bluuebunny/crossref_metadata_2025 huggingface dataset:
(Un)separated by a common language?
Authors: Murphy M. Lynne
Published: February 2016

Interest in the differences between English in Britain (or more especially England) and the United States supports a small industry, of which I am a small part. But there are those who argue that the differences are so negligible that they are not worth investigating. One of these is University of Edinburgh Professor of General Linguistics Geoffrey Pullum, who wrote a post on the topic for the Lingua Franca blog of the Chronicle of Higher Education. Pullum (2014) concluded:

Looked at seriously, the tiny differences between standard American and standard British English are trivial, barely even worth mentioning.

Pullum was motivated to make this argument for good reasons. He was fighting the exaggeration of the differences and pointing out that Britons and Americans generally understand each other well in spite of whatever differences there are. But at the same time, Pullum's argument rests on oversimplifications, just like the claims that he hopes to counter.
Seroprevalence of West Nile and Usutu viruses in military working horses and dogs, Morocco, 2012: dog as an alternative WNV sentinel species?
Authors: DURAND B. , HASKOURI H. , LOWENSKI S. , VACHIERY N. , BECK C. , LECOLLINET S.
Published: February 2016

A serosurvey of 349 military working horses and 231 military working dogs was conducted in ten sites in Morocco in 2012. This survey revealed a high level of exposure of these animals to flaviviruses: seroprevalence rates of 60% in horses and of 62% in dogs were observed using a competitive West Nile virus (WNV) enzyme-linked immunosorbent assay (cELISA). Seroneutralization test results showed that the majority of cELISA-positive results were due to exposure to WNV. Further assays conducted in vaccinated horses with a DIVA (Differentiating Infected from Vaccinated Animals) test indicated that anti-WNV antibodies had been stimulated through WNV natural infection. Moreover, in both species, seroneutralization tests suggested an exposure to Usutu virus (USUV). Data analysis did not show any significant difference of cELISA seropositivity risk between horses and dogs. Dogs may thus represent an interesting alternative to equines for the serological surveillance of WNV or USUV circulation, especially in areas where equine vaccination precludes passive surveillance (based on the detection of West Nile fever cases) in horses.
Description of Medication Administration by Emergency Medical Services during Mass-casualty Incidents in the United States
Authors: El Sayed Mazen , Tamim Hani , Mann N. Clay
Published: February 2016

Background

Emergency Medical Services (EMS) preparedness and availability of essential medications are important to reduce morbidity and mortality from mass-casualty incidents (MCIs).

Objectives

This study describes prehospital medication administration during MCIs by different EMS service levels.

Methods

The US National EMS Public-Release Research Dataset maintained by the National Emergency Medical Services Information System (NEMSIS) was used to carry out the study. Emergency Medical Services activations coded as MCI at dispatch, or by EMS personnel, were included. The Center for Medicare and Medicaid Services (CMS) service level was used for the level of service provided. A descriptive analysis of medication administration by EMS service level was carried out.

Results

Among the 19,831,189 EMS activations, 53,334 activations had an MCI code, of which 26,110 activations were included. There were 8,179 (31.3%) Advanced Life Support (ALS), 5,811 (22.3%) Basic Life Support (BLS), 399 (1.5%) Air Medical Transport (AMT; fixed or rotary), and 38 (0.2%) Specialty Care Transport (SCT) activations. More than 80 different medications from 18 groups were reported. Seven thousand twenty-one activations (26.9%) had at least one medication administered. Oxygen was most common (16.3%), followed by crystalloids (6.9%), unknown (5.2%), analgesics (3.2%) mainly narcotics, antiemetics (1.5%), cardiac/vasopressors/inotropes (0.9%), bronchodilators (0.9%), sedatives (0.8%), and vasodilators/antihypertensives (0.7%). Overall, medication administration rates and frequencies of medications groups significantly varied between EMS service levels (P<.01) except for “Analgesia (other)” (P=.40) and “Pain medications (nonsteroidal anti-inflammatory drug; NSAID)” (P=.07).

Conclusion

Medications are administered frequently in MCIs, mainly Oxygen, crystalloids, and narcotic pain medications. Emergency Medical Services systems can use the findings of this study to better prepare their stockpiles for MCIs.

El SayedM, TamimH, MannNC. Description of medication administration by Emergency Medical Services during mass-casualty incidents in the United States. Prehosp Disaster Med. 2016;31(2):141–149.
Radiologie-Update Ultraschall-Elastografie – Quintessenz für die Praxis
Authors: Franckenberg Sabine , Gubler Christoph , Frauenfelder Thomas , Rominger Marga
Published: February 2016

Zusammenfassung. Die Ultraschall-Elastografie visualisiert und misst die Elastizität von Gewebe. Abhängig von der jeweilig verwendeten Methode gibt es im Wesentlichen vier Typen der Elastografie: Strain-Elastografie (SE), Transiente Elastografie (TE), Acoustic Radiation Force Impulse Imaging (ARFI) und Shear-Wave-Elastografie (SWE). Da pathologisch verändertes Gewebe meistens eine niedrigere Elastizität aufweist als gesundes, kann die Ultraschall-Elastografie zur initalen Diagnostik und zur Verlaufskontrolle von Erkrankungen wie Leberfibrose und -zirrhose, zur ergänzenden Diagnostik bei suspekten Brustbefunden, Schilddrüsenknoten, Prostatakarzinom und vielen weiteren Organerkrankungen verwendet werden. Zum aktuellen Zeitpunkt kann die Ultraschall-Elastografie noch keine standardisierten Diagnostik-Verfahren ersetzen, diese aber sinnvoll ergänzen.
Tumour‐specific CD4 T cells eradicate melanoma via indirect recognition of tumour‐derived antigen
Authors: Shklovskaya Elena , Terry Alexandra M , Guy Thomas V , Buckley Adrian , Bolton Holly A , Zhu Erhua , Holst Jeff , Fazekas de St Groth Barbara
Published: February 2016

The importance of CD4 T cells in tumour immunity has been increasingly recognised, with recent reports describing robust CD4 T cell‐dependent tumour control in mice whose immune‐regulatory mechanisms have been disturbed by irradiation, chemotherapy, immunomodulatory therapy and/or constitutive immunodeficiency. Tumour control in such models has been attributed in large part to direct Major Histocompatibility Complex (MHC) class II‐dependent CD4 T cell killing of tumour cells. To test whether CD4 T cells can eradicate tumours without directly killing tumour cells, we developed an animal model in which tumour‐derived antigen could be presented to T‐cell receptor (TCR)‐transgenic CD4 T cells by host but not tumour MHC class II molecules. In I‐E+ mice bearing I‐Enull tumours, naive I‐E‐restricted CD4 T cells proliferated locally in tumour‐draining lymph nodes after recognising tumour‐derived antigen on migratory dendritic cells. In lymphopaenic but not immunosufficient hosts, CD4 T cells differentiated into polarised T helper type 1 (Th1) cells expressing interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα) and interleukin (IL)‐2 but little IL‐17, and cleared established tumours. Tumour clearance was enhanced by higher TCR affinity for tumour antigen‐MHC class II and was critically dependent on IFNγ, as demonstrated by early tumour escape in animals treated with an IFNγ blocking antibody. Thus, CD4 T cells and IFNγ can control tumour growth without direct T‐cell killing of tumour cells, and without requiring additional adaptive immune cells such as CD8 T cells and B cells. Our results support a role for effective CD4 T cell‐dependent tumour immunity against MHC class II‐negative tumours.
Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103-mediated suppression of KLF4
Authors: Hartmann Petra , Zhou Zhe , Natarelli Lucia , Wei Yuanyuan , Nazari-Jahantigh Maliheh , Zhu Mengyu , Grommes Jochen , Steffens Sabine , Weber Christian , Schober Andreas
Published: February 2016

MicroRNAs regulate the maladaptation of endothelial cells (ECs) to naturally occurring disturbed blood flow at arterial bifurcations resulting in arterial inflammation and atherosclerosis in response to hyperlipidemic stress. Here, we show that reduced endothelial expression of the RNAse Dicer, which generates almost all mature miRNAs, decreases monocyte adhesion, endothelial C–X–C motif chemokine 1 (CXCL1) expression, atherosclerosis and the lesional macrophage content in apolipoprotein E knockout mice (Apoe−/−) after exposure to a high-fat diet. Endothelial Dicer deficiency reduces the expression of unstable miRNAs, such as miR-103, and promotes Krüppel-like factor 4 (KLF4)-dependent gene expression in murine atherosclerotic arteries. MiR-103 mediated suppression of KLF4 increases monocyte adhesion to ECs by enhancing nuclear factor-κB-dependent CXCL1 expression. Inhibiting the interaction between miR-103 and KLF4 reduces atherosclerosis, lesional macrophage accumulation and endothelial CXCL1 expression. Overall, our study suggests that Dicer promotes endothelial maladaptation and atherosclerosis in part by miR-103-mediated suppression of KLF4.
A role for Mfb1p in region-specific anchorage of high-functioning mitochondria and lifespan in Saccharomyces cerevisiae
Authors: Pernice Wolfgang M. , Vevea Jason D. , Pon Liza A.
Published: February 2016

Previous studies indicate that replicative lifespan in daughter cells of Sacchraromyces cerevisiae depends on the preferential inheritance of young, high-functioning mitochondria. We report here that mitochondria are functionally segregated even within single mother cells in S. cerevisiae. A high-functioning population of mitochondria accumulates at the tip of the mother cell distal to the bud. We find that the mitochondrial F-box protein (Mfb1p) localizes to mitochondria in the mother tip and is required for mitochondrial anchorage at that site, independent of the previously identified anchorage protein Num1p. Deletion of MFB1 results in loss of the mother-tip-localized mitochondrial population, defects in mitochondrial function and premature replicative ageing. Inhibiting mitochondrial inheritance to buds, by deletion of MMR1, in mfb1Δ cells restores mitochondrial distribution, promotes mitochondrial function and extends replicative lifespan. Our results identify a mechanism that retains a reservoir of high-functioning mitochondria in mother cells and thereby preserves maternal reproductive capacity.
Intracellular mGluR5 plays a critical role in neuropathic pain
Authors: Vincent Kathleen , Cornea Virginia M. , Jong Yuh-Jiin I. , Laferrière André , Kumar Naresh , Mickeviciute Aiste , Fung Jollee S. T. , Bandegi Pouya , Ribeiro-da-Silva Alfredo , O’Malley Karen L. , Coderre Terence J.
Published: February 2016

Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which ∼60% is located on nuclear membranes, where activation leads to sustained Ca2+responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor-mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expressionin vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain.
Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson’s Disease
Authors: Borchert Robin J , Rittman Timothy , Passamonti Luca , Ye Zheng , Sami Saber , Jones Simon P , Nombela Cristina , Vázquez Rodríguez Patricia , Vatansever Deniz , Rae Charlotte L , Hughes Laura E , Robbins Trevor W , Rowe James B
Published: February 2016

Cognitive impairment is common in Parkinson’s disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest (‘task-free’) provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.
Mathematical modelling of phenotypic plasticity and conversion to a stem-cell state under hypoxia
Authors: Dhawan Andrew , Madani Tonekaboni Seyed Ali , Taube Joseph H. , Hu Stephen , Sphyris Nathalie , Mani Sendurai A. , Kohandel Mohammad
Published: February 2016

Hypoxia, or oxygen deficiency, is known to be associated with breast tumour progression, resistance to conventional therapies and poor clinical prognosis. The epithelial-mesenchymal transition (EMT) is a process that confers invasive and migratory capabilities as well as stem cell properties to carcinoma cells thus promoting metastatic progression. In this work, we examined the impact of hypoxia on EMT-associated cancer stem cell (CSC) properties, by culturing transformed human mammary epithelial cells under normoxic and hypoxic conditions and applying in silico mathematical modelling to simulate the impact of hypoxia on the acquisition of CSC attributes and the transitions between differentiated and stem-like states. Our results indicate that both the heterogeneity and the plasticity of the transformed cell population are enhanced by exposure to hypoxia, resulting in a shift towards a more stem-like population with increased EMT features. Our findings are further reinforced by gene expression analyses demonstrating the upregulation of EMT-related genes, as well as genes associated with therapy resistance, in hypoxic cells compared to normoxic counterparts. In conclusion, we demonstrate that mathematical modelling can be used to simulate the role of hypoxia as a key contributor to the plasticity and heterogeneity of transformed human mammary epithelial cells.
Chitinases and Imaginal disc growth factors organize the extracellular matrix formation at barrier tissues in insects
Authors: Pesch Yanina-Yasmin , Riedel Dietmar , Patil Kapil R , Loch Gerrit , Behr Matthias
Published: February 2016

The cuticle forms an apical extracellular-matrix (ECM) that covers exposed organs, such as epidermis, trachea and gut, for organizing morphogenesis and protection of insects. Recently, we reported that cuticle proteins and chitin are involved in ECM formation. However, molecular mechanisms that control assembly, maturation and replacement of the ECM and its components are not well known. Here we investigated the poorly described glyco-18-domain hydrolase family in Drosophila and identified the Chitinases (Chts) and imaginal-disc-growth-factors (Idgfs) that are essential for larval and adult molting. We demonstrate that Cht and idgf depletion results in deformed cuticles, larval and adult molting defects and insufficient protection against wounding and bacterial infection, which altogether leads to early lethality. We show that Cht2/Cht5/Cht7/Cht9/Cht12 and idgf1/idgf3/idgf4/idgf5/idgf6 are needed for organizing proteins and chitin-matrix at the apical cell surface. Our data indicate that normal ECM formation requires Chts, which potentially hydrolyze chitin-polymers. We further suggest that the non-enzymatic idgfs act as structural proteins to maintain the ECM scaffold against chitinolytic degradation. Conservation of Chts and Idgfs proposes analogous roles in ECM dynamics across the insect taxa, indicating that Chts/Idgfs are new targets for species specific pest control.
Domain swapping oligomerization of thermostable c-type cytochrome in E. coli cells
Authors: Hayashi Yugo , Yamanaka Masaru , Nagao Satoshi , Komori Hirofumi , Higuchi Yoshiki , Hirota Shun
Published: February 2016

Knowledge on domain swappingin vitrois increasing, but domain swapping may not occur regularlyin vivoand its information in cells is limited. Herein, we show that domain-swapped oligomers of a thermostablec-type cytochrome,Hydrogenobacter thermophiluscytc552, are formed inE. coliwhich expresses cytc552. The region containing the N-terminal α-helix and heme was domain-swapped between protomers in the dimer formed inE. coli. The amount of cytc552oligomers increased inE. colias the cytc552concentration was increased, whereas that of high-order oligomers decreased in the order of decrease in protein stability, indicating that domain swapping decreases in cells when the protein stability decreases. Apo cytc552was detected in the cytc552oligomer formed inE. coli, but not in that of the A5F/M11V/Y32F/Y41E/I76V mutant. The cytc552oligomer containing its apo protein may form at the periplasm, since the apo protein detected by mass measurements did not contain the signal peptide. These results show that domain-swapped cytc552oligomers were formed inE. coli, owing to the stability of the transient oligomer containing the apo protein before heme attachment. This is an indication that exceedingly stable proteins may have disadvantages forming domain-swapped oligomers in cells.
DNA barcoding reveals a mysterious high species diversity of conifer-feeding aphids in the mountains of southwest China
Authors: Chen Rui , Jiang Li-Yun , Chen Jing , Qiao Ge-Xia
Published: February 2016

The mountains of southwest China are one of the hot spots of biodiversity in the world. However, the high-altitude fauna that inhabit these mountains remain a mystery. In this study, the species diversity of the aphids of the genusCinarafrom the high-altitude coniferous forests was first assessed and then the processes and the mechanisms of speciation were discussed. Three hundreds and four aphid samples that contained 3040 individuals were collected during fourteen field surveys. The molecular clusters derived from the DNA barcodes were used to explore the species diversity. Notably, the aphid alpha-diversity was high, with as many as 94 candidate species and furthermore, 86.2% of the species collected had not been previously recorded. The centers of aphid species richness corresponded to the distributional pattern of the diversity of the host conifer plant species. The divergence time revealed that following the uplift of the Qinghai-Tibetan Plateau during the Pleistocene, the changes in the climate, ecology and host habitats were likely the most important factors that drove the rapid process of evolutionary radiation in the aphids. Our findings revealed the high species diversity of the aphids with DNA barcoding.
Hemoglobin-carbon nanotube derived noble-metal-free Fe5C2-based catalyst for highly efficient oxygen reduction reaction
Authors: Vij Varun , Tiwari Jitendra N. , Lee Wang-Geun , Yoon Taeseung , Kim Kwang S.
Published: February 2016

High performance non-precious cathodic catalysts for oxygen reduction reaction (ORR) are vital for the development of energy materials and devices. Here, we report an noble metal free, Fe5C2 nanoparticles-studded sp2 carbon supported mesoporous material (CNTHb-700) as cathodic catalyst for ORR, which was prepared by pyrolizing the hybrid adduct of single walled carbon nanotubes (CNT) and lyophilized hemoglobin (Hb) at 700 °C. The catalyst shows onset potentials of 0.92 V in 0.1 M HClO4 and in 0.1 M KOH which are as good as commercial Pt/C catalyst, giving very high current density of 6.34 and 6.69 mA cm−2 at 0.55 V vs. reversible hydrogen electrode (RHE), respectively. This catalyst has been confirmed to follow 4-electron mechanism for ORR and shows high electrochemical stability in both acidic and basic media. Catalyst CNTHb-700 possesses much higher tolerance towards methanol than the commercial Pt/C catalyst. Highly efficient catalytic properties of CNTHb-700 could lead to fundamental understanding of utilization of biomolecules in ORR and materialization of proton exchange membrane fuel cells for clean energy production.
Transthyretin participates in beta-amyloid transport from the brain to the liver- involvement of the low-density lipoprotein receptor-related protein 1?
Authors: Alemi Mobina , Gaiteiro Cristiana , Ribeiro Carlos Alexandre , Santos Luís Miguel , Gomes João Rodrigues , Oliveira Sandra Marisa , Couraud Pierre-Olivier , Weksler Babette , Romero Ignacio , Saraiva Maria João , Cardoso Isabel
Published: February 2016

Transthyretin (TTR) binds Aβ peptide, preventing its deposition and toxicity. TTR is decreased in Alzheimer’s disease (AD) patients. Additionally, AD transgenic mice with only one copy of the TTR gene show increased brain and plasma Aβ levels when compared to AD mice with both copies of the gene, suggesting TTR involvement in brain Aβ efflux and/or peripheral clearance. Here we showed that TTR promotes Aβ internalization and efflux in a human cerebral microvascular endothelial cell line, hCMEC/D3. TTR also stimulated brain-to-blood but not blood-to-brain Aβ permeability in hCMEC/D3, suggesting that TTR interacts directly with Aβ at the blood-brain-barrier. We also observed that TTR crosses the monolayer of cells only in the brain-to-blood direction, as confirmed by in vivo studies, suggesting that TTR can transport Aβ from, but not into the brain. Furthermore, TTR increased Aβ internalization by SAHep cells and by primary hepatocytes from TTR+/+ mice when compared to TTR−/− animals. We propose that TTR-mediated Aβ clearance is through LRP1, as lower receptor expression was found in brains and livers of TTR−/− mice and in cells incubated without TTR. Our results suggest that TTR acts as a carrier of Aβ at the blood-brain-barrier and liver, using LRP1.
How to unveil self-quenched fluorophores and subsequently map the subcellular distribution of exogenous peptides
Authors: Swiecicki Jean-Marie , Thiebaut Frédéric , Di Pisa Margherita , Gourdin -Bertin Simon , Tailhades Julien , Mansuy Christelle , Burlina Fabienne , Chwetzoff Serge , Trugnan Germain , Chassaing Gérard , Lavielle Solange
Published: February 2016

Confocal laser scanning microscopy (CLSM) is the most popular technique for mapping the subcellular distribution of a fluorescent molecule and is widely used to investigate the penetration properties of exogenous macromolecules, such as cell-penetrating peptides (CPPs), within cells. Despite the membrane-association propensity of all these CPPs, the signal of the fluorescently labeled CPPs did not colocalize with the plasma membrane. We studied the origin of this fluorescence extinction and the overall consequence on the interpretation of intracellular localizations from CLSM pictures. We demonstrated that this discrepancy originated from fluorescence self-quenching. The fluorescence was unveiled by a “dilution” protocol, i.e. by varying the ratio fluorescent/non-fluorescent CPP. This strategy allowed us to rank with confidence the subcellular distribution of several CPPs, contributing to the elucidation of the penetration mechanism. More generally, this study proposes a broadly applicable and reliable method to study the subcellular distribution of any fluorescently labeled molecules.
Steady State Vapor Bubble in Pool Boiling
Authors: Zou An , Chanana Ashish , Agrawal Amit , Wayner Peter C. , Maroo Shalabh C.
Published: February 2016

Boiling, a dynamic and multiscale process, has been studied for several decades; however, a comprehensive understanding of the process is still lacking. The bubble ebullition cycle, which occurs over millisecond time-span, makes it extremely challenging to study near-surface interfacial characteristics of a single bubble. Here, we create a steady-state vapor bubble that can remain stable for hours in a pool of sub-cooled water using a femtosecond laser source. The stability of the bubble allows us to measure the contact-angle and perform in-situ imaging of the contact-line region and the microlayer, on hydrophilic and hydrophobic surfaces and in both degassed and regular (with dissolved air) water. The early growth stage of vapor bubble in degassed water shows a completely wetted bubble base with the microlayer and the bubble does not depart from the surface due to reduced liquid pressure in the microlayer. Using experimental data and numerical simulations, we obtain permissible range of maximum heat transfer coefficient possible in nucleate boiling and the width of the evaporating layer in the contact-line region. This technique of creating and measuring fundamental characteristics of a stable vapor bubble will facilitate rational design of nanostructures for boiling enhancement and advance thermal management in electronics.
A Hypersweet Protein: Removal of The Specific Negative Charge at Asp21 Enhances Thaumatin Sweetness
Authors: Masuda Tetsuya , Ohta Keisuke , Ojiro Naoko , Murata Kazuki , Mikami Bunzo , Tani Fumito , Temussi Piero Andrea , Kitabatake Naofumi
Published: February 2016

Thaumatin is an intensely sweet-tasting protein that elicits sweet taste at a concentration of 50 nM, a value 100,000 times larger than that of sucrose on a molar basis. Here we attempted to produce a protein with enhanced sweetness by removing negative charges on the interacting side of thaumatin with the taste receptor. We obtained a D21N mutant which, with a threshold value 31 nM is much sweeter than wild type thaumatin and, together with the Y65R mutant of single chain monellin, one of the two sweetest proteins known so far. The complex model between the T1R2-T1R3 sweet receptor and thaumatin, derived from tethered docking in the framework of the wedge model, confirmed that each of the positively charged residues critical for sweetness is close to a receptor residue of opposite charge to yield optimal electrostatic interaction. Furthermore, the distance between D21 and its possible counterpart D433 (located on the T1R2 protomer of the receptor) is safely large to avoid electrostatic repulsion but, at the same time, amenable to a closer approach if D21 is mutated into the corresponding asparagine. These findings clearly confirm the importance of electrostatic potentials in the interaction of thaumatin with the sweet receptor.
Organization of descending neurons in Drosophila melanogaster
Authors: Hsu Cynthia T. , Bhandawat Vikas
Published: February 2016

Neural processing in the brain controls behavior through descending neurons (DNs) - neurons which carry signals from the brain to the spinal cord (or thoracic ganglia in insects). Because DNs arise from multiple circuits in the brain, the numerical simplicity and availability of genetic tools make Drosophila a tractable model for understanding descending motor control. As a first step towards a comprehensive study of descending motor control, here we estimate the number and distribution of DNs in the Drosophila brain. We labeled DNs by backfilling them with dextran dye applied to the neck connective and estimated that there are ~1100 DNs distributed in 6 clusters in Drosophila. To assess the distribution of DNs by neurotransmitters, we labeled DNs in flies in which neurons expressing the major neurotransmitters were also labeled. We found DNs belonging to every neurotransmitter class we tested: acetylcholine, GABA, glutamate, serotonin, dopamine and octopamine. Both the major excitatory neurotransmitter (acetylcholine) and the major inhibitory neurotransmitter (GABA) are employed equally; this stands in contrast to vertebrate DNs which are predominantly excitatory. By comparing the distribution of DNs in Drosophila to those reported previously in other insects, we conclude that the organization of DNs in insects is highly conserved.
Characterization of Two-Pore Channel 2 by Nuclear Membrane Electrophysiology
Authors: Lee Claire Shuk-Kwan , Tong Benjamin Chun-Kit , Cheng Cecily Wing-Hei , Hung Harry Chun-Hin , Cheung King-Ho
Published: February 2016

Lysosomal calcium (Ca2+) release mediated by NAADP triggers signalling cascades that regulate many cellular processes. The identification of two-pore channel 2 (TPC2) as the NAADP receptor advances our understanding of lysosomal Ca2+ signalling, yet the lysosome is not amenable to traditional patch-clamp electrophysiology. Previous attempts to record TPC2 single-channel activity put TPC2 outside its native environment, which not reflect TPC2’s true physiological properties. To test the feasibility of using nuclear membrane electrophysiology for TPC2 channel characterization, we constructed a stable human TPC2-expressing DT40TKO cell line that lacks endogenous InsP3R and RyR (DT40TKO-hTPC2). Immunostaining revealed hTPC2 expression on the ER and nuclear envelope. Intracellular dialysis of NAADP into Fura-2-loaded DT40TKO-hTPC2 cells elicited cytosolic Ca2+ transients, suggesting that hTPC2 was functionally active. Using nuclear membrane electrophysiology, we detected a ~220 pS single-channel current activated by NAADP with K+ as the permeant ion. The detected single-channel recordings displayed a linear current-voltage relationship, were sensitive to Ned-19 inhibition, were biphasically regulated by NAADP concentration and regulated by PKA phosphorylation. In summary, we developed a cell model for the characterization of the TPC2 channel and the nuclear membrane patch-clamp technique provided an alternative approach to rigorously investigate the electrophysiological properties of TPC2 with minimal manipulation.
Simulated effect of calcification feedback on atmospheric CO2 and ocean acidification
Authors: Zhang Han , Cao Long
Published: February 2016

Ocean uptake of anthropogenic CO2 reduces pH and saturation state of calcium carbonate materials of seawater, which could reduce the calcification rate of some marine organisms, triggering a negative feedback on the growth of atmospheric CO2. We quantify the effect of this CO2-calcification feedback by conducting a series of Earth system model simulations that incorporate different parameterization schemes describing the dependence of calcification rate on saturation state of CaCO3. In a scenario with SRES A2 CO2 emission until 2100 and zero emission afterwards, by year 3500, in the simulation without CO2-calcification feedback, model projects an accumulated ocean CO2 uptake of 1462 PgC, atmospheric CO2 of 612 ppm and surface pH of 7.9. Inclusion of CO2-calcification feedback increases ocean CO2 uptake by 9 to 285 PgC, reduces atmospheric CO2 by 4 to 70 ppm and mitigates the reduction in surface pH by 0.003 to 0.06, depending on the form of parameterization scheme used. It is also found that the effect of CO2-calcification feedback on ocean carbon uptake is comparable and could be much larger than the effect from CO2-induced warming. Our results highlight the potentially important role CO2-calcification feedback plays in ocean carbon cycle and projections of future atmospheric CO2 concentrations.
Simple understanding of quantum weak values
Authors: Qin Lupei , Feng Wei , Li Xin-Qi
Published: February 2016

In this work we revisit the important and controversial concept of quantum weak values, aiming to provide a simplified understanding to its associated physics and the origin of anomaly. Taking the Stern-Gerlach setup as a working system, we base our analysis on an exact treatment in terms of quantum Bayesian approach. We also make particular connection with a very recent work, where the anomaly of the weak values was claimed from the pure statistics in association with “disturbance” and “post-selection”, rather than the unique quantum nature. Our analysis resolves the related controversies through a clear and quantitative way.
Altered periaqueductal gray resting state functional connectivity in migraine and the modulation effect of treatment
Authors: Li Zhengjie , Liu Mailan , Lan Lei , Zeng Fang , Makris Nikos , Liang Yilin , Guo Taipin , Wu Feng , Gao Yujie , Dong Mingkai , Yang Jie , Li Ying , Gong Qiyong , Liang Fanrong , Kong Jian
Published: February 2016

The aims of this study were to 1) compare resting state functional connectivity (rs-fc) of the periaqueductal gray (PAG), a key region in the descending pain modulatory system (DPMS) between migraine without aura (MwoA) patients and healthy controls (HC) and 2) investigate how an effective treatment can influence the PAG rs-fc in MwoA patients. One hundred MwoA patients and forty-six matched HC were recruited. Patients were randomized to verum acupuncture, sham acupuncture and waiting list groups. Resting state fMRI data were collected and seed based functional connectivity analysis was applied. Compared with HC, MwoA patients showed reduced rs-fc between the PAG and rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC), key regions in the DPMS and other pain related brain regions. The reduced rs-fc between the PAG and rACC/mPFC was associated with increased migraine headache intensity at the baseline. After treatments, rs-fc between the PAG and the rACC in MwoA patients significantly increased. The changes of rs-fc among the PAG, rACC and ventral striatum were significantly associated with headache intensity improvement. Impairment of the DPMS is involved in the neural pathophysiology of migraines. Impaired DPMS in migraine patients can be normalized after effective treatment.
A novel Hsp70 inhibitor prevents cell intoxication with the actin ADP-ribosylating Clostridium perfringens iota toxin
Authors: Ernst Katharina , Liebscher Markus , Mathea Sebastian , Granzhan Anton , Schmid Johannes , Popoff Michel R. , Ihmels Heiko , Barth Holger , Schiene-Fischer Cordelia
Published: February 2016

Hsp70 family proteins are folding helper proteins involved in a wide variety of cellular pathways. Members of this family interact with key factors in signal transduction, transcription, cell-cycle control and stress response. Here, we developed the first Hsp70 low molecular weight inhibitor specifically targeting the peptide binding site of human Hsp70. After demonstrating that the inhibitor modulates the Hsp70 function in the cell, we used the inhibitor to show for the first time that the stress-inducible chaperone Hsp70 functions as molecular component for entry of a bacterial protein toxin into mammalian cells. Pharmacological inhibition of Hsp70 protected cells from intoxication with the binary actin ADP-ribosylating iota toxin from Clostridium perfringens, the prototype of a family of enterotoxins from pathogenic Clostridia and inhibited translocation of its enzyme component across cell membranes into the cytosol. This finding offers a starting point for novel therapeutic strategies against certain bacterial toxins.
The simultaneous enhancement of photorefraction and optical damage resistance in MgO and Bi2O3 co-doped LiNbO3 crystals
Authors: Zheng Dahuai , Kong Yongfa , Liu Shiguo , Chen Muling , Chen Shaolin , Zhang Ling , Rupp Romano , Xu Jingjun
Published: February 2016

For a long time that optical damage was renamed as photorefraction, here we find that the optical damage resistance and photorefraction can be simultaneously enhanced in MgO and Bi2O3co-doped LiNbO3(LN:Bi,Mg). The photorefractive response time of LN:Bi,Mg was shortened to 170 ms while the photorefractive sensitivity reached up to 21 cm2/J. Meanwhile, LN:Bi,Mg crystals could withstand a light intensity higher than 106  W/cm2without apparent optical damage. Our experimental results indicate that photorefraction doesn’t equal to optical damage. The underground mechanism was analyzed and attributed to that diffusion dominates the transport process of charge carriers, that is to say photorefraction causes only slight optical damage under diffusion mechanism, which is very important for the practical applications of photorefractive crystals, such as in holographic storage, integrated optics and 3D display.
BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit
Authors: Wang Peng , Du Chao , Chen Fei-Xue , Li Chang-Qing , Yu Yan-Bo , Han Ting , Akhtar Suhail , Zuo Xiu-Li , Tan Xiao-Di , Li Yan-Qing
Published: February 2016

The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity and this process is likely initiated by BDNF-TrkB pathway activation.
Electric Control of the Hall effect in Pt/Bi0.9La0.1FeO3 bilayers
Authors: Gao Rongli , Fu Chunlin , Cai Wei , Chen Gang , Deng Xiaoling , Zhang Hongrui , Sun Jirong , Shen Baogen
Published: February 2016

Platinum metal, being nonmagnetic and with a strong spin-orbit coupling interaction, has been deposited on weak ferromagnetic Bi0.9La0.1FeO3 thin films. The Hall effect is studied as a function of the polarization direction of multiferroic Bi0.9La0.1FeO3 thin films, as well as magnetic field (H) and temperature (T). For the two polarization directions, besides the obvious difference of the anomalous Hall resistance RAH, it increases sharply with decreasing temperature and even changes sign, thus violating the conventional expression. This observations indicate local magnetic moments in Pt caused by the local electric fields at the interface of Bi0.9La0.1FeO3 films. Also, possible proximity effects and induced magnetic ordering in Pt on weak ferromagnetic Bi0.9La0.1FeO3 thin films of both upward and downward polarization states may exist and their contribution to the spin-related measurements should not be neglected.
Delineating taxonomic boundaries in the largest species complex of black flies (Simuliidae) in the Oriental Region
Authors: Low Van Lun , Takaoka Hiroyuki , Pramual Pairot , Adler Peter H. , Ya’cob Zubaidah , Huang Yao-Te , Da Pham Xuan , Ramli Rosli , Chen Chee Dhang , Wannaket Anukhcha , Sofian-Azirun Mohd
Published: February 2016

Perspicuous assessments of taxonomic boundaries and discovery of cryptic taxa are of paramount importance in interpreting ecological and evolutionary phenomena among black flies (Simuliidae) and combating associated vector-borne diseases. Simulium tani Takaoka & Davies is the largest and perhaps the most taxonomically challenging species complex of black flies in the Oriental Region. We use a DNA sequence-based method to delineate currently recognized chromosomal and morphological taxa in the S. tani complex on the Southeast Asian mainland and Taiwan, while elucidating their phylogenetic relationships. A molecular approach using multiple genes, coupled with morphological and chromosomal data, supported recognition of cytoform K and morphoform ‘b’ as valid species; indicated that S. xuandei, cytoform L and morphoform ‘a’ contain possible cryptic species; and suggested that cytoform B is in the early stages of reproductive isolation whereas lineage sorting is incomplete in cytoforms A, C and G.
Circulating and tumor-infiltrating mucosal associated invariant T (MAIT) cells in colorectal cancer patients
Authors: Ling Limian , Lin Yuyang , Zheng Wenwen , Hong Sen , Tang Xiuqi , Zhao Pingwei , Li Ming , Ni Jingsong , Li Chenguang , Wang Lei , Jiang Yanfang
Published: February 2016

Mucosal associated invariant T (MAIT) cells are important for immune defense against infectious pathogens and regulate the pathogenesis of various inflammatory diseases. However, their roles in the development of colorectal cancer (CRC) are still unclear. This study examined the phenotype, distribution, clinical relevance and potential function of MAIT cells in CRC patients. We found that the percentages of circulating memory CD8+ MAIT cells were significantly reduced while tumor infiltrating MAIT cells were increased, especially in patients with advanced CRC. The serum CEA levels were positively correlated with the percentages of tumor infiltrating MAIT cells in CRC patients, but negatively correlated with the percentages of circulating MAIT in advanced CRC patients. Activated circulating MAIT cells from CRC patients produced lower IFN-γ, but higher IL-17. Furthermore, higher levels of Vα7.2-Jα33, IFN-γ and IL-17A were expressed in the CRC tissues. Co-culture of activated MAIT cells with HCT116 cells enhanced IL-17 expression and induced HCT116 cell cycle arrest at G2/M phase in a contact- and dose-dependent manner, which was abrogated by treatment with anti-MR1. Therefore, MAIT cells preferably infiltrate into the solid tumor in CRC patients and may participate in the immune surveillance of CRC.
Multidisciplinary investigation links backward-speech trait and working memory through genetic mutation
Authors: Prekovic Stefan , Đurđević Dušica Filipović , Csifcsák Gábor , Šveljo Olivera , Stojković Oliver , Janković Milica , Koprivšek Katarina , Covill Laura E , Lučić Milos , Van den Broeck Thomas , Helsen Christine , Ceroni Fabiola , Claessens Frank , Newbury Dianne F
Published: February 2016

Case studies of unusual traits can provide unique snapshots of the effects of modified systems. In this study, we report on an individual from a Serbian family with the ability to rapidly, accurately and voluntarily speak backwards. We consider psychological, neural and genetic correlates of this trait to identify specific relevant neural mechanisms and new molecular pathways for working memory and speech-related tasks. EEG data suggest that the effect of word reversal precedes semantic integration of visually presented backward-words and that event-related potentials above the frontal lobe are affected by both word reversal and the maintenance of backward-words in working memory. fMRI revealed that the left fusiform gyrus may facilitate the production of backward-speech. Exome sequencing identified three novel coding variants of potential significance in the RIC3, RIPK1 and ZBED5 genes. Taken together, our data suggest that, in this individual, the ability to speak backwards is afforded by an extraordinary working memory capacity. We hypothesise that this is served by cholinergic projections from the basal forebrain to the frontal cortex and supported by visual semantic loops within the left fusiform gyrus and that these neural processes may be mediated by a genetic mutation in RIC3; a chaperone for nicotinic acetylcholine receptors.
Peculiar liquid-feeding and pathogen transmission behavior of Aedes togoi and comparison with Anopheles sinensis
Authors: Lee Sang Joon , Kang Dooho , Lee Seung Chul , Ha Young-Ran
Published: February 2016

Female mosquitoes transmit various diseases as vectors during liquid-feeding. Identifying the determinants of vector efficiency is a major scientific challenge in establishing strategies against these diseases. Infection rate and transmission efficiency are interconnected with the mosquito-induced liquid-feeding flow as main indexes of vector efficiency. However, the relationship between liquid-feeding characteristics and pathogen remains poorly understood. The liquid-feeding behavior of Aedes togoi and Anopheles sinensis was comparatively investigated in conjunction with vector efficiency via micro-particle image velocimetry. The flow rates and ratio of the ejection volume of Aedes togoi were markedly higher than those of Anophels sinensis. These differences would influence pathogen re-ingestion. Wall shear stresses of these mosquito species were also clearly discriminatory affecting the infective rates of vector-borne diseases. The variations in volume of two pump chambers and diameter of proboscis of these mosquito species were compared to determine the differences in the liquid-feeding process. Liquid-feeding characteristics influence vector efficiency; hence, this study can elucidate the vector efficiency of mosquitoes and the vector-pathogen interactions and contribute to the development of strategies against vector-borne diseases.
A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2
Authors: Breitkopf Susanne B. , Yang Xuemei , Begley Michael J. , Kulkarni Meghana , Chiu Yu-Hsin , Turke Alexa B. , Lauriol Jessica , Yuan Min , Qi Jie , Engelman Jeffrey A. , Hong Pengyu , Kontaridis Maria I. , Cantley Lewis C. , Perrimon Norbert , Asara John M.
Published: February 2016

Using a series of immunoprecipitation (IP) – tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.