proteins (GCAPs) play an important role during the light response in photoreceptor cells. Mutations in these proteins are linked to distinct forms of blindness. RetGC and GCAPs exert their role at the ciliary outer segment where phototransduction takes place. We investigated the mechanisms governing GCAP1 and GCAP2 distribution to rod outer segments by expressing selected GCAP1 and GCAP2 mutants as transient transgenes in the rods of GCAP1/2 double knockout mice. We show that precluding GCAP1 direct binding to RetGC (K23D/GCAP1) prevented its distribution to rod outer segments, while preventing GCAP1 activation of RetGC post-binding (W94A/GCAP1) did not. We infer that GCAP1 translocation to the outer segment strongly depends on GCAP1 binding affinity for RetGC, which points to GCAP1 requirement to bind to RetGC to be transported. We gain further insight into the distinctive regulatory steps of GCAP2 distribution, by showing that a phosphomimic at position 201 is sufficient to retain GCAP2 at proximal compartments; and that the bovine equivalent to blindness-causative mutation G157R/GCAP2 results in enhanced phosphorylation in vitro and significant retention at the inner segment in vivo, as likely contributing factors to the pathophysiology.
An allogeneic ‘off the shelf’ therapeutic strategy for peripheral nerve tissue engineering using clinical grade human neural stem cells
Authors: O’Rourke C. , Day A. G. E. , Murray-Dunning C. , Thanabalasundaram L. , Cowan J. , Stevanato L. , Grace N. , Cameron G. , Drake R. A. L. , Sinden J. , Phillips J. B.
Published: February 2018

Artificial tissues constructed from therapeutic cells offer a promising approach for improving the treatment of severe peripheral nerve injuries. In this study the effectiveness of using CTX0E03, a conditionally immortalised human neural stem cell line, as a source of allogeneic cells for constructing living artificial nerve repair tissue was tested. CTX0E03 cells were differentiated then combined with collagen to form engineered neural tissue (EngNT-CTX), stable aligned sheets of cellular hydrogel. EngNT-CTX sheets were delivered within collagen tubes to repair a 12 mm sciatic nerve injury model in athymic nude rats. Autologous nerve grafts (autografts) and empty tubes were used for comparison. After 8 weeks functional repair was assessed using electrophysiology. Further, detailed histological and electron microscopic analysis of the repaired nerves was performed. Results indicated that EngNT-CTX supported growth of neurites and vasculature through the injury site and facilitated reinnervation of the target muscle. These findings indicate for the first time that a clinically validated allogeneic neural stem cell line can be used to construct EngNT. This provides a potential ‘off the shelf’ tissue engineering solution for the treatment of nerve injury, overcoming the limitations associated with nerve autografts or the reliance on autologous cells for populating repair constructs.
Softening due to Grain Boundary Cavity Formation and its Competition with Hardening in Helium Implanted Nanocrystalline Tungsten
Authors: Cunningham W. Streit , Gentile Jonathan M. , El-Atwani Osman , Taylor Chase N. , Efe Mert , Maloy Stuart A. , Trelewicz Jason R.
Published: February 2018

The unique ability of grain boundaries to act as effective sinks for radiation damage plays a significant role in nanocrystalline materials due to their large interfacial area per unit volume. Leveraging this mechanism in the design of tungsten as a plasma-facing material provides a potential pathway for enhancing its radiation tolerance under fusion-relevant conditions. In this study, we explore the impact of defect microstructures on the mechanical behavior of helium ion implanted nanocrystalline tungsten through nanoindentation. Softening was apparent across all implantation temperatures and attributed to bubble/cavity loaded grain boundaries suppressing the activation barrier for the onset of plasticity via grain boundary mediated dislocation nucleation. An increase in fluence placed cavity induced grain boundary softening in competition with hardening from intragranular defect loop damage, thus signaling a new transition in the mechanical behavior of helium implanted nanocrystalline tungsten.
Thermally-Conductive and Mechanically-Robust Graphene Nanoplatelet Reinforced UO2 Composite Nuclear Fuels
Authors: Yao Tiankai , Xin Guoqing , Scott Spencer Michael , Gong Bowen , Lian Jie
Published: February 2018

Low thermal transport behavior along the radial direction of nuclear fuel pellets and pellet-cladding mechanical interaction significantly impact fuel performance and the safety of current nuclear energy systems. Here we report a new strategy of advanced fuel design in which highly thermally-conductive and mechanically-robust graphene nanoplatelets are incorporated into UO2 fuel matrix to improve fuel thermal-mechanical properties. The 2D geometry of the graphene nanoplatelets enables a unique lamellar structure upon fuel consolidation by spark plasma sintering. The thermal conductivity along the radial direction of the sintered fuel pellets at room temperature reaches 12.7 and 19.1 wm−1K−1 at 1 wt.% and 5 wt.% loadings of the graphene nanoplatelets, respectively, representing at least 74% and 162% enhancements as compared to pure UO2 fuel pellets. Indentation testing suggests great capability of the 2D graphene nanoplatelets to deflect and pin crack propagation, drastically improving the crack propagation resistance of fuel matrix. The estimated indentation fracture toughness reaches 3.5 MPa·m1/2 by 1 wt.% loading of graphene nano-platelets, representing a 150% improvement over 1.4 MPa·m1/2 for pure UO2 fuel pellets. Isothermal annealing of the composite fuel indicates that the graphene nano-platelet is able to retain its structure and properties against reaction with UO2 matrix up to 1150 °C.
Intimate Partner Violence Correlates With A Higher HIV Incidence Among MSM: A 12-Month Prospective Cohort Study in Shenyang, China
Authors: Wang Hong-yi , Wang Ning , Chu Zhen-xing , Zhang Jing , Mao Xiang , Geng Wen-qing , Jiang Yong-jun , Shang Hong , Xu Jun-jie
Published: February 2018

Intimate partner violence (IPV) and HIV are highly prevalent worldwide among MSM. However, the association between IPV and HIV seroconversion is virtually unknown. This 12-month prospective cohort study was conducted among MSM in Shenyang, China to explore the causality between IPV and the incidence of HIV. Adjusted Hazard Ratios (aHRs) of HIV acquisition were derived from a multivariate time-dependent Cox model and applied to calculate population attributable fractions (PAFs). Among 476 HIV-negative MSM subjects, 89(18.7%) reported being victims of IPV in the past 3 months (P3M). IPV was significantly correlated with lower education, having more condomless anal intercourse (CAI) and being depressed (each P < 0.05). The incidence of HIV among IPV victims was 11.3/100 PY compared to 3.8/100 PY in non-IPV-victims. Furthermore, IPV victimization was independently associated with HIV seroconversion (aHR = 4.1, PAF = 37.9%). Other predictors for seroconversion included non-local residence in Liaoning province (aHR = 3.9, PAF = 45.2%), engaging in condomless receptive anal intercourse (CRAI)(aHR = 3.1, PAF = 24.2%) or CAI with casual male partners (aHR = 3.8, PAF = 26.3%) in the P3M and syphilis infection (aHR = 4.7, PAF = 33.7%) (each P < 0.05). IPV increased the HIV seroconversion risk of MSM, with a high PAF. HIV prevention programs should integrate IPV screening and intervention, and MSM affected by IPV need to be preferentially enrolled in pre-exposure prophylaxis.
Poleward upgliding Siberian atmospheric rivers over sea ice heat up Arctic upper air
Authors: Komatsu Kensuke K. , Alexeev Vladimir A. , Repina Irina A. , Tachibana Yoshihiro
Published: February 2018

We carried out upper air measurements with radiosondes during the summer over the Arctic Ocean from an icebreaker moving poleward from an ice-free region, through the ice edge, and into a region of thick ice. Rapid warming of the Arctic is a significant environmental issue that occurs not only at the surface but also throughout the troposphere. In addition to the widely accepted mechanisms responsible for the increase of tropospheric warming during the summer over the Arctic, we showed a new potential contributing process to the increase, based on our direct observations and supporting numerical simulations and statistical analyses using a long-term reanalysis dataset. We refer to this new process as “Siberian Atmospheric Rivers (SARs)”. Poleward upglides of SARs over cold air domes overlying sea ice provide the upper atmosphere with extra heat via condensation of water vapour. This heating drives increased buoyancy and further strengthens the ascent and heating of the mid-troposphere. This process requires the combination of SARs and sea ice as a land-ocean-atmosphere system, the implication being that large-scale heat and moisture transport from the lower latitudes can remotely amplify the warming of the Arctic troposphere in the summer.
Characterization of Conserved and Novel microRNAs in Lilium lancifolium Thunb. by High-Throughput Sequencing
Authors: He Xiangfeng , Shenkute Awraris Getachew , Wang Wenhe , Xu Shufa
Published: February 2018

MicroRNAs (miRNAs) are among the class of noncoding small RNA molecules and play a crucial role in post-transcriptional regulation in plants. Although Lilium is one of the most popular ornamental flowers worldwide, however, there is no report on miRNAs identification. In the present study, therefore, miRNAs and their targets were identified from flower, leaf, bulblet and bulb of Lilium lancifolium Thunb. by high-throughput sequencing and bioinformatics analysis. In this study, a total of 38 conserved miRNAs belonging to 17 miRNA families and 44 novel miRNAs were identified. In total, 366 target genes for conserved miRNAs and 415 target genes for novel miRNAs were predicted. The majority of the target genes for conserved miRNAs were transcriptional factors and novel miRNAs targeted mainly protein coding genes. A total of 53 cleavage sites belonging to 6 conserved miRNAs families and 14 novel miRNAs were identified using degradome sequencing. Twenty-three miRNAs were randomly selected, then, their credibility was confirmed using northern blot or stem-loop qRT-PCR. The results from qRT-PCR analysis showed the expression pattern of 4 LL-miRNAs was opposite to their targets. Therefore, our finding provides an important basis to understand the biological functions of miRNAs in Lilium.
Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids
Authors: Kasendra Magdalena , Tovaglieri Alessio , Sontheimer-Phelps Alexandra , Jalili-Firoozinezhad Sasan , Bein Amir , Chalkiadaki Angeliki , Scholl William , Zhang Cheng , Rickner Hannah , Richmond Camilla A. , Li Hu , Breault David T. , Ingber Donald E.
Published: February 2018

Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.
Rhamnolipids production from sucrose by engineered Saccharomyces cerevisiae
Authors: Bahia Frederico Mendonça , de Almeida Gabriela Carneiro , de Andrade Lorena Pereira , Campos Christiane Gonçalves , Queiroz Lúcio Rezende , da Silva Rayane Luzia Vieira , Abdelnur Patrícia Verardi , Corrêa José Raimundo , Bettiga Maurizio , Parachin Nádia Skorupa
Published: February 2018

Biosurfactants are biological tensioactive agents that can be used in the cosmetic and food industries. Rhamnolipids are glycolipid biosurfactants naturally produced by Pseudomonas aeruginosa and are composed of one or two rhamnose molecules linked to beta-hydroxy fatty acid chains. These compounds are green alternatives to petrochemical surfactants, but their large-scale production is still in its infancy, hindered due to pathogenicity of natural producer, high substrate and purification costs and low yields and productivities. This study, for the first time, aimed at producing mono-rhamnolipids from sucrose by recombinant GRAS Saccharomyces cerevisiae strains. Six enzymes from P. aeruginosa involved in mono-rhamnolipid biosynthesis were functionally expressed in the yeast. Furthermore, its SUC2 invertase gene was disrupted and a sucrose phosphorylase gene from Pelomonas saccharophila was also expressed to reduce the pathway’s overall energy requirement. Two strains were constructed aiming to produce mono-rhamnolipids and the pathway’s intermediate dTDP-L-rhamnose. Production of both molecules was analyzed by confocal microscopy and mass spectrometry, respectively. These strains displayed, for the first time as a proof of concept, the potential of production of these molecules by a GRAS eukaryotic microorganism from an inexpensive substrate. These constructs show the potential to further improve rhamnolipids production in a yeast-based industrial bioprocess.
Salt-bridge modulates differential calcium-mediated ligand binding to integrin α1- and α2-I domains
Authors: Brown Kyle L. , Banerjee Surajit , Feigley Andrew , Abe Hanna , Blackwell Timothy S. , Pozzi Ambra , Hudson Billy G. , Zent Roy
Published: February 2018

Integrins are transmembrane cell-extracellular matrix adhesion receptors that impact many cellular functions. A subgroup of integrins contain an inserted (I) domain within the α–subunits (αI) that mediate ligand recognition where function is contingent on binding a divalent cation at the metal ion dependent adhesion site (MIDAS). Ca2+ is reported to promote α1I but inhibit α2I ligand binding. We co-crystallized individual I-domains with MIDAS-bound Ca2+ and report structures at 1.4 and 2.15 Å resolution, respectively. Both structures are in the “closed” ligand binding conformation where Ca2+ induces minimal global structural changes. Comparisons with Mg2+-bound structures reveal Mg2+ and Ca2+ bind α1I in a manner sufficient to promote ligand binding. In contrast, Ca2+ is displaced in the α2I domain MIDAS by 1.4 Å relative to Mg2+ and unable to directly coordinate all MIDAS residues. We identified an E152-R192 salt bridge hypothesized to limit the flexibility of the α2I MIDAS, thus, reducing Ca2+ binding. A α2I E152A construct resulted in a 10,000-fold increase in Mg2+ and Ca2+ binding affinity while increasing binding to collagen ligands 20%. These data indicate the E152-R192 salt bridge is a key distinction in the molecular mechanism of differential ion binding of these two I domains.
Counting the electrons in a multiphoton ionization by elastic scattering of microwaves
Authors: Sharma A. , Slipchenko M. N. , Shneider M. N. , Wang X. , Rahman K. A. , Shashurin A.
Published: February 2018

Multiphoton ionization (MPI) is a fundamental first step in high-energy laser-matter interaction and is important for understanding the mechanism of plasma formation. With the discovery of MPI more than 50 years ago, there were numerous attempts to determine the basic physical constants of this process in direct experiments, namely photoionization rates and cross-sections of the MPI; however, no reliable data was available until now, and the spread in the literature values often reaches 2–3 orders of magnitude. This is due to the inability to conduct absolute measurements of plasma electron numbers generated by MPI, which leads to uncertainties and, sometimes, contradictions between MPI cross-section values utilized by different researchers across the field. Here, we report the first direct measurement of absolute plasma electron numbers generated at MPI of air, and subsequently we precisely determine the ionization rate and cross-section of eight-photon ionization of oxygen molecule by 800 nm photons σ8 = (3.3 ± 0.3)×10−130 W−8m16s−1. The method, based on the absolute measurement of the electron number created by MPI using elastic scattering of microwaves off the plasma volume in Rayleigh regime, establishes a general approach to directly measure and tabulate basic constants of the MPI process for various gases and photon energies.