bluuebunny/crossref_metadata_2025 huggingface dataset:
A mechanical piston action may assist pelvic–pectoral fin antagonism in tree-climbing fish
Authors: Wicaksono Adhityo , Hidayat Saifullah , Retnoaji Bambang , Rivero-Müller Adolfo , Alam Parvez
Published: October 2017

In this research, we compared the anatomy and biomechanics of two species of mudskipper vs an aquatic sandgoby in view of terrestrial locomotion. Of particular interest was the relationship (if any) of pectoral fin movement with pelvic fin movement. We show that the pelvic fins of the terrestrial mudskippers studied herein, are retractable and move antagonistically with the pectoral fins. The pelvic fin of the sandgoby studied here is contrarily non-retractable and drags on any underlying substrate that the sandgoby tries to crawl across. We find that the pelvic and pectoral fin muscles of all fish are separated, but that the pectoral fins of the mudskipper species have bulkier radial muscles than the sandgoby. By coupling a detailed morphological investigation of pectoral-pelvic fins musculature with finite element simulations, we find that unlike sandgobies, the mudskipper species are able to mechanically push the pelvic fins downward as pectoral fins retract. This allows for an instant movement of pelvic fins during the pectoral fin backward stroke and as such the pelvic fins stabilize mudskippers through Stefan attachment of their pelvic fins. This mechanism seems to be efficient and energy saving and we hypothesize that the piston-like action might benefit pelvic–pectoral fin antagonism by facilitating a mechanical down-thrust. Our research on the biomechanics of tree-climbing fish provides ideas and greater potential for the development of energetically more efficient systems of ambulation in biomimetic robots.
Political land corruption: evidence from Malta – the European Union’s smallest member state
Authors: Caruana-Galizia Paul , Caruana-Galizia Matthew
Published: October 2017

Political corruption in the land sector is pervasive, but difficult to document and effectively prosecute. This article provides new evidence on political land corruption in Malta, the European Union’s smallest member state and one of the world’s most densely populated countries. It shows how the country’s highly restrictive zoning laws, along with ade jureindependent regulator, have created opportunities for extensive and endemic corruption in the granting of land development permits in zones that are outside development. It provides an example of governments creating institutions as rent-collection instruments – not to correct market failures, but to create opportunities for corruption. The unique underlying data set was collected through an automated web-scraping program as the regulator first turned down then ignored freedom of information requests for the data.
Spent culture medium analysis from individually cultured bovine embryos demonstrates metabolomic differences
Authors: Perkel Kayla J. , Madan Pavneesh
Published: October 2017

Spent culture medium can provide valuable information regarding the physiological state of a bovine preimplantation embryos through non-invasive analysis of the sum/depleted metabolite constituents. Metabolomics has become of great interest as an adjunct technique to morphological and cleavage-rate assessment, but more importantly, in improving our understanding of metabolism. In this study,in vitroproduced bovine embryos developing at different rates were evaluated using proton nuclear magnetic resonance (1H NMR). Spent culture medium from individually cultured embryos (2-cell to blastocyst stage) were divided into two groups based on their cleavage rate fast growing (FG) and slow growing (SG; developmentally delayed by 12–24 h), then analyzed by a 600 MHz NMR spectrometer. Sixteen metabolites were detected and investigated for sum/depletion throughout development. Data indicate distinct differences between the 4-cell SG and FG embryos for pyruvate (P< 0.05,n= 9) and at the 16-cell stage for acetate, tryptophan, leucine/isoleucine, valine and histidine. Overall sum/depletion levels of metabolites demonstrated that embryos produced glutamate, but consumed histidine, tyrosine, glycine, methionine, tryptophan, phenylalanine, lysine, arginine, acetate, threonine, alanine, pyruvate, valine, isoleucine/leucine, and lactate with an overall trend of higher consumption of these metabolites by FG groups. Principal component analysis revealed distinct clustering of the plain medium, SG, and FG group, signifying the uniqueness of the metabolomic signatures of each of these groups. This study is the first of its kind to characterize the metabolomic profiles of SG and FG bovine embryos producedin vitrousing1H NMR. Elucidating differences between embryos of varying developmental rates could contribute to a better understanding of embryonic health and physiology.
The potential roles of c-Jun N-terminal kinase (JNK) during the maturation and aging of oocytes produced by a marine protostome worm
Authors: Stricker Stephen A. , Ravichandran Niharika
Published: October 2017

Previous investigations have indicated that c-Jun N-terminal kinase (JNK) regulates the maturation and aging of oocytes produced by deuterostome animals. In order to assess the roles of this kinase in a protostome, oocytes of the marine nemertean worm Cerebratulus were stimulated to mature and subsequently aged before being probed with phospho-specific antibodies against active forms of JNK and maturation-promoting factor (MPF). Based on blots of maturing oocytes, a 40-kD putative JNK is normally activated during germinal vesicle breakdown (GVBD), which begins at 30 min post-stimulation with seawater, whereas treating immature oocytes with JNK inhibitors downregulates both the 40-kD JNK signal and GVBD, collectively suggesting a 40-kD JNK may facilitate oocyte maturation. Along with this JNK activity, mature oocytes also exhibit high levels of MPF at 2 h post-stimulation. However, by ~6–8 h post-GVBD, mature oocytes lose the 40-kD JNK signal, and at ~20–30 h of aging, an ~48-kD phospho-JNK band arises as oocytes deactivate MPF and begin to lyse during a necroptotic-like mode of death. Accordingly, JNK inhibitors reduce the aging-related 48-kD JNK phosphorylation while maintaining MPF activity and retarding oocyte degradation. Such findings suggest that a 48-kD JNK may help deactivate MPF and trigger death. Possible mechanisms by which JNK activation either together with, or independently of, protein neosynthesis might stimulate oocyte degradation are discussed.
Symptom Dimensions of Depression and Apathy and Their Relationship With Cognition in Parkinson’s Disease
Authors: Szymkowicz Sarah M. , Dotson Vonetta M. , Jones Jacob D. , Okun Michael S. , Bowers Dawn
Published: October 2017

Objectives:Both depression and apathy, alone and in combination, have been shown to negatively affect cognition in patients with Parkinson’s disease (PD). However, the influence of specific symptom dimensions of depression and apathy on cognition is not well understood. The current study investigated the relationship between symptom dimensions of depression and apathy, based on factors identified in Kirsch-Darrow et al. (2011), and memory and executive function in PD.Methods:A sample of 138 non-demented individuals with PD (mean age=64.51±7.43 years) underwent neuropsychological testing and completed the Beck Depression Inventory, 2nd Edition, and Apathy Scale. Separate hierarchical regression models examined the relationship between symptom dimensions of depression and apathy (“pure” depressive symptoms, “pure” apathy, loss of interest/pleasure [anhedonia], and somatic symptoms) and three cognitive domain composites: immediate verbal memory, delayed verbal memory, and executive function.Results:After adjusting for general cognitive status and the influence of the other symptom dimensions, “pure” depressive symptoms were negatively associated with the delayed verbal memory composite (p<.034) and somatic symptoms were positively associated with the executive function composite (p<.026). No symptom dimensions were significantly related to the immediate verbal memory composite.Conclusions:Findings suggest that specific mood symptoms are associated with delayed verbal memory and executive function performance in non-demented patients with PD. Further research is needed to better understand possible mechanisms through which specific symptom dimensions of depression and apathy are associated with cognition in PD. (JINS, 2018,24, 269–282)
Population dynamics of soybean stem fly Melanagromyza sojae (Diptera: Agromyzidae) and its parasitoids in Maharashtra State of India
Authors: Fand Babasaheb B. , Gaikwad Mahesh B. , Sul Nitin T. , Kumar Mahesh , Bhagat Kiran P. , Bal Santanu K. , Minhas P.S.
Published: October 2017

The cryptic nature and lack of consistent biological control of the stem fly, Melanagromyza sojae Zehntner, an emerging pest of soybean, Glycine max (L.) Merrill, necessitated the monitoring and assessment of the impact of the parasitoid complex on seasonal regulation of the pest population. In this paper, we measure and relate, using the host density as a predictor variable, the seasonal density dependence of M. sojae parasitoids and the level of parasitism in soybean fields. The results revealed density dependence of parasitioids. The populations built up concomitant with the host insect, reached their peak during the mid-season, and declined towards the end of the crop season. A complex of 10 species of hymenopteran parasitoids comprising six species from Pteromalidae and one species each from the families Eurytomitidae, Eucoilidae, Braconidae and Eulopidae had a significant impact on M. sojae populations with a peak parasitism of ~50%. The seasonality and relative abundance of parasitoids were explored. Eurytoma sp. (Eurytomitidae) and Gronotoma sp. (Eucoilidae) were the most prevalent parasitoids throughout the season, whereas the pteromalid Sphegigaster sp. was dominant during the mid-season. The modulation of management practices aimed at conservation of these bioagents could improve the biological control of M. sojae populations. We discuss the practicality of several management options aimed at achieving this goal.
Spin crossover-induced colossal positive and negative thermal expansion in a nanoporous coordination framework material
Authors: Mullaney Benjamin R. , Goux-Capes Laurence , Price David J. , Chastanet Guillaume , Létard Jean-François , Kepert Cameron J.
Published: October 2017

External control over the mechanical function of materials is paramount in the development of nanoscale machines. Yet, exploiting changes in atomic behaviour to produce controlled scalable motion is a formidable challenge. Here, we present an ultra-flexible coordination framework material in which a cooperative electronic transition induces an extreme abrupt change in the crystal lattice conformation. This arises due to a change in the preferred coordination character of Fe(II) sites at different spin states, generating scissor-type flexing of the crystal lattice. Diluting the framework with transition-inactive Ni(II) sites disrupts long-range communication of spin state through the lattice, producing a more gradual transition and continuous lattice movement, thus generating colossal positive and negative linear thermal expansion behaviour, with coefficients of thermal expansion an order of magnitude greater than previously reported. This study has wider implications in the development of advanced responsive structures, demonstrating electronic control over mechanical motion.
Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL
Authors: Karpel-Massler Georg , Ishida Chiaki Tsuge , Bianchetti Elena , Zhang Yiru , Shu Chang , Tsujiuchi Takashi , Banu Matei A. , Garcia Franklin , Roth Kevin A. , Bruce Jeffrey N. , Canoll Peter , Siegelin Markus D.
Published: October 2017

Certain gliomas often harbor a mutation in the activity center of IDH1 (R132H), which leads to the production of the oncometabolite 2-R-2-hydroxyglutarate (2-HG). In six model systems, including patient-derived stem cell-like glioblastoma cultures, inhibition of Bcl-xL induces significantly more apoptosis in IDH1-mutated cells than in wild-type IDH1 cells. Anaplastic astrocytoma samples with mutated IDH1 display lower levels of Mcl-1 than IDH1 wild-type tumors and specific knockdown of Mcl-1 broadly sensitizes glioblastoma cells to Bcl-xL inhibition-mediated apoptosis. Addition of 2-HG to glioblastoma cultures recapitulates the effects of the IDH mutation on intrinsic apoptosis, shuts down oxidative phosphorylation and reduces ATP levels in glioblastoma cells. 2-HG-mediated energy depletion activates AMPK (Threonine 172), blunting protein synthesis and mTOR signaling, culminating in a decline of Mcl-1. In an orthotopic glioblastoma xenograft model expressing mutated IDH1, Bcl-xL inhibition leads to long-term survival. These results demonstrate that IDH1-mutated gliomas are particularly vulnerable to Bcl-xL inhibition.
Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1
Authors: Feng Yu-Xiong , Jin Dexter X. , Sokol Ethan S. , Reinhardt Ferenc , Miller Daniel H. , Gupta Piyush B.
Published: October 2017

PERK signaling is required for cancer invasion and there is interest in targeting this pathway for therapy. Unfortunately, chemical inhibitors of PERK’s kinase activity cause on-target side effects that have precluded their further development. One strategy for resolving this difficulty would be to target downstream components of the pathway that specifically mediate PERK’s pro-invasive and metastatic functions. Here we identify the transcription factor CREB3L1 as an essential mediator of PERK’s pro-metastatic functions in breast cancer. CREB3L1 acts downstream of PERK, specifically in the mesenchymal subtype of triple-negative tumors, and its inhibition by genetic or pharmacological methods suppresses cancer cell invasion and metastasis. In patients with this tumor subtype, CREB3L1 expression is predictive of distant metastasis. These findings establish CREB3L1 as a key downstream mediator of PERK-driven metastasis and a druggable target for breast cancer therapy.
FAN1 interaction with ubiquitylated PCNA alleviates replication stress and preserves genomic integrity independently of BRCA2
Authors: Porro Antonio , Berti Matteo , Pizzolato Julia , Bologna Serena , Kaden Svenja , Saxer Anja , Ma Yue , Nagasawa Kazuo , Sartori Alessandro A. , Jiricny Josef
Published: October 2017

Interstrand cross-link (ICL) hypersensitivity is a characteristic trait of Fanconi anemia (FA). Although FANCD2-associated nuclease 1 (FAN1) contributes to ICL repair, FAN1 mutations predispose to karyomegalic interstitial nephritis (KIN) and cancer rather than to FA. Thus, the biological role of FAN1 remains unclear. Because fork stalling in FAN1-deficient cells causes chromosomal instability, we reasoned that the key function of FAN1 might lie in the processing of halted replication forks. Here, we show that FAN1 contains a previously-uncharacterized PCNA interacting peptide (PIP) motif that, together with its ubiquitin-binding zinc finger (UBZ) domain, helps recruit FAN1 to ubiquitylated PCNA accumulated at stalled forks. This prevents replication fork collapse and controls their progression. Furthermore, we show that FAN1 preserves replication fork integrity by a mechanism that is distinct from BRCA2-dependent homologous recombination. Thus, targeting FAN1 activities and its interaction with ubiquitylated PCNA may offer therapeutic opportunities for treatment of BRCA-deficient tumors.
Engineering the internal surfaces of three-dimensional nanoporous catalysts by surfactant-modified dealloying
Authors: Wang Zhili , Liu Pan , Han Jiuhui , Cheng Chun , Ning Shoucong , Hirata Akihiko , Fujita Takeshi , Chen Mingwei
Published: October 2017

Tuning surface structures by bottom-up synthesis has been demonstrated as an effective strategy to improve the catalytic performances of nanoparticle catalysts. Nevertheless, the surface modification of three-dimensional nanoporous metals, fabricated by a top-down dealloying approach, has not been achieved despite great efforts devoted to improving the catalytic performance of three-dimensional nanoporous catalysts. Here we report a surfactant-modified dealloying method to tailor the surface structure of nanoporous gold for amplified electrocatalysis toward methanol oxidation and oxygen reduction reactions. With the assistance of surfactants, {111} or {100} faceted internal surfaces of nanoporous gold can be realized in a controllable manner by optimizing dealloying conditions. The surface modified nanoporous gold exhibits significantly enhanced electrocatalytic activities in comparison with conventional nanoporous gold. This study paves the way to develop high-performance three-dimensional nanoporous catalysts with a tunable surface structure by top-down dealloying for efficient chemical and electrochemical reactions.
Reducing sarcolipin expression mitigates Duchenne muscular dystrophy and associated cardiomyopathy in mice
Authors: Voit Antanina , Patel Vishwendra , Pachon Ronald , Shah Vikas , Bakhutma Mohammad , Kohlbrenner Erik , McArdle Joseph J. , Dell’Italia Louis J. , Mendell Jerry R. , Xie Lai-Hua , Hajjar Roger J. , Duan Dongsheng , Fraidenraich Diego , Babu Gopal J.
Published: October 2017

Sarcolipin (SLN) is an inhibitor of the sarco/endoplasmic reticulum (SR) Ca2+ATPase (SERCA) and is abnormally elevated in the muscle of Duchenne muscular dystrophy (DMD) patients and animal models. Here we show that reducing SLN levels ameliorates dystrophic pathology in the severe dystrophin/utrophin double mutant (mdx:utr−/−) mouse model of DMD. Germline inactivation of one allele of the SLN gene normalizes SLN expression, restores SERCA function, mitigates skeletal muscle and cardiac pathology, improves muscle regeneration, and extends the lifespan. To translate our findings into a therapeutic strategy, we knock down SLN expression in 1-month oldmdx:utr−/−mice via adeno-associated virus (AAV) 9-mediated RNA interference. The AAV treatment markedly reduces SLN expression, attenuates muscle pathology and improves diaphragm, skeletal muscle and cardiac function. Taken together, our findings suggest that SLN reduction is a promising therapeutic approach for DMD.
Large-scale water collection of bioinspired cavity-microfibers
Authors: Tian Ye , Zhu Pingan , Tang Xin , Zhou Chunmei , Wang Jianmei , Kong Tiantian , Xu Min , Wang Liqiu
Published: October 2017

Large-scale and high-efficient water collection of microfibers with long-term durability still remains challenging. Here we present well-controlled, bioinspired spindle-knot microfibers with cavity knots (named cavity-microfiber), precisely fabricated via a simple gas-in-water microfluidic method, to address this challenge. The cavity-microfiber is endowed with unique surface roughness, mechanical strength, and long-term durability due to the design of cavity as well as polymer composition, thus enabling an outstanding performance of water collection. The maximum water volume collected on a single knot is almost 495 times than that of the knot on the cavity-microfiber. Moreover, the spider-web-like networks assembled controllably by cavity-microfibers demonstrate excellent large-scale and high-efficient water collection. To maximize the water-collecting capacity, nodes/intersections should be designed on the topology of the network as many as possible. Our light-weighted yet tough, low-cost microfibers with high efficiency in directional water transportation offers promising opportunities for large-scale water collection in water-deficient areas.
Genetic rescue increases fitness and aids rapid recovery of an endangered marsupial population
Authors: Weeks Andrew R. , Heinze Dean , Perrin Louise , Stoklosa Jakub , Hoffmann Ary A. , van Rooyen Anthony , Kelly Tom , Mansergh Ian
Published: October 2017

Genetic rescue has now been attempted in several threatened species, but the contribution of genetics per se to any increase in population health can be hard to identify. Rescue is expected to be particularly useful when individuals are introduced into small isolated populations with low levels of genetic variation. Here we consider such a situation by documenting genetic rescue in the mountain pygmy possum, Burramys parvus. Rapid population recovery occurred in the target population after the introduction of a small number of males from a large genetically diverged population. Initial hybrid fitness was more than two-fold higher than non-hybrids; hybrid animals had a larger body size, and female hybrids produced more pouch young and lived longer. Genetic rescue likely contributed to the largest population size ever being recorded at this site. These data point to genetic rescue as being a potentially useful option for the recovery of small threatened populations.
Deletion of 3p13-14 locus spanning FOXP1 to SHQ1 cooperates with PTEN loss in prostate oncogenesis
Authors: Hieronymus Haley , Iaquinta Phillip J. , Wongvipat John , Gopalan Anuradha , Murali Rajmohan , Mao Ninghui , Carver Brett S. , Sawyers Charles L.
Published: October 2017

A multigenic locus at 3p13-14, spanning FOXP1 to SHQ1, is commonly deleted in prostate cancer and lost broadly in a range of cancers but has unknown significance to oncogenesis or prognosis. Here, we report that FOXP1-SHQ1 deletion cooperates with PTEN loss to accelerate prostate oncogenesis and that loss of component genes correlates with prostate, breast, and head and neck cancer recurrence. We demonstrate that Foxp1-Shq1 deletion accelerates prostate tumorigenesis in mice in combination with Pten loss, consistent with the association of FOXP1-SHQ1 and PTEN loss observed in human cancers. Tumors with combined Foxp1-Shq1 and Pten deletion show increased proliferation and anaplastic dedifferentiation, as well as mTORC1 hyperactivation with reduced Akt phosphorylation. Foxp1-Shq1 deletion restores expression of AR target genes repressed in tumors with Pten loss, circumventing PI3K-mediated repression of the androgen axis. Moreover, FOXP1-SHQ1 deletion has prognostic relevance, with cancer recurrence associated with combined loss of PTEN and FOXP1-SHQ1 genes.
Structural and electronic determinants of lytic polysaccharide monooxygenase reactivity on polysaccharide substrates
Authors: Simmons T. J. , Frandsen K. E. H. , Ciano L. , Tryfona T. , Lenfant N. , Poulsen J. C. , Wilson L. F. L. , Tandrup T. , Tovborg M. , Schnorr K. , Johansen K. S. , Henrissat B. , Walton P. H. , Lo Leggio L , Dupree P.
Published: October 2017

Lytic polysaccharide monooxygenases (LPMOs) are industrially important copper-dependent enzymes that oxidatively cleave polysaccharides. Here we present a functional and structural characterization of two closely related AA9-family LPMOs from Lentinus similis (LsAA9A) and Collariella virescens (CvAA9A). LsAA9A and CvAA9A cleave a range of polysaccharides, including cellulose, xyloglucan, mixed-linkage glucan and glucomannan. LsAA9A additionally cleaves isolated xylan substrates. The structures of CvAA9A and of LsAA9A bound to cellulosic and non-cellulosic oligosaccharides provide insight into the molecular determinants of their specificity. Spectroscopic measurements reveal differences in copper co-ordination upon the binding of xylan and glucans. LsAA9A activity is less sensitive to the reducing agent potential when cleaving xylan, suggesting that distinct catalytic mechanisms exist for xylan and glucan cleavage. Overall, these data show that AA9 LPMOs can display different apparent substrate specificities dependent upon both productive protein–carbohydrate interactions across a binding surface and also electronic considerations at the copper active site.
Superelasticity and cryogenic linear shape memory effects of CaFe2As2
Authors: Sypek John T. , Yu Hang , Dusoe Keith J. , Drachuck Gil , Patel Hetal , Giroux Amanda M. , Goldman Alan I. , Kreyssig Andreas , Canfield Paul C. , Bud’ko Sergey L. , Weinberger Christopher R. , Lee Seok-Woo
Published: October 2017

Shape memory materials have the ability to recover their original shape after a significant amount of deformation when they are subjected to certain stimuli, for instance, heat or magnetic fields. However, their performance is often limited by the energetics and geometry of the martensitic-austenitic phase transformation. Here, we report a unique shape memory behavior in CaFe2As2, which exhibits superelasticity with over 13% recoverable strain, over 3 GPa yield strength, repeatable stress–strain response even at the micrometer scale, and cryogenic linear shape memory effects near 50 K. These properties are acheived through a reversible uni-axial phase transformation mechanism, the tetragonal/orthorhombic-to-collapsed-tetragonal phase transformation. Our results offer the possibility of developing cryogenic linear actuation technologies with a high precision and high actuation power per unit volume for deep space exploration, and more broadly, suggest a mechanistic path to a class of shape memory materials, ThCr2Si2-structured intermetallic compounds.
Open-Cavity Spun Fiber Raman Lasers with Dual Polarization Output
Authors: Nuño Javier , Rizzelli Giuseppe , Gallazzi Francesca , Prieto Francisco , Pulido Concepción , Corredera Pedro , Wabnitz Stefan , Ania-Castanon Juan D.
Published: October 2017

Random distributed feedback fiber Raman lasers, where the feedback mechanism is provided by Rayleigh backscattering, have attracted a good deal of attention since they were first introduced in 2010. Their simple and flexible design, combined with good lasing efficiency and beam quality properties, comparable to those of standard cavity lasers, have led to multiple applications, particularly in the fields of fiber sensing and optical communications. In spite of these advances, the polarization properties of random fiber Raman lasers, which can strongly affect their performance in both sensing and communications, have barely been explored so far. In this article we experimentally and theoretically study the polarization properties of different open-cavity laser designs, based on either standard transmission fibers or low polarization-mode-dispersion spun fibers. By using high-power, highly-polarized pumps, we demonstrate controllable polarization-pulling and simultaneous lasing at close wavelengths with different output polarization properties in random distributed feedback fiber Raman lasers. These results advance our understanding of the polarization dynamics in ultralong lasers, and pave the way to the design of novel fiber laser sources capable of polarization-sensitive sensing and distributed amplification.
Non-muscular myosin light chain kinase triggers intermittent hypoxia-induced interleukin-6 release, endothelial dysfunction and permeability
Authors: Recoquillon Sylvain , Gómez-Guzmán Manuel , Rodier Marion , Koffi Camille , Nitiéma Mathieu , Gagnadoux Frédéric , Martínez M. Carmen , Andriantsitohaina Ramaroson
Published: October 2017

Obstructive sleep apnea is characterized by intermittent hypoxia (IH) which alters endothelial function, induces inflammation and accelerates atherosclerosis-induced cardiovascular diseases. The non-muscular myosin light chain kinase (nmMLCK) isoform contributes to endothelial cell-cell junction opening. Deletion of nmMLCK protects mice from death in septic shock models and prevents atherosclerosis in high-fat diet-fed mice. The aim of the study was to analyze the implication of nmMLCK in IH-induced vascular inflammation. Human aortic endothelial cells were exposed to 6 hours of IH in absence or presence of nmMLCK inhibitors, ML-7 (5 µM) or PIK (150 µM). IH increased reactive oxygen species (ROS) and nitric oxide (NO) production, p65-NFκB activation and IL-6 secretion. While nmMLCK inhibition did not prevent IH-induced ROS production and p65-NFκB activation, it decreased NO production and partially prevented IL-6 secretion. IH-induced IL-6 secretion and vesicle-associated membrane protein-associated vesicles re-organization were inhibited in presence of the inhibitor of protein secretion, brefeldin A, or ML-7. IH increased monocytes transendothelial migration that was partially prevented by ML-7. Finally, IH reduced endothelium-dependent relaxation to acetylcholine of aortas from wild-type but not those taken from nmMLCK-deficient mice. These results suggest that nmMLCK participates to IH-induced endothelial dysfunction resulting from cytokines secretion and endothelial permeability.
A pilot evaluation of whole blood finger-prick sampling for point-of-care HIV viral load measurement: the UNICORN study
Authors: Fidler Sarah , Lewis Heather , Meyerowitz Jodi , Kuldanek Kristin , Thornhill John , Muir David , Bonnissent Alice , Timson Georgina , Frater John
Published: October 2017

There is a global need for HIV viral load point-of-care (PoC) assays to monitor patients receiving antiretroviral therapy. UNICORN was the first study of an off-label protocol using whole blood finger-prick samples tested with and without a simple three minute spin using a clinic-room microcentrifuge. Two PoC assays were evaluated in 40 HIV-positive participants, 20 with detectable and 20 with undetectable plasma viral load (pVL) (<20 copies/ml). Using 100 µl finger-prick blood samples, the Cepheid Xpert HIV-1 Viral Load and HIV-1 Qual cartridges were compared with laboratory pVL assessment (TaqMan, Roche). For participants with undetectable viraemia by TaqMan, there was poor concordance without centrifugation with the TaqMan platform with only 40% ‘undetectable’ using Xpert VL and 25% ‘not detected’ using the Qual assay. After a 3 minute spin, 100% of samples were undetectable using either assay, showing full concordance with the TaqMan assay. Defining a lower limit of detection of 1000 copies/ml when including a spin, there was 100% concordance with the TaqMan platform with strong correlation (rho 0.95 and 0.94; p < 0.0001 for both assays). When including a simple microcentrifugation step, finger-prick PoC testing was a quick and accurate approach for assessing HIV viraemia, with excellent concordance with validated laboratory approaches.
Functional and Structural Studies of a Multidomain Alginate Lyase from Persicobacter sp. CCB-QB2
Authors: Sim Pei-Fang , Furusawa Go , Teh Aik-Hong
Published: October 2017

AlyQ from Persicobacter sp. CCB-QB2 is an alginate lyase with three domains — a carbohydrate-binding domain modestly resembling family 16 carbohydrate-binding module (CBM16), a family 32 CBM (CBM32) domain, and an alginate lyase domain belonging to polysaccharide lyase family 7 (PL7). Although AlyQ can also act on polyguluronate (poly-G) and polymannuronate (poly-M), it is most active on alginate. Studies with truncated AlyQ showed that the CBM32 domain did not contribute to enhancing AlyQ’s activity under the assayed conditions. Nevertheless, it could bind to cleaved but not intact alginate, indicating that the CBM32 domain recognises alginate termini. The crystal structure containing both CBM32 and catalytic domains show that they do not interact with one another. The CBM32 domain contains a conserved Arg that may bind to the carboxyl group of alginate. The catalytic domain, meanwhile, shares a conserved substrate-binding groove, and the presence of two negatively charged Asp residues may dictate substrate specificity especially at subsite +1. As Persicobacter sp. CCB-QB2 was unable to utilise alginate, AlyQ may function to help the bacterium degrade cell walls more efficiently.
Albumin uptake in human podocytes: a possible role for the cubilin-amnionless (CUBAM) complex
Authors: Gianesello Lisa , Priante Giovanna , Ceol Monica , Radu Claudia M. , Saleem Moin A. , Simioni Paolo , Terrin Liliana , Anglani Franca , Del Prete Dorella
Published: October 2017

Albumin re-uptake is a receptor-mediated pathway located in renal proximal tubuli. There is increasing evidence of glomerular protein handling by podocytes, but little is known about the mechanism behind this process. In this study, we found that human podocytes in vitro are committed to internalizing albumin through a receptor-mediated mechanism even after exposure to low doses of albumin. We show that these cells express cubilin, megalin, ClC-5, amnionless and Dab2, which are partners in the tubular machinery. Exposing human podocytes to albumin overload prompted an increase in CUBILIN, AMNIONLESS and CLCN5 gene expression. Inhibiting cubilin led to a reduction in albumin uptake, highlighting its importance in this mechanism. We demonstrated that human podocytes are committed to performing endocytosis via a receptor-mediated mechanism even in the presence of low doses of albumin. We also disclosed that protein overload first acts on the expression of the cubilin-amnionless (CUBAM) complex in these cells, then involves the ClC-5 channel, providing the first evidence for a possible role of the CUBAM complex in albumin endocytosis in human podocytes.
Mitochondrial genomes of the key zooplankton copepods Arctic Calanus glacialis and North Atlantic Calanus finmarchicus with the longest crustacean non-coding regions
Authors: Weydmann Agata , Przyłucka Aleksandra , Lubośny Marek , Walczyńska Katarzyna S. , Serrão Ester A. , Pearson Gareth A. , Burzyński Artur
Published: October 2017

We determined the nearly complete mitochondrial genomes of the Arctic Calanus glacialis and its North Atlantic sibling Calanus finmarchicus, which are key zooplankton components in marine ecosystems. The sequenced part of C. glacialis mitogenome is 27,342 bp long and consists of two contigs, while for C. finmarchicus it is 29,462 bp and six contigs, what makes them the longest reported copepod mitogenomes. The typical set of metazoan mitochondrial genes is present in these mitogenomes, although the non-coding regions (NCRs) are unusually long and complex. The mitogenomes of the closest species C. glacialis and C. finmarchicus, followed by the North Pacific C. sinicus, are structurally similar and differ from the much more typical of deep-water, Arctic C. hyperboreus. This evolutionary trend for the expansion of NCRs within the Calanus mitogenomes increases mitochondrial DNA density, what resulted in its similar density to the nuclear genome. Given large differences in the length and structure of C. glacialis and C. finmarchicus mitogenomes, we conclude that the species are genetically distinct and thus cannot hybridize. The molecular resources presented here: the mitogenomic and rDNA sequences, and the database of repetitive elements should facilitate the development of genetic markers suitable in pursuing evolutionary research in copepods.
Resilience and regime shifts in a marine biodiversity hotspot
Authors: Vasilakopoulos Paraskevas , Raitsos Dionysios E. , Tzanatos Evangelos , Maravelias Christos D.
Published: October 2017

Complex natural systems, spanning from individuals and populations to ecosystems and social-ecological systems, often exhibit abrupt reorganizations in response to changing stressors, known as regime shifts or critical transitions. Theory suggests that such systems feature folded stability landscapes with fluctuating resilience, fold-bifurcations, and alternate basins of attraction. However, the implementation of such features to elucidate response mechanisms in an empirical context is scarce, due to the lack of generic approaches to quantify resilience dynamics in individual natural systems. Here, we introduce an Integrated Resilience Assessment (IRA) framework: a three-step analytical process to assess resilience and construct stability landscapes of empirical systems. The proposed framework involves a multivariate analysis to estimate holistic system indicator variables, non-additive modelling to estimate alternate attractors, and a quantitative resilience assessment to scale stability landscapes. We implement this framework to investigate the temporal development of the Mediterranean marine communities in response to sea warming during 1985–2013, using fisheries landings data. Our analysis revealed a nonlinear tropicalisation of the Mediterranean Sea, expressed as abrupt shifts to regimes dominated by thermophilic species. The approach exemplified here for the Mediterranean Sea, revealing previously unknown resilience dynamics driven by climate forcing, can elucidate resilience and shifts in other complex systems.
Reconstruction of Toll-like receptor 9-mediated responses in HEK-Blue hTLR9 cells by transfection of human macrophage scavenger receptor 1 gene
Authors: Ohtsuki Shozo , Takahashi Yuki , Inoue Takao , Takakura Yoshinobu , Nishikawa Makiya
Published: October 2017

We used human Toll-like receptor 9 (hTLR9)-expressing HEK-Blue hTLR9 cells, which release secreted embryonic alkaline phosphatase (SEAP) upon response to CpG DNA, to evaluate the immunological properties of nucleic acid drug candidates. Our preliminary studies showed that phosphodiester CpG DNA hardly induced any SEAP secretion in HEK-Blue hTLR9 cells. In the current study, therefore, we developed HEK-Blue hTLR9 cells transduced with human macrophage scavenger receptor-1 (hMSR1), a cell-surface DNA receptor, and determined whether HEK-Blue hTLR9/hMSR1 cells respond to phosphorothioate (PS) CpG DNA and phosphodiester (PO) CpG DNA. We selected PS CpG2006, a single-stranded PO CpG DNA (ssCpG), and a tetrapod-like structured DNA (tetrapodna) containing ssCpG (tetraCpG) as model TLR9 ligands. Alexa Fluor 488-labeled ligands were used for flow cytometry. Unlike the mock-transfected HEK-Blue hTLR9 cells, the HEK-Blue hTLR9/hMSR1 cells efficiently took up all three CpG DNAs. SEAP release was almost proportional to the uptake. Treatment of HEK-Blue hTLR9/hMSR1 cells with an anti-hMSR1 antibody significantly reduced the uptake of ssCpG and tetraCpG. Collectively, reconstruction of TLR9-mediated responses to CpG DNA in HEK-Blue hTLR9 cells can be used to evaluate the toxicity of nucleic acid drug candidates with diverse physicochemical properties.
Spatiotemporal Variability in Phosphorus Species in the Pearl River Estuary: Influence of the River Discharge
Authors: Li Ruihuan , Xu Jie , Li Xiangfu , Shi Zhen , Harrison Paul J.
Published: October 2017

Phosphorus was the stoichiometrically limiting nutrient in the Pearl River Estuary (PRE). In order to examine how the river discharge regulates phosphorus dynamics in the PRE, the concentrations of dissolved inorganic phosphorus (DIP) and organic phosphorus (DOP), particulate inorganic phosphorus (PIP) and organic phosphorus (POP) in the water column were determined in May 2015 (spring), August 2015 (summer) and January 2016 (winter). Our results showed that all types of phosphorus were significantly lower in spring and summer than in winter. The Pearl River discharge input played an important role in regulating phosphorus dynamics. Strong vertical mixing in winter resulted in high levels of total particulate phosphorus (1.50 ± 0.97 μM) and dissolved phosphate (DIP: 1.44 ± 0.57 μM, DOP: 0.58 ± 0.42 μM) at the surface. On the other hand, the river discharge input created stratification in spring and summer, favoring the settlement of suspended particulate matter and enhancing light levels. This promoted phytoplankton growth, which was responsible for a DIP drawdown of 0.43 ± 0.37 μM in May and 0.56 ± 0.42 μM in August at the surface. Additionally, stratification restricted the bottom phosphorus replenishment. Our findings provided an insight into processes causing stoichiometric P limitation in the PRE.
Inferred father-to-son transmission of herpes simplex virus results in near-perfect preservation of viral genome identity and in vivo phenotypes
Authors: Pandey Utsav , Renner Daniel W. , Thompson Richard L. , Szpara Moriah L. , Sawtell Nancy M.
Published: October 2017

High throughout sequencing has provided an unprecedented view of the circulating diversity of all classes of human herpesviruses. For herpes simplex virus 1 (HSV-1), we and others have previously published data demonstrating sequence diversity between hosts. However the extent of variation during transmission events, or in one host over years of chronic infection, remain unknown. Here we present an initial example of full characterization of viruses isolated from a father to son transmission event. The likely occasion of transmission occurred 17 years before the strains were isolated, enabling a first view of the degree of virus conservation after decades of recurrences, including transmission and adaptation to a new host. We have characterized the pathogenicity of these strains in a mouse ocular model of infection, and sequenced the full viral genomes. Surprisingly, we find that these two viruses have preserved their phenotype and genotype nearly perfectly during inferred transmission from father to son, and during nearly two decades of episodes of recurrent disease in each human host. Given the close genetic relationship of these two hosts, it remains to be seen whether or not this conservation of sequence will occur during non-familial transmission events.
Alcohol consumption impairs the ependymal cilia motility in the brain ventricles
Authors: Omran Alzahra J. Al , Saternos Hannah C. , Althobaiti Yusuf S. , Wisner Alexander , Sari Youssef , Nauli Surya M. , AbouAlaiwi Wissam A.
Published: October 2017

Ependymal cilia protrude into the central canal of the brain ventricles and spinal cord to circulate the cerebral spinal fluid (CSF). Ependymal cilia dysfunction can hinder the movement of CSF leading to an abnormal accumulation of CSF within the brain known as hydrocephalus. Although the etiology of hydrocephalus was studied before, the effects of ethanol ingestion on ependymal cilia function have not been investigated in vivo. Here, we report three distinct types of ependymal cilia, type-I, type-II and type-III classified based upon their beating frequency, their beating angle, and their distinct localization within the mouse brain-lateral ventricle. Our studies show for the first time that oral gavage of ethanol decreased the beating frequency of all three types of ependymal cilia in both the third and the lateral rat brain ventricles in vivo. Furthermore, we show for the first time that hydin, a hydrocephalus-inducing gene product whose mutation impairs ciliary motility, and polycystin-2, whose ablation is associated with hydrocephalus are colocalized to the ependymal cilia. Thus, our studies reinforce the presence of three types of ependymal cilia in the brain ventricles and demonstrate the involvement of ethanol as a risk factor for the impairment of ependymal cilia motility in the brain.
A minimalistic and optimized conveyor belt for neutral atoms
Authors: Roy Ritayan , Condylis Paul C. , Prakash Vindhiya , Sahagun Daniel , Hessmo Björn
Published: October 2017

Here we report of a design and the performance of an optimized micro-fabricated conveyor belt for precise and adiabatic transportation of cold atoms. A theoretical model is presented to determine optimal currents in conductors used for the transportation. We experimentally demonstrate a fast adiabatic transportation of Rubidium (87Rb) cold atoms with minimal loss and heating with as few as three conveyor belt conductors. This novel design of a multilayered conveyor belt structure is fabricated in aluminium nitride (AlN) because of its outstanding thermal and electrical properties. This demonstration would pave a way for a compact and portable quantum device required for quantum information processing and sensors, where precise positioning of cold atoms is desirable.
Interactions between seagrasses and seaweeds during surge nitrogen acquisition determine interspecific competition
Authors: Alexandre Ana , Baeta Alexandra , Engelen Aschwin H. , Santos Rui
Published: October 2017

Seagrasses dominate shallow coastal environments where nitrogen (N) availability in the water column is often sporadic and mainly in the form of pulses. We investigated the N uptake competition between seagrasses and seaweeds through a series of 15N surge uptake experiments combining single-species and mixed incubations across ammonium concentrations. N surge uptake rates of seagrasses were 2 to 14-fold higher than those of seaweeds in the majority of combinations, showing that seagrasses are generally in a competitive advantage over seaweeds in N-poor environments with N-pulses. No threshold concentration of ammonium was found beyond which seaweeds performed better than seagrasses. Mixed incubations revealed interspecific interactions that affected rates positively and negatively. Uptake rates obtained in single-species incubations, therefore, cannot always be used to predict the outcome of uptake competition. Only two (Zostera marina vs. Ulva rotundata and Zostera marina vs. Codium decorticatum) of the nine combinations tested (Z. marina, Z. noltei and Cymodocea nodosa vs. U. rotundata, C. decorticatum and Dictyota dichotoma) were found to enhance macroalgal uptake. Our results showed that the surge uptake capacity of seagrasses represents an important mechanism in their N acquisition strategy that justifies their dominance in shallow oligotrophic environments.
TNFR1 inhibition with a Nanobody protects against EAE development in mice
Authors: Steeland Sophie , Van Ryckeghem Sara , Van Imschoot Griet , De Rycke Riet , Toussaint Wendy , Vanhoutte Leen , Vanhove Christian , De Vos Filip , Vandenbroucke Roosmarijn E. , Libert Claude
Published: October 2017

TNF has as detrimental role in multiple sclerosis (MS), however, anti-TNF medication is not working. Selective TNF/TNFR1 inhibition whilst sparing TNFR2 signaling reduces the pro-inflammatory effects of TNF but preserves the important neuroprotective signalsviaTNFR2. We previously reported the generation of a Nanobody-based selective inhibitor of human TNFR1, TROS that will be tested in experimental autoimmune encephalomyelitis (EAE). We specifically antagonized TNF/TNFR1 signaling using TROS in a murine model of MS, namely MOG35-55-induced EAE. Because TROS does not cross-react with mouse TNFR1, we generated mice expressing human TNFR1 in a mouse TNFR1-knockout background (hTNFR1 Tg), and we determined biodistribution of99mTc-TROS and effectiveness of TROS in EAE in those mice. Biodistribution analysis demonstrated that intraperitoneally injected TROS is retained more in organs of hTNFR1 Tg mice compared to wild type mice. TROS was also detected in the cerebrospinal fluid (CSF) of hTNFR1 Tg mice. Prophylactic TROS administration significantly delayed disease onset and ameliorated its symptoms. Moreover, treatment initiated early after disease onset prevented further disease development. TROS reduced spinal cord inflammation and neuroinflammation, and preserved myelin and neurons. Collectively, our data illustrate that TNFR1 is a promising therapeutic target in MS.
The ANK repeats of Notch-4/Int3 activate NF-κB canonical pathway in the absence of Rbpj and causes mammary tumorigenesis
Authors: Raafat Ahmed , Bargo Sharon , McCurdy David , Callahan Robert
Published: October 2017

Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in the mammary gland have two phenotypes exhibited with 100% penetrance: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch-4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. Interestingly, WAP-Int3/Rbpj knockout mice have normal mammary gland development but still developed mammary tumors with a slightly longer latency than the WAP-Int3 mice. Thus, Notch-induced mammary tumor development is Rbpj-independent. Here, we show that Int3 activates NF-κB in HC11 cells in absence of Rbpj through an association with the IKK signalosome. Int3 induced the canonical NF-κB activity and P50 phosphorylation in HC11 cells without altering the NF-κB2 pathway. The minimal domain within the Int3 protein required to activate NF-κB consists of the CDC10/Ankyrin (ANK) repeats domain. Treatment of WAP-Int3 tumor bearing mice with an IKK inhibitor resulted in tumor regression. In a soft agar assay, treatment of HC11-Int3 cells with P50-siRNA caused a significant decrease in colony formation. In addition, Wap-Int3/P50 knockout mice did not develop mammary tumors. This data indicates that the activation of NF-κB canonical signaling by Notch-4/Int3 is ANK repeats dependent, Rbpj-independent, and is mediated by IKK activation and P50 phosphorylation causing mammary tumorigenesis.