bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemispheric asymmetries in the orientation and location of the lateral geniculate nucleus in dyslexia
Authors: Giraldo‐Chica Mónica , Schneider Keith A.
Published: January 2018

Human brain asymmetry reflects normal specialization of functional roles and may derive from evolutionary, hereditary, developmental, experiential, and pathological factors (Toga & Thompson, 2003). Geschwind and Galaburda (1985) suggested that processing difficulties in dyslexia are due to structural differences between hemispheres. Because of its potential significance to the controversial magnocellular theory of dyslexia, we investigated hemispheric differences in the human lateral geniculate nucleus (LGN), the primary visual relay and control nucleus in the thalamus, in subjects with dyslexia compared to normal readers. We acquired and averaged multiple high‐resolution proton density (PD) weighted structural magnetic resonance imaging (MRI) volumes to measure in detail the anatomical boundaries of the LGN in each hemisphere. We observed hemispheric asymmetries in the orientation of the nucleus in subjects with dyslexia that were absent in controls. We also found differences in the location of the LGN between hemispheres in controls but not in subjects with dyslexia. Neither the precise anatomical differences in the LGN nor their functional consequences are known, nor is it clear whether the differences might be causes or effects of dyslexia.
Metal–Thiobenzoato Complexes: Synthesis, Structure, and Processing as Carbon‐Supported Nanoparticles
Authors: Vallejo‐Sánchez Daniel , Beobide Garikoitz , Castillo Oscar , Lanchas Mónica , Luque Antonio , Pérez‐Yáñez Sonia , Román Pascual
Published: January 2018

Six new compounds of formula [M(TBn)2L] [TBn: thiobenzoato; M: PdII, ZnII, CdII; L: 2,2′‐bipyridine (bpy), 1,10‐phenanthroline (phen), 1,2‐di‐(4‐pyridil)‐ethylene (bpe), neocuproine (neo), adenine (ade)] are obtained by the reaction of M(CH3COO)2·2H2O with thiobenzoic acid and N‐heterocyclic ligands. The use of chelating ligands and adenine leads to monomeric compounds: [Pd(TBn)2(bpy)] (PdBPY), [Pd(TBn)2(phen)] (PdPHEN), [Zn(TBn)2(neo)] (ZnNEO), [Cd(TBn)2(neo)] (CdNEO), and [Cd(TBn)2(ade)(CH3OH)] (CdADE). In these compounds, the metal is bonded to the sulfur atoms of two TBn anions, while the remaining coordination positions are completed by the donor atoms of the ancillary ligands. The bridging capability of the bpe ligand gives rise to the polymeric [Cd(TBn)2(µ‐bpe)]n (CdBPE) compound. The presence of direct sulfur–metal bonds and carbon‐rich coligands enables these complexes to yield, by means of a dry thermolysis process, a set of metallic and metal–sulfide nanoparticles embedded into a carbonaceous support. The process to produce the latter materials consists of aerobic thermolysis using moderate temperatures (300–500 °C) and short exposure times (minute scale). Analysis of the XRD patterns and SEM/TEM images reveals that the carbonaceous matrix hosts well‐dispersed nanocrystallites. The influence of the metal(II) atom, ancillary ligand, and thermal treatment parameters on the crystalline phase, size, and purity of the resulting carbon‐supported nanoparticles is discussed.
Photoelectrochemical Performance of BiVO4 Photoanodes Integrated with [NiFe]‐Layered Double Hydroxide Nanocatalysts
Authors: Sinclair Timothy S. , Gray Harry B. , Müller Astrid M.
Published: January 2018

Invited for the cover of this issue are AstridàM. Müller and co‐workers from California Institute of Technology, Pasadena, California, USA. The cover image shows a drawing of an integrated photoanode whose active materials are laser‐synthesized highly efficient [NiFe]‐layered double hydroxide or Co3O4 water oxidation nanocatalysts and sunlight‐absorbing BiVO4.
One‐Pot Multi‐Component Synthesis of Triarylacrylonitriles Directly by Using CaC2 as a Concise Acetylene Source and K4[Fe(CN)6] as an Eco‐Friendly Cyanide Source
Authors: Song Geyang , Li Zheng
Published: January 2018

An efficient method for the one‐pot multicomponent synthesis of triarylacrylonitriles from various aryl iodides directly by using calcium carbide as a concise acetylene source and potassium hexacyanoferrate(II) as an eco‐friendly cyanide source is described. This protocol benefits from safe, inexpensive and easy‐to‐handle starting materials, good substrate tolerance and simple work‐up procedure.
Distributed heuristic adaptive power control algorithms in femto cellular networks for improved performance
Authors: Kundu Anindita , Majumder Subhashis , Misra Iti Saha , Sanyal Salil K.
Published: January 2018

Adaptiveness of femto base station's (FBS's) transmission power (TP) is crucial in determining Quality of Service and ecofriendliness of a network. Joint power optimization and admission control problems have been reformulated to identify the TP of v already deployed FBSs, and the problem is shown to be computationally hard. Accordingly, an adaptive distributed heuristic called power search algorithm (PSA) is proposed. A learning algorithm analytically identifies the received signal strength‐based coverage of each FBS in all directions during planning. A 3‐dimensional reference matrix, ie, REF, for each FBS, is thereby formulated and stored in the corresponding FBSs. Power search algorithm handles call admission/termination at run time. For call admission, PSA identifies the serving FBS and the required minimum TP. A suitable data structure is also maintained by PSA for efficient call handling. A new call is dropped if its admission degrades the Quality of Service of existing end‐users. For call termination, change in TP is triggered if the highest power level of the FBS was being exercised to serve this particular user. The worst‐case run‐time complexity of PSA turns out to be O(log2N), where N is the number of TP levels of a particular FBS. Comparing with existing heuristics, improved performance of PSA includes highest throughput and signal‐to‐interference‐plus‐noise ratio while minimizing starvation and cumulative TP with lower complexity even for high end‐user density. Exhaustive simulation reveals that the probability of an end‐user having signal‐to‐interference‐plus‐noise ratio above 0 dB is 0.83 even in the worst case scenario. Accordingly, the proposed PSA is claimed to be superior.
Astrocytes expressing ALS‐linked mutant FUS induce motor neuron death through release of tumor necrosis factor‐alpha
Authors: Kia Azadeh , McAvoy Kevin , Krishnamurthy Karthik , Trotti Davide , Pasinelli Piera
Published: January 2018

Mutations in fused in sarcoma (FUS) are linked to amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease affecting both upper and lower motor neurons. While it is established that astrocytes contribute to the death of motor neurons in ALS, the specific contribution of mutant FUS (mutFUS) through astrocytes has not yet been studied. Here, we used primary astrocytes expressing a N‐terminally GFP tagged R521G mutant or wild‐type FUS (WTFUS) and show that mutFUS‐expressing astrocytes undergo astrogliosis, damage co‐cultured motor neurons via activation of an inflammatory response and produce conditioned medium (ACM) that is toxic to motor neurons in isolation. Time lapse imaging shows that motor neuron cultures exposed to mutFUS ACM, but not WTFUS ACM, undergo significant cell loss, which is preceded by progressive degeneration of neurites. We found that Tumor Necrosis Factor‐Alpha (TNFα) is secreted into ACM of mutFUS‐expressing astrocytes. Accordingly, mutFUS astrocyte‐mediated motor neuron toxicity is blocked by targeting soluble TNFα with neutralizing antibodies. We also found that mutant astrocytes trigger changes to motor neuron AMPA receptors (AMPAR) that render them susceptible to excitotoxicity and AMPAR‐mediated cell death. Our data provide the first evidence of astrocytic involvement in FUS‐ALS, identify TNFα as a mediator of this toxicity, and provide several potential therapeutic targets to protect motor neurons in FUS‐linked ALS.
Neuromodulation with single‐element transcranial focused ultrasound in human thalamus
Authors: Legon Wynn , Ai Leo , Bansal Priya , Mueller Jerel K.
Published: January 2018

Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical tissue in humans. tFUS confers high spatial resolutions with deep focal lengths and as such, has the potential to noninvasively modulate neural targets deep to the cortex in humans. We test the ability of single‐element tFUS to noninvasively modulate unilateral thalamus in humans. Participants (N = 40) underwent either tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that contains the ventro‐posterior lateral (VPL) nucleus of thalamus. Somatosensory evoked potentials (SEPs) were recorded from scalp electrodes contralateral to median nerve stimulation. Activity of the unilateral sensory thalamus was indexed by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity by subsequent inflexions of the SEP and through time/frequency analysis. Participants also under went tactile behavioral assessment during either the tFUS or sham condition in a separate experiment. A detailed acoustic model using computed tomography (CT) and magnetic resonance imaging (MRI) is also presented to assess the effect of individual skull morphology for single‐element deep brain neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham. There is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities. These results were accompanied by alpha and beta power attenuation as well as time‐locked gamma power inhibition. Furthermore, participants performed significantly worse than chance on a discrimination task during tFUS stimulation.
Emergence of the neural network underlying phonological processing from the prereading to the emergent reading stage: A longitudinal study
Authors: Yu Xi , Raney Talia , Perdue Meaghan V. , Zuk Jennifer , Ozernov‐Palchik Ola , Becker Bryce L. C. , Raschle Nora M. , Gaab Nadine
Published: January 2018

Numerous studies have shown that phonological skills are critical for successful reading acquisition. However, how the brain network supporting phonological processing evolves and how it supports the initial course of learning to read is largely unknown. Here, for the first time, we characterized the emergence of the phonological network in 28 children over three stages (prereading, beginning reading, and emergent reading) longitudinally. Across these three time points, decreases in neural activation in the left inferior parietal cortex (LIPC) were observed during an audiovisual phonological processing task, suggesting a specialization process in response to reading instruction/experience. Furthermore, using the LIPC as the seed, a functional network consisting of the left inferior frontal, left posterior occipitotemporal, and right angular gyri was identified. The connection strength in this network co‐developed with the growth of phonological skills. Moreover, children with above‐average gains in phonological processing showed a significant developmental increase in connection strength in this network longitudinally, while children with below‐average gains in phonological processing exhibited the opposite trajectory. Finally, the connection strength between the LIPC and the left posterior occipitotemporal cortex at the prereading level significantly predicted reading performance at the emergent reading stage. Our findings highlight the importance of the early emerging phonological network for reading development, providing direct evidence for the Interactive Specialization Theory and neurodevelopmental models of reading.
Linking late cognitive outcome with glioma surgery location using resection cavity maps
Authors: Hendriks Eef J. , Habets Esther J. J. , Taphoorn Martin J. B. , Douw Linda , Zwinderman Aeilko H. , Vandertop W. Peter , Barkhof Frederik , Klein Martin , De Witt Hamer Philip C.
Published: January 2018

Patients with a diffuse glioma may experience cognitive decline or improvement upon resective surgery. To examine the impact of glioma location, cognitive alteration after glioma surgery was quantified and related to voxel‐based resection probability maps. A total of 59 consecutive patients (range 18–67 years of age) who had resective surgery between 2006 and 2011 for a supratentorial nonenhancing diffuse glioma (grade I–III, WHO 2007) were included in this observational cohort study. Standardized neuropsychological examination and MRI were obtained before and after surgery. Intraoperative stimulation mapping guided resections towards neurological functions (language, sensorimotor function, and visual fields). Maps of resected regions were constructed in standard space. These resection cavity maps were compared between patients with and without new cognitive deficits (z‐score difference >1.5 SD between baseline and one year after resection), using a voxel‐wise randomization test and calculation of false discovery rates. Brain regions significantly associated with cognitive decline were classified in standard cortical and subcortical anatomy. Cognitive improvement in any domain occurred in 10 (17%) patients, cognitive decline in any domain in 25 (42%), and decline in more than one domain in 10 (17%). The most frequently affected subdomains were attention in 10 (17%) patients and information processing speed in 9 (15%). Resection regions associated with decline in more than one domain were predominantly located in the right hemisphere. For attention decline, no specific region could be identified. For decline in information speed, several regions were found, including the frontal pole and the corpus callosum. Cognitive decline after resective surgery of diffuse glioma is prevalent, in particular, in patients with a tumor located in the right hemisphere without cognitive function mapping.
Hearing and seeing meaning in noise: Alpha, beta, and gamma oscillations predict gestural enhancement of degraded speech comprehension
Authors: Drijvers Linda , Özyürek Asli , Jensen Ole
Published: January 2018

During face‐to‐face communication, listeners integrate speech with gestures. The semantic information conveyed by iconic gestures (e.g., a drinking gesture) can aid speech comprehension in adverse listening conditions. In this magnetoencephalography (MEG) study, we investigated the spatiotemporal neural oscillatory activity associated with gestural enhancement of degraded speech comprehension. Participants watched videos of an actress uttering clear or degraded speech, accompanied by a gesture or not and completed a cued‐recall task after watching every video. When gestures semantically disambiguated degraded speech comprehension, an alpha and beta power suppression and a gamma power increase revealed engagement and active processing in the hand‐area of the motor cortex, the extended language network (LIFG/pSTS/STG/MTG), medial temporal lobe, and occipital regions. These observed low‐ and high‐frequency oscillatory modulations in these areas support general unification, integration and lexical access processes during online language comprehension, and simulation of and increased visual attention to manual gestures over time. All individual oscillatory power modulations associated with gestural enhancement of degraded speech comprehension predicted a listener's correct disambiguation of the degraded verb after watching the videos. Our results thus go beyond the previously proposed role of oscillatory dynamics in unimodal degraded speech comprehension and provide first evidence for the role of low‐ and high‐frequency oscillations in predicting the integration of auditory and visual information at a semantic level.
Targeting Pin1 by inhibitor API‐1 regulates microRNA biogenesis and suppresses hepatocellular carcinoma development
Authors: Pu Wenchen , Li Jiao , Zheng Yuanyuan , Shen Xianyan , Fan Xin , Zhou Jian‐Kang , He Juan , Deng Yulan , Liu Xuesha , Wang Chun , Yang Shengyong , Chen Qiang , Liu Lunxu , Zhang Guolin , Wei Yu‐Quan , Peng Yong
Published: January 2018

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, but there are few effective treatments. Aberrant microRNA (miRNA) biogenesis is correlated with HCC development. We previously demonstrated that peptidyl‐prolyl cis‐trans isomerase NIMA‐interacting 1 (Pin1) participates in miRNA biogenesis and is a potential HCC treatment target. However, how Pin1 modulates miRNA biogenesis remains obscure. Here, we present in vivo evidence that Pin1 overexpression is directly linked to the development of HCC. Administration with the Pin1 inhibitor (API‐1), a specific small molecule targeting Pin1 peptidyl‐prolyl isomerase domain and inhibiting Pin1 cis‐trans isomerizing activity, suppresses in vitro cell proliferation and migration of HCC cells. But API‐1‐induced Pin1 inhibition is insensitive to HCC cells with low Pin1 expression and/or low exportin‐5 (XPO5) phosphorylation. Mechanistically, Pin1 recognizes and isomerizes the phosphorylated serine‐proline motif of phosphorylated XPO5 and passivates phosphorylated XPO5. Pin1 inhibition by API‐1 maintains the active conformation of phosphorylated XPO5 and restores XPO5‐driven precursor miRNA nuclear‐to‐cytoplasm export, activating anticancer miRNA biogenesis and leading to both in vitro HCC suppression and HCC suppression in xenograft mice. Conclusion: Experimental evidence suggests that Pin1 inhibition by API‐1 up‐regulates miRNA biogenesis by retaining active XPO5 conformation and suppresses HCC development, revealing the mechanism of Pin1‐mediated miRNA biogenesis and unequivocally supporting API‐1 as a drug candidate for HCC therapy, especially for Pin1‐overexpressing, extracellular signal–regulated kinase–activated HCC. (Hepatology 2018).
Chemical and thyroid hormone profile of the bone marrow interstitial fluid in hematologic disorders and patients without primary hematologic disorders
Authors: Krashin Eilon , Ellis Martin , Cohen Keren , Viner Maya , Neumark Eran , Rashid Gloria , Ashur‐Fabian Osnat
Published: January 2018

Bone marrow interstitial fluid (BMIF) has not been well characterized. BMIF was isolated from 60 patients including plasma cell dyscrasias (PCD, n = 33), other primary hematologic disorders (OHD, n = 15), and patients with secondary or nonhemtologic disorders (NHD, n = 12) and analyzed for an array of chemical constituents. These included total cholesterol, glucose, phosphate, creatinine, urea, total protein, albumin, globulins, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, sodium, osmolarity, free triiodothyronine (free T3), total triiodothyronine (total T3), and free tetraiodothyronine (free T4). Levels of BMIF components were compared between patient groups and to plasma levels. Compared with plasma, total cholesterol, total protein, total bilirubin, sodium, and calculated osmolarity were lower in BMIF in all groups (P < 0.05). Calculated globulins and aspartate aminotransferase were lower in BMIF of PCD patients and patients with NHD. Albumin was lower in BMIF of patients with PCD and patients with OHD. Lastly, free T4 was significantly higher in BMIF of patients with PCD and patients with OHD. Similar results were demonstrated in a separate analysis performed in patients with multiple myeloma. To conclude, the chemical and thyroid hormone composition of BMIF differs significantly from plasma in several key constituents.
Testing for nonlinear unit roots in the presence of a structural break with an application to the qualified PPP during the 1997 Asian financial crisis
Authors: Habimana Olivier , Månsson Kristofer , Sjölander Pär
Published: January 2018

This paper applies Monte Carlo simulations to evaluate the size and power properties in the presence of a structural break, for the standard Augmented Dickey‐Fuller (ADF) test versus nonlinear exponential smooth transition autoregressive unit root tests. The break causes the tests to be undersized, and the statistical power considerably decreases. Moreover, the effect is intensified in small samples and very much increased for more persistent nonlinear series. As a remedy, we modify the standard ADF and exponential smooth transition autoregressive unit root tests in order to adjust for a structural break. This improves both the power and the size considerably, even though the empirical size still is lower than the nominal one. More persistent series are more affected by structural breaks, and the new tests are most powerful under the existence of a rather persistent nonlinear data generating process (which is an empirically relevant and common type of data generating process). The proposed tests are applied to investigate mean reversion in the real effective exchange rates of 5 East and Southeast Asian countries, taking into account the structural change in exchange rate regime brought about by the 1997 Asian financial crisis. The empirical findings corroborate our simulation results; the modified more powerful tests are able to reject the unit root in all 5 countries, whereas the tests that do not consider the structural break could only reject in one of these cases.
Electron microscopy of Drosophila garland cell nephrocytes: Optimal preparation, immunostaining and STEM tomography
Authors: Hochapfel Florian , Denk Lucia , Maaßen Christine , Zaytseva Yulia , Rachel Reinhard , Witzgall Ralph , Krahn Michael P.
Published: January 2018

Due to its structural and molecular similarities to mammalian podocytes, the Drosophila nephrocyte emerged as a model system to study podocyte development and associated diseases. Similar to podocytes, nephrocytes establish a slit diaphragm between foot process‐like structures in order to filter the hemolymph. One major obstacle in nephrocyte research is the distinct visualization of this subcellular structure to assess its integrity. Therefore, we developed a specialized dissection and fixation protocol, including high pressure freezing and freeze substitution techniques, to improve the preservation of the intricate ultrastructural details necessary for electron microscopic assessment. By means of scanning transmission electron microscopy (STEM) tomography, a three‐dimensional dataset was generated to further understand the complex architecture of the nephrocyte channel system. Moreover, a staining protocol for immunolabeling of ultrathin sections of Epon‐embedded nephrocytes is discussed, which allows the reliable detection of GFP‐tagged fusion proteins combined with superior sample preservation. Due to the growing number of available GFP‐trap fly lines, this approach is widely applicable for high resolution localization studies in wild type and mutant nephrocytes.
Spontaneous up‐regulation of SIRT1 during osteogenesis contributes to stem cells’ resistance to oxidative stress
Authors: Li Mao , Yan Jinku , Chen Xi , Tam Whitney , Zhou Long , Liu Tao , Pan Guoqing , Lin Jun , Yang Huilin , Pei Ming , He Fan
Published: January 2018

Osteogenic differentiation of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) is a central event in bone formation. However, oxidative stress has a deleterious impact on BM‐MSC osteogenesis. In this study, we hypothesized that oxidative stress influenced BM‐MSC osteogenesis differently in the early or late stages, in which silent information regulator type 1 (SIRT1) played a critical role. A continuous exposure to sublethal concentrations of hydrogen peroxide (H2O2), ranging from 25 to 100 µM for 21 days, resulted in the complete inhibition of BM‐MSC osteogenesis. We found that a 7‐day treatment with H2O2 inhibited the lineage commitment of BM‐MSCs toward osteoblasts, as evidenced by a significant reduction of alkaline phosphatase activity (a typical marker for early osteogenesis). However, moderate oxidative stress did not affect late‐differentiated BM‐MSCs, as there were comparable levels of matrix mineralization (a typical marker for late osteogenesis). In addition, we observed a spontaneous up‐regulation of SIRT1 and intracellular antioxidant enzymes such as superoxide dismutase 2, catalase, and glutathione peroxidase 1, which accounted for the enhanced resistance to oxidative stress upon osteogenic differentiation. Activation of SIRT1 by resveratrol rescued the effect of H2O2 on early‐differentiated BM‐MSCs and inhibition of SIRT1 by nicotinamide intensified the effect of H2O2 on late‐differentiated BM‐MSCs, indicating that the SIRT1‐mediated pathway was actively involved in MSC osteogenesis and antioxidant mechanisms. Our findings uncovered the relationship between SIRT1 and resistance to H2O2‐induced oxidative stress during BM‐MSC osteogenesis, which could provide a new strategy for protecting MSCs from extracellular oxidative stress.
A novel cell line generated using the CRISPR/Cas9 technology as universal quality control material for KRAS G12V mutation testing
Authors: Jia Shiyu , Zhang Rui , Lin Guigao , Peng Rongxue , Gao Peng , Han Yanxi , Fu Yu , Ding Jiansheng , Wu Qisheng , Zhang Kuo , Xie Jiehong , Li Jinming
Published: January 2018

Background

KRAS mutations are the key indicator for EGFR monoclonal antibody‐targeted therapy and acquired drug resistance, and their accurate detection is critical to the clinical decision‐making of colorectal cancer. However, no proper quality control material is available for the current detection methods, particularly next‐generation sequencing (NGS). The ideal quality control material for NGS needs to provide both the tumor mutation gene and the matched background genomic DNA, which is uncataloged in public databases, to accurately distinguish germline polymorphisms and somatic mutations.

Methods

We developed a novel KRAS G12V mutant cell line using the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 (Cas9) technique to make up for the deficiencies in existing quality control material and further validated the feasibility of the cell line as quality control material by amplification refractory mutation system (ARMS), Sanger sequencing, digital PCR (dPCR), and NGS.

Results

We verified that the edited cell line specifically had the G12V mutation, and the validation results presented a high consistency among the four methods of detection. The three cell lines screened contained the G12V mutation and the mutation allele fractions of G12V‐1, G12V‐2, and G12V‐3 were 52.01%, 82.06%, and 17.29%, respectively.

Conclusion

The novel KRAS G12V cell line generated using the CRISPR/Cas9 gene editing system is suitable as a quality control material for all current detection methods and provides a new direction in the development of quality control material.
Tributyltin induces distinct effects on cortical and trabecular bone in female C57Bl/6J mice
Authors: Watt James , Baker Amelia H. , Meeks Brett , Pajevic Paola D. , Morgan Elise F. , Gerstenfeld Louis C. , Schlezinger Jennifer J.
Published: January 2018

The retinoid X receptors (RXR), peroxisome proliferator activated receptor gamma (PPARγ), and liver X receptors (LXR) all have been shown to regulate bone homeostasis. Tributyltin (TBT) is an environmental contaminant that is a dual RXRα/β and PPARγ agonist. TBT induces RXR, PPARγ, and LXR‐mediated gene transcription and suppresses osteoblast differentiation in vitro. Bone marrow multipotent mesenchymal stromal cells derived from female C57BL/6J mice were more sensitive to suppression of osteogenesis by TBT than those derived from male mice. In vivo, oral gavage of 12 week old female, C57Bl/6J mice with 10 mg/kg TBT for 10 weeks resulted in femurs with a smaller cross‐sectional area and thinner cortex. Surprisingly, TBT induced significant increases in trabecular thickness, number, and bone volume fraction. TBT treatment did not change the Rankl:Opg RNA ratio in whole bone, and histological analyses showed that osteoclasts in the trabecular space were minimally reduced. In contrast, expression of cardiotrophin‐1, an osteoblastogenic cytokine secreted by osteoclasts, increased. In primary bone marrow macrophage cultures, TBT marginally inhibited the number of osteoclasts that differentiated, in spite of significantly suppressing expression of osteoclast markers Nfatc1, Acp5, and Ctsk and resorptive activity. TBT induced expression of RXR‐ and LXR‐dependent genes in whole bone and in vitro osteoclast cultures. However, only an RXR antagonist, but not an LXR antagonist, significantly inhibited TBTs ability to suppress osteoclast differentiation. These results suggest that TBT has distinct effects on cortical versus trabecular bone, likely resulting from independent effects on osteoblast and osteoclast differentiation that are mediated through RXR.
Metformin attenuates folic‐acid induced renal fibrosis in mice
Authors: Yi Hao , Huang Chunling , Shi Ying , Cao Qinghua , Zhao Yongli , Zhang Ling , Chen Jason , Pollock Carol A. , Chen Xin‐Ming
Published: January 2018

Progressive tubulointerstitial fibrosis has been recognized as a common pathological process that leads to the progression of all chronic kidney disease (CKD). Innovative strategies are needed to both prevent and treat CKD. Inflammatory and fibrotic signaling pathways play central roles in the progression of CKD regardless of aetiology. Hence, targeting inflammatory and fibrotic responses holds promise to limit renal fibrosis. Metformin has been the most prescribed glucose‐lowering medicine worldwide, and its potential for many other therapeutic applications is also being explored intensively. Increasing evidence indicates metformin may limit renal fibrosis. However, the exact mechanisms whereby metformin limits renal injury are not fully understood. The anti‐fibrotic effects of metformin, independent of improved glycaemic control was examined in a folic acid‐induced mouse model of nephropathy for 14 days. Human proximal tubular cells (HK2 cells) exposed to TGF‐β1 were used in in vitro models to examine mechanistic pathways. Folic acid induced nephropathy was associated with the overexpression of inflammatory markers MCP‐1, F4/80, type IV collagen, fibronectin and TGF‐β1 compared to control groups, which were partially attenuated by metformin treatment. In vitro studies confirmed that metformin inhibited TGF‐β1 induced inflammatory and fibrotic responses through Smad3, ERK1/2, and P38 pathways in human renal proximal tubular cells. These results suggest that metoformin attenuates folic acid‐induced renal interstitial fibrogenesis through TGF‐β1 signaling pathways.
Hedgehog signaling pathway: Epigenetic regulation and role in disease and cancer development
Authors: Fattahi Sadegh , Pilehchian Langroudi Maryam , Akhavan‐Niaki Haleh
Published: January 2018

The evolutionarily conserved Hedgehog (Hh) signaling pathway have critical roles in development and homeostasis of tissues. Under physiological conditions, Hh is controlled at different levels via stem cell maintenance and tissue regeneration. Aberrant activation of this signaling pathway may occur in a wide range of human diseases including different types of cancer. In this review we present a concise overview on the key genes composing Hh signaling pathway and provide recent advances on the molecular mechanisms that regulate Hh signaling pathway from extracellular and receptors to the cytoplasmic and nuclear machinery with a highlight on the role of microRNAs. Furthermore, we focus on critical studies demonstrating dysregulation of the Hh pathway in human disease development, and potential therapeutic implications. Finally, we introduce recent therapeutic drugs acting as Shh signaling pathway inhibitors, including those in clinical trials and preclinical studies.
Are Two Reasons Better Than One? The Role of Appeal Type in Consumer Responses to Sustainable Products
Authors: Edinger‐Schons Laura Marie , Sipilä Jenni , Sen Sankar , Mende Gina , Wieseke Jan
Published: January 2018

In the face of the growing prevalence of multiple appeals to sustainable consumption in marketers’ sustainable product communications, we examine the efficacy, in terms of consumer reactions, of adding an extrinsic appeal (e.g., “Purchase this green product to save money!”) to an intrinsic appeal (e.g., “Purchase this green product to save the environment!”) based communication for a sustainable product. Three studies provide support for our basic assertion that, compared to an intrinsic appeal, joint appeals (i.e., an intrinsic and extrinsic appeal together) reduce consumer preference for sustainable products. As well, these studies demonstrate that this adverse effect of joint appeals is based on a lowering of consumers’ attributions of the company's sustainability efforts to intrinsic motives (e.g., to the company's genuine concern for the environment). Finally, not all consumers react adversely to joint appeals; relative to intrinsic appeals, such appeals increase, rather than decrease, the intrinsic attributions and sustainable product preferences for consumers with lower involvement with sustainable consumption.
Consumers Avoid Buying From Firms With Higher CEO‐to‐Worker Pay Ratios
Authors: Mohan Bhavya , Schlager Tobias , Deshpandé Rohit , Norton Michael I.
Published: January 2018

We document a novel driver of consumer behavior: pay ratio disclosure. Swiss corporation performance data gathered during a legally mandated pay ratio referendum reveals that salient high pay ratios are associated with decreased firm sales (Pilot Study). An incentive‐compatible field experiment shows that, when ratios are revealed, consumers avoid firms with high ratios relative to competitors (Study 1). Finally, the effect of high pay ratios also depends on consumers’ political ideology: Democrats and Independents show decreased purchase intentions for products sold by firms with high ratios, whereas Republicans are unaffected (Study 2).
Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism
Authors: Pierce Janet D. , Gupte Raeesa , Thimmesch Amanda , Shen Qiuhua , Hiebert John B. , Brooks William M. , Clancy Richard L. , Diaz Francisco J. , Harris Janna L.
Published: January 2018

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over‐the‐counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra‐arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline‐TBI, (2) ubiquinol 30 minutes before TBI (UB‐PreTBI), or (3) ubiquinol 30 minutes after TBI (UB‐PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C‐terminal hydrolase‐L1 (UCH‐L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury‐induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.
Annotation of gut bacterial taxonomic and functional diversity in Spodoptera litura and Spilosoma obliqua
Authors: Bapatla Kiran G. , Singh Arjun , Yeddula Srujana , Patil Ramanagouda H.
Published: January 2018

The insect gut has been the house of many taxonomically and physiologically diverse groups of microbial colonizers as symbionts and commensals, which are evolving to support the physiological requirement of insects. Lepidoptera is one of the important family of class hexapoda, comprising agriculture insect pest Spodoptera litura and Spilosoma obliqua. Information on gut microbiota and their functional role in these insects was meager to elucidate the wide‐ranging survivalist mechanisms. In this context, we analyzed the composition, diversity and functional role of gut bacteria in S. litura and S. obliqua collected from soybean and sunflower crops, respectively, using Next Generation Sequencing of 16S rRNA. A total of 3427 and 206 Operation Taxonomic Units (OTUs) were identified in S. litura and S. obliqua gut metagenome, respectively. Highest number of sequences were annotated to unclassified bacteria (34%), followed by Proteobacteria (27%), and Chlorobi (14%) in S. litura, while S. obliqua has significant representation of Firmicutes (48%), followed by Bacteroidetes (20%), and unclassified bacteria (11%). Functionality of both metagenomes revealed, high abundance of ammonia oxidizers (20.1 58.0%) followed by relative abundance of detoxifying processes – dehalogenation (17.4–41.2%) and aromatic hydrocarbons degradation (1.1–3.1%). This study highlights the significance of the inherent microbiome of two defoliators in shaping the metagenome for nutrition and detoxifying the chemical molecules, and opens an avenue for exploring role of insect gut bacteria in host selection, metabolic endurance of insecticides and synergistic or agonistic mechanisms inside gut of insects feeding on insect‐resistant biotech crops.
Raman spectrum of ethane in methane environment
Authors: Petrov Dmitry V.
Published: January 2018

Changes are investigated in the positions, half‐widths, and intensities of the Q‐branches of the main ethane Raman bands (ν3, 2ν6, 2ν2, 2ν8, and ν1) in the methane/ethane mixture depending on methane concentration at the fixed pressure of 25 bar. It was found that with increasing methane fraction, the above‐mentioned ethane Raman bands, with the exception of ν3, are shifted to the high wavenumbers, and the bands of 2ν8/ν1 Fermi doublet demonstrate a violation of the linear dependence of the intensity on the concentration. The data obtained will be useful for diagnostics of natural gas composition using Raman spectroscopy.
Emergency Department Patient Perceptions of Transvaginal Ultrasound for Complications of First‐Trimester Pregnancy
Authors: Panebianco Nova , Shofer Frances , O'Conor Katie , Wihbey Tristan , Mulugeta Lakeisha , Baston Cameron M , Suzuki Evan , Alghamdi Adel , Dean Anthony
Published: January 2018

Objectives

Emergency department (ED) transvaginal ultrasound (US) is underused in clinical practice. This study assessed pregnant women's perceptions of ED transvaginal US in terms of pain, embarrassment, anxiety, and willingness to receive the procedure. Secondary variables include physicians' perceptions of patients' experiences.

Methods

Women undergoing US examinations for complications of first‐trimester pregnancy were prospectively surveyed before any US and after ED and/or radiology transvaginal US. Patients' and physicians' assessments of pain, embarrassment, and anxiety were measured with visual analog scales (0–100).

Results

A total of 398 women were enrolled. In the pre‐US survey, the median anxiety score was 14 (interquartile range, 3–51), and 96% of patients were willing to have an ED transvaginal US if necessary. Of those who had ED transvaginal US, 96% would agree to have another examination. Patients reported minimal pain/embarrassment, and there was no difference if performed in the ED versus radiology (median pain, 11.5 versus 13; P = .433; median embarrassment, 7 versus 4; P = .345). Of the 48 who had both ED and radiology transvaginal US, 85% thought the ED transvaginal US was worthwhile. Physicians accurately assessed patient's embarrassment and pain (mean differences, 3.5 and –1.9, respectively; P > .25 for both); however, they overestimated them relative to the pelvic examination (mean difference for embarrassment, 12.8; P < .0001; pain, 8.0; P = .01).

Conclusions

Pregnant ED patients report low levels of anxiety, pain, and embarrassment, and after ED transvaginal US, 96% would agree to have the examination again. There is no difference in pain/embarrassment between ED and radiology transvaginal US. Emergency department physicians accurately assessed patients' pain and embarrassment with ED transvaginal US but overestimated them compared to the pelvic examination.
Unique Transitions in Morphology and Characteristics of Porous Poly(Lactic Acid) Enantiomers
Authors: Kanno Tomonari , Uyama Hiroshi
Published: January 2018

This study examines unique changes in the morphology and physical properties of monolithic poly(lactic acid) (PLA) enantiomers. It is revealed for the first time that PLA monoliths containing stereocomplex (sc) crystals are successfully produced using enantiomeric poly(L‐lactic acid) (PLLA) and poly(D‐lactic acid) (PDLA) using a simple phase separation process with ternary solvent (1,4‐dioxane/2‐butanone/water). The basic structure of the monoliths is changed drastically from needle‐like to spherical morphology until reaching a PLLA/PDLA ratio to equivalence. The PLA monolith prepared from a stoichiometric amount of PLLA/PDLA has high sc crystallinity without any homochiral crystals, and it shows higher melting temperature (226 °C), surface area (131 m2 g−1), and water contact angle (144.5°) compared with those of neat PLLA (180 °C, 86 m2 g−1, and 137.5°, respectively). Moreover, this sc‐PLA monolith exhibits excellent resistance to several good solvents of PLLA, whereas the pristine PLLA monolith is dissolved instantly in these solvents.
Smectic‐B Liquid Single Crystal Elastomers as Efficient Optical Mechanotransducers
Authors: Escalera‐López Daniel , Garcia‐Amorós Jaume , Velasco Dolores
Published: January 2018

Carbazole‐based liquid single‐crystal elastomers (LSCEs) are valuable materials to convert mechanical forces into optical signals, i.e., optical mechanotransduction. The identification and rationalization of the different structural factors governing the mechanotransduction process are essential to guide the future design of these smart sensing materials. Herein, how the type of mesophase displayed by the elastomer impacts its transducing capabilities is explored. Remarkably, smectic‐B LSCEs are significantly more efficient mechanotransducers than their nematic analogs, independent of the length of the flexible spacer that connects the fluorogenic monomers to the main polymeric backbone. In this instance, the fluorogenic moieties are located within the smectic lamellae formed by the mesogenic units, thereby forcing a stronger interaction between both the platforms and resulting in a much more effective fluorescence quenching upon deformation.
Weighted boundedness of the 2‐fold product of Hardy–Littlewood maximal operators
Authors: Carro María J. , Roure Eduard
Published: January 2018

We study new weighted estimates for the 2‐fold product of Hardy–Littlewood maximal operators defined by . This operator appears very naturally in the theory of bilinear operators such as the bilinear Calderón–Zygmund operators, the bilinear Hardy–Littlewood maximal operator introduced by Calderón or in the study of pseudodifferential operators. To this end, we need to study Hölder's inequality for Lorentz spaces with change of measures
urn:x-wiley:0025584X:media:mana201700271:mana201700271-math-0002Unfortunately, we shall prove that this inequality does not hold, in general, and we shall have to consider a weaker version of it.
Microstructures and mechanical properties of as‐cast titanium–zirconium–molybdenum ternary alloys
Authors: Yang C.D. , Wang S.P. , Shi J.J. , Wang C.H. , Ren Z.M. , Cao G.H.
Published: January 2018

In this study titanium–zirconium–molybdenum alloys (Ti50Zr50)100‐xMox (xMo; x = 0 at.%, 1 at.%, 3 at.%, 5 at.% or 7 at.%) were investigated, focusing on the effect of molybdenum addition on their microstructures and mechanical properties. Transmission electron microscopy observations revealed that the binary Ti50Zr50 alloy was composed entirely of an acicular hexagonal structure of the α’ phase. When the molybdenum content was 1 at.%, the alloy was composed of β and ω phases. However, when 3 at.% or more molybdenum was added, only the equiaxed, retained β phase was observed. Tensile tests at room temperature indicated that the mechanical properties of the 1Mo alloy were inferior owing to the embrittlement effects of the ω phase and the difficulty of dislocation motion through the ω phase. Our research suggested that the 5Mo alloy had excellent ductility (16.5 %) as well as adequate strength (780 MPa). The improved mechanical properties were attributed to the enhanced stability of the β phase and the disappearance of the ω phase.
Planktonic microbial profiling in water samples from a Brazilian Amazonian reservoir
Authors: Cabral Bianca C. A. , Hoffmann Luísa , Budowle Bruce , Ürményi Turán P. , Moura‐Neto Rodrigo S. , Azevedo Sandra M. F. O. , Silva Rosane
Published: January 2018

Our comprehension of the dynamics and diversity of freshwater planktonic bacterial communities is far from complete concerning the Brazilian Amazonian region. Therefore, reference studies are urgently needed. We mapped bacterial communities present in the planktonic communities of a freshwater artificial reservoir located in the western Amazonian basin. Two samples were obtained from rainy and dry seasons, the periods during which water quality and plankton diversity undergo the most significant changes. Hypervariable 16S rRNA and shotgun sequencing were performed to describe the first reference of a microbial community in an Amazonian lentic system. Microbial composition consisted mainly of Betaproteobacteria, Cyanobacteria, Alphaproteobacteria, and Actinobacteria in the dry period. The bacteria distribution in the rainy period was notably absent of Cyanobacteria. Microcystis was observed in the dry period in which the gene cluster for cyanotoxins was found. Iron acquisition gene group was higher in the sample from the rainy season. This work mapped the first inventory of the planktonic microbial community of a large water reservoir in the Amazon, providing a reference for future functional studies and determining other communities and how they interact.
Differential impact of CX3CL1 on lung cancer prognosis in smokers and non‐smokers
Authors: Su Ying‐Chieh , Chang Han , Sun Shih‐Jung , Liao Cheng‐Yi , Wang Ling‐Yi , Ko Jiunn‐Lang , Chang Jinghua T.
Published: January 2018

CX3CL1 is a unique chemokine, expressed in both soluble and membrane bound forms, which mediates different biological activities. Recent studies have revealed the potential of CX3CL1 signaling pathway as a target for the treatment of inflammation and cancer. The correlation between expression of CX3CL1 and prognosis of patients varies among cancers. In this study, based on CX3CL1 immunohistochemistry in non‐small cell lung cancer, CX3CL1 levels were positively associated with cancer stage (Pearson chi‐square, P = 0.048) and lymph node status (P = 0.033). Interestingly, survival effects of CX3CL1 were only observed in patients with smoking history and adenocarcinoma (AD, log rank, P = 0.027), but not in patients with squamous cell carcinoma (SQ). The median survival time of patients with smoking history and low level CX3CL1 expressing AD was 1538 days, while that of patients with smoking history and high level CX3CL1 expressing AD was 396 days. Cox regression models showed adverse effects of high CX3CL1 levels only in AD patients with smoking history (hazard ratio = 3.01, p = 0.034), but not in AD patients without smoking history or in SQ patients with smoking history. The results of this study suggest that CX3CL1 plays different roles in lung tumorigenesis in smokers and non‐smokers, and different CX3CL1‐based therapeutic strategies are needed depending on patient smoking status and tumor type. Furthermore, high level of CX3CL1 expression enhances nodal metastasis by activating JNK & MMP2/MMP9 activity in lung cancer cells.