bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Effects on Radiation Responses in Nonhuman Primates: Identification of Biofluid Small Molecule Signatures by Gas Chromatography – Mass Spectrometry Metabolomics
Authors: Pannkuk Evan L. , Laiakis Evagelia C. , Girgis Michael , Dowd Sarah E. , Dhungana Suraj , Nishita Denise , Bujold Kim , Bakke James , Gahagen Janet , Authier Simon , Chang Polly , Fornace Albert J.
Published: April 2019

Whole body exposure to ionizing radiation (IR) (> 0.7 Gy) damages tissues leading to a range of physical symptoms contributing to acute radiation syndrome (ARS). Radiation biodosimetry aims to determine characteristic early biomarkers indicative of radiation exposure (generally at doses > 2 Gy) and is a necessity for effective triage in the event of an unanticipated radiological incident and emergency preparedness. Radiation metabolomics can address this aim by assessing metabolic perturbations following various emergency scenarios (e.g., elapsed time to medical care, absorbed dose, combined injury). Gas chromatography – mass spectrometry (GC-MS) is a standardized platform ideal for chromatographic separation, identification, and quantification of metabolites to discriminate molecular signatures that can be utilized in assessing radiation injury. We performed GC time-of-flight (TOF) MS for global profiling of nonhuman primate (NHP) urine and serum samples up to 60 d after a single 4 Gy γ-ray total body exposure. Multivariate statistical analysis showed a higher separation of groups from urine signatures vs. serum signatures. We identified biofluid markers involved in amino acid, lipid, purine, and serotonin metabolism, some of which may indicate host microbiome dysbiosis. Sex differences were observed amino acid fold changes in serum samples. Additionally, we explored mitochondrial dysfunction by analysis of tricarboxylic acid (TCA) intermediates with a GC tandem quadrupole (TQ) MS platform in samples collected in a time course during the first week (1, 3, 5, and 7 d) after exposure. By adding this temporal component to our previous work exploring dose effects at a single time point of 7 d, we observed the highest fold changes occurring at 3 d, returning closer to basal levels by 7 d. These results emphasize the utility of both MS-based metabolomics for biodosimetry and complementary analytical platforms for increased metabolome coverage.
The First Report on Cryptococcus Profiles of Isolates from Patients Attending Dr George Mukhari Academic Hospital, South Africa
Authors: Jiyane Elliot Zwelibanzi , Nemarude Mis Leah , Nchabeleng Maphoshane
Published: April 2019

Introduction

Cryptococcosis is a fungal opportunistic infection that is vastly diagnosed among immune-compromised patients. Reduced susceptibility on commonly used antifungals is of concern. In the communities served by Dr. George Mukhari Tertiary (DGMT-Laboratory) Laboratory is not available.

Methodology

E-test method was used to determine if isolates with reduced susceptibility to antifungals fluconazole, voriconazole and amphotericin-B had emerged. A multiplex Polymerase Chain Reaction (PCR) method was used to further identify serotypes that are circulating at Dr. George Mukhari Tertiary (DGMT-Hospital) Hospital.

Results

E-test strips were interpreted as resistance, intermediate or susceptible in relation to each serotype identified. Of the 50 incident isolates tested, 100% were inhibited by both voriconazole and amphotericin-B. Fluconazole was resistance to 50% of incident isolates.

Conclusion

C. neoformansserotype A is the predominant serotype in the area served by DGMT-Laboratory, accounting for 96% of the isolates. It is important for public health to continuously monitor resistance emergence.
Microbial Similarity Between Students in a Common Dormitory Environment Reveals the Forensic Potential of Individual Microbial Signatures
Authors: Richardson Miles , Gottel Neil , Gilbert Jack A , Lax Simon
Published: April 2019

The microbiota of the built environment is an amalgamation of both human and environmental sources. While human sources have been examined within single-family households or in public environments, it is unclear what effect a large number of cohabitating people have on the microbial communities of their shared environment. We sampled the public and private spaces of a college dormitory, disentangling individual microbial signatures and their impact on the microbiota of common spaces. We compared multiple methods for marker gene sequence clustering, and found that Minimum Entropy Decomposition (MED) was best able to distinguish between the microbial signatures of different individuals, and was able to uncover more discriminative taxa across all taxonomic groups. Further, weighted UniFrac- and random forest-based graph analyses uncovered two distinct spheres of hand or shoe associated samples. For hand-associated samples, connection between cliques was enriched for hands, implicating them as a primary means of transmission. By contrast, shoe-associated samples were found to be freely interacting, with individual shoes more connected to each other than to the floors they interact with. Individual interactions were highly dynamic, with groups of samples originating from individuals clustering freely with other individuals, while all floor and shoe samples consistently clustered together.

Importance

Humans leave behind a microbial trail, regardless of intention. This may allow for the identification of individuals based on the ‘microbial signatures’ they shed in built environments. In a shared living environment, these trails intersect, and through interaction with common surfaces may become homogenized, potentially confounding our ability to link individuals to their associated microbiota. We sought to understand the factors that influence the mixing of individual signatures, and how best to process sequencing data to best tease apart these signatures.
Leptin and adiponectin correlations with body composition and lipid profile in children with Autism Spectrum Disorder
Authors: Castro Kamila , Faccioli Larissa Slongo , Perry Ingrid Schweigert , Santos Riesgo Rudimar dos
Published: April 2019

Leptin and adiponectin have effects on the regulation of appetite and body composition, but evidence of these relationships in children is still limited. Even though investigations of their role in children with ASD are incipient, the nutritional aspects and eating difficulties that these patients may present are increasingly highlighted, often leading to inadequate nutritional status. This cross-sectional controlled study investigated the levels of adipokines in ASD children in comparison with healthy controls, and their correlations with nutritional aspects and lipid profile. A total of 80 participants (40 ASD and 40 controls) were included and evaluated through anthropometric variables, body composition, and blood samples. ASD participants showed higher levels of leptin, no changes of adiponectin levels in comparison with typically developing children, and a positive correlation between leptin and fat mass. This novel finding supports the role of leptin as a marker of adiposity in ASD children, which is reiterated by the higher leptin/adiponectin ratio and its correlation with fat mass in patients. Inverse correlation of leptin with HDL-cholesterol could only in certain cases be related to the higher adiposity in patients when compared to controls. These results highlight also the importance of assessing the nutritional status of this population.
TeraVR Empowers Precise Reconstruction of Complete 3-D Neuronal Morphology in the Whole Brain
Authors: Wang Yimin , Li Qi , Liu Lijuan , Zhou Zhi , Wang Yun , Kong Lingsheng , Zhong Ning , Chai Renjie , Luo Xiangfeng , Guo Yike , Hawrylycz Michael , Luo Qingming , Gu Zhongze , Xie Wei , Zeng Hongkui , Peng Hanchuan
Published: April 2019

Neuron morphology is recognized as a key determinant of cell type, yet the quantitative profiling of a mammalian neuron’s complete three-dimensional (3-D) morphology remains arduous when the neuron has complex arborization and long projection. Whole-brain reconstruction of neuron morphology is even more challenging as it involves processing tens of teravoxels of imaging data. Validating such reconstructions is extremely laborious. We developed TeraVR, an open-source virtual reality annotation system, to address these challenges. TeraVR integrates immersive and collaborative 3-D visualization, interaction, and hierarchical streaming of teravoxel-scale images. Using TeraVR, we produced precise 3-D full morphology of long-projecting neurons in whole mouse brains and developed a collaborative workflow for highly accurate neuronal reconstruction.
Time elapsed between Zika and dengue virus infections affects antibody and T cell responses
Authors: Pérez-Guzmán Erick X. , Pantoja Petraleigh , Serrano-Collazo Crisanta , Hassert Mariah A. , Ortiz-Rosa Alexandra , Rodríguez Idia V. , Giavedoni Luis , Hodara Vida , Parodi Laura , Cruz Lorna , Arana Teresa , White Laura J. , Martínez Melween I. , Weiskopf Daniela , Brien James D. , de Silva Aravinda , Pinto Amelia K. , Sariol Carlos A.
Published: April 2019

The role of Zika virus (ZIKV) immunity on subsequent dengue virus (DENV) infections is relevant to anticipate the dynamics of forthcoming DENV epidemics in areas with previous ZIKV exposure. We study the effect of ZIKV infection with various strains on subsequent DENV immune response after 10 and 2 months of ZIKV infection in rhesus macaques. Our results show that a subsequent DENV infection in animals with early- and middle-convalescent periods to ZIKV do not promote an increase in DENV viremia nor pro-inflammatory status. Previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV, and different time intervals between infections alter the magnitude and durability of such responses—more after longer ZIKV pre-exposure. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.
Oral prescription opioid-seeking behavior in male and female mice
Authors: Phillips Alysabeth G. , McGovern Dillon J. , Lee Soo , Ro Kyu , Huynh David T. , Elvig Sophie K. , Fegan Katelynn N. , Root David H.
Published: April 2019

A significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug-seeking. However, intravenous models may not model oral users, and the preference to self-administer orally appears to be partially influenced by the user’s sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally self-administered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated robust cue-induced reinstatement. In separate mice we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior in the absence of postprandial or prior water self-administration training. During self-administration, we found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal steroid studies were performed in which we found divergent responses where ovariectomy enhanced and orchiectomy suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that 1) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, 2) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and 3) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes.
Estimating Attentional Set-Shifting Dynamics in Varying Contextual Bandits
Authors: Kour George , Morris Genela
Published: April 2019

In this paper, we aim at estimating, on a trial-by-trial basis, the underlying decision-making process of an animal in a complex and changing environment. We propose a method for identifying the set of stochastic policies employed by the agent and estimating the transition dynamics between policies based on its behavior in a multidimensional discrimination task for measuring the properties of attentional set-shifting of the subject (both intra- and extra-dimensional). We propose using theNon-Homogeneous Hidden Markov Models(NHMMs) framework, to consider environmental state and rewards for modeling decision-making processes in a varying version of “Contextual Bandits”. We employ the Expectation-Maximization (EM) procedure for estimating the model’s parameters similar to the Baum-Welch algorithm used to train standard HMMs. To measure the model capacity to estimate underlying dynamics, Monte Carlo analysis is employed on synthetically generated data and compared to the performance of classical HMM.
ThePseudomonas aeruginosaaccessory genome elements influence virulence towardsCaenorhabditis elegans
Authors: Vasquez-Rifo Alejandro , Veksler-Lublinsky Isana , Cheng Zhenyu , Ausubel Frederick M. , Ambros Victor
Published: April 2019

Multicellular animals and bacteria frequently engage in predator-prey and host-pathogen interactions, such as the well-studied relationship betweenPseudomonas aeruginosaand the nematodeCaenorhabditis elegans. This study investigates the genomic and genetic basis of bacterial-driven variability inP. aeruginosavirulence towardsC. elegans. Natural isolates ofP. aeruginosathat exhibit diverse genomes display a broad range of virulence towardsC. elegans. Using gene association and genetic analysis, we identified accessory genome elements that correlate with virulence, including both known and novel virulence determinants. Among the novel genes, we found a viral-like mobile element, thetegblock, that impairs virulence and whose acquisition is restricted by CRISPR-Cas systems. Further genetic and genomic evidence suggests that spacer-targeted elements preferentially associate with lower virulence and suggest a positive, albeit indirect, role for host CRISPR-Cas systems in the restriction of accessory genome elements that may be detrimental to virulence.
Predation strategies of the bacterium Bdellovibrio bacteriovorus result in overexploitation and bottlenecks
Authors: Summers J. Kimberley , Kreft Jan-Ulrich
Published: April 2019

With increasing antimicrobial resistance, alternatives for treating infections or removing resistant bacteria are urgently needed, such as the bacterial predator Bdellovibrio bacteriovorus or bacteriophage. Therefore, we need to better understand microbial predator-prey dynamics. We developed mass-action mathematical models of predation for chemostats, which capture the low substrate concentration and slow growth typical for intended application areas of the predators such as wastewater treatment, aquaculture or the gut. Our model predicted that predator survival required a minimal prey size, explaining why Bdellovibrio is much smaller than its prey. A too good predator (attack rate too high, mortality too low) overexploited its prey leading to extinction (tragedy of the commons). Surprisingly, a predator taking longer to produce more offspring outcompeted a predator producing fewer offspring more rapidly (rate versus yield trade-off). Predation was only efficient in a narrow region around optimal parameters. Moreover, extreme oscillations under a wide range of conditions led to severe bottlenecks. A bacteriophage outcompeted Bdellovibrio due to its higher burst size and faster life cycle. Together, results suggest that Bdellovibrio would struggle to survive on a single prey, explaining why it must be a generalist predator and suggesting it is better suited than phage to environments with multiple prey.

Importance

The discovery of antibiotics led to a dramatic drop in deaths due to infectious disease. Increasing levels of antimicrobial resistance, however, threaten to reverse this progress. There is thus a need for alternatives, such as therapies based on phage and predatory bacteria that kill bacteria regardless of whether they are pathogens or resistant to antibiotics. To best exploit them, we need to better understand what determines their effectiveness. By using a mathematical model to study bacterial predation in realistic slow growth conditions, we found that the generalist predator Bdellovibrio is most effective within a narrow range of conditions for each prey. For example, a minimum prey size is required, and the predator should not be too good as this would result in over-exploitation risking extinction. Together these findings give insights into the ecology of microbial predation and help explain why Bdellovibrio needs to be a generalist predator.
De novoemergence of adaptive membrane proteins from thymine-rich intergenic sequences
Authors: Vakirlis Nikolaos , Acar Omer , Hsu Brian , Coelho Nelson Castilho , Van Oss S. Branden , Wacholder Aaron , Medetgul-Ernar Kate , Iannotta John , McLysaght Aoife , Camacho Carlos J. , O’Donnell Allyson F. , Ideker Trey , Carvunis Anne-Ruxandra
Published: April 2019

Recent evidence demonstrates that novel protein-coding genes can arisede novofrom intergenic loci. This evolutionary innovation is thought to be facilitated by the pervasive translation of intergenic transcripts, which exposes a reservoir of variable polypeptides to natural selection. Do intergenic translation events yield polypeptides with useful biochemical capacities? The answer to this question remains controversial. Here, we systematically characterized howde novoemerging coding sequences impact fitness. In budding yeast, overexpression of these sequences was enriched in beneficial effects, while their disruption was generally inconsequential. We found that beneficial emerging sequences have a strong tendency to encode putative transmembrane proteins, which appears to stem from a cryptic propensity for transmembrane signals throughout thymine-rich intergenic regions of the genome. These findings suggest that novel genes with useful biochemical capacities, such as transmembrane domains, tend to evolvede novowithin intergenic loci that already harbored a blueprint for these capacities.
Hierarchical recurrent state space models reveal discrete and continuous dynamics of neural activity inC. elegans
Authors: Linderman Scott , Nichols Annika , Blei David , Zimmer Manuel , Paninski Liam
Published: April 2019

Modern recording techniques enable large-scale measurements of neural activity in a variety of model organisms. The dynamics of neural activity shed light on how organisms process sensory information and generate motor behavior. Here, we study these dynamics using optical recordings of neural activity in the nematodeC. elegans. To understand these data, we develop state space models that decompose neural time-series into segments with simple, linear dynamics. We incorporate these models into a hierarchical framework that combines partial recordings from many worms to learn shared structure, while still allowing for individual variability. This framework reveals latent states of population neural activity, along with the discrete behavioral states that govern dynamics in this state space. We find stochastic transition patterns between discrete states and see that transition probabilities are determined by both current brain activity and sensory cues. Our methods automatically recover transition times that closely match manual labels of different behaviors, such as forward crawling, reversals, and turns. Finally, the resulting model can simulate neural data, faithfully capturing salient patterns of whole brain dynamics seen in real data.
Liquid-Liquid Phase Separation is Driven by Large-Scale Conformational Unwinding and Fluctuations of Intrinsically Disordered Protein Molecules
Authors: Majumdar Anupa , Dogra Priyanka , Maity Shiny , Mukhopadhyay Samrat
Published: April 2019

Liquid-liquid phase separation occurs via a multitude of transient, non-covalent, intermolecular interactions resulting in phase transition of intrinsically disordered proteins/regions (IDPs/IDRs) and other biopolymers into mesoscopic, dynamic, non-stoichiometric, supramolecular condensates. IDPs resemble associative polymers possessing stereospecific “stickers” and flexible “spacers” that govern the transient chain-chain interactions and fluidity in phase-separated liquid droplets. However, the fundamental molecular origin of phase separation remains elusive. Here we present a unique case to demonstrate that unusual conformational expansion events coupled with solvation and fluctuations drive phase separation of tau, an IDP associated with Alzheimer’s disease. Using intramolecular excimer emission as a powerful proximity readout, we show the unraveling of polypeptide chains within the protein-rich interior environment that can promote critical interchain contacts. Using highly-sensitive picosecond time-resolved fluorescence depolarization measurements, we directly capture rapid large-amplitude torsional fluctuations in the extended chains that can control the relay of making-and-breaking of noncovalent intermolecular contacts maintaining the internal fluidity. Our observations, together with the existing polymer theories, suggest that such an orchestra of concerted molecular shapeshifting events involving chain expansion, solvation, and fluctuations can provide additional favorable free energies to overcome the entropy of mixing term during phase separation. The interplay of these key molecular parameters can also be of prime importance in modulating the mesoscale material property of liquid-like condensates and their maturation of into pathological gel-like and solid-like aggregates.
A new method of brain stimulation at ultra-high frequency
Authors: Jamali Yousef , Jamali Mohammad , Golshani Mehdi
Published: April 2019

Nerve stimulation via micro-electrode implants is one of the neurostimulation approaches which is used frequently in the medical treatment of some brain disorders, neural prosthetics, brain-machine interfaces and also in the cyborg. In this method, the electrical stimulation signal can be categorized by the frequency band: low frequency, high frequency, and ultra-high frequency. The stimulation should be less destructive, more smooth, and controllable. In this article, we present a brief description of the mechanism underlying the ultra-high frequency stimulation. In the flowing, from an informatics perspective, we propose a state-of-the-art, low destructive, and highly efficient stimulation method at the low amplitude ultra-high frequency signal. In this method, we have tried to reduce the adaptation of the nerve system by modulating the stimulation signal via a low frequency rectangular random wave. By this method, we could reach the “almost zero discharge” with minimum destructive effect in the experimental test on the fish nervous system.
Transient Receptor Potential Ankyrin1 channel is endogenously expressed in T cells and regulates immune functions
Authors: Sahoo Subhransu Sekhar , Majhi Rakesh Kumar , Tiwari Ankit , Acharya Tusar , Kumar P Sanjai , Saha Somdatta , Goswami Chandan , Chattopadhyay Subhasis
Published: April 2019

Transient Receptor Potential channel subfamily A member 1 (TRPA1) is a non selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the role of TRPA1 towards T cell responses remains scanty. In this work, we explored the endogenous expression of TRPA1 in T cells. By RT-PCR we confirmed the expression of TRPA1 in T cell at RNA level. Using confocal microscopy as well as flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. The endogenous expression of TRPA1 is confirmed by using another antibody. TRPA1 was primarily located at the cell surface. TRPA1-specific activator namely AITC increases intracellular Ca2+-levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca2+-levels in T cells. Such Ca2+-influx can also be influenced by chelation of intracellular Ca2+ as well as extracellular Ca2+. TRPA1 expression was found to be increased during αCD3/αCD28 (TCR) or ConA driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of CD25, CD69 in ConA/TCR stimulated T cells and secretion of cytokines like TNF, IFN-γ and IL-2 suggesting that endogenous activity of TRPA1 may be involved in T cell activation. Collectively these results may have implication in T cell-mediated responses and possible role of TRPA1 in immunological disorders.
Reproductive capacity of Varroa destructor in four different honey bee subspecies
Authors: Odemer Richard
Published: April 2019

Varroa tolerance as a consequence of host immunity may contribute substantially to reduce worldwide colony declines. Therefore, special breeding programs were established and varroa surviving populations investigated to understand mechanisms behind this adaptation. Here we studied the reproductive capacity in the three most common subspecies of the European honey bee (Carnica, Mellifera, Ligustica) and the F2 generation of a varroa surviving population, to identify if managed host populations possibly have adapted over time already. Both, singly infested drone and worker brood were assessed to determine fertility and fecundity of varroa foundresses in their respective group. We found neither parameter to be significantly different within the four subspecies, demonstrating that no adaptations have occurred in terms of the reproductive success of Varroa destructor. In all groups mother mites reproduce equally successful and are potentially able to cause detrimental damage to their host when not being treated sufficiently. The data further suggests that a population once varroa tolerant does not necessarily inherit this trait to following generations after the F1, which could be of particular interest when selecting populations for resistance breeding. Reasons and consequences are discussed.

HIGHLIGHTS

Varroa reproduction has been investigated in four different honey bee subspecies

No differences could be observed, neither in drone nor in worker brood

In managed bee populations, host immunity against V. destructor has not been established

GRAPHICAL ABSTRACT

Illustrations after Gullan & Cranston 2014
Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer’s Disease
Authors: Patel Hamel , Iniesta Raquel , Stahl Daniel , Dobson Richard J.B , Newhouse Stephen J
Published: April 2019

Background

A significant number of studies have investigated the use of blood-derived gene expression profiling as a biomarker for Alzheimer’s Disease (AD). However, the typical approach of developing classification models trained on subjects with AD and complimentary cognitive healthy controls may result in markers of general illness rather than being AD-specific. Incorporating additional related neurological and age-related disorders during the classification model development process may lead to the discovery of an AD-specific expression signature.

Methods

Two XGBoost classification models were developed and optimised. The first used the typical approach, training on 160 AD and 160 cognitively normal controls, while the second was trained in 6318 AD and 6318 mixed controls. Up-sampling was performed in each training set to the minority classes to avoid sampling bias, and both classification models were evaluated in an independent dataset consisting of 127 AD and 687 mixed controls. The mixed control group represents a heterogeneous ageing population consisting of Parkinson’s Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Bipolar Disorder, Schizophrenia, Coronary Artery Disease, Rheumatoid Arthritis, Chronic Obstructive Pulmonary Disease, and cognitively healthy subjects.

Results

The typical approach resulted in a 74 gene classification model with a validation performance of 58.3% sensitivity, 30.3% specificity, 13.4% PPV and 79.7% NPV. In contrast, the second approach resulted in a 28 gene classification model with an overall improved validation performance of 46.5% sensitivity, 95.6% specificity, 66.3% PPV and 90.6% NPV.

Conclusions

The addition of related neurological and age-related disorders into the AD classification model developmental process identified a more AD-specific expression signature, with improved ability to distinguish AD from other related diseases and cognitively healthy controls. However, this was at the cost of sensitivity. Further improvement is still required to identify a robust blood transcriptomic signature specific to AD.
TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis
Authors: Vlachou Denise , Bjarnason Georg A. , Giacchetti Sylvie , Lévi Francis , Rand David A.
Published: April 2019

Recent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of diseases including cancer and heart disease. Therefore, there is a need for tools to measure the functional state of the circadian clock and its downstream targets in patients. We provide such a tool and demonstrate its clinical relevance by an application to breast cancer where we find a strong link between survival and our measure of clock dysfunction. We use a machine-learning approach and construct an algorithm called TimeTeller which uses the multi-dimensional state of the genes in a transcriptomics analysis of a single biological sample to assess the level of circadian clock dysfunction. We demonstrate how this can distinguish healthy from malignant tissues and demonstrate that the molecular clock dysfunction metric is a potentially new prognostic and predictive breast cancer biomarker that is independent of the main established prognostic factors.
Identification of Ca-rich dense granules in human platelets using scanning transmission X-ray microscopy
Authors: Trinh Tung X. , Kwon Sook Jin , Gerelkhuu Zayakhuu , Choi Jang-Sik , Song Jaewoo , Yoon Tae Hyun
Published: April 2019

Whole mount (WM) platelet preparations followed by transmission electron microscopy (TEM) observation is the standard method currently used to assess dense granule (DG) deficiency (DGD). However, due to electron density-based contrast mechanism in TEM, other granules such as α-granules might cause false DGs detection. Herein, scanning transmission X-ray microscopy (STXM), was used to identify DGs and minimize false DGs detection of human platelets. STXM image stacks of human platelets were collected at the calcium (Ca) L2,3absorption edge and then converted to optical density maps. Ca distribution maps obtained by subtracting the optical density map at pre-edge region from those obtained at post-edge region were used for identification of DGs based on richness of Ca. Dense granules were successfully detected by using STXM method without false detection based on Ca maps for 4 human platelets. Spectral analysis of granules in human platelets confirmed that DGs contained richer Ca content than other granules. Image analysis of Ca maps provided quantitative parameters which would be useful for developing image-based DG diagnosis models. Therefore, we would like to propose STXM as a promising approach for better DG identification and DGD diagnosis, as a complementary tool to the current WM TEM approach.
Exploring Deep Physiological Models for Nociceptive Pain Recognition
Authors: Thiam Patrick , Bellmann Peter , Kestler Hans A. , Schwenker Friedhelm
Published: April 2019

Standard feature engineering involves manually designing and assessing measurable descriptors based on some expert knowledge in the domain of application, followed by the selection of the best performing set of designed features in order to optimize an inference model. Several studies have shown that this whole manual process can be efficiently replaced by deep learning approaches which are characterized by the integration of feature engineering, feature selection and inference model optimization into a single learning process. Such techniques have proven to be very successful in the domain of image processing and have been able to attain state-of-the-art performances while significantly outperforming traditional approaches based on hand-crafted features. In the following work, we explore deep learning approaches for the analysis of physiological signals. More precisely, deep learning architectures are designed for the assessment of measurable physiological channels in order to perform an accurate classification of different levels of artificially induced nociceptive pain. Most of the previous works related to pain intensity classification based on physiological signals rely on a carefully designed set of hand-crafted features in order to achieve a relatively good classification performance. Therefore, the current work aims at building competitive pain intensity classification models without the need of domain specific expert knowledge for the generation of relevant features. The assessment of the designed deep learning architectures is based on the BioVid Heat Pain Database (Part A) and experimental validation demonstrates that the proposed uni-modal architecture for the electrodermal activity (EDA) and the deep fusion approaches significantly outperform previous classification methods reported in the literature, with respective average performances of 85.03% and 83.76% for the binary classification experiment consisting of the discrimination between the baseline level and the pain tolerance level (T0vs.T4) in a Leave-One-Subject-Out (LOSO) cross-validation evaluation setting.
Non-disclosure of tuberculosis diagnosis by patients to their household members in south western Uganda
Authors: Nyangoma Miria , Bajunirwe Francis , Atwine Daniel
Published: April 2019

Background

Tuberculosis (TB) non-disclosure by adult patients to all household members is a setback to TB control efforts. It reduces the likelihood that household contacts will seek early TB screening, initiation on preventive or curative treatment, but also hinders the implementation of infection controls and home-based directly observed treatment. Therefore, this study aimed at determining the level of TB non-disclosure, its predictors and effects of disclosure to household members on adult patients at a large regional referral hospital in south-western Uganda.

Methods

Cross-sectional study. Questionnaires administered to collect patients’ sociodemographic and their TB disclosure data. Non-disclosure was considered if a patient did not reveal their TB diagnosis to all household members within 2 weeks post-treatment initiation. Univariate and multivariate logistic regression models were fitted for predictors of non-disclosure.

Results

Enrolled 62 patients, 74% males, mean age of 32 years, and median of five people per household. Non-disclosure rate was 30.6%. Post-disclosure experiences were positive in 98.3% of patients, while negative experiences suggestive of severe stigma occurred in 24.6% of patients. Being female (OR 6.5, 95% CI: 1.42-29.28) and belonging to Muslim faith (OR 12.4, 95% CI: 1.42-109.05) predicted TB non-disclosure to household members.

Conclusions

There is a high rate of TB non-disclosure to household members by adult patients in rural Uganda, with the highest vulnerability seen among female and Muslim patients. Interventions enhancing TB disclosure at household level while minimizing negative effects of stigma should be developed and prioritized.
Crystal structure variations in the series SrLnCuS3 (Ln = La, Pr, Sm, Gd, Er and Lu)
Authors: Ruseikina Anna V. , Solovyov Leonid A. , Grigoriev Maksim V. , Andreev Oleg V.
Published: April 2019

The crystal structures of the complex sulfides SrLnCuS3 (Ln = Sm, Gd, Er and Lu) have been determined and refined using powder X-ray diffraction. The crystals are found to be orthorhombic, with the structure type changing consecutively in the order BaLaCuS3 → Eu2CuS3 → KZrCuS3 as the Ln3+ ionic radius decreases in the order La/Pr → Sm/Gd → Er/Lu. Variations of the structure parameters along the series of compounds studied are analyzed, and an effect caused by crystallochemical contraction on the stabilization of the respective structure types is demonstrated.
Intellectual property challenges for the roads of innovation in Brazil
Authors: Vasconcelos Cleiton Rodrigues de , Silva Daniel Pereira da
Published: April 2019

Purpose

This paper aims to present reflections and points of interest on the performance of Brazil and highlight the advances and challenges in relation to the intellectual property (IP) system; the authors highlight some scientific, economic and technological indicators on the main IP objects registered in the National Industrial Property of Brazil (INPI).

Design/methodology/approach

A structured literature reviews the main indicators of IP of Brazil (2013-2017), related to the scientific and economic factors more evidenced in the global scenario, with emphasis on the investment of national GDP in R&D activities, the allocation of resources from the government sector and private initiative, as in other emerging economies, such as the BRICS.

Findings

Despite Brazil’s progressive efforts to achieve greater efficiency in the public IP management system, GDP investment in R&D activities for 2019 is still below the OECD average of 2.3 per cent, and the IP indicators in the areas of patent registration, industrial designs and technology contracts have been declining.

Research limitations/implications

Because of the difference between the laws of the countries on IP rights, the more incisive comparison could not be established among the emerging economies, highlighting the need for a standardization between the different international legislations.

Originality/value

In the scientific field, this paper allows understanding the performance of the Brazilian IP system, and the categories that require greater investments, strengthen the IP culture and stimulate integration between the international IP systems, as it is a recurrent discussion in different research studies. Originally, the paper brought together economic and scientific indicators going beyond the traditional approach that deals with IP only restricting to the quantitative of patents.
Illicit finance and money laundering trends in Eurasia
Authors: Cassella Stefan
Published: April 2019

Purpose

The purpose of this paper is to review recent examples of sophisticated money laundering operations involving financial institutions in Eurasia, including Russia and Moldova, and the resulting flow of licit and illicit capital from that part of the world to the UK, the USA, and other Western countries.

Design/methodology/approach

Relying on materials from publicly available sources, the study uses several case studies to illustrate various money laundering methods with a view toward identifying common elements and aspects of the schemes that might be considered new or innovative.

Findings

In particular, the study examines the roles that lax anti-money laundering compliance by financial institutions and the use of shell corporations designed to conceal the beneficial ownership of the companies and their assets have played in virtually all of the money laundering schemes.

Originality/value

The paper discusses the risks that these emerging money laundering methods pose to Western countries and their financial institutions and the approaches that governments might take to minimize those risks and raise the barriers for the laundering of illicit funds within their jurisdictions.
Universal basic education in Nigeria: can non-state actors make a difference?
Authors: Kolade Oluwaseun
Published: April 2019

Purpose

Against the backdrop of falling standards and failing government policies in the education sector in Nigeria, this paper aimed to investigate how and why non-state actors can make a significant impact on the achievement of Sustainable Development Goals for universal basic education (UBE).

Design/methodology/approach

This study draws from semi-structured interviews of 15 heads and proprietors – six state-funded schools, six faith schools and three other privately owned schools – to examine and compare the different motivations, guiding principles and overall impact of these actors in the education sector.

Findings

Religious actors, along with private providers, are making a significant contribution to the provision of basic education in Nigeria. Students from faith schools tend to perform better academically and they also tend to be more disciplined and resourceful. However, because these schools are fee-paying, fewer households are able to access them.

Practical implications

The findings highlight the need to facilitate better cooperation and knowledge transfer activities between public, private and faith schools. It also emphasises the need for better government commitment and investment in provision of resources and facilities, effort in regulating the curriculum and regular inspection and quality monitoring of public schools.

Originality/value

The study highlights, on the one hand, the superior capacity of non-state actors – especially religious actors – to deploy their vast social capital towards the mobilisation of funds and human resources. On the other hand, while they have made inroads in their share of total national school enrolment, non-state actors have not made significant impact on access to quality education, owing to high fees and entry barriers faced by poorer households.
Plasma Exchange Is Highly Effective for Anti‐Neutrophil Cytoplasmic Antibody‐Associated Vasculitis Patients With Rapidly Progressive Glomerulonephritis Who Have Advanced to Dialysis Dependence: A Single‐Center Case Series
Authors: Nishida Reimi , Kaneko Shuzo , Usui Joichi , Kawamura Tetsuya , Tsunoda Ryoya , Tawara Takashi , Fujita Akiko , Nagai Kei , Kai Hirayasu , Morito Naoki , Saito Chie , Yamagata Kunihiro
Published: April 2019

Plasma exchange (PEX) can be an effective treatment in anti‐neutrophil cytoplasmic antibody‐associated vasculitis with severe renal damage; however, it is still controversial. Among cases of newly diagnosed AAV with rapidly progressive glomerulonephritis at our department from 2008 onward, 11 patients who received PEX (seven cases for severe renal damage [R‐PEX] and four cases for lung hemorrhage [L‐PEX]) were retrospectively analyzed. All cases of R‐PEX were dependent on hemodialysis at the beginning of PEX and all received seven sessions of PEX (50 mL/kg or 1.3 plasma volume per exchange) within 2 weeks. All cases became dialysis‐independent within 8 weeks, with 3‐ and 12‐month cumulative renal survival rates of 100% and 80%, respectively. All cases of L‐PEX retained their renal function. In rapidly developing, newly dialysis‐dependent antibody‐associated vasculitis with rapidly progressive glomerulonephritis patients with normal renal function before disease onset, standard PEX can be expected to induce sufficient renal recovery to establish dialysis independence.
rsmove—An r package to bridge remote sensing and movement ecology
Authors: Remelgado Ruben , Wegmann Martin , Safi Kamran
Published: April 2019

Remote sensing is a valuable tool in movement ecology. However, the way it is combined with animal movement data is far from optimal as most studies overlook differences in the spatial, temporal and thematic resolutions between both data types.

rsmove uses a pixel‐based approach to link animal tracking and remote sensing data that bridge the gap between these two disciplines while respecting the limitations of the latest. Additionally, if offers standardize methods to pre‐analyse the connection between animal movement and environmental change.

The package guides the choice of study sites, satellite data and environmental predictors though data mining and visualization tools. rsmove offers a simple methodology to analyse animal–environment interactions that helps avoid unnecessary, time‐consuming satellite data processing through an informed decision process.

The package offers a basis for a better communication between ecologists and remote sensing experts contributing to the definition of clear remote sensing data requirements. Additionally, it provides future studies on animal movement tools for a more critical approach on the selection of environmental data supporting the reproducibility of animal movement studies.
Cannabinoids and their actions: An update
Authors: Alexander Stephen P. H. , Molina‐Holgado Francisco
Published: April 2019

Linked Articles

This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
Design, synthesis, and antimycobacterial activity of novel ciprofloxacin derivatives
Authors: Cilliers Pieter , Seldon Ronnett , Smit Frans J. , Aucamp Janine , Jordaan Audrey , Warner Digby F. , N'Da David D.
Published: April 2019

Tuberculosis is the deadliest infectious disease affecting humankind with a death toll of approximately 1.7 million people in 2016. The increasing prevalence of multidrug‐resistant strains of the causative pathogen, Mycobacterium tuberculosis (Mtb) which results in reduced effectiveness of the current therapies, underscores the urgent need for the development of new antitubercular drugs. In the search for such drugs, we investigated two series of ciprofloxacin (CPX) derivatives (analogues and hybrids). We herein report the design, synthesis, and biological activity of these series against the human virulent Mtb H37Rv strain in vitro. The small propionyl analogue 11 (MIC90 1.6 μM; SI > 61) and the large cholesteryl hybrid 32 (MIC90 2.0 μM; SI > 6) were the most active derivatives, comparable to CPX (MIC90 1.8 μM). However, the slightly less active but non‐cytotoxic para‐fluorobenzyl hybrid 28 (MIC90 3.7 μM; SI 27) was more selective toward bacteria than 32. Thus, the CPX derivatives 11 and 28 were identified as preferred antitubercular hits for further investigation including distribution, metabolism and pharmacokinetic parameters determination and in vivo activity assessment in animal models.
Molecular insights into hypomineralized enamel
Authors: Malmberg Per , Norén Jörgen G. , Bernin Diana
Published: April 2019

Hypomineralized enamel may be found in connection with the condition molar incisor hypomineralization (MIH), which has a prevalence of around 15% in most parts of the world. Molar incisor hypomineralization is associated with extensive objective and subjective problems, such as hypersensitivity of the affected teeth, enamel breakdown, and problems with retention of restorations. The etiology behind MIH has not yet been elucidated, but a number of possible factors, which affect the same or different functions of ameloblasts during their different stages of maturation, have been suggested. The aim of this study was to utilize multi‐nuclear, solid‐state nuclear magnetic resonance (ss‐NMR) and time‐of‐flight secondary ion mass spectroscopy (ToF‐SIMS) to elucidate any differences, at a molecular level, between enamel powder prepared from normal, healthy teeth and enamel powder prepared from teeth diagnosed with MIH. 31P and 23Na ss‐NMR confirmed the presence of and two different Na+ sites in hypomineralized enamel, suggesting a heterogeneous chemical composition. The content of organic components was higher in hypomineralized enamel, as shown by both 13C ss‐NMR and ToF‐SIMS, indicating the presence of higher numbers of proteins and phospholipids. The interplay between both is necessary for the formation and mineralization of enamel, which might be disturbed or halted in hypomineralized enamel.