bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Corneal Endothelial Cell Assessment From Tissues Preserved in Serum-Based and Synthetic Storage Media
Authors: Parekh Mohit , Ruzza Alessandro , Ponzin Diego , Ahmad Sajjad , Ferrari Stefano
Published: August 2019

Purpose:

To assess the difference between endothelial cells from tissues preserved in media supplemented with fetal bovine serum (FBS) and recombinant human serum albumin (rHSA).

Methods:

In a donor-matched study, 48 tissues were preserved for 28 days at 31°C in Cornea Max and Cornea Syn supplemented with FBS and rHSA, respectively. Endothelial cells were visualized by 2 masked observers before and after preservation. Endothelial cell density (ECD) and the number of iatrogenic folds were counted manually. Alizarin red staining and tight junction protein (Zonula Occludens-1) were used to assess cell morphology (hexagonality and polymorphism). Intraobserver and interobserver cell counts were recorded and analyzed. Wilcoxon and one-way analysis of variance tests were used, where P < 0.05 was deemed statistically significantly different.

Results:

Significant amount of iatrogenic folds were observed in the tissues supplemented with FBS compared with rHSA postpreservation (P = 0.0007). Approximately 69% and 71% hexagonal cells (P = 0.0303) and 29% and 26% polymorphic cells (P = 0.0234) were observed in the FBS and rHSA groups, respectively. Postpreservation, operator 1 counted 1766 cells/mm2 in FBS and 1864 cells/mm2 in rHSA. Operator 2 counted 1702 cells/mm2 in FBS and 1858 cells/mm2 in rHSA. ECD counts from FBS (interoperator) were statistically significant (P = 0.0429). However, significance was not observed in the ECD counts (interoperator) from the rHSA-preserved tissues (P = 0.8738).

Conclusions:

rHSA-supplemented media allow better visualization of the corneal endothelial cells. This reduces the rate of discard observed due to counting errors. Use of rHSA improves the current standard of care and reduces the use of animal-derived products.
Adjuvant and neoadjuvant therapy for pancreatic cancer
Authors: Maeda Shimpei , Unno Michiaki , Yu Jun
Published: August 2019

Pancreatic cancer still remains a major cause of cancer-related mortality; however, there is a slight but continuous improvement in survival over the past 2 decades. Progress in chemotherapy has contributed to the survival improvement in patients with any stage of pancreatic cancer. In this review, we summarize the currently available evidence regarding adjuvant and neoadjuvant therapy with a focus mainly on randomized controlled trial. The median overall survival in resected pancreatic cancer patients has significantly improved to 22.8 to 54.4 months with the use of adjuvant therapy from 11 to 20.2 months with a strategy of observation only. Recent data from randomized trials support the use of neoadjuvant therapy for patients with resectable or borderline resectable pancreatic cancer. But given a variety of neoadjuvant regimens and different definitions of resectability status, data should be interpreted with caution. Several other trials are ongoing and will provide further evidence.
Evaluation of Renal Function Disorder With Urinary Neutrophil Gelatinase–associated Lipocalin Level in Patients With β-Thalassemia Major
Authors: Karaman Kamuran , Şahin Serdar , Geylan Hadi , Yaşar Akkiz Şahin , Çetin Mecnun , Kömüroğlu Ahmet U. , Öner Ahmet F.
Published: August 2019

Background and Aim:

Neutrophil gelatinase–associated lipocalin (NGAL) is found in the granules of human neutrophils, with many diverse functions. Expression of NGAL is induced under various pathophysiological conditions, for example, infection, inflammation, kidney injury, cardiovascular disease, burn injury, and intoxication, and it has an important antiapoptotic and anti-inflammatory role.

Patients and Methods:

A total of 37 patients with thalassemia disease β-thalassemia major (24 male and 13 female individuals) and 37 healthy controls (17 male and 20 female) were enrolled in this study. All patients were regularly transfused, and all of them were using oral chelator, deferasirox.

Results:

NGAL and cystatin C levels were significantly higher in the case group than in the control group.

Conclusion:

In patients with β-thalassemia major, renal damage can occur owing to regular blood transfusion. Urinary NGAL levels in these patients may be considered as a marker for early renal injury.
Information and Training Needs of Pediatric Oncologists in Complementary and Integrative Medicine: A Cross-Sectional Study
Authors: Reis Daniela , Güthlin Corina , Schildmann Jan , Zuzak Tycho J. , Hilje Clara C. , Längler Alfred
Published: August 2019

More than one third of all German pediatric patients with cancer use complementary and integrative medicine (CIM). Parents want to discuss the topic of CIM with their pediatric oncologists (POs); however, POs mostly do not feel confident discussing these topics. POs report openness to receiving further information and training, but CIM training opportunities in medical education seem rare. We investigated POs’ information and training needs and preference patterns regarding CIM training content with a paper-based or online survey. A total of 101 POs from Germany completed the survey. Only 11.4% agreed to being sufficiently informed of CIM. The participants stated needing further CIM information very often (8.6%), often (38.7%), or occasionally (44.1%). They considered an overview of CIM therapies and information about relaxation methods, herbal remedies, and acupuncture for cancer-related symptoms such as lack of appetite, nausea, or vomiting as most important in CIM training material, and also the topics of adverse effects and summary of evidence. Finally, POs reported on clinical situations in which a need for further information on CIM emerged. The results of our study indicate that there is a need for a structured training that offers knowledge and skills on the subject of patient counseling on CIM in pediatric oncology.
Improving Respiratory Support Practices to Reduce Chronic Lung Disease in Premature Infants
Authors: Levesque Bernadette M. , Burnham Laura , Cardoza Natasha , Adams Marsha , Cohen Robyn , Mirochnick Mark , Fujii Alan , Sinha Bharati
Published: August 2019

Introduction:

We implemented a bundle of respiratory care practices and optimized delivery of continuous positive airway pressure (CPAP) to reduce the incidence of chronic lung disease (CLD) among very low birth weight (VLBW) infants born before 33 weeks gestation.

Methods:

Our multidisciplinary task force utilized 6 plan-do-study-act cycles to test our interventions. The primary outcome was the quarterly percentage of infants diagnosed with CLD; other outcomes included the percentage of infants initially managed with CPAP, intubation <72 hours of age, use of a nasal cannula, and days of ventilation, oxygen, and/or CPAP. Process measures included compliance with each of the 5 components of the bundle; balancing measures included mortality and complications of prematurity.

Results:

Demographics were similar in the 55 infants born before and 76 infants born after the task force interventions, except for gestational age, which was lower before. CLD decreased by 55.5% (from 37.5% to 16.7%). Quarterly percentage of infants requiring intubation decreased from 87.5% to 40.8%. Quarterly average days of ventilation decreased from 11.2 to 6.1, and days of supplemental oxygen declined from 44.1 to 25.4, while the use of CPAP increased. There were no differences in adverse events including mortality, pneumothorax, use of postnatal steroids, or any retinopathy of prematurity. The incidence of patent ductus arteriosus declined from 60% to 33% (P < 0.01).

Conclusions:

We reduced the incidence of CLD among our very low birth weight infants born before 33 weeks gestation by over 50% without increasing any measured adverse outcomes. The incidence of patent ductus arteriosus declined.
Immediate Reconstruction of Amputated Ear With Fascia Flap
Authors: Kim Beom-Jun , You Jae-Pil , Jung Jae-A , You Hi-Jin , Kim Deok-Woo
Published: August 2019

Background:

Various surgical methods have been used for reconstruction of an amputated ear, including microsurgical replantation and delayed reconstruction using synthetic material or autologous rib cartilage. The authors share our experience of immediate reconstruction using amputated cartilage and discuss the advantages compared to other techniques of reconstruction.

Materials and Methods:

The authors retrospectively reviewed the medical records of 3 patients who underwent immediate reconstruction of amputated ear by a single operator. In the cases, the amputees were washed; the skin and cartilage were separated. The ear cartilage was fixed to its original position with non-absorbable suture. Regional fascia flap was elevated and covered the ear cartilage. The amputee skin was redraped to cover the fascia flap. Several months after the operation, photographic assessment was done.

Results:

All 3 cases showed well-defined convolution, tolerable skin color, and patient satisfaction without any major complications. A patient showed mild temporal incision site alopecia.

Conclusion:

The above immediate reconstruction method can achieve reliable and favorable result with minimal complications.
Morphological and molecular evidence for range extension and first occurrence of the Japanese seahorse,Hippocampus mohnikei(Bleeker 1853) in a bay-estuarine system of Goa, central west coast of India
Authors: Sanaye Sushant , Khandeparker Rakhee , Sreepada Rayadurga Anantha , Shivaramu Mamatha Singanahalli , Kankonkar Harshada , Narvekar Jayu , Gauthankar Mukund
Published: August 2019

Accurate information of taxonomy and geographic range of seahorse species (genusHippocampus) is the first step in preparing threat assessments and designing effective conservation measures. Here, we report the range expansion and first occurrence of the Japanese seahorse,Hippocampus mohnikei(Bleeker, 1853) from the Mandovi estuarine ecosystem of Goa, central west coast of India (CWCI) based on morpho-molecular analyses. The morphometric and meristic traits particularly, short snout (29–35% head length), double cheek spine, low coronet and long tail (51.2–57.9% of standard length), 11 trunk rings, 37–39 tail rings, 15–16 dorsal and 12–14 fin rays observed in four collected specimens matched with the reported key diagnostic morphological criteria of vouchered specimens ofH. mohnikei. The seahorse mitochondrial cytochrome oxidase subunit I (COI) and cytochromeb(Cytb) genes were partially sequenced for conclusive genetic identification of the species under study. Molecular analysis showed that all four individuals of seahorse species clustered together suggesting a monophyletic lineage. Using the maximum similarity with GenBank database, maximum likelihood network and subsequent morphological analysis, the identity of the collected seahorse species was reconfirmed asH. mohnikei. With this new report, the geographic range ofH. mohnikeiextended significantly to the westward side from its previously known range. This new sighting ofH. mohnikeicould indicate a long-distance dispersal facilitated by due to prevailing oceanic circulation in the Indo-Pacific region or increased habitat suitability in bay-estuarine systems of Goa, CWCI. Comparison of the pair-wise genetic distances (Kimura 2-parameter) based on COI and Cytbsequences revealed that the specimens examined in this study are genetically closer toH. mohnikeipopulations from Vietnam and Thailand than they are to those in Japan and China. To test the hypothesis whetherH. mohnikeiare vagrants or previously unreported established population, long-term inter-annual sampling and analyses are warranted.
A comparison of automated and manual co-registration for magnetoencephalography
Authors: Houck Jon M. , Claus Eric D.
Published: August 2019

Magnetoencephalography (MEG) is a neuroimaging technique that accurately captures the rapid (sub-millisecond) activity of neuronal populations. Interpretation of functional data from MEG relies upon registration to the participant’s anatomical MRI. The key remaining step is to transform the participant’s MRI into the MEG head coordinate space. Although both automated and manual approaches to co-registration are available, the relative accuracy of two approaches has not been systematically evaluated. The goal of the present study was to compare the accuracy of manual and automated co-registration. Resting MEG and T1-weighted MRI data were collected from 90 participants. Automated and manual co-registration were performed on the same subjects, and the inter-method reliability of the two methods assessed using the intra-class correlation. Median co-registration error for both methods was within acceptable limits. Inter-method reliability was in the “good” range for co-registration error, and the “good” to “excellent” range for translation and rotation. These results suggest that the output of the automated co-registration procedure is comparable to that achieved using manual co-registration.
Simultaneous optimization of donor and acceptor substrate specificity for transketolase by a small but smart library
Authors: Yu Haoran , López Roberto Icken Hernández , Steadman David , Méndez-Sánchez Daniel , Higson Sally , Cázares-Körner Armando , Ward John M. , Hailes Helen C. , Dalby Paul A.
Published: August 2019

A narrow substrate range is a major limitation in exploiting enzymes more widely as catalysts in synthetic organic chemistry. For enzymes using two substrates, the simultaneous optimization of both substrate specificities, is also required for the rapid expansion of accepted substrates. Transketolase catalyses the reversible transfer of a C2-ketol unit from a donor substrate to an aldehyde acceptor and suffers the limitation of narrow substrate scope for widely industrial applications. Herein, transketolase from E. coli was engineered to simultaneously accept both pyruvate as a novel donor substrate, and unnatural acceptor aldehydes, including propanal, pentanal, hexanal and 3-formylbenzoic acid. Twenty single-mutant variants were firstly designed and characterized experimentally. Beneficial mutations were then recombined to construct a small but smart library. Screening of this library identified the best variant with a 9.2-fold improvement in the yield towards pyruvate and propionaldehyde, relative to WT. Pentanal and hexanal were used as acceptors to determine stereoselectivities of the reactions, which were found to be higher than 98% ee for the S configuration. Three variants were identified to be active for the reaction between pyruvate and 3-formylbenzoic acid. The best variant was able to convert 47% of substrate into product within 24 h, whereas no conversion was observed for WT. Docking experiments suggested a cooperation between the mutations responsible for donor and acceptor acceptances, that would promote the activity towards both the acceptor and donor. The variants obtained have the potential to be used for developing catalytic pathways to a diverse range of high-value products.
A VP2/3-derived peptide exhibits potent antiviral activity against BK and JC polyomaviruses by targeting a novel VP1 binding site
Authors: Kane Joshua R. , Fong Susan , Shaul Jacob , Frommlet Alexandra , Frank Andreas O. , Knapp Mark , Bussiere Dirksen E. , Kim Peter , Ornelas Elizabeth , Cuellar Carlos , Abend Johanna R. , Wartchow Charles A.
Published: August 2019

In pursuit of effective therapeutics for human polyomaviruses, we identified a peptide derived from the BK polyomavirus (BKV) minor structural proteins VP2/3 that is a potent inhibitor of BKV infection with no observable cellular toxicity. The thirteen amino acid peptide binds to major structural protein VP1 in a new location within the pore with a low nanomolarKD. Alanine scanning of the peptide identified three key residues, substitution of each of which results in ∼1000-fold loss of affinity with a concomitant reduction in antiviral activity. NMR spectroscopy and an X-ray structurally-guided model demonstrate specific binding of the peptide to the pore of the VP1 pentamer that constitutes the BKV capsid. Cell-based assays with the peptide demonstrate nanomolar inhibition of BKV infection and suggest that the peptide likely blocks the viral entry pathway between endocytosis and escape from the host cell ER. The peptide motif is highly conserved among the polyomavirus clade, and homologous peptides exhibit similar binding properties for JC polyomavirus and inhibit infection with similar potency to BKV in a model cell line. Substitutions within VP1 or VP2/3 residues involved in VP1-peptide interaction negatively impact viral infectivity, potentially indicating the peptide-binding site within the VP1 pore is relevant for VP1-VP2/3 interactions. The inhibitory potential of the peptide-binding site first reported here may present a novel target for development of new anti-polyomavirus therapies. In summary, we present the first anti-polyomavirus inhibitor that acts via a novel mechanism of action by specifically targeting the pore of VP1.
Large-scale changes to mRNA polyadenylation in temporal lobe epilepsy
Authors: Parras Alberto , de Diego-Garcia Laura , Alves Mariana , Beamer Edward , Conte Giorgia , Morgan James , Ollà Ivana , Hernandez-Santana Yasmina , Delanty Norman , Farrell Michael A. , O’Brien Donncha F. , Henshall David C. , Méndez Raúl , Lucas José J. , Engel Tobias
Published: August 2019

The molecular mechanisms that shape the gene expression landscape during the development and maintenance of chronic states of brain hyperexcitability are incompletely understood. Here we show that cytoplasmic mRNA polyadenylation, a posttranscriptional mechanism for regulating gene expression, undergoes widespread reorganisation in temporal lobe epilepsy. Specifically, over 25% of the hippocampal transcriptome displayed changes in their poly(A) tail in mouse models of epilepsy, particular evident in the chronic phase. The expression of cytoplasmic polyadenylation binding proteins (CPEB1-4) was found to be altered in the hippocampus in mouse models of epilepsy and temporal lobe epilepsy patients and CPEB4 target transcripts were over-represented among those showing poly(A) tail changes. Supporting an adaptive function, CPEB4-deficiency leads to an increase in seizure severity and neurodegeneration in mouse models of epilepsy. Together, these findings reveal an additional layer of gene expression control during epilepsy and point to novel targets for seizure control and disease-modification in epilepsy.
A widespread role for SLC transmembrane transporters in resistance to cytotoxic drugs
Authors: Girardi Enrico , César-Razquin Adrián , Papakostas Konstantinos , Lindinger Sabrina , Konecka Justyna , Hemmerich Jennifer , Kickinger Stefanie , Kartnig Felix , Ingles-Prieto Alvaro , Fiume Giuseppe , Ringler Anna , Lardeau Charles-Hugues , Kandasamy Richard Kumaran , Kubicek Stefan , Ecker Gerhard F. , Superti-Furga Giulio
Published: August 2019

The activity and potency of a drug is inherently affected by the metabolic state of its target cell. Solute Carriers (SLCs) represent the largest family of transmembrane transporters in humans and constitute major determinants of cellular metabolism. Several SLCs have been shown to be required for the uptake of individual chemical compounds into cellular systems, but systematic surveys of transporter-drug relationships in human cells are currently lacking. We performed a series of genetic screens in the haploid human cell line HAP1 using a set of 60 cytotoxic compounds representative of the chemical space populated by approved drugs. By using a SLC-focused CRISPR/Cas9 lentiviral library, we identified transporters whose absence induced resistance to the drugs tested. Among the hundreds of drug-SLC relationships identified, we confirmed the role of the folate transporter SLC19A1 on the activity of antifolates and of SLC29A1 on several nucleoside analogs. Among the newly discovered dependencies, we identified the transporters SLC11A2/SLC16A1 for artemisinin derivatives and SLC35A2/SLC38A5 for cisplatin. The functional dependence on SLCs observed for a significant proportion of the compounds screened suggested a widespread role for SLCs in the uptake and cellular activity of cytotoxic drugs and provided an experimentally validated set of SLC-drug associations for a number of clinically relevant compounds.
Transcriptome Analysis of xa5-mediated Resistance to Bacterial Leaf Streak in Rice (Oryza sativa L.)
Authors: Xie Xiaofang , Chen Zhiwei , Guan Huazhong , Zheng Yan , Zhang Jing , Qin Mingyue , Wu Weiren
Published: August 2019

Bacterial leaf steak (BLS) caused by Xanthomonas oryzae pv. oryzicola (Xoc) is a devastating disease in rice production. The resistance to BLS in rice is a quantitatively inherited trait, of which the molecular mechanism is still unclear. It has been proved that xa5, a recessive bacterial blast resistance gene, is the most possible candidate gene of the QTL qBlsr5a for BLS resistance. To study the molecular mechanism of xa5 function in BLS resistance, we created transgenic lines with RNAi of Xa5 (LOC_Os05g01710) and used RNA-seq to analyze the transcriptomes of a Xa5-RNAi line and the wild-type line at 9 h after inoculation with Xoc, with the mock inoculation with water as control. The results showed that Xa5-RNAi could (1) increase the resistance to BLS as expected from xa5; (2) alter (mainly up-regulate) the expression of hundreds of genes, most of which were related to disease resistance; and (3) greatly enhance the response of thousands of genes to Xoc infection, especially of the genes involved in cell death pathways, suggesting that xa5 displays BLS resistance effect probably mainly because of the enhanced response of the cell death-related genes to Xoc infection.
In silicoanalysis ofCDC73gene revealing 11 novel SNPs associated with Jaw Tumor Syndrome
Authors: Abdelmoneim Abdelrahman H. , Mohammed Alaa I. , Gadim Esraa O. , A.Mohammed Mayada , Hamza Sara H. , Mirghani Sara A. , Mahmoud Thwayba A. , Hassan Mohamed A.
Published: August 2019

Back ground

hyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the effect of SNPs onCDC73structure and function using different bioinformatics tools.

Method

Computational analysis using eight differentin-silicotools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, PMut and Imutant were used to identify the impact on the structure and/or function ofCDC73gene that might be causing jaw tumour.

Results

From (733) SNPs identified in theCDC73gene we found that only Eleven were deleterious to the function and structure of protein and expected to cause syndrome.

Conclusion

Eleven substantial genetic/molecular aberrations inCDC73gene were identified that could serve as actionable targets for chemotherapeutic intervention in patients whose disease is no longer surgically curable.
Effects of dietary NFC/NDF on rumen microbiomes of Karakul sheep based on Three Generations of Full-length Amplifiers sequencing
Authors: Pu Xuanxuan , Guo Xuefeng , Jiang Chenyu , Liu Junfeng , Zhang Xiuping , Zhang Sujiang , Cheng Long , Shan Anshan
Published: August 2019

An study was was conducted to investigate the effects of dietary(non fibrous carbohydrate) NFC/(neutral detergent fiber)NDF on ruminal bacteria in Karakul sheep. Twelve Karakul sheep were assigned randomly to four dietary treatments of NFC/NDF (0.78, 1.23, 1.61 and 2.00 respectively) as group 1, 2, 3 to 4. The experiment lasted for four periods, period I (1~18 d), II (19~36 d), III (37~54 d) and IV (55~72 d). Ruminal digesta were collected consecutively for three days to measure pH and bacteria per period. The results indicated that the average ruminal pH and amounts of OTUs were decreased with the increase of dietary NFC/NDF for four periods. At phylum level, Bacteroidetes and Firmicutes were the predominant bacteria of four periods, Bacteroidetes were decreased, while the relative abundance of Firmicutes was increased with dietary NFC/NDF for four periods, but the difference wasn’t significant (P>0.05). At genus level, the most relative abundance genus was unidentified-Lachnospiraceae which reached the highest in group 3 for four periods, but the difference wasn’t significant (P>0.05). Conclusion: ruminal pH and bacteria were decreased with the increase of dietary NFC/NDF and the most dominant bacteria were not change with dietary NFC/NDF and periods in Karakul sheep.
Cryo-EM structure of full-length HIV-1 Env bound with the Fab of antibody PG16
Authors: Pan Junhua , Peng Hanqin , Chen Bing , Harrison Stephen C.
Published: August 2019

The HIV-1 envelope protein (Env) is the target of neutralizing antibodies and the template for vaccine immunogen design. The dynamic conformational equilibrium of trimeric Env influences its antigenicity and potential immunogenicity. Antibodies that bind at the trimer apex stabilize a “closed” conformation characteristic of the most difficult to neutralize isolates. A goal of vaccine development is therefore to mimic the closed conformation in a designed immunogen. A disulfide-stabilized, trimeric Env ectodomain -- the “SOSIP” construct -- has many of the relevant properties; it is also particularly suitable for structure determination. Some single-molecule studies have, however, suggested that the SOSIP trimer is not a good representation of Env on the surface of a virion or an infected cell. We isolated Env (fully cleaved to gp120 and gp41) from the surface of expressing cells using tagged, apex-binding Fab PG16 and determined the structure of the PG16-Env complex by cryo-EM to an overall resolution of 4.6 Å. Placing the only purification tag on the Fab ensured that the isolated Env was continuously stabilized in its closed, native conformation. The Env structure in this complex corresponds closely to the SOSIP structures determined by both x-ray crystallography and cryo-EM. Although the membrane-interacting elements are not resolved in our reconstruction, we can make inferences about the connection between ectodomain and membrane-proximal external region (MPER) by reference to the published cryo-tomography structure of an Env “spike” and the NMR structure of the MPER-transmembrane segment. We discuss these results in view of the conflicting interpretations in the literature.
Mapping the living mouse brain neural architecture: strain specific patterns of brain structural and functional connectivity
Authors: Karatas Meltem , Noblet Vincent , Nasseef Md Taufiq , Bienert Thomas , Reisert Marco , Hennig Jürgen , Yalcin Ipek , Kieffer Brigitte Lina , von Elverfeldt Dominik , Harsan Laura-Adela
Published: August 2019

Mapping the structural and functional brain connectivity fingerprints became an essential approach in neurology and experimental neuroscience because network properties can underlie behavioral phenotypes. In mouse models, revealing strain related patterns of brain wiring have a tremendous importance, since these animals are used to answer questions related to neurological or neuropsychiatric disorders. C57BL/6 and BALB/cJ inbred strains are primary “genetic backgrounds” for brain disease modelling and for testing therapeutic approaches. Nevertheless, extensive literature describes basal differences in the behavioral, neuroanatomical and neurochemical profiles of the two strains, which raises the question whether the observed effects are pathology specific or depend on the genetic background. Here we performed a systematic comparative exploration of brain structure and function of C57BL/6 and BALB/cJ mice via Magnetic Resonance Imaging (MRI). We combined voxel-based morphometry (VBM), diffusion MRI and high resolution fiber mapping (hrFM) and resting state functional MRI (rs-fMRI) and depicted brain-wide dissimilarities in the morphology and “connectome” features in the two strains. Particularly C57BL/6 animals show bigger and denser frontal cortical areas, cortico-striatal tracts and thalamic and midbrain pathways, and higher density of fibers in the genu and splenium of the corpus callosum. These features are fairly reflected in the functional connectograms that emphasize differences in “hubness”, frontal cortical and basal forbrain connectivity. We demonstrate strongly divergent reward-aversion circuitry patterns and some variations of the default mode network features. Inter-hemispherical functional connectivity showed flexibility and adjustment regarding the structural patterns in a strain specific manner. We further provide high-resolution tractograms illustrating also inter-individual variability across inter-hemispherical callosal pathways in the BALB/cJ strain.
Dynamic control of cortical head-direction signal by angular velocity
Authors: Finkelstein Arseny , Rouault Hervé , Romani Sandro , Ulanovsky Nachum
Published: August 2019

The sense of direction requires accurate tracking of head direction at different turning-velocities, yet it remains unclear how this is achieved in the mammalian brain. Here we recorded head-direction cells in bat dorsal presubiculum and found that, surprisingly, the head-direction signal in this cortical region was dynamically controlled by angular velocity. In most neurons, a sharp head-direction tuning emerged at some angular velocity, but was absent at other velocities – resulting in a 4-fold increase in head-direction cell abundance. The head-direction tuning changed as a function of angular velocity primarily via a redistribution of spikes between the neuron’s preferred and null directions – while keeping the average firing-rate constant. These results could not be explained by existing ‘ring-attractor’ models of the head-direction system. We propose a novel recurrent network model that accounts for the observed dynamics of head-direction cells. This model predicts that the new classes of cells we found can improve the sensitivity of the head-direction system to directional sensory cues, and support angular-velocity integration.
Using a novel web application for thermodynamic characterization ofTel22G-quadruplex unfolding
Authors: Prislan I. , Sajko S. , Poklar Ulrih N. , Fuerst L.
Published: August 2019

Measuring and quantifying thermodynamic parameters that determine stability of and interactions between biological macromolecules is an essential and necessary complement to structural studies. Although several laboratories are able to obtain basic thermodynamic parameters for the observed process, the data interpretation and analysis quality of reported data can be extremely tedious. We have started to develop a web application that will help users to perform thermodynamic characterization of G-quadruplex unfolding. The application can perform global fitting of calorimetric and spectroscopic data, and it uses a three-state equilibrium model to obtain thermodynamic parameters for each transition step: the Gibbs energy, the enthalpy, and the heat capacity. As well as these, the application can define the number of K+ions and the number of water molecules being released or taken up during the unfolding. To test our application, we used UV spectroscopy, circular dichroism, and differential scanning calorimetry, to monitor folding and unfolding of a model 22-nucleotide-long sequence of human 3’-telomeric overhang, known asTel22. The obtained data was fed to the web application and global fit revealed that unfolding ofTel22involves at least one intermediate state, and that K+ions are released during the unfolding, whereas water molecules are taken up.

STATEMENT OF SIGNIFICANCE

The laws of thermodynamics provide tools for the use of elegant mathematical expressions to describe stabilities and interactions of biological macromolecule. Even though thermodynamic profiles of simple transitions (e.g., two state) can be obtained in a relatively straightforward manner, performing thermodynamic analysis of complex/ multistep transitions or global analysis of several experimental data requires some experiences and skills. In the present study we are demonstrating how newly developed web application can be used to provide better understanding of driving forces responsible for the structural interconversion of G-quadruplex structures. We have tested this web application with experimental data obtained from monitoring thermal folding/ unfolding of the 5’-AG3T2AG3T2AG3T2AG3-3’ (Tel22) DNA sequence. We believe that this application can be used as a research and/or teaching tool, and it will allow comparisons of the thermodynamic parameters obtained between different laboratories.
A nutritional memory impairs survival, transcriptional and metabolic response to dietary restriction in old mice
Authors: Hahn Oliver , Drews Lisa F. , Nguyen An , Tatsuta Takashi , Gkioni Lisonia , Hendrich Oliver , Zhang Qifeng , Langer Thomas , Pletcher Scott , Wakelam Michael J. O. , Beyer Andreas , Grönke Sebastian , Partridge Linda
Published: August 2019

Dietary restriction (DR) during adulthood can greatly extend lifespan and improve metabolic health in diverse species. However, whether DR in mammals is still effective when applied for the first time at old age remains elusive. Here, we conducted a late-life DR switch experiment employing 800 mice, by switching old animals from ad libitum (AL) to DR and vice versa. Strikingly, the switch from DR-to-AL acutely increased mortality, while the switch from AL-to-DR caused only a weak and gradual increase in survival, highlighting a memory of earlier nutrition. A significant association between fat preservation and survival response pointed to the white adipose tissue (WAT) as a potential memory source. Consistently, post-switch RNA-seq profiling in liver and WAT demonstrated that the transcriptional and metabolic program of chronic DR remained largely refractory to the AL-to-DR switch specifically in adipose tissue. Integration of lipidomics confirmed impaired membrane lipogenesis and limited mitochondrial copy number increase under late-life DR as functional consequences of this memory effect. Together, our results provide evidence for a nutritional memory as a limiting factor for DR-induced longevity and metabolic remodeling of WAT in mammals.
Occurrence and stability of hetero-hexamer associations formed by β-carboxysome CcmK shell components
Authors: Garcia-Alles Luis F. , Root Katharina , Maveyraud Laurent , Aubry Nathalie , Lesniewska Eric , Mourey Lionel , Zenobi Renato , Truan Gilles
Published: August 2019

The carboxysome is a bacterial micro-compartment (BMC) subtype that encapsulates enzymatic activities necessary for carbon fixation. Carboxysome shells are composed of a relatively complex cocktail of proteins, their precise number and identity being species dependent. Shell components can be classified in two structural families, the most abundant class associating as hexamers (BMC-H) that are supposed to be major players for regulating shell permeability. Up to recently, these proteins were proposed to associate as homo-oligomers. Genomic data, however, demonstrated the existence of paralogs coding for multiple shell subunits. Here, we studied cross-association compatibilities among BMC-H CcmK proteins of Synechocystis sp. PCC6803. Co-expression in Escherichia coli proved a consistent formation of hetero-hexamers combining CcmK1 and CcmK2 or, remarkably, CcmK3 and CcmK4 subunits. Unlike CcmK1/K2 hetero-hexamers, the stoichiometry of incorporation of CcmK3 in associations with CcmK4 was low. Cross-interactions implicating other combinations were weak, highlighting a structural segregation of the two groups that could relate to gene organization. Sequence analysis and structural models permitted to localize interactions that would favor formation of CcmK3/K4 hetero-hexamers. Attempts to crystallize these CcmK3/K4 associations conducted to the unambiguous elucidation of a CcmK4 homo-hexamer structure. Yet, subunit exchange could not be demonstrated in vitro. Biophysical measurements showed that hetero-hexamers are thermally less stable than homo-hexamers, and impeded in forming larger assemblies. These novel findings are discussed in frame with reported data to propose a functional scenario in which minor CcmK3/K4 incorporation in shells would introduce sufficient local disorder as to allow shell remodeling necessary to adapt rapidly to environmental changes.
Metabolic Control of Viral Infection through PPAR-α Regulation of STING Signaling
Authors: Tao Lili , Lowe Alexandria , Wang Guoxun , Dozmorov Igor , Chang Tyron , Yan Nan , Reese Tiffany A.
Published: August 2019

Peroxisomal proliferator activated receptors (PPARs) are sensors of dietary lipids and pharmacological targets in the treatment of metabolic disorders. PPAR ligands are also immunosuppressive. However, their function during infection is debated and the mechanisms that underlie their immunoregulatory properties are unclear. We investigated the consequences of PPAR activation during herpesvirus infection. We found that activation of PPAR-α increased herpesvirus replication, suppressed type I interferon production and induced reactive oxygen species (ROS). We discovered that ROS induced by PPAR-α stimulation suppressed the cytoplasmic DNA sensing pathway after direct activation of stimulator of interferon (STING), the ER adapter downstream of cytoplasmic DNA recognition. Although high ROS induces inflammasome activation and cytokine production, we found that ROS inhibited interferon production after cytoplasmic DNA recognition. Treatment of mice with a clinically relevant agonist of PPAR-α increased herpesvirus replication and pathogenesis, comparable to levels observed previously in type I interferon receptor knockout mice. These findings reveal that activation of PPAR-α regulates immunity to cytoplasmic DNA and DNA virus infection through inhibition of interferon. Moreover, these results demonstrate that STING signaling and interferon production is regulated by ROS.
Enhancement of corrosion protection of low nickel austenitic stainless steel by electroactive polyimide-CuO composites coating in chloride environment
Authors: Malav Jeetendra Kumar , Rathod Ramesh C. , Tandon Vipin , Patil Awanikumar P.
Published: August 2019

Purpose

The purpose of this study is to improve the anticorrosion performance of low nickel stainless steel (AISI 201) in 3.5% NaCl by electroactive polyimide/copper oxide (EPI/CuO) composites coating.

Design/methodology/approach

Electroactive polyimide/copper oxide (EPI/CuO) composites were prepared by oxidative coupling polymerization followed by thermal imidization method.

Findings

The functional and structural properties of composites were characterized by X-ray diffraction, Fourier transmission infra-red and ultra violet-visible spectroscopy and the surface topography was characterized by field emission scanning electron microscope analysis and anticorrosion performance in 3.5 Wt.% NaCl was evaluated by electrochemical techniques. The obtained results of electrochemical techniques measurement indicated that the composites coated samples give better corrosion protection against attacking electrolyte.

Originality/value

The ever-increasing price of nickel (Ni) is driving the industries to use low-Ni austenitic stainless steels (ASSs). However, it exhibits relatively poor corrosion resistance as compared with conventional Cr-Ni ASSs. Nonetheless, its corrosion resistance can be enhanced by polymeric (electroactive polyimide [EPI]) coating. CuO particles exhibit the hydrophobic properties and can be used as inorganic filler to incorporate in EPI to further enhance the corrosion protection. The present research paper is beneficial for industries to use low-cost AISI 201, enhance its corrosion resistance and replace the use of costly conventional Cr-Ni ASSs.
Corrosion resistance of composite coating used for fastener protection
Authors: Lin Zhifeng , Xu Likun , Li Xiangbo , Wang Li , Guo Weimin , Wu Chuanjie , Yang Yi
Published: August 2019

Purpose

The purpose of this paper is to examine the performance of a fastener composite coating system, sherardized (SD) coating/zinc-aluminum (ZA) coating whether it has good performance in marine environment.

Design/methodology/approach

In this paper, SD coating was fabricated on fastener surface by solid-diffusion method. ZA coating was fabricated by thermal sintering method. Corrosion behaviours of the composite coating were investigated with potentiodynamic polarization curves, open circuit potential and electrochemical impedance spectroscopy methods.

Findings

Neutral salt spray (NSS) and deep sea exposure tests revealed that the composite coating had excellent corrosion resistance. Polarization curve tests showed that corrosion current density of the sample with composite coating was significantly decreased, indicating an effective corrosion protection of the composite coating. OCP measurement of the sample in NaCl solution demonstrated that the composite coating had the best cathodic protection effect. The good corrosion resistance of the composite coating was obtained by the synergy of SD and ZA coating.

Practical implications

SD/ZA coating can be used in marine environment to prolong the life of carbon steel fastener.

Social implications

SD/ZA composite coating can reduce the risk and accident caused by failed fastener, avoid huge economic losses.

Originality/value

A new kind of composite coating was explored to protect the carbon steel fastener in marine environment. And the composite coating has the long-term anti-corrosion performance both in simulated and marine environment test.
Salt spray corrosion and electrochemical corrosion performances of Dacromet fabricated Zn–Al coating
Authors: Liu Xiaoxiao , Kong Dejun
Published: August 2019

Purpose

This study aims to investigate the salt spray corrosion (SSC) and electrochemical corrosion of obtained Zn–Al coating, which provided a basis for comprehensive analysis of corrosion behavior of Zn–Al coating.

Design/methodology/approach

A Zn–Al coating was fabricated on Q235A steel using a Dacromet method. The SSC and electrochemical corrosion performances in 3.5 Wt.% NaCl solution were investigated using an SSC chamber and electrochemical workstation, respectively, and the corrosion mechanism of Zn–Al coating was discussed.

Findings

The Dacromet fabricated Zn–Al coating is primarily composed of Zn and Al phases, its residual stress of −11.1 ± 4 MPa is compressive stress, which is beneficial to improve its corrosion resistance. In the SSC process, the corrosion product of Zn5(OH)8Cl2H2O enhances the corrosion resistance of Zn–Al coating, which provides sufficient cathodic protection for the substrate. The corrosion potential of Zn–Al coating is lower than that of substrate, which provides sufficient cathodic protection to the substrate, the Zn–Al coating in the immersion periods is protected by the corrosion product and Zn–Al sheets.

Originality/value

In this study, a Zn–Al coating was first fabricated on Q235A steel using a Dacromet method.
Microstructure, hardness and corrosion behaviour of friction-stir processed AA5083
Authors: Ramalingam Vaira Vignesh , Ramasamy Padmanaban , Datta Madhav
Published: August 2019

Purpose

The purpose of this study is to refine the microstructure and improve the corrosion behaviour of aluminium alloy AA5083 by subjecting it to friction stir processing (FSP).

Design/methodology/approach

FSP trials are conducted as per central composite design, by varying tool rotation speed, tool traverse speed and shoulder diameter at three levels. The microstructure is examined and the hardness is measured for both the base material and the processed workpieces. The corrosion behaviour of the base material and processed workpieces is studied using potentiodynamic polarization technique for three different testing temperatures, and the corrosion current and corrosion rate are calculated.

Findings

The results reveal that FSP refined the grains, dispersed secondary phases, increased the hardness and improved the corrosion resistance of most of the friction stir processed specimens than the base material at all the three testing temperatures. Grain refinement and fine dispersion of ß phase improves the hardness and corrosion resistance of most of the FSPed specimens. However partial dissolution of ß phase decreases the hardness in some of the specimens. Most of the FSPed specimens displayed more positive potential than the base material at all the testing temperatures representing a higher nobility than the base material, as a result of fine dispersion of secondary phase particles in the matrix. Large pits formed on the surface of the base specimen indicating a higher corrosion rate at all three testing temperatures. The SEM image of FSPed specimens reveals the occurrence of very few pits and minimal corrosion products on the surface, which indicates lower corrosion rate.

Originality/value

The corrosion mechanism of the friction stir-processed AA5083 specimens is found to be a combination of activation and concentration polarization.
Spatial synchrony of population dynamics: Empirical testing of mechanisms
Authors: Zytynska Sharon E.
Published: August 2019

In Focus:Vindstad, O. P. L., Jepsen, J. U., Yoccoz, N. G., Bjørnstad, O. N., Mesquita, M. d. S., & Ims, R. A. (2019). Spatial synchrony in sub‐arctic geometrid moth outbreaks reflects dispersal in larval and adult life cycle stages.Journal of Animal Ecology, 88, 1134–1145.https://doi.org/10.1111/1365-2656.12959. Spatial synchrony of population dynamics is a common phenomenon, but the understanding of underlying mechanisms is supported more by theoretical than empirical studies. Vindstad et al. (2019) use a 19‐year dataset on two moth species to disentangle the effects of different drivers of dispersal on the synchrony of populations. They show that geographic distance, species dispersal capabilities, a dispersal barrier and the prevailing wind direction are all factors that influence spatial synchrony. With current climate change and ongoing habitat fragmentation, understanding how dispersal influences spatial synchrony of population fluctuations, and the effect on population viability, is essential to predict future impacts on our ecosystems.
Chronic consumption of a high‐fat diet rich in corn oil activates intrinsic cell death pathway and induces several ultrastructural changes in the atria of healthy and type 1 diabetic rat
Authors: Eid Refaat A. , Eleawa Samy M. , Alkhateeb Mahmoud A. , Aldera Hussain , Zaki Mohamed Samir Ahmed , Al‐Shraim Mubarak , Saeed Mansour A. , El‐kott Attalla Farag , Alaa Eldeen Muhammad , Alassiri Mohammed , Alshehri Majed M. , Salem Al‐Shudiefat Abd Al‐Rahman , Khalil Mohammad A.
Published: August 2019

This study investigates the effect of chronic consumption of a high‐fat diet rich in corn oil (CO‐HFD) on atrial cells ultrastructure, antioxidant levels and markers of intrinsic cell death of both control and type 1 diabetes mellitus (T1DM)‐induced rats. Adult male rats (10 rats/group) were divided into four groups: control fed standard diet (STD) (3.82 kcal/g, 9.4% fat), CO‐HFD (5.4 kcal/g, 40% fat), T1DM fed STD, and T1DM + CO‐HFD. CO‐HFD and T1DM alone or in combination impaired systolic and diastolic functions of rats and significantly reduced levels of GSH and the activity of SOD, enhanced lipid peroxidation, increased protein levels of P53, Bax, cleaved caspase‐3, and ANF and decreased levels of Bcl‐2 in their atria. Concomitantly, atrial cells exhibited fragmentation of the myofibrils, disorganized mitochondria, decreased number of atrionatriuretic factor (ANF) granules, and loss of gap junctions accompanied by changes in capillary walls. Among all treatments, the severity of all these findings was more severe in T1DM and most profound in the atria of T1DM + CO‐HFD. In conclusion, chronic consumption of CO‐HFD by T1DM‐induced rats elicits significant biochemical and ultrastructural damage to rat atrial cells accompanied by elevated oxidative stress and mitochondria‐mediated cell death.