bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neurobiology of Panic Disorder: Toward an Integrated Model
Authors: Stein Dan J.
Published: August 2016

Panic disorder (PD) is a complex, multidimensional psychiatric disorder characterized by the presence of panic attacks as well as anticipatory anxiety and panic-related phobias (eg, agoraphobia). Although the etiology of this disabling disorder remains unclear, advances in basic neuroscience and in imaging studies have led to a greater understanding of the neurocircuitry and neurochemistry that are involved in modulating fear and anxiety and that are relevant to understanding PD. A preliminary integrated model can be outlined, but there is a need for additional research that cuts across genetic investigation, provocation studies, neuroimaging techniques, and treatment trials. As research continues and greater insight into the mechanisms underlying PD is achieved, additional treatment strategies may emerge.
The Role of Race and Ethnicity in Utilizing Atypical Antipsychotics
Authors: Nasrallah Henry A.
Published: August 2016

Atypical antipsychotics have become widely accepted as the first-line standard of care in the treatment of psychotic disorders, such as schizophrenia and bipolar disorder, which occur in ethnically and racially diverse patients. Accumulating data indicate that ethnicity factors may impact the efficacy and safety of atypical antipsychotics. Given the increasingly heterogeneous ethnic and racial composition of the United States, it is important for practicing clinicians to understand how race and ethnicity may influence the pharmacotherapeutic use of atypical antipsychotics.

The three articles in this supplement to CNS Spectrums, address how race and ethnicity may influence the efficacy, safety, tolerability, and dosing of atypical antipsychotics in today’s heterogeneous patient population.

L. DiAnne Bradford, PhD, reviews the most recent advances in ethnopharmacology and how gender, race, and ethnicity can influence, through metabolic biotransformation, the pharmacokinetic and pharmacodynamic properties of atypical antipsychotics. Dr. Bradford will also review how antipsychotic-related adverse events may be associated with the differences in oxidative enzyme activity across ethnic and racial groups and how these factors should be given careful consideration in the management of patients of different ethnic/genetic profiles.

David C. Henderson, MD, examines the emerging data that suggest metabolic differences among various racial and ethnic groups may predispose patients to serious medical complications, such as obesity, dyslipidemia, and diabetes mellitus. Dr. Henderson discusses the impact of these racial/ethnic metabolic differences when clinicians are prescribing atypical antipsychotics and also compares the risks of metabolic issues associated with specific agents within the class of atypical antipsychotics.
The Differential Diagnosis of Pseudobulbar Affect (PBA): Distinguishing PBA Among Disorders of Mood and Affect
Authors: Arciniegas David B. , Lauterbach Edward C. , Ginsberg David L. , Anderson Karen E. , Chow Tiffany W. , Flashman Laura A. , Hurley Robin A. , Kaufer Daniel I. , McAllister Thomas W. , Reeve Alison , Schiffer Randolph B. , Silver Jonathan M.
Published: August 2016

This monograph summarizes the proceedings of a roundtable meeting convened to discuss pseudobulbar affect (PBA). Two didactic lectures were presented, followed by a moderated discussion among 11 participants. Post-meeting manuscript development synthesized didactic- and discussion-based content and incorporated additional material from the neuroscience literature. A conceptual framework with which to distinguish between disorders of mood and affect is presented first, and disorders of affect regulation are then reviewed briefly. A detailed description of the most common of these disorders, PBA, is the focus of the remainder of the monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA are reviewed, and current and emerging methods of evaluation and treatment of persons with PBA are discussed. The material presented in this monograph will help clinicians better recognize, diagnose, and treat PBA, and will form a foundation for understanding and interpreting future studies of this condition.
Defining and Diagnosing Involuntary Emotional Expression Disorder
Authors: Cummings Jeffrey L. , Arciniegas David B. , Brooks Benjamin R. , Herndon Robert M. , Lauterbach Edward C. , Pioro Erik P. , Robinson Robert G. , Scharre Douglas W. , Schiffer Randolph B. , Weintraub Daniel
Published: August 2016

Uncontrollable episodes of emotional expression occur in a variety of neurological conditions. This emotional disinhibition syndrome is characterized by episodes of crying or laughing that are unrelated to or out of proportion to the eliciting stimulus. This syndrome is common among patients with amyotrophic lateral sclerosis, multiple sclerosis, stroke, and traumatic brain injury and a variety of terms and definitions have been used to describe it. The confusing nomenclature has been a barrier to understanding, diagnosis, and treatment of this disorder. The authors propose a unifying term, involuntary emotional expression disorder (IEED), and provide diagnostic criteria for this disorder.
Introduction: An Overview of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Study
Authors: McEvoy Joseph P.
Published: August 2016

In September 2005, the National Institute of Mental Health published phase 1 results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, a large-scale, double-blind trial comparing the relative effectiveness of five antipsychotics used to treat patients with schizophrenia: perphenazine, a conventional antipsychotic that has been commercially available since the 1950s, and four atypical agents—olanzapine, quetiapine, risperidone, and ziprasidone—that were introduced in the 1990s. The broad intention of the CATIE study is to determine if the atypical agents used offer any demonstrable clinical and public health advantages over the conventional agents. Concerns over costs and side effects (eg, pronounced weight gain and lipid disturbances) associated with the newer, atypical antipsychotics, as well as doubts about superior efficacy relative to older, conventional agents, served as an impetus to the trial.

The study design chosen for the CATIE study—that of a “large, simple” trial—sought to bypass the limitations of clinical studies that are conducted when pharmaceutical companies seek regulatory approval of a new medication. Studies done in pursuance of drug approval attempt to establish safety and efficacy in controlled clinical settings so as to determine if a drug works at all, and if its use entails specific side effects. Hence, they are typically placebo-controlled and short-term, enroll a small homogeneous population (eg, initially hospitalized patients with no psychiatric or medical comorbidities), forbid or restrict the use of concomitant medications, and take as their endpoints well-defined side effects and measures of core psychopathology. These restrictions heighten the risk that the study findings may not be widely applicable to patients outside the confines of the protocol.
Sexuality in Men and Women With Epilepsy
Authors: Harden Cynthia L.
Published: August 2016

Most people with epilepsy maintain normal reproductive and sexual lives. However, a significant minority of women with epilepsy (20% to 30%) have some degree of sexual dysfunction, including problems with libido, arousal, and orgasm. Men with epilepsy are at risk for decreased sexual functioning, including sexual interest and sexual performance, at least in part because of increased sex hormone-binding globulin levels and lower bioactive testosterone levels, particularly in association with the use of enzyme-inducing antiepileptic drugs, such as phenytoin and carbamazepine. A decrease in bioactive testosterone levels probably has a significant effect on the sexuality of women with epilepsy as well. Antiepileptic drugs may also affect sexual function in women through alterations of serotonergic neurotransmission. Epilepsy itself appears to have the potential to affect sexual function. The amygdala is emerging as a brain structure with significant involvement in sexuality in patients with epilepsy, as shown by alterations in sexual functioning after temporal lobectomy. Preliminary evidence suggests that people with temporal lobe epilepsy have reduced genital blood flow in response to erotic stimulation; the etiology of this phenomenon is not well understood, but disruption of the limbic and frontal cortex by epileptic activity may be implicated. Psychosocial factors, including sexual anxiety and stigma associated with epilepsy, can also affect the sexual life of patients with epilepsy.
Sexual Dysfunction and Psychotropic Medications
Authors: Stimmel Glen L. , Gutierrez Mary A.
Published: August 2016

Psychotropic drugs are often associated with sexual dysfunction. The frequency of antidepressant-associated sexual dysfunction is greatly underestimated in clinical trials that rely on patient self-report of these adverse events. Direct inquiry reveals that delayed orgasm/ejaculation occurs in ≥50% and anorgasmia in at least one third of patients given selective serotonin reuptake inhibitors. Antidepressant-induced sexual dysfunction can be successfully managed. A different antidepressant without significant sexual effects, such as bupropion or mirtazapine, can often be substituted. Other strategies involve drug holidays or adjunctive therapy with drugs such as sildenafil. Dopamine antagonist antipsychotic drugs are most commonly associated with decreased libido. The newer atypical antipsychotics, with less effect on dopamine, are less commonly associated with sexual dysfunction. Sexual dysfunction is commonly reported with seizure disorders, and many anticonvulsant drugs affect levels of sex hormones. Because sexual dysfunction can be related to many factors, care must be taken to establish the patient's baseline sexual functioning before the initiation of psychotropic drug therapy and to rule out other etiologies before drugs are implicated as causative.
Social Influences on the Concept of Fibromyalgia
Authors: Merskey Harold
Published: August 2016

Despite relevant evidence of physical illness promoting fibromyalgia syndrome (FMS), some authors claim that it is a psychological illness, or due to “psychological amplification.” Good evi-dence for such views is lacking. Selection processes lead to increased rates of psychological illness in general practice and in specialist practice. The phys-ical distress of FMS can increase both anxiety and depression. Questionable research supported by the insurance industry has tended to provide nega-tive and disparaging views of pain. Current imag-ing studies support the view that central effects connected with FMS relate to the processing of noxious stimulation more than affective disorder.
Mechanisms of Fibromyalgia Pain
Authors: Staud Roland
Published: August 2016

Chronic musculoskeletal pain is highly prevalent in the United States and includes inflammatory and non-inflammatory syndromes, such as low back pain (reported by 59 million Americans in the past 3 months), neck pain (reported by 30.1 million Americans in the past 3 months), clinical osteoarthritis (reported by 27 million Americans in the past 3 months), and fibromyalgia (FM). FM affects between 2% to 4% of the US population or 12 million people. Inflammatory pain conditions commonly reported by patients include rheumatoid arthritis (2.5 million) and gout (3 million), among others. This article will focus primarily on FM, which is a chronic pain condition that predominately affects women.

The current diagnostic criteria for FM include chronic widespread pain for at least 3 months and the presence of widespread mechanical tenderness. A patient with suspected FM must report pain in all four body quadrants and have at least 11 of 18 tender points for a positive diagnosis to be made. Tender points are areas of the body where pressure is applied until pain threshold is achieved. In addition to pain and tenderness, FM patients very frequently describe widespread stiffness and fatigue, disrupted or poor sleep, dyscognition, and mild soft tissue swelling. Patients often also report symptoms of anxiety and depression.
Emotional Regulation: Implications for the Psychobiology of Psychotherapy
Authors: Stein Dan J.
Published: August 2016

A range of studies have contributed to understanding the psychobiology of emotional regulation. Functional imaging studies have demonstrated that cortico-limbic circuitry plays an important role in mediating processes such as reappraisal and suppression. Dorsolateral prefrontal cortex may be important in conscious reframing, while ventromedial prefrontal cortex and orbitofrontal cortex may be particularly important in emotion evaluation. Gene variants and early environments impact underlying emotional regulation and its neurobiology. It may be hypothesized that during interventions such as psychotherapy there are improvements in emotional regulation, together with the normalization of related psycho-biological mechanisms.
Characteristics and Symptomatology of Patients Diagnosed with Unipolar Depression at Risk for Undiagnosed Bipolar Disorder: A Bipolar Survey
Authors: Bolge Susan C. , Thompson Thomas , Bourne Eric , Nanry Kevin
Published: August 2016

Objective: To identify characteristics of patients diagnosed with unipolar depression who may have undiagnosed bipolar disorder.

Methods: Patients diagnosed with unipolar depression by a healthcare provider were identified through the Consumer Health Sciences National Health and Wellness Survey. Manic symptoms, comorbid conditions, psychiatric symptomatology, use of healthcare resources, and patient demographics were identified through Internet-based questionnaires. A self-report adapted version of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria identified symptoms consistent with a manic episode. Psychological well-being was measured by the Psychological General Well-Being Index.

Results: Of the 1,602 respondents who met inclusion criteria, 219 (14% or ~1 out of 7) reported symptoms consistent with a manic episode and were considered at risk for undiagnosed bipolar disorder. These respondents were younger and had a lower socioeconomic status. At-risk patients rated their depression as more severe and experienced greater impairment of psychological well-being. More than 70% of those at risk reported speaking with a healthcare provider about their mania symptoms. Comorbid mental disorders, especially anxiety-related conditions, were common in these patients.

Conclusion: These findings underscore the importance of evaluating unipolar patients for bipolar disorder and may help clinicians identify symptoms and comorbidities associated with patients with unipolar depression at risk for undiagnosed bipolar disorder.
Bipolar Disorder: A National Health Concern
Authors: McIntyre Roger S. , Konarski Jakub Z.
Published: August 2016

Bipolar disorders are prevalent, disabling, and costly diseases that often pursue an inexorable course. Underdetection, misdiagnosis, and diagnostic delay frequently and unnecessarily interfere with appropriate treatment of the disorder. Mortality studies in bipolar disorder underscore the relevance of both unnatural and natural causes of death, inviting the need for improved preventative and primary health care for bipolar patients. The treatment framework for bipolar disorder must recognize and anticipate the multidirnensionality and comorbidity of this illness. Pharmacotherapy is necessary, with multiple concomitant medications required for most patients, In addition, adjunctive psychosocial interventions offer enhanced compliance and may beneficially influence psychopathological and functional outcomes. This article emphasizes the public health concern of bipolr disorder, and provides tactics to enhance detection of cryptic bipolar states, underscore the clinical and pathophysiological relevance of comorbidity in bipolar disorder, and provide a framework for multimodality therapy for this condition.
Emerging Treatment Options in Treatment-Resistant Depression and Anxiety Disorders
Authors: IsHak Waguih William , Rapaport Mark H. , Gotto Jennifer G.
Published: August 2016

Management strategies for treatment-resistant depression and anxiety disorders have evolved over the last decade. Our understanding of the factors that impair recovery from an episode of major depression has increased, leading to the development of more precise diagnostic methodology that highlight the presence of comorbid conditions. New medications, creative uses of existing medications, increased empirical data about augmentation strategies, and the development of innovative nonpharmacologic interventions are responsible for a marked expansion in treatment options. Traditionally, augmentations with lithium, thyroid hormones, or electroconvulsive therapy have demonstrated effectiveness in some patients with treatment-resistant mood disorders. Among the promising treatments in both depression and anxiety is augmentation using low-dose antipsychotics medications, combining antidepressants of different classes, and the addition of psychotherapy. Nonpharmacologic interventions that may have potential include transcranial magnetic stimulation, deep-brain stimulation, and vagus-nerve stimulation. This article provides a brief review of the available data summarizing existing and new treatment strategies in depression and anxiety disorders.
The use of patient-level outcomes to inform treatment
Authors: Slade Mike
Published: August 2016

Objective – The assessment of outcome for any purpose is not undertaken routinely in European mental health services. This paper discusses the merits of using outcome data to inform the planning of mental health care for individual patients, and provides practical advice to support the implementation of this new approach to working. Method – The use of outcomes in North America and Europe is briefly reviewed. A conceptual basis is proposed for routine outcome assessment – the ongoing measurement and use of outcome data to inform decisions about whether to continue, change or curtail treatment. A cognitive psychology model is developed which indicates that the routine use of outcomes will improve mental health care. Perceived problems with routine outcome assessment are discussed, and principles for implementation are identified. Results – Outcomes are used mainly for generating local-level (rather than patient-level) data in North America, and rarely used in Europe. The use of outcome data routinely may facilitate reflective clinical practice, a model of decision-making which leads to a higher quality of clinical care than automated problem-solving. One issue relates to the use of standardised assessments designed for research purposes in clinical settings, and this is being addressed through the development of a new generation of outcome measures which are explicitly designed for clinical use. However, most clinicians remain unconvinced of the benefits of routine outcome assessment, and relevant research is currently underway across Europe which will address this concern. Scientific principles to maximise quality and pragmatic principles to maximise the chances of successful implementation are identified. Conclusions – The routine use of outcomes will become increasingly prominent in European mental health services. This provides clinicians with an opportunity to improve the quality of clinical care offered to patients.
A systematic review of the European Agency for the Evaluation of Medicinal Products (EMEA) recommendations on the conduct of clinical trials in psychiatry
Authors: Guaiana Giuseppe , Barbui Corrado
Published: August 2016

Objective – This article critically reviews the European Agency for the Evaluation of Medicinal Products (EMEA) recommendations on the conduct of clinical trials in psychiatry. The EMEA is a regulatory body which provides the institutions of the European Community with the best possible scientific advice on the quality, safety, and efficacy of medicinal products. Method – Systematic review of recommendations, guide-lines and official documents available in the EMEA web site. Results – Out of nearly 400 documents, we identified 4 documents on the conduct of clinical trials in specific psychiatric disorders and 5 on the use of placebo or active comparator in evaluating a new drug's efficacy and on methodological issues in establishing difference and equivalence of effect. The EMEA recommends clinical trials to detect a difference between the compound under investigation and placebo, and to assess at least non-inferiority against an active comparator. A placebo arm is intended to validate the study. The EMEA supports the use of placebo only when there is no serious risk for the patient. In schizophrenia, depression and bipolar disorder the Agency suggests that a three-arm study is the design of choice, to demonstrate superiority against placebo and a similar balance against an active comparator. Conclusions – Despite the many effective therapeutic options available for the pharmacological management of psychiatric disorders, the EMEA regulatory process still relies on the demonstration of efficacy in absolute terms, against a placebo. We discuss this position and put at issue the possibility of developing a new generation of trials to demonstrate superiority of effect of new compounds over reference ones.
Does Apolipoprotein e4 Status Moderate the Association of Family Environment with Long-Term Child Functioning following Early Moderate to Severe Traumatic Brain Injury? A Preliminary Study
Authors: Treble-Barna Amery , Zang Huaiyu , Zhang Nanhua , Martin Lisa J. , Yeates Keith Owen , Taylor H. Gerry , Wade Shari L. , Kurowski Brad G.
Published: August 2016

Objectives:To examine whether apolipoprotein e4 (APOE) status moderates the association of family environment with child functioning following early traumatic brain injury (TBI).Methods:Sixty-five children with moderate to severe TBI and 70 children with orthopedic injury (OI) completed assessments 6, 12, 18 months, and 3.5 and 6.8 years post injury. DNA was extracted from saliva samples and genotyped for APOE e4 status. Linear mixed models examined moderating effects of APOE e4 status on associations between two family environment factors (parenting style, home environment) and three child outcomes (executive functioning, behavioral adjustment, adaptive functioning).Results:Children with TBI who were carriers of the e4 allele showed poorer adaptive functioning relative to non-carriers with TBI and children with OI in the context of low authoritarianism. At high levels of authoritarianism, non-carriers with TBI showed the poorest adaptive functioning among groups. There were no main effects or interactions involving APOE and executive functioning or behavioral adjustment.Conclusions:The APOE e4 allele was detrimental for long-term adaptive functioning in the context of positive parenting, whereas in less optimal parenting contexts, being a non-carrier was detrimental. We provide preliminary evidence for an interaction of APOE e4 status and parenting style in predicting long-term outcomes following early TBI. (JINS, 2016,22, 859–864)
Spatial clustering of tuning in mouse primary visual cortex
Authors: Ringach Dario L. , Mineault Patrick J. , Tring Elaine , Olivas Nicholas D. , Garcia-Junco-Clemente Pablo , Trachtenberg Joshua T.
Published: August 2016

The primary visual cortex of higher mammals is organized into two-dimensional maps, where the preference of cells for stimulus parameters is arranged regularly on the cortical surface. In contrast, the preference of neurons in the rodent appears to be arranged randomly, in what is termed a salt-and-pepper map. Here we revisited the spatial organization of receptive fields in mouse primary visual cortex by measuring the tuning of pyramidal neurons in the joint orientation and spatial frequency domain. We found that the similarity of tuning decreases as a function of cortical distance, revealing a weak but statistically significant spatial clustering. Clustering was also observed across different cortical depths, consistent with a columnar organization. Thus, the mouse visual cortex is not strictly a salt-and-pepper map. At least on a local scale, it resembles a degraded version of the organization seen in higher mammals, hinting at a possible common origin.
Selective directed self-assembly of coexisting morphologies using block copolymer blends
Authors: Stein A. , Wright G. , Yager K. G. , Doerk G. S. , Black C. T.
Published: August 2016

Directed self-assembly (DSA) of block copolymers is an emergent technique for nano-lithography, but is limited in the range of structures possible in a single fabrication step. Here we expand on traditional DSA chemical patterning. A blend of lamellar- and cylinder-forming block copolymers assembles on specially designed surface chemical line gratings, leading to the simultaneous formation of coexisting ordered morphologies in separate areas of the substrate. The competing energetics of polymer chain distortions and chemical mismatch with the substrate grating bias the system towards either line/space or dot array patterns, depending on the pitch and linewidth of the prepattern. This is in contrast to the typical DSA, wherein assembly of a single-component block copolymer on chemical templates generates patterns of either lines/spaces (lamellar) or hexagonal dot arrays (cylinders). In our approach, the chemical template encodes desired local spatial arrangements of coexisting design motifs, self-assembled from a single, sophisticated resist.
PTH/SDF-1α cotherapy induces CD90+CD34− stromal cells migration and promotes tissue regeneration in a rat periodontal defect model
Authors: Wang Fang , Du Lingqian , Ge Shaohua
Published: August 2016

Stromal cell-derived factor-1α (SDF-1α) is a key stem cell homing factor that is crucial for recruitment of stem cells to many diseased organs. However, the therapeutic activity of SDF-1α is potentially limited by N-terminal cleavage at position-2 proline by a cell surface protein CD26/dipeptidyl peptidase-IV (DPP-IV). Parathyroid hormone (PTH) is a DPP-IV inhibitor and has been suggested as a promising agent for periodontal tissue repair. The purpose of this study was to explore the effects of a cell-free system comprising SDF-1α and scaffold plus PTH systemic application on periodontal tissue regeneration in vivo. The results showed that PTH/SDF-1α cotherapy improved the quantity of regenerated bone and resulted in better organization of ligament interface. We further investigated the possible mechanisms and found that PTH/SDF-1α cotherapy enhanced CD90+CD34− stromal cells migration in vivo, increased the number of CXCR4 + cells in periodontal defects, induced early bone osteoclastogenesis and enhanced the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and collagen I (Col I) in newly formed bone tissue. In conclusion, this cell-free tissue engineering system with local administration of SDF-1α and systemic application of PTH could be employed to induce CD90+CD34− stromal cells recruitment and promote periodontal tissue regeneration.
Evaluation of micro Electroretinograms Recorded with Multiple Electrode Array to Assess Focal Retinal Function
Authors: Fujii Momo , Sunagawa Genshiro A. , Kondo Mineo , Takahashi Masayo , Mandai Michiko
Published: August 2016

Full-field electroretinograms (ERGs) are used to objectively assess the mass function of the retina, whereas focal ERGs are used to evaluate the focal retinal function. The purpose of this study was to determine the usefulness of a multiple electrode array (MEA) system for recording ex vivo micro ERGs (mERGs) together with multiunit spike responses of the retinal ganglion cells (RGCs) to assess focal retinal function in isolated mouse retinas. The a- and b-waves of the full-field ERGs were present in the mERG. The b-wave was blocked by L-AP4, an inhibitor of the mGluR6 receptor and the OFF-component was blocked by exposure to PDA, an antagonist of ionotropic glutamate receptors, with a corresponding RGC responses. mERGs were also recorded from mice with progressive retinal degeneration, the C57BL/6J-Pde6brd1-2J/J (rd1) mice, from which conventional full-field ERGs are non-recordable. A blockade of the glutamate receptors indicated that the negative wave of rd1 mice do not originate from the photoreceptors but from the second or third order neurons. This technique of recording mERGs will be useful in assessing the focal properties of the retinas obtained from eyes with pathology and also to follow the recovery of the physiology of the retina in regenerative studies.
A novel human-specific splice isoform alters the critical C-terminus of Survival Motor Neuron protein
Authors: Seo Joonbae , Singh Natalia N. , Ottesen Eric W. , Lee Brian M. , Singh Ravindra N.
Published: August 2016

Spinal muscular atrophy (SMA), a leading genetic disease of children and infants, is caused by mutations or deletions of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to skipping of exon 7. SMN2 predominantly produces SMNΔ7, an unstable protein. Here we report exon 6B, a novel exon, generated by exonization of an intronic Alu-like sequence of SMN. We validate the expression of exon 6B-containing transcripts SMN6B and SMN6BΔ7 in human tissues and cell lines. We confirm generation of SMN6B transcripts from both SMN1 and SMN2. We detect expression of SMN6B protein using antibodies raised against a unique polypeptide encoded by exon 6B. We analyze RNA-Seq data to show that hnRNP C is a potential regulator of SMN6B expression and demonstrate that SMN6B is a substrate of nonsense-mediated decay. We show interaction of SMN6B with Gemin2, a critical SMN-interacting protein. We demonstrate that SMN6B is more stable than SMNΔ7 and localizes to both the nucleus and the cytoplasm. Our finding expands the diversity of transcripts generated from human SMN genes and reveals a novel protein isoform predicted to be stably expressed during conditions of stress.
Genome Wide Association Study Identifies L3MBTL4 as a Novel Susceptibility Gene for Hypertension
Authors: Liu Xin , Hu Cheng , Bao Minghui , Li Jing , Liu Xiaoyan , Tan Xuerui , Zhou Yong , Chen Yequn , Wu Shouling , Chen Shuohua , Zhang Rong , Jiang Feng , Jia Weiping , Wang Xingyu , Yang Xinchun , Cai Jun
Published: August 2016

Hypertension is a major global health burden and a leading risk factor for cardiovascular diseases. Although its heritability has been documented previously, contributing loci identified to date account for only a small fraction of blood pressure (BP) variation, which strongly suggests the existence of undiscovered variants. To identify novel variants, we conducted a three staged genetic study in 21,990 hypertensive cases and normotensive controls. Four single nucleotide polymorphisms (SNPs) at three new genes (L3MBTL4 rs403814, Pmeta = 6.128 × 10−9; LOC729251 and TCEANC) and seven SNPs at five previously reported genes were identified as being significantly associated with hypertension. Through functional analysis, we found that L3MBTL4 is predominantly expressed in vascular smooth muscle cells and up-regulated in spontaneously hypertensive rats. Rats with ubiquitous over-expression of L3MBTL4 exhibited significantly elevated BP, increased thickness of the vascular media layer and cardiac hypertrophy. Mechanistically, L3MBTL4 over-expression could lead to down-regulation of latent transforming growth factor-β binding protein 1 (LTBP1) and phosphorylation activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which is known to trigger the pathological progression of vascular remodeling and BP elevation. These findings pinpointed L3MBTL4 as a critical contributor to the development and progression of hypertension and uncovers a novel target for therapeutic intervention.
The aged lymphoid tissue environment fails to support naïve T cell homeostasis
Authors: Becklund Bryan R. , Purton Jared F. , Ramsey Chris , Favre Stéphanie , Vogt Tobias K. , Martin Christopher E. , Spasova Darina S. , Sarkisyan Gor , LeRoy Eric , Tan Joyce T. , Wahlus Heidi , Bondi-Boyd Brea , Luther Sanjiv A. , Surh Charles D.
Published: August 2016

Aging is associated with a gradual loss of naïve T cells and a reciprocal increase in the proportion of memory T cells. While reduced thymic output is important, age-dependent changes in factors supporting naïve T cells homeostasis may also be involved. Indeed, we noted a dramatic decrease in the ability of aged mice to support survival and homeostatic proliferation of naïve T cells. The defect was not due to a reduction in IL-7 expression, but from a combination of changes in the secondary lymphoid environment that impaired naïve T cell entry and access to key survival factors. We observed an age-related shift in the expression of homing chemokines and structural deterioration of the stromal network in T cell zones. Treatment with IL-7/mAb complexes can restore naïve T cell homeostatic proliferation in aged mice. Our data suggests that homeostatic mechanisms that support the naïve T cell pool deteriorate with age.
Disruption of dmc1 Produces Abnormal Sperm in Medaka (Oryzias latipes)
Authors: Chen Ji , Cui Xiaojuan , Jia Shaoting , Luo Daji , Cao Mengxi , Zhang Yunsheng , Hu Hongling , Huang Kaiyao , Zhu Zuoyan , Hu Wei
Published: August 2016

DMC1 is a recombinase that is essential for meiotic synapsis. Experiments in extensive species of eukaryotes have indicated the independent role of DMC1 in repairing double strand breaks (DSBs) produced during meiosis I. Mutation of dmc1 in mice and human often leads to obstacles in spermatogenesis and male sterility. Here, we report on the disruption of dmc1 in male medaka (Oryzias latipes). Synapsis was disturbed in the mutant medaka testis nuclei, as observed in mice and other organisms. Unexpectedly, the mutant medaka could produce a few sperm and, although most of these had multiple tail or multiple head malformations, some of them could swim and few of them even had insemination ability. Our transcriptome analysis showed that there was not a remarkable change in the expression of most of the genes involved in the pathways associated with the meiotic DNA repair and flagella assembly. Our results provided an indication of the accessory mechanisms that might be involved in the repair of DSBs during meiosis. In a species besides humans, we provided evidence that disorders in meiosis recombination might lead to the malformation of sperm.
ATF3 controls proliferation of osteoclast precursor and bone remodeling
Authors: Fukasawa Kazuya , Park Gyujin , Iezaki Takashi , Horie Tetsuhiro , Kanayama Takashi , Ozaki Kakeru , Onishi Yuki , Takahata Yoshifumi , Yoneda Yukio , Takarada Takeshi , Kitajima Shigetaka , Vacher Jean , Hinoi Eiichi
Published: August 2016

Bone homeostasis is maintained by the sophisticated coupled actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Here we identify activating transcription factor 3 (ATF3) as a pivotal transcription factor for the regulation of bone resorption and bone remodeling under a pathological condition through modulating the proliferation of osteoclast precursors. The osteoclast precursor-specific deletion of ATF3 in mice led to the prevention of receptor activator of nuclear factor-κB (RANK) ligand (RANKL)-induced bone resorption and bone loss, although neither bone volume nor osteoclastic parameter were markedly altered in these knockout mice under the physiological condition. RANKL-dependent osteoclastogenesis was impaired in vitro in ATF3-deleted bone marrow macrophages (BMM). Mechanistically, the deficiency of ATF3 impaired the RANKL-induced transient increase in cell proliferation of osteoclast precursors in bone marrow in vivo as well as of BMM in vitro. Moreover, ATF3 regulated cyclin D1 mRNA expression though modulating activator protein-1-dependent transcription in the osteoclast precursor and the introduction of cyclin D1 significantly rescued the impairment of osteoclastogenesis in ATF3-deleted BMM. Therefore, these findings suggest that ATF3 could have a pivotal role in osteoclastogenesis and bone homeostasis though modulating cell proliferation under pathological conditions, thereby providing a target for bone diseases.
Deformation behavior of metallic glasses with shear band like atomic structure: a molecular dynamics study
Authors: Zhong C. , Zhang H. , Cao Q. P. , Wang X. D. , Zhang D. X. , Ramamurty U. , Jiang J. Z.
Published: August 2016

Molecular dynamics simulations were employed to investigate the plastic deformation within the shear bands in three different metallic glasses (MGs). To mimic shear bands, MG specimens were first deformed until flow localization occurs, and then the volume of the material within the localized regions was extracted and replicated. Homogeneous deformation that is independent of the size of the specimen was observed in specimens with shear band like structure, even at a temperature that is far below the glass transition temperature. Structural relaxation and rapid cooling were employed to examine the effect of free volume content on the deformation behavior. This was followed by detailed atomic structure analyses, employing the concepts of Voronoi polyhedra and “liquid-like” regions that contain high fraction of sub-atomic size open volumes. Results suggest that the total fraction of atoms in liquid-like regions is a key parameter that controls the plastic deformation in MGs. These are discussed in the context of reported experimental results and possible strategies for synthesizing monolithic amorphous materials that can accommodate large tensile plasticity are suggested.
Stimulated Raman photoacoustic spectroscopy for chemical-contrast imaging of a sample deeply buried in scattering media
Authors: Banno Motohiro , Nagashima Ami , Yui Hiroharu
Published: August 2016

The development of a wavelength-variable stimulated Raman scattering photoacoustic spectrometer and its application to a sample buried in highly scattering media are presented.
Phosphine-catalyzed cage carbon functionalization of o-carborane: facile synthesis of alkenylcarboranes
Authors: Zheng Fangrui , Leung Tsz-Fai , Chan Ka-Wing , Sung Herman H. Y. , Williams Ian D. , Xie Zuowei , Jia Guochen
Published: August 2016

Phosphines can efficiently catalyze alkenylation of o-carborane with electron-deficient alkynes, which represents the first example of organocatalysis in o-carborane functionalization.
Two-coordinate terminal zinc hydride complexes: synthesis, structure and preliminary reactivity studies
Authors: Dawkins Michael J. C. , Middleton Ewart , Kefalidis Christos E. , Dange Deepak , Juckel Martin M. , Maron Laurent , Jones Cameron
Published: August 2016

The first examples of essentially two-coordinate, monomeric zinc hydride complexes have been stabilised by incorporation of “super bulky” amide ligands. Crystallographic studies show them to possess near linear N–Zn–H fragments (see picture).
Consequences of conformational flexibility in hydrogen-bond-driven self-assembly processes
Authors: Berrocal José Augusto , Di Meo Florent , García-Iglesias Miguel , Gosens Ronald P. J. , Meijer E. W. , Linares Mathieu , Palmans Anja R. A.
Published: August 2016

Chiral, conformationally flexible C3-symmetrical trisamides self-assemble into helical aggregates but a helical bias is only expressed in linear alkane solvents and not in cyclic ones.
The light–matter interaction of a single semiconducting AlGaN nanowire and noble metal Au nanoparticles in the sub-diffraction limit
Authors: Sivadasan A. K. , Madapu Kishore K. , Dhara Sandip
Published: August 2016

Near field scanning optical microscopy is used for imaging as well as understanding the intrinsic properties of semiconducting and noble-metal nanostructures of sub-diffraction size.
Short-term beef consumption promotes systemic oxidative stress, TMAO formation and inflammation in rats, and dietary fat content modulates these effects
Authors: Van Hecke Thomas , Jakobsen Louise M. A. , Vossen Els , Guéraud Françoise , De Vos Filip , Pierre Fabrice , Bertram Hanne C. S. , De Smet Stefaan
Published: August 2016

High beef consumption induces oxidative stress in gastrointestinal mucosae and extra-gastrointestinal organs such as the heart and kidneys.
An imidazolium-modified chiral rhodium/diamine-functionalized periodic mesoporous organosilica for asymmetric transfer hydrogenation of α-haloketones and benzils in aqueous medium
Authors: Zhou Feng , Hu Xiaoying , Gao Ming , Cheng Tanyu , Liu Guohua
Published: August 2016

An imidazolium-modified chiral rhodium/diamine-functionalized periodic mesoporous organosilica is developed, which greatly promotes asymmetric transfer hydrogenation of α-haloketones and benzils in aqueous medium.
Half molecular exchange of IgGs in the blood of healthy humans: chimeric lambda-kappa-immunoglobulins containing HL fragments of antibodies of different subclasses (IgG1–IgG4)
Authors: Sedykh Sergey E. , Lekchnov Evgenii A. , Prince Viktor V. , Buneva Valentina N. , Nevinsky Georgy A.
Published: August 2016

It was shown that blood antibodies undergo extensive post-transcriptional half-molecule exchange by HL-fragments. Human blood IgGs contain 8.8 ± 2.7% (range 2.6–14%) chimeric kappa-lambda IgGs, which consist of IgG1–IgG4.
Design, synthesis and biological evaluation of caffeoyl benzanilides as dual inhibitors of HIV integrase and CCR5
Authors: Sun Xuefeng , Fan Ningning , Xu Weisi , Sun Yixing , Xie Xin , Guo Ying , Ma Liying , Liu Junyi , Wang Xiaowei
Published: August 2016

Novel series of caffeoyl benzanilides have been synthesized and evaluated as dual inhibitors of HIV-1 CCR5/IN. Compound 9a exhibited the possibility of being a dual inhibitor of HIV-1.
X-ray fluorescence microscopic measurement of elemental distribution in the mouse retina with age
Authors: Grubman Alexandra , Guennel Philipp , Vessey Kirstan A. , Jones Michael W. M. , James Simon A. , de Jonge Martin D. , White Anthony R. , Fletcher Erica L.
Published: August 2016

The biologically important metals such as zinc, copper and iron play key roles in retinal function, yet no study has mapped the spatio-temporal distribution of retinal biometals in healthy or diseased retina.
Highly efficient anion transport mediated by 1,3-bis(benzimidazol-2-yl)benzene derivatives bearing electron-withdrawing substituents
Authors: Peng Chen-Chen , Zhang Meng-Jia , Sun Xiao-Xiao , Cai Xiong-Jie , Chen Yun , Chen Wen-Hua
Published: August 2016

1,3-Bis(benzimidazol-2-yl)benzene derivatives bearing strong electron-withdrawing substituents were found to exhibit highly efficient anion transport.
Construction of a neutral linear supramolecular polymer via orthogonal donor–acceptor interactions and pillar[5]arene-based molecular recognition
Authors: Chen Panpan , Mondal Julfikar Hassan , Zhou Yujuan , Zhu Huangtianzhi , Shi Bingbing
Published: August 2016

A neutral linear supramolecular polymer was efficiently constructed by donor–acceptor interactions and pillar[5]arene-based molecular recognition through hierarchical orthogonal strategies.
Ultrafast diffusion-controlled thiol–ene based crosslinking of silicone elastomers with tailored mechanical properties for biomedical applications
Authors: Nguyen Khai D. Q. , Megone William V. , Kong Dexu , Gautrot Julien E.
Published: August 2016

Thiol-ene coupling enables the metal-free ultra-fast (seconds) crosslinking of polysiloxanes.
Investigation of Fe doped ZnO thin films by X-ray absorption spectroscopy
Authors: Yadav Ashok Kumar , Haque Sk Maidul , Tripathi Shilpa , Shukla Dinesh , Ahmed Md. A. , Phase D. M. , Bandyopadhyay S. , Jha S. N. , Bhattacharyya D.
Published: August 2016

XANES and EXAFS studies have been carried out on Fe doped ZnO thin films having different Fe doping concentration ranging from 1% to 10% and the observed ferromagnetism in the samples is explained in the light of XANES and EXAFS observations.
Zein bio-nanoparticles: a novel green nanopolymer as a dispersive solid-phase extraction adsorbent for separating and determining trace amounts of azorubine in different foodstuffs
Authors: Zargar Behrooz , Pourreza Nahid , Bayat Elahe , Hatamie Amir
Published: August 2016

A new, easy, and green method using zein nanoparticles as a dispersive solid-phase extraction (DSPE) adsorbent has been used for the preconcentration of azorubine (a well-known chemical dye additive) as a model compound in foodstuffs.
Supersaturation-dependent polymorphic outcome and transformation rate ofl-glutamic acid
Authors: Liang Shanshan , Duan Xuezhi , Zhang Xiangyang , Qian Gang , Zhou Xinggui
Published: August 2016

A link between the predominant conformer in supersaturatedl-Glu aqueous solution and the polymorphic outcome is built using FTIR.
Colossal dielectric performance of pure barium titanate ceramics consolidated by spark plasma sintering
Authors: Yang X. , Li D. , Ren Z. H. , Zeng R. G. , Gong S. Y. , Zhou D. K. , Tian H. , Li J. X. , Xu G. , Shen Z. J. , Han G. R.
Published: August 2016

The pure BaTiO3nanoceramics have a high permittivity up to 6 × 104and a low dielectric loss. The polaron dipoles configured by oxygen vacancies and Ti3+cations within grains could contribute to the colossal dielectric permittivity of the ceramics.
Structural, optical and photo-electrochemical properties of hydrothermally grown ZnO nanorods arrays covered with α-Fe2O3 nanoparticles
Authors: Chakraborty Mohua , Roy Dhrubojyoti , Biswas Amrita , Thangavel R. , Udayabhanu G.
Published: August 2016

A low cost hydrothermal method and subsequent wet-chemical process has been used for the preparation of a ZnO nanorod (NR) array film grown on tin doped indium oxide (ITO) coated glass substrates, post decorated by α-Fe2O3 nanoparticles (NPs).
Molecular sieve mediated sequential Knoevenagel condensation/decarboxylative Michael addition reaction: efficient and mild conditions for the synthesis of 3,3-disubstituted oxindoles with an all carbon quaternary center
Authors: Guo Yi-Lin , Li Yu-Hsun , Chang Hsuan-Hao , Kuo Ting-Shen , Han Jeng-Liang
Published: August 2016

A mild, catalyst-free and efficient molecular sieve mediated sequential Knoevenagel condensation/decarboxylative Michael additon reaction has been developed. A broad scope of 3,3-disubstituted oxindoles were synthesized in good to excellent yields.
C–H functionalization of azines. Anodic dehydroaromatization of 9-(hetero)aryl-9,10-dihydroacridines
Authors: Shchepochkin A. V. , Chupakhin O. N. , Charushin V. N. , Steglenko D. V. , Minkin V. I. , Rusinov G. L. , Matern A. I.
Published: August 2016

A simple and efficient electrochemical method for the oxidative conversion of dihydroacridines into the corresponding 9-(hetero)aryl-N-methylacridinium salts has been developed. Current–voltage characteristics of dihydroacridines are given.
The influence of straight pore blockage on the selectivity of methanol to aromatics in nanosized Zn/ZSM-5: an atomic Cs-corrected STEM analysis study
Authors: Ma Yunhai , Cai Dali , Li Yiru , Wang Ning , Muhammad Usman , Carlsson Anna , Tang Dong , Qian Weizhong , Wang Yao , Su Dangsheng , Wei Fei
Published: August 2016

Here we report the direct atomic scale observation of ZSM-5 pores and the influence of extra-framework Al on methanol to aromatic (MTA).
Exploring template-bound dinuclear copper porphyrin nanorings by EPR spectroscopy
Authors: Richert Sabine , Cremers Jonathan , Anderson Harry L. , Timmel Christiane R.
Published: August 2016

Electron paramagnetic resonance spectroscopy reveals the molecular geometry and metal–ligand interactions in template-bound ten-membered bis-copper porphyrin nanorings.
A photoluminescent covalent triazine framework: CO2 adsorption, light-driven hydrogen evolution and sensing of nitroaromatics
Authors: Bhunia Asamanjoy , Esquivel Dolores , Dey Subarna , Fernández-Terán Ricardo , Goto Yasutomo , Inagaki Shinji , Van Der Voort Pascal , Janiak Christoph
Published: August 2016

Porous PCTF-8 has a fluorescence quantum yield of 31% which is quenched by trinitrophenol, and Pt@PCTF-8 yields H2 with visible light.