bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome‐wide and digital polymerase chain reaction epigenetic assessments of alcohol consumption
Authors: Philibert Robert , Dogan Meesha , Noel Amanda , Miller Shelly , Krukow Brianna , Papworth Emma , Cowley Joseph , Knudsen April , Beach Steven R. H. , Black Donald
Published: April 2018

The lack of readily employable biomarkers of alcohol consumption is a problem for clinicians and researchers. In 2014, we published a preliminary DNA methylation signature of heavy alcohol consumption that remits as a function of abstinence. Herein, we present new genome‐wide methylation findings from a cohort of additional subjects and a meta‐analysis of the data. Using DNA from 47 consecutive heavy drinkers admitted for alcohol detoxification in the context of alcohol treatment and 47 abstinent controls, we replicate the 2014 results and show that 21,221 CpG residues are differentially methylated in active heavy drinkers. Meta‐analysis of all data from the 448,058 probes common to the two methylation platforms shows a similarly profound signature with confirmation of findings from other groups. Principal components analyses show that genome‐wide methylation changes in response to alcohol consumption load on two major factors with one component accounting at least 50% of the total variance in both smokers and nonsmoking alcoholics. Using data from the arrays, we derive a panel of five methylation probes that classifies use status with a receiver operator characteristic area under the curve (AUC) of 0.97. Finally, using droplet digital polymerase chain reaction (PCR), we convert these array‐based findings to two marker assays with an AUC of 0.95 and a four marker set AUC of 0.98. We conclude that DNA methylation assessments are capable of quantifying alcohol use status and suggest that readily employable digital PCR approaches for substance consumption may find widespread use in alcohol‐related research and patient care.
Anthropometric and ultrasound measures of maternal adiposity in the first trimester of pregnancy
Authors: Kennedy Narelle , Quinton Ann , Peek Michael John , Lanzarone Valeria , Benzie Ron , Nanan Ralph
Published: April 2018

Aim

Estimations of central adiposity in pregnancy is a difficult undertaking due to physiological changes that occur in the body. Therefore, the value of some anthropometric measures particularly in pregnancy, such as body mass index (BMI), waist and hip measures are in doubt. The aim was to compare ultrasound (US) measured abdominal subcutaneous fat (USSFT) with other simple anthropometric methods for obesity assessment, evaluating these measures in pregnancy.

Method

Recruited from a larger study, anthropometric measurements were performed between 11–14 weeks’ gestation on 575 women. Measuring height, weight, hip, waist circumference, skin‐folds of the triceps, thigh and supra‐iliac and USSFT. Percentage maternal fat mass was calculated using skin‐fold measures. Correlations of these measures were performed to gauge relationships.

Results

The anthropometric measures demonstrated good correlation (0.54–0.93) between individual adipose measures skin‐folds, waist, hip, waist to height ratio (WSR) and USSFT with BMI, percentage fat mass and weight. USSFT correlated well with all anthropometric measures (0.54–0.73) correlating best with waist, WSR, BMI and weight. Waist/hip ratio demonstrated a poor correlation with USSFT, BMI, percentage fat mass and weight (0.3–0.41). Mean anthropometric measures were stratified across BMI categories describing adiposity distribution.

Conclusion

USSFT correlates well with most anthropometric measures in early pregnancy. Limitations of the gravid uterus on waist measurements, hydration and compressibility of skin‐fold measures and pregnancy influences on weight and BMI assessments could be overcome using US measures. There is a potential for post hoc evaluation using US for pregnancy complications. Maternal research could benefit from a more accurate measure of adiposity.
A Universal Organic Cathode for Ultrafast Lithium and Multivalent Metal Batteries
Authors: Fan Xiulin , Wang Fei , Ji Xiao , Wang Ruixing , Gao Tao , Hou Singyuk , Chen Ji , Deng Tao , Li Xiaogang , Chen Long , Luo Chao , Wang Luning , Wang Chunsheng
Published: April 2018

Low‐cost multivalent battery chemistries (Mg2+, Al3+) have been extensively investigated for large‐scale energy storage applications. However, their commercialization is plagued by the poor power density and cycle life of cathodes. A universal polyimides@CNT (PI@CNT) cathode is now presented that can reversibly store various cations with different valences (Li+, Mg2+, Al3+) at an extremely fast rate. The ion‐coordination charge storage mechanism of PI@CNT is systemically investigated. Full cells using PI@CNT cathodes and corresponding metal anodes exhibit long cycle life (>10000 cycles), fast kinetics (>20 C), and wide operating temperature range (−40 to 50 °C), making the low‐cost industrial polyimides universal cathodes for different multivalent metal batteries. The stable ion‐coordinated mechanism opens a new foundation for the development of high‐energy and high‐power multivalent batteries.
Ligand‐Unsupported Cuprophilicity in the Preparation of Dodecacopper(I) Complexes and Raman Studies
Authors: Harisomayajula N. V. Satyachand , Wu Bo‐Han , Lu Duan‐Yen , Kuo Ting‐Shen , Chen I‐Chia , Tsai Yi‐Chou
Published: April 2018

Synthesis and characterization of two dodecacopper(I) extended metal atom chains (EMAC) assembled by two hexadentate bis(pyridylamido)amidinate‐supported hexacopper(I) string complexes (monomers) via the ligand‐unsupported cuprophilicity are described. In addition to short unsupported Cu−Cu contacts, two hexacopper fragments in these two dodecacopper EMACs show a bent conformation based on X‐ray crystallography. Compared with their THF‐bound hexacopper(I) monomers and protonated ligands, these ligand‐unsupported cuprophilic interactions are shown to be weak by Raman spectroscopy. DFT calculations suggest the ligand‐unsupported cuprophilicity originate from weak attractive orbital interactions, and the strength is estimated to be 2.4 kcal mol−1.
CRISPR interference–mediated metabolic engineering of Corynebacterium glutamicum for homo‐butyrate production
Authors: Yoon Jinkyung , Woo Han Min
Published: April 2018

Combinatorial metabolic engineering enabled the development of efficient microbial cell factories for modulating gene expression to produce desired products. Here, we report the combinatorial metabolic engineering of Corynebacterium glutamicum to produce butyrate by introducing a synthetic butyrate pathway including phosphotransferase and butyrate kinase reactions and repressing the essential acn gene‐encoding aconitase, which has been targeted for downregulation in a genome‐scale model. An all‐in‐one clustered regularly interspaced short palindromic repeats interference system for C. glutamicum was used for tunable downregulation of acn in an engineered strain, where by‐product‐forming reactions were deleted and the synthetic butyrate pathway was inserted, resulting in butyrate production (0.52 ± 0.02 g/L). Subsequently, biotin limitation enabled the engineered strain to produce butyrate (0.58 ± 0.01 g/L) without acetate formation for the entire duration of the culture. These results demonstrate the potential homo‐production of butyrate using engineered C. glutamicum. This method can also be applied to other industrial microorganisms.
Retrievable hydrogels for ovarian follicle transplantation and oocyte collection
Authors: Rios Peter D. , Kniazeva Ekaterina , Lee Hoi Chang , Xiao Shuo , Oakes Robert S. , Saito Eiji , Jeruss Jacqueline S. , Shikanov Ariella , Woodruff Teresa K. , Shea Lonnie D.
Published: April 2018

Cancer survivorship rates have drastically increased due to improved efficacy of oncologic treatments. Consequently, clinical concerns have shifted from solely focusing on survival to quality of life, with fertility preservation as an important consideration. Among fertility preservation strategies for female patients, ovarian tissue cryopreservation and subsequent reimplantation has been the only clinical option available to cancer survivors with cryopreserved tissue. However, follicle atresia after transplantation and risk of reintroducing malignant cells have prevented this procedure from becoming widely adopted in clinics. Herein, we investigated the encapsulation of ovarian follicles in alginate hydrogels that isolate the graft from the host, yet allows for maturation after transplantation at a heterotopic (i.e., subcutaneous) site, a process we termed in vivo follicle maturation. Survival of multiple follicle populations was confirmed via histology, with the notable development of the antral follicles. Collected oocytes (63%) exhibited polar body extrusion and were fertilized by intracytoplasmic sperm injection and standard in vitro fertilization procedures. Successfully fertilized oocytes developed to the pronucleus (14%), two‐cell (36%), and four‐cell (7%) stages. Furthermore, ovarian follicles cotransplanted with metastatic breast cancer cells within the hydrogels allowed for retrieval of the follicles, and no mice developed tumors after removal of the implant, confirming that the hydrogel prevented seeding of disease within the host. Collectively, these findings demonstrate a viable option for safe use of potentially cancer‐laden ovarian donor tissue for in vivo follicle maturation within a retrievable hydrogel and subsequent oocyte collection. Ultimately, this technology may provide novel options to preserve fertility for young female patients with cancer.
Improving culture performance and antibody production in CHO cell culture processes by reducing the Warburg effect
Authors: Buchsteiner Maria , Quek Lake‐Ee , Gray Peter , Nielsen Lars K.
Published: April 2018

Lactate is one of the key waste metabolites of mammalian cell culture. High lactate levels are caused by high aerobic glycolysis, also known as the Warburg effect, and are usually associated with adverse culture performance. Therefore, reducing lactate accumulation has been an ongoing challenge in the cell culture development to improve growth, productivity, and process robustness. The pyruvate dehydrogenase complex (PDC) plays a crucial role for the fate of pyruvate, as it converts pyruvate to acetyl coenzyme A (acetyl‐CoA). The PDC activity can be indirectly increased by inhibiting the PDC inhibitor, pyruvate dehydrogenase kinase, using dichloroacetate (DCA), resulting in less pyruvate being available for lactate formation. Here, Chinese hamster ovary cells were cultivated either with 5 mM DCA or without DCA in various batch and fed‐batch bioreactor processes. In all cultures, DCA increased peak viable cell density (VCD), culture length and final antibody titer. The strongest effect was observed in a fed batch with media and glucose feeding in which peak VCD was increased by more than 50%, culture length was extended by more than 3 days, and the final antibody titer increased by more than twofold. In cultures with DCA, lactate production and glucose consumption during exponential growth were on average reduced by approximately 40% and 35%, respectively. Metabolic flux analysis showed reduced glycolytic fluxes, whereas fluxes in the tricarboxylic acid (TCA) cycle were not affected, suggesting that cultures with DCA use glucose more efficiently. In a proteomics analysis, only few proteins were identified as being differentially expressed, indicating that DCA acts on a posttranslational level. Antibody quality in terms of aggregation, charge variant, and glycosylation pattern was unaffected. Subsequent bioreactor experiments with sodium lactate and sodium chloride feeding indicated that lower osmolality, rather than lower lactate concentration itself, improved culture performance in DCA cultures. In conclusion, the addition of DCA to the cell culture improved culture performance and increased antibody titers without any disadvantages for cell‐specific productivity or antibody quality.
Scalable synthesis and validation of PAMAM dendrimer‐N‐acetyl cysteine conjugate for potential translation
Authors: Sharma Rishi , Sharma Anjali , Kambhampati Siva P. , Reddy Rajsekar Rami , Zhang Zhi , Cleland Jeffrey L. , Kannan Sujatha , Kannan Rangaramanujam M.
Published: April 2018

Dendrimer‐N‐acetyl cysteine (D‐NAC) conjugate has shown significant promise in multiple preclinical models of brain injury and is undergoing clinical translation. D‐NAC is a generation‐4 hydroxyl‐polyamidoamine dendrimer conjugate where N‐acetyl cysteine (NAC) is covalently bound through disulfide linkages on the surface of the dendrimer. It has shown remarkable potential to selectively target and deliver NAC to activated microglia and astrocytes at the site of brain injury in several animal models, producing remarkable improvements in neurological outcomes at a fraction of the free drug dose. Here we present a highly efficient, scalable, greener, well‐defined route to the synthesis of D‐NAC, and validate the structure, stability and activity to define the benchmarks for this compound. This newly developed synthetic route has significantly reduced the synthesis time from three weeks to one week, uses industry‐friendly solvents/reagents, and involves simple purification procedures, potentially enabling efficient scale up.
Molecular and Biological Catalysts Coimmobilization on Electrode by Combining Diazonium Electrografting and Sequential Click Chemistry
Authors: Zhang Lin , Vilà Neus , Walcarius Alain , Etienne Mathieu
Published: April 2018

A generic approach has been developed for sequential heterogeneous surface modification of electrodes. The strategy, which is applicable for a wide range of functional groups, involves two main steps. In the first one, azide‐alkene bifunctionalized electrodes are obtained by electrochemical reduction of a mixture of diazonium salts generated in situ from the corresponding 4‐azidoaniline and 4‐vinylaniline. In that way, we provide reactive sites that are available for further selective functionalization in a sequential process based on ‘click reactions’, in which subsequent immobilization of the targeted molecules is achieved by the azide‐alkyne cycloaddition Huisgen reaction and alkene‐thiol coupling. Feasibility of the method has been first demonstrated for the coimmobilization of two distinct redox moieties (cobaltocenium and ferrocene) as evidenced by cyclic voltammetry and X‐ray photoelectron spectroscopy measurements. The versatility of the sequential method has then been exploited for the coimmobilization of a molecular electrocatalyst [Cp*Rh(bpy) Cl]+ and a biological catalyst, a NAD‐dependent dehydrogenase, that were proved to act in cascade in the electroenzymatic reduction of D‐fructose to D‐sorbitol. Such simple combination of diazonium chemistry and robust chemical reactions (‘click chemistry’) is promising for the environmentally friendly heterogeneous modification of electrodes with multiple chemical and biological catalysts.
Influence of Marangoni stress on the variation in number of coalescence cascade stages
Authors: Haldar Krishnayan , Chakraborty Samarshi , Chakraborty Sudipto
Published: April 2018

The present work is an experimental and theoretical study on surfactant‐laden liquid drop impact on a liquid pool. When the drop breaks into a secondary droplet after impinging, then it is called partial coalescence. If this happens successively in self‐similar manner then it is called coalescence cascade. Three different types of surfactants, cationic, anionic, and non‐ionic, are used as drop fluid and water as the liquid pool. Here we report how the surfactant types and concentrations affect the number of stages in coalescence cascade. The experimental outcome revealed that the number of stages in cascade decreases with increasing surfactant concentration. Also, we determine that drop viscosity, density, and size play a crucial role while comparing the stages of cascade among three types of surfactants. We also perform scaling analysis to determine the contribution of inertial and surface forces in the cascade. A theoretical analysis using lubrication approximation has also been carried out to justify the experimental observations. The coalescence process is actually triggered by the drainage of entrapped air between the drop and pool. The theoretical analysis reveals that the faster air drainage rate and acceleration induces a strong Marangoni stress for necking and quick pinch off. Finally, it is shown that Marangoni flow, originated due to the surface tension difference between the drop and pool, is responsible for partial coalescence and a number of coalescence stages in cascade.
The use of indirectly bonded 13C‐1H (INCH) shift correlation spectra for ab initio structure elucidation of natural products and other complex organic compounds; A personal and historical perspective
Authors: Reynolds William F.
Published: April 2018

This article reviews the use of long‐range shift correlation spectra for structure elucidation of natural products and other complex organic compounds from the early 1980's to the present. Much of it is written from the personal viewpoint of someone who has been involved in this area of research since its earliest days. The first section covers the early use of long‐range correlation spectra in the 1980's. The second section covers the development of specialized pulse sequences for this type of acquisition. It begins with three 13C‐detected sequences, followed by heteronuclear multiple bond correlation (HMBC) and some modified versions of HMBC and, finally, longer range correlation sequences based on the heteronuclear single quantum multiple bond correlation sequence. The third section covers various sequences designed to distinguish between 2‐bond and longer range 13C‐1H correlations. Unfortunately, none of these can make this distinction for non‐protonated carbons. Only the 1,1‐ADEQUATE sequence can make this distinction but its very low sensitivity limits its usefulness. The next section focuses on ways of avoiding getting incorrect structures of organic compounds, an ongoing problem in natural product research. The last section includes likely short‐term developments and possible long‐term developments in NMR methodology that would be beneficial for small molecule structure elucidation.
Solid‐state NMR studies of chemical exchange in ion conductors for alternative energy applications
Authors: Smiley Danielle L. , Goward Gillian R.
Published: April 2018

Here we describe the selective inversion methodology for quantifying the rates of site‐specific ion exchange in materials such as lithium ion battery cathode frameworks. This strategy is shown to be robust in the presence of paramagnetic centers and viable and efficient for the evaluation of hopping rates, in spite of varying initial conditions for the NMR experiment. This is contrasted with 2D EXSY methodology, and selective inversion is shown to be preferable for a number of reasons articulated herein. Work in this area in our group was guided by insights into chemical exchange processes provide by our friend and colleague, Prof. Alex D. Bain. We dedicate this short review to him.
A magnet moment silenced: A tribute to my friend and mentor Alex D. Bain
Authors: Kay Lewis E.
Published: April 2018

Alex D. Bain was an exceptional NMR spectroscopist who played an important role in the development of modern NMR methods and whose keen intellect and wonderful personal qualities endeared him to faculty and students alike who often sought him out for NMR advice. In this brief recollection, I will focus on a number of seminal contributions that Alex made that greatly influenced my research, illustrating how they changed the practice of modern NMR spectroscopy and laid the foundation for new experiments that are currently in widespread use.
Fabrication of an Oil Spill Collector Package by Using Polyurethane Foam Wrapped with Superhydrophobic ZnO Microrods/Carbon Cloth
Authors: Khosravi Maryam , Azizian Saeid
Published: April 2018

A new package, including polyurethane foam wrapped with superhydrophobic ZnO microrods/carbon cloth with long‐life elasticity, was fabricated and was utilized for oil spill clean‐up. First, the carbon cloth (CC) was coated with ZnO microrods, which were modified with stearic acid (SA) to obtain superhydrophobic and superoleophilic properties. The coating process was conducted in mild conditions, involving the hydrothermal growth of ZnO microrods on the surface of the carbon cloth. The obtained hydrophobic sample was modified to a superhydrophobic one by adsorption of stearic acid (SA) on its surface. The prepared sample (CC/ZnO/SA) was characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), Fourier transform infrared spectra (FTIR), attenuated total reflectance Fourier‐transform infrared spectroscopy (ATR‐FTIR), and contact angle measurements. The prepared sample shows a water contact angle (WCA) of 160°. A piece of polyurethane foam was wrapped with the prepared superhydrophobic CC/ZnO/SA making an oil collecting package, which can float on the water surface and absorb various oils from the water surface in both static and turbulent conditions very quickly. The prepared package exhibits excellent mechanical robustness and can be used several times for oil/water separation without capacity decrease. The kinetics of oil spill absorption by the prepared package were studied, too.
Assessing the suitable habitat for reintroduction of brown trout (Salmo trutta forma fario) in a lowland river: A modeling approach
Authors: Boets Pieter , Gobeyn Sacha , Dillen Alain , Poelman Eddy , Goethals Peter L. M.
Published: April 2018

Huge efforts have been made during the past decades to improve the water quality and to restore the physical habitat of rivers and streams in western Europe. This has led to an improvement in biological water quality and an increase in fish stocks in many countries. However, several rheophilic fish species such as brown trout are still categorized as vulnerable in lowland streams in Flanders (Belgium). In order to support cost‐efficient restoration programs, habitat suitability modeling can be used. In this study, we developed an ensemble of habitat suitability models using metaheuristic algorithms to explore the importance of a large number of environmental variables, including chemical, physical, and hydromorphological characteristics to determine the suitable habitat for reintroduction of brown trout in the Zwalm River basin (Flanders, Belgium), which is included in the Habitats Directive. Mean stream velocity, water temperature, hiding opportunities, and presence of pools or riffles were identified as the most important variables determining the habitat suitability. Brown trout mainly preferred streams with a relatively high mean reach stream velocity (0.2–1 m/s), a low water temperature (7–15°C), and the presence of pools. The ensemble of models indicated that most of the tributaries and headwaters were suitable for the species. Synthesis and applications. Our results indicate that this modeling approach can be used to support river management, not only for brown trout but also for other species in similar geographical regions. Specifically for the Zwalm River basin, future restoration of the physical habitat, removal of the remaining migration barriers and the development of suitable spawning grounds could promote the successful restoration of brown trout.
Parental chronic widespread pain and the association with chronic widespread pain in adult offspring: Family‐linkage data from the Norwegian HUNT Study
Authors: Zadro J.R. , Nilsen T.I.L. , Shirley D. , Amorim A.B. , Ferreira P.H. , Mork P.J.
Published: April 2018

Background

Individuals experiencing chronic widespread pain (CWP) have greater disability and poorer quality of life compared to those with other chronic painful conditions; although research identifying risk factors for CWP is lacking. We aimed to investigate whether parental CWP increases the risk of offspring CWP, and if offspring body mass index (BMI) and leisure time physical activity modify this association.

Methods

We included 6589 parent–offspring trios participating in the Norwegian HUNT Study in 1995–1997 and 2006–2008. Logistic regression was used to calculate adjusted odd ratios (ORs) (95% confidence intervals, CIs) as estimates of relative risk for offspring CWP. We analysed the joint effect of parental CWP and offspring BMI or leisure time physical activity on offspring risk of CWP and calculated the relative excess risk due to interaction (RERI).

Results

In total, 886 (13.5%) offspring developed CWP during follow‐up. Having one (OR = 1.23, 95% CI, 1.05–1.44) or both parents with CWP (OR = 1.89, 95% CI, 1.50–2.38) increased the risk of offspring CWP. In analyses of joint effects, ORs were 1.84 (95% CI, 1.31–2.56) and 3.35 (95% CI, 1.94–5.77) in normal weight and obese offspring, respectively, when both parents had CWP. The estimate of RERI suggested some synergistic effect (RERI = 1.19, 95% CI, −0.68 to 3.05), although precision was low. Risk of CWP was similar in active (OR = 2.05, 95% CI, 1.56–2.70) and inactive (OR = 1.96, 95% CI, 1.31–2.91) offspring when both parents had CWP.

Conclusion

Parental CWP increases the risk of CWP in adult offspring, particularly if both parents have CWP and offspring are obese. This highlights a familial predisposition for CWP and an important target group for preventive measures.

Significance

The parent–offspring transmission of CWP is stronger in obese offspring (particularly when both parents have CWP). This study is the first to investigate the interaction between modifiable lifestyle factors, familial factors and CWP.
A new sequential injection analysis‐capillary electrophoresis system with amperometric detection
Authors: Fernández Feito Rodrigo , Dinsdale Richard M. , Guwy Alan J. , Premier Giuliano C.
Published: April 2018

A novel and fully automated sequential injection analysis manifold coupled to a capillary electrophoresis apparatus with amperometric detection, is described. The sequential injection manifold was isolated from the high voltage by inserting an air plug into the circuit. Small buffer reservoirs were used to avoid the need to pump fresh buffer to the interface during the electrophoretic separation. No decoupling device was used to mitigate the interference from the high voltage electric field, instead the potential shift induced by the separation voltage, was accounted for. The new hydrodynamic injection method presented is based on the overpressure created in the circuit when a pinch valve is closed for a predetermined time. The injection method yields RSD values of peak height and area below 2.55 and 1.82%, respectively, at different durations of valve closure (n = 5). The capillary and working electrode alignment was achieved by adapting a commercial available capillary union. When the electrode was replaced, the alignment method proved to be very reliable, yielding RSD values of peak height and area lower than 2.64 and 2.08%, respectively (n = 8). Using this system with a gold microelectrode, dopamine, and epinephrine could be quantified within the concentration range of 1–500 μM and detected at a concentration of 0.3 μM. The methods here presented could be applied for the development of new capillary electrophoresis systems with amperometric detection and/or to the design of fully automated systems for online process monitoring purposes.
NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage
Authors: Begum Ghazala , Otsu Masahiro , Ahmed Usman , Ahmed Zubair , Stevens Adam , Fulton Daniel
Published: April 2018

Glutamate receptor subunit 4 (GluA4) is highly expressed by neural cells sensitive to excitotoxicity, and is the predominant subunit expressed by oligodendrocyte precursor cells (OPC) during a key period of vulnerability to hypoxic‐ischemic injury. Therefore, transcriptional networks downstream of excitotoxic GluA4 activation represent a promising area for therapeutic intervention. In this work, we identify the CCAAT binding transcription factor NF‐Yb as a novel transcriptional regulator of Gria4 (GluA4 gene), and a controller of excitotoxic death in the oligodendroglial lineage. We describe a novel regulatory region within Gria4 containing CCAAT sequences whose binding by NF‐Yb is regulated by excitotoxicity. Excitotoxicity‐induced alterations in NF‐Yb binding are associated with changes in Gria4 transcription, while knockdown of NF‐Yb alters the transcription of reporter constructs containing this regulatory region. Data from immortalized and primary OPC reveal that RNAi and pharmacological disruption of NF‐Yb alter Gria4 transcription, with the latter inducing apoptosis and influencing a set of apoptotic genes similarly regulated during excitotoxicity. These data provide the first definition of a trans‐acting mechanism regulating Gria4, and identify the NF‐Y network as a potential source of pharmacological targets for promoting OPC survival.
CD97 Promotes Tumor Aggressiveness Through the Traditional G Protein–Coupled Receptor–Mediated Signaling in Hepatocellular Carcinoma
Authors: Yin Yin , Xu Xiaoliang , Tang Junwei , Zhang Wenjie , Zhangyuan Guangyan , Ji Jie , Deng Lei , Lu Shuai , Zhuo Han , Sun Beicheng
Published: April 2018

Cluster of differentiation 97 (CD97) is a member of the epidermal growth factor seven‐transmembrane family belonging to the class B G protein–coupled receptors (GPCRs). The protein affects tumor aggressiveness through its cellular ligand CD55 stimulation and exhibits adhesive properties. Studies have demonstrated the involvement of CD97 in dedifferentiation, migration, invasiveness, and metastasis of tumors. However, little information is currently available on the specific role of CD97 in hepatocellular carcinoma (HCC). Here, we have shown that CD97 up‐regulation in HCCs is positively correlated with tumor metastasis. Functionally, CD97 promoted cell migration and invasion in vitro. In an in vivo mouse model, overexpression of CD97 in HCC cells led to accelerated lung metastasis. Mechanistically, CD97 cooperated with the altered regulator, GPCR kinase 6 (GRK6), to mediate GPCR desensitization and internalization. Down‐regulation of GRK6 suppressed CD97 internalization and promoted CD97 expression. Integrated regulatory interactions between CD97 and GRK6 stimulated downstream matrix metalloproteinase 2/9 secretion and, consequently, HCC metastasis. Conclusion: Our collective findings support the utility of CD97 as an effective potential prognosticator and therapeutic target for HCC.
Amyloid fibrils induce dysfunction of hippocampal glutamatergic silent synapses
Authors: Bie Bihua , Wu Jiang , Foss Joseph F. , Naguib Mohamed
Published: April 2018

Silent glutamatergic synapses lacking functional AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionate) receptors exist in several brain regions including the hippocampus. Their involvement in the dysfunction of hippocampal glutamatergic transmission in the setting of Alzheimer's disease (AD) is unknown. This study demonstrated a decrease in the percentage of silent synapses in rats microinjected with amyloid fibrils (Aβ1–40) into the hippocampal CA1. Also, pairing low‐frequency electric stimuli failed to induce activation of the hippocampal silent synapses in the modeled rats. Immunoblotting studies revealed a decreased expression of GluR1 subunits in the hippocampal CA1 synaptosomal preparation, indicating a potential reduction in the GluR1 subunits anchoring in postsynaptic density in the modeled rats. We also noted a decreased expression of phosphorylated cofilin, which regulates the function of actin cytoskeleton and receptor trafficking, and reduced expression of the scaffolding protein PSD95 in the hippocampal CA1 synaptosome in rats injected with Aβ1–40. Taken together, this study illustrates dysfunction of hippocampal silent synapse in the rodent model of AD, which might result from the impairments of actin cytoskeleton and postsynaptic scaffolding proteins induced by amyloid fibrils.
Modulation of hippocampal excitability via the hydroxycarboxylic acid receptor 1
Authors: Herrera‐López Gabriel , Galván Emilio J.
Published: April 2018

In addition to its prominent role as an energetic substrate in the brain, lactate is emerging as a signaling molecule capable of controlling neuronal excitability. The finding that the lactate‐activated receptor (hydroxycarboxylic acid receptor 1; HCA1) is widely expressed in the brain opened up the possibility that lactate exerts modulation of neuronal activity via a transmembranal receptor‐linked mechanism. Here, we show that lactate causes biphasic modulation of the intrinsic excitability of CA1 pyramidal cells. In the low millimolar range, lactate or the HCA1 agonist 3,5‐DHBA reduced the input resistance and membrane time constant. In addition, activation of HCA1 significantly blocked the fast inactivating sodium current and increased the delay from inactivation to a conducting state of the sodium channel. As the observed actions occurred in the presence of 4‐CIN, a blocker of the neuronal monocarboxylate transporter, the possibility that lactate acted via neuronal metabolism is unlikely. Consistently, modulation of the intrinsic excitability was abolished when CA1 pyramidal cells were dialyzed with pertussis toxin, indicating the dependency of a Gαi/o‐protein‐coupled receptor. The activation of HCA1 appears to serve as a restraining mechanism during enhanced network activity and may function as a negative feedback for the astrocytic production of lactate.
siRNA release from gold nanoparticles by nanosecond pulsed laser irradiation and analysis of the involved temperature increase
Authors: Rudnitzki Florian , Feineis Susanne , Rahmanzadeh Ramtin , Endl Elmar , Lutz Johanna , Groll Jürgen , Hüttmann Gereon
Published: April 2018

Nanosecond pulsed laser irradiation can trigger a release of nucleic acids from gold nanoparticles, but the involved nanoeffects are not fully understood yet. Here we investigate the release of coumarin labeled siRNA from 15 to 30 nm gold particles after nanosecond pulsed laser irradiation. Temperatures in the particle and near the surface were calculated for the different radiant exposures. Upon irradiation with laser pulses of 4 nanosecond duration release started for both particle sizes at a calculated temperature increase of approximately 500 K. Maximum coumarin release was observed for 15 nm particles after irradiation with radiant exposure of 80 mJ cm−2 and with 32 mJ cm−2 for 30 nm particles. This corresponds to a temperature increase of 815 and 900 K, respectively. Our results show that the molecular release by nanosecond pulsed irradiation is based on a different mechanism compared to continuous or femtosecond irradiation. Local temperatures are considerably higher and it is expected that bubble formation plays a crucial role in release and damage to cellular structures.
The 2‐surviving rate of planar graphs with average degree lower than
Authors: Gordinowicz Przemysław
Published: April 2018

Let G be any connected graph on n vertices, . Let k be any positive integer. Suppose that a fire breaks out at some vertex of G. Then, in each turn firefighters can protect at most k vertices of G not yet on fire; Next the fire spreads to all unprotected neighbors of burning vertices. The k‐surviving rate of G, denoted by , is the expected fraction of vertices that can be saved from the fire, provided that the starting vertex is chosen uniformly at random. In this note, it is shown that for any planar graph G with average degree , where , there is . In particular, the result implies a significant improvement of the bound for 2‐surviving rate for triangle‐free planar graphs (Esperet et al. ) and for planar graphs without 4‐cycles (Kong et al. ). The proof is done using the separator theorem for planar graphs.
Correlation between herpes zoster and stroke—A case–control study
Authors: Hosamirudsari Hadiseh , Rashed Parisa , Afsari Farhad , Akbarpour Samaneh , Bagherzadeh Aliasghar
Published: April 2018

Cerebrovascular accident is the second most common cause of death in the world. Herpes zoster (HZ) is reported to be a major trigger of the stroke syndrome. Considering the high prevalence of stroke in Iran, we carried out a study to assess the correlation between stroke and HZ. This is one of the very few studies carried out on this correlation in Asian nations. One hundred and five cases and 105 controls were included in this study. The cases had been diagnosed with stroke by a neurologist and confirmed by brain imaging. The controls had never had any type of stroke. Both groups were between 30 and 90 years of age. We looked for the HZ infection in both groups. Logistic regression analysis was used to evaluate the association between stroke and HZ. The mean age of the cases was 63.95 ± 12.24 years and the man age of the controls was 66.99 ± 14.58 years. There was a significant difference in the HZ infection between the cases and the controls (P < .0001). Head zoster (including ophthalmic zoster) was significantly higher in the case group than the control group (P < .0001). The risk of stroke was the highest 2‐4 weeks after the onset of HZ and the incidences of ischemic stroke were higher than those of hemorrhagic stroke (P < .0001). In an analysis adjusted for the age, sex, and hypertension, HZ was found to be associated with an increased risk of stroke (odds ratio, 5.84; 95% confidence interval, 1.98‐8.23). Close monitoring is suggested for cerebrovascular diseases in patients who have had the head zoster, especially in the first month after the infection.
Is the mixture of human cytomegalovirus genotypes frequent in infants with congenital infection at birth in a high seroprevalence population?
Authors: Garcia de Figueiredo Glauciane , Marques Adriana Aparecida , Mussi‐Pinhata Marisa Márcia , Silva Wilson Araújo , Yamamoto Aparecida Yulie
Published: April 2018

It is still not well known, in a population with high human cytomegalovirus (HCMV) seroprevalence, whether a child with congenital infection harbors multiple viral strains at birth, and whether the prolonged viral excretion in these children is secondary to the persistence of the same viral strain. To verify the genomic diversity of HCMV detected in congenitally infected children, the nucleotide viral sequences from urine and/or saliva obtained at birth from 14 newborns with congenital infection and breast milk obtained from mothers of 5 of these children were analyzed. Among the 14 children, 10 had sequential samples until the median age of 10 months. The viral nucleotide sequences in the breast milk were compared with those identified in the respective children at birth. The differentiation of viral strains was based on the variability of 3 regions of viral genes (UL55/gB, UL144, and UL73/gN). In 13/14 children (92.8%), a single genotype was observed at birth. Different viral genotypes were found in 1 child (7.2%). Among the sequential samples from 10 children, the same genotype obtained at birth was detected in 9/10 (90%), and in 1 of them (10%), a genotype change in the urine was found. More than 1 HCMV strain in milk was observed in 2 mothers (2/5, 40%). In a population with high seroprevalence, a single genotype was found in the majority of infected children. Reinfection did not frequently occur in the first months of life. Maternal reinfection does not seem to be a rare event in transmitter mothers.
Epidemiological and molecular investigation of a measles outbreak in Punjab, Pakistan, 2013‐2015
Authors: Zaidi Syed Sohail Zahoor , Hameed Abdul , Ali Naeem , Rana Muhammad Suleman , Umair Massab , Alam Muhammad Masroor , Aamir Uzma Bashir , Khurshid Adnan , Sharif Salmaan , Shaukat Shahzad , Angez Mehar , Mujtaba Ghulam , Arshad Yasir , Akthar Ribqa , Sufian Mian Muhammad , Mehmood Nayab
Published: April 2018

Despite the availability of an effective vaccine, the measles virus continues to cause significant morbidity and mortality in children worldwide. Molecular characterization of wild‐type measles strains is an invaluable component of epidemiological studies or surveillance systems that provides important information pertinent to outbreak linkages and transmission pathways. Serum samples and throat swabs were collected from suspected measles cases from the Punjab province of Pakistan (2013‐2015) and further tested for measles immunoglobulin M (IgM) through enzyme‐linked immunosorbent assay and reverse‐transcriptase polymerase chain reaction for molecular characterization. Among the total of 5415 blood samples, 59% tested positive for measles IgM. Males had a higher infection rate (55%) than females (45%), and the highest frequency of positive cases (63%) was found in the age group of 0 to 5 years. Partial sequencing of the nucleoprotein gene showed that 27 strains belonged to the B3 genotype, whereas 2 viruses were identified as D4. On phylogenetic analysis, Pakistani B3 strains were found to be closely related to previously reported indigenous strains and those from neighboring countries of Iran and Qatar. This is the first report on the detection of the measles B3 genotype from Punjab, Pakistan. The current study shows a high burden of measles infections in Punjab province owing to poor routine immunization coverage in major cities. It is imperative that national health authorities adopt strategic steps on an urgent basis for improvement of routine immunization coverage. Molecular epidemiology of the measles viruses circulating in different parts of the country can provide useful data to manage future outbreaks.
Factors affecting residual/recurrent cervical intraepithelial neoplasia after cervical conization with negative margins
Authors: Fan Aiping , Wang Chen , Han Cha , Wang Yingmei , Xue Fengxia , Zhang Liqin
Published: April 2018

To identify factors for predicting residual or recurrent cervical intraepithelial neoplasia (CIN) after cervical conization with negative margins. A total of 172 patients with histologically verified high‐grade squamous intraepithelial lesions who underwent conization with negative margins were recruited at the General Hospital of Tianjin Medical University from December 2006 to January 2016. Follow‐up comprised clinical examination, a liquid‐based cytology test, a human papillomavirus (HPV) DNA genotyping test, colposcopy assessment, and if indicated, colposcopy‐directed punch biopsy. The Kaplan‐Meier method was used to analyze the median recurrent time, whereas log‐rank tests and Cox regression models were used to determine the predictors of residual/recurrent CIN. Fourteen residual/recurrent cases (8.1%) were identified in 172 patients. In univariate analysis, cytologic abnormalities on follow‐up (P = .000), conization method (P = .017), HPV positivity at any visit (P = .000), persistent HPV infection postconization (P = .000), persistent infection with the same HPV genotype (P = .000), and HPV positivity at 18 months after conization (P = .000) were predictive factors of residual/recurrent CIN. The results of multivariate analysis further revealed that persistent HPV infection postconization (P = .035), HPV positivity at 18 months after conization (P = .017), and cytologic abnormalities on follow‐up (P = .000) had an increased risk of residual/recurrent CIN. During follow‐up, patients with persistent HPV infection or cytologic abnormalities were at high risk of residual/recurrent CIN and should be identified for close surveillance and monitoring. Meanwhile, patients with HPV who became negative within 18 months after treatment had a low risk of recurrence.
Electrical remodelling and response following cardiac resynchronization therapy: A novel analysis of intracardiac electrogram using a quadripolar lead
Authors: Toner Liam , Flannery Darragh , Sugumar Hariharan , Ord Michelle , Lin Tina , O'Donnell David
Published: April 2018

Background

Cardiac resynchronization therapy (CRT) improves morbidity and mortality in patients with heart failure. Although structural remodelling correlates with improved long‐term outcomes, the role of electrical remodelling is poorly understood. This study aimed to evaluate electrical remodelling following CRT using a quadripolar left ventricular (LV) lead and to correlate this with structural remodelling.

Methods

Consecutive patients undergoing initial CRT implantation using a quadripolar LV lead were enrolled. Patients were followed up for 12 months. Twelve lead ECG, transthoracic echocardiogram, and evaluation of intracardiac electrograms (EGM) were performed. Measures included right and left ventricular lead intrinsic delay, RV‐pacing to LV‐sensing (RVp‐LVs) delay, and LV‐pacing to RV‐sensing (LVp‐RVs) delay. The electrical changes were then correlated with echocardiographic response to CRT, defined by ≥15% relative reduction in LVESV and ≥ 5% absolute improvement in EF on TTE. Activation sequence was determined using the quadripolar lead.

Results

Forty patients were enrolled. Mean intrinsic RV‐LV EGM values decreased from 121.9 ± 14.7 ms to 109.1 ± 15.0 ms (P < .01), mean RVp‐LVs EGM values from 146.7 ± 16.7 ms to 135.1 ± 13.1 ms, (P < .01), and mean LVp‐RVs EGM values from 155.7 ± 18.1 ms to 144.2 ± 17.1 ms (P < .01). The improvement in intrinsic RV‐LV EGM was 14.9 ± 8.5 ms in responders vs 8.9 ± 7.9 ms in nonresponders to CRT (P < .05). Changes in activation sequence did not correlate with CRT response.

Conclusions

This novel study used EGMs from a quadripolar LV lead to demonstrate electrical remodelling occurs following CRT. A nonsignificant trend suggests that electrical remodelling in CRT is greater in responders compared to nonresponders, although further study is needed.
Iatrogenic subclavian arteriovenous fistula during permanent pacemaker implantation: Closed by endovascular coiling
Authors: Bera Debabrata , Dharia Tejas , Trivedi Aniruddh , Rao Anand , Pawar Prashant Dilip , Bachani Neeta , Shah Vihang , Panicker Gopi , Lokhandwala Yash
Published: April 2018

Iatrogenic arteriovenous fistula is a unique complication during pacemaker implantation. A 55‐year‐old man was posted for pacemaker implantation for recurrent unexplained syncope with trifascicular AV block. After axillary/subclavian venous puncture and introduction of RV lead, arterial spurting was immediately noticed as the the sheath was peeled away. After dissecting the overlying pectoralis muscle, deep sutures and manual compression achieved hemostasis. However, Subclavian arteriogram revealed an arteriovenous fistula from a lateral thoracic artery branch to the innominate vein. Hilal coils were deployed near the fistulous orifice, leading to complete resolution of the leak. After 3 days, pacemaker was implanted from right side. A multidisciplinary approach was the key to successful outcome.