In situ analysis of gelatinolytic activity in human dentin

Publication date: February 2018
Source:Acta Histochemica, Volume 120, Issue 2
Author(s): Thiago Henrique Scarabello Stape, Leo Tjäderhane, Arzu Tezvergil-Mutluay, Wagner Gomes Da Silva, Alan Roger dos Santos Silva, Wander José da Silva, Marcelo Rocha Marques
Matrix metalloproteinases (MMPs) such as gelatinases are differentially expressed in human tissues. These enzymes cleave specific substrates involved in cell signaling, tissue development and remodeling and tissue breakdown. Recent evidences show that gelatinases are crucial for normal dentin development and their activity is maintained throughout the entire tooth function in the oral cavity. Due to the lack of information about the exact location and activity of gelatinases in mature human dentin, the present study was designed to examine gelatinolytic levels in sound dentin. In situ zymography using confocal microscopy was performed on both mineralized and demineralized dentin samples. Sites presenting gelatinase activity were identified throughout the entire biological tissue pursuing different gelatinolytic levels for distinct areas: predentin and dentinal tubule regions presented higher gelatinolytic activity compared to intertubular dentin. Dentin regions with higher gelatinolytic activity immunohistochemically were partially correlated with MMP-2 expression. The maintenance of gelatinolytic activity in mature dentin may have biological implications related to biomineralization of predentin and tubular/peritubular dentinal regions, as well as regulation of defensive mechanisms of the dentin-pulp complex.



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Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development

Publication date: Available online 4 February 2018
Source:Acta Histochemica
Author(s): Tina Becic, Darko Kero, Katarina Vukojevic, Snjezana Mardesic, Mirna Saraga-Babic
The expression pattern of fibroblast growth factors FGF8 and FGF2 and their receptor FGFR1, transcription factors MSX-1 and MSX-2, as well as cell proliferation (Ki-67) and cell death associated caspase-3, p19 and RIP5 factors were analyzed in histological sections of eight 4th-9th-weeks developing human limbs by immunohistochemistry and semi-thin sectioning. Increasing expression of all analyzed factors (except FGF8) characterized both the multilayered human apical ectodermal ridge (AER), sub-ridge mesenchyme (progress zone) and chondrocytes in developing human limbs. While cytoplasmic co-expression of MSX-1 and MSX-2 was observed in both limb epithelium and mesenchyme, p19 displayed strong cytoplasmic expression in non-proliferating cells. Nuclear expression of Ki-67 proliferating cells, and partly of MSX-1 and MSX-2 was detected in the whole limb primordium. Strong expression of factors p19 and RIP5, both in the AER and mesenchyme of human developing limbs indicates their possible involvement in control of cell senescence and cell death. In contrast to animal studies, expression of FGFR1 in the surface ectoderm and p19 in the whole limb primordium might reflect interspecies differences in limb morphology. Expression of FGF2 and downstream RIP5 gene, and transcription factors Msx-1 and MSX-2 did not show human-specific changes in expression pattern. Based on their spatio-temporal expression during human limb development, our study indicates role of FGFs and Msx genes in stimulation of cell proliferation, limb outgrowth, digit elongation and separation, and additionally MSX-2 in control of vasculogenesis. The cascade of orchestrated gene expressions, including the analyzed developmental factors, jointly contribute to the complex human limb development.



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Expression profile of polycomb group proteins in odontogenic keratocyst and ameloblastoma

Publication date: Available online 4 February 2018
Source:Acta Histochemica
Author(s): Puangwan Lapthanasupkul, Rachai Juengsomjit, Sopee Poomsawat, Tawepong Arayapisit
Polycomb group (PcG) proteins are repressive chromatin modifiers required for proliferation and development. PcG proteins form two large repressive complexes, namely, Polycomb Repressive Complex 1 and 2. These proteins have been shown to drive tumorigenesis by repressing cell-type specific sets of target genes. Using immunohistochemistry, we investigated the expression patterns of five human PcG proteins, including Bmi-1, Ring1b, Mel-18, Ezh2, and Suz12, in various cellular components of odontogenic keratocysts (OKCs), ameloblastomas and, pericoronal follicles (PFs). In OKCs, expression of PcG proteins were found in the majority of cases while the expression pattern was relatively different for each PcG proteins. All PcG proteins were strongly expressed in the basal cells while some proteins showed variable expression in the parabasal and luminal cell layer of OKCs. In ameloblastomas, almost all PcG proteins showed a similar expression pattern of moderate to strong staining in the peripheral ameloblast-like cells and metaplastic squamous cells. Some of the central stellate reticulum-like cells also showed positive reaction to most PcG proteins. In PFs, most PcG proteins were intensely expressed in odontogenic epithelium lining the follicles, except Mel-18 and Suz12. The present study provides the initial evidence regarding epigenetic involvement by PcG proteins in these odontogenic lesions. Although these proteins are known to be in the same repressive group proteins, differential expression patterns of these proteins in OKCs and ameloblastomas indicates that these proteins may play different roles in pathogenesis of these odontogenic lesions.



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Apelin/APJ expression in the heart and kidneys of hypertensive rats

Publication date: Available online 1 February 2018
Source:Acta Histochemica
Author(s): Rahime Sekerci, Nuray Acar, Filiz Tepekoy, Ismail Ustunel, Nigar Keles-Celik
Hypertension is an important health problem that is manifested by systemic arterial blood pressure being permanently elevated and leading to serious complications. Hypertension is the basis for coronary heart diseases, heart failure, kidney damage, cerebrovascular diseases. Due to ethical concerns, there is no detailed study of the mechanism, side effects and treatment of hypertension in humans. For this reason, specific studies related to the organ of hypertension are performed in experimental animals. The heart and kidney tissue, which are the most important organs that hypertension has damaged, have formed specific organs of our work.In our experimental study, a total of 35 (hypertensive group: 20, control group: 15) Rattus Norvegicus Wistar albino rats were used. In order to obtain our hypertension model, our experimental animals were given L-NAME together with drinking water for six weeks. After six weeks, the experimental procedures were terminated. Heart and kidney tissues of the hypertensive and control group were obtained. Expression of apelin and apelin receptor (APJ) was demonstrated by immunohistochemical and Western Blot protocols.Hypertrophic cardiac atrium of the hearts of the large cavities, interventricular septum and myocardium to the disintegration, as well as an increase in the diameter of the coronary artery has been observed. In general, kidney tissues of the hypertensive group showed narrowing in cortical renal structures and enlargement in structures in the renal medulla.As a result, in hypertensive cases, there was an increase in expression of Apelin and APJ receptor in heart tissue, and a decrease in expression of Apelin and APJ receptor in kidney tissue. We think that our findings may contribute to experimental or clinical studies related to hypertension and apelin.



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Oxidative Cross-Linking of Proteins to DNA Following Ischemia-Reperfusion Injury

Publication date: Available online 11 March 2018
Source:Free Radical Biology and Medicine
Author(s): Arnold Groehler, Stefan Kren, Qinglu Li, Maggie Robledo-Villafane, Joshua Schmidt, Mary Garry, Natalia Tretyakova
Myocardial infarction (MI) is a life-threatening condition that can occur when blood flow to the heart is interrupted due to a blockage in one or more of the coronary vessels. Current treatments of MI rapidly restore blood flow to the affected myocardium using thrombolytic agents or angioplasty. Adverse effects including inflammation, tissue necrosis, and ventricular dysfunction are, however, not uncommon following reperfusion therapy. These conditions are thought to be caused by a sudden influx of reactive oxygen species (ROS) to the affected myocardium. We employed the model of left anterior descending artery ligation/reperfusion surgery in a rat model to show that ischemia/reperfusion injury is associated with the formation of toxic DNA-protein cross-links (DPCs) in cardiomyocytes. Mass spectrometry based experiments have revealed that these conjugates were formed by a free radical mechanism and involved thymidine residues of DNA and tyrosine side chains of proteins (dT-Tyr). Quantitative proteomics experiments have identified nearly 90 proteins participating in hydroxyl radical-induced DPC formation, including ROS scavengers, contractile proteins, and regulators of apoptosis. Global proteome changes were less pronounced and included increased expression of mitochondrial proteins required for aerobic respiration and biomarkers of sarcomere breakdown following ischemia/reperfusion injury. Overall, our results are consistent with a model where sudden return of oxygen to ischemic tissues induces oxidative stress, inflammation, and the formation of DNA-protein cross-links that may contribute to reperfusion injury by dysregulating gene expression and inducing cardiomyocyte death.

Graphical abstract

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Editorial board

Publication date: March 2018
Source:Microbes and Infection, Volume 20, Issue 3





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Evaluation of the quality of the reporting of phase II clinical trials in oncology: a systematic review

Publication date: Available online 10 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Romain Rivoirard, Julien Langrand-Escure, Mathieu Oriol, Fabien Tinquaut, Franck Chauvin, Chloé Rancoule, Nicolas Magné, Aurélie Bourmaud
ObjectiveTo describe the current state of knowledge concerning the quality of reporting in phase II clinical trials in oncology and to describe the various methods published allowing this quality evaluation.Methodsdatabases including MEDLINE and COCHRANE were searched. Reviews and meta-analyses analyzing the quality of the reporting of phase II trials in oncology were included. Descriptive analysis of the results was performed.ResultsThirteen publications were retained. Only 2 publications adopted a systematic approach of evaluation of the quality of reporting by overall scores. The Key Methodological Score (KMS), proposed by Grellety et al., gathering 3 items, seemed adapted for such an evaluation. A score of 3/3 was found in 16.1% of the 156 phase II trials analyzed by this score. The other reviews used a qualitative analysis to evaluate the reporting, via an analysis of a single criterion, generally the statistical plan of the study. This item was considered as having been correctly reported in less than 50% of the analyzed articles.ConclusionThe quality of reporting in phase II trials in oncology is a field that has been investigated very little (13 publications). When it is studied, the estimated level of quality is not satisfactory, whatever the method employed. The use of an overall score of evaluation is a path which should be pursued, in order to get reliable results. It also seems necessary to propose strong recommendations, which would create a consensus for the methodology and the reporting of these studies.



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Nephronectin is Correlated with Poor Prognosis in Breast Cancer and Promotes Metastasis via its Integrin-Binding Motifs

Publication date: April 2018
Source:Neoplasia, Volume 20, Issue 4
Author(s): Tonje S. Steigedal, Jimita Toraskar, Richard P. Redvers, Marit Valla, Synnøve N. Magnussen, Anna M. Bofin, Signe Opdahl, Steinar Lundgren, Bedrich L. Eckhardt, John M. Lamar, Judy Doherty, Richard O. Hynes, Robin L. Anderson, Gunbjørg Svineng
Most cancer patients with solid tumors who succumb to their illness die of metastatic disease. While early detection and improved treatment have led to reduced mortality, even for those with metastatic cancer, some patients still respond poorly to treatment. Understanding the mechanisms of metastasis is important to improve prognostication, to stratify patients for treatment, and to identify new targets for therapy. We have shown previously that expression of nephronectin (NPNT) is correlated with metastatic propensity in breast cancer cell lines. In the present study, we provide a comprehensive analysis of the expression pattern and distribution of NPNT in breast cancer tissue from 842 patients by immunohistochemical staining of tissue microarrays from a historic cohort. Several patterns of NPNT staining were observed. An association between granular cytoplasmic staining (in <10% of tumor cells) and poor prognosis was found. We suggest that granular cytoplasmic staining may represent NPNT-positive exosomes. We found that NPNT promotes adhesion and anchorage-independent growth via its integrin-binding and enhancer motifs and that enforced expression in breast tumor cells promotes their colonization of the lungs. We propose that NPNT may be a novel prognostic marker in a subgroup of breast cancer patients.



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Prognostication of superficial Barrett's carcinoma: a Japanese multicenter study

Publication date: Available online 10 March 2018
Source:Human Pathology
Author(s): Junko Aida, Tatsuro Ishizaki, Tomio Arai, Kaiyo Takubo
Endoscopic resection (ER) has become the standard therapy for superficial Barrett's carcinoma (BC) in Japan and other countries. Patients undergoing ER sometimes require additional treatment because of recurrence of lymph node metastasis (LNM). We attempted to clarify the histopathologic risk factors for LNM, and the difference between these risk factors for Japanese patients and the conventional risk factors documented for Western patients. This multi-center study included 12 leading institutions belonging to the Japan Research Society for Early Esophageal Cancer and Chromoendoscopy, and was based on a questionnaire designed to gather data on the features of superficial BC cases, except for high-grade intraepithelial neoplasia, treated at those institutions. These features were assessed using the standardized pathologic approach employed in Japan, whereby surgically and endoscopically resected specimens are cut into parallel slices 4–5mm and 2mm thick, respectively. Seventy-four surgically resected (SR) and 201 ER specimens were analyzed separately. Significant risk factors for LNM were almost the same as conventional risk factors, such as tumor size (cut-off value; 17.5mm) and depth, vessel infiltration, presence of poorly differentiated components, and the depth (cut-off value; 990μm) and width (cut-off value; 4300μm) of the submucosal component, in addition to growth pattern (a protruding or flat elevated pattern) and the presence of infiltrative growth. Histopathologic examination revealed that BC cases without invasion to the deep muscularis mucosae (DMM) had almost no risk of LNM. Detailed histopathologic evaluation of thin-slice preparations of ER specimens is considered highly important for prognostication.



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Pre-concentration of Zn(II) ions from aqueous solutions using meso-porous pyridine-enrobed magnetite nanostructures

Publication date: 15 August 2018
Source:Food Chemistry, Volume 257
Author(s): H. Vojoudi, A. Badiei, A. Amiri, A. Banaei, G.M. Ziarani, K. Schenk-Joß
A simple, cheap and efficient method for pre-concentrating and separating Zn(II) ions from aqueous solutions and real samples has been designed. The method was implemented in a prototype featuring interchangeable chromatography-column-like cartridges, filled with meso-porous silica nanostructures, allowing easy exchange of the type and quantity of the sorbent. The adsorbents inside the column are held in place by means of porous polymer nano-fibre membranes. The effects of various parameters on the adsorption of Zn(II) ions from aqueous solutions were investigated. Maximal adsorption (∼99%) was found for Zn(II) ions amongst a mixture of Cu(II), Co(II), Ni(II), Ag(I), Au(III), Pd(II) and Pb(II) in aqueous solution. The procedure was tested for pre-concentrating and determining traces of zinc in real samples of meat, fish and hen marketed in Tehran. A desorption process using 0.5 mol L⁻¹ HCl as eluent, showed ∼97% recovery of the Zn(II) ions adsorbed on the MSMPP sorbent.

Graphical abstract

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Scarless Breast Reconstruction: Indications and Techniques for Optimizing Aesthetic Outcomes in Autologous Breast Reconstruction

Summary: Breast reconstruction that leaves no visible scars on the breast is possible for a subset of patients. This article reviews a cohort of 10 patients who underwent 14 autologous breast reconstructions. To achieve a reconstruction without visible breast scars, the mastectomy and autologous reconstruction are carried out through a periareolar incision. At the completion of the reconstruction, a small skin paddle is externalized through the mastectomy incision and in a subsequent stage entirely incorporated into a nipple areola reconstruction. Following completion of the breast and nipple areola reconstruction, a tattoo is performed that extends beyond the perimeter of the reconstructed areola and conceals all scars on the breast mound. The ideal candidate for this technique has a small or medium size breast, which is non- or minimally ptotic, and a donor site that can yield a flap larger than the volume of the native breast. In properly selected patients, this technique consistently yields high-quality results, which match or even surpass the aesthetics of the original breast.

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Reexploring the Anatomy of the Distal Humerus for its Role in Providing Vascularized Bone

Background: The lateral arm flap is used for composite defects in need of vascularized soft tissue, skin, and bone. From its original description, the distal humeral metaphysis can be included with the flap, supplied by the periosteal extensions of the posterior branch of the radial collateral artery. We sought to reexplore the anatomy of the lateral arm to determine its utility as a donor site for vascularized bone. Methods: Twelve fresh, silicone-injected cadaver dissections were performed. Arteriovenous anatomy, pedicle length and diameter, and anatomic variability as well as photo documentation was recorded. Results: The distal extent of the deltoid, lateral intermuscular septum and lateral humeral epicondyle were identified before the dissection. A septocutaneous perforator was consistently located 10 cm proximal to the lateral humeral epicondyle, which could be used for a skin paddle to monitor. Harvest of a 1.5 cm × 2 cm corticocancellous bone graft was performed. Average pedicle length was 9.1 ± 1.1 cm, and average pedicle diameter was 1.74 ± 0.52 mm. The inferior lateral cutaneous nerve of the arm and the posterior cutaneous nerve of the forearm were consistently identified and preserved. Conclusion: The predictable anatomy of the lateral distal humerus make it an ideal donor site for small segments of vascularized bone.

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Editorial Board

Publication date: March 2018
Source:The Journal of Prosthetic Dentistry, Volume 119, Issue 3





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Sponsoring Organizations and Liaisons

Publication date: March 2018
Source:The Journal of Prosthetic Dentistry, Volume 119, Issue 3





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Table of Contents

Publication date: March 2018
Source:The Journal of Prosthetic Dentistry, Volume 119, Issue 3





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The Essentials

Publication date: March 2018
Source:The Journal of Prosthetic Dentistry, Volume 119, Issue 3





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News and Notes

Publication date: March 2018
Source:The Journal of Prosthetic Dentistry, Volume 119, Issue 3





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Author's Response

Publication date: March 2018
Source:The Journal of Prosthetic Dentistry, Volume 119, Issue 3
Author(s): Lyndon Cooper




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Re: “Comments on a Recent Article on a Prevalent and Disabling Disease”

Publication date: Available online 10 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Lars Norgen




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Transthoracic Ultrasound Imaging of the Descending Thoracic Aorta: Could We, Should We, and Would We?

Publication date: Available online 10 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Y.Y. Go, P. Lancellotti




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Commentary on “The Relationship Between Serum Interleukin-1α and Asymptomatic Infrarenal Abdominal Aortic Aneurysm Size, Morphology, and Growth Rates”

Publication date: Available online 10 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): John D. Kakisis, George Geroulakos




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Novel compound heterozygous mutations in KREMEN1 confirm it as a disease gene for ectodermal dysplasia

Abstract

Ectodermal dysplasia (ED) is a heterogeneous group of disorders caused by mutations in at least thirteen genes. Recently, a study reported Palestinian patients with ED from consanguineous families with a homozygous mutation in KREMEN1 (Kringle-containing transmembrane protein 1) and proposed it to be a causative gene for the autosomal recessive ED 13, hair/tooth type (ECTD13; OMIM #617392). A Thai family, parents and two children affected with ED, was recruited. The study was exempted from review by the Institutional Review Board, Faculty of Medicine, Chulalongkorn University (IRB584/60). Written informed consents of each participant were obtained according to the Declaration of Helsinki. Mutation analyses were performed as described previously.

This article is protected by copyright. All rights reserved.

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Pulmonary function in subjects with psoriasis: A cross-sectional population study

Abstract

Psoriasis is a prevalent chronic inflammatory disease associated with comorbidities, e.g. cardiometabolic diseases, inflammatory bowel disease, and depression that may share an inflammatory origin. Smoking increases the risk of psoriasis and the disease has also been linked to chronic obstructive pulmonary disease (COPD) and asthma, with evidence of shared inflammatory cytokine-mediated mechanisms. Moreover, subjects with psoriasis display increased risk of infections, especially respiratory infections including pneumonia. However, only a small single-center study of pulmonary function in subjects with psoriasis is available.

This article is protected by copyright. All rights reserved.

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Recurrent erysipelas of the face with hyperimmune reaction to group C streptococcus

Abstract

We present the case of a 73-year-old-woman, admitted in 2014 for n erysipelas of the face (figure 1a) beginning 3 days before, with red oedematous papules of the left temple, hyperthermia and chills the day after. Clinical examination did not find lymphadenopathy or skin lesion especially at her left ear. Blood samples showed a raised C reactive protein (CRP) to 120 mg/L without leukocytosis. Antinuclear antibodies were negative. Viral serologies (HIV, hepatitis C and B, EBV, parvovirus B19, VZV, mumps), viral PCR assay (EBV, parvovirus B19, CMV, VZV) and bacterial blood cultures were all negative Histopathological findings revealed a reactive infiltrate without vasculitis and necrosis.

This article is protected by copyright. All rights reserved.

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Differential blood cellular profile in patients with moderate to severe psoriasis treated with classical systemic therapies: A step forward in personalised medicine

Abstract

patients with moderate to severe psoriasis are difficult to treat with topical therapy only and they usually require additional systemic therapy. Despite this, a significant percentage of patients on these therapies shows an inadequate response to these drugs. Treatment decisions are often difficult as they usually rely on subjective terms. Therefore, finding indicators that predict efectiveness or failure to classical systemic therapy is an urgent need. The objective of this study was to analyse whether the phenotype of peripheral blood mononuclear cells (PBMC) would be different in responder or non-responder patients to classical systemic therapy, and thus could be used as a efectiveness predictor of this therapy effectiveness. These predictor markers could help physicians to choose the best individualised treatment for psoriasis patients.

This article is protected by copyright. All rights reserved.

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Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses

Abstract

Background

In addition to the extent of atypical keratinocytes throughout the epidermis, actinic keratoses (AKs) are histologically characterized by downward directed basal layer expansion. It is not known if this growth pattern correlates with the risk of developing invasive squamous cell carcinoma (iSCC).

Objective

To characterize the prevalence of downward directed basal layer expansion of AKs adjacent to iSCC.

Methods

The epidermis overlying and adjacent to iSCCs was assessed histologically. We determined the histological grade (AKI-III), basal growth pattern (PROI-III) and accompanying parameters such as adnexal involvement.

Results

Of 307 lesions, 52.4% of AKs were histologically classified as AKI, 38.1% as AKII, and 6.8% as AKIII (chi-squared; P<0.0001). 2.6% of adjacent epidermis did not show any atypical keratinocytes. The epidermis adjacent to iSCCs was classified as having a PROI basal growth pattern in 25.7%, PROII in 31.9%, and PROIII in 39.4% cases. 2.9% of AKs showed no basal growth (chi-squared; P<0.0001).118 (48.8%) AKs showed extension into adnexal structures. These AKs were graded as PROI in 18.6%, PROII in 30.5%, and PROIII in 50.8%. The epidermis above iSCCs could only be assessed for upwards directed growth and showed no significant differences in the three AK grades (P=0.4211).

Conclusions

Basal proliferative AKs as well as atypical keratinocytes restricted to the lower third of the epidermis are most commonly seen adjacent to iSCC with less evidence for full thickness epidermal dysplasia. Our study supports the important role of dysplastic keratinocytes in the epidermal basal layer and their potential association with iSCC.

This article is protected by copyright. All rights reserved.

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Population-based prevalence of Eosinophilic (Shulman's) Fasciitis: a capture-recapture study

Abstract

Our knowledge of Eosinophilic fasciitis (EF), also known as Shulman's syndrome, is limited, and its prevalence has not been estimated so far. We conducted a regional survey which aimed at estimating the prevalence of EF in Alsace, a Region in the North-East of France. We retrospectively collected EF cases from the first of January 1983 to the 30^th of March 2015 among Alsace residents aged >18 years, then performed a capture-recapture analysis with the prevalent cases in 2015.

This article is protected by copyright. All rights reserved.

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Sulfated Zwitterionic Poly(Sulfobetaine Methacrylate) Hydrogels Promote Complete Skin Regeneration

Publication date: Available online 11 March 2018
Source:Acta Biomaterialia
Author(s): Jiang Wu, Zecong Xiao, Anqi Chen, Huacheng He, Chaochao He, Xintao Shuai, Xiaokun Li, Shengfu Chen, Yanxian Zhang, Baiping Ren, Jie Zheng, Jian Xiao
Skin wound healing is a still long-history challenging problem and impeded by the foreign-body reaction including severe inflammation response, poor neovascularization, incomplete re-epithelialization and defective ECM remodeling. Development of biocompatible polymers, in combination with specific drugs or growth factors, has been considered as a promising strategy to treat skin wounds. Significant research efforts have been made to develop poly(ethylene glycol) PEG-based polymers for wound healing, however less efforts has been paid to zwitterionic materials, some of which have demonstrated their super low-fouling property in vitro and anti-inflammatory property in vivo. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied them to full-thickness cutaneous wounds in mice. The healing effects of SBMA hydrogels on the wound closure, re-epithelialization ratio, ECM remodeling, angiogenesis, and macrophage responses during wound healing processes were histologically evaluated by in vivo experiments. Collective results indicate that SBMA hydrogels promote full-thickness excisional acute wound regeneration in mice by enhancing angiogenesis, decreasing inflammation response, and modulating macrophage polarization. Consistently, the incorporation of SBMA into PEG hydrogels also improved the overall wound healing efficiency as compared to pure PEG hydrogels. This work demonstrates zwitterionic SBMA hydrogels as promising wound dressings for treating full-thickness excisional skin wounds.SignificanceDevelopment of highly effective wound regeneration system is practically important for biomedical applications. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied it to full-thickness cutaneous wounds in mice, in comparison with PEG hydrogels as a control. We are the first to examine and reveal the difference between zwitterionic SBMA hydrogels and PEG hydrogels using a full-thickness excisional mice model. Overall, a series of in vivo systematic tests demonstrated that zwitterionic SBMA hydrogels exhibited superior wound healing property in almost all aspects as compared to PEG hydrogels.

Graphical abstract

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PRELIM II(EDI BOARD)

Publication date: March 2018
Source:Neuroscience Research, Volume 128





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Comparative review of adult midbrain and striatum neurogenesis with classical neurogenesis

Publication date: Available online 12 January 2018
Source:Neuroscience Research
Author(s): Parisa Farzanehfar
Parkinson's Disease (PD) motor symptoms are caused by loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of the midbrain. Dopamine cell replacement therapy (DA CRT), either by cell transplantation or endogenous repair, has been a potential treatment to replace dead cells and improve PD motor symptoms. Adult midbrain and striatum have been studied for many years to find evidence of neurogenesis. Although the literature is controversial, recent research has revived the possibility of neurogenesis here. This paper aims to review the process of neurogenesis (by focusing on gene expression patterns) in the adult midbrain/striatum and compare it with classical neurogenesis that occurs in developing midbrain, Sub Ventricular Zone (SVZ) and Sub Granular Zone (SGZ) of the adult brain.



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Optical measurement of glutamate in slice preparations of the mouse retina

Publication date: Available online 6 March 2018
Source:Neuroscience Research
Author(s): M. Ohkuma, M. Kaneda, S. Yoshida, A. Fukuda, E. Miyachi
Signaling by glutamatergic synapses plays an important role in visual processing in the retina. In this study, we used an enzyme-linked fluorescence assay system to monitor the dynamics of extracellular glutamate in a slice preparation from the mouse retina. High K stimulation induced an elevation of fluorescence in the inner plexiform layer (IPL) of the retina when glutamate transporters were inhibited by dl-threo-β-benzyloxyaspartic acid (TBOA). The high K-induced fluorescence signals in the IPL were inhibited by the calcium channel blocker Cd²⁺. Blockade of GABAergic and glycinergic circuits by picrotoxin and strychnine also elevated the fluorescence signals in the IPL. Thus, the enzyme-linked fluorescence assay system might be useful for monitoring the bulk concentration of extracellular glutamate released by synapses in the inner retina.



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Stimulation-induced changes in diffusion and structure of calmodulin and calmodulin-dependent protein kinase II proteins in neurons

Publication date: Available online 1 February 2018
Source:Neuroscience Research
Author(s): Morteza Heidarinejad, Hideki Nakamura, Takafumi Inoue
Calcium/calmodulin-dependent protein kinase II (CaMKII) and calmodulin (CaM) play essential roles in synaptic plasticity, which is an elementary process of learning and memory. In this study, fluorescence correlation spectroscopy (FCS) revealed diffusion properties of CaM, CaMKIIα and CaMKIIβ proteins in human embryonic kidney 293 (HEK293) cells and hippocampal neurons. A simultaneous multiple-point FCS recording system was developed on a random-access two-photon microscope, which facilitated efficient analysis of molecular dynamics in neuronal compartments. The diffusion of CaM in neurons was slower than that in HEK293 cells at rest, while the diffusion in stimulated neurons was accelerated and indistinguishable from that in HEK293 cells. This implied that activity-dependent binding partners of CaM exist in neurons, which slow down the diffusion at rest. Diffusion properties of CaMKIIα and β proteins implied that major populations of these proteins exist as holoenzymatic forms. Upon stimulation of neurons, the diffusion of CaMKIIα and β proteins became faster with reduced particle brightness, indicating drastic structural changes of the proteins such as dismissal from holoenzyme structure and further fragmentation.



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TNFR2 mediated TNF-α signaling and Nf-κB activation in hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice

Publication date: Available online 23 February 2018
Source:Neuroscience Research
Author(s): Nabanita Ghosh, Soham Mitra, Priyobrata Sinha, Nilkanta Chakrabarti, Arindam Bhattacharyya
1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) −induced neuroinflammation and its impact in hippocampus remain elusive till date. Our present study includes the time dependent changes of inflammatory molecules in mouse hippocampus during MPTP treatment. MPTP treatment increased level of TNF-α, enhanced expression of TNFR2 along with PI3 kinase (PI3K) induced phosphorylation of Akt resulting in persistent nuclear factor-κB (NF-κB) activation. The expressions gradually increased from Day1 post-MPTP treatment, maximally at Day3 post-treatment. MPTP induced translocation of p65 and p52, two subunits of NF-κB family, to nucleus where they had been found to dimerize. Therefore, MPTP induced TNF-α signaling through TNFR2 mediated pathway and recruited p65-p52 dimer in hippocampal nucleus which is reported to have protective effect on hippocampal neurons indicated by unchanged neuronal count in hippocampus in treated groups with respect to control. Our finding suggests that this unique NF-κB dimer plays some role in providing inherent protection to hippocampus during MPTP-treatment.



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Local anesthetic effect of docosahexaenoic acid on the nociceptive jaw-opening reflex in rats

Publication date: Available online 23 February 2018
Source:Neuroscience Research
Author(s): Kazuki Mitome, Shiori Takehana, Katsuo Oshima, Yoshihito Shimazu, Mamoru Takeda
Although docosahexaenoic acid (DHA) administration suppresses sodium channels in primary afferent sensory neurons, the acute local effect of DHA on the trigeminal nociceptive reflex remains to be elucidated, in vivo. Therefore, the aim of the present study was to investigate whether local administration of DHA attenuates the nociceptive jaw-opening reflex (JOR) in vivo in the rat. The JOR evoked by electrical stimulation of the tongue was recorded by a digastric muscle electromyogram (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG response was significantly increased in proportion to the electrical stimulation intensity (1–5 x threshold). At 3 x threshold, local administration of DHA (0.1, 10 and 25 mM) dose-dependently inhibited the dEMG response, and lasted 40 min. Maximum inhibition of the dEMG signal amplitude was seen within approximately 10 min. The mean magnitude of inhibition of the dEMG signal amplitude by DHA (25 mM) was almost equal to the local anesthetic, 1% lidocaine (37 mM), a sodium channel blocker. These findings suggest that DHA attenuates the nociceptive JOR via possibly blocking sodium channels, and strongly support the idea that DHA is a potential therapeutic agent and complementary alternative medicine for the prevention of acute trigeminal nociception.



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Loss of GPRC5B impairs synapse formation of Purkinje cells with cerebellar nuclear neurons and disrupts cerebellar synaptic plasticity and motor learning

Publication date: Available online 23 February 2018
Source:Neuroscience Research
Author(s): Takamitsu Sano, Ayako Kohyama-Koganeya, Masami O. Kinoshita, Tetsuya Tatsukawa, Chika Shimizu, Eriko Oshima, Kazuyuki Yamada, Tung Dinh Le, Takumi Akagi, Koujiro Tohyama, Soichi Nagao, Yoshio Hirabayashi
GPRC5B is a membrane glycoprotein robustly expressed in mouse cerebellar Purkinje cells (PCs). Its function is unknown. In Gprc5b^−/− mice that lack GPRC5B, PCs develop distal axonal swellings in deep cerebellar nuclei (DCN). Numerous misshapen mitochondria, which generated excessive amounts of reactive oxygen species (ROS), accumulated in these distal axonal swellings. In primary cell cultures of Gprc5b^−/− PCs, pharmacological reduction of ROS prevented the appearance of such swellings. To examine the physiological role of GPRC5B in PCs, we analyzed cerebellar synaptic transmission and cerebellum-dependent motor learning in Gprc5b^−/− mice. Patch-clamp recordings in cerebellum slices in vitro revealed that the induction of long-term depression (LTD) at parallel fiber-PC synapses was normal in adult Gprc5b^−/− mice, whereas the induction of long-term potentiation (LTP) at mossy fiber-DCN neuron synapses was attenuated in juvenile Gprc5b^−/− mice. In Gprc5b^−/− mice, long-term motor learning was impaired in both the rotarod test and the horizontal optokinetic response eye movement (HOKR) test. These observations suggest that GPRC5B plays not only an important role in the development of distal axons of PCs and formation of synapses with DCN neurons, but also in the synaptic plasticity that underlies long-term motor learning.



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Monitoring brain neuronal activity with manipulation of cardiac events in a freely moving rat

Publication date: Available online 15 February 2018
Source:Neuroscience Research
Author(s): Yu Shikano, Yuji Ikegaya, Takuya Sasaki
Behavioral and cognitive studies have demonstrated that brain functions are affected by the activity states of the peripheral organs, such as the cardiac and respiratory systems. However, detailed neurophysiological mechanisms underlying the body-brain interactions remain unknown. In this study, we developed a method for manipulating activity levels of the heart using direct cardiac stimulation and vagus nerve stimulation that can be combined with recording cerebral local field potentials using a microdrive system, electrocardiograms, electromyograms, in a freely moving rat. With this method, the electrical stimulation to the heart increases heart rates up to 14 Hz, whereas the vagus nerve stimulation decreases heart rates to 3 Hz. Transient electrical artifacts arising from the peripheral stimulation are not contaminated in cortical local field potential signals low-pass filtered at 150 Hz and distinguishable from extracellular multiunit signals. The technique will contribute to understanding the neurophysiological correlate of mind-body associations in health and disease.



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The differential roles of PEA15 phosphorylations in reactive astrogliosis and astroglial apoptosis following status epilepticus

Publication date: Available online 10 February 2018
Source:Neuroscience Research
Author(s): Jin-Young Park, Tae-Cheon Kang
Up to this day, the roles of PEA15 expression and its phosphorylation in seizure-related events have not been still unclear. In the present study, we found that PEA15 was distinctly phosphorylated in reactive astrocytes and apoptotic astrocytes in the rat hippocampus following LiCl-pilocarpine-induced status epilepticus (SE, a prolonged seizure activity). PEA15-serine (S) 104 phosphorylation was up-regulated in reactive astrocytes following SE, although PEA15 expression and its S116 phosphorylation were unaltered. Bisindolylmaleimide (BIM), a protein kinase C (PKC) inhibitor, attenuated SE-induced reactive astrogliosis, but phorbol 12-myristate 13-acetate (PMA, a PKC activator) aggravated it. Unlike reactive astrocytes, PEA15-S116 phosphorylation was reduced in apoptotic astrocytes. However, PEA15 expression and its S104 phosphorylation were unchanged in apoptotic astrocyte. Neither BIM nor PMA affected SE-induced astroglial apoptosis. PEA15 expression and its phosphorylations were not relevant to SE-induced CA1 neuronal death. These findings indicate that PEA15-S104 and S116 phosphorylations may play a role in reactive astrogliosis and prevention of astroglial apoptosis, respectively. Therefore, we suggest that the selective manipulation of PEA15 phosphorylations may regulate apoptotic and/or proliferative signals in astrocytes.



http://ift.tt/2GgidUH

U1 small nuclear RNA overexpression implicates autophagic-lysosomal system associated with AD

Publication date: Available online 1 February 2018
Source:Neuroscience Research
Author(s): Zhi Cheng, Zhanqiang Du, Baohui Zhai, Zhuo Yang, Tao Zhang
Recently, we reported that presenilin 1 considerably increased the expression level of U1 small nuclear RNA (snRNA) accompanied with the adverse change of amyloid precursor protein (APP) expression, β-amyloid (Aβ) production and cell apoptosis. In the present study, it was found that U1 snRNA overexpression significantly elevated the expression level of autophagy. Moreover, rapamycin further enhanced the Aβ production and cell apoptosis, whereas these processes were effectively inhibited by 3-MA. Acridine orange staining images showed that U1 snRNA overexpression not only activated autophagy pathway, but also led to the autophagic-lysosomal system dysfunction in cells. Immunofluorescence assay showed autophagic vacuoles localization with APP, which was the precursor protein of main component of toxic protein in AD. Meanwhile, the superoxide dismutase activity was remarkably decreased and MDA level was significantly increased by U1 snRNA overexpression in cells, suggesting that there was a possible pathway to elucidate how the U1 snRNA overexpression induced cell damage. We further found that U1 snRNA overexpression altered lysosomal biogenesis and autophagic-lysosomal fusion. In combination with our previous results, it suggests that the malfunction of autophagy pathway provides important insight into molecular mechanisms of augment the aggregation of Aβ and induction of cell apoptosis contributed to AD.



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Gamma oscillations in the entorhinal-hippocampal circuit underlying memory and dementia

Publication date: Available online 10 February 2018
Source:Neuroscience Research
Author(s): Tomoaki Nakazono, Heechul Jun, Mathew Blurton-Jones, Kim N. Green, Kei M. Igarashi
Gamma oscillations that occur within the entorhinal cortex-hippocampal circuitry play important roles in the formation and retrieval of memory in healthy brains. Recent studies report that gamma oscillations are impaired in the entorhinal-hippocampal circuit of Alzheimer's disease (AD) patients and AD animal models. Here we review the latest advancements in studies of entorhinal-hippocampal gamma oscillations in healthy memory and dementia. This review is especially salient for readers in Alzheimer's research field not familiar with in vivo electrophysiology. Recent studies have begun to show a causal link between gamma oscillations and AD pathology, suggesting that gamma oscillations may even offer a plausible future therapeutic target.



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Generation of Pax6-IRES-EGFP knock-in mouse via the cloning-free CRISPR/Cas9 system to reliably visualize neurodevelopmental dynamics

Publication date: Available online 31 January 2018
Source:Neuroscience Research
Author(s): Yukiko U. Inoue, Yuki Morimoto, Mikio Hoshino, Takayoshi Inoue
Pax6 encodes a transcription factor that plays pivotal roles in eye development, early brain patterning, neocortical arealization, and so forth. Visualization of Pax6 expression dynamics in these events could offer numerous advantages to neurodevelopmental studies. While CRISPR/Cas9 system has dramatically accelerated one-step generation of knock-out mouse, establishment of gene-cassette knock-in mouse via zygote injection has been considered insufficient due to its low efficiency. Recently, an improved CRISPR/Cas9 system for effective gene-cassette knock-in has been reported, where the native form of guide RNAs (crRNA and tracrRNA) assembled with recombinant Cas9 protein are directly delivered into mouse fertilized eggs. Here we apply this strategy to insert IRES-EGFP-pA cassette into Pax6 locus and achieve efficient targeted insertions of the 1.8 kb reporter gene. In Pax6-IRES-EGFP mouse we have generated, EGFP-positive cells reside in the eyes and cerebellum as endogenous Pax6 expressing cells at postnatal day 2. At the early embryonic stages when the embryos are transparent, EGFP-positive regions can be easily identified without PCR-based genotyping, precisely recapitulating the endogenous Pax6 expression patterns. Remarkably, at E12.5, the graded expression patterns of Pax6 in the developing neocortex now become recognizable in our knock-in mice, serving a sufficiently sensitive and useful tool to precisely visualize neurodevelopmental processes.



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Ethological and multi-behavioral analysis of learning and memory performance in laboratory rodent models

Publication date: Available online 9 February 2018
Source:Neuroscience Research
Author(s): Hiroyuki Arakawa, Yoshio Iguchi
Behavioral studies using animal models have widely contributed to advancing our understanding of the neuroregulatory mechanisms of human cognitive states and disorders. A variety of behavioral tests and theoretical models have been developed that provide a standardized toolbox of behavioral test paradigms available to researchers, and thus allow rapid progress in studies of the molecular-genetic bases of behavior relevant to neurocognitive diseases. However, a growing effort to utilize standardized paradigms has overlooked the diverse behavioral characteristics of test rodents expressed in standardized test situations. This review describes two popular test paradigms for cognitive assessment in rodents: social recognition and fear conditioning tasks. An extensive assessment of observed behavior during testing indicates a need to further elucidate the sequential strategic processes employed by test animals in conjunction with the use of standardized test settings and dependent variables. The present study calls specific attention to the considerable but improvable problem of the appropriateness and applicability of these standardized test paradigms; it thereby unravels the essential contribution of multi-behavioral assessment to further advancing neuroscience research using rodent behavioral models.



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Calcium-binding protein, secretagogin, specifies the microcellular tegmental nucleus and intermediate and ventral parts of the cuneiform nucleus of the mouse and rat

Publication date: Available online 3 February 2018
Source:Neuroscience Research
Author(s): Toshio Kosaka, Katsuko Kosaka
Secretagogin (SCGN) is a recently discovered calcium binding protein of the EF hand family, cloned from β cells of pancreatic island of Langerhans and endocrine cells of the gastrointestinal gland. SCGN characterizes some particular neuron groups in various regions of the nervous system and is considered as one of the useful neuron subpopulation markers. In the present study we reported that SCGN specifically labelled a particular neuronal cluster in the brainstem of the mice and rats. The comparison of the SCGN immunostaining with the choline acetyltransferase immunostaining and acetylcholinesterase staining clearly indicated that the particular cluster of SCGN positive neurons corresponded to the microcellular tegmental nucleus (MiTg) and the ventral portion of the cuneiform nucleus (CnF), both of which are components of the isthmus. The analyses in mice indicated that SCGN positive neurons in the MiTg and CnF were homogeneous in size and shape, appearing to compose a single complex: their somata were small comparing with the adjacent cholinergic neurons in the pedunculotegmantal nucleus, 10.5 vs 16.0 μm in diameter, and extended 2–3 slender smooth processes. SCGN might be one of significant markers to reconsider the delineations of the structures of the mouse, and presumably rat, brainstem.



http://ift.tt/2Fy1E5I

Real-time imaging of synaptic vesicle exocytosis by total internal reflection fluorescence (TIRF) microscopy

Publication date: Available online 2 February 2018
Source:Neuroscience Research
Author(s): Mitsuharu Midorikawa
Synaptic vesicles are one of the smallest organelle in the cell with their sizes far below the diffraction limit of the light microscopy. Exocytosis at the synapse is tightly regulated reaction which typically occurs within a millisecond after the arrival of an action potential. It has been assumed that synaptic vesicles have to be ready for immediate exocytosis upon the arrival of final trigger before exocytosis. But direct observation of the pre-exocytotic synaptic vesicle dynamics have been lacking. Total internal reflection microscopy (TIRFM) is a fluorescence microscopy which has best z-axis resolution (∼100 nm) as a light microscopy, and is close to that of the ultrathin section used for electron microscopy. Although its application is limited to the objects just beneath the plasma membrane, TIRFM has revealed dynamics of various organelles and proteins. We recently managed to dissociate mammalian neuronal presynaptic terminals and let the exocytotic sites adhere tightly to the coverslip. There, TIRFM revealed the detailed dynamics of pre-exocytotic vesicles. Our work opened up the way to visualize dynamics of sub-diffraction limited sized organelle in a real time, and will be useful for direct visualization of various synaptic components in the future.



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PRELIM II(EDI BOARD)

Publication date: February 2018
Source:Neuroscience Research, Volume 127





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The presynaptic active zone: molecules, plasticity, and diseases

Publication date: February 2018
Source:Neuroscience Research, Volume 127
Author(s): Stephan Sigrist, Toshihisa Ohtsuka




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Editorial Board

Publication date: March 2018
Source:Brain and Development, Volume 40, Issue 3





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An infant case of diffuse cerebrospinal lesions and cardiomyopathy caused by a BOLA3 mutation

Publication date: Available online 2 March 2018
Source:Brain and Development
Author(s): Makoto Nishioka, Yuji Inaba, Mitsuo Motobayashi, Yosuke Hara, Ryusuke Numata, Yoshiro Amano, Kunihiko Shingu, Yoichiro Yamamoto, Kei Murayama, Akira Ohtake, Yozo Nakazawa
Introduction: Mitochondrial dysfunction results in a wide range of organ disorders through diverse genetic abnormalities. We herein present the detailed clinical course of an infant admitted for extensive, rapidly progressing white matter lesions and hypertrophic cardiomyopathy due to a BOLA3 gene mutation.Case: A 6-month-old girl with no remarkable family or past medical history until 1 month prior presented with developmental regression and feeding impairment. Ultrasound cardiography and brain magnetic resonance imaging (MRI) respectively disclosed the presence of hypertrophic cardiomyopathy and symmetrical deep white matter lesions. She was transferred to our hospital at age 6 months. High lactate levels in her cerebrospinal fluid suggested mitochondrial dysfunction. Despite vitamin supplementation therapy followed by a ketogenic diet, the patient began exhibiting clusters of myoclonic seizures and respiratory failure. Brain and spinal cord MRI revealed rapid progression of the white matter lesions. She died at 10 months of age. Fibroblasts obtained pre-mortem displayed low mitochondrial respiratory chain complex I and II activity. A homozygous H96R (c. 287 A > G) mutation was identified in the BOLA3 gene.Discussion: No reported case of a homozygous BOLA3 gene mutation has survived past 1 year of life. BOLA3 appears to play a critical role in the electron transport system and production of iron-sulfur clusters that are related to lipid metabolism and enzyme biosynthesis.



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Editorial Board

Publication date: April 2018
Source:Brain and Development, Volume 40, Issue 4





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Fazio-Londe syndrome in siblings from India with different phenotypes

Publication date: Available online 2 March 2018
Source:Brain and Development
Author(s): Vykuntaraju K. Gowda, Tamilarasan Udhayabanu, Perumal Varalakshmi, Varunvenkat M. Srinivasan, Balasubramaniem Ashokkumar
BackgroundFazio-Londe syndrome also called progressive bulbar palsy of childhood is a very rare motor neuron disease of pediatric age group characterized by progressive paralysis of lower cranial nerves.ObjectiveTo describe Fazio-Londe syndrome in sibling with different phenotype.MethodsA 6 years old female child presented with inability to close eyes, difficulty in swallowing, respiratory muscle weakness and voice change since 5 yr of age. Examination showed lower motor neuron facial nerve palsy, absent gag reflex, tongue atrophy, fasciculation, limb wasting and exaggerated deep tendon reflexes. An 11 year old boy, elder sibling of the above child presented with similar complaints at 10 years of age, other than later onset and lack of respiratory problem. Genetic testing in both cases confirmed the diagnosis of Fazio-Londe Syndrome.ConclusionIn any child who presents with progressive bulbar palsy with lower motor neuron facial palsy a diagnosis of Fazio-Londe Syndrome should be considered and family members should also be screened.



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New quantitative method for evaluation of motor functions applicable to spinal muscular atrophy

Publication date: March 2018
Source:Brain and Development, Volume 40, Issue 3
Author(s): Naoki Matsumaru, Ryo Hattori, Takashi Ichinomiya, Katsura Tsukamoto, Zenichiro Kato
ObjectiveThe aim of this study was to develop and introduce new method to quantify motor functions of the upper extremity.MethodsThe movement was recorded using a three-dimensional motion capture system, and the movement trajectory was analyzed using newly developed two indices, which measure precise repeatability and directional smoothness. Our target task was shoulder flexion repeated ten times. We applied our method to a healthy adult without and with a weight, simulating muscle impairment. We also applied our method to assess the efficacy of a drug therapy for amelioration of motor functions in a non-ambulatory patient with spinal muscular atrophy. Movement trajectories before and after thyrotropin-releasing hormone therapy were analyzed.ResultsIn the healthy adult, we found the values of both indices increased significantly when holding a weight so that the weight-induced deterioration in motor function was successfully detected. From the efficacy assessment of drug therapy in the patient, the directional smoothness index successfully detected improvements in motor function, which were also clinically observed by the patient's doctors.ConclusionWe have developed a new quantitative evaluation method of motor functions of the upper extremity. Clinical usability of this method is also greatly enhanced by reducing the required number of body-attached markers to only one. This simple but universal approach to quantify motor functions will provide additional insights into the clinical phenotypes of various neuromuscular diseases and developmental disorders.



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Announcements and reports

Publication date: March 2018
Source:Brain and Development, Volume 40, Issue 3





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A novel germline PIGA mutation causes early-onset epileptic encephalopathies in Chinese monozygotic twins

Publication date: Available online 2 March 2018
Source:Brain and Development
Author(s): Ling-ling Xie, Xiao-jie Song, Tian-yi Li, Li Jiang
We report a case of 14-month-old male monozygotic twins showing early-onset intractable epilepsy, delayed psychomotor development, hypotonia, opisthotonus, and dysmorphism. They presented with refractory partial and secondary generalized tonic-clonic or myoclonic seizures since age of 6 months. Electroencephalograms mainly revealed fast activity in left occipital region and generalized high amplitude polyspikes and wave. Brain MRI was normal. A de novo germline hemizygous mutation, C.110 T > C (p.37 M > T), in exon 2 of PIGA was confirmed, which indicated that a novel germline mutation in PIGA leads to early-onset epileptic encephalopathies.



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A novel mutation in sphingosine-1-phosphate lyase causing congenital brain malformation

Publication date: Available online 2 March 2018
Source:Brain and Development
Author(s): Daniel Bamborschke, Matthias Pergande, Kerstin Becker, Friederike Körber, Jörg Dötsch, Anne Vierzig, Lutz T. Weber, Sebahattin Cirak
IntroductionRecently recessive mutations in sphingosine-1-phosphate lyase (SGPL1) have been published as a cause of syndromic congenital nephrotic syndrome with adrenal insufficiency. We have identified a case with fetal hydrops and brain malformations due to a mutation in SGPL1.Case reportWe report a patient presenting with severe fetal hydrops, congenital nephrotic syndrome and adrenal calcifications. MRI imaging showed generalized cortical atrophy with simplified gyral pattern and hypoplastic temporal lobes as well as cerebellar hypoplasia and hyperintensity in the pons. The boy deceased at 6 weeks of age. Via whole exome sequencing, we identified a novel homozygous frameshift mutation c.1233delC (p.Phe411Leufs^∗56) in SGPL1.ConclusionIn our patient, we describe a novel mutation in sphingosine-1-phosphate lyase (SGPL1) leading to severe brain malformation. Neurodevelopmental phenotypes have been reported earlier, but not described in detail. To this end, we present a review on all published SGPL1-mutations and genotype-phenotype correlations focusing on neurodevelopmental outcomes. We hypothesized on the severe neurological phenotypes, which might be due to disruption of neuronal autophagy. Mutations in SGPL1 shall be considered in the differential diagnosis of fetal hydrops as well as congenital brain malformations and neuropathies.



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Reply to the letter to the editor by Josef Finsterer and Sinda Zarrouk-Mahjoub.osef Finsterer and Sinda Zarrouk-Mahjoub

Publication date: Available online 2 March 2018
Source:Brain and Development
Author(s): Hitoshi Osaka, Takeshi Kouga




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Announcements and reports

Publication date: April 2018
Source:Brain and Development, Volume 40, Issue 4





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Cover

Publication date: April 2018
Source:Brain and Development, Volume 40, Issue 4





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Contents

Publication date: April 2018
Source:Brain and Development, Volume 40, Issue 4





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Identification of sleep hypoventilation in young individuals with Becker muscular dystrophy: A pilot study

Publication date: Available online 8 March 2018
Source:Brain and Development
Author(s): Yuko Nakamura, Yoshiaki Saito, Norika Kubota, Wataru Matsumura, Chika Hosoda, Akiko Tamasaki-Kondo, Yoko Nishimura, Yoshihide Sunada, Masuyuki Fukada, Takako Ohno, Yoshihiro Maegaki, Masafumi Matsuo, Yasuko Tokita
AimTo report on sleep hypercapnia in Becker muscular dystrophy (BMD) at earlier stages than ever recognized.Subjects and methodsThis retrospective study examined nocturnal hypercapnia in six young Becker muscular dystrophy (BMD) patients with deletions of one or more exons of DMD gene. Clinical information, consecutive data on forced vital capacity (FVC%), forced expiratory volume in one second (FEV1%), peak expiratory flow (PEF%), peak cough flow (PCF), average PCO2 in all-night monitoring, and left ventricular ejection fraction (LVEF) were reviewed.ResultsIn five BMD patients, including three who were still ambulant, nocturnal average PCO2 was elevated to >45 mmHg at 12–31 years of age. Noninvasive positive pressure ventilation was initiated in four patients. Gradual declines in FVC% and PEF% were evident in one BMD patient with exon 3–7 deletion, whereas these functions did not change in the remaining BMD patients. PCF, FEV1%, and LVEF were less informative for the assessment of respiratory function in this patient series.ConclusionSleep hypercapnia was present in certain BMD patients, which was unexpected from the routine pulmonary function tests. Individualized assessment of nocturnal PCO2, partly based on the deletion types, should be further explored in the clinical practice of BMD patients.



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De novo HDAC8 mutation causes Rett-related disorder with distinctive facial features and multiple congenital anomalies

Publication date: Available online 5 March 2018
Source:Brain and Development
Author(s): Tomoko Saikusa, Munetsugu Hara, Kazuhiro Iwama, Kotaro Yuge, Chihiro Ohba, Jun-ichiro Okada, Tadashi Hisano, Yushiro Yamashita, Nobuhiko Okamoto, Hirotomo Saitsu, Naomichi Matsumoto, Toyojiro Matsuishi
We present a unique 11-year-old girl showing clinical features of Rett-related disorder with distinctive facial features and multiple congenital anomalies including ocular hypertelorism, arched eyebrows, a broad nose, dental anomalies, congenital heart disease, truncal obesity, and epilepsy. A novel de novo mutation in histone deacetylase 8 (HDAC8) (c.652G > T, p.Gly218Cys) was confirmed by whole exome sequencing and Sanger sequencing. X-chromosome inactivation analysis on DNA isolated from peripheral blood lymphocytes revealed a completely skewed pattern associated with an inactive maternal allele. Late clinical loss of acquired purposeful hand movements and psychomotor deterioration may be a feature of Rett-related disorder, while distinctive facial features and multiple congenital anomalies are reminiscent of Cornelia de Lange syndrome.



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Leigh syndrome with spinal cord involvement due to a hemizygous NDUFA1 mutation

Publication date: Available online 3 March 2018
Source:Brain and Development
Author(s): Akihiko Miyauchi, Hitoshi Osaka, Masako Nagashima, Mari Kuwajima, Yukifumi Monden, Masakazu Kohda, Yoshihito Kishita, Yasushi Okazaki, Kei Murayama, Akira Ohtake, Takanori Yamagata
Leigh syndrome, which is a common phenotype of pediatric mitochondrial disease, is a progressive neurodegenerative disease. The typical neuroimaging findings of Leigh syndrome include bilateral symmetric lesions in the basal ganglia and/or the brainstem. However, there are a few reports on spinal cord involvement in patients with Leigh syndrome. In the present case, magnetic resonance imaging (MRI) obtained during infancy revealed symmetric lesions in the substantia nigra of a patient with Leigh syndrome with an NDUFA1 mutation; lesions of the bilateral putamen and brainstem were subsequently observed. Additionally, our patient presented large and extended spinal cord lesions. Therefore, this case is suggesting that we should consider the occurrence of spinal cord lesions as an atypical finding in Leigh syndrome.



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Effect of botulinum toxin type A treatment in children with cerebral palsy: Sequential physical changes for 3 months after the injection

Publication date: Available online 3 March 2018
Source:Brain and Development
Author(s): Mayumi Matsuda, Kazuhide Tomita, Arito Yozu, Tomohiro Nakayama, Jyunko Nakayama, Haruka Ohguro, Nobuaki Iwasaki
PurposeThis study investigated the sequential physical changes after botulinum toxin type A (BTX-A) injected in children with cerebral palsy.MethodsNine children with cerebral palsy were included. Measurements were performed before treatment and 4 weeks, 8 weeks, and 12 weeks after treatment. We used video-recorded gait in the sagittal plane. The maximum flexion and extension angles of the hip, knee and ankle joints, step length, gait speed, and observational gait were measured using the Foot Contact Scale (FCS) and the Physician's Rating Scale (PRS). We also measured the lower limb range of motion (ROM), Modified Tardieu Scale (MTS), knee joint extension torque, and Gross Motor Function Measure-66 (GMFM-66).ResultsThe ankle dorsiflexion ROM, GMFM-66, and the maximum dorsiflexion angle of the ankle during gait were significantly increased at 8 weeks after treatment, and knee joint extension torque was significantly increased at 12 weeks after treatment.ConclusionMaximum effects of BTX-A treatment do not occur during the early stage after treatment. Therefore, long-term intervention with rehabilitation between BTX-A treatment may be more effective than implementing rehabilitation for only a brief period.



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Cover

Publication date: March 2018
Source:Brain and Development, Volume 40, Issue 3





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Culture-free, highly sensitive, quantitative detection of bacteria from minimally processed samples using fluorescence imaging by smartphone

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Sajal Shrivastava, Won-Il Lee, Nae-Eung Lee
A critical unmet need in the diagnosis of bacterial infections, which remain a major cause of human morbidity and mortality, is the detection of scarce bacterial pathogens in a variety of samples in a rapid and quantitative manner. Herein, we demonstrate smartphone-based detection of Staphylococcus aureus in a culture-free, rapid, quantitative manner from minimally processed liquid samples using aptamer-functionalized fluorescent magnetic nanoparticles. The tagged S. aureus cells were magnetically captured in a detection cassette, and then fluorescence was imaged using a smartphone camera with a light-emitting diode as the excitation source. Our results showed quantitative detection capability with a minimum detectable concentration as low as 10 cfu/ml by counting individual bacteria cells, efficiently capturing S. aureus cells directly from a peanut milk sample within 10 min. When the selectivity of detection was investigated using samples spiked with other pathogenic bacteria, no significant non-specific detection occurred. Furthermore, strains of S. aureus from various origins showed comparable results, ensuring that the approach can be widely adopted. Therefore, the quantitative fluorescence imaging platform on a smartphone could allow on-site detection of bacteria, providing great potential assistance during major infectious disease outbreaks in remote and resource-limited settings.

Graphical abstract

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Sorption of selected pharmaceuticals by a river sediment: role and mechanisms of sediment or Aldrich humic substances

Abstract

Sorption of pharmaceuticals onto sediments is frequently related to organic matter content. Thus, the present work aimed to compare the effect of humic substances (HS) extracted from a river sediment versus Aldrich (HS) on the sorption of selected pharmaceuticals onto this river sediment. The results exhibited no "unique" effect of the presence of HS from the same origin. Thus, the sediment HS increased the sorption of sulfamethoxazole (SMX), diclofenac (DCF), and trimethoprim (TMP), but reduced the sorption of atenolol (ATN). The presence of Aldrich HS increased the sorption of TMP and ATN and decreased the sorption of SMX and DCF. Fluorescence quenching measurements revealed that these effects cannot be explained only by the presence of pharmaceutical HS associations. The use of several sorption models suggested that the sorption of SMX, DCF, and ATN involves multilayer mechanisms. Furthermore, it was pointed out that the presence of HS does not change the sorption mechanisms although it was observed interaction between HS and the sediment. Indeed, the sediment HS sorbs onto the sediment whereas the Aldrich HS tends to mobilize organic compounds from the sediment to the solution.

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Modes of selenium occurrence and LCD modeling of selenite desorption/adsorption in soils around the selenium-rich core, Ziyang County, China

Abstract

Studying the modes of selenium occurrence in high-Se soils and its behaviors can improve understanding and evaluating its cycling, flux, and balance in geo-ecosystems and its influence on health. In this paper, using a modified sequential chemical extraction technique, seven operationally defined selenium fractions and Se valence distribution were determined about five soils in which paddy was planted (W1, W2, W3, W4, W5) and five soils in which maize was planted (H1, H2, H3, H4, H5) around the selenium-rich core, Ziyang County, Shaanxi Province, China. The results show that selenium fractions in the soils mainly include sulfide/selenide and base-soluble Se, and ligand-exchangeable Se is also high for five soils in which paddy was planted. For water-soluble Se, Se (IV) is main Se valence and almost no Se (VI) was determined about five soils in which paddy was planted, while almost 1:1 of Se (IV) and Se (VI) coexist about five soils in which maize was planted. For exchangeable Se, similar results were found. For the first time, two typical high-Se soils (W1 soil and H1 soil) were chosen to measure the pH-dependent solid-solution distribution of selenite in the pH range 3–9, and the results were explained using LCD (ligand and charge distribution) adsorption modeling. The desorbed selenite concentrations from the two soils are in general underestimated by the model due to a comparable binding affinity of phosphate and selenite on goethite and much lower amount of total selenite than total reactively adsorbed phosphate. The pH dependency of adsorption of selenite added to the soil can be successfully described with the LCD model for W1 soil. Whereas considering the influence of Al-oxides, by lowering selenite adsorption affinity constant K of Se adsorption on goethite by 16 times, the LCD model can describe the adsorption much better. The results can help to understand selenium cycling, flux, and balance in typical high-Se soils.

http://ift.tt/2Ikd3aL

Distillers’ grains anaerobic digestion residue biochar used for ammonium sorption and its effect on ammonium leaching from an Ultisol

Abstract

The aim of this work was to explore the potential application of biochar from distillers' grains anaerobic digestion residue pyrolyzed at 700 °C (ADR-DG₇₀₀) to ammonium (NH₄⁺) adsorption from aqueous solution, as well as its effect on NH₄⁺ leaching from an Ultisol. The adsorption kinetic of NH₄⁺ on the ADR-DG₇₀₀ could be described by an Elovich model (R² = 0.995), and the combined Langmuir-Freundlich model (R² = 0.997) fitted the isotherm data better than the Langmuir, Freundlich, Redlich-Peterson, and Temkin models with a maximum adsorption of 11.41 mg N g⁻¹. The NH₄⁺ adsorption on ADR-DG₇₀₀ was mainly controlled by the cation exchange, the surface complexation with oxygen-containing functional groups of carboxyl C〓O (C▬O) and carbohydrate C▬OH, as well as the electrostatic interactions with Si▬O▬Si functional group. In addition, the ADR-DG₇₀₀ soil application reduced 2.48–20.67% of NH₄⁺-N leaching loss after nitrogen fertilizer application in an Ultisol. These results suggested that the ADR-DG₇₀₀ could be a sorbent for NH₄⁺-contaminated water as well as an inhibitor for soil NH₄⁺ leaching.

http://ift.tt/2p5DxUS

Heavy metals transfer in the olive tree and assessment of food contamination risk

Abstract

Due to constraints of fresh water for agricultural irrigation, wastewater was used for irrigation of agricultural land as alternative water resources in arid and semi-arid Tunisian regions. However, long-term irrigation may cause contamination by heavy metals in the soil as well as for crops, thus becoming a threat to humans. To understand the effect of irrigation with wastewater on the concentrations of heavy metals Cr, Cu, Mn, Zn, and Pb, in soil and plants, soil samples and plants were collected and analyzed. Results have shown that all soil samples do not exhibit extreme values. The content of heavy metals in the surface layer (0–30 cm) is much higher than that in depth. Overall, the concentrations of Mn, Pb, Cu, Cr, and Zn in soil were found to be lower than the authorized national safety limits. Moreover, the content in both parts of forage crops have not exceeded the WHO standard. For olive trees, no negative values were found in the different organs, which was also true for the extracted oil. An exception happened for the oils produced from fallen olives in direct contact with the wastewater and the soil. Therefore, to ensure food security and wastewater use for irrigation, monitoring and control of pollution is required.

Graphical abstract

Biomass production from treated wastewater without risk

http://ift.tt/2IkTCyH

Quantification of polychlorinated biphenyl contamination using human placenta as biomarker from Punjab Province, Pakistan

Abstract

The present study biomonitored the placental polychlorinated biphenyl (PCB) concentrations in women from Punjab Province, Pakistan, that provides the pioneer data for occurrence and body burden of PCBs in placental tissues from South Asian women. The ∑₃₄PCB concentrations in placental tissues were ranged from 20.2 to 115.98 ng/g lipid weight (lip. wt.), with predominance of tetra-PCB (54.67%). The levels of ∑₈DL-PCBs and ∑₆-indicator PCBs were ranged from 2.03 to 27.64 ng/g (lip. wt.) and 1.71 to 30.8 ng/g (lip. wt.), respectively. The WHO-TEQ2005 values for DL-PCBs were ranged from 1.18 × 10⁻⁵ to 0.067 ng/g (lip. wt.), with highest value evaluated for CB-126. The estimated daily intake (EDI) for DL-PCBs was ranged from 9.27 × 10⁻⁸ to 5.25 × 10⁻⁴ pg WHO-TEQ/kg body weight (bw), which was within the tolerable daily intake (TDI) values established by international organizations. The spatial distribution patterns of Σ₃₄PCB concentrations from study area have shown relative higher concentrations in samples from urban and industrial cities than rural areas, and industrial and urban releases along with e-waste handling were recognized as vital PCB sources in the environment. In order to ascertain the transplacental transfer of PCBs, the fetal growth parameters were correlated with the ∑₃₄PCB concentrations in placental tissues. The relationship between ∑₃₄PCB concentrations in placental tissues and infant's anthropometric measures through multiple linear regression showed a negative correlation of infant's body weight (R² = 0.0728), crown to heel length (R² = 0.068), head circumference (R² = 0.0342), chest circumference (R² = 0.0001), and mid arm circumference (R² = 0.0096) that noticeably highlights the inhibited fetal anthropometric development associated with maternal PCB bioaccumulation. Hence, an immediate elimination of ongoing PCB addition in the studied area has been emphasized and further investigations are suggested to appropriately manage the public and neonatal health risks in the region.

http://ift.tt/2p5DsAy