Quantitative multiphoton microscopy of murine urinary bladder morphology during in situ uniaxial loading

Publication date: Available online 22 September 2017
Source:Acta Biomaterialia
Author(s): Jack Hornsby, Donna M Daly, David Grundy, Fangzhou Cheng, Anne M Robertson, Paul N Watton, Mark S Thompson
Urodynamic tests are the gold standard for the diagnosis of bladder dysfunction, and the mechanical compliance of the bladder is an important parameter in these tests. The bladder wall has a layered structure, differentially affected by pathology, so knowledge of the contribution and role of these layers and their constituents to overall bladder compliance will enhance interpretation of these clinical tests. In this study we document the functional morphology of the detrusor and lamina propria of the murine bladder wall using a custom in-situ tensile loading system under multiphoton microscopy (MPM) observation in unloaded state and under incremental uniaxial stretch. Features in the stress-stretch curves of bladder samples were then directly related to corresponding MPM images. Collagen organisation across wall depth was quantified using image analysis techniques. The hypothesis that the lamina propria deformed at low strain by unfolding of the rugae and rearranging collagen fibrils was confirmed. A novel 'pocket' feature in the detrusor was observed along with extensive rearrangement of fibrils in two families at different depths, providing higher stiffness at high stretches in the detrusor. The very different deformations of detrusor and lamina propria were accommodated by the highly coiled structure of collagen in the lamina propria. Imaging and mechanical studies presented here allow gross mechanical response to be attributed to specific components of the bladder wall and further, may be used to investigate the impact of microstructural changes due to pathology or aging, and how they impair tissue functionality.Statement of significanceThis article reports the first in-situ multiphoton microscopy observations of microstructural deformation under uniaxial tensile loading of ex vivo bladder. We describe collagen rearrangement through the tissue thickness and relate this directly to the stress-stretch behaviour. We confirm for the first time the unfolding of rugae and realignment of fibrils in the lamina propria during extension and the rapid stiffening as two fibril families in the detrusor are engaged. This technique provides new insight into microstructure function and will enhance understanding of the impact of changes due to pathology or aging.

Graphical abstract

http://ift.tt/2yvtV9P

Determination and in vitro bioaccessibility evaluation of Ca, Cu, Fe, K, Mg, Mn, Mo, Na, P and Zn in linseed and sesame

Publication date: March 2018
Source:Microchemical Journal, Volume 137
Author(s): Laís A. Souza, Thaís L. Souza, Filipe B. Santana, Rennan G.O. Araujo, Leonardo S.G. Teixeira, Daniele C.M.B. Santos, Maria Graças A. Korn
Given the importance of knowing the real nutritional value of food, the main objective of this study was to evaluate the total elements concentrations and bioaccessibility of Ca, Cu, Fe, K, Mg, Mn, Mo, Na, P and Zn in linseed and sesame samples. A full 2⁴ factorial design was applied to optimize the microwave assisted acid digestion of the samples. Total elements concentrations were obtained by inductively coupled plasma optical emission spectrometry (ICP OES). Extraction procedures were performed using the Unified Bioaccessibility Method (UBM) to evaluate the bioaccessibility. The highest total content, in μgg⁻¹, were observed for K (4526–9768), P (3418–7014) and Mg (2527–4633), whereas Mo (<0.11–2.6), Cu (12−32) and Mn (12–61) presented the lowest concentrations. The highest bioaccessible fractions in gastric phase were observed for K (16–26%), Mg (22–28%), Mn (19–27%), P (25–36%) and Zn (16–25%). In addition, it was found through the application of in vitro simulated gastrointestinal digestion that only a minor fraction of total Fe and Cu was potentially bioaccessible in this samples.



http://ift.tt/2ywKAKj

Ultrasound irradiation effect on morphological properties of a 3D nano zinc(II) supramolecular coordination polymer

Publication date: March 2018
Source:Ultrasonics Sonochemistry, Volume 41
Author(s): Hai Ning Chang, Suo Xia Hou, Zeng Chuan Hao, Guang Hua Cui
Nano-structures of [Zn(L)(atpt)]n (1) (L=1,2-bis(2-methylbenzimidazol-1-ylmethyl)benzene and H2atpt=2-aminoterephthalic acid) were obtained by hydrothermal and sonochemical approaches, characterized by scanning electron microscopy (SEM), IR, powder X-ray diffraction (PXRD), and elemental analysis. CP 1 features a 2D (4,4) network with the point symbol {4⁴.6²}, the 3D supramolecular architecture in CP 1 is controlled through π⋯π stacking interactions. The influence of various concentrations of initial reagents, power of ultrasound irradiation, and ultrasound time on the morphology and size of nano-structured CP 1 were studied in detail. In addition, the luminescence and photocatalytic properties of the nanoparticles of CP 1 for the degradation of methyl blue (MB) have also been investigated.

Graphical abstract

http://ift.tt/2wGDTrt

Horticultural performance and elemental nutrient concentrations on ‘Fuji’ grafted on apple rootstocks under New York State climatic conditions

Publication date: 3 January 2018
Source:Scientia Horticulturae, Volume 227
Author(s): Gemma Reig, Jaume Lordan, Gennaro Fazio, Michael A. Grusak, Stephen Hoying, Lailang Cheng, Poliana Francescatto, Terence Robinson
A study was carried out to determine the horticultural performance and leaf and fruit elemental nutrient concentrations of 48 apple rootstocks grafted on 'Fuji' apple cultivar, and grown on a commercial farm in the Hudson Valley (Milton) New York State, USA from 2005 to 2015. Tree circumference was measured at the end of each year, and fruit yield data were collected from the third year (2007) to the eleventh year (2015). Leaf and fruit macro- and microelements were evaluated at the tenth year of the study. Most of the rootstocks evaluated survived well in the Hudson Valley conditions, with the exception of the Geneva^® (G or CG) rootstocks CG.4002 and CG.5030. The smallest trees were on CG.2034, M.27 and JM.4 and had the lowest cumulative yield and the lowest cumulative number of fruits, and medium to low fruit size, but the highest cumulative yield efficiency (kgcm⁻²). Other rootstocks, such as the dwarfing CG.2002, CG.2426, CG.4008, CG.5757, M.9 and the semi-dwarfing rootstock CG.6006, also had higher yield efficiencies. On the other hand, the medium vigor CG rootstocks such as CG.6001, CG.6253, CG.6976, and CG.8189 had high cumulative yield and high cumulative fruit number, and medium to high yield efficiency. Rootstocks had a significant influence on most of the fruit and leaf mineral concentration (dry weight basis). G.935, G.222 and CG.5257 conferred some of the highest values of fruit boron whereas M.9, M.27 and PiAu51.11 had the lowest. Fruit phosphorous values were closely associated with leaf boron, leaf potassium, and leaf sodium. Fruit calcium was highest in G.214, CG.2406, G.969, JM.4 and CG.5757, while the lowest values were with JM.1, PiAu51.11, and JTE-C. Fruit nitrogen values were lowest in M.7, PiAu51.4, B.54-118, and CG.8534 and the highest values were in the dwarfing rootstock CG.2034 and semi-dwarfing rootstock CG.4011. Weak but significant positive correlations were found between fruit size and leaf and fruit Mg, and leaf C. Significant correlations were found between nutrients: leaf B, P and K were highly positively correlated, and leaf Zn with leaf Mn and leaf Na. A strong positive correlation was found between fruit P and fruit K, fruit P and fruit B, and moderate positive correlation between fruit S and fruit K suggesting similar mechanisms of rootstock induction for these nutrients. These nutrient data are being utilized to customize scion nutrient requirements to rootstock-induced nutrient profiles.



http://ift.tt/2wGXtUy

Band gap engineering of ZnMnO diluted magnetic semiconductor by alloying with ZnS

Publication date: 15 January 2018
Source:Journal of Magnetism and Magnetic Materials, Volume 446
Author(s): Z.A. Yunusov, Sh. U. Yuldashev, Y.H. Kwon, D.Y. Kim, S.J. Lee, H.C. Jeon, H. Jung, A. Kim, T.W. Kang
In this paper we report the results on the fabrication of diluted magnetic semiconductors Zn1−xMnxO1−ySy thin films with manganese x=0.05 and sulfur 0≤y≤0.15 compositions, respectively, by using ultrasonic spray pyrolysis method. The influence of the sulfur concentration on the band gap energy, structural and magnetic properties have been studied by using optical transmission, X-ray diffraction and superconducting quantum interference device (SQUID) measurements, respectively. The morphology and composition of samples were studied by using Scanning Electron Microscope (SEM) and X-ray photoelectron spectroscopy (XPS). With increasing of the sulfur concentration the band gap energy of composition decreases, while the magnetization increases proportional to the sulfur concentration.



http://ift.tt/2yvri7O

Preliminary assessment on exposure of four typical populations to potentially toxic metals by means of skin wipes under the influence of haze pollution

Publication date: 1 February 2018
Source:Science of The Total Environment, Volumes 613–614
Author(s): Zhiguo Cao, Mengmeng Wang, Qiaoying Chen, Yajie Zhang, Wenjing Dong, Tianfang Yang, Guangxuan Yan, Xin Zhang, Yunqing Pi, Benye Xi, Qingwei Bu
To investigate the exposure risk of human beings to nine potentially toxic metals (PTMs), namely, Cu, Cr, Zn, As, Cd, Pb, Ni, Mn, and Co, skin wipe samples were collected from four types of populations, namely, children, undergraduates, security guards, and professional drivers, under different haze pollution levels in Xinxiang, China by using Ghost wipes. The Ghost wipes were quantitatively analyzed by inductively coupled plasma mass spectrometry (ICP-MS) after microwave digestion. Generally, Zn (ND-1350μg/m² for undergraduates, ND-2660μg/m² for security guards, ND-2460μg/m² for children, and ND-2530μg/m² for professional drivers) showed the highest concentration among the four populations, followed by Cu (0.02–83.4μg/m² for undergraduates, ND-70.2μg/m² for security guards, 23.2–487μg/m² for children, and ND-116μg/m² for professional drivers). As (ND-5.7μg/m² for undergraduates, ND-2.3μg/m² for security guards, ND-21.1μg/m² for children, and ND-11.0μg/m² for professional drivers) and Co (ND-6.0μg/m² for undergraduates, ND-7.9μg/m² for security guards, ND-13.4μg/m² for children, and ND-2.1μg/m² for professional drivers) showed the lowest concentrations in all populations. Remarkable differences were found among the four populations and PTM levels decreased in the following order: children, professional drivers, security guards, and undergraduates. Gender variation was discovered for undergraduates and children. Generally, PTM contamination in skin wipes collected during a light haze pollution level was generally higher than that during a heavy haze pollution level, but PTM contamination was comparable between the two haze pollution levels for children. Non-carcinogenic exposure risks to As, Cd, and Pb for all populations were higher than those for the other six elements but all of them were within the acceptable safety threshold, indicating no apparent non-carcinogenic risk.

Graphical abstract

http://ift.tt/2wHo9Vr

Size-exclusion HPLC analysis of trace element distributions in hepatic and gill cytosol of Vardar chub (Squalius vardarensis Karaman) from mining impacted rivers in north-eastern Macedonia

Publication date: 1 February 2018
Source:Science of The Total Environment, Volumes 613–614
Author(s): Nesrete Krasnići, Zrinka Dragun, Marijana Erk, Sheriban Ramani, Maja Jordanova, Katerina Rebok, Vasil Kostov
Many bioindicators have not yet been well characterized regarding their tendency to bind trace elements by different cytosolic biomolecules in response to trace element exposure. Accordingly, our principal aim was to define the cytosolic distributions of Cd, Co, Cu, Fe, Mn, Mo, Se, and Zn among the biomolecules of different molecular masses in liver and gills of Vardar chub (Squalius vardarensis Karaman), a representative fish species of Macedonian rivers, and to determine distribution changes which occur as a consequence of increased exposure to specific trace elements. Additionally, we aimed to confirm the presence of heat-stable biomolecules in chub hepatic and gill cytosols. Distribution profiles were obtained by separation of cytosols and heat-treated cytosols using size-exclusion high performance-liquid chromatography, and by offline determination of trace element concentrations using high resolution inductively coupled plasma-mass spectrometry. Distribution profiles of trace elements were mainly characterized by several peaks encompassing different ranges of molecular masses, as a sign of incorporation of trace elements in various biomolecules within hepatic and gill cytosols. Especially interesting finding was probable binding of Fe to ferritin, which was especially pronounced in the liver, as a sign of important liver function in Fe storage. Furthermore, association with heat-stable proteins, metallothioneins (MT), was indicated for Cd, Cu, and Zn in the hepatic cytosol, as well as for Cd in the gill cytosol, whereas a sign of Zn-MT association was not observed in the gills. The presence of Mo- and Se-binding heat-stable compounds of very low molecular masses (<10kDa) in the cytosol was determined for both liver and the gills. Trace elements under all studied conditions were found associated to the same biomolecules, and only their proportions associated to specific cytosolic compounds have changed as a consequence of their increased bioaccumulation in the liver and gills of Vardar chub.

Graphical abstract

http://ift.tt/2wFYSuD

Antibiotic Prophylaxis for Surgical Procedures: A Systematic Review [Internet].

SBU's Conclusions The medical/clinical advantages of antibiotic prophylaxis must be weighed against the risk of increasing numbers of antibiotic resistant strains of bacteria. Development of resistance is more gradual in Sweden than in other countries, but resistant bacteria spread beyond national boundaries.

http://ift.tt/2yvRA9V

Personal name in Igbo Culture: A dataset on randomly selected personal names and their statistical analysis

Publication date: December 2017
Source:Data in Brief, Volume 15
Author(s): Hilary I. Okagbue, Abiodun A. Opanuga, Muminu O. Adamu, Paulinus O. Ugwoke, Emmanuela C.M. Obasi, Grace A. Eze
This data article contains the statistical analysis of Igbo personal names and a sample of randomly selected of such names. This was presented as the following: 1). A simple random sampling of some Igbo personal names and their respective gender associated with each name. 2). The distribution of the vowels, consonants and letters of alphabets of the personal names. 3). The distribution of name length. 4). The distribution of initial and terminal letters of Igbo personal names. The significance of the data was discussed.



http://ift.tt/2xXgXVk

A dataset on tail risk of commodities markets

Publication date: December 2017
Source:Data in Brief, Volume 15
Author(s): Robert J. Powell, Duc H. Vo, Thach N. Pham, Abhay K. Singh
This article contains the datasets related to the research article "The long and short of commodity tails and their relationship to Asian equity markets"(Powell et al., 2017) [1]. The datasets contain the daily prices (and price movements) of 24 different commodities decomposed from the S&P GSCI index and the daily prices (and price movements) of three share market indices including World, Asia, and South East Asia for the period 2004–2015. Then, the dataset is divided into annual periods, showing the worst 5% of price movements for each year. The datasets are convenient to examine the tail risk of different commodities as measured by Conditional Value at Risk (CVaR) as well as their changes over periods. The datasets can also be used to investigate the association between commodity markets and share markets.



http://ift.tt/2jTwZJN

Breast cancer patients in Nigeria: Data exploration approach

Publication date: December 2017
Source:Data in Brief, Volume 15
Author(s): Pelumi E. Oguntunde, Adebowale O. Adejumo, Hilary I. Okagbue
Breast cancer is the type of cancer that develops from breast tissue; it is mostly common in women and it is one of the most studied diseases, largely because of its high mortality (second to lung cancer). However, it occurs in males also. This article presents a statistical study of the distribution of age, gender, length of stay, mode of diagnosis, status (dead or alive) after treatment and the location of breast cancer among 300 patients admitted in the University of Ilorin teaching hospital, Ilorin, Nigeria. The study covers a period of five (5) years; from 2011 to 2016 and logistic regression was used to perform the basic analysis in this study. It was discovered that the age of patients and the location of the breast cancer (right or left) contributes significantly to the survival of the patients. However, early detection and treatment of the disease is highly encouraged. This study also recommends that awareness should be taken to the grassroots and males should not be excluded from this discussion.



http://ift.tt/2xY8Xn5

Diabetes alters vascular mechanotransduction data: Pressure-induced regulation of mTor and associated signaling in the rat inferior vena cava

Publication date: December 2017
Source:Data in Brief, Volume 15
Author(s): Kevin M. Rice, Nandini D.P.K. Manne, Ravikumar Arvapalli, Gautam K. Ginjupalli, Eric R. Blough
Diabetes is a multifaceted disease with various etiologies. The complexity of this pathology creates a myriad of factors that must be considered when addressing surgical outcomes and prognosis. Of vital importance to cardiovascular surgery is the viability of homographic vein grafts. Due to the fact, diabetic patients have a higher rate of vein graph failure, a greater understanding of the effect diabetes has on vascular mechano-transductive response is critical to improving patient prognosis. This article represents data regarding a study published in Cardiovascular Diabetology (Rice et al., 2006) [1] and Open Journal of Endocrine and Metabolic Diseases (Rice et al., 2015) [2] with the purpose of evaluating the effect of pressurization on rat inferior venae cavae (IVC). Here we provide the information about the method and processing of raw data related to our prior publish work and Data in Brief articles (Rice et al., Submitted for publication) [3,4]. The data contained in this article evaluates the contribution of mTor signaling and associated proteins. IVC from lean and obese animals were exposed to a 30min perfusion of 120mm Hg pressure and evaluated for changes in expression and phosphorylation of mTor, p70s6k, GSK3β, and 4EBP-1.



http://ift.tt/2jOEHol

Plant Cytokinesis: Terminology for Structures and Processes

Publication date: Available online 21 September 2017
Source:Trends in Cell Biology
Author(s): Andrei Smertenko, Farhah Assaad, František Baluška, Magdalena Bezanilla, Henrik Buschmann, Georgia Drakakaki, Marie-Theres Hauser, Marcel Janson, Yoshinobu Mineyuki, Ian Moore, Sabine Müller, Takashi Murata, Marisa S. Otegui, Emmanuel Panteris, Carolyn Rasmussen, Anne-Catherine Schmit, Jozef Šamaj, Lacey Samuels, L. Andrew Staehelin, Daniel Van Damme, Geoffrey Wasteneys, Viktor Žárský
Plant cytokinesis is orchestrated by a specialized structure, the phragmoplast. The phragmoplast first occurred in representatives of Charophyte algae and then became the main division apparatus in land plants. Major cellular activities, including cytoskeletal dynamics, vesicle trafficking, membrane assembly, and cell wall biosynthesis, cooperate in the phragmoplast under the guidance of a complex signaling network. Furthermore, the phragmoplast combines plant-specific features with the conserved cytokinetic processes of animals, fungi, and protists. As such, the phragmoplast represents a useful system for understanding both plant cell dynamics and the evolution of cytokinesis. We recognize that future research and knowledge transfer into other fields would benefit from standardized terminology. Here, we propose such a lexicon of terminology for specific structures and processes associated with plant cytokinesis.



http://ift.tt/2yw2OLS

Single Nucleotide Polymorphism relevance learning with Random Forests for Type 2 diabetes risk prediction

Publication date: Available online 22 September 2017
Source:Artificial Intelligence in Medicine
Author(s): Beatriz López, Ferran Torrent-Fontbona, Ramón Viñas, José Manuel Fernández-Real
ObjectiveThe use of artificial intelligence techniques to find out which Single Nucleotide Polymorphisms (SNPs) promote the development of a disease is one of the features of medical research, as such techniques may potentially aid early diagnosis and help in the prescription of preventive measures. In particular, the aim is to help physicians to identify the relevant SNPs related to Type 2 diabetes, and to build a decision-support tool for risk prediction.MethodsWe use the Random Forest (RF) technique in order to search for the most important attributes (SNPs) related to diabetes, giving a weight (degree of importance), ranging between 0 and 1, to each attribute. Support Vector Machines and Logistic Regression have also been used since they are two other machine learning techniques that are well-established in the health community. Their performance has been compared to that achieved by RF. Furthermore, the relevance of the attributes obtained through the use of RF has then been used to perform predictions with k-Nearest Neighbour method weighting attributes in the similarity measure according to the relevance of the attributes with RF.ResultsTesting is performed on a set of 677 subjects. RF is able to handle the complexity of features' interactions, overfitting, and unknown attribute values, providing the SNPs' relevance with an up to 0.89 area under the ROC curve in terms of risk prediction. RF outperforms all the other tested machine learning techniques in terms of prediction accuracy, and in terms of the stability of the estimated relevance of the attributes.ConclusionsThe Random Forest is a useful method for learning predictive models and the relevance of SNPs without any underlying assumption.



http://ift.tt/2hobrQF

Finding discriminative and interpretable patterns in sequences of surgical activities

Publication date: Available online 22 September 2017
Source:Artificial Intelligence in Medicine
Author(s): Germain Forestier, François Petitjean, Pavel Senin, Laurent Riffaud, Pierre-Louis Henaux, Pierre Jannin
ObjectiveSurgery is one of the riskiest and most important medical acts that is performed today. Understanding the ways in which surgeries are similar or different from each other is of major interest to understand and analyze surgical behaviors. This article addresses the issue of identifying discriminative patterns of surgical practice from recordings of surgeries. These recordings are sequences of low-level surgical activities representing the actions performed by surgeons during surgeries.Materials and methodTo discover patterns that are specific to a group of surgeries, we use the vector space model (VSM) which is originally an algebraic model for representing text documents. We split long sequences of surgical activities into subsequences of consecutive activities. We then compute the relative frequencies of these subsequences using the tf*idf framework and we use the Cosine similarity to classify the sequences. This process makes it possible to discover which patterns discriminate one set of surgeries recordings from another set.ResultsExperiments were performed on 40 neurosurgeries of anterior cervical discectomy (ACD). The results demonstrate that our method accurately identifies patterns that can discriminate between (1) locations where the surgery took place, (2) levels of expertise of surgeons (i.e., expert vs. intermediate) and even (3) individual surgeons who performed the intervention. We also show how the tf*idf weight vector can be used to both visualize the most interesting patterns and to highlight the parts of a given surgery that are the most interesting.ConclusionsIdentifying patterns that discriminate groups of surgeon is a very important step in improving the understanding of surgical processes. The proposed method finds discriminative and interpretable patterns in sequences of surgical activities. Our approach provides intuitive results, as it identifies automatically the set of patterns explaining the differences between the groups.

Graphical abstract

http://ift.tt/2hoMGE0

Special section on artificial intelligence for diabetes

Publication date: Available online 22 September 2017
Source:Artificial Intelligence in Medicine
Author(s): Beatriz López, Clare Martin, Pau Herrero Viñas




http://ift.tt/2hoB0Bn

Contents

Publication date: November 2017
Source:Neurobiology of Aging, Volume 59





http://ift.tt/2yiyvHl

Establishing the role of rare coding variants in known Parkinson's disease risk loci

Publication date: November 2017
Source:Neurobiology of Aging, Volume 59
Author(s): Iris E. Jansen, J. Raphael Gibbs, Mike A. Nalls, T. Ryan Price, Steven Lubbe, Jeroen van Rooij, André G. Uitterlinden, Robert Kraaij, Nigel M. Williams, Alexis Brice, John Hardy, Nicholas W. Wood, Huw R. Morris, Thomas Gasser, Andrew B. Singleton, Peter Heutink, Manu Sharma
Many common genetic factors have been identified to contribute to Parkinson's disease (PD) susceptibility, improving our understanding of the related underlying biological mechanisms. The involvement of rarer variants in these loci has been poorly studied. Using International Parkinson's Disease Genomics Consortium data sets, we performed a comprehensive study to determine the impact of rare variants in 23 previously published genome-wide association studies (GWAS) loci in PD. We applied Prix fixe to select the putative causal genes underneath the GWAS peaks, which was based on underlying functional similarities. The Sequence Kernel Association Test was used to analyze the joint effect of rare, common, or both types of variants on PD susceptibility. All genes were tested simultaneously as a gene set and each gene individually. We observed a moderate association of common variants, confirming the involvement of the known PD risk loci within our genetic data sets. Focusing on rare variants, we identified additional association signals for LRRK2, STBD1, and SPATA19. Our study suggests an involvement of rare variants within several putatively causal genes underneath previously identified PD GWAS peaks.



http://ift.tt/2yifDsd

MultiTEP platform–based DNA vaccines for alpha-synucleinopathies: preclinical evaluation of immunogenicity and therapeutic potency

Publication date: November 2017
Source:Neurobiology of Aging, Volume 59
Author(s): Hayk Davtyan, Karen Zagorski, Irina Petrushina, Konstantin Kazarian, Natalie R.S. Goldberg, Janet Petrosyan, Mathew Blurton-Jones, Eliezer Masliah, David H. Cribbs, Michael G. Agadjanyan, Anahit Ghochikyan
We have previously demonstrated that anti-beta amyloid DNA vaccine (AV-1959D) based on our proprietary MultiTEP platform technology is extremely immunogenic in mice, rabbits, and monkeys. Importantly, MultiTEP platform enables development of vaccines targeting pathological molecules involved in various neurodegenerative disorders. Taking advantage of the universality of MultiTEP platform, we developed DNA vaccines targeting 3 B-cell epitopes (amino acids [aa]85-99, aa109-126, and aa126-140) of human alpha-synuclein (hα-Syn) separately or all 3 epitopes simultaneously. All 4 DNA vaccines (1) generate high titers of anti-hα-Syn antibodies and (2) induce robust MultiTEP-specific T-helper cell responses without activation of potentially detrimental autoreactive anti-hα-Syn T-helper cells. Generated antibodies recognize misfolded hα-Syn produced by neuroblastoma cells, hα-Syn in the brain tissues of transgenic mouse strains and in the brain tissues of dementia with Lewy body cases. Based on these results, the most promising vaccine targeting 3 B-cell epitopes of hα-Syn simultaneously (PV-1950D) has been chosen for ongoing preclinical assessment in mouse models of hα-Syn with the aim to translate it to the human clinical trials.



http://ift.tt/2xnrBBA

Tau positron emission tomography using [18F]THK5351 and cerebral glucose hypometabolism in Alzheimer's disease

Publication date: November 2017
Source:Neurobiology of Aging, Volume 59
Author(s): Jae Myeong Kang, Sang-Yoon Lee, Seongho Seo, Hye Jin Jeong, Sung-Ho Woo, Hyon Lee, Yeong-Bae Lee, Byeong Kil Yeon, Dong Hoon Shin, Kee Hyung Park, Hyejin Kang, Nobuyuki Okamura, Shozo Furumoto, Kazuhiko Yanai, Victor L. Villemagne, Joon-Kyung Seong, Duk L. Na, Tatsuo Ido, Jaelim Cho, Kyoung-Min Lee, Young Noh
This study aims to evaluate the clinical validity of [¹⁸F]THK5351 positron emission tomography (PET) for the assessment of disease progression and symptoms in Alzheimer's disease (AD). Fifty-one patients with AD dementia, 30 patients with amnestic mild cognitive impairment (aMCI), and 43 controls with normal cognition (NC) were included. All subjects underwent [¹⁸F]THK5351 PET, 3.0-T magnetic resonance imaging, and detailed neuropsychological tests. Regions of interest and voxel-based statistical analyses were performed. In patients with AD dementia, [¹⁸F]THK5351 retention was greater in most association cortices as well as the limbic area compared to NC or aMCI participants. Patients with aMCI also showed higher THK5351 retention in those areas compared to NC. [¹⁸F]THK5351 retention significantly correlated with neuropsychological test results. Negative correlations between [¹⁸F]THK5351 and [¹⁸F] fluorodeoxyglucose were observed in AD dementia and aMCI groups. Mirror images of [¹⁸F]THK5351 retention and glucose hypometabolism in [¹⁸F] fluorodeoxyglucose were noticeable in the focal variants of AD. [¹⁸F]THK5351 PET reflects disease severity and symptoms in AD. Our results suggest [¹⁸F]THK5351 is reflective of tau-related AD pathology.



http://ift.tt/2yixWNV