bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization and characterization of n-hexane extracts of arabica coffee ground (Coffea arabica L.) fromgayo plateau as source of natural antioxidant
Authors: Nurman Salfauqi , Lamona Asmeri , Nasir Muhammad
Published: September 2019

Arabica coffee is a major commodity crop in the Gayo Plateau, Aceh Province. Utilization of coffee in the area only as a raw material for making coffee drinks and produce waste that is not utilized. The aim of this study is optimization and characterization of n-hexane extract of Arabica Gayo coffee ground (Coffeaarabica L.) as a source of natural antioxidant. The extraction process used soxhlet method with n-hexane solvent. Characterization of arabica coffee ground oil consist ofanalysis of functional group using FTIR, component analysis using GC-MS and antioxidant analysis using DPPH method. The optimum time of the soxhletprocess of Arabica coffee is 180 minutes with rendement of 9,54%, analysis of functional group shows CH2 asymmetric stretch at 2922 cm−1, CH2 symmetric stretch at 2853 cm−1, C=O asymmetric stretch at 1741 cm−1, CH2 bending at 1458 cm−1, C-CH3 vibration at 1159 cm−1 and CH vibration at 718 cm−1. The main component of Arabica Gayo coffee ground oil is 1,2-benzenedicarboxylic acid, bis(2-ethylhexyl) ester with an area of 18.09%, antioxidant activitiy of Arabica Gayo coffee ground oil is very weak with IC50 value = 1222,31 ppm.
Identification of Magnetite Material (Fe3O4) Based on Natural Materials as Catalyst for Industrial Raw Material Application
Authors: Maulinda  , Zein Ikramullah , Jalil Zulkarnain
Published: September 2019

Identification of magnetite nanoparticles synthesized from natural iron sand with a chemical treatment that is by using thecoprecipitation method on temperature and heated spaces, using a pair of acids and bases, i.e. HCL as a solvent NH4OH and as its precipation. The Crystal structure, the percentage of elements, the particle size and properties of the magnetism material characterization by XRD, XRF identification testing, and permagraph. From the results obtained in the Analysis that the value of the percentage purity of Fe3O4 are derived from Natural Sands before Extraction is of 81.42%, and once on extract 86.73% increase to its purity. From the results of the analysis of properties of ferrite magnet to Fe3O4from sand iron retrieved the value of Saturation Magnetization (Ms) produced amounted to 0.29 T, or residual magnetization Remanence (Br) of 0081 T, and Coercivityy(Hc) amounted to 1.82 kA/m expected data analysis results may explain the comparison characteristics in structure and magnetic properties of material with a natural sand Fe3O4 Aldrich so it can be an additional related information value added (added value) the local SDA.
Design, fabrication and performance analysis of a horizontal axis wind turbine using hawk wing system at Baru Beach, Yogyakarta, Indonesia
Authors: Widodo  , Syamsiro M , Iskandar M , Mujiyono
Published: September 2019

South Java Coast in Indonesia is a potential location for developing wind power due to the abundant wind resources. One of the prospective areas is Baru beach, Srandakan, Bantul, Yogyakarta. In this area, the wind speed could reach 0-12 m/s with the average speed was 6 m/s. The objective of this research is to design and manufacture of Hawk Wings blades. The blades were hardly stop when spinning resulting quick rotation and high torque which were suitable for the wind characteristics at Baru beach. The windmill installation consists of some main components, i.e. blade, AC generator 3 phases, tower and foundation, wind orientation control, rectifier, battery, and load. The direct method using 2000 watt generator was used to design the wind mill. The blade was disassembled and then installed to the generator axis. The DC electricity was used as a power for charging 12 volt batteries. At Baru beach, the blade with a radius of 95 cm, width 24 cm base, 8 cm wide end a angle of 0-37° produced rotation of 0-2000 rpm, and voltage of 0-48 volts. The tests were carried out for 38 hours resulted in 3224,86 watt hour energy. As a result, the average of 1 hour production process generated electrical energy in the form of DC at 84.86 watt-hour.
Solar cell and thermoelectric hybrid generators
Authors: Prapawan T.
Published: September 2019

This research presents the study of the production of hybrid systems co-generating electricity of solar cells and thermoelectric heat loss from solar cells to thermoelectric. The system used in the experiment consists of a 10 watt solar panel, size 350 mm × 250 mm × 25 mm, supported by metal plates for heat and installed with a thermoelectric 10 thermoelectric solar cell module installed, will install the thermal side of the thermoelectric under the panel solar cell. The cold side is cooled by the heatsink. The built system will experiment in open space. Notify all day the heat that is lost under the solar cell and supported by metal plates is used to generate electricity with thermoelectric. Which can convert the heat energy into DC power according to the phenomena of according to the seebeck effect. From the results of the experiment, it was found that the average heating temperature was 59.42 degrees celcius. The average cold temperature is 37.37 degrees celcius at 12:30 PM. The maximum temperature difference is 24 degrees celcius. The voltage is 0.98 mV DC. The current is 224.65 mA. The average power output from the solar cell is 5.36 W and The average power output from thermoelectric is 220.16 mW.
Jordan decompositions of cocenters of reductive 𝑝-adic groups
Authors: He Xuhua , Kim Ju-Lee
Published: September 2019

Cocenters of Hecke algebras

H

\mathcal {H}

play an important role in studying mod

ℓ
\ell

or

C

\mathbb C

harmonic analysis on connected

p
p

-adic reductive groups. On the other hand, the depth

r
r

Hecke algebra

H

r
+

\mathcal {H}_{r^+}

is well suited to study depth

r
r

smooth representations. In this paper, we study depth

r
r

rigid cocenters

H

¯

r
+

r
i
g

\overline {\mathcal {H}}^\mathrm {rig}_{r^+}

of a connected reductive

p
p

-adic group over rings of characteristic zero or

ℓ
≠
p

\ell \neq p

. More precisely, under some mild hypotheses, we establish a Jordan decomposition of the depth

r
r

rigid cocenter, hence find an explicit basis of

H

¯

r
+

r
i
g

\overline {\mathcal {H}}^\mathrm {rig}_{r^+}

.
Predicting disease-associated circular RNAs using deep forests combined with positive-unlabeled learning methods
Authors: Zeng Xiangxiang , Zhong Yue , Lin Wei , Zou Quan
Published: September 2019

Identification of disease-associated circular RNAs (circRNAs) is of critical importance, especially with the dramatic increase in the amount of circRNAs. However, the availability of experimentally validated disease-associated circRNAs is limited, which restricts the development of effective computational methods. To our knowledge, systematic approaches for the prediction of disease-associated circRNAs are still lacking. In this study, we propose the use of deep forests combined with positive-unlabeled learning methods to predict potential disease-related circRNAs. In particular, a heterogeneous biological network involving 17 961 circRNAs, 469 miRNAs, and 248 diseases was constructed, and then 24 meta-path-based topological features were extracted. We applied 5-fold cross-validation on 15 disease data sets to benchmark the proposed approach and other competitive methods and used Recall@k and PRAUC@k to evaluate their performance. In general, our method performed better than the other methods. In addition, the performance of all methods improved with the accumulation of known positive labels. Our results provided a new framework to investigate the associations between circRNA and disease and might improve our understanding of its functions.
Genetic marker gene, recQ, differentiating Bacillus subtilis and the closely related Bacillus species
Authors: Heo Jun , Kim Jeong-Seon , Hong Seung-Beom , Park Byeong-Yong , Kim Soo-Jin , Kwon Soon-Wo
Published: September 2019

RecQ, which encodes a DNA helicase, was selected in searching for a marker gene of Bacillus subtilis and related species via genome mining. RecQ gene sequence similarity of type strains among Bacillus species used in this study ranged from 66.2% to 96.6%, whereas orthologous average nucleotide identity ranged from 72.6% to 95.8%. According to the phylogenetic tree based on recQ sequences, each type strain of all Bacillus species or subspecies used in this study was placed in a unique taxonomic position. Four B. subtilis subspecies, Bacillus tequilensis and Bacillus vallismortis were grouped in one cluster (cluster A). Strains of B. subtilis subsp. subtilis were classified into A1 cluster, and divided into subgroups. Isolates from Natto, Japanese fermented bean food, were classified into one subgroup, whereas those from Cheonggukjang, Korean fermented bean food, were divided into several subgroups within A1. Type strains of Bacillus halotolerans and Bacillus mojavensis were grouped into another cluster (cluster B), related to cluster A. Bacillus siamensis, Bacillus velezensis and Bacillus amyloliquefaciens were grouped into an independent cluster (cluster E). Sequencing of recQ was useful for the classification or differentiation of B. subtilis and closely related species. Therefore, recQ gene can be applied to the classification of these taxa.
Intracellular galectins control cellular responses commensurate with cell surface carbohydrate composition
Authors: Hong Ming-Hsiang , Lin Wei-Han , Weng I-Chun , Hung Yu-Hsien , Chen Hung-Lin , Chen Huan-Yuan , Chen Peilin , Lin Chun-Hung , Yang Wei Yuan , Liu Fu-Tong
Published: September 2019

Galectins are β-galactoside-binding animal lectins primarily found in the cytosol, while their carbohydrate ligands are mainly distributed in the extracellular space. Cytosolic galectins are anticipated to accumulate on damaged endocytic vesicles through binding to glycans initially displayed on the cell surface and subsequently located in the lumen of the vesicles, and this can be followed by cellular responses. To facilitate elucidation of the mechanism underlying this process, we adopted a model system involving induction of endocytic vesicle damage with light that targets the endocytosed amphiphilic photosensitizer disulfonated aluminum phthalocyanine. We demonstrate that the levels of galectins around damaged endosomes are dependent on the composition of carbohydrates recognized by the proteins. By super resolution imaging, galectin-3 and galectin-8 aggregates were found to be distributed in distinct microcompartments. Importantly, galectin accumulation is significantly affected when cell surface glycans are altered. Furthermore, accumulated galectins can direct autophagy adaptor proteins toward damaged endocytic vesicles, which are also significantly affected following alteration of cell surface glycans. We conclude that cytosolic galectins control cellular responses reflect dynamic modifications of cell surface glycans.
WISDOM project – V. Resolving molecular gas in Keplerian rotation around the supermassive black hole in NGC 0383
Authors: North Eve V , Davis Timothy A , Bureau Martin , Cappellari Michele , Iguchi Satoru , Liu Lijie , Onishi Kyoko , Sarzi Marc , Smith Mark D , Williams Thomas G
Published: September 2019

As part of the mm-Wave Interferometric Survey of Dark Object Masses (WISDOM), we present a measurement of the mass of the supermassive black hole (SMBH) in the nearby early-type galaxy NGC 0383 (radio source 3C 031). This measurement is based on Atacama Large Millimeter/sub-millimeter Array (ALMA) cycle 4 and 5 observations of the 12CO(2–1) emission line with a spatial resolution of 58 × 32 pc2 (0.18 arcsec × 0.1 arcsec). This resolution, combined with a channel width of 10 km s−1, allows us to well resolve the radius of the black hole sphere of influence (measured as RSOI = 316 pc  =  0.98 arcsec), where we detect a clear Keplerian increase of the rotation velocities. NGC 0383 has a kinematically relaxed, smooth nuclear molecular gas disc with weak ring/spiral features. We forward model the ALMA data cube with the Kinematic Molecular Simulation (KinMS) tool and a Bayesian Markov Chain Monte Carlo method to measure an SMBH mass of (4.2 ± 0.7) × 109 M⊙, a F160W-band stellar mass-to-light ratio that varies from 2.8 ± 0.6 M⊙/L$_{\odot ,\, \mathrm{F160W}}$ in the centre to 2.4 ± 0.3 M⊙$/\rm L_{\odot ,\, \mathrm{F160W}}$ at the outer edge of the disc and a molecular gas velocity dispersion of 8.3 ± 2.1 km s−1(all 3σ uncertainties). We also detect unresolved continuum emission across the full bandwidth, consistent with synchrotron emission from an active galactic nucleus. This work demonstrates that low-J CO emission can resolve gas very close to the SMBH ($\approx 140\, 000$ Schwarzschild radii) and hence that the molecular gas method is highly complimentary to megamaser observations, as it can probe the same emitting material.
How to add massive neutrinos to your ΛCDM simulation – extending cosmology rescaling algorithms
Authors: Zennaro Matteo , Angulo Raúl E , Aricò Giovanni , Contreras Sergio , Pellejero-Ibáñez Marcos
Published: September 2019

Providing accurate predictions for the spatial distribution of matter and luminous tracers in the presence of massive neutrinos is an important task, given the imminent arrival of highly accurate large-scale structure observations. In this work, we address this challenge by extending cosmology-rescaling algorithms to massive neutrino cosmologies. In this way, a ΛCDM simulation can be modified to provide non-linear structure formation predictions in the presence of a hot component of arbitrary mass, and, if desired, to include non-gravitational modifications to the clustering of matter on large scales. We test the accuracy of the method by comparing its predictions to a suite of simulations carried out explicitly including a neutrino component in its evolution equations. We find that, for neutrino masses in the range Mν ∈ [0.06, 0.3] eV the matter power spectrum is recovered to better than $1{{\ \rm per\ cent}}$ on all scales k < 2 h Mpc−1. Similarly, the halo mass function is predicted at a few per cent level over the range Mhalo ∈ [1012, 1015] h−1 M⊙, and so do also the multipoles of the galaxy two-point correlation function in redshift space over r ∈ [0.1, 200] h−1 Mpc. We provide parametric forms for the necessary transformations, as a function of Ωm and Ων for various target redshifts.
The Genetic Background Modulates the Evolution of Fluoroquinolone-Resistance in Mycobacterium tuberculosis
Authors: Castro Rhastin A D , Ross Amanda , Kamwela Lujeko , Reinhard Miriam , Loiseau Chloé , Feldmann Julia , Borrell Sonia , Trauner Andrej , Gagneux Sebastien
Published: September 2019

Fluoroquinolones (FQ) form the backbone in experimental treatment regimens against drug-susceptible tuberculosis. However, little is known on whether the genetic variation present in natural populations of Mycobacterium tuberculosis (Mtb) affects the evolution of FQ-resistance (FQ-R). To investigate this question, we used nine genetically distinct drug-susceptible clinical isolates of Mtb and measured their frequency of resistance to the FQ ofloxacin (OFX) in vitro. We found that the Mtb genetic background led to differences in the frequency of OFX-resistance (OFX-R) that spanned two orders of magnitude and substantially modulated the observed mutational profiles for OFX-R. Further, in vitro assays showed that the genetic background also influenced the minimum inhibitory concentration and the fitness effect conferred by a given OFX-R mutation. To test the clinical relevance of our in vitro work, we surveyed the mutational profile for FQ-R in publicly available genomic sequences from clinical Mtb isolates, and found substantial Mtb lineage-dependent variability. Comparison of the clinical and the in vitro mutational profiles for FQ-R showed that 51% and 39% of the variability in the clinical frequency of FQ-R gyrA mutation events in Lineage 2 and Lineage 4 strains, respectively, can be attributed to how Mtb evolves FQ-R in vitro. As the Mtb genetic background strongly influenced the evolution of FQ-R in vitro, we conclude that the genetic background of Mtb also impacts the evolution of FQ-R in the clinic.
OGRDB: a reference database of inferred immune receptor genes
Authors: Lees William , Busse Christian E , Corcoran Martin , Ohlin Mats , Scheepers Cathrine , Matsen Frederick A , Yaari Gur , Watson Corey T ,   The AIRR Community, Collins Andrew , Shepherd Adrian J
Published: September 2019

High-throughput sequencing of the adaptive immune receptor repertoire (AIRR-seq) is providing unprecedented insights into the immune response to disease and into the development of immune disorders. The accurate interpretation of AIRR-seq data depends on the existence of comprehensive germline gene reference sets. Current sets are known to be incomplete and unrepresentative of the degree of polymorphism and diversity in human and animal populations. A key issue is the complexity of the genomic regions in which they lie, which, because of the presence of multiple repeats, insertions and deletions, have not proved tractable with short-read whole genome sequencing. Recently, tools and methods for inferring such gene sequences from AIRR-seq datasets have become available, and a community approach has been developed for the expert review and publication of such inferences. Here, we present OGRDB, the Open Germline Receptor Database (https://ogrdb.airr-community.org), a public resource for the submission, review and publication of previously unknown receptor germline sequences together with supporting evidence.
Disruption of MIR396e and MIR396f improves rice yield under nitrogen-deficient conditions
Authors: Zhang Jinshan , Zhou Zhenyu , Bai Jinjuan , Tao Xiaoping , Wang Ling , Zhang Hui , Zhu Jian-Kang
Published: September 2019

The microRNA miR396 directly represses GROWTH-REGULATING FACTORs (OsGRFs) and has been implicated in regulating rice yield and in nitrogen assimilation. Overexpressing the miR396 targets OsGRF4 and OsGRF6 improves rice yield via increased grain size and panicle branching, respectively. Here, we used CRISPR/Cas9 to assess the function of miR396 genes in rice. Knockout of MIR396ef (MIR396e and MIR396f), but not other isoforms, enhanced both grain size and panicle branching, resulting in increased grain yield. Importantly, under nitrogen-deficient conditions, mir396ef mutants showed an even higher relative increase in grain yield as well as elevated above-ground biomass. Furthermore, we identified OsGRF8 as a new target of miR396, in addition to the known targets OsGRF4 and OsGRF6. Disruption of the miR396-targeting site in OsGRF8 was sufficient to both enlarge grain size and elongate panicles. Our results suggest that rice-seed and panicle development are regulated by miR396ef-GRF4/6/8-GIF1/2/3 modules and that miR396ef are promising targets of genome editing for breeding environmentally friendly rice varieties that require less nitrogen fertilization.
Carceral Spaces and Social Reproduction: Exploring Export Processing Zones in Sri Lanka and Prisons in Argentina
Authors: Pereyra-Iraola Victoria , Gunawardana Samanthi J
Published: September 2019

The article reflects on the ways in which social reproduction intersects with (im)mobility in export-processing zones in Sri Lanka and the outskirts of prisons in Argentina. Framing factories and prisons as “carceral spaces” and drawing upon diverse case study materials, it focuses on (i) the daily circulations and waiting that take place around these closely regulated sites and (ii) the relations of care that emerge in these sites. The article analyzes how gendered care work can be an active form of agency and resistance to structural confinement and violence, which is nevertheless embedded in broader forms of depletion.
Do we know who they are? On the identity of Pholoe (Annelida: Sigalionidae: Pholoinae) species from northern Europe
Authors: Meißner Karin , Götting Miriam , Nygren Arne
Published: September 2019

Pholoe species described from northern European coastal waters are studied here, based on morphological and molecular methods. We confirm the current taxonomic status of P. assimilis, P. baltica, P. inornata and P. pallida. All species descriptions are reviewed and refined, barcodes are provided allowing the identification of these species based on molecular markers. Expanding morphological methods by using confocal laser scanning microscopy has added new characters to species diagnoses and makes species identification more secure. The reliability of characters traditionally used for identification of Pholoe species is evaluated. The newly presented identification key allows the delimitation of the four species reported for European coastal waters and also includes P. minuta and P. longa. The latter have been originally described from Greenland, but were often reported from European coastal waters. The results of our studies provide new insights into the distribution of the different species. Relationships of Pholoe species from mainly northern European waters are analysed based on molecular mitochondrial and nuclear markers. We stress the need for the prospective development of a precise terminology for prostomial appendages in Pholoe by including fine anatomical studies.
Ongoing revision of Echiniscoididae (Heterotardigrada: Echiniscoidea), with the description of a new interstitial species and genus with unique anal structures
Authors: Møbjerg Nadja , Jørgensen Aslak , Kristensen Reinhardt M
Published: September 2019

Marine tidal heterotardigrades (Echiniscoididae) have gained increasing interest owing to their unique adaptations and evolutionary position, bridging marine and limnoterrestrial taxa. Echiniscoididae was established to accommodate the marine genera Anisonyches and Echiniscoides. However, it has become apparent that Anisonyches, with its claw configuration, median cirrus and seminal receptacles, clearly has little or no affinity to tidal echiniscoidids with supernumerary claws. Consequently, we establish Anisonychidae fam. nov. to accommodate Anisonyches in a paraphyletic Arthrotardigrada and discuss its affinity to other heterotardigrade taxa. We recently split Echiniscoides into Isoechiniscoides and Echiniscoides s.l. The latter remains a miscellany of species complexes and undescribed genera, and it has become evident that a larger number of echiniscoidids belonging to Echiniscoides, Isoechiniscoides and undescribed genera coexist in intertidal sediments. Here, we erect Neoechiniscoides aski gen. nov., sp. nov. from Roscoff, France, which has a unique anal system, characterized by prominent lateral lobes with a set of wing-like structures. Phylogenetic analyses based on COI sequences infer a close relationship between N. aski, an undescribed species from Roscoff and unidentified species from Maine, USA. We propose that the new genus includes the former Echiniscoides species Echiniscoides pollocki and Echiniscoides horningi, which we hereby transfer.
Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of Trypanosoma brucei brucei
Authors: Balogun Emmanuel Oluwadare , Inaoka Daniel Ken , Shiba Tomoo , Tsuge Chiaki , May Benjamin , Sato Tomohiro , Kido Yasutoshi , Nara Takeshi , Aoki Takashi , Honma Teruki , Tanaka Akiko , Inoue Masayuki , Matsuoka Shigeru , Michels Paul A. M. , Watanabe Yoh‐Ichi , Moore Anthony L. , Harada Shigeharu , Kita Kiyoshi
Published: September 2019

African trypanosomiasis, sleeping sickness in humans or nagana in animals, is a potentially fatal neglected tropical disease and a threat to 65 million human lives and 100 million small and large livestock animals in sub‐Saharan Africa. Available treatments for this devastating disease are few and have limited efficacy, prompting the search for new drug candidates. Simultaneous inhibition of the trypanosomal glycerol kinase (TGK) and trypanosom alalternative oxidase (TAO) is considered a validated strategy toward the development of new drugs. Our goal is to develop a TGK‐specific inhibitor for coadministration with ascofuranone (AF), the most potent TAO inhibitor. Here, we report on the identification of novel compounds with inhibitory potency against TGK. Importantly, one of these compounds (compound 17) and its derivatives (17a and 17b) killed trypanosomes even in the absence of AF. Inhibition kinetics revealed that derivative 17b is a mixed‐type and competitive inhibitor for TGK and TAO, respectively. Structural data revealed the molecular basis of this dual inhibitory action, which, in our opinion, will aid in the successful development of a promising drug to treat trypanosomiasis. Although the EC50 of compound 17b against trypanosome cells was 1.77 μM, it had no effect on cultured human cells, even at 50 μM.—Balogun, E. O., Inaoka, D. K., Shiba, T., Tsuge, C., May, B., Sato, T., Kido, Y., Nara, T., Aoki, T., Honma, T., Tanaka, A., Inoue, M., Matsuoka, S., Michels, P. A. M., Watanabe, Y.‐I., Moore, A. L., Harada, S., Kita, K. Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of Trypanosoma brucei brucei. FASEB J. 33, 13002–13013 (2019). www.fasebj.org
Data-driven discovery of changes in clinical code usage over time: a case-study on changes in cardiovascular disease recording in two English electronic health records databases (2001-2015)
Authors: Rockenschaub Patrick , Nguyen Vincent , Aldridge Rob W. , Acosta Dionisio , García-Gómez Juan M , Sáez Carlos
Published: September 2019

Objectives

To demonstrate how data-driven variability methods can be used to identify changes in disease recording in two English electronic health records databases between 2001-2015.

Design

Repeated cross-sectional analysis that applied data-driven temporal variability methods to assess month-by-month changes in routinely-collected medical data. A measure of difference between months was calculated based on joint distributions of age, gender, socio-economic status and recorded cardiovascular diseases. Distances between months were used to identify temporal trends in data recording.

Setting

400 English primary care practices from the Clinical Practice Research Datalink (CPRD GOLD) and 451 hospital trusts from the Hospital Episode Statistics (HES).

Main outcomes

The proportion of patients (CPRD GOLD) and hospital admissions (HES) with a recorded cardiovascular disease (CPRD GOLD: coronary heart disease, heart failure, peripheral arterial disease, stroke; HES: International Classification of Disease ICD codes I20-I69/G45).

Results

Both databases showed gradual changes in cardiovascular disease recording between 2001 and 2008. The recorded prevalence of included cardiovascular diseases in CPRD GOLD increased by 47%-62%, which partially reversed after 2008. For hospital records in HES, there was a relative decrease in angina pectoris (−34.4%) and unspecified stroke (−42.3%) over the same time period, with a concomitant increase in chronic coronary heart disease (+14.3%). Multiple abrupt changes in the use of myocardial infarction codes in hospital were found in March/April 2010, 2012 and 2014, possibly linked to updates of clinical coding guidelines.

Conclusions

Identified temporal variability could be related to potentially non-medical causes such as updated coding guidelines. These artificial changes may introduce temporal correlation among diagnoses inferred from routine data, violating the assumptions of frequently used statistical methods. Temporal variability measures provided an objective and robust technique to identify, and subsequently account for, those changes in electronic health records studies without any prior knowledge of the data collection process.
Succinylation Links Metabolic Reductions to Amyloid and Tau Pathology
Authors: Yang Yun , Tapias Victor , Acosta Diana , Xu Hui , Chen Huanlian , Bhawal Ruchika , Anderson Elizabeth , Ivanova Elena , Lin Hening , Sagdullaev Botir T. , Klein William L. , Viola Kirsten L. , Gandy Sam , Haroutunian Vahram , Beal M. Flint , Eliezer David , Zhang Sheng , Gibson Gary E.
Published: September 2019

Abnormalities in glucose metabolism and misfolded protein deposits composed of the amyloid-β peptide (Aβ) and tau are the three most common neuropathological hallmarks of Alzheimer’s disease (AD), but their relationship(s) to the disease process or to each other largely remains unclear. In this report, the first human brain quantitative lysine succinylome together with a global proteome analysis from controls and patients reveals that lysine succinylation contributes to these three key AD-related pathologies. Succinylation, a newly discovered protein post-translational modification (PTM), of multiple proteins, particularly mitochondrial proteins, declines with the progression of AD. In contrast, amyloid precursor protein (APP) and tau consistently exhibit the largest AD-related increases in succinylation, occurring at specific sites in AD brains but never in controls. Transgenic mouse studies demonstrate that succinylated APP and succinylated tau are detectable in the hippocampus concurrent with Aβ assemblies in the oligomer and insoluble fiber assembly states. Multiple biochemical approaches revealed that succinylation of APP alters APP processing so as to promote Aβ accumulation, while succinylation of tau promotes its aggregation and impairs its microtubule binding ability. Succinylation, therefore, is the first single PTM that can be added in parallel to multiple substrates, thereby promoting amyloidosis, tauopathy, and glucose hypometabolism. These data raise the possibility that, in order to show meaningful clinical benefit, any therapeutic and/or preventative measures destined for success must have an activity to either prevent or reverse the molecular pathologies attributable to excess succinylation.
Network Analysis of Inflammatory Bowel Disease Reveals PTPN2 As New Monogenic Cause of Intestinal Inflammation
Authors: Parlato Marianna , Pazmandi Julia , Nian Qing , Charbit-Henrion Fabienne , Bègue Bernadette , Martin Emmanuel , Thian Marini , Müller Felix , Maggioni Marco , Duclaux-Loras Rémi , Rieux-Laucat Frederic , Molina Thierry-Jo , Latour Sylvain , Ruemmele Frank , Menche Jörg , Rodrigues-Lima Fernando , Boztug Kaan , Cerf-Bensussan Nadine
Published: September 2019

BACKGROUND & AIMS

Genome-wide association studies (GWAS) have uncovered multiple loci associated with inflammatory bowel disease (IBD), yet delineating functional consequences is complex. We used a network-based approach to uncover traits common to monogenic and polygenic forms of IBD in order to reconstruct disease relevant pathways and prioritize causal genes.

METHODS

We have used an iterative random walk with restart to explore network neighborhood around the core monogenic IBD cluster and disease-module cohesion to identify functionally relevant GWAS genes. Whole exome sequencing was used to screen a cohort of monogenic IBD for germline mutations in top GWAS genes. One mutation was identified and validated by a combination of biochemical approaches.

RESULTS

Monogenic IBD genes clustered siginificantly on the molecular networks and had central roles in network topology. Iterative random walk from these genes allowed to rank the GWAS genes, among which 14 had high disease-module cohesion and were selected as putative causal genes. As a proof of concept, a germline loss of function mutation was identified in PTPN2, one of the top candidates, as a novel genetic etiology of early-onset intestinal autoimmunity. The mutation abolished the catalytic activity of the enzyme, resulting in haploinsufficiency and hyper-activation of the JAK/STAT pathway in lymphocytes.

CONCLUSIONS

Our network-based approach bridges the gap between large-scale network medicine prediction and single-gene defects and underscores the crucial need of fine tuning the JAK/STAT pathway to preserve intestinal immune homeostasis. Our data provide genetic-based rationale for using drugs targeting the JAK/STAT pathway in IBD.
Time-dependent modulation of spinal excitability during action observation in the macaque monkey
Authors: Jerjian S.J. , Lemon R.N. , Kraskov A.
Published: September 2019

Neurons in the primate motor cortex, including identified pyramidal tract neurons projecting to the spinal cord, respond to the observation of others’ actions, yet this does not cause movement in the observer. Here, we investigated changes in spinal excitability during action observation by monitoring short latency electromyographic responses produced by single shocks delivered directly to the pyramidal tract. Responses in hand and digit muscles were recorded from two adult rhesus macaques while they performed, observed or withheld reach-to-grasp and hold actions. We found modest grasp-specific facilitation of hand muscle responses during hand shaping for grasp, which persisted when the grasp was predictable but obscured from the monkey’s vision. We also found evidence of a more general inhibition before observed movement onset, and the size of this inhibition effect was comparable to the inhibition after an explicit NoGo signal. These results confirm that the spinal circuitry controlling hand muscles is modulated during action observation, and this may be driven by internal representations of actions. The relatively modest changes in spinal excitability during observation suggest net corticospinal outflow exerts only minor, sub-threshold changes on hand motoneuron pools, thereby preventing any overflow of mirror activity into overt movement.
Efferent Modulation of Spontaneous Lateral Line Activity During and after Zebrafish Motor Commands
Authors: Lunsford Elias T. , Skandalis Dimitri A. , Liao James C.
Published: September 2019

Accurate sensory processing during movement requires the animal to distinguish between external (exafferent) and self-generated (reafferent) stimuli to maintain sensitivity to biologically relevant cues. The lateral line system in fishes is a mechanosensory organ that experiences reafferent sensory feedback via detection of fluid motion relative to the body generated during behaviors such as swimming. For the first time in larval zebrafish (Danio rerio), we employed simultaneous recordings of lateral line and motor activity to reveal the activity of afferent neurons arising from endogenous feedback from hindbrain efferent neurons during locomotion. Frequency of spontaneous spiking in posterior lateral line afferent neurons decreased during motor activity and was absent for more than half of swimming trials. Targeted photoablation of efferent neurons abolished the afferent inhibition that was correlated to swimming, indicating that inhibitory efferent neurons are necessary for modulating lateral line sensitivity during locomotion. We monitored calcium activity with Tg(elav13:GCaMP6s) fish and found synchronous activity between putative cholinergic efferent neurons and motor neurons. We examined correlates of motor activity to determine which may best predict the attenuation of afferent activity and therefore what components of the motor signal are translated through the corollary discharge. Swim duration was most strongly correlated to the change in afferent spike frequency. Attenuated spike frequency persisted past the end of the fictive swim bout, suggesting that corollary discharge also affects the glide phase of burst and glide locomotion. The duration of the glide in which spike frequency was attenuated increased with swim duration but decreased with motor frequency. Our results detail a neuromodulatory mechanism in larval zebrafish that adaptively filters self-generated flow stimuli during both the active and passive phases of locomotion.
Cerebellar Purkinje cell microcircuits are essential for tremor
Authors: Brown Amanda M , White Joshua J , van der Heijden Meike E , Lin Tao , Sillitoe Roy V
Published: September 2019

Tremor is currently ranked as the most common movement disorder. The brain regions and neural signals that initiate the debilitating shakiness of different body parts remain unclear. Here, we found that genetically silencing cerebellar Purkinje cell activity blocked tremor in mice that were given the tremorgenic drug harmaline. We show in awake behaving mice that the onset of tremor is coincident with rhythmic Purkinje cell firing, which alters the output of their target cerebellar nuclei cells. We mimic the tremorgenic action of the drug with optogenetics and present evidence that highly patterned Purkinje cell activity drives a powerful tremor in otherwise normal mice. Modulating the altered activity with deep brain stimulation directed to the Purkinje cell output in the cerebellar nuclei reduced tremor in freely moving mice. Together, the data implicate Purkinje cell connectivity as a neural substrate for tremor and a gateway for signals that mediate the disease.
Genetic integration of behavioural and endocrine components of the stress response
Authors: Houslay T.M. , Earley R.L. , White S.J. , Lammers W. , Grimmer A.J. , Travers L.M. , Johnson E.L. , Young A.J. , Wilson A.J.
Published: September 2019

The vertebrate stress response comprises a suite of behavioural and physiological traits that must be functionally integrated to ensure organisms cope adaptively with acute stressors. Natural selection should favour functional integration, leading to a prediction of genetic integration of these traits. Despite the implications of such genetic integration for our understanding of human and animal health, as well as evolutionary responses to natural and anthropogenic stressors, formal quantitative genetic tests of this prediction are lacking. Here we demonstrate that acute stress response components in Trinidadian guppies are both heritable and integrated on the major axis of genetic covariation. This integration could either facilitate or constrain evolutionary responses to selection, depending upon the alignment of selection with this axis. Such integration also suggests artificial selection on the genetically correlated behavioural responses to stress could offer a viable non-invasive route to the improvement of health and welfare in captive animal populations.
False memory in nonhuman animals
Authors: Millin Paula M. , Riccio David C.
Published: September 2019

This paper examines recent evidence from behavioral and neuroscience research with nonhuman animals that suggests the intriguing possibility that they, like their human counterparts, are vulnerable to creating false memories. Once considered a uniquely human memory phenomenon, the creation of false memories in lower animals can be seen especially readily in studies involving memory for source, or contextual attributes. Furthermore, evidence of “implanted” misinformation has also been obtained. Here, we review that research and consider its relevance to our empirical understanding of false memories, as well as speculate about its potential clinical implications for trauma memory.
Single prolonged stress alters neural activation in the periacqueductal gray and midline thalamic nuclei during emotional learning and memory
Authors: Della Valle Rebecca , Mohammadmirzaei Negin , Knox Dayan
Published: September 2019

Clinical and preclinical studies that have examined the neurobiology of persistent fear memory in posttraumatic stress disorder (PTSD) have focused on the medial prefrontal cortex, hippocampus, and amygdala. Sensory systems, the periaqueductal gray (PAG), and midline thalamic nuclei have been implicated in fear and extinction memory, but whether neural activity in these substrates is sensitive to traumatic stress (at baseline or during emotional learning and memory) remains unexplored. To address this, we used the single prolonged stress (SPS) model of traumatic stress. SPS and control rats were either subjected to fear conditioning (CS-fear) or presented with CSs alone (CS-only) during fear conditioning. All rats were then subjected to extinction training and testing. A subset of rats were euthanized after each behavioral stage and c-Fos and c-Jun used to measure neural activation in all substrates. SPS lowered c-Jun levels in the dorsomedial and lateral PAG at baseline, but the elevated c-Jun expression in the PAG during emotional learning and memory. SPS also altered c-Fos expression during fear and extinction learning/memory in midline thalamic nuclei. These findings suggest changes in neural function in the PAG and midline thalamic nuclei could contribute to persistent fear memory induced by traumatic stress. Interestingly, SPS effects were also observed in animals that never learned fear or extinction (i.e., CS-only). This raises the possibility that traumatic stress could have broader effects on the psychological function that are dependent on the PAG and midline thalamic nuclei.
Fit for purpose? Exploring competence in quality management
Authors: Martin Jason , Elg Mattias , Gremyr Ida
Published: September 2019

Purpose

The purpose of this paper is to use competence theory to explore the fit between actual competencies of quality management (QM) practitioner and the perception of QM competence needs in organisations.

Design/methodology/approach

This paper is based on a cross-case quantitative study design featuring a survey of QM practitioners (n = 249) within eight large Swedish organisations. The research instrument was a questionnaire covering seven themes within QM. The analysis is based on descriptive statistics.

Findings

The results show that while the perception of formal QM competence may seem sufficient, the evolving nature of QM requires knowledge, skills and attitudes that are also apt for more external and explorative perspectives. There is a bias towards competence for exploitative QM rather than explorative QM. Organisational logics preserving and possibly reinforcing a perceived “competence lag” in organisations are identified and described.

Originality/value

Few empirical studies within QM explore the competencies required for QM practices. This paper contributes to QM research in providing arguments for adopting the competence theory as a foundation for organising current and future QM work.
A house of sustainability-based approach for green product design
Authors: Upadhyay Parijat , Kumar Anup
Published: September 2019

Purpose

Investors are looking for the organizations which have robust strategy and planning method meeting the current and future guidelines and policies on environmental regulations to improve sustainability. Thus, most of the business units have been striving to incorporate sustainability into process and product or service design in such a way that carbon footprint should be minimized. Sustainable product and service design remain a challenge for industrial organizations because of the involvement of multifaceted factors in the design endeavor. The purpose of this paper is to develop a methodology to include sustainability functions at the design phase of the product or process.

Design/methodology/approach

The authors have modified the house of quality concept, and grey relational analysis-house of sustainability process is proposed in this paper, which includes consideration of all sustainability dimensions including environmental at the design phase of the product or process development. The process has been explained with an example of retail service design.

Findings

The proposed approach incorporates the specific business environment and the type of product to be designed with all three levels of sustainability by design. By capturing all sustainability dimensions in the design stage itself, various issues may be taken care of at the initial stage of operations, which are likely to affect sustainability in all activities of the supply chain and the organization as a whole. Thus the proactive sustainable designing considerably eases and improves the sustainability reporting and meeting the legislative guidelines prescribed by the governmental agencies of the country.

Originality/value

A novel methodology has been proposed to include sustainability functions at the design phase, which is strategically useful for sustainable operations and to develop a sustainable product or process.
What is the Main Processing Factor Influencing Staphylococcus Species Diversity in Different Manufacturing Units?
Authors: Fraqueza Maria João , Rocha João Miguel , Laranjo Marta , Potes Maria Eduarda , Fialho Ana Rita , Fernandes Maria José , Fernandes Maria Helena , Barreto António , Semedo‐Lemsaddek Teresa , Elias Miguel
Published: September 2019

The microbiota of traditional dry‐cured sausages and industrial environment was assessed to characterize the diversity of coagulase‐negative staphylococci (CNS), and establish potential relationships with hygiene level or technological characteristics. Eight processing units from South Portugal were audited according to a checklist of requirements. Environmental and products’ samples at different production stages were evaluated regarding hygiene and safety criteria. CNS were recovered, characterized, and their potential use as starters evaluated. Low genetic diversity was observed for Staphylococcus xylosus, whereas Staphylococcus equorum showed diverse genetic profiles. Staphylococcus xylosus predominated in products with a long period of cold smoking, Staphylococcus saprophyticus in products with a long period of hot smoking, Staphylococcus epidermidis in products with a short period of cold smoking, and S. equorum in nonsmoked products. Most S. xylosus were resistant to tetracycline, whereas S. equorum were susceptible. Antibioresistance restricted the selection of starters due to safety recommendations.

Practical Application

The present manuscript highlighted a few staphylococci strains that could potentially be used as starter cultures in fermented meat products. These selected strains do not show resistance to antimicrobials, exhibit adequate technological features, and are well adapted to the industrial environments of meat processing industries using different processing technologies. Therefore, the selected strains ready to be used in the manufacturing of traditional fermented meat products to ensure safety, standardize product properties, and shorten ripening.