bluuebunny/crossref_metadata_2025 huggingface dataset:
REVIEWING TRANSFERABILITY IN ECONOMIC EVALUATIONS ORIGINATING FROM EASTERN EUROPE
Authors: Mandrik Olena , Knies Saskia , Kalo Zoltan , Severens Johan L.
Published: March 2016

Objectives:The aim of this study is to analyze the quality and transferability issues reported in published peer-reviewed English-language economic evaluations based in healthcare settings of the Central and Eastern European (CEE) and former Soviet countries.

Methods:A systematic search of economic evaluations of healthcare interventions was performed for Armenia, Azerbaijan, Belarus, Bulgaria, Estonia, Georgia, Turkmenistan, Kazakhstan, Lithuania, the former Yugoslav Republic of Macedonia, Republic of Moldova, Romania, the Russian Federation, Serbia, Slovenia, and Ukraine. The included studies were assessed according to their characteristics, quality (using Drummond's checklist), use of local data, and the transferability of inputs and results, if addressed.

Results:Most of the thirty-four economic evaluations identified were conducted from a healthcare or payer perspective (74 percent), with 47 percent of studies focusing on infectious diseases. The least frequently and transparently addressed parameters were the items’ stated perspectives, relevant costs included, accurately measured costs in appropriate units, outcomes and costs credibly valued, and uncertainties addressed. Local data were often used to assess unit costs, baseline risk, and resource usage, while jurisdiction-specific utilities were included in only one study. Only 32 percent of relevant studies discussed the limitations of using foreign data, and 36 percent of studies discussed the transferability of their own study results to other jurisdictions.

Conclusions:Transferability of the results is not sufficiently discussed in published economic evaluations. To simplify the transferability of studies to other jurisdictions, the following should be comprehensively addressed: uncertainty, impact of influential parameters, and data transferability. The transparency of reporting should be improved.
Introduction: Morgenthau in America
Authors: Navari Cornelia
Published: March 2016

Hans J. Morgenthau is generally considered to have been a political realist and the transmitter of continental Realpolitik into American letters. But he has also been claimed as an idealist, as a constructivist, and as an ethicist. Some of these claims make sense if we understand that Morgenthau was trained as a lawyer in the German historical tradition. Others can be made sense of if we understand that—self-consciously a “European”—he was continuously adapting his ideas to an American audience and, in the process, being socialized into an American experience. The essays in this roundtable illustrate the “Americanization” of Morgenthau.
Robots and Respect: Assessing the Case Against Autonomous Weapon Systems
Authors: Sparrow Robert
Published: March 2016

There is increasing speculation within military and policy circles that the future of armed conflict is likely to include extensive deployment of robots designed to identify targets and destroy them without the direct oversight of a human operator. My aim in this paper is twofold. First, I will argue that the ethical case for allowing autonomous targeting, at least in specific restricted domains, is stronger than critics have typically acknowledged. Second, I will attempt to defend the intuition that, even so, there is something ethically problematic about such targeting. I argue that an account of the nonconsequentialist foundations of the principle of distinction suggests that the use of autonomous weapon systems (AWS) is unethical by virtue of failing to show appropriate respect for the humanity of our enemies. However, the success of the strongest form of this argument depends upon understanding the robot itself as doing the killing. To the extent that we believe that, on the contrary, AWS are only a means used by combatants to kill, the idea that the use of AWS fails to respect the humanity of our enemy will turn upon an account of what is required by respect, which is essential conventional. Thus, while the theoretical foundations of the idea that AWS are weapons that are “evil in themselves” are weaker than critics have sometimes maintained, they are nonetheless sufficient to demand a prohibition of the development and deployment of such weapons.
The role of a multidisciplinary student team in the community management of chronic obstructive pulmonary disease
Authors: Clarke Herchel , Voss Miranda
Published: March 2016

Objective

To determine whether a community-based, multidisciplinary team consisting of home-based caregivers and supervised students could improve the functional status and quality of life of patients living with chronic obstructive pulmonary disease (COPD) in a low-income, peri-urban setting in South Africa.

Methods

This was a quasi-experimental study conducted over three months. Attention was paid to health literacy, inhaler technique, respiratory conditioning and nutrition.

Results

Health literacy was poor and most patients were not using their inhalers correctly. Five of 12 patients found exercising challenging and withdrew from the study early. In the remaining seven patients, statistically significant improvements in FEV1%, and quality of life scores were seen at three months. Improvements in exercise tolerance and BODE prognostic index did not reach statistical significance.

Conclusion

A home-based multidisciplinary student team can improve the functional status and the quality of life in patients living with COPD in a low-income setting. This approach offers a suitable model for community-based service learning.
Some Useful Sources
Authors: Sen Robin , Churchill Harriet
Published: March 2016

This useful sources paper provides selective lists of: first, the generic and critical literature about family support; second, the UK policy and practice literature about intensive family support services; third, the international policy and practice literature about intensive family support services; and, finally, a number of web resources.
Tracing the domestication of the Andean root crop arracacha (Arracacia xanthorrhizaBancr.): a molecular survey confirms the selection of a wild form apt to asexual reproduction
Authors: Morillo Eduardo , Sécond Gérard
Published: March 2016

Andean arracacha (Arracacia xanthorrhizaBancr.) is a valuable but poorly known vegetatively reproduced root crop whose origin is still unresolved. Wild tuberous forms are present in the presumed areas of domestication and have a perennial or monocarpic life history. To elucidate the origin of the cultivated form, we surveyed a molecular analysis with amplified fragment length polymorphisms (AFLPs) in a representative sample of this crop and its wild relatives from Ecuador and Peru, the presumed areas of domestication. Wild species with tuberous and non-tuberous roots were included, as well as the perennial and monocarpic forms of the presumed wild ancestor. While the two wild varieties ofA. xanthorrhizawere closest to the cultivars, they were distinguished by AFLPs. Unexpectedly, two clearly distinct groups were formed among the cultivars, one of which was significantly closer to the monocarpic wild form. However, the chloroplast DNA survey revealed greater similarity between all of the cultivars and the wild perennialA. xanthorrhiza. These results combined with the morphological and life history features, confirms the hypothesis that arracacha domestication started from the wild perennial form. We suggest this scenario of domestication followed by an unsuspected introgression in the cultivation, resulting in two cryptic genetic groups, well distinguished at the molecular level. This is an important revelation with implications in genetic resource conservation and breeding standpoints in this promissory crop.
Culture is the Solution: the Civilizing Mission of Egypt’s Culture Palaces
Authors: Winegar Jessica
Published: March 2016

Since the early 1990s, the Egyptian government has devoted significant resources to new culture projects. Unprecedented numbers of new cultural institutions have been built or renovated throughout the country, including libraries, museums, culture palaces and houses, and creativity centers. These host thousands of public programs every year. The government has also started two new television channels devoted specifically to culture(thaqafa). Book fairs and art biennials have increased in number and expanded, new cultural periodicals and book series have been published, and new cultural competitions and prizes created. Nearly every day in the state press, one finds articles and announcements detailing cultural events and programs, as well as editorials on the importancethaqafato Egyptian society.
Depression
Authors: Petermann Franz , de Vries Ulrike
Published: March 2016

Zusammenfassung. Depressive Störungen zählen zu den häufigsten Formen psychischer Störungen. Aufgrund ihrer hohen Prävalenz und weitreichenden Komplikationen besitzen sie eine besondere klinische, gesundheitspolitische und gesundheitsökonomische Bedeutung. Insbesondere für die betroffenen Patienten sind die mit der Depression einhergehenden Krankheitsfolgen und Belastungen erheblich. Umso wichtiger ist daher die Erforschung patientennaher Merkmale, die möglicherweise Einfluss auf den Krankheitsverlauf nehmen, um so die Passung zwischen Behandlungsbedarf und Behandlungsangebot noch weiter zu verbessern. Diese patientennahen Merkmale müssen thematisiert und hinsichtlich ihrer Bedeutung für die Therapieplanung diskutiert werden.
Posttraumatisches Wachstum bei Menschen mit Querschnittlähmung
Authors: Stöckler Christiane , Petermann Franz , Kobelt Axel
Published: March 2016

Zusammenfassung. Die vorliegende Arbeit untersucht das Konzept des posttraumatischen Wachstums anhand einer Stichprobe von Menschen mit einer traumatisch bedingten Querschnittlähmung (N = 70). Neben dem Ausmaß an posttraumatischem Wachstum werden mit varianzanalytischen Verfahren der Zusammenhang zwischen posttraumatischem Wachstum und weiteren Einzelmerkmalen der Probanden (Alter, Geschlecht, Lähmungshöhe, seelische Belastung, Schwere der Erschütterung, Unterstützung durch Familie, Freunde und andere querschnittgelähmte Personen, in Anspruch genommene psychologische Hilfe) ermittelt. Posttraumatisches Wachstum wird mit der deutschen Version des Posttraumatic Growth Inventory (PTGI) und die seelische Belastung mit den Depression, Anxiety and Stress Scales (DASS) gemessen. Alle anderen Merkmale werden anhand von Einzelitems erhoben. 62,9 % der Teilnehmer gaben an, posttraumatisches Wachstum in einem Ausmaß mittlerer Stärke erlebt zu haben. Weitere Faktoren, die mit posttraumatischem Wachstum in Zusammenhang stehen, konnten nicht eindeutig identifiziert werden. Folgen für die praktische Anwendung und zukünftige Forschungsarbeiten werden diskutiert.
Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array
Authors:   The UK Genetic Prostate Cancer Study Collaborators, Saunders Edward J ,   The UK ProtecT Study Collaborators,   The PRACTICAL Consortium Australian Prostate Cancer BioResource, Dadaev Tokhir , Leongamornlert Daniel A , Olama Ali Amin Al , Benlloch Sara , Giles Graham G , Wiklund Fredrik , Grönberg Henrik , Haiman Christopher A , Schleutker Johanna , Nordestgaard Børge G , Travis Ruth C , Neal David , Pasayan Nora , Khaw Kay-Tee , Stanford Janet L , Blot William J , Thibodeau Stephen N , Maier Christiane , Kibel Adam S , Cybulski Cezary , Cannon-Albright Lisa , Brenner Hermann , Park Jong Y , Kaneva Radka , Batra Jyotsna , Teixeira Manuel R , Pandha Hardev , Govindasami Koveela , Muir Ken , Easton Douglas F , Eeles Rosalind A , Kote-Jarai Zsofia
Published: March 2016

Background:

Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of ∼100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B.

Methods:

Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes.

Results:

Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant.

Conclusions:

MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers.
A long non-coding RNA interacts with Gfra1 and maintains survival of mouse spermatogonial stem cells
Authors: Li L , Wang M , Wang M , Wu X , Geng L , Xue Y , Wei X , Jia Y , Wu X
Published: March 2016

Spermatogonial stem cells (SSCs) are unique male germline stem cells that support spermatogenesis and male fertility. Long non-coding RNAs (lncRNA) have been identified as key regulators of stem cell fate; however, their role in SSCs has not been explored. Here, we report that a novel spermatogonia-specific lncRNA (lncRNA033862) is essential for the survival of murine SSCs. LncRNA033862 is expressed in early spermatogonia including SSC and was among 805 lncRNAs identified by global expression profiling as responsive to glial cell-derived neurotrophic factor (GDNF), a growth factor required for SSC self-renewal and survival. LncRNA033862 is an antisense transcript of the GDNF receptor alpha1 (Gfra1) that lacks protein coding potential and regulates Gfra1 expression levels by interacting with Gfra1 chromatin. Importantly, lncRNA033862 knockdown severely impairs SSC survival and their capacity to repopulate recipient testes in a transplantation assay. Collectively, our data provide the first evidence that long non-coding RNAs (lncRNAs) regulate SSC fate.
IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways
Authors: Shi J , Wang H , Guan H , Shi S , Li Y , Wu X , Li N , Yang C , Bai X , Cai W , Yang F , Wang X , Su L , Zheng Z , Hu D
Published: March 2016

Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by excessive hypercellularity and extracellular matrix (ECM) component deposition. Autophagy is a tightly regulated physiological process essential for cellular maintenance, differentiation, development, and homeostasis. Previous studies show that IL10 has potential therapeutic benefits in terms of preventing and reducing HS formation. However, no studies have examined IL10-mediated autophagy during the pathological process of HS formation. Here, we examined the effect of IL10 on starvation-induced autophagy and investigated the molecular mechanism underlying IL10-mediated inhibition of autophagy in HS-derived fibroblasts (HSFs) under starvation conditions. Immunostaining and PCR analysis revealed that a specific component of the IL10 receptor, IL10 alpha-chain (IL10Rα), is expressed in HSFs. Transmission electron microscopy and western blot analysis revealed that IL10 inhibited starvation-induced autophagy and induced the expression of p-AKT and p-STAT3 in HSFs in a dose-dependent manner. Blocking IL10R, p-AKT, p-mTOR, and p-STAT3 using specific inhibitors (IL10RB, LY294002, rapamycin, and cryptotanshinone, respectively) showed that IL10 inhibited autophagy via IL10Rα-mediated activation of STAT3 (the IL10R-STAT3 pathway) and by directly activating the AKT-mTOR pathway. Notably, these results suggest that IL10-mediated inhibition of autophagy is facilitated by the cross talk between STAT3, AKT, and mTOR; in other words, the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways. Finally, the results also indicate that mTOR-p70S6K is the molecule upon which these two pathways converge to induce IL10-mediated inhibition of autophagy in starved HSFs. In summary, the findings reported herein shed light on the molecular mechanism underlying IL10-mediated inhibition of autophagy and suggest that IL10 is a potential therapeutic agent for the treatment of HS.
The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles
Authors: Orme Mariam H. , Liccardi Gianmaria , Moderau Nina , Feltham Rebecca , Wicky-John Sidonie , Tenev Tencho , Aram Lior , Wilson Rebecca , Bianchi Katiuscia , Morris Otto , Monteiro Domingues Celia , Robertson David , Tare Meghana , Wepf Alexander , Williams David , Bergmann Andreas , Gstaiger Matthias , Arama Eli , Ribeiro Paulo S. , Meier Pascal
Published: March 2016

Caspases provide vital links in non-apoptotic regulatory networks controlling inflammation, compensatory proliferation, morphology and cell migration. How caspases are activated under non-apoptotic conditions and process a selective set of substrates without killing the cell remain enigmatic. Here we find that the Drosophila unconventional myosin CRINKLED (CK) selectively interacts with the initiator caspase DRONC and regulates some of its non-apoptotic functions. Loss of CK in the arista, border cells or proneural clusters of the wing imaginal discs affects DRONC-dependent patterning. Our data indicate that CK acts as substrate adaptor, recruiting SHAGGY46/GSK3-β to DRONC, thereby facilitating caspase-mediated cleavage and localized modulation of kinase activity. Similarly, the mammalian CK counterpart, MYO7A, binds to and impinges on CASPASE-8, revealing a new regulatory axis affecting receptor interacting protein kinase-1 (RIPK1)>CASPASE-8 signalling. Together, our results expose a conserved role for unconventional myosins in transducing caspase-dependent regulation of kinases, allowing them to take part in specific signalling events.
Differences in Trait Impulsivity Indicate Diversification of Dog Breeds into Working and Show Lines
Authors: Fadel Fernanda Ruiz , Driscoll Patricia , Pilot Malgorzata , Wright Hannah , Zulch Helen , Mills Daniel
Published: March 2016

Impulsiveness describes the inability to inhibit behaviour in the presence of salient cues. Trait-level impulsivity exists on a continuum and individual differences can be adaptive in different contexts. While breed related differences in behavioural tendency in the domestic dog (Canis familiaris) are well established, the phenomenon within lines of a breed which have been selected more recently is not well studied, although it may challenge the popular notion of breed-typical behaviour. We describe differences in impulsivity between and within two dog breeds with working and show lines selected for different levels of impulsivity: Border Collies (herding work) and Labrador Retrievers (gun work). Recent show line selection might have lessened differences in impulsivity between breeds. We tested this hypothesis on a dataset of 1161 individuals assessed using a validated psychometric tool (Dog Impulsivity Assessment Scale - DIAS). Collies were more impulsive on average, consistent with the original purpose of breed selection. Regarding line, working Collies differed from working Labradors, but show lines from the two breeds were not significantly different. Altered or relaxed artificial selection for behavioural traits when appearance rather than behaviour become the primary focus for breeders may reduce average differences in impulsivity between breeds in show lines.
Carnosic acid slows photoreceptor degeneration in the Pde6brd10 mouse model of retinitis pigmentosa
Authors: Kang Kai , Tarchick Matthew J. , Yu Xiaoshan , Beight Craig , Bu Ping , Yu Minzhong
Published: March 2016

The photoreceptor cell death associated with the various genetic forms of retinitis pigmentosa (RP) is currently untreatable and leads to partial or complete vision loss. Carnosic acid (CA) upregulates endogenous antioxidant enzymes and has proven neuroprotective in studies of neurodegenerative models affecting the brain. In this study, we examined the potential effect of CA on photoreceptor death in the Pde6brd10 mouse model of RP. Our data shows that CA provided morphological and functional preservation of photoreceptors. CA appears to exert its neuroprotective effects through inhibition of oxidative stress and endoplasmic reticulum stress.
Nitrogen acquisition by plants and microorganisms in a temperate grassland
Authors: Liu Qianyuan , Qiao Na , Xu Xingliang , Xin Xiaoping , Han Jessie Yc , Tian Yuqiang , Ouyang Hua , Kuzyakov Yakov
Published: March 2016

Nitrogen (N) limitation is common in most terrestrial ecosystems, often leading to strong competition between microorganisms and plants. The mechanisms of niche differentiation to reduce this competition remain unclear. Short-term15N experiments with NH4+, NO3−and glycine were conducted in July, August and September in a temperate grassland to evaluate the chemical, spatial and temporal niche differentiation by competition between plants and microorganisms for N. Microorganisms preferred NH4+and NO3−, while plants preferred NO3−. Both plants and microorganisms acquired more N in August and September than in July. The soil depth had no significant effects on microbial uptake, but significantly affected plant N uptake. Plants acquired 67% of their N from the 0–5 cm soil layer and 33% from the 5–15 cm layer. The amount of N taken up by microorganisms was at least seven times than plants. Although microorganisms efficiently compete for N with plants, the competition is alleviated through chemical partitioning mainly in deeper soil layer. In the upper soil layer, neither chemical nor temporal niche separation is realized leading to strong competition between plants and microorganisms that modifies N dynamics in grasslands.
Bacterial associations reveal spatial population dynamics in Anopheles gambiae mosquitoes
Authors: Buck Moritz , Nilsson Louise K. J. , Brunius Carl , Dabiré Roch K. , Hopkins Richard , Terenius Olle
Published: March 2016

The intolerable burden of malaria has for too long plagued humanity and the prospect of eradicating malaria is an optimistic, but reachable, target in the 21st century. However, extensive knowledge is needed about the spatial structure of mosquito populations in order to develop effective interventions against malaria transmission. We hypothesized that the microbiota associated with a mosquito reflects acquisition of bacteria in different environments. By analyzing the whole-body bacterial flora of An. gambiae mosquitoes from Burkina Faso by 16 S amplicon sequencing, we found that the different environments gave each mosquito a specific bacterial profile. In addition, the bacterial profiles provided precise and predicting information on the spatial dynamics of the mosquito population as a whole and showed that the mosquitoes formed clear local populations within a meta-population network. We believe that using microbiotas as proxies for population structures will greatly aid improving the performance of vector interventions around the world.
Intracellular acidification is required for full activation of the sweet taste receptor by miraculin
Authors: Sanematsu Keisuke , Kitagawa Masayuki , Yoshida Ryusuke , Nirasawa Satoru , Shigemura Noriatsu , Ninomiya Yuzo
Published: March 2016

Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. The sweet taste induced by MCL is more intense when acidification occurs with weak acids as opposed to strong acids. MCL interacts with the human sweet receptor subunit hTAS1R2, but the mechanisms by which the acidification of MCL activates the sweet taste receptor remain largely unexplored. The work reported here speaks directly to this activation by utilizing a sweet receptor TAS1R2 + TAS1R3 assay. In accordance with previous data, MCL-applied cells displayed a pH dependence with citric acid (weak acid) being right shifted to that with hydrochloric acid (strong acid). When histidine residues in both the intracellular and extracellular region of hTAS1R2 were exchanged for alanine, taste-modifying effect of MCL was reduced or abolished. Stronger intracellular acidification of HEK293 cells was induced by citric acid than by HCl and taste-modifying effect of MCL was proportional to intracellular pH regardless of types of acids. These results suggest that intracellular acidity is required for full activation of the sweet taste receptor by MCL.
Transcriptional induction of the heat shock protein B8 mediates the clearance of misfolded proteins responsible for motor neuron diseases
Authors: Crippa Valeria , D’Agostino Vito G. , Cristofani Riccardo , Rusmini Paola , Cicardi Maria E. , Messi Elio , Loffredo Rosa , Pancher Michael , Piccolella Margherita , Galbiati Mariarita , Meroni Marco , Cereda Cristina , Carra Serena , Provenzani Alessandro , Poletti Angelo
Published: March 2016

Neurodegenerative diseases (NDs) are often associated with the presence of misfolded protein inclusions. The chaperone HSPB8 is upregulated in mice, the human brain and muscle structures affected during NDs progression. HSPB8 exerts a potent pro-degradative activity on several misfolded proteins responsible for familial NDs forms. Here, we demonstrated that HSPB8 also counteracts accumulation of aberrantly localized misfolded forms of TDP-43 and its 25 KDa fragment involved in most sporadic cases of Amyotrophic Lateral Sclerosis (sALS) and of Fronto Lateral Temporal Dementia (FLTD). HSPB8 acts with BAG3 and the HSP70/HSC70-CHIP complex enhancing the autophagic removal of misfolded proteins. We performed a high-through put screening (HTS) to find small molecules capable of inducing HSPB8 in neurons for therapeutic purposes. We identified two compounds, colchicine and doxorubicin, that robustly up-regulated HSPB8 expression. Both colchicine and doxorubicin increased the expression of the master regulator of autophagy TFEB, the autophagy linker p62/SQSTM1 and the autophagosome component LC3. In line, both drugs counteracted the accumulation of TDP-43 and TDP-25 misfolded species responsible for motoneuronal death in sALS. Thus, analogs of colchicine and doxorubicin able to induce HSPB8 and with better safety and tolerability may result beneficial in NDs models.
Insight into determinants of substrate binding and transport in a multidrug efflux protein
Authors: Alegre Kamela O. , Paul Stephanie , Labarbuta Paola , Law Christopher J.
Published: March 2016

Multidrug resistance arising from the activity of integral membrane transporter proteins presents a global public health threat. In bacteria such as Escherichia coli, transporter proteins belonging to the major facilitator superfamily make a considerable contribution to multidrug resistance by catalysing efflux of myriad structurally and chemically different antimicrobial compounds. Despite their clinical relevance, questions pertaining to mechanistic details of how these promiscuous proteins function remain outstanding and the role(s) played by individual amino acid residues in recognition, binding and subsequent transport of different antimicrobial substrates by multidrug efflux members of the major facilitator superfamily requires illumination. Using in silico homology modelling, molecular docking and mutagenesis studies in combination with substrate binding and transport assays, we identified several amino acid residues that play important roles in antimicrobial substrate recognition, binding and transport by Escherichia coli MdtM, a representative multidrug efflux protein of the major facilitator superfamily. Furthermore, our studies suggested that ‘aromatic clamps’ formed by tyrosine and phenylalanine residues located within the substrate binding pocket of MdtM may be important for antimicrobial substrate recognition and transport by the protein. Such ‘clamps’ may be a structurally and functionally important feature of all major facilitator multidrug efflux proteins.
Dynamics of spinal microglia repopulation following an acute depletion
Authors: Yao Yao , Echeverry Stefania , Shi Xiang Qun , Yang Mu , Yang Qiu Zi , Wang Guan Yun Frances , Chambon Julien , Wu Yi Chen , Fu Kai Yuan , De Koninck Yves , Zhang Ji
Published: March 2016

Our understanding on the function of microglia has been revolutionized in the recent 20 years. However, the process of maintaining microglia homeostasis has not been fully understood. In this study, we dissected the features of spinal microglia repopulation following an acute partial depletion. By injecting intrathecally Mac-1-saporin, a microglia selective immunotoxin, we ablated 50% microglia in the spinal cord of naive mice. Spinal microglia repopulated rapidly and local homeostasis was re-established within 14 days post-depletion. Mac-1-saporin treatment resulted in microglia cell proliferation and circulating monocyte infiltration. The latter is indeed part of an acute, transient inflammatory reaction that follows cell depletion and was characterized by an increase in the expression of inflammatory molecules and by the breakdown of the blood spinal cord barrier. During this period, microglia formed cell clusters and exhibited a M1-like phenotype. MCP-1/CCR2 signaling was essential in promoting this depletion associated spinal inflammatory reaction. Interestingly, ruling out MCP-1-mediated secondary inflammation, including blocking recruitment of monocyte-derived microglia, did not affect depletion-triggered microglia repopulation. Our results also demonstrated that newly generated microglia kept their responsiveness to peripheral nerve injury and their contribution to injury-associated neuropathic pain was not significantly altered.
Overcoming doxorubicin resistance of cancer cells by Cas9-mediated gene disruption
Authors: Ha Jong Seong , Byun Juyoung , Ahn Dae-Ro
Published: March 2016

In this study, Cas9 system was employed to down-regulate mdr1 gene for overcoming multidrug resistance of cancer cells. Disruption of the MDR1 gene was achieved by delivery of the Cas9-sgRNA plasmid or the Cas9-sgRNA ribonucleoprotein complex using a conventional gene transfection agent and protein transduction domain (PTD). Doxorubicin showed considerable cytotoxicity to the drug-resistant breast cancer cells pre-treated with the RNA-guided endonuclease (RGEN) systems, whereas virtually non-toxic to the untreated cells. The potency of drug was enhanced in the cells treated with the protein-RNA complex as well as in those treated with plasmids, suggesting that mutation of the mdr1 gene by intracellular delivery of Cas9-sgRNA complex using proper protein delivery platforms could recover the drug susceptibility. Therefore, Cas9-mediated disruption of the drug resistance-related gene can be considered as a promising way to overcome multidrug resistance in cancer cells.
In vivo visualization and quantification of collecting lymphatic vessel contractility using near-infrared imaging
Authors: Chong Chloé , Scholkmann Felix , Bachmann Samia B. , Luciani Paola , Leroux Jean-Christophe , Detmar Michael , Proulx Steven T.
Published: March 2016

Techniques to image lymphatic vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting lymphatic vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting lymphatic vessel function in mice, and to establish anin vivosystem for evaluation of contractile agonists and antagonists using near-infrared fluorescence imaging. The flank collecting lymphatic vessel in mice was exposed using a surgical technique and a near-infrared tracer was infused into the inguinal lymph node. Collecting lymphatic vessel contractility and valve function could be easily visualized after the infusion. A diameter tracking method was established and the diameter of the vessel was found to closely correlate to near-infrared fluorescence signal. Phasic contractility measures of frequency and amplitude were established using an automated algorithm. The methods were validated by tracking the vessel response to topical application of a contractile agonist, prostaglandin F2α, and by demonstrating the potential of the technique for non-invasive evaluation of modifiers of lymphatic function. These new methods will enable high-resolution imaging and quantification of collecting lymphatic vessel function in animal models and may have future clinical applications.
Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice
Authors: Matsushita Yuki , Sakai Yasunari , Shimmura Mitsunori , Shigeto Hiroshi , Nishio Miki , Akamine Satoshi , Sanefuji Masafumi , Ishizaki Yoshito , Torisu Hiroyuki , Nakabeppu Yusaku , Suzuki Akira , Takada Hidetoshi , Hara Toshiro
Published: March 2016

Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8–10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6–8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain.
New fossil insect order Permopsocida elucidates major radiation and evolution of suction feeding in hemimetabolous insects (Hexapoda: Acercaria)
Authors: Huang Di-Ying , Bechly Günter , Nel Patricia , Engel Michael S. , Prokop Jakub , Azar Dany , Cai Chen-Yang , van de Kamp Thomas , Staniczek Arnold H. , Garrouste Romain , Krogmann Lars , dos Santos Rolo Tomy , Baumbach Tilo , Ohlhoff Rainer , Shmakov Alexey S. , Bourgoin Thierry , Nel André
Published: March 2016

With nearly 100,000 species, the Acercaria (lice, plant lices, thrips, bugs) including number of economically important species is one of the most successful insect lineages. However, its phylogeny and evolution of mouthparts among other issues remain debatable. Here new methods of preparation permitted the comprehensive anatomical description of insect inclusions from mid-Cretaceous Burmese amber in astonishing detail. These “missing links” fossils, attributed to a new order Permopsocida, provide crucial evidence for reconstructing the phylogenetic relationships in the Acercaria, supporting its monophyly, and questioning the position of Psocodea as sister group of holometabolans in the most recent phylogenomic study. Permopsocida resolves as sister group of Thripida + Hemiptera and represents an evolutionary link documenting the transition from chewing to piercing mouthparts in relation to suction feeding. Identification of gut contents as angiosperm pollen documents an ecological role of Permopsocida as early pollen feeders with relatively unspecialized mouthparts. This group existed for 185 million years, but has never been diverse and was superseded by new pollenivorous pollinators during the Cretaceous co-evolution of insects and flowers. The key innovation of suction feeding with piercing mouthparts is identified as main event that triggered the huge post-Carboniferous radiation of hemipterans, and facilitated the spreading of pathogenic vectors.
Circulating human cytomegalovirus-encoded HCMV-miR-US4-1 as an indicator for predicting the efficacy of IFNα treatment in chronic hepatitis B patients
Authors: Pan Yi , Wang Nan , Zhou Zhenxian , Liang Hongwei , Pan Chaoyun , Zhu Dihan , Liu Fenyong , Zhang Chen-Yu , Zhang Yujing , Zen Ke
Published: March 2016

The efficacy of interferon α (IFNα) therapy for chronic hepatitis B (CHB) patients is about 40% and often associates with adverse side-effects, thus identification of an easy accessible biomarker that can predict the outcome of IFNα treatment for individual CHB patients would be greatly helpful. Recent reports by us and others show that microRNAs encoded by human cytomegalovirus (HCMV) were readily detected in human serum and can interfere with lymphocyte responses required by IFNα therapeutic effect. We thus postulate that differential expression profile of serum HCMV miRNAs in CHB patients may serve as indicator to predict the efficacy of IFNα treatment for CHB patients. Blood was drawn from 56 individual CHB patients prior to IFNα treatment. By quantifying 13 HCMV miRNAs in serum samples, we found that the levels of HCMV-miR-US4-1 and HCMV-miR-UL-148D were significantly higher in IFNα-responsive group than in IFNα-non-responsive group. In a prospective study of 96 new CHB patients, serum level of HCMV-miR-US4-1 alone classified those who were and were not responsive to IFN-α treatment with correct rate of 84.00% and 71.74%, respectively. In conclusion, our results demonstrate that serum HCMV-miR-US4-1 can serve as a novel biomarker for predicting the outcome of IFNα treatment in CHB patients.
Colorimetric method for rapid detection of Oxacillin resistance in Staphylococcus aureus and its comparison with PCR for mec A gene
Authors: Ghanwate Niraj , Thakare Prashant , Bhise P. R. , Gawande Sonali
Published: March 2016

Rapid and accurate detection of Methicillin Resistant Staphylococcus aureus (MRSA) is an important role of clinical microbiology laboratories to avoid treatment failure. The detection of MRSA is based on phenotypic assays which require at least 24 h to perform. Detection of the mecA gene or of PBP 2a is the “gold standard”, but not always available. The aim of this study was to evaluate a rapid method for detection of MRSA by using 3 (4, 5 dimethyl thiazole -2-yl) -2, 5 diphenyl tetrazolium bromide (MTT). Total 126 isolates of MRSA were collected from tertiary healthcare center and were confirmed by oxacillin screening agar test as per CLSI guidelines. Amplification of mecA gene was performed by using PCR. MTT assay was carried out for all the isolates in 96 well Microtitre plate and compared with standard methods of CLSI. Out of 126 isolates, 98 were found to be mecA positive. MTT method was found to be 98.98% sensitive and 96.43% specific. The MTT based colorimetric method is rapid and simple test for screening of oxacillin resistance in Staphylococcus aureus. It significantly shortens the time to just 7 h required to obtained a drug susceptibility test and could be useful to screen MRSA.
FNDC5 is produced in the stomach and associated to body composition
Authors: Barja-Fernández S. , Folgueira C. , Castelao C. , Al-Massadi O. , Bravo S. B. , Garcia-Caballero T. , Leis R. , Pardo M. , Casanueva F. F. , Seoane L. M.
Published: March 2016

The fibronectin type III domain-containing protein 5 (FNDC5) discovered in 2002 has recently gained attention due to its potential role in protecting against obesity. In rat, no data exist regarding FNDC5 production and regulation in the stomach. The aim of the present work was to determine the expression of FNDC5 in the rat stomach and its potential regulation by body composition. The present data shows FNDC5 gene expression in the gastric mucosa. Immunohistochemical studies found FNDC5 immunopositivity in chief cells of gastric tissue. By the use of three different antibodies FNDC5 was found expressed in gastric mucosa and secreted by the stomach. The rate of gastric FNDC5 secretion parallels the circulating levels of FNDC5. The body fat mass increase after intervention with high fat diet coincided with a decrease in the secretion of FNDC5 from the stomach and a diminution in the FNDC5 circulating levels. In summary, the present data shows, for the first time, the expression of FNDC5 in the stomach of rats and its regulation by body composition, suggesting a potential role of gastric FNDC5 in energy homeostasis.
High desolvation temperature facilitates the ESI-source H/D exchange at non-labile sites of hydroxybenzoic acids and aromatic amino acids
Authors: Zherebker Alexander , Kostyukevich Yury , Kononikhin Alexey , Roznyatovsky Vitaliy A. , Popov Igor , Grishin Yuri K. , Perminova Irina V. , Nikolaev Eugene
Published: March 2016

H/D exchange coupled with high-resolution mass spectrometry has become a powerful analytical approach for structural investigations of complex organic matrices.
Synthesis and thermodynamic study of transition metal ion (Mn2+, Co2+, Cu2+, and Zn2+) exchanged zeolites A and Y
Authors: Wu Lili , Navrotsky Alexandra
Published: March 2016

The enthalpy of formation and ion exchange for transition metal containing zeolites A and Y were investigated by calorimetry.
Hierarchical photocatalysts
Authors: Li Xin , Yu Jiaguo , Jaroniec Mietek
Published: March 2016

The design, fabrication, performance and applications of hierarchical semiconductor photocatalysts are thoroughly reviewed and apprised.
Polymer nanocomposites from self-assembled polystyrene-grafted carbon nanotubes
Authors: Oliveira Elaine Y. S. , Bode Ralf , Escárcega-Bobadilla Martha V. , Zelada-Guillén Gustavo A. , Maier Gerhard
Published: March 2016

Supramolecular self-assembly and anisotropic patchiness generate long-range networks in polymer-grafted carbon nanotubes, opening new possibilities using industrially attractive processes.
Upconversion nanoparticles with a strong acid-resistant capping
Authors: Recalde Ileana , Estebanez Nestor , Francés-Soriano Laura , Liras Marta , González-Béjar María , Pérez-Prieto Julia
Published: March 2016

β-NaYF4:Yb3+,Er3+ upconversion nanoparticles coated with a thin shell of a biocompatible copolymer comprising 2-hydroxyethylmethacrylate and 2-acrylamido-2-methyl-1-propanesulfonsulfonic acid are water-dispersible and remarkably resistant to strong acidic conditions.
Research on the post-chain extension of aqueous polyurethane dispersions
Authors: Peng Xiaomeng , Wang Wusheng , Ma Naiyu , Guo Wenhe , Yu Xuekang , Chen Xin
Published: March 2016

The post-chain extension efficiency of APUDs were influenced by the particle size and the “cage effect” whatever the water or polyamine as the chain extender. The post-chain reaction mechanism: (a) small particle size; (b) big particle size.
pHEMA hydrogels with pendant triazinyl-β-cyclodextrin as an efficient and recyclable reservoir for loading and release of plant-based mosquito repellents: a new aqueous mosquito repellent formulation
Authors: Delong Wang , Weibin Ma , Mingchen Jia , Zhonglin Yang , Juntao Feng , Xing Zhang
Published: March 2016

Poly(2-hydroxyethyl methacrylate) hydrogels with pendant β-cyclodextrins as an efficient and recyclable reservoir for loading and release of plant-based mosquito repellents.
Dynamic hysteresis and scaling behaviours of lead-free 0.94Bi0.5Na0.5TiO3–0.06BaTiO3 bulk ceramics
Authors: Wang Chun-Ming , Lau Kenny , Wang Qian
Published: March 2016

The dynamic hysteresis and scaling behaviours of MPB composition BNT-6BT were investigated, which exhibits three-stage evolution of scaling behaviors at medium-high frequency and two-stage linear scaling behaviors at low frequency in the E0 term.
Design of a dual-bed catalyst system with microporous carbons and urea-supported mesoporous carbons for highly effective removal of NOx at room temperature
Authors: Li Jun , Yin Di , Long Donghui , Wang Jitong , Ling Licheng , Qiao Wenming
Published: March 2016

A dual-bed catalyst system is designed for highly effective remove of NOx at room temperature, which consists of a microporous spherical activated carbon (SAC) layer and a urea-supported spherical mesoporous carbon (SMC) layer.
Overcharge protection of lithium-ion batteries above 4 V with a perfluorinated phenothiazine derivative
Authors: Kaur Aman Preet , Casselman Matthew D. , Elliott Corrine F. , Parkin Sean R. , Risko Chad , Odom Susan A.
Published: March 2016

A new fluorinated phenothiazine derivative mitigates excess current in an overcharging lithium-ion cell containing a high-voltage cathode by shuttling it across the electrolyte via redox reactions at the electrode/electrolyte interfaces.
Photo-/cathodoluminescence and energy transfer properties of novel Ce3+singly doped and Ce3+/Tb3+codoped NaBaScSi2O7phosphors
Authors: Li Gen , Wang Yuhua , Zeng Wei , Chen Wenbo , Han Shaochun , Guo Haijie , Li Yanyan
Published: March 2016

A series of novel Ce3+singly doped and Ce3+/Tb3+codoped color-tunable NaBaScSi2O7phosphors were synthesizedviathe solid state method.
Rational syntheses of helical π-conjugated oligopyrrins with a bipyrrole linkage: geometry control of bis-copper(ii) coordination
Authors: Zhang Kai , Savage Mathew , Li Xin , Jiang Yu , Ishida Masatoshi , Mitsuno Koki , Karasawa Satoru , Kato Tatsuhisa , Zhu Weihua , Yang Sihai , Furuta Hiroyuki , Xie Yongshu
Published: March 2016

Rational syntheses of long-chain helical π-conjugated oligopyrrins and their bis-copper complexes afford systematically modulated optical and magnetic properties.
Synergistic action of thermoresponsive and hygroresponsive elements elicits rapid and directional response of a bilayer actuator
Authors: Zhang Lidong , Desta Israel , Naumov Panče
Published: March 2016

A bilayer actuator composed of thermoresponsive and thermo/hygroresponsive elements is developed, which undergoes fast, directional and autonomous curling with a speed of up to 0.7 m s−1and recovers its shape by hydration.
Spectroscopic and kinetic evidence for redox cycling, catalase and degradation activities of MnIII(TPPS) in a basic aqueous peroxide medium
Authors: Procner M. , Orzeł Ł. , Stochel G. , van Eldik R.
Published: March 2016

MnIII(TPPS) is oxidized by an excess of hydrogen peroxide in basic aqueous solution to yield MnV(TPPS) and/or MnIVTPPS, and subsequently reduced back to MnIII(TPPS) to reveal redox cycling, catalase and degradation activities.
Organometallic molecular wires as versatile modules for energy-level alignment of the metal–molecule–metal junction
Authors: Sugimoto Kaho , Tanaka Yuya , Fujii Shintaro , Tada Tomofumi , Kiguchi Manabu , Akita Munetaka
Published: March 2016

Organometallic Ru molecular wires show significantly higher conductance compared to their organic counterpart due to high-lying HOMOs.
Ether and siloxane functionalized ionic liquids and their mixtures as electrolyte for lithium-ion batteries
Authors: Chavan Santosh N. , Tiwari Aarti , Nagaiah Tharamani C. , Mandal Debaprasad
Published: March 2016

The present study deals with an investigation of two novel imidazolium ionic liquids bearing ether–ether (1O2O2-Im-2O1) or ether–siloxane (1O2O2-Im-1SiOSi) functionalities with TFSI anion and their mixtures with propylene carbonate as electrolytes in lithium-ion batteries.
Intramolecular sensitization of americium luminescence in solution: shining light on short-lived forbidden 5f transitions
Authors: Sturzbecher-Hoehne M. , Yang P. , D'Aléo A. , Abergel R. J.
Published: March 2016

Multidentate chromophore-bearing ligands are used to sensitize luminescence emission from trivalent americium, providing insight on the resulting complex coordination properties.