bluuebunny/crossref_metadata_2025 huggingface dataset:
Conservative Management of Pituitary Macroadenoma Contacting the Optic Apparatus
Authors: Ryu Won Hyung A. , Tam Samantha , Rotenberg Brian , Labib Mohamed Ahmed , Lee Donald , Nicolle David A. , Uum Stan Van , Duggal Neil
Published: September 2016

Objectives:

To describe the tumor characteristics and visual function in conservatively managed patients with non-functioning pituitary macroadenoma (NFMA) that contacted/compressed the visual pathway.

Design:

Retrospective case-series.

Setting:

Tertiary-care academic institution.

Participants:

Six patients with diagnosis of NFMA.

Main Outcome:

Visual function and radiological characteristics of the optic apparatus and pituitary tumor.

Results:

All patients had radiological evidence of optic apparatus compression but only one had visual field defect at the initial presentation. While two of the six patients developed visual field changes during follow-up (41±34.8 months), the patient with visual field defect at the time of diagnosis improved to normal vision.

Conclusions:

Select NFMAs that contact the optic apparatus, without visual dysfunction, may be managed with close ophthalmological and radiographic monitoring, depending on tumor and imaging characteristics. This may be of particular relevance in patients considered to have a high peri-operative risk, such as advanced age or significant co-morbidities.
Appropriateness of Lumbar Spine Referrals to a Neurosurgical Service
Authors: Findlay J. Max , Deis Nathan
Published: September 2016

Background:

Patients with lumbar spine complaints are often referred for surgical assessment. Only those with clinical and radiological evidence of nerve root compression are potential candidates for surgery and appropriate for surgical assessment. This study examines the appropriateness of lumbar spine referrals made to neurosurgeons in Edmonton, Alberta.

Methods:

Lumbar spine referrals to a group of ten neurosurgeons at the University of Alberta were reviewed over three two month intervals. Clinical criteria for “appropriateness” for surgical assessment were as follows: •“Appropriate” referrals were those that stated leg pain was the chief complaint, or those that described physical exam evidence of neurological deficit, and imaging reports (CT or MRI) were positive for nerve root compression. •“Uncertain” referrals were those that reported both back and leg pain without specifying which was greater, without mention of neurologic deficit, and when at least possible nerve root compression was reported on imaging. •“Inappropriate” referrals contained no mention of leg symptoms or signs of neurological deficit, and/or had no description of nerve root compression on imaging.

Results:

Of the 303 referrals collected, 80 (26%) were appropriate, 92 (30%) were uncertain and 131 (44%) were inappropriate for surgical assessment.

Conclusions:

Physicians seeking specialist consultations for patients with lumbar spine complaints need to be better informed of the criteria which indicate an appropriate referral for surgical treatment, namely clinical and radiological evidence of nerve root compression. Avoiding inappropriate referrals could reduce wait-times for both surgical consultation and lumbar spine surgery for those patients requiring it.
Surgical Activity of First-Year Canadian Neurosurgical Residents
Authors: Fallah Aria , Ebrahim Shanil , Haji Faizal , Gillis Christopher , Girgis Fady , Howe Kathryn , Ibrahim George M. , Radic Julia , Shahideh Mehdi , Wallace M. Christopher
Published: September 2016

Introduction:

Surgical activity is probably the most important component of surgical training. During the first year of surgical residency, there is an early opportunity for the development of surgical skills, before disparities between the skill sets of residents increase in future years. It is likely that surgical skill is related to operative volumes. There are no published guidelines that quantify the number of surgical cases required to achieve surgical competency. The aim of this study was to describe the current trends in surgical activity in a recent cohort of first-year Canadian neurosurgical trainees.

Methods:

This study utilized retrospective database review and survey methodology to describe the current state of surgical training for first-year neurosurgical trainees. A committee of five residents designed this survey in an effort to capture factors that may influence the operative activity of trainees.

Results:

Nine out of a cohort of 20 first-year Canadian neurosurgical trainees that began training in July of 2008 participated in the study. The median number of cases completed by a resident during the initial three month neurosurgical rotation was 66, within which the trainee was identified as the primary surgeon in 12 cases. Intracranial hemorrhage and cerebrospinal fluid diversion procedures were the most common operations to have the trainee as primary surgeon.

Conclusion:

Based on this pilot study, it appears that the operative activity of Canadian first-year residents is at least equivalent to the residents of other studied training systems with respect to volume and diversity of surgical activity.
ON THE VARIATIONAL CONSTANT ASSOCIATED TO THE -HARDY INEQUALITY
Authors: WARD A. D.
Published: September 2016

Let$\unicode[STIX]{x1D6FA}$be a domain in$\mathbb{R}^{m}$with nonempty boundary. In Ward [‘On essential self-adjointness, confining potentials and the$L_{p}$-Hardy inequality’, PhD Thesis, NZIAS Massey University, New Zealand, 2014] and [‘The essential self-adjointness of Schrödinger operators on domains with non-empty boundary’,Manuscripta Math.150(3) (2016), 357–370] it was shown that the Schrödinger operator$H=-\unicode[STIX]{x1D6E5}+V$, with domain of definition$D(H)=C_{0}^{\infty }(\unicode[STIX]{x1D6FA})$and$V\in L_{\infty }^{\text{loc}}(\unicode[STIX]{x1D6FA})$, is essentially self-adjoint provided that$V(x)\geq (1-\unicode[STIX]{x1D707}_{2}(\unicode[STIX]{x1D6FA}))/d(x)^{2}$. Here$d(x)$is the Euclidean distance to the boundary and$\unicode[STIX]{x1D707}_{2}(\unicode[STIX]{x1D6FA})$is the nonnegative constant associated to the$L_{2}$-Hardy inequality. The conditions required for a domain to admit an$L_{2}$-Hardy inequality are well known and depend intimately on the Hausdorff or Aikawa/Assouad dimension of the boundary. However, there are only a handful of domains where the value of$\unicode[STIX]{x1D707}_{2}(\unicode[STIX]{x1D6FA})$is known explicitly. By obtaining upper and lower bounds on the number of cubes appearing in the$k\text{th}$generation of the Whitney decomposition of$\unicode[STIX]{x1D6FA}$, we derive an upper bound on$\unicode[STIX]{x1D707}_{p}(\unicode[STIX]{x1D6FA})$, for$p>1$, in terms of the inner Minkowski dimension of the boundary.
Explaining and Understanding State Intervention into the Lives of ‘Troubled’ Families
Authors: Parr Sadie
Published: September 2016

This article focuses attention on explaining and understanding state intervention into the lives of families deemed ‘troublesome’ with specific attention on the Troubled Families Programme. Launched in 2011, in part as a response to the London riots, the Troubled Families Programme represented an escalation and intensification of state intervention into the lives of families. Policy analyses have provided important perspectives on how we should explain and understand this government agenda as part of a process of neoliberal state crafting. This article offers a critical yet productive examination of these perspectives, arguing that their utility lies in how they can be employed, and therefore modified and adapted, in conjunction with studies of local practice which emphasise the messy realities of policy enactment and, with that, the possibility for contestation and challenge. Such an approach, based broadly on the tenets of critical realism, is founded on an alternative conception of state power, one that sees state power as having a more complex quality that is dependent on the agency of local actors.
Factors Related to Suicide in LGBT Populations
Authors: Skerrett Delaney Michael , Kõlves Kairi , De Leo Diego
Published: September 2016

Abstract. Background: There is evidence of heightened vulnerability to nonfatal suicidal behaviors among LGBT populations yet a paucity of studies into fatal behaviors. Aim: The specific aim of this article was to identify factors related to suicide in LGBT individuals in Australia. Method: The psychological autopsy (PA) method with a matched case-control study design was used. PA interviews were conducted with 27 next-of-kin of an LGBT person that had died by suicide. Three living LGBT controls per suicide case, matched by age and gender, were also interviewed. Results: The key factors relating to suicide in LGBT people were a lack of acceptance by family and self (reflected in higher internalized homophobia and shame), negative feelings about own sexuality/gender, and dissatisfaction with appearance. LGBT people who died by suicide also tended to go through coming out milestones 2 years earlier than controls. There was a higher prevalence of aggressive behaviors and a more predominant history of physical and sexual abuse. Additionally, there was greater incidence of depression and anxiety and alcohol and substance use disorders. Conclusion: Specific predictive factors for suicide in LGBT populations in Australia were identified, including significantly poorer mental health outcomes and more violence across an array of measures.
We Need a New Definition for "Magma"
Authors: Glazner Allen , Bartley John , Coleman Drew
Published: September 2016

Confusion over the meaning of "magma" can generate popular misperceptions, including a nonexistent molten sea underneath Yellowstone National Park. We propose a different definition.
Aquatic Plants May Accelerate Arctic Methane Emissions
Authors: Heisman Rebecca
Published: September 2016

About two thirds of the gas produced by a study area near Barrow, Alaska, came from increasingly abundant greenery covering only 5% of the landscape, researchers estimate.
Top Arctic Science Diplomats Convene at White House Next Week
Authors: Showstack Randy
Published: September 2016

Precipitous transformations from climate change add impetus for this international meeting to guide cooperative research in the northern polar region, U.S. official says.
Transport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity
Authors: McVicker Derrick P. , Awe Adam M. , Richters Karl E. , Wilson Rebecca L. , Cowdrey Diana A. , Hu Xindao , Chapman Edwin R. , Dent Erik W.
Published: September 2016

Synaptic plasticity often involves changes in the structure and composition of dendritic spines. Vesicular cargos and organelles enter spines either by exocytosing in the dendrite shaft and diffusing into spines or through a kinesin to myosin hand-off at the base of spines. Here we present evidence for microtubule (MT)-based targeting of a specific motor/cargo pair directly into hippocampal dendritic spines. During transient MT polymerization into spines, the kinesin KIF1A and an associated cargo, synaptotagmin-IV (syt-IV), are trafficked in unison along MTs into spines. This trafficking into selected spines is activity-dependent and results in exocytosis of syt-IV-containing vesicles in the spine head. Surprisingly, knockdown of KIF1A causes frequent fusion of syt-IV-containing vesicles throughout the dendritic shaft and diffusion into spines. Taken together, these findings suggest a mechanism for targeting dendritic cargo directly into spines during synaptic plasticity and indicate that MT-bound kinesins prevent unregulated fusion by sequestering vesicular cargo to MTs.
Molecular transport through large-diameter DNA nanopores
Authors: Krishnan Swati , Ziegler Daniela , Arnaut Vera , Martin Thomas G. , Kapsner Korbinian , Henneberg Katharina , Bausch Andreas R. , Dietz Hendrik , Simmel Friedrich C.
Published: September 2016

DNA-based nanopores are synthetic biomolecular membrane pores, whose geometry and chemical functionality can be tuned using the tools of DNA nanotechnology, making them promising molecular devices for applications in single-molecule biosensing and synthetic biology. Here we introduce a large DNA membrane channel with an ≈4 nm diameter pore, which has stable electrical properties and spontaneously inserts into flat lipid bilayer membranes. Membrane incorporation is facilitated by a large number of hydrophobic functionalizations or, alternatively, streptavidin linkages between biotinylated channels and lipids. The channel displays an Ohmic conductance of ≈3 nS, consistent with its size, and allows electrically driven translocation of single-stranded and double-stranded DNA analytes. Using confocal microscopy and a dye influx assay, we demonstrate the spontaneous formation of membrane pores in giant unilamellar vesicles. Pores can be created both in an outside-in and an inside-out configuration.
Low-oxygen waters limited habitable space for early animals
Authors: Tostevin R. , Wood R. A. , Shields G. A. , Poulton S. W. , Guilbaud R. , Bowyer F. , Penny A. M. , He T. , Curtis A. , Hoffmann K. H. , Clarkson M. O.
Published: September 2016

The oceans at the start of the Neoproterozoic Era (1,000–541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (∼550–541 Ma). In combination with Fe-based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 μM) was a key requirement for the development of early animal-based ecosystems.
Intercalated water layers promote thermal dissipation at bio–nano interfaces
Authors: Wang Yanlei , Qin Zhao , Buehler Markus J. , Xu Zhiping
Published: September 2016

The increasing interest in developing nanodevices for biophysical and biomedical applications results in concerns about thermal management at interfaces between tissues and electronic devices. However, there is neither sufficient knowledge nor suitable tools for the characterization of thermal properties at interfaces between materials of contrasting mechanics, which are essential for design with reliability. Here we use computational simulations to quantify thermal transfer across the cell membrane–graphene interface. We find that the intercalated water displays a layered order below a critical value of ∼1 nm nanoconfinement, mediating the interfacial thermal coupling, and efficiently enhancing the thermal dissipation. We thereafter develop an analytical model to evaluate the critical value for power generation in graphene before significant heat is accumulated to disturb living tissues. These findings may provide a basis for the rational design of wearable and implantable nanodevices in biosensing and thermotherapic treatments where thermal dissipation and transport processes are crucial.
Elevated Adiponectin Levels Suppress Perivascular and Aortic Inflammation and Prevent AngII-induced Advanced Abdominal Aortic Aneurysms
Authors: Wågsäter Dick , Vorkapic Emina , van Stijn Caroline M. W. , Kim Jason , Lusis Aldons J. , Eriksson Per , Tangirala Rajendra K.
Published: September 2016

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by aortic dilation and rupture leading to sudden death. Currently, no non-surgical treatments are available and novel therapeutic targets are needed to prevent AAA. We investigated whether increasing plasma levels of adiponectin (APN), a pleiotropic adipokine, provides therapeutic benefit to prevent AngII-induced advanced AAA in a well-established preclinical model. In the AngII-infused hyperlipidemic low-density lipoprotein receptor-deficient mouse (LDLR−/−) model, we induced plasma APN levels using a recombinant adenovirus expressing mouse APN (AdAPN) and as control, adenovirus expressing green florescent protein (AdGFP). APN expression produced sustained and significant elevation of total and high-molecular weight APN levels and enhanced APN localization in the artery wall. AngII infusion for 8 weeks induced advanced AAA development in AdGFP mice. Remarkably, APN inhibited the AAA development in AdAPN mice by suppressing aortic inflammatory cell infiltration, medial degeneration and elastin fragmentation. APN inhibited the angiotensin type-1 receptor (AT1R), inflammatory cytokine and mast cell protease expression and induced lysyl oxidase (LOX) in the aortic wall, improved systemic cytokine profile and attenuated adipose inflammation. These studies strongly support APN therapeutic actions through multiple mechanisms inhibiting AngII-induced AAA and increasing plasma APN levels as a strategy to prevent advanced AAA.
Altered Biomarkers in Trophoblast Cells Obtained Noninvasively Prior to Clinical Manifestation of Perinatal Disease
Authors: Bolnick Jay M. , Kohan-Ghadr Hamid-Reza , Fritz Rani , Bolnick Alan D. , Kilburn Brian A. , Diamond Michael P. , Armant D. Randall , Drewlo Sascha
Published: September 2016

A contributing factor to poor placental perfusion, leading to intrauterine growth restriction and preeclampsia, is the failure of invading extravillous trophoblast (EVT) cells to remodel the maternal uterine arteries during the first and second trimesters of pregnancy. Noninvasive assessment of EVT cells in ongoing pregnancies is possible beginning three weeks after conception, using trophoblast retrieval and isolation from the cervix (TRIC). Seven proteins were semi-quantified by immunofluorescence microscopy in EVT cells obtained between gestational weeks 6 and 20 from pregnancies with normal outcomes (N = 29) and those with intrauterine growth restriction or preeclampsia (N = 12). Significant differences were measured in expression of PAPPA, FLT1, ENG, AFP, PGF, and LGALS14, but not LGALS13 or the lineage marker KRT7. These findings provide for the first time direct evidence of pathology-associated protein dysregulation in EVT cells during early placentation. The TRIC platform provides a novel approach to acquire molecular signatures of EVT cells that can be correlated with pregnancy outcome.
Identification of putative chemosensory receptor genes from yellow peach moth Conogethes punctiferalis (Guenée) antennae transcriptome
Authors: Ge Xing , Zhang Tiantao , Wang Zhenying , He Kanglai , Bai Shuxiong
Published: September 2016

The yellow peach moth, Conogethes punctiferalis, is an extremely important polyphagous insect in Asia. The chemosensory systems of moth play an important role in detecting food, oviposition sites and mate attraction. Several antennal chemosensory receptors are involved in odor detection. Our study aims to identify chemosensory receptor genes for potential applications in behavioral responses of yellow peach moth. By transcriptomic analysis of male and female antennae, 83 candidate chemosensory receptors, including 62 odorant receptors, 11 ionotropic receptors and 10 gustatory receptors were identified. Through Blast and sequence alignment, the highly conserved co-receptor Orco was annotated, eight unigenes clustered into pheromone receptors, and two clustered as sugar receptor. Among the IRs, one unigenes was similar with co-receptors IR25a. Expression levels of 50 odorant receptors were further evaluated by quantitative real-time PCR in antennae. All the ORs tested were detected in antennae and some of which were associated with sex-biased expression. The chemosensory receptors identified in C. punctiferalis provide a foundational resource for further analysis on olfaction for behavior. The expression profiles of ORs in antennae indicated variant functions in olfactory recognition, and our results provided the possibility for the potential application of semiochemical to control this pest moth.
Titanium dioxide nanoparticles strongly impact soil microbial function by affecting archaeal nitrifiers
Authors: Simonin Marie , Richaume Agnès , Guyonnet Julien P. , Dubost Audrey , Martins Jean M. F. , Pommier Thomas
Published: September 2016

Soils are facing new environmental stressors, such as titanium dioxide nanoparticles (TiO2-NPs). While these emerging pollutants are increasingly released into most ecosystems, including agricultural fields, their potential impacts on soil and its function remain to be investigated. Here we report the response of the microbial community of an agricultural soil exposed over 90 days to TiO2-NPs (1 and 500 mg kg−1 dry soil). To assess their impact on soil function, we focused on the nitrogen cycle and measured nitrification and denitrification enzymatic activities and by quantifying specific representative genes (amoA for ammonia-oxidizers, nirK and nirS for denitrifiers). Additionally, diversity shifts were examined in bacteria, archaea, and the ammonia-oxidizing clades of each domain. With strong negative impacts on nitrification enzyme activities and the abundances of ammonia-oxidizing microorganism, TiO2-NPs triggered cascading negative effects on denitrification enzyme activity and a deep modification of the bacterial community structure after just 90 days of exposure to even the lowest, realistic concentration of NPs. These results appeal further research to assess how these emerging pollutants modify the soil health and broader ecosystem function.
A Single Talent Immunogenic Membrane Antigen and Novel Prognostic Predictor: voltage-dependent anion channel 1 (VDAC1) in Pancreatic Cancer
Authors: Wang Weibin , Zhang Taiping , Zhao Wenjing , Xu Lai , Yang Yu , Liao Quan , Zhao Yupei
Published: September 2016

Immunogenic membrane antigens associated with multiple biological functions of human cancer cells, have significant value in molecule diagnosis and targeted therapy. Here we screened immunogenic membrane antigens in pancreatic cancer by immunobloting IgG purified from sera of 66 pancreatic cancer patients with membrane proteins separated from two-dimensional PAGE of human pancreatic cancer cell line SWl990 and identified voltage-dependent anion channel 1 (VDAC1) as one of the potential immunogenic membrane antigens. Further studies focusing on VDAC1 demonstrated that VDAC1 mRNA and protein were significantly expressed in the tested pancreatic cancer cell lines. VDAC1 silencing with RNAi significantly decreased cell growth, invasion and migration in the pancreatic cancer cell line Capan-1. Additionally, VDAC1 expression was upregulated in pancreatic cancer tissue compared with normal pancreas samples and patients with low VDAC1 expression had a significantly greater median survival compared to those with high expression (27.0 months vs. 17.8 months, P = 0.039). In multivariable analysis, VDAC1 staining was an independent prognostic factor for survival [(Hazard-Ratio) HR = 1.544, 95% CI = 0.794–3.0, P = 0.021]. These results demonstrated that VDAC1 may be a candidate immunogenic membrane antigen for pancreatic cancer, a potential independent prognostic marker and an ideal drug target.
Liprin-α1 and ERC1 control cell edge dynamics by promoting focal adhesion turnover
Authors: Astro Veronica , Tonoli Diletta , Chiaretti Sara , Badanai Sabrina , Sala Kristyna , Zerial Marino , de Curtis Ivan
Published: September 2016

Liprin-α1 and ERC1 are interacting scaffold proteins regulating the motility of normal and tumor cells. They act as part of plasma membrane-associated platforms at the edge of motile cells to promote protrusion by largely unknown mechanisms. Here we identify an amino-terminal region of the liprin-α1 protein (liprin-N) that is sufficient and necessary for the interaction with other liprin-α1 molecules. Similar to liprin-α1 or ERC1 silencing, expression of the liprin-N negatively affects tumor cell motility and extracellular matrix invasion, acting as a dominant negative by interacting with endogenous liprin-α1 and causing the displacement of the endogenous ERC1 protein from the cell edge. Interfering with the localization of ERC1 at the cell edge inhibits the disassembly of focal adhesions, impairing protrusion. Liprin-α1 and ERC1 proteins colocalize with active integrin β1 clusters distinct from those colocalizing with cytoplasmic focal adhesion proteins and influence the localization of peripheral Rab7-positive endosomes. We propose that liprin-α1 and ERC1 promote protrusion by displacing cytoplasmic adhesion components to favour active integrin internalization into Rab7-positive endosomes.
IMNGS: A comprehensive open resource of processed 16S rRNA microbial profiles for ecology and diversity studies
Authors: Lagkouvardos Ilias , Joseph Divya , Kapfhammer Martin , Giritli Sabahattin , Horn Matthias , Haller Dirk , Clavel Thomas
Published: September 2016

The SRA (Sequence Read Archive) serves as primary depository for massive amounts of Next Generation Sequencing data and currently host over 100,000 16S rRNA gene amplicon-based microbial profiles from various host habitats and environments. This number is increasing rapidly and there is a dire need for approaches to utilize this pool of knowledge. Here we created IMNGS (Integrated Microbial Next Generation Sequencing), an innovative platform that uniformly and systematically screens for and processes all prokaryotic 16S rRNA gene amplicon datasets available in SRA and uses them to build sample-specific sequence databases and OTU-based profiles. Via a web interface, this integrative sequence resource can easily be queried by users. We show examples of how the approach allows testing the ecological importance of specific microorganisms in different hosts or ecosystems and performing targeted diversity studies for selected taxonomic groups. The platform also offers a complete workflow forde novoanalysis of users’ own raw 16S rRNA gene amplicon datasets for the sake of comparison with existing data. IMNGS can be accessed atwww.imngs.org.
Flyglow: Single-fly observations of simultaneous molecular and behavioural circadian oscillations in controls and an Alzheimer’s model
Authors: Khabirova Eleonora , Chen Ko-Fan , O’Neill John S. , Crowther Damian C.
Published: September 2016

Circadian rhythms are essential for health and are frequently disturbed in disease. A full understanding of the causal relationships between behavioural and molecular circadian rhythms requires simultaneous longitudinal observations over time in individual organisms. Current experimental paradigms require the measurement of each rhythm separately across distinct populations of experimental organisms, rendering the comparability of the resulting datasets uncertain. We therefore developed FLYGLOW, an assay using clock gene controlled luciferase expression detected by exquisitely sensitive EM-CCD imaging, to enable simultaneous quantification of parameters including locomotor, sleep consolidation and molecular rhythms in single flies over days/weeks. FLYGLOW combines all the strengths of existing techniques and also allows powerful multiparametric paired statistics. We found the age-related transition from rhythmicity to arrhythmicity for each parameter occurs unpredictably, with some flies showing loss of one or more rhythms during middle-age. Using single-fly correlation analysis of rhythm robustness and period we demonstrated the independence of the peripheral clock from circadian behaviours in wild type flies as well as in an Alzheimer’s model. FLYGLOW is a useful tool for investigating the deterioration of behavioural and molecular rhythms in ageing and neurodegeneration. This approach may be applied more broadly within behavioural neurogenetics research.
Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter
Authors: Wang Li-Ying , Ravi Vidhya M. , Leblanc Gérard , Padrós Esteve , Cladera Josep , Perálvarez-Marín Alex
Published: September 2016

Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.
Ultrabroadband Design for Linear Polarization Conversion and Asymmetric Transmission Crossing X- and K- Band
Authors: Zhang Linbo , Zhou Peiheng , Chen Haiyan , Lu Haipeng , Xie Haiyan , Zhang Li , Li En , Xie Jianliang , Deng Longjiang
Published: September 2016

In this work, a high-efficiency and broadband reflective converter using ultrathin planar metamaterial (MM) composed of single-layered SRR is firstly realized. Numerical and experimental results demonstrate that the cross-polarization conversion reflectance above 0.84 is achieved from 8.6 to 18.6 GHz for linearly polarized (LP) incident waves under normal incidence. Subsequently, a multi-layered MM based on SRR enables a dramatic improvement of the recently demonstrated asymmetric transmission (AT) effect. Theoretical and measured results present that strong one-way transmission of two orthogonally polarized waves crossing C- and K- band has been observed. These two separated AT pass-bands have a function of selective polarization filter, which can be switched on/off by changing the polarization state of incident waves. The physical mechanisms are elucidated by taking advantage of electric fields and current distributions. Considering the broad bandwidth and the dual band, we believe that these two structures will be beneficial for designing polarization-controlled and selective transmission converter.
Linking in domain-swapped protein dimers
Authors: Baiesi Marco , Orlandini Enzo , Trovato Antonio , Seno Flavio
Published: September 2016

The presence of knots has been observed in a small fraction of single-domain proteins and related to their thermodynamic and kinetic properties. The exchanging of identical structural elements, typical of domain-swapped proteins, makes such dimers suitable candidates to validate the possibility that mutual entanglement between chains may play a similar role for protein complexes. We suggest that such entanglement is captured by the linking number. This represents, for two closed curves, the number of times that each curve winds around the other. We show that closing the curves is not necessary, as a novel parameter G′, termed Gaussian entanglement, is strongly correlated with the linking number. Based on 110 non redundant domain-swapped dimers, our analysis evidences a high fraction of chains with a significant intertwining, that is with |G′| > 1. We report that Nature promotes configurations with negative mutual entanglement and surprisingly, it seems to suppress intertwining in long protein dimers. Supported by numerical simulations of dimer dissociation, our results provide a novel topology-based classification of protein-swapped dimers together with some preliminary evidence of its impact on their physical and biological properties.
Species specific exome probes reveal new insights in positively selected genes in nonhuman primates
Authors: Su Zheng , Zhang Junjie , Kumar Chanchal , Molony Cliona , Lu Hongchao , Chen Ronghua , Stone David J. , Ling Fei , Liu Xiao
Published: September 2016

Nonhuman primates (NHP) are important biomedical animal models for the study of human disease. Of these, the most widely used models in biomedical research currently are from the genus Macaca. However, evolutionary genetic divergence between human and NHP species makes human-based probes inefficient for the capture of genomic regions of NHP for sequencing and study. Here we introduce a new method to resequence the exome of NHP species by a designed capture approach specifically targeted to the NHP, and demonstrate its superior performance on four NHP species or subspecies. Detailed investigation on biomedically relevant genes demonstrated superior capture by the new approach. We identified 28 genes that appeared to be pseudogenized and inactivated in macaque. Finally, we identified 187 genes showing strong evidence for positive selection across all branches of the primate phylogeny including many novel findings.
The MADS-Box transcription factor Bcmads1 is required for growth, sclerotia production and pathogenicity of Botrytis cinerea
Authors: Zhang Zhanquan , Li Hua , Qin Guozheng , He Chang , Li Boqiang , Tian Shiping
Published: September 2016

MADS-box transcription factors are highly conserved in eukaryotic species and involved in a variety of biological processes. Little is known, however, regarding the function of MADS-box genes in Botrytis cinerea, a fungal pathogen with a wide host range. Here, the functional role of the B. cinerea MADS-box gene, Bcmads1, was characterized in relation to the development, pathogenicity and production of sclerotia. The latter are formed upon incubation in darkness and serve as survival structures during winter and as the female parent in sexual reproduction. Bcmads1 is indispensable for sclerotia production. RT-qPCR analysis suggested that Bcmads1 modulated sclerotia formation by regulating the expression of light-responsive genes. Bcmads1 is required for the full virulence potential of B. cinerea on apple fruit. A comparative proteomic analysis identified 63 proteins, representing 55 individual genes that are potential targets of Bcmads1. Among them, Bcsec14 and Bcsec31 are associated with vesicle transport. Deletion of Bcsec14 and Bcsec31 resulted in a reduction in the virulence and protein secretion of B. cinerea. These results suggest that Bcmads1 may influence sclerotia formation by modulating light responsive gene expression and regulate pathogenicity by its effect on the protein secretion process.
Exposure to HT-2 toxin causes oxidative stress induced apoptosis/autophagy in porcine oocytes
Authors: Zhang Yue , Han Jun , Zhu Cheng-Cheng , Tang Feng , Cui Xiang-Shun , Kim Nam-Hyung , Sun Shao-Chen
Published: September 2016

T-2 toxin is a main type A trichothecene mycotoxin which is the most toxic trichothecence. T-2 toxin has posed various toxic effects on human and animals in vigorous cell proliferation tissues like lymphoid, hematopoietic and gastrointestinal tissues, while HT-2 toxin is the major metabolite which is deacetylated by T-2 toxin. In this study, we focused on the toxic effects of HT-2 on porcine oocyte maturation. We treated the porcine oocyte with HT-2 toxin in vitro, and we first found that HT-2 treatment inhibited porcine oocyte polar body extrusion and cumulus cell expansion. We observed the disrupted meiotic spindle morphology after treatment, which might be due to the reduced p-MAPK protein level. Actin distribution was also disturbed, indicating that HT-2 affects cytoskeleton of porcine oocytes. We next explored the causes for the failure of oocyte maturation after HT-2 treatment. We found that HT-2 treated oocytes showed the increased ROS level, which indicated that oxidative stress had occurred. We also detected autophagy as well as early apoptosis in the treatment oocytes. Due to the fact that oxidative stress could induced apoptosis, our results indicated that HT-2 toxin caused oxidative stress induced apoptosis and autophagy, which further affected porcine oocyte maturation.
Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin
Authors: Rother Magdalena B. , Jensen Kristin , van der Burg Mirjam , van de Bovenkamp Fleur S. , Kroek Roel , van IJcken Wilfred F. J. , van der Velden Vincent H. J. , Cupedo Tom , Olstad Ole K. , van Dongen Jacques J. M. , van Zelm Menno C.
Published: September 2016

Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently used proximal V, D and J genes in complete IGH gene rearrangements, despite normal Ig locus contraction. Fewer N-nucleotides were added in IGH gene rearrangements in the context of low TdT and XRCC4 expression. Moreover, fetal progenitor-B cells expressed lower levels of IL7Rα than their pediatric counterparts. Analysis of progenitor-B cells from IL7Rα-deficient patients revealed that TdT expression and N-nucleotides additions in Dh-Jh junctions were dependent on functional IL7Rα. Thus, IL7Rα affects TdT expression, and decreased expression of this receptor underlies at least in part the skewed Ig repertoire formation in fetal B-cell precursors. These new insights provide a better understanding of the formation of adaptive immunity in the developing fetus.
Blocking 5-HT2 receptor restores cardiovascular disorders in type 1 experimental diabetes
Authors: García-Pedraza José-Ángel , Ferreira-Santos Pedro , Aparicio Rubén , Montero María-José , Morán Asunción
Published: September 2016

This study aimed to determine whether the serotonergic modulation, through selective 5-HT2 receptor blockade, restores cardiovascular disturbances in type 1 diabetic rats. Diabetes was induced by alloxan (150 mg/kg, s.c.) and maintained for 4 weeks. 5-HT2 receptor was blocked by sarpogrelate (30 mg/kg.day; 14 days; p.o.). Systolic blood pressure (SBP), heart rate (HR), glycaemia and body weight (BW) were monitored periodically. Animals were sacrificed at the end of the study and the heart, right kidney and thoracic aorta were removed; plasma samples were also obtained. Left ventricular hypertrophy index (LVH) and renal hypertrophy index (RH) were determined. Vascular function was studied in aorta rings; additionally, superoxide anion (O2•−) production (by lucigenin-enhanced chemiluminescence) and lipid peroxidation (by thiobarbituric acid reactive substances assay) were measured. Neither alloxan nor sarpogrelate treatments altered HR, LVH or endothelium-independent relaxation. SBP, glycaemia, BW, RH, O2•− production and lipid peroxidation were significantly altered in diabetic animals compared with controls. Sarpogrelate treatment considerably decreased SBP, RH, O2•− production and lipid peroxidation. Endothelium-dependent relaxation was severely reduced in diabetic animal aortas compared to controls; sarpogrelate treatment markedly improved it. Our outcomes show that selectively blocking 5-HT2 receptors has beneficial effects on impaired cardiovascular parameters in diabetes.
Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities
Authors: Zhan Guanqun , Qu Xiaolan , Liu Junjun , Tong Qingyi , Zhou Junfei , Sun Bin , Yao Guangmin
Published: September 2016

Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2 and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary.
Single-pulse enhanced coherent diffraction imaging of bacteria with an X-ray free-electron laser
Authors: Fan Jiadong , Sun Zhibin , Wang Yaling , Park Jaehyun , Kim Sunam , Gallagher-Jones Marcus , Kim Yoonhee , Song Changyong , Yao Shengkun , Zhang Jian , Zhang Jianhua , Duan Xiulan , Tono Kensuke , Yabashi Makina , Ishikawa Tetsuya , Fan Chunhai , Zhao Yuliang , Chai Zhifang , Gao Xueyun , Earnest Thomas , Jiang Huaidong
Published: September 2016

High-resolution imaging offers one of the most promising approaches for exploring and understanding the structure and function of biomaterials and biological systems. X-ray free-electron lasers (XFELs) combined with coherent diffraction imaging can theoretically provide high-resolution spatial information regarding biological materials using a single XFEL pulse. Currently, the application of this method suffers from the low scattering cross-section of biomaterials and X-ray damage to the sample. However, XFELs can provide pulses of such short duration that the data can be collected using the “diffract and destroy” approach before the effects of radiation damage on the data become significant. These experiments combine the use of enhanced coherent diffraction imaging with single-shot XFEL radiation to investigate the cellular architecture of Staphylococcus aureus with and without labeling by gold (Au) nanoclusters. The resolution of the images reconstructed from these diffraction patterns were twice as high or more for gold-labeled samples, demonstrating that this enhancement method provides a promising approach for the high-resolution imaging of biomaterials and biological systems.
High Fructose Diet inducing diabetes rapidly impacts olfactory epithelium and behavior in mice
Authors: Rivière Sébastien , Soubeyre Vanessa , Jarriault David , Molinas Adrien , Léger-Charnay Elise , Desmoulins Lucie , Grebert Denise , Meunier Nicolas , Grosmaitre Xavier
Published: September 2016

Type 2 Diabetes (T2D), a major public health issue reaching worldwide epidemic, has been correlated with lower olfactory abilities in humans. As olfaction represents a major component of feeding behavior, its alteration may have drastic consequences on feeding behaviors that may in turn aggravates T2D. In order to decipher the impact of T2D on the olfactory epithelium, we fed mice with a high fructose diet (HFruD) inducing early diabetic state in 4 to 8 weeks. After only 4 weeks of this diet, mice exhibited a dramatic decrease in olfactory behavioral capacities. Consistently, this decline in olfactory behavior was correlated to decreased electrophysiological responses of olfactory neurons recorded as a population and individually. Our results demonstrate that, in rodents, olfaction is modified by HFruD-induced diabetes. Functional, anatomical and behavioral changes occurred in the olfactory system at a very early stage of the disease.
Dual-Wavelength Terahertz Metasurfaces with Independent Phase and Amplitude Control at Each Wavelength
Authors: Ding Jun , Xu Ningning , Ren Han , Lin Yuankun , Zhang Weili , Zhang Hualiang
Published: September 2016

We have designed, fabricated and characterized dual-wavelength metasurfaces that function at two assigned terahertz wavelengths with independent phase and amplitude control at each wavelength. Specifically, we have designed a dual-wavelength achromatic metasurface-based deflector deflecting the incident wave to the same direction at two selected wavelengths, which has circumvented the critical limitation of strong wavelength dependence in the planar metasurface-based devices caused by the resonant nature of the plasmonic structures. As a proof of concept demonstration, the designed dual-wavelength achromatic deflector has been fabricated and characterized experimentally. The numerical simulations, theoretical predictions and experimental results agree very well with each other, demonstrating the property of independently manipulating the phase profiles at two wavelengths. Furthermore, another unique feature of the designed metasurface is that it can independently tailor both the phase and amplitude profiles at two wavelengths. This property has been numerically validated by engineering a metasurface-based device to simultaneously generate two diffraction orders at two desired wavelengths.
Transcranial focused ultrasound stimulation of human primary visual cortex
Authors: Lee Wonhye , Kim Hyun-Chul , Jung Yujin , Chung Yong An , Song In-Uk , Lee Jong-Hwan , Yoo Seung-Schik
Published: September 2016

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.
Sexually dimorphic gene expressions in eels: useful markers for early sex assessment in a conservation context
Authors: Geffroy Benjamin , Guilbaud Florian , Amilhat Elsa , Beaulaton Laurent , Vignon Matthias , Huchet Emmanuel , Rives Jacques , Bobe Julien , Fostier Alexis , Guiguen Yann , Bardonnet Agnès
Published: September 2016

Environmental sex determination (ESD) has been detected in a range of vertebrate reptile and fish species. Eels are characterized by an ESD that occurs relatively late, since sex cannot be histologically determined before individuals reach 28 cm. Because several eel species are at risk of extinction, assessing sex at the earliest stage is a crucial management issue. Based on preliminary results of RNA sequencing, we targeted genes susceptible to be differentially expressed between ovaries and testis at different stages of development. Using qPCR, we detected testis-specific expressions of dmrt1, amh, gsdf and pre-miR202 and ovary-specific expressions were obtained for zar1, zp3 and foxn5. We showed that gene expressions in the gonad of intersexual eels were quite similar to those of males, supporting the idea that intersexual eels represent a transitional stage towards testicular differentiation. To assess whether these genes would be effective early molecular markers, we sampled juvenile eels in two locations with highly skewed sex ratios. The combined expression of six of these genes allowed the discrimination of groups according to their potential future sex and thus this appears to be a useful tool to estimate sex ratios of undifferentiated juvenile eels.