bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Genetics of the Neuronal Ceroid Lipofuscinoses
Authors: Mole Sara E 
Published: January 2014

Abstract

The neuronal ceroid lipofuscinoses (NCLs) are a group of clinically and genetically heterogenenous neurodegenerative disorders characterised by the accumulation of autofluorescent storage material in many cell types. Most display autosomal recessive inheritance. More than 400 mutations have been described in 13 genes:
PPT1
,
TPP1
,
CLN3
,
CLN5
,
CLN6
,
MFSD8
,
CLN8
,
CTSD, GRN, ATP13A2, KCTD7, CTSF
and
DNAJC5
, and none show obvious mutation hotspots. The functions of most of these genes remain elusive. The majority of the genetic defects identified are private, but there are geographically widespread or localised common founder mutations. The NCLs exemplify both phenotypic convergence and divergence, and there can be very wide disease severity caused by mutations in the same gene. Some recently identified mutations are in genes that are associated with other diseases. The recent expansion of knowledge in the genetic understanding of the NCLs is leading to improved diagnostic approaches, and the recent adoption of a new nomenclature.

Key Concepts:

More than 400 mutations are known across 13 genes causing disease in families diagnosed with NCL.

Most NCLs are autosomal recessive.

NCLs are a heterogenous group of disorders with common features of progressive degeneration of the brain, and often the retina, and intracellular storage of material similar to ceroid and lipofuscin.

NCLs are monogenic disorders.

One type of NCL is autosomal dominant.

There remain families diagnosed with NCL in which the genetic cause is not yet determined.
Hennig, Emil Hans Willi (The Father of Cladism)
Authors: Minelli Alessandro 
Published: January 2014

Abstract

Emil Hans Willi Hennig was a German systematist and entomologist. As a specialist in Diptera, he published a fundamental treatise on dipteran larvae and taxonomic monographs on several families. Hennig, however, is best known for his theoretical and methodological contributions to biological systematics. Indeed, he is considered the founder of phylogenetic systematics, or cladistics. Hennig articulated a method by which the evolutionary relationships of organisms (phylogeny) can be reconstructed and this reconstruction is subsequently turned into a hierarchical classification. This method contrasted with the mainstream approach to biological systematics adopted till the 1960s, but eventually succeeded to replace it, although in a modified version in respect to Hennig's original outline. Hennig's phylogenetic systematics has heavily impacted other biological disciplines, especially biogeography.
Behavioural Genetics in the Postgenomics Era
Authors: Charney Evan 
Published: January 2014

Abstract

There is growing evidence that the complexity of higher organisms does not correlate with the ‘complexity’ of the genome (the human genome contains fewer protein coding genes than corn, and many genes are preserved across species). Rather, complexity is associated with the complexity of the pathways and processes whereby the cell utilises the
deoxyribonucleic acid
molecule, and much else, in the process of phenotype formation. These processes include the activity of the epigenome, noncoding
ribonucleic acids
, alternative splicing and post‐translational modifications. Not accidentally, all of these processes appear to be of particular importance for the human brain, the most complex organ in nature. Because these processes can be highly environmentally reactive, they are a key to understanding behavioural plasticity and highlight the importance of the developmental process in explaining behavioural outcomes.

Key Concepts:

Humans possess fewer protein‐coding genes than maize (i.e. corn) and about the same number as a nematode.

There is now strong evidence that the complexity of higher organisms correlates with the relative amount of noncoding RNA rather than the number of protein‐coding genes.

Epigenetic processes are key to every aspect of human development from cellular differentiation to learning and memory.

Epigenetic mechanisms provide an explanation on the molecular level as to how the pre‐ and postnatal environments can impact offspring's behaviour.

Alternative splicing is one mechanism that enables the human body to create over 100 000 proteins with a genome that contains only 20 000 protein coding genes.

Each gene in the human genome is not ‘encoded’ for the production of a single protein.

Isoforms can have very different and even antithetical physiological effects.

Alternative splicing patterns are modulated in response to external stimuli, such as depolarisation of neurons, activation of signal transduction cascades and stress.

Post‐translational modification supplements alternative splicing as a means of creating protein diversity with a limited number of protein coding genes.

DNA is not the sole biological agent of inheritance.
Using Event Centrality to Predict Depressive Symptoms after a Romantic Conflict: A Prospective Design
Authors: Boals Adriel 
Published: January 2014

SummaryUsing cross‐sectional analyses, event centrality has been shown to be related to a number of poor psychological outcomes, including depressive symptoms and posttraumatic stress disorder symptoms. In the current study, we examined the ability of event centrality of a recent conflict in or breakup of a romantic relationship to prospectively predict depressive symptoms. Replicating previous findings, ratings of event centrality to a recent romantic conflict or breakup were significantly associated with depressive symptoms and posttraumatic stress disorder symptoms at Time 1. These relationships remained significant after controlling for closure and perceived insight. In addition, Time 1 event centrality prospectively predicted Time 2 depressive symptoms, particularly for participants who were split from their romantic partners at Time 2. This prediction remained significant after controlling for Time 1 depressive symptoms. The results of the study suggest that levels of event centrality for romantic conflicts prospectively predict subsequent mental health outcomes. Copyright © 2014 John Wiley & Sons, Ltd.
Examining the Life Script of African‐Americans: A Test of the Cultural Life Script
Authors: Coleman Justin T. 
Published: January 2014

SummaryLife scripts are expectations of the timings of important events in the normative life and are considered to represent an idealized lifecourse. However, whether they always represent an idealized lifecourse has not yet been tested in groups that may experience an increased prevalence of negative emotional events, such as historically unfairly treated minorities. In the present study, 255 African‐American adults completed a test of the life script. To ascertain the existence of a unique, African‐American life script, half nominated events likely to happen in the prospective life of a typical infant and half nominated those events for a prototypical infant of their race. Whereas some novel events specifically relevant to African‐Americans were mentioned in the current study, and a larger proportion of infrequently mentioned events were present compared with previous studies, overall, the findings support the expectations of the life script, as described by Rubin and Berntsen. Copyright © 2014 John Wiley & Sons, Ltd.
Active smoking status in chronic rhinosinusitis is associated with higher serum markers of inflammation and lower serum eosinophilia
Authors: Berania Ilyes , Endam Leandra Mfuna , Filali‐Mouhim Abdelali , Boisvert Pierre , Boulet Louis‐Philippe , Bossé Yohan , Desrosiers Martin 
Published: January 2014

BackgroundSmoking negatively affects postoperative evolution in patients with chronic rhinosinusitis (CRS); however, the mechanism remains incompletely described. In the lung, smoking increases expression of proinflammatory genes and is associated with an elevation of inflammatory serum markers. Our objective is to determine the impact of smoking on these biomarkers in CRS.MethodsTwo existing populations of patients previously phenotyped for genetic association studies (206 patients with refractory CRS and 408 patients with CRS and nasal polyposis) were stratified according to self‐reported smoking status and available serum biomarkers (complete blood count [CBC], total immunoglobulin E [IgE]). Asthma and bacterial cultures were evaluated.ResultsActive smoking was low in both groups (genetics of chronic rhinosinusitis 1 [GCRS1]: 11.2%; genetics of chronic rhinosinusitis 2 [GCRS2]: 9.4%). Total white blood cell (WBC) count was significantly higher in active smokers than in those who had never smoked and ex‐smokers. Serum eosinophilia and prevalence of self‐reported asthma was lower in active smokers than never‐smokers. In the GCRS2 population, endoscopically‐collected cultures trended toward a lower recovery rate of Staphylococcus aureus in smokers (p = 0.07). Never‐smokers and ex‐smokers had similar levels of WBCs and eosinophils.ConclusionOur study reveals that active tobacco smoking is associated with increases in markers of systemic inflammation in patients with CRS. The proinflammatory effect of smoking seems not only to act locally on sinus mucosa as previously described, but may also influence levels of inflammatory biomarkers systemically, suggesting that smoking‐induced changes have profound implications for health. Nevertheless, these changes may be potentially reversible; thus smoking cessation in CRS patients is strongly advised, and may have an impact on response of CRS to therapy.
Preparation of a liquid benzoxazine based on cardanol and the thermal stability of its graphene oxide composites
Authors: Xu Guo‐mei , Shi Tiejun , Liu Jianhua , Wang Qidong 
Published: January 2014

ABSTRACTA novel liquid benzoxazine was synthesized by Mannich reaction of cardanol, paraformaldehyde, and allylamine. The benzoxazine structure was characterized by 1H‐NMR and FTIR. The liquid benzoxazine could dissolve easily in many solvents. The curing behavior of the benzoxazine was characterized by differential scanning calorimetry (DSC) and its curing temperature was about 233°C. A benzoxazine‐functional silane coupling agent (BFSca) was synthesized with paraformaldehyde, phenolphthalein, and aminopropyltriethoxysilane. Graphene oxide (GO) was also made via improved Hummer's method. Then benzoxazine/GO composites were prepared using BFSca by solution blending and the curing behaviors of the composites were also characterized by IR, DSC, and thermogravimetric analysis. The minimum curing temperature and the highest 5% weight loss temperature for the composites was, respectively, 185 and 399.8°C. The SEM images of benzoxazine/GO composites demonstrated that BFSca had improved the dispersion of GO in the benzoxazine and also enhanced the thermal decomposition temperature of the composites. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40353.
Palladium‐Catalyzed Coupling Reaction of Perfluoroarenes with Diarylzinc Compounds
Authors: Ohashi Masato , Doi Ryohei , Ogoshi Sensuke 
Published: January 2014

AbstractThis report describes the first Pd0‐catalyzed cross‐coupling of hexafluorobenzene (C6F6) with diarylzinc compounds to give a variety of pentafluorophenyl arenes. This reaction could be applied to other perfluoroarenes, such as octafluorotoluene, pentafluoropyridine, and perfluoronaphthalene, to give the corresponding polyfluorinated coupling products. The optimal ligand in this catalytic reaction was PCy3, and lithium iodide was indispensable as an additive for the coupling reaction. One of the roles of lithium iodide in this catalytic reaction was to promote the oxidative addition of one CF bond of C6F6 to palladium. Stoichiometric reactions revealed that an expected oxidative‐addition product, trans‐[Pd(C6F5)I(PCy3)2], generated from the reaction of [Pd(PCy3)2] with C6F6 in the presence of lithium iodide, was not involved in the catalytic cycle. Instead, a transient three‐coordinate, monophosphine‐ligated species, [Pd(C6F5)I(PCy3)], emerged as a potential intermediate in the catalytic cycle. Therefore, we isolated a novel PdII complex, [Pd(C6F5)I(PCy3)(py)], in which pyridine (py) acted as a labile ligand to generate the transient species. In fact, in the presence of lithium iodide, this PdII complex was found to react smoothly with diphenylzinc to give the desired pentafluorophenyl benzene, whereas the same reaction conducted in the absence of lithium iodide resulted in a decreased yield of pentafluorophenyl benzene, which indicated that the other role of lithium iodide was to enhance the reactivity of the organozinc species during the transmetalation step.
Controllable Blinking‐to‐Nonblinking Behavior of Aqueous CdTeS Alloyed Quantum Dots
Authors: Dong Chaoqing , Liu Heng , Zhang Aidi , Ren Jicun 
Published: January 2014

AbstractSemiconductor quantum dots (QDs) are very important optical nanomaterials with a wide range of potential applications. However, the blinking of single QDs is an intrinsic drawback for some biological and photoelectric applications based on single‐dot emission. In this work, we systematically investigated the effects of certain synthetic conditions on the blinking behavior of aqueous CdTeS alloyed QDs, and observed that blinking behaviors of QDs were able to be controlled by the structure and concentration of the thiol compounds that were used as surface ligands. In optimal conditions, completely nonblinking QDs were prepared using certain thiol ligands as stabilizers in aqueous phase. The suppressed blinking mechanism was mainly attributed to elimination of QDs surface traps by coordination of thiol ligands with vacant Cd atoms, formation of appropriate CdS coating on QDs, and controlling the growth dynamics of QDs. Nonblinking QDs show high quantum yield, small size, and good solubility, and will be applied to some fields that were previously limited by blinking of traditional QDs.
Hückel and Möbius Expanded para‐Benziporphyrins: Synthesis and Aromaticity Switching
Authors: Szyszko Bartosz , Sprutta Natasza , Chwalisz Paulina , Stępień Marcin , Latos‐Grażyński Lechosław 
Published: January 2014

AbstractThe four expanded p‐benziporphyrins A,C‐di‐p‐benzi[24]pentaphyrin(1.1.1.1.1), N‐fused A‐p‐benzi[24]pentaphyrin, A,D‐di‐p‐benzi[28]hexaphyrin(1.1.1.1.1.1), and A,C‐di‐p‐benzi[28]hexaphyrin(1.1.1.1.1.1) were obtained in three‐component Lindsey‐type macrocyclizations. These compounds were explored as macrocyclic ligands and as potential aromaticity switches. A BODIPY‐like difluoroboron complex was obtained from the A,C‐di‐p‐benzi[24]pentaphyrin, whereas A,C‐di‐p‐benzi[28]hexaphyrin yielded a Möbius‐aromatic PdII complex containing fused pyrrole and phenylene subunits. Conformational behavior, tautomerism, and acid‐base chemistry of the new macrocycles were characterized by means of NMR spectroscopy and DFT calculations. Free base N‐fused A‐p‐benzi[24]pentaphyrin showed temperature‐dependent Hückel–Möbius aromaticity switching, whereas the A,C‐di‐p‐benzi[28]hexaphyrin formed a Möbius‐aromatic dication.
Total Synthesis and Structure Revision of Didemnaketal B
Authors: Fuwa Haruhiko , Muto Takashi , Sekine Kumiko , Sasaki Makoto 
Published: January 2014

AbstractDidemnaketal B, a structurally complex spiroacetal that exhibits potent HIV‐1 protease inhibitory activity, was originally discovered by Faulkner and his colleagues from the ascidian Didemnum sp. collected at Palau. Its absolute configuration was proposed on the basis of degradation/derivatization experiments of the authentic sample. However, our total synthesis of the proposed structure of didemnaketal B questioned the stereochemical assignment made by Faulkner et al. Here we describe in detail our first total synthesis of the proposed structure 2 of didemnaketal B, which features 1) a convergent synthesis of the C7–C21 spiroacetal domain by means of a strategy exploiting Suzuki–Miyaura coupling, 2) an Evans syn‐aldol reaction and a vinylogous Mukaiyama aldol reaction for the assembly of the C1–C7 acyclic domain, and 3) a Nozaki–Hiyama–Kishi reaction for the construction of the C21–C28 side chain domain. The NMR spectroscopic discrepancies observed between synthetic 2 and the authentic sample as well as careful inspection of the Faulkner’s stereochemical assignment led us to postulate that the absolute configuration of the C10–C20 domain of 2 has been erroneously assigned. Accordingly, the total synthesis of the revised structure 65 was achieved to show that the NMR spectroscopic properties of synthetic 65 were in good agreement with those of the authentic sample. Furthermore, application of the phenylglycine methyl ester (PGME) method to the C7–C21 spiroacetal domain enabled us to establish the absolute configuration of didemnaketal B.
Origin of the dopaminergic innervation of adult neurogenic areas
Authors: Höglinger Günter U. , Arias‐Carrión Oscar , Ipach Bastian , Oertel Wolfgang H. 
Published: January 2014

ABSTRACTAdult neurogenesis, a specific form of brain plasticity in mammals occurring in the subventricular zone (SVZ) and the subgranular zone (SGZ), is subject to complex regulations. Dopamine has been identified as a regulatory factor in rodents, nonhuman primates, and humans. We therefore studied in detail the origin of the dopaminergic innervation to the SVZ and SGZ in rodents. Postmortem anterograde and retrograde tracing combined with immunofluorescence procedures indicate a topographic organization of midbrain dopaminergic projections toward the SVZ. The substantia nigra pars compacta (SNc) projects specifically into the rostral migratory stream, the anterior SVZ, and the dorsal part of the medial and posterior SVZ. In contrast, the ventral tegmental area (VTA) innervates specifically the ventral part of the medial and posterior SVZ. Both VTA and SNc dopaminergic neurons innervate homogenously the lower and upper blade of the dentate gyrus, including the SGZ. Based on these findings, we suggest that the neurogenic areas are in a position to be differentially affected by region‐specific changes in dopamine signaling, the functional implication of which must be further elucidated. J. Comp. Neurol. 522:2336–2348, 2014. © 2014 Wiley Periodicals, Inc.
Axotomy‐induced target disconnection promotes an additional death mechanism involved in motoneuron degeneration in amyotrophic lateral sclerosis transgenic mice
Authors: Haulcomb Melissa M. , Mesnard Nichole A. , Batka Richard J. , Alexander Thomas D. , Sanders Virginia M. , Jones Kathryn J. 
Published: January 2014

ABSTRACTThe target disconnection theory of amyotrophic lateral sclerosis (ALS) pathogenesis suggests that disease onset is initiated by a peripheral pathological event resulting in neuromuscular junction loss and motoneuron (MN) degeneration. Presymptomatic mSOD1G93A mouse facial MN (FMN) are more susceptible to axotomy‐induced cell death than wild‐type (WT) FMN, which suggests additional CNS pathology. We have previously determined that the mSOD1 molecular response to facial nerve axotomy is phenotypically regenerative and indistinguishable from WT, whereas the surrounding microenvironment shows significant dysregulation in the mSOD1 facial nucleus. To elucidate the mechanisms underlying the enhanced mSOD1 FMN loss after axotomy, we superimposed the facial nerve axotomy model on presymptomatic mSOD1 mice and investigated gene expression for death receptor pathways after target disconnection by axotomy vs. disease progression. We determined that the TNFR1 death receptor pathway is involved in axotomy‐induced FMN death in WT and is partially responsible for the mSOD1 FMN death. In contrast, an inherent mSOD1 CNS pathology resulted in a suppressed glial reaction and an upregulation in the Fas death pathway after target disconnection. We propose that the dysregulated mSOD1 glia fail to provide support the injured MN, leading to Fas‐induced FMN death. Finally, we demonstrate that, during disease progression, the mSOD1 facial nucleus displays target disconnection‐induced gene expression changes that mirror those induced by axotomy. This validates the use of axotomy as an investigative tool in understanding the role of peripheral target disconnection in the pathogenesis of ALS. J. Comp. Neurol. 522:2349–2376, 2014. © 2014 Wiley Periodicals, Inc.
Evaluation of the effect of fluconazole and ketoconazole on the pharmacokinetics of tofacitinib in healthy adult subjects
Authors: Gupta Pankaj , Chow Vincent , Wang Ronnie , Kaplan Irina , Chan Gary , Alvey Christine , Ni Grace , Ndongo Marie‐Noella , LaBadie Robert R. , Krishnaswami Sriram 
Published: January 2014

AbstractTofacitinib is a novel, oral JAK inhibitor that is being investigated as a targeted immunomodulator. Tofacitinib is predominantly metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP2C19. Two Phase 1, randomized, open‐label, single sequence studies in 24 healthy subjects (12 per study) characterized the effects of fluconazole (moderate CYP3A4/potent CYP2C19 inhibitor) and ketoconazole (potent CYP3A4 inhibitor) on tofacitinib pharmacokinetics. In the fluconazole study, subjects received a single tofacitinib 30 mg dose. After 72 hours, subjects received fluconazole 400 mg, followed by 200 mg once daily (QD; days 2–7) plus tofacitinib 30 mg on day 5. In the ketoconazole study, a single tofacitinib 10 mg dose was administered. After 24 hours, subjects received ketoconazole (400 mg QD; days 1–3) plus tofacitinib 10 mg on day 3. Treatment comparisons were made using mixed‐effect models. Tofacitinib area under the curve and maximal plasma concentration increased by 79% and 27%, respectively, with fluconazole co‐administration and by 103% and 16%, respectively, with ketoconazole co‐administration. Tofacitinib half‐life increased by approximately 1 hour during co‐administration with fluconazole or ketoconazole. Co‐administration of moderate to potent CYP3A4 inhibitors is likely to increase the systemic exposure of tofacitinib and thus may warrant dosage adjustments or restrictions.
Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone
Authors: Langsjoen Peter H. , Langsjoen Alena M. 
Published: January 2014

AbstractThe bioavailability of the reduced form of coenzyme Q10 (ubiquinol) was compared to oxidized coenzyme Q10 (ubiquinone) with identical soft gel capsule excipients by measuring steady state plasma coenzyme Q10 (CoQ10) levels in 12 healthy volunteers. After baseline levels of ubiquinol, ubiquinone, total CoQ10, α‐tocopherol, and total cholesterol were obtained, follow‐up lab work was performed after 4 weeks of 200 mg/day of ubiquinone, after 4 weeks washout, and after 4 weeks of 200 mg/day of ubiquinol. Plasma total CoQ10 increased from 0.9 to 2.5 µg/mL (P < 0.001) after 4 weeks of ubiquinone and increased from 0.9 to 4.3 µg/mL (P < 0.001) after 4 weeks of ubiquinol. Total CoQ10/cholesterol ratio increased from 0.2 to 0.7 µmol/mmol after 4 weeks of ubiquinone and increased from 0.2 to 1.2 µmol/mmol after 4 weeks of ubiquinol. Both the increase in plasma CoQ10 and the increase in CoQ10/cholesterol ratio were significantly better after ubiquinol (P < 0.005 and P < 0.001, respectively) than after ubiquinone indicating superior bioavailability. Plasma ubiquinol/total CoQ10 ratio increased from baseline during ubiquinol supplementation (P < 0.005) and remained unchanged after ubiquinone supplementation. No side effects were noted in this study.