bluuebunny/crossref_metadata_2025_split huggingface dataset:
δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine synthetase (ACVS): discovery and perspectives
Authors: Tahlan Kapil , Moore Marcus A , Jensen Susan E 
Published: October 2016

Abstract
The δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine (ACV) tripeptide is the first dedicated intermediate in the biosynthetic pathway leading to the penicillin and cephalosporin classes of β-lactam natural products in bacteria and fungi. It is synthesized nonribosomally by the ACV synthetase (ACVS) enzyme, which has been purified and partially characterized from many sources. Due to its large size and instability, many details regarding the reaction mechanism of ACVS are still not fully understood. In this review we discuss the chronology and associated methodology that led to the discovery of ACVS, some of the main findings regarding its activities, and some recent/current studies being conducted on the enzyme. In addition, we conclude with perspectives on what can be done to increase our understating of this very important protein in the future.
Flunarizine rescues reduced lifespan in CLN3 triple knock‐out Caenorhabditis elegans model of batten disease
Authors: Kwon Young Joon , Falk Marni J. , Bennett Michael J. 
Published: October 2016

AbstractCLN3 disease (Spielmeyer‐Vogt‐Sjogren‐Batten disease, previously known as classic juvenile neuronal ceroid lipofuscinosis, NCL) is a pediatric‐onset progressive neurodegenerative disease characterized by progressive vision loss, seizures, loss of cognitive and motor function, and early death. While no precise biochemical mechanism or therapies are known, the pathogenesis of CLN3 disease involves intracellular calcium accumulation that may trigger apoptosis. Our prior work in in vitro cell models of CLN3 deficiency suggested that FDA‐approved calcium channel antagonists may have therapeutic value. To further evaluate the potential efficacy of this approach in an otherwise untreatable disorder, we sought to compare the therapeutic effects and underlying mechanisms in an animal model of CLN3 disease. Here, we used the well‐characterized XT7 complete cln‐3 knockout strain of C. elegans to evaluate the therapeutic efficacy of calcium channel antagonist therapy in a living animal model of Batten disease. Therapeutic effects of five calcium channel antagonists were evaluated on XT7 animal lifespan and in vivo mitochondrial physiology. Remarkably, maximal therapeutic efficacy in this model animal was observed with 1 μM flunarizine, the identical concentration previously identified in cell‐based neuronal models of CLN3 disease. Specifically, flunarizine rescued the short lifespan of XT7 worms and prevented their pathophysiologic mitochondrial accumulation. These results confirm the treatment efficacy and dosing of flunarizine in cln‐3 disease in a translational model organism. Clinical treatment trials in CLN3 human patients are now needed to test the dosing regimen and efficacy of flunarizine in individuals suffering with this otherwise untreatable and ultimately lethal neurologic disease.
Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans
Authors: Mez Jesse , Chung Jaeyoon , Jun Gyungah , Kriegel Joshua , Bourlas Alexandra P. , Sherva Richard , Logue Mark W. , Barnes Lisa L. , Bennett David A. , Buxbaum Joseph D. , Byrd Goldie S. , Crane Paul K. , Ertekin-Taner Nilüfer , Evans Denis , Fallin M. Daniele , Foroud Tatiana , Goate Alison , Graff-Radford Neill R. , Hall Kathleen S. , Kamboh M. Ilyas , Kukull Walter A. , Larson Eric B. , Manly Jennifer J. ,   Alzheimer's Disease Genetics Consortium, Haines Jonathan L. , Mayeux Richard , Pericak-Vance Margaret A. , Schellenberg Gerard D. , Lunetta Kathryn L. , Farrer Lindsay A. 
Published: October 2016

AbstractIntroductionAfrican Americans' (AAs) late‐onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.MethodsWe conducted a genome‐wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome‐wide set of single‐nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs.ResultsTwo SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome‐wide significant evidence of association with the posterior liability.DiscussionAn informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.
Oppositional brand choice: Using brands to respond to relationship frustration
Authors: Brick Danielle J. , Fitzsimons Gavan J. 
Published: October 2016

AbstractWithin close relationships individuals feel a variety of emotions toward their partner, often including frustration. In the present research we suggest a novel way in which individuals respond to frustration with their partner is through their choice of brands. Specifically, we introduce the concept of oppositional brand choice, which we define as occurring when individuals choose a brand for themselves that is in opposition to the one they believe their partner prefers. Importantly, we posit that this effect is specific to individuals who are low in relationship power. Across several studies, including a subliminal priming lab study, we find that people who are lower in relationship power and are frustrated with their partner make significantly more oppositional brand choices. Further, we find that this effect is not due to a shift in underlying brand preferences. The current research has implications for theory in brand choice, close relationships, emotions, and social power.
Predictors of Sexual Distress in Women with Desire and Arousal Difficulties: Distinguishing Between Personal, Partner, and Interpersonal Distress
Authors: Hendrickx Lies , Gijs Luk , Janssen Erick , Enzlin Paul 
Published: October 2016

ABSTRACTIntroductionAlthough impaired sexual function is relatively common, not all sexual impairments are associated with distress. To date, most studies on protective and risk factors for sexual distress have asked about distress in a more general manner and have failed to distinguish different dimensions of sexual distress.AimTo examine the association of several intra- and interpersonal factors with personal, perceived partner, and interpersonal distress due to an impairment in sexual functioning in women.MethodsThis study is a cross-sectional representative population-based survey with a two-level random selection of Flemish women 14 to 80 years old from the Belgian National Register. The data of 520 sexually active heterosexual women with a partner (weighted N) and impairment in sexual desire (n = 291) and/or sexual arousal (n = 273) were used for analysis.Main Outcome MeasuresDemographic information was obtained, and the five-item Mental Health Inventory, the Marital Adjustment subscale of the Maudsley Marital Questionnaire, and the four-item Dyadic Sexual Communication Questionnaire were used. Presence and severity of sexual impairments and associated sexual distress were assessed using the Sexual Functioning Scale.ResultsSeverity and number of sexual impairments were predictive of all types of sexual distress. Also, for desire and arousal impairments, lower mental well-being predicted personal distress, and lower relationship satisfaction predicted perceived partner distress. For desire impairments, lower relationship satisfaction and less communication about sexual needs were predictive of interpersonal distress. For impairments in sexual arousal, lower mental well-being and lower relationship satisfaction were predictive of interpersonal distress.ConclusionPersonal, perceived partner, and interpersonal distress due to sexual impairments have different types of predictors. Clinical assessment and treatment could benefit from differentiating between different types of distress and the intra- and interpersonal factors that are associated with them.
Aspergillus section Nidulantes (formerly Emericella): Polyphasic taxonomy, chemistry and biology
Authors: Chen A.J. , Frisvad J.C. , Sun B.D. , Varga J. , Kocsubé S. , Dijksterhuis J. , Kim D.H. , Hong S.-B. , Houbraken J. , Samson R.A. 
Published: October 2016

Aspergillus section Nidulantes includes species with striking morphological characters, such as biseriate conidiophores with brown-pigmented stipes, and if present, the production of ascomata embedded in masses of Hülle cells with often reddish brown ascospores. The
majority of species in this section have a sexual state, which were named Emericella in the dual name nomenclature system. In the present study, strains belonging to subgenus Nidulantes were subjected to multilocus molecular phylogenetic analyses using internal transcribed spacer
region (ITS), partial β-tubulin (BenA), calmodulin (CaM) and RNA polymerase II second largest subunit (RPB2) sequences. Nine sections are accepted in subgenus Nidulantes including the new section Cavernicolus. A polyphasic approach using morphological
characters, extrolites, physiological characters and phylogeny was applied to investigate the taxonomy of section Nidulantes. Based on this approach, section Nidulantes is subdivided in seven clades and 65 species, and 10 species are described here as new. Morphological characters
including colour, shape, size, and ornamentation of ascospores, shape and size of conidia and vesicles, growth temperatures are important for identifying species. Many species of section Nidulantes produce the carcinogenic mycotoxin sterigmatocystin. The most important mycotoxins in
Aspergillus section Nidulantes are aflatoxins, sterigmatocystin, emestrin, fumitremorgins, asteltoxins, and paxillin while other extrolites are useful drugs or drug lead candidates such as echinocandins, mulundocandins, calbistrins, varitriols, variecolins and terrain. Aflatoxin
B<inf>1</inf> is produced by four species: A. astellatus, A. miraensis, A. olivicola, and A. venezuelensis.
Utilization of Health Services Among Adults With RecurrentClostridium difficileInfection: A 12-Year Population-Based Study
Authors: Kuntz Jennifer L. , Baker Jennifer M. , Kipnis Patricia , Li Sherian Xu , Liu Vincent , Xie Yang , Marcella Stephen , Escobar Gabriel J. 
Published: October 2016

BACKGROUNDConsiderable efforts have been dedicated to developing strategies to prevent and treat recurrentClostridium difficileinfection (rCDI); however, evidence of the impact of rCDI on patient healthcare utilization and outcomes is limited.OBJECTIVETo compare healthcare utilization and 1-year mortality among adults who had rCDI, nonrecurrent CDI, or no CDI.METHODSWe performed a nested case-control study among adult Kaiser Foundation Health Plan members from September 1, 2001, through December 31, 2013. We identified CDI through the presence of a positive laboratory test result and divided patients into 3 groups: patients with rCDI, defined as CDI in the 14–57 days after initial CDI; patients with nonrecurrent CDI; and patients who never had CDI. We conducted 3 matched comparisons: (1) rCDI vs no CDI; (2) rCDI vs nonrecurrent CDI; (3) nonrecurrent CDI vs no CDI. We followed patients for 1 year and compared healthcare utilization between groups, after matching patients on age, sex, and comorbidity.RESULTSWe found that patients with rCDI consistently have substantially higher levels of healthcare utilization in various settings and greater 1-year mortality risk than both patients who had nonrecurrent CDI and patients who never had CDI.CONCLUSIONSPatients who develop an initial CDI are generally characterized by excess underlying, severe illness and utilization. However, patients with rCDI experience even greater adverse consequences of their disease than patients who do not experience rCDI. Our results further support the need for continued emphasis on identifying and using novel approaches to prevent and treat rCDI.Infect Control Hosp Epidemiol.2016;1–8
Predictability of helminth parasite host range using information on geography, host traits and parasite community structure
Authors: DALLAS TAD , PARK ANDREW W. , DRAKE JOHN M. 
Published: October 2016

SUMMARYHost–parasite associations are complex interactions dependent on aspects of hosts (e.g. traits, phylogeny or coevolutionary history), parasites (e.g. traits and parasite interactions) and geography (e.g. latitude). Predicting the permissive host set or the subset of the host community that a parasite can infect is a central goal of parasite ecology. Here we develop models that accurately predict the permissive host set of 562 helminth parasites in five different parasite taxonomic groups. We developed predictive models using host traits, host taxonomy, geographic covariates, and parasite community composition, finding that models trained on parasite community variables were more accurate than any other covariate group, even though parasite community covariates only captured a quarter of the variance in parasite community composition. This suggests that it is possible to predict the permissive host set for a given parasite, and that parasite community structure is an important predictor, potentially because parasite communities are interacting non-random assemblages.
Distinctive distribution of HPV genotypes in cervical cancers in multi-ethnic Suriname: implications for prevention and vaccination
Authors: GRUNBERG M. G. , CHAN M. , ADHIN M. R. 
Published: October 2016

SUMMARYSuriname is ranked as high-risk country for cervical cancer, but recent national data of HPV prevalence and distribution in cervical cancer is scarce. In a retrospective cross-sectional study, cervical cancer incidence, HPV prevalence and HPV-type-specific distribution were investigated in all cervical cancer cases (n = 111), diagnosed in two consecutive years. HPV presence and type-specific prevalence were determined in paraffin-embedded biopsies utilizing master-nested multiplex PCR assays, targeting 14 HPV types. The age-standardized incidence rate of cervical cancer was 22·4/100 000 women, justifying revision of the current international ranking of Suriname. Eleven HPV types were detected, with the most common types in descending order of frequency: 16, 18, 45, 66, 58/52/35. HPV16 was predominant, although with markedly low presence (25%). HPV16 or 18 infections were detected in 43% of the cases, while 28% were untyped, implicating a divergent HPV-type distribution in Suriname with significant variation in the prevalence of less common high-risk virus types and/or presence of HPV16 variants. HPV-type distribution differed between ethnic groups. A vaccination efficacy of just 28–30% was anticipated, next to an uneven vaccination impact in different ethnic groups, cautioning Suriname and other multi-ethnic countries to tailor the information presented to different ethnic communities.
The endocrinology of human caregiving and its intergenerational transmission
Authors: Bos Peter A. 
Published: October 2016

AbstractVariation in the quality of parental care has a tremendous impact on a child's social–emotional development. Research investigating the predictors of this variability in human caregiving behavior has mostly focused on learning mechanisms. Evidence is currently accumulating for the complementary underlying role of steroid hormones and neuropeptides. An overview is provided of the hormones and neuropeptides relevant for human caregiving behavior. Then the developmental factors are described that stimulate variability in sensitivity to these hormones and neuropeptides, which may result in variability in the behavioral repertoire of caregiving. The role of genetic variation in neuropeptide and steroid receptors, the role of testosterone and oxytocin during fetal development and parturition, and the impact of experienced caregiving in childhood on functioning of the neuroendocrine stress and oxytocin system are discussed. Besides providing a heuristic framework for further research on the ontogenetic development of human caregiving, a neuroendocrine model is also presented for the intergenerational transmission of caregiving practices. Insight into the underlying biological mechanisms that bring about maladaptive caregiving behavior, such as neglect and insensitive parenting, will hopefully result in more efficient approaches to reduce the high prevalence of such behavior and to minimize the impact on those affected.
The prosurvival protein BAG3: a new participant in vascular homeostasis
Authors: Carrizzo Albino , Damato Antonio , Ambrosio Mariateresa , Falco Antonia , Rosati Alessandra , Capunzo Mario , Madonna Michele , Turco Maria C , Januzzi James L , De Laurenzi Vincenzo , Vecchione Carmine 
Published: October 2016

AbstractBcl2-associated athanogene 3 (BAG3), is constitutively expressed in a few normal cell types, including myocytes, peripheral nerves and in the brain, and is also expressed in certain tumors. To date, the main studies about the role of BAG3 are focused on its pro-survival effect in tumors through various mechanisms that vary according to cellular type. Recently, elevated concentrations of a soluble form of BAG3 were described in patients affected by advanced stage of heart failure (HF), identifying BAG3 as a potentially useful biomarker in monitoring HF progression. Despite the finding of high levels of BAG3 in the sera of HF patients, there are no data on its possible role on the modulation of vascular tone and blood pressure levels. The aim of this study was to investigate the possible hemodynamic effects of BAG3 performing both in vitro and in vivo experiments. Through vascular reactivity studies, we demonstrate that BAG3 is capable of evoking dose-dependent vasorelaxation. Of note, BAG3 exerts its vasorelaxant effect on resistance vessels, typically involved in the blood pressure regulation. Our data further show that the molecular mechanism through which BAG3 exerts this effect is the activation of the PI3K/Akt signalling pathway leading to nitric oxide release by endothelial cells. Finally, we show that in vivo BAG3 administration is capable of regulating blood pressure and that this is dependent on eNOS regulation since this ability is lost in eNOS KO animals.
Functional KCa1.1 channels are crucial for regulating the proliferation, migration and differentiation of human primary skeletal myoblasts
Authors: Tajhya Rajeev B , Hu Xueyou , Tanner Mark R , Huq Redwan , Kongchan Natee , Neilson Joel R , Rodney George G , Horrigan Frank T , Timchenko Lubov T , Beeton Christine 
Published: October 2016

AbstractMyoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1.1 (BK, Slo1, KCNMA1), regulates myoblast proliferation, migration, and fusion. We also show a loss of plasma membrane expression of the pore-forming α subunit of KCa1.1 in DM1 myoblasts. Inhibiting the function of KCa1.1 in healthy myoblasts induced an increase in cytosolic calcium levels and altered nuclear factor kappa B (NFκB) levels without affecting cell survival. In these normal cells, KCa1.1 block resulted in enhanced proliferation and decreased matrix metalloproteinase secretion, migration, and myotube fusion, phenotypes all observed in DM1 myoblasts and associated with disease pathogenesis. In contrast, introducing functional KCa1.1 α-subunits into DM1 myoblasts normalized their proliferation and rescued expression of the late myogenic marker Mef2. Our results identify KCa1.1 channels as crucial regulators of skeletal myogenesis and suggest these channels as novel therapeutic targets in DM1.
Mitochondrial angiotensin receptors in dopaminergic neurons. Role in cell protection and aging-related vulnerability to neurodegeneration
Authors: Valenzuela Rita , Costa-Besada Maria A , Iglesias-Gonzalez Javier , Perez-Costas Emma , Villar-Cheda Begoña , Garrido-Gil Pablo , Melendez-Ferro Miguel , Soto-Otero Ramon , Lanciego Jose L , Henrion Daniel , Franco Rafael , Labandeira-Garcia Jose L 
Published: October 2016

AbstractThe renin–angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the ‘classical’ humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related diseases. The local brain RAS plays a major role in brain function and neurodegeneration. It is normally assumed that the effects are mediated by the cell-surface-specific G-protein-coupled angiotensin type 1 and 2 receptors (AT1 and AT2). A combination of in vivo (rats, wild-type mice and knockout mice) and in vitro (primary mesencephalic cultures, dopaminergic neuron cell line cultures) experimental approaches (confocal microscopy, electron microscopy, laser capture microdissection, transfection of fluorescent-tagged receptors, treatments with fluorescent angiotensin, western blot, polymerase chain reaction, HPLC, mitochondrial respirometry and other functional assays) were used in the present study. We report the discovery of AT1 and AT2 receptors in brain mitochondria, particularly mitochondria of dopaminergic neurons. Activation of AT1 receptors in mitochondria regulates superoxide production, via Nox4, and increases respiration. Mitochondrial AT2 receptors are much more abundant and increase after treatment of cells with oxidative stress inducers, and produce, via nitric oxide, a decrease in mitochondrial respiration. Mitochondria from the nigral region of aged rats displayed altered expression of AT1 and AT2 receptors. AT2-mediated regulation of mitochondrial respiration represents an unrecognized primary line of defence against oxidative stress, which may be particularly important in neurons with increased levels of oxidative stress such as dopaminergic neurons. Altered expression of AT1 and AT2 receptors with aging may induce mitochondrial dysfunction, the main risk factor for neurodegeneration.
A sulfur host based on titanium monoxide@carbon hollow spheres for advanced lithium–sulfur batteries
Authors: Li Zhen , Zhang Jintao , Guan Buyuan , Wang Da , Liu Li-Min , Lou Xiong Wen 
Published: October 2016

AbstractLithium–sulfur batteries show advantages for next-generation electrical energy storage due to their high energy density and cost effectiveness. Enhancing the conductivity of the sulfur cathode and moderating the dissolution of lithium polysulfides are two key factors for the success of lithium–sulfur batteries. Here we report a sulfur host that overcomes both obstacles at once. With inherent metallic conductivity and strong adsorption capability for lithium-polysulfides, titanium monoxide@carbon hollow nanospheres can not only generate sufficient electrical contact to the insulating sulfur for high capacity, but also effectively confine lithium-polysulfides for prolonged cycle life. Additionally, the designed composite cathode further maximizes the lithium-polysulfide restriction capability by using the polar shells to prevent their outward diffusion, which avoids the need for chemically bonding all lithium-polysulfides on the surfaces of polar particles.