Electrophysiological correlates of performance monitoring under social observation in patients with social anxiety disorder and healthy controls

Publication date: Available online 11 November 2017
Source:Biological Psychology
Author(s): Rolf Voegler, Jutta Peterburs, Hannah Lemke, Sebastian Ocklenburg, Roman Liepelt, Thomas Straube
Previous research suggests that electrophysiological correlates of performance monitoring, in particular the error-related negativity (ERN), vary according to psychopathology and context factors. The present study examined the effect of social context on behavioral and electrophysiological correlates of performance monitoring in healthy adult subjects and in patients with social anxiety disorder (SAD). Participants performed two runs of a Go/NoGo flanker task in different social conditions: in the observation condition, they were observed by a confederate while performing the task, whereas there was no observation in the control condition. Behavioral data showed that accuracy and response times were not modulated by social observation and also did not systematically differ between groups. Post-error slowing was more pronounced in patients, independent of observation condition. ERN amplitudes were generally increased under social observation as compared to the control condition regardless of group (patients, controls). No effects of social context or group were found for PE, NoGo-N2, and NoGo-P3. Exploratory analysis revealed a late sustained parietal negativity to errors in patients as compared to controls. Taken together, the present findings emphasize the importance of social context for the processes underlying performance monitoring. However, the notion of altered error monitoring reflected in an altered ERN in SAD is not supported by our data.



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Atmospheric-pressure chemical purification of detonation-synthesized nanodiamond by using perchloric acid: Intensive parametric study to control sp3/sp2carbon ratio

Publication date: Available online 12 November 2017
Source:Diamond and Related Materials
Author(s): Seung Pyo Hong, Sang Wook Ha, Seung Whan Lee
Controlled- and high-sp³/sp² carbon ratio of the detonation-synthesized nanodiamond (DND) may play a very important role in many applications. Here, we demonstrated an atmospheric-pressure process of chemical purification using perchloric acid (HClO4) and intensively studied the control parameters including the reaction temperature, DND loading amount, and processing time. The sp³/sp² carbon ratio was characterized using UV-Raman spectroscopy (325nm) and is evaluated based on the intensity ratio (IDia/IG) of the diamond peak and G band peak at 1325cm⁻¹ and 1590cm⁻¹, respectively. Through the combination of control parameters, we successfully controlled the intensity ratio of IDia/IG at the range from 0.28 to 1.5 and achieved 15.5% higher than compared with commercial DND. In addition, we also investigated the electrical conductivity of DND vs. intensity ratio of IDia/IG and the results show that lower intensity ratio of IDia/IG have higher electrical conductivity because of non-diamond carbon.

Graphical abstract

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Monitoring of uranium concentrations in water samples collected near potentially hazardous objects in North-West Tajikistan

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): P. Zoriy, M. Schläger, K. Murtazaev, J. Pillath, M. Zoriy, B. Heuel-Fabianek
The water contamination near ecologically problematic objects was investigated between 2009 and 2014 in North-West Tajikistan as a part of a joint project between Forschungszentrum Jülich and Khujand State University. The main part of this work was the determination of uranium in water samples collected near the Degmay tailings dump, the Taboshar pit lake and the Syr Darya river. More than 130 water samples were collected and analyzed to monitor the uranium concentration near the investigated areas. Two different mass spectrometers and an ion chromatograph were used for element concentration measurements. Based on the results obtained, the uranium influence of the Degmay tailings on the rivers Khoja-Bakyrgan-Say and Syr Darya and surrounding water was not found. The uranium concentration in water samples was monitored for a lengthy period at seven locations Great differences in the uranium concentration in waters collected in 2010, 2011, 2012, 2013 for each location were not observed. Drinking water samples from the region of North-West Tajikistan were analyzed and compared with the World Health Organization's guidelines. Seven out of nine drinking water samples near Taboshar exceeded the WHO guideline value for uranium concentrations (30 μg/L). The average uranium concentration of water samples from Syr Darya for the period from 2009 to 2014 was determined to be 20.1 (±5.2) μg/L. The uranium contamination of the Syr Darya was determined from the western border to the eastern border and the results are shown in this paper.



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Recovery stress formation in FeMnSi based shape memory alloys: Impact of precipitates, texture and grain size

Publication date: 5 February 2018
Source:Materials & Design, Volume 139
Author(s): A. Arabi-Hashemi, W.J. Lee, C. Leinenbach
FeMnSi based shape memory alloys are considered for engineering applications such as prestressing of concrete or coupling devices. For this, a high recovery stress is desired which forms when the FeMnSi alloy is first elongated and then heated above the austenite transformation temperature under mechanical constraints. In this work, we study the impact of three different microstructural properties on the recovery stress of Fe17Mn5Si10Cr4Ni1(V,C) shape memory alloys: Precipitates, texture and grain size. Precipitates allowed varying the recovery stress in a broad range between 255MPa and 564MPa. A recovery stress of 564MPa was achieved by a combination of a high materials yield strength σ0.1 of 536MPa and a shape recovery of 14%. The [001] grain orientation with a low Schmid factor has a beneficial impact on the recovery stress due to a higher yield strength when compared with the [011] orientation. A decrease of the grain size caused a Hall-Petch strengthening but had no influence on the recovery stress. However the pseudo-elasticity increased for a decrease of grain size.

Graphical abstract

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Experimental and numerical study on soft-hard-soft (SHS) cement based composite system under multiple impact loads

Publication date: 5 February 2018
Source:Materials & Design, Volume 139
Author(s): Jun Wu, Xuemei Liu, Hongyuan Zhou, Liang Li, Zhongxian Liu
The performance of the newly developed soft-hard-soft (SHS) cement based composite system under multiple impact loading was investigated using a combined numerical and experimental study. Such a composite consists of three layers including Geogrid (GST) reinforced asphalt concrete (AC) on the top, high strength concrete (HSC) layer in the middle, and fiber reinforced cementitious composites (FRCC) at the bottom. A Hard-Soft-Hard (HSH) composite pavement was also proposed and tested for comparison purpose. In addition, the experimental results were compared with standard rigid and flexible pavements. The SHS composite system exhibits minimum damage, higher energy absorption and significant improved impact resistance against multiple impact loading compared with the other three types of pavements. A 3D finite element (FE) model was also established and confirmed the experimental results for the SHS composite pavement. Following the FE model, intensive parametric study was conducted to investigate the factors to enhance the impact resistance of the SHS composite system. The results can guide the upgrade options for runway pavement and be used for further development of the protective composite.

Graphical abstract

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Equination (inoculation of horsepox): An early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine

Publication date: Available online 11 November 2017
Source:Vaccine
Author(s): José Esparza, Livia Schrick, Clarissa R. Damaso, Andreas Nitsche
For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was not until 1939 when it was shown that vaccinia, the smallpox vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus. A favorite candidate for a vaccinia ancestor has been the horsepox virus. Edward Jenner himself suspected that cowpox derived from horsepox and he also believed that "matter" obtained from either disease could be used as preventative of smallpox. During the 19th century, inoculation with cowpox (vaccination) was used in Europe alongside with inoculation with horsepox (equination) to prevent smallpox. Vaccine-manufacturing practices during the 19th century may have resulted in the use of virus mixtures, leading to different genetic modifications that resulted in present-day vaccinia strains. Horsepox, a disease previously reported only in Europe, has been disappearing on that continent since the beginning of the 20th century and now seems to have become extinct, although the virus perhaps remains circulating in an unknown reservoir. Genomic sequencing of a horsepox virus isolated in Mongolia in 1976 indicated that, while closely related to vaccinia, this horsepox virus contained additional, potentially ancestral sequences absent in vaccinia. Recent genetic analyses of extant vaccinia viruses have revealed that some strains contain ancestral horsepox virus genes or are phylogenetically related to horsepox virus. We have recently reported that a commercially produced smallpox vaccine, manufactured in the United States in 1902, is genetically highly similar to horsepox virus, providing a missing link in this 200-year-old mystery.



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YAP-Dependent AXL Overexpression Mediates Resistance to EGFR Inhibitors in NSCLC

Publication date: December 2017
Source:Neoplasia, Volume 19, Issue 12
Author(s): Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer. In EGFR-addicted lung cancer cell lines (HCC4006 and HCC827) rendered resistant to several EGFR inhibitors, we observed that resistance was associated to YAP activation. Indeed, YAP silencing impaired the maintenance of resistance, while YAP overexpression decreased the responsiveness to EGFR inhibitors in sensitive parental cells. In our models, we identified the AXL tyrosine kinase receptor as the main YAP downstream effector responsible for sustaining YAP-driven resistance: in fact, AXL expression was YAP dependent, and pharmacological or genetic AXL inhibition restored the sensitivity of resistant cells to the anti-EGFR drugs. Notably, YAP overactivation and AXL overexpression were identified in a lung cancer patient upon acquisition of resistance to EGFR TKIs, highlighting the clinical relevance of our in vitro results. The reported data demonstrate that YAP and its downstream target AXL play a crucial role in resistance to EGFR TKIs and suggest that a combined inhibition of EGFR and the YAP/AXL axis could be a good therapeutic option in selected NSCLC patients.



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Geometric and dosimetric accuracy of dynamic tumor tracking during volumetric-modulated arc therapy using a gimbal mounted linac

Publication date: Available online 11 November 2017
Source:Radiotherapy and Oncology
Author(s): Tomohiro Ono, Yuki Miyabe, Kunio Takahashi, Mami Akimoto, Nobutaka Mukumoto, Yoshitomo Ishihara, Mitsuhiro Nakamura, Takashi Mizowaki, Masahiro Hiraoka
PurposeThe aim was to examine the feasibility of a dynamic tumor-tracking volumetric modulated arc therapy (DTT-VMAT) technique using a gimbal-mounted linac and assess its positional, mechanical and dosimetric accuracy.Materials and methodsDTT-VMAT was performed using a surrogated signal-based technique. The positional tracking accuracy was evaluated as the difference between the predicted and detected target positions for various wave patterns. Mechanical accuracy measurements included gantry, multileaf collimator (MLC) and gimbal positions. The differences between the command and the measured positions were evaluated for various wave patterns. Dosimetric verification was performed using Gafchromic EBT3 films in the benchmark phantom and two clinical cases.ResultsThe root mean square error (RMSE) of the positional accuracy was within 0.31 mm. The RMSE of mechanical accuracy was within 0.14° for the gantry, 0.11 ± 0.02 mm for the MLC and 0.13 mm for the gimbal positions. The passing rate of the 3%/3 mm gamma index was greater than 83.3% and 91.2% for the benchmark phantom and two clinical cases, respectively.ConclusionsThe positional, mechanical and dosimetric accuracy of DTT-VMAT were evaluated. DTT-VMAT with a gimbal-mounted linac had sufficient accuracy and presents a new strategy for treatment of several tumors with respiratory motion.



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Industry interests in gambling research: Lessons learned from other forms of hazardous consumption

Publication date: March 2018
Source:Addictive Behaviors, Volume 78
Author(s): S. Cowlishaw, S.L. Thomas
Research indicates that the evidential bases for many harm reduction policies targeting hazardous consumptions (including tobacco, alcohol and gambling) have been distorted by commercial industries that derive revenue from such commodities. These distortions are best illustrated by research on tobacco and alcohol, which indicates similar tactics used by industries to determine favourable policy environments through engineering of evidence, among other approaches. Although there is concern that gambling research is similarly vulnerable to commercial interests, the relevant literature lags far behind other fields and the aim of this paper is to increase familiarity with tactics used by industries for influencing research. It summarises the conceptual and empirical bases for expecting conflicts between goals of public health and companies that profit from hazardous consumptions. It also summarises evidence describing practices deployed by tobacco corporations, which include third-party techniques and the selective funding of research to manufacture doubt and deflect attention away from the consequences of smoking. It then reviews both early and emerging evidence indicating similar strategies used by alcohol industry, and uses this literature to view practices of the gambling industry. It argues that parallels regarding selective funding of research and third-party techniques provide grounds for strong concern about commercial influences on gambling research, and implementation of precautionary approaches to management of vested interests.



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To create or to recall original ideas: Brain processes associated with the imagination of novel object uses

Publication date: Available online 11 November 2017
Source:Cortex
Author(s): Mathias Benedek, Till Schües, Roger E. Beaty, Emanuel Jauk, Karl Koschutnig, Andreas Fink, Aljoscha C. Neubauer
This fMRI study investigated what brain processes contribute to the generation of new ideas. Brain activation was measured while participants generated new original object uses, recalled original object uses, or recalled common object uses. Post-scan evaluations were used to confirm what ideas were newly generated on the spot or actually retrieved from memory. When compared to the recall of common ideas, the generation of new and old original ideas showed a similar activation pattern including activation of bilateral parahippocampal and mPFC regions, suggesting that the construction of new ideas builds on similar processes like the reconstruction of original ideas from episodic memory. As a difference, the generation of new object uses involved higher activation of a focused cluster in the left supramarginal gyrus compared to the recall of original ideas. This finding adds to the converging evidence that the left supramarginal gyrus is crucially involved in the construction of novel representations, potentially by integrating memory content in new ways and supporting executively demanding mental simulations. This study deepens our understanding of how creative thought builds on and goes beyond memory.



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Human laterality for manipulation and gestural communication related to 60 everyday activities: impact of multiple individual-related factors

Publication date: Available online 11 November 2017
Source:Cortex
Author(s): Jacques Prieur, Stéphanie Barbu, Catherine Blois-Heulin
Literature on laterality emphasises the importance of implementing a comprehensive investigation of humans' and non-humans' laterality for both non-communication and communication functions. Adopting a global approach should enhance our understanding of the mechanistic drivers of human brain functional lateralisation and help to explore further the nature of the left-hemispheric systems for both functions. This study investigated human laterality for both functions by taking, for the first time, numerous behaviours and multiple potential influential factors into consideration. We analysed replies to the Rennes Laterality Questionnaire that takes into account simultaneously: participants' behavioural, demographic and social characteristics as well as their genetic/social learning components and collateral factors such as health problems. We collected and analysed a large data set including 450,220 item responses (317,594 items related to behavioural laterality and 132,626 items related to personal information) by 5,904 participants. The majority of participants were right-lateralised for nine behavioural categories. The laterality of right-lateralised individuals for the behaviours considered varied very little between behavioural categories, contrary to the laterality of ambiguously- and left-lateralised individuals. This is the first evidence of the stability of right-lateralised individuals and the relative flexibility of ambiguously- and left-lateralised individuals with regards to behavioural laterality related to 60 everyday activities. Moreover, the laterality patterns of our study population were linked in particular to the following individual-related factors: demographic characteristics (current continent of residence), social characteristics (socio-professional group and study level), and collateral factors (writing hand, forced right-hand use, guiding eye, and health problems related to ear and back). We discuss our findings in relation to the evolutionary roots of human brain lateralisation for non-communication and communication functions.



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A 3D supramolecular network as highly selective and sensitive luminescent sensor for PO43− and Cu2+ ions in aqueous media

Publication date: March 2018
Source:Dyes and Pigments, Volume 150
Author(s): Yuan Xie, Shigang Ning, Yong Zhang, Zilong Tang, Shaowei Zhang, Ruiren Tang
A 2D coordination polymer, {[Zn(btca)(py)2]}n (1), (H2btca = benzotriazole-5-carboxylic acid, py = pyridine), has been prepared with high yield by the hydrothermal reaction of H2btca and Zn(NO3)2·6H2O in the presence of py, which has been further characterized by kinds of methods combining elemental analysis, thermogravimetric (TG) analysis, infrared (IR) spectrum, powder X-ray diffraction (PXRD), and X-ray single-crystal diffraction. In 1, each Zn²⁺ adopts a five-coordinated pentagonal bipyramid geometry with one O atom from one carboxylate group of btca²⁻ ligand and four N atoms from two btca²⁻ ligands and two py molecules. Adjacent Zn²⁺ are connected by btca²⁻ ligands to generate a 2D layer with the 'fes'-type topology, which could further form a 3D supramolecular network through hydrogen bonds interactions. Furthermore, the luminescent results reveal that the detection limit of 1 as a luminescent sensor to probe Cu²⁺ and PO4³⁻ could reach 3 and 45 ppm, respectively, suggesting that 1 can sensitively and selectively detect Cu²⁺ and PO4³⁻ in aqueous solution.

Graphical abstract

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In vivo assessment of polydatin, a natural polyphenol compound, on arsenic-induced free radical overproduction, gene expression, and genotoxicity

Abstract

Arsenic (As) is a well-known contaminant of global groundwater. Its exposure causes several hazardous effects on animals and human via oxidative stress. The present study examined the effect of polydatin (PD) on free radical overproduction in rats exposed to As. Thirty-five male rats randomly allocated into five equal groups. To the control group, physiological saline was given orally and to the second group only 100 mg/L As was given by drinking water for 60 days. The other groups were treated with As (100 mg/L) and PD orally at 50, 100, and 200 mg/kg/day, respectively. Treatment with As enhanced malondialdehyde level but decreased glutathione level in blood, liver, kidney, brain, lung, and heart of rats. Also, As decreased superoxide dismutase and catalase activities of erythrocyte, liver, kidney, brain, lung, and heart in rats. Furthermore, As treatment gave rise to increased DNA damage and gene expressions of interleukin 1 beta (IL-1β), nuclear factor kappa beta (NFκB), p53, and tumor necrosis factor-α (TNF-α) in the lung, brain, kidney, and liver. However, treatment of PD ameliorated As-exposed lipid peroxidation, antioxidant enzymes activities, DNA damage, gene expressions, and histopathological changes in tissues. In conclusion, PD has a dose-dependent protective effect on lipid peroxidation and antioxidant defense mechanism in rats against As exposure.

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Heavy metal distribution in Tiaoxi River’s sediment

Abstract

According to current study, seven surface sediments and three sediment cores were collected from three typical areas of Tiaoxi River, which were living area, agricultural area, and industrial area. The water quantity into the Lake Taihu from the Tiaoxi River accounted for almost one third of the total water quantity by all rivers into the Lake Taihu. To study geochemical features and pollution history of heavy metals in three typical areas of Tiaoxi River, total content and chemical fractionations of Cu, Pb, Cd, Cr, Mn, Zn, Fe, As, and Hg were analyzed for surface and core sediments using the speciation extraction procedure, proposed by the Commission of the European Communities Bureau of Reference (BCR), together with grain size and organic carbon measurements. The results showed that the concentration of nine heavy metals and the variation characteristics of Zn, Cu, Fe, Mn, and Cr are different among five cores, which has shown that the river responses to natural and anthropogenic activities were dissimilar in various areas. BCR sequential extraction showed contents of Cr, Fe, and Cu were dominated in the remaining parts. Non-residual fractions for Zn and Mn contained major portions. Based on RAC (risk assessment core), the risk of Mn was high to very high in the three typical areas, and the risk of Zn was medium in the three typical areas.

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Impact of on-site sanitation systems on groundwater sources in a coastal aquifer in Chennai, India

Abstract

On-site sanitation is the most preferred mode of sanitation due to expensive off-site sanitation. The increasing population especially in the peri-urban areas has led to increasing use of on-site sanitation systems in India. However, the habitations in the vicinity of these systems do not have centralised water supply and are dependent on groundwater sources. However, there is concern about leaching of faecal coliforms and nitrate from the septic tanks to the underlying aquifer. The present study is attempted at two sites in the coastal city of Chennai where on-site sanitation is prevailing. The sample locations (16 nos.) are selected in such a way that groundwater sources are situated in the vicinity of on-site sanitation systems. The groundwater sources are the bore wells installed by the private agencies. It is observed that parameters considered key parameters to study the impact of the on-site sanitation systems, namely Na2⁺, Cl⁻, NO₃⁻, faecal coliform and total dissolved solids, exceed the concentration limits recommended by the Bureau of Indian Standards. The piper diagram analysis identifies that the predominant cations and anions are respectively Na⁺, and Cl⁻, SO₄⁻ and HCO₃⁻.The Gibbs plot shows ground water quality is dominated by the evaporation process in both the seasons. The Cl/HCO₃ ratio in many samples confirms the seawater intrusion in the study area. Elevated concentrations of faecal coliforms in all the samples (16 nos.) confirm the significant amount of groundwater pollution from the on-site sanitation systems. It is desired that policy planners and implementation agencies should undertake detailed scientific and hydrogeological studies of the region in order to examine the feasibility of implementing on-site sanitation systems.

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Distinctive accumulation patterns of heavy metals in Sardinella aurita (Clupeidae) and Mugil cephalus (Mugilidae) tissues

Abstract

The present study assessed the impact of metal pollution on two widely consumed types of wild fish Sardinella aurita and Mugil cephalus captured from the Gulf of Gabes (Tunisia) which is currently experiencing acute environmental problems. A study of the Cd, Cu, Zn, and Pb levels present in the studied site and vital in fish tissues (gills, liver, gonad, and muscle) was undertaken. As expected, muscle, liver, and gonad tissues contained the highest concentrations of all metals except for Zn. The metal levels showed a significant variation of accumulation between species with overall effects of the tested tissues. In addition, the results address the significant effects of the species/tissue interaction. Liver sections showed structural alterations consisting mainly of a significant desquamation of the tissue, a fibroblast proliferation, and a lipid droplet accumulation in both species. Additionally, the presence of skeletal abnormalities affecting the vertebral column was observed in the M. cephalus specimens. As a whole, our data provide the first evidence of distinctive metal accumulation patterns in vital fish tissues as well as the interspecific difference that can be correlated with the biological habits of the two selected models, S. aurita and M. cephalus, known respectively as pelagic and benthopelagic species.

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Lying in wait: Limiting factors on a low-density ungulate population and the latent traits that can facilitate escape from them

Publication date: November 2017
Source:Acta Oecologica, Volume 85
Author(s): Kyle Joly, Tim Craig, Matthew D. Cameron, Adrian E. Gall, Mathew S. Sorum
Predation, habitat, hunting, and environmental conditions have all been implicated as regulatory mechanisms in ungulate populations. The low-density equilibrium hypothesis predicts that in low-density populations, predators regulate their prey and that the population will not escape unless predation pressure is eased. We evaluated survival of adult and juvenile moose (Alces alces) in north-central Alaska to determine whether or not the population supported the hypothesis. We instrumented adult male and female moose with radiocollars and used aerial observations to track parturition and subsequent survival of juvenile moose. Generalized linear mixed-effects models were used to assess survival. Adult annual survival rates were high (∼89%), but may be negatively influenced by winter conditions. Migratory status did not affect moose survivorship or productivity. Approximately 60% of the calf crop died before 5 months of age. Productivity was significantly lower in the northern section of the study area where there is less high-quality habitat, suggesting that, even in this low-density population, nutrition could be a limiting factor. It appears that predation on young calves, winter weather, and nutritional constraints may be interacting to limit this population. Latent traits, such as overproduction of calves and migratory behavior, which do not currently enhance fitness, may persist within this population so that individuals with these traits can reap benefits when environmental conditions change.



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Cyclin-dependent kinase 5 regulates MAPK/ERK signaling in the skin of mice

Publication date: Available online 11 November 2017
Source:Acta Histochemica
Author(s): Xuexian Liu, Pengqian Zhang, Kaiyuan Ji, Junzhen Zhang, Shanshan Yang, Bin Du, Shuaipeng Hu, Ruiwen Fan
Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine/threonine kinase that has been shown to play important roles in many tissues except the nervous system. We previously reported that CDK5 showed differential expression in the transcriptome profiles of the skin of alpacas with different hair colors. To understand the functional role of CDK5 in hair color determination, we constructed CDK5-knockdown mice and identified the effect on the mitogen-activated protein kinase (MAPK) pathway in the mouse skin. Quantitative real-time polymerase chain reaction, co-immunoprecipitation, and western blotting were performed to analyze the effects of CDK5-knockdown on the MAPK pathway in mice. The results showed that MAP3K6 was inhibited by phosphorylated CDK5 through its activator CDK7. The decrease in MAP3K6 levels caused down-regulation of MEK1 and ERK expression, leading to the up-regulation of miR-143-3p, which targets MAP3K6 via Dicer. Taken together, our findings indicate that CDK5 functions in regulating the MAPK pathway. Given that MAP3K6 was inhibited in two directions, this mechanism can provide insight into the contributions of the MAPK/ERK pathway to the inhibition of melanin production.



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Extending the Structural View of Class B GPCRs

Publication date: Available online 11 November 2017
Source:Trends in Biochemical Sciences
Author(s): Chris de Graaf, Gaojie Song, Can Cao, Qiang Zhao, Ming-Wei Wang, Beili Wu, Raymond C. Stevens
The secretin-like class B family of G protein-coupled receptors (GPCRs) are key players in hormonal homeostasis. Recent structures of various receptors in complex with a variety of orthosteric and allosteric ligands provide fundamental new insights into the function and mechanism of class B GPCRs, including: (i) ligand-induced changes in the relative orientation of the extracellular and transmembrane receptor domains; (ii) intramolecular interaction networks that stabilize conformational changes to accommodate intracellular G protein binding; and (iii) allosteric modulation of receptor activation. This review provides a comprehensive analysis of the structural, biochemical, and pharmacological data on class B GPCRs for understanding ligand–receptor interaction and modulation mechanisms and assessing the potential implications for drug discovery for the secretin-like GPCR family.



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Feel the Way With a Vibrotactile Compass: Does a Navigational Aid Aid Navigation?.

Author: Weisberg, Steven M.; Badgio, Daniel; Chatterjee, Anjan

DOI: 10.1037/xlm0000472

Publication Date: POST AUTHOR CORRECTIONS, 9 November 2017

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