bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial Kluver-Bucy Syndrome: Two Cases
Authors: Carroll Brendan T. , Goforth Harold W. , Raimonde Lisa A.
Published: August 2016

Kluver-Bucy syndrome (KBS) is a rare neuropsychiatric disorder that may be characterized by visual agnosia, placidity, altered sexual activity, hypermetamorphosis, and hyperorality. Patients with KBS present with a complex behavioral syndrome. KBS is usually associated with lesions of the amygdala or amygdaloid pathways. However, partial KBS may occur in the absence of the classic bilateral temporal lesions. Pharmacologic treatment options have been developed from the results of case reports, which suggest that carbamazepine and antipsychotics may be helpful. We present the cases of two patients with partial KBS who responded favorably to antipsychotic medication.
William James and the Religious Experience
Authors: Trimble Michael
Published: August 2016

A centenary is often an excuse for reminding people of the life and work of a predecessor, especially if the material is of contemporary relevance. Published 100 years ago, William James' The Varieties of Religious Experience, remains the most revealing investigation into the psychology of religion. James, a nonpracticing MD, turned his thoughts to psychology and philosophy. The book was considered “one of the great books of our time” and in it, James bravely tackled a subject that many then, and perhaps now, considered taboo.

James' aim was to study religious experiences as he would any other psychological phenomena, accepting their reality and vulnerability to scientific enquiry. His definition of religion was “the feelings, acts, and experiences of individual men in their solitude, so far as they apprehend themselves to stand in relation to whatever they may consider the divine.” He was concerned with immediate personal experiences, which he considered to be universal to humanity.

In his lecture, “Religion and Neurology,” he explored the potential psychophysical associations of religious feelings. In order to understand the nature of religious experience, James emphasized the need to study those for whom religion was “an acute fever,” and not to dwell long on those whose commerce with the deity was “second hand.” The ones to study were the “geniuses of the religious line.” However, he warned that they “like many other geniuses that have brought forth fruits effective enough for commemoration in the pages of biography, have often shown symptoms of nervous instability.” He pointed out that “insane conditions” have a considerable advantage for studies of this kind because they isolate specific factors of the mental life that become available for investigation.
The Clinical Evaluation of Common Sexual Concerns
Authors: Halvorsen John G.
Published: August 2016

Whose job is it to discover and manage patients' sexual concerns? If you believe that you have a role to play, just what is that role and how will you perform it? Sexual disorders are common, yet infrequently diagnosed. A willingness to inquire about sexual function is the most critical diagnostic step for clinicians. Once a problem is discovered, a systematic diagnostic process can uncover etiologic organic and psychogenic factors using customary diagnostic tools, including taking a psychosexual and medical history, comprehensive and focused physical examinations, psychological assessment instruments, laboratory tests, and special procedures.
The Development of Single-Isomer Molecules: Why and How
Authors: Hutt Andrew J.
Published: August 2016

Until relatively recently the three-dimensional nature of drug molecules has been largely neglected, with approximately 25% of marketed drugs being mixtures of agents rather than single chemical entities. These mixtures are not combinations of drugs but mixtures of stereoisomers, generally racemates of synthetic chiral drugs. The individual enantiomers present in such mixtures frequently differ in both their pharmacodynamic and pharmacokinetic profiles as a result of stereochemical discrimination on interaction with chiral biological macromolecules (enzymes and receptors). The use of such mixtures may present problems if their adverse effects are associated with the less active stereoisomer or do not show stereoselectivity. In addition, interactions between enantiomers may occur such that the observed activity of the racemate is not simply the product of the effects of the individual enantiomers. Since the mid-1980s there has been an ongoing “racemate-versus-enantiomer” debate with the potential advantages of single-isomer products, including improved selectivity of action and potential increase in therapeutic index, being highlighted. As a result, regulatory authorities have issued guidelines for dealing with chiral molecules, and the number of single enantiomer agents presented for evaluation has increased. Racemic mixtures may still be developed but require justification such that the risk-benefit ratio may be assessed. In addition to new chemical entities, a number of “old” mixtures are being re-examined as potential single-isomer products, the chiral switches, with the potential for an improved therapeutic profile and possibly new indications. However, for the majority of agents currently marketed as mixtures, relatively little is known concerning the pharmacological or toxicological properties of the individual enantiomers.
Great Expectations in Stereochemistry: Focus on Antidepressants
Authors: DeVane C. Lindsay , Boulton David W.
Published: August 2016

Chirality has become an increasingly important consideration in the development of psychoactive drugs because enantiomers often show major differences in their pharmacokinetic and pharmacologic properties. This review illustrates the implications of stereochemistry in clinical psychopharmacology using the antidepressant class of drugs as a focus. In many cases, a better understanding of stereochemistry can improve therapeutic outcomes. For example, with citalopram, the racemic formulation is effective for depression as well as panic and obsessive-compulsive disorders. However, the S-enantiomer, escitalopram, is at least twice as potent as racemic citalopram as an inhibitor of serotonin reuptake, implying that it can be used at lower doses, while offering an improved therapeutic index as well as an improved safety profile and reduced drug interaction liability. Clinical trial data support these advantages. Continuing research on the stereochemical properties of psychoactive drugs should simplify the characterization of dose-response relationships, and clarify the effects of disease states, genetic polymorphisms, pregnancy, age, and gender on stereoselective pharmacokinetics and pharmacodynamics. Better understanding of the fate of chiral psychotropic agents and the factors that influence their stereoselective disposition and actions will provide a rational basis for their expanded use in various patient populations.
INFRASTRUCTURE AND INEQUALITY: INSIGHTS FROM INCORPORATING KEY ECONOMIC FACTS ABOUT HOUSEHOLD HETEROGENEITY
Authors: Klenert David , Mattauch Linus , Edenhofer Ottmar , Lessmann Kai
Published: August 2016

We study the impacts of investment in public capital on equity and efficiency. Taking into account stylized facts on wealth accumulation, we model agent heterogeneity through differences in saving behavior, income source and time preference. We find that in the long run, public investment is Pareto-improving and that it reduces inequality in wealth, welfare, and income at the same time, if it is financed by a capital tax. Consumption tax financing is also Pareto-improving but distribution-neutral. Only for labor tax financing, a trade-off between equity and efficiency occurs. Additionally, we find that agents differ in their preferred tax rates.The results for capital and labor tax financing are valid for both, the case of decreasing and constant returns to accumulable factors.
Bilingual language interference initiates error detection: Evidence from language intrusions
Authors: DECLERCK MATHIEU , LEMHÖFER KRISTIN , GRAINGER JONATHAN
Published: August 2016

In the current study, we investigated bilingual error detection by measuring the repair rate of language intrusions (i.e., involuntary production of nontarget language words) that arose while bilinguals produced sentences in a language switching context. This allowed us to compare two prominent accounts of error detection in a bilingual setting. According to the conflict monitoring account, error detection is initiated by interference. Since language switching increases bilingual language interference, error detection should be better in switch relative to repetition trials. According to the perceptual loop theory, error detection is based on language comprehension. Since language switching is known to impair language comprehension, it follows that error detection should be worse in switch relative to repetition trials. The results showed that the repair rate of language intrusions was higher in switch than repetition trials, thus providing evidence that bilingual language interference instigates error detection, in line with the conflict monitoring account.
Classified or Coverup? The Effect of Redactions on Conspiracy Theory Beliefs
Authors: Nyhan Brendan , Dickinson Franklin , Dudding Sasha , Dylgjeri Enxhi , Neiley Eric , Pullerits Christopher , Seog Minae , Simpson Andy , Szilagyi Heather , Walmsley Colin
Published: August 2016

Conspiracy theories are prevalent among the public. Governments frequently release official documents attempting to explain events that inspire these beliefs. However, these documents are often heavily redacted, a practice that lay epistemic theory suggests might be interpreted as evidence for a conspiracy. To investigate this possibility, we tested the effect of redactions on beliefs in a well-known conspiracy theory. Results from two preregistered experiments indicate that conspiracy beliefs were higher when people were exposed to seemingly redacted documents compared to when they were exposed to unredacted documents that were otherwise identical. In addition, unredacted documents consistently lowered conspiracy beliefs relative to controls while redacted documents had reduced or null effects, suggesting that lay epistemic interpretations of the redactions undermined the effect of information in the documents. Our findings, which do not vary by conspiracy predispositions, suggest policymakers should be more transparent when releasing documents to refute misinformation.
The Effects of Nicotine and Nicotine Abstinence on Stress-Induced	Cardiovascular Reactivity
Authors: VanderKaay Tomasulo Melissa M. , Scanlin Matthew C. , Patterson Stephen M.
Published: August 2016

Abstract. The effects of 12 hr nicotine administration and abstinence on stress-induced cardiovascular reactivity were assessed within Light/Intermittent cigarette smokers and Habitual cigarette smokers. One hundred thirty-two male smokers (66 Habitual, 66 Light/Intermittent) were assigned to a Nicotine (21 mg) or Placebo patch condition. Cardiovascular reactivity was assessed during Baseline, a 6-min mental arithmetic task (Paced Auditory Serial Arithmetic Task) and a 5-min mirror-tracing task (Star Mirror Tracing Task). Within the Nicotine condition, Light/Intermittent smokers showed greater cardiac output (CO) increases, smaller stroke volume decreases, and smaller total peripheral resistance (TPR) increases than Light/Intermittent smokers in the Placebo condition. No condition differences in cardiovascular reactivity were demonstrated for Habitual smokers. Light/Intermittent smokers also showed greater CO increases than Habitual smokers during the mirror-tracing task but during the Nicotine condition only. During mental arithmetic, Light/Intermittent smokers had greater CO increases and smaller TPR increases than Habitual smokers across nicotine conditions. Habitual smokers responded to stress with increases in peripheral responses whereas Light/Intermittent smokers responded myocardially. Light/Intermittent smokers may have increased density of β-adrenergic receptors whereas Habitual smokers may have decreased density due to chronic smoking.
Transcriptional landscapes at the intersection of neuronal apoptosis and substance P-induced survival: exploring pathways and drug targets
Authors: Paparone S , Severini C , Ciotti M T , D’Agata V , Calissano P , Cavallaro S
Published: August 2016

A change in the delicate equilibrium between apoptosis and survival regulates the neurons fate during the development of nervous system and its homeostasis in adulthood. Signaling pathways promoting or protecting from apoptosis are activated by multiple signals, including those elicited by neurotrophic factors, and depend upon specific transcriptional programs. To decipher the rescue program induced by substance P (SP) in cerebellar granule neurons, we analyzed their whole-genome expression profiles after induction of apoptosis and treatment with SP. Transcriptional pathways associated with the survival effect of SP included genes encoding for proteins that may act as pharmacological targets. Inhibition of one of these, theMycpro-oncogene by treatment with 10058-F4, reverted in a dose-dependent manner the rescue effect of SP. In addition to elucidate the transcriptional mechanisms at the intersection of neuronal apoptosis and survival, our systems biology-based perspective paves the way towards an innovative pharmacology based on targets downstream of neurotrophic factor receptors.
Context‐dependent regulation of Th17‐associated genes and IFNγ expression by the transcription factor NFAT5
Authors: Alberdi Maria , Iglesias Marcos , Tejedor Sonia , Merino Ramón , López‐Rodríguez Cristina , Aramburu Jose
Published: August 2016

Stress‐activated transcription factors influence T‐cell function in different physiopathologic contexts. NFAT5, a relative of nuclear factor κB and the calcineurin‐activated NFATc transcription factors, protects mammalian cells from hyperosmotic stress caused by the elevation of extracellular sodium levels. In T cells exposed to hypernatremia, NFAT5 not only induces osmoprotective gene products but also cytokines and immune receptors, which raises the question of whether this factor could regulate other T‐cell functions in osmostress‐independent contexts. Here we have used mice with a conditional deletion of Nfat5 in mature T lymphocytes to explore osmostress‐dependent and ‐independent functions of this factor. In vitro experiments with CD4 T cells stimulated in hyperosmotic medium showed that NFAT5 enhanced the expression of IL‐2 and the Th17‐associated gene products RORγt and IL‐23R. By contrast, NFAT5‐deficient CD4 T cells activated in vivo by anti‐CD3 antibody exhibited a different activation profile and were skewed towards enhanced interferon γ (IFNγ) and IL‐17 expression and attenuated Treg responses. Using a model of experimental colitis, we observed that mice lacking NFAT5 in T cells exhibited exacerbated intestinal colitis and enhanced expression of IFNγ in draining lymph nodes and colon. These results show that NFAT5 can modulate different T‐cell responses depending on stress conditions and stimulatory context.
Ascarosides coordinate the dispersal of a plant-parasitic nematode with the metamorphosis of its vector beetle
Authors: Zhao Lilin , Zhang Xinxing , Wei Yanan , Zhou Jiao , Zhang Wei , Qin Peijun , Chinta Satya , Kong Xiangbo , Liu Yunpeng , Yu Haiying , Hu Songnian , Zou Zhen , Butcher Rebecca A. , Sun Jianghua
Published: August 2016

Insect vectors are required for the transmission of many species of parasitic nematodes, but the mechanisms by which the vectors and nematodes coordinate their life cycles are poorly understood. Here, we report that ascarosides, an evolutionarily conserved family of nematode pheromones, are produced not only by a plant-parasitic nematode, but also by its vector beetle. The pinewood nematode and its vector beetle cause pine wilt disease, which threatens forest ecosystems world-wide. Ascarosides secreted by the dispersal third-stage nematode LIII larvae promote beetle pupation by inducing ecdysone production in the beetle and up-regulating ecdysone-dependent gene expression. Once the beetle develops into the adult stage, it secretes ascarosides that attract the dispersal fourth-stage nematode LIV larvae, potentially facilitating their movement into the beetle trachea for transport to the next pine tree. These results demonstrate that ascarosides play a key role in the survival and spread of pine wilt disease.
Type 2 diabetes, but not obesity, prevalence is positively associated with ambient temperature
Authors: Speakman John R. , Heidari-Bakavoli Sahar
Published: August 2016

Cold exposure stimulates energy expenditure and glucose disposal. If these factors play a significant role in whole body energy balance, and glucose homeostasis, it is predicted that both obesity and type 2 diabetes prevalence would be lower where it is colder. Previous studies have noted connections between ambient temperature and obesity, but the direction of the effect is confused. No previous studies have explored the link of type 2 diabetes to ambient temperature. We used county level data for obesity and diabetes prevalence across the mainland USA and matched this to county level ambient temperature data. Average ambient temperature explained 5.7% of the spatial variation in obesity and 29.6% of the spatial variation in type 2 diabetes prevalence. Correcting the type 2 diabetes data for the effect of obesity reduced the explained variation to 26.8%. Even when correcting for obesity, poverty and race, ambient temperature explained 12.4% of the variation in the prevalence of type 2 diabetes, and this significant effect remained when latitude was entered into the model as a predictor. When obesity prevalence was corrected for poverty and race the significant effect of temperature disappeared. Enhancing energy expenditure by cold exposure will likely not impact obesity significantly, but may be useful to combat type 2 diabetes.
Inactivation of hypoxia-induced YAP by statins overcomes hypoxic resistance tosorafenib in hepatocellular carcinoma cells
Authors: Zhou Tian-yi , Zhuang Lin-han , Hu Yan , Zhou Yu-lu , Lin Wen-kai , Wang Dan-dan , Wan Zi-qian , Chang Lin-lin , Chen Ying , Ying Mei-dan , Chen Zi-bo , Ye Song , Lou Jian-shu , He Qiao-jun , Zhu Hong , Yang Bo
Published: August 2016

Sorafenib is a multikinase inhibitor used as a first-line treatment for advanced hepatocellular carcinoma (HCC), but it has shown modest to low response rates. The characteristic tumour hypoxia of advanced HCC maybe a major factor underlying hypoxia-mediated treatment failure. Thus, it is urgent to elucidate the mechanisms of hypoxia-mediated sorafenib resistance in HCC. In this study, we found that hypoxia induced the nuclear translocation of Yes associate-Protein (YAP) and the subsequent transactivation of target genes that promote cell survival and escape apoptosis, thereby leading to sorafenib resistance. Statins, the inhibitors of hydroxymethylglutaryl-CoA reductase, could ameliorate hypoxia-induced nuclear translocation of YAP and suppress mRNA levels of YAP target genes both in vivo and in vitro. Combined treatment of statins with sorafenib greatly rescued the loss of anti-proliferative effects of sorafenib under hypoxia and improved the inhibitory effects on HepG2 xenograft tumour growth, accompanied by enhanced apoptosis as evidenced by the increased sub-G1 population and PARP cleavage. The expression levels of YAP and its target genes were highly correlated with poor prognosis and predicted a high risk of HCC patients. These findings collectively suggest that statins utilization maybe a promising new strategy to counteract hypoxia-mediated resistance to sorafenib in HCC patients.
IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo
Authors: Kritikou Joanna S. , Dahlberg Carin I. M. , Baptista Marisa A. P. , Wagner Arnika K. , Banerjee Pinaki P. , Gwalani Lavesh Amar , Poli Cecilia , Panda Sudeepta K. , Kärre Klas , Kaech Susan M. , Wermeling Fredrik , Andersson John , Orange Jordan S. , Brauner Hanna , Westerberg Lisa S.
Published: August 2016

To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp and suffer from immunodeficiency with increased risk to develop lymphoreticular malignancies. NK cells from WAS patients fail to form lytic synapses, however, the functional outcome in vivo remains unknown. Here, we show that WASp KO NK cells had decreased capacity to degranulate and produce IFNγ upon NKp46 stimulation and this was associated with reduced capacity to kill MHC class I-deficient hematopoietic grafts. Pre-treatment of WASp KO NK cells with IL-2 ex vivo restored degranulation, IFNγ production and killing of MHC class I negative hematopoietic grafts. Moreover, WASp KO mice controlled growth of A20 lymphoma cells that naturally produced IL-2. WASp KO NK cells showed increased expression of DNAM-1, LAG-3 and KLRG1, all receptors associated with cellular exhaustion and NK cell memory. NK cells isolated from WAS patient spleen cells showed increased expression of DNAM-1 and had low to negative expression of CD56, a phenotype associated with NK cells exhaustion. Finally, in a cohort of neuroblastoma patients we identified a strong correlation between WASp, IL-2 and patient survival.
A high-throughput in vitro ring assay for vasoactivity using magnetic 3D bioprinting
Authors: Tseng Hubert , Gage Jacob A. , Haisler William L. , Neeley Shane K. , Shen Tsaiwei , Hebel Chris , Barthlow Herbert G. , Wagoner Matthew , Souza Glauco R.
Published: August 2016

Vasoactive liabilities are typically assayed using wire myography, which is limited by its high cost and low throughput. To meet the demand for higher throughput in vitro alternatives, this study introduces a magnetic 3D bioprinting-based vasoactivity assay. The principle behind this assay is the magnetic printing of vascular smooth muscle cells into 3D rings that functionally represent blood vessel segments, whose contraction can be altered by vasodilators and vasoconstrictors. A cost-effective imaging modality employing a mobile device is used to capture contraction with high throughput. The goal of this study was to validate ring contraction as a measure of vasoactivity, using a small panel of known vasoactive drugs. In vitro responses of the rings matched outcomes predicted by in vivo pharmacology and were supported by immunohistochemistry. Altogether, this ring assay robustly models vasoactivity, which could meet the need for higher throughput in vitro alternatives.
The ability of apolipoprotein E fragments to promote intraneuronal accumulation of amyloid beta peptide 42 is both isoform and size-specific
Authors: Dafnis Ioannis , Argyri Letta , Sagnou Marina , Tzinia Athina , Tsilibary Effie C. , Stratikos Efstratios , Chroni Angeliki
Published: August 2016

The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer’s disease (AD). ApoE4 is more susceptible to proteolysis than apoE2 and apoE3 isoforms and carboxyl-terminal truncated apoE4 forms have been found in AD patients’ brain. We have previously shown that a specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (Aβ42) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis. Here, we show that these effects are allele-dependent and absolutely require the apoE4 background. Furthermore, the exact length of the fragment is critical since longer or shorter length carboxyl-terminal truncated apoE4 forms do not elicit the same effects. Structural and thermodynamic analyses showed that apoE4-165 has a compact structure, in contrast to other carboxyl-terminal truncated apoE4 forms that are instead destabilized. Compared however to other allelic backgrounds, apoE4-165 is structurally distinct and less thermodynamically stable suggesting that the combination of a well-folded structure with structural plasticity is a unique characteristic of this fragment. Overall, our findings suggest that the ability of apoE fragments to promote Aβ42 intraneuronal accumulation is specific for both the apoE4 isoform and the particular structural and thermodynamic properties of the fragment.
Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly
Authors: Kweon Hae-Jin , Kim Dong-Il , Bae Yeonju , Park Jae-Yong , Suh Byung-Chang
Published: August 2016

Acid-sensing ion channels (ASICs) are proton-activated cation channels that play important roles as typical proton sensors during pathophysiological conditions and normal synaptic activities. Among the ASIC subunits, ASIC2a and ASIC2b are alternative splicing products from the same gene, ACCN1. It has been shown that ASIC2 isoforms have differential subcellular distribution: ASIC2a targets the cell surface by itself, while ASIC2b resides in the ER. However, the underlying mechanism for this differential subcellular localization remained to be further elucidated. By constructing ASIC2 chimeras, we found that the first transmembrane (TM1) domain and the proximal post-TM1 domain (17 amino acids) of ASIC2a are critical for membrane targeting of the proteins. We also observed that replacement of corresponding residues in ASIC2b by those of ASIC2a conferred proton-sensitivity as well as surface expression to ASIC2b. We finally confirmed that ASIC2b is delivered to the cell surface from the ER by forming heteromers with ASIC2a, and that the N-terminal region of ASIC2a is additionally required for the ASIC2a-dependent membrane targeting of ASIC2b. Together, our study supports an important role of ASIC2a in membrane targeting of ASIC2b.
Internal pH regulation facilitates in situ long-term acclimation of massive corals to end-of-century carbon dioxide conditions
Authors: Wall M. , Fietzke J. , Schmidt G. M. , Fink A , Hofmann L. C. , de Beer D. , Fabricius K. E.
Published: August 2016

The resilience of tropical corals to ocean acidification depends on their ability to regulate the pH within their calcifying fluid (pHcf). Recent work suggests pHcf homeostasis under short-term exposure to pCO2 conditions predicted for 2100, but it is still unclear if pHcf homeostasis can be maintained throughout a corals lifetime. At CO2 seeps in Papua New Guinea, massive Porites corals have grown along a natural seawater pH gradient for decades. This natural gradient, ranging from pH 8.1–7.4, provides an ideal platform to determine corals’ pHcf (using boron isotopes). Porites maintained a similar pHcf (~8.24) at both a control (pH 8.1) and seep-influenced site (pH 7.9). Internal pHcf was slightly reduced (8.12) at seawater pH 7.6 and decreased to 7.94 at a site with a seawater pH of 7.4. A growth response model based on pHcf mirrors the observed distribution patterns of this species in the field. We suggest Porites has the capacity to acclimate after long-time exposure to end-of-century reduced seawater pH conditions and that strong control over pHcf represents a key mechanism to persist in future oceans. Only beyond end-of-century pCO2 conditions do they face their current physiological limit of pH homeostasis and pHcf begins to decrease.
Human Prostate Cancer Hallmarks Map
Authors: Datta Dipamoy , Aftabuddin Md. , Gupta Dinesh Kumar , Raha Sanghamitra , Sen Prosenjit
Published: August 2016

Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process.
Three-dimensional Reconstruction of the Microstructure of Human Acellular Nerve Allograft
Authors: Zhu Shuang , Zhu Qingtang , Liu Xiaolin , Yang Weihong , Jian Yutao , Zhou Xiang , He Bo , Gu Liqiang , Yan Liwei , Lin Tao , Xiang Jianping , Qi Jian
Published: August 2016

The exact inner 3D microstructure of the human peripheral nerve has been a mystery for decades. Therefore, it has been difficult to solve several problems regarding peripheral nerve injury and repair. We used high-resolution X-ray computed microtomography (microCT) to scan a freeze-dried human acellular nerve allograft (hANA). The microCT images were then used to reconstruct a 3D digital model, which was used to print a 3D resin model of the nerve graft. The 3D digital model of the hANA allowed visualization of all planes. The magnified 3D resin model clearly showed the nerve bundles and basement membrane tubes of the hANA. Scanning electron microscopy (SEM) was used to analyse the microstructure of the hANA. Compared to the SEM images, the microCT image clearly demonstrated the microstructure of the hANA cross section at a resolution of up to 1.2 μm. The 3D digital model of the hANA facilitates a clear and easy understanding of peripheral nerve microstructure. Furthermore, the enlarged 3D resin model duplicates the unique inner structure of each individual hANA. This is a crucial step towards achieving 3D printing of a hANA or nerve that can be used as a nerve graft.
Reverse surface-polariton cherenkov radiation
Authors: Tao Jin , Wang Qi Jie , Zhang Jingjing , Luo Yu
Published: August 2016

The existence of reverse Cherenkov radiation for surface plasmons is demonstrated analytically. It is shown that in a metal-insulator-metal (MIM) waveguide, surface plasmon polaritons (SPPs) excited by an electron moving at a speed higher than the phase velocity of SPPs can generate Cherenkov radiation, which can be switched from forward to reverse direction by tuning the core thickness of the waveguide. Calculations are performed in both frequency and time domains, demonstrating that a radiation pattern with a backward-pointing radiation cone can be achieved at small waveguide core widths, with energy flow opposite to the wave vector of SPPs. Our study suggests the feasibility of generating and steering electron radiation in simple plasmonic systems, opening the gate for various applications such as velocity-selective particle detections.
Treatment with an orally bioavailable prodrug of 17β-estradiol alleviates hot flushes without hormonal effects in the periphery
Authors: Merchenthaler Istvan , Lane Malcolm , Sabnis Gauri , Brodie Angela , Nguyen Vien , Prokai Laszlo , Prokai-Tatrai Katalin
Published: August 2016

Estrogen deprivation has a profound effect on the female brain. One of the most obvious examples of this condition is hot flushes. Although estrogens relieve these typical climacteric symptoms, many women do not want to take them owing to unwanted side-effects impacting, for example, the uterus, breast and blood. Therefore, there is a need for developing safer estrogen therapies. We show here that treatment with 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a novel brain-targeting bioprecursor prodrug of the main human estrogen, 17β-estradiol, alleviates hot flushes in rat models of thermoregulatory dysfunction of the brain. Oral administration of DHED elicits a significant reduction of tail skin temperature (TST) rise representing hot flushes in the morphine-dependent ovariectomized rat model and results in the restoration of estrogen deprivation-induced loss of diurnal rhythm in TST. These beneficial effects occur without detrimental peripheral hormonal exposure; thus, the treatment avoids potentially harmful stimulation of estrogen-sensitive peripheral organs, including the uterus and the anterior pituitary, or the proliferation of MCF-7a breast cancer cell xenografts. Our promising preclinical assessments warrant further considerations of DHED for the development of a brain-selective 17β-estradiol therapy to relieve hot flushes without undesirable peripheral side-effects.
Preparation and Catalytic Activity for Aerobic Glucose Oxidation of Crown Jewel Structured Pt/Au Bimetallic Nanoclusters
Authors: Zhang Haijun , Wang Liqiong , Lu Lilin , Toshima Naoki
Published: August 2016

Understanding of the “structure-activity” relations for catalysts at an atomic level has been regarded as one of the most important objectives in catalysis studies. Bimetallic nanoclusters (NCs) in its many types, such as core/shell, random alloy, cluster-in-cluster, bi-hemisphere and crown jewel (one kind of atom locating at the top position of another kind of NC), attract significant attention owing to their excellent optical, electronic and catalytic properties. PVP-protected crown jewel-structured Pt/Au (CJ-Pt/Au) bimetallic nanoclusters (BNCs) with Au atoms located at active top sites were synthesized via a replacement reaction using 1.4-nm Pt NCs as mother clusters even considering the fact that the replacement reaction between Pt and Au3+ions is difficult to be occurred. The prepared CJ-Pt/Au colloidal catalysts characterized by UV-Vis, TEM, HR-TEM and HAADF-STEM-EELS showed a high catalytic activity for aerobic glucose oxidation and the top Au atoms decorating the Pt NCs were about 15 times more active than the Au atoms of Au NCs with similar particle size.
Msh2 deficiency leads to dysmyelination of the corpus callosum, impaired locomotion and altered sensory function in mice
Authors: Diouf Barthelemy , Devaraju Prakash , Janke Laura J. , Fan Yiping , Frase Sharon , Eddins Donnie , Peters Jennifer L. , Kim Jieun , Pei Deqing , Cheng Cheng , Zakharenko Stanislav S. , Evans William E.
Published: August 2016

A feature in patients with constitutional DNA-mismatch repair deficiency is agenesis of the corpus callosum, the cause of which has not been established. Here we report a previously unrecognized consequence of deficiency in MSH2, a protein known primarily for its function in correcting nucleotide mismatches or insertions and deletions in duplex DNA caused by errors in DNA replication or recombination. We documented that Msh2 deficiency causes dysmyelination of the axonal projections in the corpus callosum. Evoked action potentials in the myelinated corpus callosum projections of Msh2-null mice were smaller than wild-type mice, whereas unmyelinated axons showed no difference. Msh2-null mice were also impaired in locomotive activity and had an abnormal response to heat. These findings reveal a novel pathogenic consequence of MSH2 deficiency, providing a new mechanistic hint to previously recognized neurological disorders in patients with inherited DNA-mismatch repair deficiency.
A Catalogue of Altered Salivary Proteins Secondary to Invasive Ductal Carcinoma: A Novel In Vivo Paradigm to Assess Breast Cancer Progression
Authors: Streckfus Charles F. , Bigler Lenora
Published: August 2016

The objective of this manuscript is to introduce a catalogue of salivary proteins that are altered secondary to carcinoma of the breast. The catalogue of salivary proteins is a compilation of twenty years of research by the authors and consists of 233 high and low abundant proteins which have been identified by LC-MS/MS mass spectrometry, 2D-gel analysis and by enzyme-linked immunosorbent assay. The body of research suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be useful in the study of breast cancer progress, treatment efficacy and the tailoring of individualized patient care.
Sub-Millisecond Response Time in a Photorefractive Composite Operating under CW Conditions
Authors: Moon Jong-Sik , Stevens Tyler E. , Monson Todd C. , Huber Dale L. , Jin Sung-Ho , Oh Jin-Woo , Winiarz Jeffrey G.
Published: August 2016

Extensive study of photorefractive polymeric composites photosensitized with semiconductor nanocrystals has yielded data indicating that the inclusion of such nanocrystals enhances the charge-carrier mobility, and subsequently leads to a reduction in the photorefractive response time. Unfortunately, the included nanocrystals may also act as a source of deep traps, resulting in diminished diffraction efficiencies as well as reduced two beam coupling gain coefficients. Nonetheless, previous studies indicate that this problem is mitigated through the inclusion of semiconductor nanocrystals possessing a relatively narrow band-gap. Here, we fully exploit this property by doping PbS nanocrystals into a newly formulated photorefractive composite based on molecular triphenyldiamine photosensitized with C60. Through this approach, response times of 399 μs are observed, opening the door for video and other high-speed applications. It is further demonstrated that this improvement in response time occurs with little sacrifice in photorefractive efficiency, with internal diffraction efficiencies of 72% and two-beam-coupling gain coefficients of 500 cm−1 being measured. A thorough analysis of the experimental data is presented, supporting the hypothesized mechanism of enhanced charge mobility without the accompaniment of superfluous traps. It is anticipated that this approach can play a significant role in the eventual commercialization of this class of materials.
MicroRNA-16 is putatively involved in the NF-κB pathway regulation in ulcerative colitis through adenosine A2a receptor (A2aAR) mRNA targeting
Authors: Tian Ting , Zhou Yu , Feng Xiao , Ye Shicai , Wang Hao , Wu Weiyun , Tan Wenkai , Yu Caiyuan , Hu Juxiang , Zheng Rong , Chen Zonghao , Pei Xinyu , Luo Hesheng
Published: August 2016

MicroRNAs (miRNAs) act as important post-transcriptional regulators of gene expression by targeting the 3′-untranslated region of their target genes. Altered expression of miR-16 is reported in human ulcerative colitis (UC), but its role in the development of the disease remains unclear. Adenosine through adenosine A2a receptor (A2aAR) could inhibit nuclear factor-kappaB (NF-κB) signaling pathway in inflammation. Here we identified overexpression of miR-16 and down-regulation of A2aAR in the colonic mucosa of active UC patients. We demonstrated that miR-16 negatively regulated the expression of the A2aAR at the post-transcriptional level. Furthermore, transfection of miR-16 mimics promoted nuclear translocation of NF-κB p65 protein and expression of pro-inflammatory cytokines, IFN-γ and IL-8 in colonic epithelial cells. Treatment with miR-16 inhibitor could reverse these effects in cells. The A2aAR-mediated effects of miR-16 on the activation of the NF-κB signaling pathway were confirmed by the A2aAR knockdown assay. Our results suggest that miR-16 regulated the immune and inflammatory responses, at least in part, by suppressing the expression of the A2aAR to control the activation of the NF-κB signaling pathway.
Extracorporeal delivery of a therapeutic enzyme
Authors: Zhang Chun , Pu Jun , Yang Xiaolan , Feng Tao , Liu Fang , Wang Deqiang , Hu Xiaolei , Gao Ang , Liu Hongbo , Zhan Chang-Guo , Liao Fei
Published: August 2016

To remove circulating harmful small biochemical(s)/substrates causing/deteriorating certain chronic disease, therapeutic enzyme(s) delivered via vein injection/infusion suffer(s) from immunoresponse after repeated administration at proper intervals for a long time and short half-lives since delivery. Accordingly, a novel, generally-applicable extracorporeal delivery of a therapeutic enzyme is proposed, by refitting a conventional hemodialysis device bearing a dialyzer, two pumps and connecting tubes, to build a routine extracorporeal blood circuit but a minimal dialysate circuit closed to circulate the therapeutic enzyme in dialysate. A special quantitative index was derived to reflect pharmacological action and thus pharmacodynamics of the delivered enzyme. With hyperuricemic blood in vitro and hyperuricemic geese, a native uricase via extracorporeal delivery was active in the dialysate for periods much longer than that in vivo through vein injection and exhibited the expected pharmacodynamics to remove uric acid in hyperuricemic blood in vitro and multiple forms of uric acid in hyperuricemic geese. Therefore, the extracorporeal delivery approach of therapeutic enzymes was effective to remove unwanted circulating small biochemical(s)/substrates and was expected to avoid immunogenicity problems of therapeutic enzymes after repeated administration at proper intervals for a long time due to no contacts with macromolecules and cells in the body.
What is the mechanism of formation of hydroxyaluminosilicates?
Authors: Beardmore James , Lopez Xabier , Mujika Jon I. , Exley Christopher
Published: August 2016

The formation of hydroxyaluminosilicates is integral to the biogeochemical cycles of aluminium and silicon. The unique inorganic chemistry which underlies their formation explains the non-essentiality in biota of both of these elements. However, the first steps in the formation of hydroxyaluminosilicates were hitherto only theoretical and plausibly only accessible in silico. Herein we have used computational chemistry to identify and define for the first time these unique and ultimately critically important reaction steps. We have used density-functional theory combined with solvent continuum models to confirm first, the nature of the reactants, an aluminium hydroxide dimer and silicic acid, second, the reaction products, two distinct hydroxyaluminosilicates A and B and finally, how these are the precursors to highly insoluble hydroxyaluminosilicates the role of which has been and continues to be to keep inimical aluminium out of biota.
Discovery of a new function of curcumin which enhances its anticancer therapeutic potency
Authors: Nagahama Koji , Utsumi Tomoya , Kumano Takayuki , Maekawa Saeko , Oyama Naho , Kawakami Junji
Published: August 2016

Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.
Development of an HPLC-MS method for the determination of natural pteridines in tomato samples
Authors: Martín-Tornero Elísabet , Gómez David González , Durán-Merás Isabel , Espinosa-Mansilla Anunciación
Published: August 2016

A simple HPLC-MS method was developed for the determination of natural pteridines that may be found in tomatoes.
Controlled drug release to cancer cells from modular one-photon visible light-responsive micellar system
Authors: Poelma Saemi O. , Oh Seung Soo , Helmy Sameh , Knight Abigail S. , Burnett G. Leslie , Soh H. Tom , Hawker Craig J. , Read de Alaniz Javier
Published: August 2016

We present a one-photon visible light-responsive micellar system for efficient, on-demand delivery of small molecules.
Hollow silica nanospheres coated with insoluble calcium salts for pH-responsive sustained release of anticancer drugs
Authors: Guo Yuming , Fang Qilong , Li Han , Shi Weike , Zhang Jie , Feng Jing , Jia Weili , Yang Lin
Published: August 2016

Hollow silica nanospheres coated with pH-sensitive insoluble calcium salts are prepared for pH-responsive sustained release of anticancer drugs.
Stability and reactivity control of carbenoids: recent advances and perspectives
Authors: Gessner Viktoria H.
Published: August 2016

This feature article highlights the current state of the art in the chemistry of main group metal carbenoids with focus on stability and reactivity control and novel applications.
Photolysis of a bola-type supra-amphiphile promoted by water-soluble pillar[5]arene-induced assembly
Authors: Guo Shuwen , Liu Xin , Yao Chenhao , Lu Chengxi , Chen Qingxin , Hu Xiao-Yu , Wang Leyong
Published: August 2016

A novel monolayer supramolecular vesicle assembled from a pillararene-based bola-type supra-amphiphile was successfully constructed, which showed excellent photodegradable properties and might have potential applications in phototherapy.
The photoenhanced aging process of soot by the heterogeneous ozonization reaction
Authors: Han Chong , Liu Yongchun , He Hong
Published: August 2016

Light can dramatically enhance the heterogeneous aging process of soot by O3, leading to the formation of various oxygen-containing species.
Chiral sensing of amino acids and proteins chelating with EuIIIcomplexes by Raman optical activity spectroscopy
Authors: Wu Tao , Kessler Jiří , Bouř Petr
Published: August 2016

Chiroptical spectroscopy of lanthanides sensitively reflects their environment and finds various applications including probing protein structures.
Gas phase ultraviolet and infrared spectroscopy on a partial peptide of β2-adrenoceptor SIVSF-NH2 by a laser desorption supersonic jet technique
Authors: Ishiuchi Shun-ichi , Yamada Kohei , Oba Hikari , Wako Hiromichi , Fujii Masaaki
Published: August 2016

Laser desorption supersonic jet laser spectroscopy has been applied to a penta-peptide, Ser-Ile-Val-Ser-Phe-NH2 (SIVSF-NH2), which is a partial sequence of a binding site in a β2-adrenaline receptor protein.
Quantitative determination of activation energies in mechanochemical reactions
Authors: Fischer Franziska , Wenzel Klaus-Jürgen , Rademann Klaus , Emmerling Franziska
Published: August 2016

First determination of the apparent activation energy for a mechanochemical reaction.
Mode specificity of the dissociative chemisorption of HOD on rigid Cu(111): an approximate full-dimensional quantum dynamics study
Authors: Liu Tianhui , Zhang Zhaojun , Chen Jun , Fu Bina , Zhang Dong H.
Published: August 2016

The approximate 9D dissociation probabilities for HOD/Cu(111) are obtained to investigate the influence of the mode specificity on reaction dynamics.
Fe–Si networks in Na2FeSiO4 cathode materials
Authors: Wu P. , Wu S. Q. , Lv X. , Zhao X. , Ye Z. , Lin Z. , Wang C. Z. , Ho K. M.
Published: August 2016

Using a combination of adaptive genetic algorithm search, motif-network search scheme and first-principles calculations, we have systematically studied the low-energy crystal structures of Na2FeSiO4.
Asymmetric reductive amination by a wild-type amine dehydrogenase from the thermophilic bacteria Petrotoga mobilis
Authors: Mayol Ombeline , David Sylvain , Darii Ekaterina , Debard Adrien , Mariage Aline , Pellouin Virginie , Petit Jean-Louis , Salanoubat Marcel , de Berardinis Véronique , Zaparucha Anne , Vergne-Vaxelaire Carine
Published: August 2016

Biocatalytic potential of a new wild-type amine dehydrogenase used in an enzyme-catalyzed synthesis of an enantiomerically pure primary amine.