Aqueous synthesis of Ag and Mn co-doped In2S3/ZnS quantum dots with tunable emission for dual-modal targeted imaging

Publication date: Available online 18 December 2016
Source:Acta Biomaterialia
Author(s): Pei-Yu Lai, Chih-Ching Huang, Tzung-Han Chou, Keng-Liang Ou, Jia-Yaw Chang
Here, we present the microwave-assisted synthesis of In2S3/ZnS core/shell quantum dots (QDs) co-doped with Ag⁺ and Mn²⁺ (referred to as AgMn:In2S3/ZnS). Ag⁺ altered the optical properties of the host QDs, whereas the spin magnetic moment (S = 5/2) of Mn²⁺ efficiently induced the longitudinal relaxation of water protons. To the best of our knowledge, this is the first report of the aqueous synthesis of color-tunable AgMn:In2S3/ZnS core/shell QDs with magnetic properties. The synthetic procedure is rapid, facile, reproducible, and scalable. The obtained QDs offered a satisfactory quantum yield (45%), high longitudinal relaxivity (6.84 s^–1 mM^–1), and robust photostability. In addition, they exhibited excellent stability over a wide pH range (5–12) and high ionic strength (0.15–2.0 M NaCl). As seen by confocal microscopy and magnetic resonance imaging, AgMn:In2S3/ZnS conjugated to hyaluronic acid (referred to as AgMn:In2S3/ZnS@HA) efficiently and specifically targeted cluster determinant 44, a receptor overexpressed on cancer cells. Moreover, AgMn:In2S3/ZnS@HA showed negligible cytotoxicity in vitro and in vivo, rendering it a promising diagnostic probe for dual-modal imaging in clinical applications.

Graphical abstract

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Injectable Hyaluronic Acid Down-regulates Interferon Signaling Molecules, IGFBP3 and IFIT3 in the Bovine Intervertebral Disc

Publication date: Available online 18 December 2016
Source:Acta Biomaterialia
Author(s): Zepur Kazezian, Zhen Li, Mauro Alini, Sibylle Grad, Abhay Pandit
Low back pain which is a major cause of disability for people aged between 20 and 50 years imposes a serious socio-economic burden. The current focus of regenerative medicine is on identifying molecular markers to facilitate the design of targeted therapeutics. Previously, we have demonstrated that expression of the anti-proliferative interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and pro-apoptotic insulin-like growth factor-binding protein-3 (IGFBP3), are up-regulated as downstream targets of the inflammatory cytokine interferon α (IFNα) signaling pathway in the human annulus fibrosus (AF). Here, we hypothesized that injection of hyaluronic acid (HA) would have an anti-inflammatory and matrix modulatory effect on injured and IFNα2β inflamed bovine intervertebral discs (IVD). Discs with an AF defect and challenged with IFNα2β were used in a bovine IVD organ culture model to test the effect of HA on the IFNα2β pathway, as well as the matrix proteins aggrecan and collagen I. qRT-PCR was used to assess the gene expression of IFNα2β signaling molecules. Additionally, immunostaining was used to measure protein expression. Our results show that HA treatment significantly down-regulates IFNAR1, IFNAR2, STAT1/2, JAK1, IFIT3 and IGFBP3 mRNA expression in the inflamed groups. Protein analysis confirmed the PCR results. In the extracellular matrix, aggrecan and collagen I were up-regulated while ADAMTS4 was down-regulated upon treatment of the injured and inflamed discs with HA. Hence, HA demonstrates both an anti-inflammatory role, resulting in the down-regulation of IFIT3 and IGFBP3 in the AF, and a matrix modulatory effect by up-regulating aggrecan and collagen I expression.Statement of significanceThe pro-inflammatory environment of the degenerated IVD represents a challenge for regenerative therapies. The study demonstrates that hyaluronan acts as an anti-inflammatory molecule by down-regulating IFNAR1 and IFNAR2, the signalling molecules STAT1, STAT2, JAK1 and the downstream apoptotic targets IGFBP3 and IFIT3. We also demonstrated that hyaluronan modulates the disc matrix environment by increasing aggrecan and collagen I synthesis and down-regulating ADAMTS4 that degrades the matrix under inflammatory conditions. The significance of this work lies in the fact that hyaluronan acts as an anti-inflammatory molecule by shifting the disc environment towards a more anabolic state and by promoting native IVD matrix production.

Graphical abstract

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Self-assembled supramolecular polymers with tailorable properties that enhance cell attachment and proliferation

Publication date: Available online 18 December 2016
Source:Acta Biomaterialia
Author(s): Chih-Chia Cheng, Duu-Jong Lee, Jem-Kun Chen
Self-assembled supramolecular scaffolds, a combination of noncovalent interactions within a biocompatible polymer substrate, can be used for efficient construction of highly-controlled self-organizing hierarchical structures; these newly-developed biomaterials exhibit excellent mechanical properties, tunable surface hydrophilicity, low cytotoxicity and high biodegradability, making them highly attractive for tissue engineering and regenerative medicine applications. Herein, we demonstrate a novel supramolecular poly(ε-caprolactone) (PCL) containing self-complementary sextuple hydrogen-bonded uracil-diamidopyridine (U-DPy) moieties, which undergoes spontaneous self-assembly to form supramolecular polymer networks. Inclusion of various U-DPy contents enhanced the mechanical strength and viscosities of the resulting materials by up to two orders of magnitude compared to control PCL. Surface wettability and morphological studies confirmed physically-crosslinked films can be readily tailored to provide the desired surface properties. Cell viability assays indicated the excellent in vitro biocompatibility of U-DPy-functionalized substrates and indicate the potential of these materials for various biomedical applications. More importantly, mouse fibroblast NIH/3T3 cells cultured on these substrates displayed a more elongated cell morphology and had substantially higher cell densities than cells seeded on control PCL substrate, which indicates that introduction of U-DPy moieties into polymer matrixes could be used to create tissue culture surfaces that enhance cell attachment and proliferation. This new system is suggested as a potential route towards the practical realization of next-generation tissue-engineering scaffolds.Statement of SignificanceIn this study, we report a significant breakthrough in development of self-assembled supramolecular polymers to form well-defined scaffolds through self-complementary hydrogen-bonding interactions. These newly developed materials exhibited extremely good mechanical properties, fine-tunable hydrophilic characteristics and excellent biocompatibility due to hydrogen-bond-induced physical cross-linking. Importantly, cell adhesion and proliferation assays indicated that these substrates efficiently promoted the growth of mouse embryonic fibroblasts NIH/3T3 cells in vitro. Thus, this finding provides a simple and effective route for the development of next-generation tissue-engineering scaffolds that have improved mechanical properties, increased surface hydrophilicity and can enhance the growth and biological activity of adherent cells.

Graphical abstract

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A simple basis for determination of the Modulus and Hydraulic Conductivity of human ocular surface using nano-indentation

Publication date: Available online 18 December 2016
Source:Acta Biomaterialia
Author(s): M.V. Swain, J. Nohava, P. Eberwein
This paper presents a simple analysis based upon Darcy's Law and indentation contact mechanics to determine the effective hydraulic conductivity and elastic modulus of fluid filled tissues. The approach is illustrated with the mechanical response of the human ocular surface using a 500 μm radius spherical tipped indenter. Indentations of various regions of the ocular surface including the corneal stroma, limbal region and sclera have been conducted. Force-control indentations were made to a maximum force, which was maintained before unloading. Measurements of the indentation response of cornea at three different loading rates were also made. Elastic like response was observed during loading, which was followed by extensive creep prior to unloading.Statement of significanceThis manuscript attempts to provide a relatively simply model for the contact loading of fluid containing tissues and materials. It shows that the response of such materials provides a basis for determining the effective modulus and effective hydraulic conductivity (permeability) in much the same manner that hardness and modulus do for the indentation of elastic-plastic materials. Eye tissue with its anisotropic elastic and permeability properties is used to illustrate the approach.

Graphical abstract

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Sustained tobramycin release from polyphosphate double network hydrogels

Publication date: Available online 18 December 2016
Source:Acta Biomaterialia
Author(s): Dwight D. Lane, Amber K. Fessler, Seungah Goo, Dustin L. Williams, Russell J. Stewart
Sustained local delivery of antibiotics from a drug reservoir to treat or prevent bacterial infections can avoid many of the drawbacks of systemic administration of antibiotics. Prolonged local release of high concentrations of antibiotics may also be more effective at treating bacteria in established biofilm populations that are resistant to systemic antibiotics. A double network hydrogel comprising an organic polyphosphate pre-polymer network polymerized within a polyacrylamide network de-swelled to about 50% of its initial volume when the polyphosphate network was crosslinked with polycationic tobramycin, an aminoglycoside antibiotic. The antibiotic-loaded hydrogels contained approximately 200 mg/ml of tobramycin. The hydrogels continuously released daily amounts of tobramycin above the Pseudomonas aeruginosa minimal bactericidal concentration for greater than 50 days, over the pH range 6.0 to 8.0, and completely eradicated established P. aeruginosa biofilms within 72 h in a flow cell bioreactor. The presence of physiological concentrations of Mg²⁺ and Ca²⁺ ions doubled the cumulative release over 60 days. The polyphosphate hydrogels show promise as materials for sustained localized tobramycin delivery to prevent post-operative P. aeruginosa infections including infections established in biofilms.Statement of SignificancePolyphosphate hydrogels were loaded with high concentrations of tobramycin. The hydrogels provided sustained release of bactericidal concentrations of tobramycin for 50 days, and were capable of completely eradicating P. aeruginosa in established biofilms. The hydrogels have potential for localized prevention or treatment of P. aeruginosa infections.

Graphical abstract

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Controlling the selective and directional migration of hepatocytes by a complementary density gradient of glycosylated hyperbranched polymers and poly(ethylene glycol) molecules

Publication date: Available online 18 December 2016
Source:Acta Biomaterialia
Author(s): Su Liang, Shan Yu, Ning Zhou, Jun Deng, Changyou Gao
Repair and regeneration of defected tissues and organs depends strongly on the directional migration of targeted cells, for example, the enhancement of directional migration of hepatocytes could be helpful in liver regeneration and transplantation. Herein a complementary gradient of galactose-modified hyperbranched polymers (LA-HPMA) and poly(ethylene glycol) (PEG) molecules was designed and prepared on a same substrate. Characterizations of X-ray photoelectron spectrometry and quartz crystal microbalance with dissipation (QCM-d) demonstrated the unidirectional change in grafting density of LA-HPMA and PEG molecules, respectively. On the LA-HPMA/PEG complementary gradient surface, the human hepatoma (HepG2) cells showed preferential orientation and enhanced directional migration toward the region of lower PEG density and higher LA-HPMA density. By contrast, the mouse embryonic fibroblasts (NIH3T3) showed random migration irrelevant to the gradient. The success of the complementary gradient relies on the specific interaction between galactose and asialoglyco protein receptor (ASGPR) expressed on HepG2 cells.SignificanceA continuous complementary gradient of glycosylated hyperbranched polymers and PEG is fabricated to govern cell-substrate interaction.Selective and directional migration of hepatocytes over fibroblasts is achieved on the complementary gradient.A new perspective on designing complex biomaterials for desired tissue regeneration.

Graphical abstract

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Title page

Publication date: September–December 2016
Source:Current Problems in Cancer, Volume 40, Issues 5–6





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Table of Contents

Publication date: September–December 2016
Source:Current Problems in Cancer, Volume 40, Issues 5–6





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Amyloidosis: A rare disease with varied manifestations

Publication date: September–December 2016
Source:Current Problems in Cancer, Volume 40, Issues 5–6
Author(s): Beata Holkova




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Title page

Publication date: March–August 2016
Source:Current Problems in Cancer, Volume 40, Issues 2–4





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Table of Contents

Publication date: March–August 2016
Source:Current Problems in Cancer, Volume 40, Issues 2–4





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Adaptation to Leftward Shifting Prisms Alters Motor Interhemispheric Inhibition

Adaptation to rightward shifting prisms (rightward prism adaptation, RPA) ameliorates neglect symptoms in patients while adaptation to leftward shifting prisms (leftward prism adaptation, LPA) induces neglect-like behaviors in healthy subjects. It has been hypothesized that prism adaptation (PA) modulates interhemispheric balance between the parietal cortices by inhibiting the posterior parietal cortex (PPC) contralateral to the prismatic deviation, but PA's effects on interhemispheric inhibition (IHI) have not been directly investigated. Since there are hyper-excitable connections between the PPC and primary motor cortex (M1) in the left hemisphere of neglect patients, we reasoned that LPA might mimic right hemisphere lesions by reducing parietal IHI, hyper-exciting the left PPC and PPC-M1 connections, and in turn altering IHI at the motor level. Namely, we hypothesized that LPA would increase IHI from the left to the right M1. We examined changes in left-to-right and right-to-left IHI between the 2 M1s using the ipsilateral silent period (iSP) (Meyer et al. 1995) before and after either LPA or RPA. The iSP was significantly longer after LPA but only from left-to-right and it did not change at all after RPA. This is the first physiological demonstration that LPA alters IHI in the healthy brain.

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Parsing the Role of the Hippocampus in Approach-Avoidance Conflict

The hippocampus plays a central role in the approach–avoidance conflict that is central to the genesis of anxiety. However, its exact functional contribution has yet to be identified. We designed a novel gambling task that generated approach–avoidance conflict while controlling for spatial processing. We fit subjects' behavior using a model that quantified the subjective values of choice options, and recorded neural signals using functional magnetic resonance imaging (fMRI). Distinct functional signals were observed in anterior hippocampus, with inferior hippocampus selectively recruited when subjects rejected a gamble, to a degree that covaried with individual differences in anxiety. The superior anterior hippocampus, in contrast, uniquely demonstrated value signals that were potentiated in the context of approach–avoidance conflict. These results implicate the anterior hippocampus in behavioral avoidance and choice monitoring, in a manner relevant to understanding its role in anxiety. Our findings highlight interactions between subregions of the hippocampus as an important focus for future study.

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Genetic engineering: CREATE-ing genome-wide designed mutations

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Transcriptional architecture of the mammalian circadian clock

Next-generation sequencing approaches have yielded new insights into circadian function. Here, Takahashi reviews genome-wide analyses of the clock transcriptional feedback loop in mammals, which reveal a global circadian regulation of transcription factor occupancy, RNA polymerase II recruitment and initiation, nascent transcription and chromatin remodelling.

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Cutaneous Merkel cell carcinoma: multiple asynchronous primary lesions in a patient on immunosuppressive therapy

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New guidelines for management of febrile seizures in Japan

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Jun Natsume, Shin-ichiro Hamano, Kuniaki Iyoda, Hideaki Kanemura, Masaya Kubota, Masakazu Mimaki, Shinichi Niijima, Takuya Tanabe, Harumi Yoshinaga, Noriko Kojimahara, Hirohumi Komaki, Kenji Sugai, Tokiko Fukuda, Yoshihiro Maegaki, Hideo Sugie
In 2015, the Japanese Society of Child Neurology released new guidelines for the management of febrile seizures, the first update of such guidelines since 1996. In 1988, the Conference on Febrile Convulsions in Japan published "Guidelines for the Treatment of Febrile Seizures." The Task Committee of the Conference proposed a revised version of the guidelines in 1996; that version released in 1996 was used for the next 19years in Japan for the clinical management of children with febrile seizures. Although the guidelines were very helpful for many clinicians, new guidelines were needed to reflect changes in public health and the dissemination of new medical evidence. The Japanese Society of Child Neurology formed a working group in 2012, and published the new guidelines in March 2015. The guidelines include emergency care, application of electroencephalography, neuroimaging, prophylactic diazepam, antipyretics, drugs needing special attention, and vaccines. While the new guidelines contain updated clinical recommendations, many unsolved questions remain. These questions should be clarified by future clinical research.



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Prenatal irradiation–induced brain neuropathology and cognitive impairment

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Bo Yang, Bo Xu Ren, Feng Ru Tang
Embryo/fetus is much more radiosensitive than neonatal and adult human being. The main potential effects of pre-natal radiation exposure on the human brain include growth retardation, small head/brain size, mental retardation, neocortical ectopias, callosal agenesis and brain tumor which may result in a lifetime poor quality of life. The patterns of prenatal radiation-induced effects are dependent not only on the stages of fetal development, the sensitivity of tissues and organs, but also on radiation sources, doses, dose rates. With the increased use of low dose radiation for diagnostic or radiotherapeutic purposes in recent years, combined with postnatal negative health effect after prenatal radiation exposure to fallout of Chernobyl nuclear power plant accident, the great anxiety and unnecessary termination of pregnancies after the nuclear disaster, there is a growing concern about the health effect of radiological examinations or therapies in pregnant women. In this paper, we reviewed current research progresses on pre-natal ionizing irradiation–induced abnormal brain structure changes. Subsequent postnatal neuropsychological and neurological diseases were provided. Relationship between irradiation and brain aging was briefly mentioned. The relevant molecular mechanisms were also discussed. Future research directions were proposed at the end of this paper. With limited human data available, we hoped that systematical review of animal data could relight research interests on prenatal low dose/dose rate irradiation–induced brain microanatomical changes and subsequent neurological and neuropsychological disorders.



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The pathology of incipient polymicrogyria

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Phedias Diamandis, David Chitayat, Ants Toi, S. Blaser, Patrick Shannon
ObjectiveTo characterise the early tissue changes of post encephaloclastic polymicrogyria in the human fetus.MethodsWe identified and reviewed the clinical histories and autopsy pathology of post ischemic fetal cerebral cortical injury at less than 30weeks gestational age (GA). The histology of local cortical abnormalities was examined with neuronal, glial, microglial and vascular immunohistochemical markers.ResultsWe identified eight cases ranging from 18 to 29weeks GA: 5 cases show full thickness cortical infarcts and 3 show periSylvian post-ischemic necrosis of the cerebral cortex. The maximal age is less than 10weeks after injury. There are abnormalities in gross fissuration as early as one month after injury. Disruption of the pia limitans was associated with a microglial and glial response and full thickness cortical injury. Macrophages were often seen accumulating deep to abnormal cortex. Hyperplasia of the subpial granular cell layer was universal in perilesional cortex. Cajal Retzius neuron hyperplasia, aggregation, and both superficial and deep displacement were noted. Where there was loss and dispersal of early cortical pyramidal neurons there was usually no pseudolaminar necrosis. Radial glia by 18weeks GA showed altered growth patterns and lateral branching. Altered migration of primitive elements was often prominent. Particularly prior to 20weeks GA subadjacent subplate neurons showed striking hypertrophy.ConclusionsThe array of histological changes encompasses all tissue elements of the affected brains, early in the evolution polymicrogyria. Although subpial alterations were ubiquitous, not all changes are referable to alterations in the pia limitans. The role of the necroinflammatory response in the genesis of abnormal cytoarchitecture deserves further study.



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Longitudinal change in white matter in preterm infants without magnetic resonance imaging abnormalities: Assessment of serial diffusion tensor imaging and their relationship to neurodevelopmental outcomes

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Satoshi Kidowaki, Masafumi Morimoto, Kei Yamada, Koji Sakai, Masashi Zuiki, Hiroshi Maeda, Satoshi Yamashita, Takashi Morita, Tatsuji Hasegawa, Tomohiro Chiyonobu, Sachiko Tokuda, Hajime Hosoi
PurposeWe used diffusion tensor imaging (DTI) to evaluate longitudinal changes in fractional anisotropy (FA) of white matter tracts in preterm infants without abnormal magnetic resonance imaging (MRI) findings. Imaging was conducted at term equivalent age (TEA) and 1year of corrected age. Furthermore, we assessed correlations between FA and neurodevelopmental outcomes at 3years of corrected age to investigate brain prematurity of preterm infants without MRI abnormalities.MethodsPreterm infants underwent serial MRI at TEA and 1year of corrected age. Of these, 13 infants entered a retrospective study, undergoing neurodevelopmental assessment at 3years of corrected age. These infants were divided into two groups depending on gestational age (GA): <26weeks and ⩾26weeks. DTI-based tractography was performed to obtain the FA of the motor tract, sensory tract, superior cerebellar peduncle, middle cerebellar peduncle, and corpus callosum. FA was compared between two groups, and correlations between FA and neurodevelopmental outcomes were assessed.ResultsFA of the splenium at TEA was significantly different between the two groups divided according to GA. However, this difference was no longer observed at 1year of corrected age. There was no correlation between FA of the splenium at TEA and neurodevelopmental assessment scores at 3years of corrected age.ConclusionsAt TEA, FA of the splenium was lower in younger GA infants without MRI abnormalities, but this may not affect subsequent neurodevelopmental outcomes.



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Editorial Board

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1





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Efficacy of bezafibrate on fibroblasts of glutaric acidemia type II patients evaluated using an in vitro probe acylcarnitine assay

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Kenji Yamada, Hironori Kobayashi, Ryosuke Bo, Jamiyan Purevsuren, Yuichi Mushimoto, Tomoo Takahashi, Yuki Hasegawa, Takeshi Taketani, Seiji Fukuda, Seiji Yamaguchi
IntroductionWe evaluated the effects of bezafibrate (BEZ) on β-oxidation in fibroblasts obtained from patients with glutaric acidemia type II (GA2) of various clinical severities using an in vitro probe (IVP) assay.MethodsCultured fibroblasts from 12 patients with GA2, including cases of the neonatal-onset type both with and without congenital anomalies (the prenatal- and neonatal-onset forms, respectively), the infantile-onset, and the myopathic forms, were studied. The IVP assay was performed by measuring acylcarnitines (ACs) in the cell culture medium of fibroblasts incubated with palmitic acid for 96h in the presence of 0–800μM BEZ using tandem mass spectrometry.ResultsThe IVP assay showed that 100μM BEZ markedly reduced the level of palmitoylcarnitine (C16) in the neonatal-onset, infantile-onset, and myopathic forms of GA2, either increasing or maintaining a high level of acetylcarnitine (C2), which serves as an index of energy production via β-oxidation. In the prenatal-onset form, although a small reduction of C16 was also observed in the presence of 100μM BEZ, the level of C2 remained low. At concentrations higher than 100μM, BEZ further decreased the level of ACs including C16, but a concentration over 400μM decreased the level of C2 in most cases.DiscussionBEZ at 100μM was effective for all GA2 phenotypes except for the prenatal-onset form, as a reduction of C16 without deterioration of C2 is considered to indicate improvement of β-oxidation. The effects of higher doses BEZ could not be estimated by the IVP assay but might be small or nonexistent.



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A Japanese case of β-ureidopropionase deficiency with dysmorphic features

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Tomoyuki Akiyama, Takashi Shibata, Harumi Yoshinaga, Tomiko Kuhara, Yoko Nakajima, Takema Kato, Yasuhiro Maeda, Morimasa Ohse, Makio Oka, Misao Kageyama, Katsuhiro Kobayashi
β-Ureidopropionase deficiency is a rare autosomal recessive disease affecting the last step of pyrimidine degradation, and it is caused by a mutation in the UPB1 gene. Approximately 30 cases have been reported to date, with a phenotypical variability ranging from asymptomatic to severe neurological illness. Non-neurological symptoms have been rarely reported. We describe a case of this disease with developmental delay and dysmorphic features. Gas chromatography–mass spectrometry-based urine metabolomics demonstrated significant (⩾+4.5 standard deviation after logarithmic transformation) elevations of β-ureidopropionic acid and β-ureidoisobutyric acid, strongly suggesting a diagnosis of β-ureidopropionase deficiency. Subsequent quantitative analysis of pyrimidines by liquid chromatography–tandem mass spectrometry supported this finding. Genetic testing of the UPB1 gene confirmed compound heterozygosity of a novel mutation (c.976C>T) and a previously-reported mutation (c.977G>A) that is common in East Asians. β-Ureidopropionase deficiency is probably underdiagnosed, considering a wide phenotypical variability, non-specific neurological presentations, and an estimated prevalence of 1/5000–6000. Urine metabolomics should be considered for patients with unexplained neurological symptoms.



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Cerebral arteriopathy associated with heterozygous Arg179Cys mutation in the ACTA2 gene: Report in 2 newborn siblings

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Jose de Grazia, Ignacio Delgado, Angel Sanchez-Montanez, Susana Boronat, Miguel del Campo, Elida Vazquez
Mutations in the ACTA2 gene lead to a multisystemic smooth muscle dysfunction syndrome that causes vascular disease, congenital mydriasis, and variable presentation of urinary and gastrointestinal problems. The heterozygous Arg179 mutation is associated with a distinctive cerebrovascular phenotype. We report the cases of two newborn siblings with heterozygous ACTA2 Arg179Cys substitution and provide neuroimaging exams that demonstrate the distinctive cerebrovascular phenotype, also associated with variable degree of hypoplasia of the vertebro-basilar circulation as well as hypoxic-ischemic lesions.



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Epileptic phenotype of FGFR3-related bilateral medial temporal lobe dysgenesis

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Tetsuya Okazaki, Yoshiaki Saito, Riyo Ueda, Takeya Awashima, Yoko Nishimura, Isao Yuasa, Yuki Shinohara, Kaori Adachi, Masayuki Sasaki, Eiji Nanba, Yoshihiro Maegaki
Hypochondroplasia (HCH) is a skeletal dysplasia, characterized by short stature and macrocephaly. Clinical symptoms and radiological and histopathological features of HCH are similar, but milder than those seen in achondroplasia. Particularly, HCH patients with Asn540Lys mutation in the FGFR3 gene are reported to have medial temporal lobe dysgenesis and epilepsy.We report a 3-year-old girl who developed recurrent epileptic apnea, which started immediately after birth. The apneic seizures were refractory to antiepileptic medications; ictal electroencephalography showed rhythmic activity originating from the left or right temporal areas and rarely from the right frontal area. Macrocephaly was noted since birth. Neuroimaging revealed bilateral dysgenesis and hypometabolism of the medial temporal structures as well as perfusion changes in the left lateral temporofrontal areas during the ictal period. Clonazepam was initiated and acetazolamide dosage was increased at 6months, resulting in complete seizure control after 8months of age. Genetic analysis identified an Asn540Lys (c.1620 C>A) mutation in the FGFR3 gene. Characteristic bone findings on the lumbar spine, iliac bone, and femur were retrospectively confirmed on X-rays during infancy.This was the first report that delineated the epilepsy phenotype in FGFR3-related bilateral medial temporal lobe dysgenesis; such findings would lead to an early diagnosis and better epilepsy management.



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Two mild cases of Dravet syndrome with truncating mutation of SCN1A

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Toru Takaori, Akira Kumakura, Atsushi Ishii, Shinichi Hirose, Daisuke Hata
BackgroundSCN1A is the gene that codes for the neuronal voltage-gated sodium-channel alpha-subunit 1. It is generally considered that an SCN1A truncating mutation causes the severe phenotype of Dravet syndrome.PatientsWe describe 11- and 4-year-old male patients presenting with mild Dravet syndrome with a truncating mutation of SCN1A. The former patient showed moderate mental retardation; however, seizure was controlled to almost one incident a year by levetiracetam and topiramate. Carbamazepine was also effective, which is atypical of Dravet syndrome. The latter patient showed a borderline developmental quotient and did not have episodes of afebrile seizure.ConclusionTwo patients presented with mild Dravet syndrome, even though they had a truncating mutation of SCN1A. Not all truncating mutations of SCN1A cause the severe phenotype of Dravet syndrome.



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A case of Dravet syndrome with cortical myoclonus indicated by jerk-locked back-averaging of electroencephalogram data

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Yoshinori Kobayashi, Yoshiyuki Hanaoka, Tomoyuki Akiayma, Iori Ohmori, Mamoru Ouchida, Toshiyuki Yamamoto, Makio Oka, Harumi Yoshinaga, Katsuhiro Kobayashi
We report a female patient with Dravet syndrome (DS) with erratic segmental myoclonus, the origin of which was first identified in the cerebral cortex by the detection of myoclonus-associated cortical discharges. The discharges were disclosed through jerk-locked back-averaging of electroencephalogram (EEG) data using the muscle activity of myoclonus as triggers. The detected spikes on the contralateral parieto-central region preceded myoclonic muscle activity in the forearms by 28–46ms. The patient was six months old at the time of examination, and was developing normally before seizure onset at two months of age. She suffered from recurrent afebrile or febrile generalized tonic–clonic seizures that often developed into status epilepticus. Interictal EEG and brain magnetic resonance imaging (MRI) showed no significant findings. The amplitudes of the somatosensory-evoked potentials were not extremely large. She has a chromosomal microdeletion involving SCN1A and adjacent genes.



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Quinidine therapy for West syndrome with KCNTI mutation: A case report

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Masataka Fukuoka, Ichiro Kuki, Hisashi Kawawaki, Shin Okazaki, Kiyohiro Kim, Yuka Hattori, Hitomi Tsuji, Megumi Nukui, Takeshi Inoue, Yoko Yoshida, Takehiro Uda, Sadami Kimura, Yukiko Mogami, Yasuhiro Suzuki, Nobuhiko Okamoto, Hirotomo Saitsu, Naomichi Matsumoto
The KCNT1 gene encodes the sodium-dependent potassium channel, with quinidine being a partial antagonist of the KCNT1 channel. Gain-of-function KCNT1 mutations cause early onset epileptic encephalopathies including migrating partial seizures of infancy (MPSI). At 5months of age, our patient presented with epileptic spasms and hypsarrhythmia by electroencephalogram. Psychomotor retardation was observed from early infancy. The patient was diagnosed with West syndrome. Consequently, various anti-epileptic drugs, adrenocorticotropic hormone therapy (twice), and ketogenic diet therapy were tried. However, the epileptic spasms were intractable. Whole exome sequencing identified a KCNT1 mutation (c.1955G>T; p.G652V). At 2years and 6months, the patient had daily epileptic spasms despite valproate and lamotrigine treatment, and was therefore admitted for quinidine therapy. With quinidine therapy, decreased epileptic spasms and decreased epileptiform paroxysmal activity were observed by interictal EEG. Regarding development, babbling, responsiveness, oral feeding and muscle tone were ameliorated. Only transient diarrhea was observed as an adverse effect. Thus, quinidine therapy should be attempted in patients with West syndrome caused by KCNT1 mutations, as reported for MPSI.



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A case of acute encephalopathy with biphasic seizures and late reduced diffusion: Utility of arterial spin labeling sequence

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Keita Kuya, Shinya Fujii, Fuminori Miyoshi, Koyo Ohno, Yuki Shinohara, Yoshihiro Maegaki, Toshihide Ogawa
A 1-year-old boy was admitted because of febrile status epilepticus (FSE). A secondary cluster of seizures was seen on day 5 after onset, and the patient eventually displayed developmental delay. Conventional magnetic resonance imaging (MRI) showed no abnormal findings on day 1 after onset, but showed reduced diffusion in the subcortical regions of bilateral frontal lobes on day 5 after onset. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was diagnosed. Arterial spin labeling (ASL) revealed reduced cerebral blood flow (CBF) in bilateral frontal lobes on day 1 after onset and showed increased CBF in the corresponding region in the subacute phase. Outcomes after prolonged febrile seizures are usually good, but mental deficit and/or epilepsy often remain in AESD. Discriminating between these syndromes is difficult, because no useful biomarkers have been identified. Reduced CBF in bilateral frontal lobes was observed on ASL on day 1 of FSE in the present case, and this finding may be predictive of developing AESD.



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Neurogenic muscle hypertrophy in a 12-year-old girl

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1
Author(s): Matija Zutelija Fattorini, Alenka Gagro, Tomislav Dapic, Goran Krakar, Josip Marjanovic
Muscular hypertrophy secondary to denervation is very rare, but well-documented phenomena in adults. This is the first report of a child with neurogenic unilateral hypertrophy due to S1 radiculopathy. A 12-year-old girl presented with left calf hypertrophy and negative history of low back pain or trauma. The serum creatinine kinase level and inflammatory markers were normal. Magnetic resonance imaging showed muscle hypertrophy of the left gastrocnemius and revealed a protruded lumbar disc at the L5-S1 level. The protruded disc abuts the S1 root on the left side. Electromyography showed mild left S1 radiculopathy. Passive stretching and work load might clarify the origin of neurogenic hypertrophy but there is still a need for further evidence. Clinical, laboratory, magnetic resonance imaging and electromyography findings showed that S1 radiculopathy could be a cause of unilateral calf swelling in youth even in the absence of a history of back or leg pain.



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Announcements and reports

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1





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Cover

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1





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Contents

Publication date: January 2017
Source:Brain and Development, Volume 39, Issue 1





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Reconsideration of the diagnosis and treatment of childhood migraine: A practical review of clinical experiences

Publication date: Available online 18 December 2016
Source:Brain and Development
Author(s): Yoshiaki Saito, Gaku Yamanaka, Hideki Shimomura, Kazuhiro Shiraishi, Tomoyuki Nakazawa, Fumihide Kato, Yuko Shimizu-Motohashi, Masayuki Sasaki, Yoshihiro Maegaki
ObjectiveTo provide insight into the wide spectrum of migraine during childhood to establish practical and comprehensive treatment strategies.BackgroundAlthough recent studies have confirmed the effect of anti-migraine agents in childhood headaches fulfilling the criteria of migraine without aura, there have been no studies regarding the efficacy of these drugs in childhood migraine without aura not filling the diagnostic criteria.MethodsIn total, 154 patients with a clinical diagnosis of migraine, with onset of repetitive headaches at the age of ⩽15years, were retrospectively included from clinics in seven tertiary medical centers.ResultsPatients' diagnoses included migraine with aura (n=49), migraine without aura (n=65), clinical migraine without aura not fulfilling International Classification of Headache Disorders-3 beta criteria (suspected migraine without aura; n=38), and hemiplegic migraine (n=2). Abortive medicine was effective in 74 of 97 patients, and preventive medicine was effective in 61 of 84 patients. Drugs with high efficacy were acetaminophen and ibuprofen for abortive therapy and cyproheptadine, amitriptyline, and propranolol for preventive therapy. Psychosocial problems were less common, and abnormalities on electroencephalography were more common in the suspected migraine without aura group. Otherwise, clinical features and drug responsibility were comparable among the migraine with aura, migraine without aura, and suspected migraine without aura groups. Retrospectively, experts clinically diagnosed childhood migraine without aura when the headache met at least one of the three criteria B, C, and D in International Classification of Headache Disorders-3 beta in addition to A and E. Abortive and preventive medication including paroxetine (n=2) benefited 10 and 15 of the 33 patients with daily headache, respectively. Psychotherapy/counseling (n=4), treatment for orthostatic dysregulation (n=4), and elimination of stressors (n=3) markedly alleviated headache in this group.ConclusionOur results indicated that those with suspected migraine without aura not filling International Classification of Headache Disorders diagnostic criteria should be included in the treatment for migraine. Treatment should also be targeted to comorbid developmental disorders, orthostatic dysregulation, and psychosocial problems in patients with refractory daily headaches.



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One-pot large-area synthesis of graphitic filamentous nanocarbon-aligned carbon thin layer/carbon nanotube forest hybrid thin films and their corrosion behaviors in simulated seawater condition

Publication date: Available online 18 December 2016
Source:Chemical Engineering Journal
Author(s): Namjo Jeong, Eunjin Jwa, Chansoo Kim, Ji Yeon Choi, Joo-youn Nam, Kyo Sik Hwang, Ji-Hyung Han, Han-ki Kim, Soon-Chul Park, Yong Seog Seo, Moon Seok Jang
In this work, we demonstrate the large-area synthesis of graphitic filamentous nanocarbon-aligned carbon thin layer (GFNACTL) on Cu foil by chemical vapor deposition of C2H2 at 700 °C at 5 Torr pressure. The thickness of the GFNACTL can be controlled to vary in the range 50–4000 nm by varying the synthesis time. The graphitic filamentous nanocarbon with outer diameters ∼10–20 nm have highly oriented and well-connected graphitic structures that are stacked perpendicular to the growth direction. This result shows that the presence of a native oxide layer on the Cu foil was beneficial for the GFNACTL growth. Our approach can be extended to the one-pot synthesis of GFNACTL/carbon nanotube (CNT) forest hybrid thin films. The tip growth of CNTs with diameters of ∼ 50 nm was catalyzed on the GFNACTL by Cu41Sn11 nanoparticles. Corrosion measurements were performed in 0.6 M NaCl solution. Electrochemical analysis revealed a strong improvement in corrosion resistance as compared to pure Cu specimens, indicating the superior uniformity and promise of the GFNACTL/ CNT forest hybrid thin films for application as a protective coating.

Graphical abstract

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Fluorescent nanodiamonds engage innate immune effector cells: a potential vehicle for targeted anti-tumor immunotherapy

Publication date: Available online 18 December 2016
Source:Nanomedicine: Nanotechnology, Biology and Medicine
Author(s): Lorena P. Suarez-Kelly, Amanda R. Campbell, Isaac V. Rampersaud, Ambika Bumb, Min S. Wang, Jonathan P. Butchar, Susheela Tridandapani, Lianbo Yu, Arfaan A. Rampersaud, William E. Carson
Fluorescent nanodiamonds (FNDs) are nontoxic, infinitely photostable, and emit fluorescence in the near infrared region. Natural killer (NK) cells and monocytes are part of the innate immune system and are crucial to the control of carcinogenesis. FND-mediated stimulation of these cells may serve as a strategy to enhance anti-tumor activity. FNDs were fabricated with a diameter of 70±28nm. Innate immune cell FND uptake, viability, surface marker expression, and cytokine production were evaluated in vitro. Evaluation of fluorescence emission from the FNDs was conducted in an animal model. In vitro results demonstrated that treatment of immune cells with FNDs resulted in significant dose-dependent FND uptake, no compromise in cell viability, and immune cell activation. FNDs were visualized in an animal model. Hence, FNDs may serve as novel agents with "track and trace" capabilities to stimulate innate immune cell anti-tumor responses, especially as FNDs are amenable to surface-conjugation with immunomodulatory molecules.

Graphical abstract

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Importance of soil NO emissions for the total atmospheric NOx budget of Saxony, Germany

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Saúl Molina-Herrera, Edwin Haas, Rüdiger Grote, Ralf Kiese, Steffen Klatt, David Kraus, Tatjana Kampffmeyer, Rainer Friedrich, Henning Andreae, Benjamin Loubet, Christof Ammann, László Horváth, Klaus Larsen, Carsten Gruening, Arnoud Frumau, Klaus Butterbach-Bahl
Soils are a significant source for the secondary greenhouse gas NO and assumed to be a significant source of tropospheric NOx in rural areas. Here we tested the LandscapeDNDC model for its capability to simulate magnitudes and dynamics of soil NO emissions for 22 sites differing in land use (arable, grassland and forest) and edaphic as well as climatic conditions. Overall, LandscapeDNDC simulated mean soil NO emissions agreed well with observations (r² = 0.82). However, simulated day to day variations of NO did only agree weakly with high temporal resolution measurements, though agreement between simulations and measurements significantly increased if data were aggregated to weekly, monthly and seasonal time scales. The model reproduced NO emissions from high and low emitting sites, and responded to fertilization (mineral and organic) events with pulse emissions. After evaluation, we linked the LandscapeDNDC model to a GIS database holding spatially explicit data on climate, land use, soil and management to quantify the contribution of soil biogenic NO emissions to the total NOx budget for the State of Saxony, Germany. Our calculations show that soils of both agricultural and forest systems are significant sources and contribute to about 8% (uncertainty range: 6–13%) to the total annual tropospheric NOx budget for Saxony. However, the contributions of soil NO emission to total tropospheric NOx showed a high spatial variability and in some rural regions such as the Ore Mts., simulated soil NO emissions were by far more important than anthropogenic sources.



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Iron nanomedicines induce Toll-like receptor activation, cytokine production and complement activation

Publication date: March 2017
Source:Biomaterials, Volume 119
Author(s): Johan J.F. Verhoef, A. Marit de Groot, Marc van Moorsel, Jeffrey Ritsema, Nataliia Beztsinna, Coen Maas, Huub Schellekens
Approximately a dozen of intravenous iron nanomedicines gained marketing authorization in the last two decades. These products are generally considered as safe, but have been associated with an increased risk for hypersensitivity-like reactions of which the underlying mechanisms are unknown. We hypothesized that iron nanomedicines can trigger the innate immune system. We hereto investigated the physico-chemical properties of ferric gluconate, iron sucrose, ferric carboxymaltose and iron isomaltoside 1000 and comparatively studied their interaction with Toll-like receptors, the complement system and peripheral blood mononuclear cells. Two out of four formulations appeared as aggregates by Scanning Transmission Electron Microscopy analysis and were actively taken up by HEK293T- and peripheral blood mononuclear cells in a cholesterol-dependent manner. These formulations triggered in vitro activation of intracellular Toll-like receptors 3, -7 and -9 in a dose- and serum-dependent manner. In parallel experiments, we determined that these compounds activated the complement system. Finally, we found that uptake of aggregation-prone iron nanomedicines by peripheral blood mononuclear cells in whole blood induced production of the proinflammatory cytokine IL-1β, but not IL-6.



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Editorial board

Publication date: February 2017
Source:Biomaterials, Volume 117





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Glucose modulates antimicrobial photodynamic inactivation of Candida albicans in biofilms

Publication date: Available online 18 December 2016
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Luis Cláudio Suzuki, Ilka Tiemy Kato, Renato Araujo Prates, Caetano Padial Sabino, Tania Mateus Yoshimura, Tamires Oliveira Silva, Martha Simões Ribeiro
Candida albicans biofilm is a main cause of infections associated with medical devices such as catheters, contact lens and artificial joint prosthesis. The current treatment comprises antifungal chemotherapy that presents low success rates. Photodynamic inactivation (PDI) involves the combination of a photosensitizing compound (PS) and light to generate oxidative stress that has demonstrated effective antimicrobial activity against a broad-spectrum of pathogens, including C. albicans. This fungus senses glucose inducing an upregulation of membrane transporters that can facilitate PS uptake into the cell. The aim of this study was to evaluate the effects of glucose on methylene blue (MB) uptake and its influence on PDI efficiency when combined to a red LED with central wavelength at λ=660nm. C. albicans biofilms were grown on hydrogel disks. Prior to PDI assays, MB uptake tests were performed with and without glucose-sensitization. In this system, the optimum PS administration was determined as 500μM of MB in contact with the biofilm during 30min before irradiation. Irradiation was performed during 3, 6, 9, 12, 15 and 18min with irradiance of 127.3mW/cm². Our results showed that glucose was able to increase MB uptake in C. albicans cells. In addition, PDI without glucose showed a higher viability reduction until 6min; after 9min, glucose group demonstrated a significant decrease in cell viability when compared to glucose-free group. Taking together, our data suggest that glucose is capable to enhance MB uptake and modulate photodynamic inactivation of C. albicans biofilm.

Graphical abstract

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Multicolor imaging of hydrogen peroxide level in living and apoptotic cells by a single fluorescent probe

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Ying Wen, Fengfeng Xue, Haichuang Lan, Zhenhua Li, Shuzhang Xiao, Tao Yi
To understand the entangled relationship between reactive oxygen species (ROS) and apoptosis, there is urgent need for simultaneous dynamic monitoring of these two important biological events. In this study, we have developed a fluorescent probe, pep4-NP1, which can simultaneously detect H2O2 and caspase 3, the respective markers of ROS and apoptosis. The probe contains a H2O2 fluorescence reporter (NP1) and Cy5 fluorescent chromophore connected by a caspase 3 specific recognition peptide. The detecting strategy was realized through a controllable fluorescence resonance energy transfer (FRET) process between NP1 and Cy5 of pep4-NP1, after reaction with H2O2, which was verified by molecular calculation and in vitro spectral studies. In the absent of caspase 3, the accumulation of H2O2 induces red fluorescence of pep4-NP1 centered at 663nm in living cells due to the existence of FRET. In contrast, FRET is inhibited in apoptotic cells due to cleavage of the peptide spacer of pep4-NP1 by over-expressed caspase 3. Consequently, green fluorescence (555nm) predominated when labelling production of H2O2 in apoptotic cells. Moreover, Pep4-NP1 shows excellent selectivity towards H2O2 and caspase 3 on their respective reaction sites. Therefore, pep4-NP1 can distinguish endogenously generated H2O2 between living cells and apoptotic cells with different fluorescence wavelengths, providing additional information on the ROS production pathways.



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Unilateral chronic pain may neglect the healthy side

Publication date: Available online 18 December 2016
Source:Cortex
Author(s): Sophie Jacquin-Courtois, Laure Christophe, Eric Chabanat, Karen T. Reilly, Yves Rossetti




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The “Proust Phenomenon”: odor-evoked autobiographical memories triggered by direct amygdala stimulation in human

Publication date: Available online 18 December 2016
Source:Cortex
Author(s): Fabrice Bartolomei, Stanislas Lagarde, Samuel Médina Villalon, Aileen McGonigal, Christian G. Benar




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Functional anatomy of the macaque temporo-parieto-frontal connectivity

Publication date: Available online 18 December 2016
Source:Cortex
Author(s): Elena Borra, Giuseppe Luppino
The primate parietal lobe is primarily dedicated to the processing of sensory information for the guidance of motor behavior, based on the integration of sensory with motor signals (sensorimotor transformations), mediated by specific, strong, and reciprocal connections with the motor cortex. Sensorimotor transformations have been regarded as an automatic process carried out independently from the temporal cortex, which is considered the location where sensory information is used for perceptual processes. However, both human and non-human primate studies have shown interactions between these two regions in different aspects of sensorimotor and cognitive processes. Connectional studies in macaques have provided a detailed description of the possible neural substrate for these interactions. Specifically, temporo-parietal connections almost exclusively involve the inferior parietal lobule (IPL) and display a fine topographic organization, providing the substrate for the role of the macaque IPL in "perception-based" control of motor behavior. Particularly, more rostral IPL areas are involved in motor and cognitive motor functions related to hand action organization and oculomotor control as well as in action and intention understanding, whereas more caudal IPL areas are involved in multisensory integration for the construction of space representations for guiding arm and eye motor behavior. Temporal and IPL-interconnected areas also share connections with specific ventral frontal areas and are thus part of large-scale cortical networks in which the various nodes are linked through "dorsal" temporo-parieto-frontal and "ventral" temporo-frontal pathways. Anatomical and functional studies suggest homologies between human and macaque temporo-parieto-frontal connectivity; they also suggest that higher-order functions of the human IPL could have evolved from the exploitation and adaptation of phylogenetically older neural mechanisms that occur in macaque brains. Thus, connectional data from macaque studies appear essential for understanding human brain mechanisms, even in cases of cognitive abilities undeveloped in other animals, and for interpreting clinical data, including disconnection syndromes.



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How specialized are writing-specific brain regions? An fMRI study of writing, drawing and oral spelling

Publication date: Available online 18 December 2016
Source:Cortex
Author(s): Samuel Planton, Marieke Longcamp, Patrice Péran, Jean-François Démonet, Mélanie Jucla
Several brain imaging studies identified brain regions that are consistently involved in writing tasks; the left premotor and superior parietal cortices have been associated with the peripheral components of writing performance as opposed to other regions that support the central, orthographic components. Based on a meta-analysis by Planton, Jucla, Roux, and Demonet (2013), we focused on five such writing areas and questioned the task-specificity and hemispheric lateralization profile of the brain response in an fMRI experiment where 16 right-handed participants wrote down, spelled out orally object names, and drew shapes from object pictures. All writing-related areas were activated by drawing, and some of them by oral spelling, thus questioning their specialization for written production. The graphemic/motor frontal area, a subpart of the superior premotor cortex close to Exner's area (Roux et al., 2009), was the only area with a writing-specific lateralization profile, that is, clear left lateralization during handwriting, and bilateral activity during drawing. Furthermore, the relative lateralization and levels of activation in the superior parietal cortex, ventral premotor cortex, ventral occipitotemporal cortex and right cerebellum across the three tasks brought out new evidence regarding their respective contributions to the writing processes.



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Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex

Publication date: Available online 18 December 2016
Source:Cortex
Author(s): Martin V. Sale, Abbey S. Nydam, Jason B. Mattingley
Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 minutes following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity.



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The role of the IFG and pSTS in syntactic prediction: evidence from a parametric study of hierarchical structure in fMRI

Publication date: Available online 18 December 2016
Source:Cortex
Author(s): William Matchin, Christopher Hammerly, Ellen Lau
Sentences encode hierarchical structural relations among words. Several neuroimaging experiments aiming to localize combinatory operations responsible for creating this structure during sentence comprehension have contrasted short, simple phrases and sentences to unstructured controls. Some of these experiments have revealed activation in the left inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS), associating these regions with basic syntactic combination. However, the wide variability of these effects across studies raises questions about this interpretation. In an fMRI experiment, we provide support for an alternative hypothesis: these regions underlie top-down syntactic predictions that facilitate sentence processing but are not necessary for building syntactic structure. We presented stimuli with three levels of structure: unstructured lists, two-word phrases, and simple, short sentences; and two levels of content: natural stimuli with real words and stimuli with open-class items replaced with pseudowords (jabberwocky). While both the phrase and sentence conditions engaged syntactic combination, our experiment only encouraged syntactic prediction in the sentence condition. We found increased activity for both natural and jabberwocky sentences in the left IFG (pars triangularis and pars orbitalis) and pSTS relative to unstructured word lists and two-word phrases, but we did not find any such effects for two-word phrases relative to unstructured word lists in these areas. Our results are most consistent with the hypothesis that increased activity in IFG and pSTS for basic contrasts of structure reflects syntactic prediction. The pars opercularis of the IFG showed a response profile consistent with verbal working memory. We found incremental effects of structure in the anterior temporal lobe (ATL), and increased activation only for sentences in the angular gyrus/temporal-parietal junction (AG/TPJ) – both regions showed these effects for stimuli with all real words. These findings support a role for the ATL in semantic combination and the AG/TPJ in thematic processing.



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Bimetal-organic frameworks/polymer core-shell nanofibers derived heteroatom-doped carbon materials as electrocatalysts for oxygen reduction reaction

Publication date: April 2017
Source:Carbon, Volume 114
Author(s): Qijian Niu, Junxia Guo, Binling Chen, Jun Nie, Xindong Guo, Guiping Ma
In this work, Zn-Co-ZIF-n(shell)/PAN(core) nanofibers were well-designed and prepared through bimetal zeolitic imidazolate frameworks (ZIFs) grown on the surface of 2-Methylimidazole/Polyacrylonitrile (MIM/PAN) electrospun nanofibers. After carbonization of Zn-Co-ZIF-n/PAN nanofibers (n was the molar ratio of Zn/Co before carbonization), the core layer was converted to nitrogen-doped carbon nanofibers (NCNFs) and the shell layer was converted to Zn/Co bimetal nanoparticles coated with graphitic carbon layer (Zn/Co@C). It was found that Zn/Co@C-NCNFs are featured with hierarchical network structure and high surface area. Further doped by nitrogen species and embedded by Zn/Co bimetal nanoparticles, it exhibited excellent electrocatalytic performance for oxygen reduction reaction (ORR), better than the reference samples. By further investigating the electrocatalytic performance, the optimized sample Zn/Co@C-NCNFs (0.50) derived from Zn-Co-ZIF-0.50/PAN at 800 °C carbonization exhibited excellent electrocatalytic activity (the onset and half-wave potentials were −0.099 V and −0.20 V vs. Ag/AgCl, respectively and nearly four electron selectivity (3.69)). Moreover, its methanol tolerance and duration stability was better than that of the commercial 20 wt% Pt/C. It provides an effective strategy to design non-precious metal electrocatalysts from the Zn-Co-ZIF-n/PAN nanofibers or other MOFs/polymer nanofibers for ORR in fuel cells.

Graphical abstract

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Metal homeostasis in infectious disease: recent advances in bacterial metallophores and the human metal-withholding response

Publication date: April 2017
Source:Current Opinion in Chemical Biology, Volume 37
Author(s): Wilma Neumann, Anmol Gulati, Elizabeth M Nolan
A tug-of-war between the mammalian host and bacterial pathogen for nutrients, including first-row transition metals (e.g. Mn, Fe, Zn), occurs during infection. Here we present recent advances about three metal-chelating metabolites that bacterial pathogens deploy when invading the host: staphylopine, staphyloferrin B, and enterobactin. These highlights provide new insights into the mechanisms of bacterial metal acquisition and regulation, as well as the contributions of host-defense proteins during the human innate immune response. The studies also underscore that the chemical composition of the microenvironment at an infection site can influence bacterial pathogenesis and the innate immune system.



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Distal Pb-Zn-Ag veins associated with the world-class Donggou porphyry Mo deposit, southern North China craton

Publication date: April 2017
Source:Ore Geology Reviews, Volume 82
Author(s): Zhan-Ke Li, Shi-Jian Bi, Jian-Wei Li, Wen Zhang, David R. Cooke, David Selby
The southern North China craton hosts numerous world-class porphyry Mo and Pb-Zn-Ag vein deposits. Whether or not the Pb-Zn-Ag veins are genetically associated with the porphyry Mo system remains contentious. Here we focus on the genetic relationships between the Sanyuangou Pb-Zn-Ag vein deposit and the world-class Donggou porphyry Mo deposit, and discuss the potential implications from the spatial and temporal relationships between porphyry and vein systems in the southern North China craton.At Sanyuangou, vein-hosted sulfide mineralization mainly comprises pyrite, sphalerite, and galena, with minor chalcopyrite, pyrrhotite, bornite, tetrahedrite, covellite, polybasite and argentite. The mineralization is hosted by a quartz diorite stock, which has a zircon U-Pb age of 1756±9Ma. However, sericite from alteration selvages of Pb-Zn-Ag sulfide mineralization yields a well-defined ⁴⁰Ar/³⁹Ar plateau age of 115.9±0.9Ma. Although nominally younger, the sericite ⁴⁰Ar/³⁹Ar age is similar to the age of the nearby Donggou porphyry Mo deposit (zircon U-Pb age of 117.8±0.9; molybdenite Re-Os ages of 117.5±0.8Ma and 116.4±0.6Ma). Pyrite from Donggou has elevated contents of Mo and Bi, whereas pyrite from Sanyuangou is enriched in Cu, Zn, Pb, Ag, Au, and As. This trace element pattern is consistent with metal zonation typically observed in porphyry related metallogenic systems. Pyrite grains from Sanyuangou have lead isotopes overlapping those from Donggou (17.273–17.495 vs. 17.328–17.517 for ²⁰⁶Pb/²⁰⁴Pb, 15.431–15.566 vs. 15.408–15.551 for ²⁰⁷Pb/²⁰⁴Pb, and 37.991–38.337 vs. 38.080–38.436 for ²⁰⁸Pb/²⁰⁴Pb). Collectively, the geological, geochronological, and geochemical data support a magmatic-hydrothermal origin for the Sanyuangou Pb-Zn-Ag deposit and confirm that the Pb-Zn-Ag veins and the Donggou Mo deposit form a porphyry-related magmatic-hydrothermal system.Given the widespread Pb-Zn-Ag veins and Mo mineralized porphyries in many districts of the southern North China craton, the model derived from this study has broad implications for further exploration of Mo and Pb-Zn-Ag resources in the area.

Graphical abstract

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Genesis of Luobuzhen Pb–Zn veins: Implications for porphyry Cu systems and exploration targeting at Luobuzhen-Dongshibu in western Gangdese belt, southern Tibet

Publication date: April 2017
Source:Ore Geology Reviews, Volume 82
Author(s): Xiang Sun, Youye Zheng, Miao Li, Haitao Ouyang, Qiangqiang Liu, Xinkui Jing, Guoping Sun, Qingjie Song
Porphyry systems are known to form in magmatic arc environment and commonly include porphyry Cu, epithermal Pb–Zn–Au–Ag, skarn polymetallic mineralization, etc. The systems are rarely reported in collisional zones, such as the Gangdese belt in southern Tibet where many postcollisional porphyry copper deposits occurred. In addition, other types of mineral systems are rarely present except porphyry copper mineralization in the Gangdese belt. In this study, we present Pb–Zn-bearing quartz veins at Luobuzhen in the western Gangdese belt. The Luobuzhen Pb–Zn veins cross-cut dacite of the Linzizong Group with zircon U–Pb age of 50.1±0.2Ma and monzogranite with zircon U–Pb age of 17.1±0.1Ma. Ore minerals include sphalerite, galena, chalcopyrite, and pyrite; gangue minerals are quartz with minor chlorite and sericite. Primary fluid inclusions of quartz are liquid-rich, aqueous, and two-phase inclusions. The homogenization temperatures of these primary inclusions are moderate to high (267–400°C), and salinities range from 8.9 to 18.4wt.% NaCl equiv. Quartz has δ¹⁸OSMOW values of 6.2–9.3‰, while sulfides have δ³⁴SV-CDT values of −5.1‰ to 0.1‰, ²⁰⁶Pb/²⁰⁴Pb of 18.722–18.849, ²⁰⁷Pb/²⁰⁴Pb of 15.640–15.785, and ²⁰⁸Pb/²⁰⁴Pb of 39.068–39.560. These data suggest that magmatic fluids with contribution from meteoric water, magmatic sulfur, and lead derived from upper crust and metasomatized mantle by Indian continental materials would be critical for the Luobuzhen base metal mineralization.The Dongshibu area, located at ∼2km east of the Luobuzhen, is characterized by high concentrations of Cu (up to 1450ppm) and Mo (up to 130ppm) of stream sediments, which is quite different from high concentrations in Pb, Zn, Ag, and Au shown in the Luobuzhen area. In addition, porphyry copper mineralization-related alteration and veins/veinlets occur in the Miocene monzogranite at Dongshibu. The monzogranite is characterized by high Sr/Y ratios, which are also shown on ore-forming intrusions in the Gangdese postcollisional porphyry copper deposits, and shows similar zircon Hf isotopes to the ore-related high Sr/Y intrusions from the Zhunuo porphyry copper deposit which is located ∼20km northeast of the Luobuzhen-Dongshibu. A comprehensive analysis allows us to infer that the base metal veins at Luobuzhen are components of a porphyry Cu system with porphyry Cu mineralization likely present at Dongshibu and epithermal Au–Ag veins possibly occurring at Luobuzhen, which are indicative of the existence of porphyry copper systems in collisional zones. The potential porphyry Cu mineralization and epithermal Au–Ag veins should be targeted in future exploration at Luobuzhen-Dongshibu.

Graphical abstract

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NIPTL-Novo: Non-isobaric peptide termini labeling assisted peptide de novo sequencing

Publication date: 10 February 2017
Source:Journal of Proteomics, Volume 154
Author(s): Shen Zhang, Yichu Shan, Shurong Zhang, Zhigang Sui, Lihua Zhang, Zhen Liang, Yukui Zhang
A simple and effective de novo sequencing strategy assisted by non-isobaric peptide termini labeling, NIPTL-Novo, was established. The y-series ions and b-series ions of peptides can be clearly distinguished according to the different mass tags incorporated in N-terminus and C-terminus. This is helpful for improving the accuracy of peptide sequencing and increasing the sequencing speed. For the spectra commonly identified by both de novo sequencing and database searching software (Mascot or Maxquant), NIPTL-Novo gave identical result to more than 85% of these spectra. Furthermore, the quantitative profiling of the sample can be performed simultaneously along with de novo sequencing. Finally, this strategy can be applied to discover the peptides with potential mutation sites by combining with mass-defect based isotopic labeling.SignificanceThe aim of the research presented in this paper is to establish a simple but effective de novo sequencing strategy based on non-isobaric peptide termini labeling, named NIPTL-Novo. First, different mass tags incorporated in N-terminus and C-terminus generated by non-isobaric peptide termini labeling will help to distinguish both b and y ion series, which significantly simplify the MS/MS spectra and reduce the time consumption for de novo sequencing. Second, the isolation window of this strategy is just 4Da, much smaller than most existed labeling assisted de novo sequencing methods, which reduces the interferences caused by co-fragmentation ions. Third, the quantitative profiling of the sample can be performed simultaneously along with the de novo sequencing, and the quantitative accuracy is comparable to other chemical labeling methods. Finally, this strategy was expanded to the analysis of peptide mutation with combination of mass-defect based labeling, and two reliable mutated peptides were discovered.

Graphical abstract

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Development of highly reinforced acrylonitrile butadiene rubber composites via controlled loading of sol-gel titania

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Chayan Das, Naresh D. Bansod, Bharat P. Kapgate, Uta Reuter, Gert Heinrich, Amit Das
Remarkable improvement in mechanical properties of acrylonitrile butadiene rubber (NBR) composites is achieved by incorporating nano-titania that is synthesised in solution of the raw rubber using titanium n-butoxide (TNB) as the titania precursor. This is achieved by designed and controlled incorporation of titania that resulted in very good dispersion of titania of nanometric dimension in rubber matrix and enhanced rubber-filler interaction. This sol-gel transformation is carried out under optimised reaction condition. Surface modification of titania by a silane coupling agent (bis-(3-triethoxysilylpropyl)-tetrasulfide, TESPT) causes further improvement in filler dispersion and composite properties when added in the reactive sol-gel system during in situ titania generation rather than it's external addition in the titania filled NBR during mixing and compounding. Thorough characterisation of the composites are done that encompasses a wide range of studies on thermal, morphological, mechanical, dielectric, dynamic mechanical, rheological and antifungal properties. The results are analysed on a comparative basis to investigate the effect of in situ incorporation and in situ surface modification of titania on the composite properties.

Graphical abstract

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Interlayer-expanded MoS2

Publication date: Available online 16 December 2016
Source:Materials Today
Author(s): Kowsalya Devi Rasamani, Farbod Alimohammadi, Yugang Sun
Motivated by the novel properties of two-dimensional materials, MoS2 has been extensively explored with discoveries surging in the recent years. Such impressive progress benefits from the success in synthesizing nanostructured MoS2 with precisely controlled parameters including edge density and crystalline phase. In this review, we focus on the synthesis of MoS2 with expanded interlayer spacing and their applications in energy storage, catalysis and environmental remediation, highlighting the importance of tuning interlayer spacing on improving performance of MoS2. The challenges faced in this emerging research area and perspective research directions are also discussed.



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IDD Newsletter November 2016

IDD NEWSLETTER – November 2015 (PDF File, 9.42 MB)
VOLUME 44 NUMBER 4 NOVEMBER 2016
IODINE GLOBAL NETWORK (formerly ICCIDD Global Network) is a nongovernmental organization dedicated to sustained optimal iodine
nutrition and the elimination of iodine deficiency throughout the world.

The post IDD Newsletter November 2016 appeared first on American Thyroid Association.

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MRI-guided breast vacuum biopsy: Localization of the lesion without contrast-agent application using diffusion-weighted imaging

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Nicole Berger, Zsuzsanna Varga, Thomas Frauenfelder, Andreas Boss
ObjectiveIn magnetic resonance-guided breast vacuum biopsies, the contrast agent for targeting suspicious lesions can typically be applied only once during an intervention, due to the slow elimination of the gadolinium chelate from the extracellular fluid space. This study evaluated the feasibility of diffusion-weighted imaging (DWI) for lesion targeting in vacuum assisted magnetic resonance imaging (MRI) biopsies.ConclusionDWI may be used as an alternative to dynamic contrast-enhanced MRI with the advantage of reproducibility. However, the targeted lesion requires the characteristics of a mass-like lesion, substantial diffusion restriction, and a minimum size of approximately 1cm.



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The impact of spin coupling signal loss on fat content characterization in multi-echo acquisitions with different echo spacing

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): K. Nikiforaki, G.C. Manikis, T. Boursianis, K. Marias, A. Karantanas, T.G. Maris
PurposeThis study aimed to assess the effect of echo spacing in transverse magnetization (T2) signal decay of gel and fat (oil) samples. Additionally, we assess the feasibility of using spin coupling as a determinant of fat content.MethodsPhantoms of known T2 values, as well as vegetable oil phantoms, were scanned at 1.5T scanner with a multi echo FSE sequence of variable echo spacing above and below the empirical threshold of 20ms for echo train signal modulation (6.7, 13.6, 26.8, and 40ms). T2 values were calculated from monoexponential fitting of the data. Relative signal loss between the four acquisitions of different echo spacing was calculated.ResultsAgreement in the T2 values of water gel phantom was observed in all acquisitions as opposed to fat phantom (oil) samples. Relative differences in signal intensity between two successive sequences of different echo spacing on composite fat/water regions of interest was found to be linearly correlated to fat fraction of the ROI.ConclusionThe sample specific degree of signal loss that was observed between different fat samples (vegetable oils) can be attributed to the composition of each sample in J coupled fat components. Hence, spin coupling may be used as a determinant of fat content.



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