bluuebunny/crossref_metadata_2025 huggingface dataset:
Young lives cut short: The relationship between firearms and pediatric suicide
Authors: McLoughlin Robert J. , Hazeltine Max , Dacier Brittany M. , Hirsh Michael P. , Cleary Muriel A. , Aidlen Jeremy T.
Published: March 2019

BACKGROUND

To describe the demographic characteristics and burden of pediatric suicides by firearm in the United States using a large all-payer pediatric inpatient care database.

METHODS

Children and young adults (<21 years old) were identified with an International Classification of Diseases, Ninth Revision diagnosis of suicide and self-inflicted injury with a firearm (SIF) in the Kids' Inpatient Database for the study years of 2006, 2009, and 2012. National estimates were obtained using case weighting. Multivariable logistic regression was performed to examine the association between SIF and risk factors while adjusting for various sociodemographic characteristics using separate models incorporating mental health diagnoses.

RESULTS

There were a total of 613 hospitalizations for SIF during the years under study. Almost four hospitalizations per week occurred, and in-hospital mortality was 39.1%. The mean age of the study population was 17.3 years, and this population was predominantly male (87.5%), white (62.4%), resided in an urban area (43.8%), lived in the south (51.3%), and within the lowest income quartile (33.8%). Mental health (38.3%) and mood disorders (28.3%) were common. Males had a markedly increased likelihood of hospitalization for SIF (adjusted odds ratio [aOR], 7.56; 95% confidence interval [CI], 5.54–10.30). Children and adolescents from rural environments and those in the south were more likely to have a hospitalization for SIF than respective comparison groups. Using separate regression models, a diagnosis of any mental health disorder increased the likelihood of hospitalization for a SIF (aOR, 11.9: 95% CI, 9.51–14.9), mood disorders (aOR, 17.2; 95% CI, 13.3–22.3), and depression (aOR, 21.3; 95% CI, 16.1–28.3).

CONCLUSION

Pediatric hospitalizations for SIF are a common occurrence with high associated mortality. The prevalence of mental health disorders and their impact on this population highlight the need for early identification and intervention for individuals at risk.

LEVEL OF EVIDENCE

Epidemiological, level III.
Differences in Gene Expression in Older Compared With Younger Kidney Transplant Recipients
Authors: Schaenman Joanna M. , Rossetti Maura , Lum Erik , Abdalla Basmah , Bunnapradist Suphamai , Pham Thu-Phuong , Danovitch Gabriel , Reed Elaine F. , Cole Steve
Published: March 2019

Background

For the growing numbers of older transplant patients, increased incidence of infection and death compared with younger patients may limit the many benefits provided by transplantation. However, little is known about age-associated immune dysfunction in the older transplant recipient.

Methods

A cohort of 60 kidney transplant recipients, 23 older (≥ 60y) and 37 younger (30-59y), matched on antithymocyte induction and donor type (living vs deceased) was evaluated. Gene expression in peripheral blood mononuclear cells 3 months after kidney transplantation was analyzed to compare differences between older and younger patients.

Results

Proinflammatory genes were upregulated in older kidney transplant patients, including cytokines IL1-β and IL-6. Downregulated genes were associated with B-cell and T-cell function, including CCR7 and CD27. Analysis of predicted transcription factor binding suggested an increase in proinflammatory transcription factor CCAAT/enhancer binding protein β-binding sites in older patients, whereas interferon regulatory factor 2 transcription factor binding sites were less prevalent.

Conclusions

Older kidney transplant recipients exhibited multiple differences in gene expression compared with younger patients, with upregulation of proinflammatory genes and downregulation of adaptive immune response genes. These findings may explain the mechanism of increased vulnerability to infection and malignancy observed in older transplant patients.
Impact of Different Clinical Perfusates During Normothermic Ex Situ Liver Perfusion on Pig Liver Transplant Outcomes in a DCD Model
Authors: Linares-Cervantes Ivan , Kollmann Dagmar , Goto Toru , Echeverri Juan , Kaths Johan Moritz , Hamar Matyas , Urbanellis Peter , Mazilescu Laura , Rosales Roizar , Bruguera Claudia , Oquendo Fabiola , Ganesh Sujani , Adeyi Oyedele A. , Yip Paul , Selzner Nazia , Selzner Markus
Published: March 2019

Background

Human albumin/dextran (HA-D), bovine-gelatin (BG), and packed red blood cells plus plasma have been used in European and North-American clinical trials of normothermic ex situ liver perfusion (NEsLP). We compared the effects of these perfusates in a porcine model during NEsLP and after transplantation.

Methods

Porcine livers were retrieved 30 minutes after circulatory death. After 5 hours of NEsLP, grafts were transplanted. Three groups (n = 6) were assessed (HA-D vs BG vs whole blood [WB]). One group of static cold storage (SCS) was evaluated for comparison with the perfusion groups. Hemodynamic variables, liver and endothelial injury, and function were assessed during NEsLP and posttransplantation.

Results

Hepatic artery flow was higher since the beginning of NEsLP in the HA-D group (HA-D, 238 ± 90 mL/min vs BG, 97 ± 33 mL/min vs WB, 148 ± 49 mL/min; P = 0.01). Hyaluronic acid was lower in the HA-D at the end of perfusion (HA-D, 16.28 ± 7.59 ng/μL vs BG, 76.05 ± 15.30 ng/μL vs WB, 114 ± 46 ng/μL; P < 0.001). After transplant, aspartate aminotransferase was decreased in the HA-D group when compared with the rest of the groups (HA-D, 444 ± 226 IU/L vs BG, 1033 ± 694 IU/L vs WB, 616 ± 444 IU/L vs SCS, 2235 ± 1878 IU/L). At 5 hours after transplant, lactate was lower in the HA-D group (HA-D, 3.88 ± 1.49 mmol/L vs BG, 7.79 ± 2.68 mmol/L vs WB, 8.16 ± 3.86 mmol/L vs SCS, 9.06 ± 3.54 mmol/L; P = 0.04). International Normalized Ratio was improved in HA-D group compared to the rest of the groups (HA-D, 1.23 ± 0.30 vs BG, 1.63 ± 0.20 vs WB, 1.50 ± 0.31 vs SCS, 1.97 ± 1.55; P = 0.03) after transplantation. In contrast, BG displayed lower aspartate aminotransferase levels during NEsLP (HA-D, 183 ± 53 IU/L vs BG, 142 ± 52 IU/L vs WB, 285 ± 74 IU/L; P = 0.01) and less cleaved-caspase-3 staining (HA-D, 2.05 ± 0.73% vs BG, 0.95 ± 1.14% vs WB, 1.74 ± 0.54% vs SCS, 7.95 ± 2.38%) compared with the other groups. On the other hand, the bile from the WB showed higher pH (HA-D, 7.54 ± 0.11 vs BG, 7.34 ± 0.37 vs WB, 7.59 ± 0.18) and lower glucose levels (HA-D, 0.38 ± 0.75 mmol/L vs BG, 1.42 ± 1.75 mmol/L vs WB, 0 ± 0 mmol/L) by the end of perfusion.

Conclusions

Overall HA-D displayed more physiologic conditions during NEsLP that were reflected in less graft injury and improved liver function and survival after transplantation. Optimization of the perfusates based on the beneficial effects found with these different solutions would potentially improve further the outcomes through the use of NEsLP in marginal grafts.
Development of a deep amplicon sequencing method to determine the proportional species composition of piroplasm haemoprotozoa as an aid in their control
Authors: Chaudhry Umer , Ali Qasim , Rashid Imran , Shabbir Muhammad Zubair , Abbas Muhammad , Numan Muhammad , Evans Mike , Ashraf Kamran , Morrison Ivan , Morrison Liam , Sargison Neil D.
Published: March 2019

Piroplasmosis is caused by tick-borne haemoprotozoa of the generaTheileriaandBabesia. These parasitic infections can cause serious impact on the health of livestock and production. Multiple piroplasm species can infect a single host, but reliable molecular diagnostic tools are needed with which to understand the composition of these complex parasite communities.TheileriaandBabesiavary in their epidemiology, drug sensitivity, pathogenicity and interaction of co-infecting species, but are similar in the animals, become persistent carriers after recovery from primary infection, acting as reservoir hosts. Here, we describe for the first time the use of a deep amplicon sequencing platform to identify proportions of piroplasm species in co-infecting communities and develop the concept of a “haemoprotobiome”. First, four phenotypically-verified species ofTheileriaandBabesiawere used to prepare mock pools with random amounts of the parasites and amplified with four different numbers of PCR cycles to assess sequence representation of each species. Second, we evaluated the detection threshold of the deep amplicon sequencing assay for each of the four species and to assess the accuracy of proportional quantification of all four species. Finally, we applied the assay to the field samples to afford insight of the species composition of piroplasm communities in small and large ruminants in the Punjab province of Pakistan. The “haemoprotobiome” concept has several potential applications in veterinary and human research, including understanding of responses to drug treatment; parasite epidemiology and ecology; species interactions during mixed infections; and parasite control strategies.
Presynaptic boutons that contain mitochondria are more stable
Authors: Lees Robert M. , Johnson James D. , Ashby Michael C.
Published: March 2019

Addition and removal of presynaptic terminals reconfigures neuronal circuits of the mammalian neocortex, but little is known about how this presynaptic structural plasticity is controlled. Since mitochondria can regulate presynaptic function, we investigated whether the presence of axonal mitochondria relates to structural plasticity of presynaptic boutons in mouse neocortex. We found that the overall density of axonal mitochondria did not appear to influence loss and gain of boutons. However, positioning of mitochondria at individual presynaptic sites did relate to increased stability of those boutons. In line with this, synaptic localisation of mitochondria increased as boutons aged and showed differing patterns of localisation aten passantandterminauxboutons. These results suggest that mitochondria accumulate locally at boutons over time to increase bouton stability.
Molecular mechanisms for intestinal HCO3-secretion and its regulation by guanylin in seawater-acclimated eels
Authors: Takei Yoshio , Wong Marty K.S. , Ando Masaaki
Published: March 2019

The intestine of marine teleosts secretes HCO3-into the lumen and precipitates Ca2+and Mg2+in the imbibed seawater as carbonates to decrease luminal fluid osmolality and facilitate water absorption. However, reports on studies on the hormonal regulation of HCO3-secretion are just emerging. Here, we showed that guanylin (GN) applied to the mucosal side of intestinal epithelia increased HCO3-secretion in seawater-acclimated eels. The effect of GN on HCO3-secretion was slower than that on the short-circuit current, and the time-course of the GN effect was similar to that of bumetanide. Mucosal bumetanide and serosal 4,4’-dinitrostilbene-2,2’-disulfonic acid (DNDS) inhibited the GN effect, suggesting an involvement of apical Na+-K+-2Cl-cotransporter (NKCC2) and basolateral Cl-/HCO3-exchanger (AE)/Na+-HCO3-cotransporter (NBC) in the GN effect. However, mucosal DNDS and diphenylamine-2-carboxylic acid (DPC) failed to inhibit the GN effect, showing that apical AE and Cl-channel are not involved. To identify molecular species of possible transporters involved in the GN effect, we performed RNA-seq analyses followed by quantitative real-time PCR after transfer of eels to seawater. Among the genes upregulated after seawater transfer, those of Slc26a3a, b (DRAa, b) and Slc26a6a, c (Pat-1a, c) on the apical membrane of the intestinal epithelial cells, and those of Sls4a4a (NBCe1a), Slc4a7 (NBCn1), Slc4a10a (NBCn2a) and Slc26a1 (Sat-1) on the basolateral membrane were candidate transporters involved in HCO3-secretion. Judging from the slow effect of GN, we suggest that GN inhibits NKCC2b on the apical membrane and decreases cytosolic Cl-and Na+, which then activates apical DNDS-insensitive DRAa, b and basolateral DNDS-sensitive NBCela, n1, n2a to enhance transcellular HCO3-flux across the intestinal epithelia of seawater-acclimated eels.
Ultra-compliant carbon nanotube stretchable direct bladder interface
Authors: Yan Dongxiao , Bruns Tim M. , Wu Yuting , Zimmerman Lauren L. , Stephan Chris , Cameron Anne P. , Yoon Euisik , Seymour John P.
Published: March 2019

The bladder, stomach, intestines, heart, and lungs all move dynamically to achieve their purpose. A long-term implantable device that can attach onto an organ, sense its movement, and deliver current to modify the organ function would be useful in many therapeutic applications. The bladder, for example, is a smooth muscle organ that can suffer from incomplete contractions that result in urinary retention with patients requiring using catheterization. Those affected may benefit from a combination of strain sensor and electrical stimulator to better control bladder emptying. We describe the materials and design of such a device made from thin layer carbon nanotube (CNT) and Ecoflex 00-50 and demonstrate its function with in vivo feline bladders. During bench-top characterization, the resistive and capacitive sensors exhibited reliable output throughout 5,000 stretching cycles under physiology condition. In vivo measurement with piezoresistive device showed a high correlation between sensor resistance and volume. Stimulation driven from Pt-PDMS composite electrodes successfully induced bladder contraction. We present method for reliable connection and packaging of medical grade wire to the CNT device. This work is an important step toward the translation of low-durometer elastomers, stretchable CNT percolation and Pt-PDMS composite, which are ideal for large strain bioelectric applications to sense or modulate dynamic organ states.
CGAT-core: a python framework for building scalable, reproducible computational biology workflows
Authors: Cribbs Adam , Luna-Valero Sebastian , George Charlotte , Sudbery Ian M , Berlanga-Taylor Antonio J , Sansom Steven N , Smith Thomas , Ilott Nicholas E , Johnson Jethro , Scaber Jakub , Brown Katherine , Sims David , Heger Andreas
Published: March 2019

In the genomics era computational biologists regularly need to process, analyse and integrate large and complex biomedical datasets. Analysis inevitably involves multiple dependent steps, resulting in complex pipelines or workflows, often with several branches. Large data volumes mean that processing needs to be quick and efficient and scientific rigour requires that analysis be consistent and fully reproducible. We have developed CGAT-core, a python package for the rapid construction of complex computational workflows. CGAT-core seamlessly handles parallelisation across high performance computing clusters, integration of Conda environments, full parameterisation, database integration and logging. To illustrate our workflow framework, we present a pipeline for the analysis of RNAseq data using pseudo-alignment.
Increased hippocampal excitability and altered learning dynamics mediate cognitive mapping deficits in human aging
Authors: Diersch Nadine , Valdes-Herrera Jose P , Tempelmann Claus , Wolbers Thomas
Published: March 2019

Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are unknown. Here, we report findings from a behavioral and a fMRI experiment where older and younger adults performed a spatial learning task in a photorealistic virtual environment. We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex/parieto-occipital sulcus and anterior hippocampus did not change systematically as a function learning in older compared to younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits are linked to an increase in hippocampal excitability. Together, these results provide important insights into how human aging affects computations in the brain’s navigation system, highlighting the critical role of the hippocampus.
The distinct phenotypic signatures of dispersal and stress in an arthropod model: from physiology to life history
Authors: Dahirel Maxime , Masier Stefano , Renault David , Bonte Dries
Published: March 2019

Dispersing individuals are expected to encounter costs during transfer and in the novel environment, and may also have experienced stress in their natal patch. Given this, a non-random subset of the population should engage in dispersal and eventually show divergent stress-related responses towards new conditions. Dispersal allows escape from stress, but is equally subjecting individuals to it.

Physiological shifts expressed in the metabolome form a major part of responses to stress exposure and are expected to be associated with the dispersal phenotype, thereby shaping physiological dispersal syndromes. We analyzed how metabolic profiles and life-history traits varied between dispersers and residents of the model two-spotted spider miteTetranychus urticae, and whether and how these syndromes varied with exposure to a stressful new host plant (tomato). Regardless of the effect of host plant, we found a physiological dispersal syndrome where, relative to philopatric individuals, dispersers were characterized by lower leaf consumption rates and a lower concentration of several amino acids, indicating a potential dispersal-foraging trade-off. As a possible consequence of this lower food intake, dispersers also showed a lower reproductive performance. Responses to tomato exposure were consistent with this plant being a stressor forTetranychus urticae, including reduced fecundity and reduced feeding by mites. Tomato-exposed mites laid larger eggs, which can be interpreted as a plastic response to food stress, increasing the likelihood of survival to maturity. Contrary to what could be expected from the costs of dispersal and stress resistance and from previous meta-population level studies, there was no interaction between dispersal status and host plant for any of the examined traits, indicating that the impacts of a new stressful host plant are equally incurred by residents and dispersers.

We thus provide novel insights in the processes that shape dispersal and the putative feedbacks on ecological dynamics in spatially structured populations.
Tissue mechanics controls T-cell activation and metabolism
Authors: Meng Kevin P. , Majedi Fatemeh S. , Thauland Timothy J. , Butte Manish J.
Published: March 2019

Upon immunogenic challenge, lymph nodes become mechanically stiff as immune cells proliferate within their encapsulated environments, and with resolution, they reestablish a soft, baseline state. We found that these mechanical changes in the microenvironment promote and then restrict T-cell activation and metabolic reprogramming. Sensing of tissue mechanics by T cells requires the mechanosensor YAP. Unlike in other cells where YAP promotes proliferation, YAP in T cells suppresses proliferation in a stiffness-dependent manner by directly restricting the translocation of NFAT into the nucleus. YAP regulates T-cell responses against viral infections and in autoimmune diabetes. Our work reveals a new paradigm whereby tissue mechanics fine-tunes adaptive immune responses in health and disease.

One Sentence Summary

Tissue mechanics regulates T cells.
Differences in proteome response to cold acclimation inZoysia japonicacultivars with different levels of freeze tolerance
Authors: Brown J.M. , Holloway H. McCamy P. , DaCosta Michelle , Bernstein Rachael P. , Lu Jefferson , Tuong Tan D. , Patton Aaron J. , Dunne Jeffrey C. , Arellano Consuelo , Livingston David P. , Milla-Lewis Susana R.
Published: March 2019

Zoysiagrasses (Zoysiaspp.) are warm season turfgrasses primarily grown in the southern and transition zones of the United States. An understanding of the physiological changes that zoysiagrasses undergo during cold acclimation may shed light on physiological phenotypic traits useful in selection of freeze tolerant genotypes. We investigated the relationship between cold acclimation, protein expression, and freeze tolerance in cold-acclimated (CA) and non-acclimated (NCA) plants ofZoysia japonicaSteud. cultivars ‘Meyer’ (freeze-tolerant) and ‘Victoria’ (freeze-susceptible). Freeze tolerance was assessed using chambers reaching −6, −8, −10, and −12°C. Additionally, meristematic tissues from the grass crowns of ‘Meyer’ and ‘Victoria’ were harvested for proteomic analysis after a four week cold acclimation period. Freeze testing indicated that cold acclimation accounted for a 1.9-fold increase in plant survival compared to the non-acclimation treatment. Overall, proteomic analysis identified 62 protein spots having at least a twofold change in abundance under cold acclimation. Nine and 22 unique protein spots were identified for Meyer and Victoria, respectively, with increased abundance (up-regulated) or decreased abundance (down-regulated). In addition, 23 shared protein spots were found among the two cultivars having differential expression in response to cold acclimation. In Meyer, protein response to cold acclimation was primarily upregulated, while in Victoria, protein response was primarily downregulated. These cold acclimation responsive proteins were found to be involved primarily in transcription, metabolism, protein destination and storage, and energy production. As identified through MALDI-TOF/TOF mass spectrometry followed matching of protein homologues against the NCBI Arabidopsis database, major proteins of interest for their association with cold acclimation were LEA 3, MAPK, SOD, GAST1, Phytochrome A, ATP synthase, AGP, PLD, and PSII. Further investigation of these proteins and their functional categories may contribute to increase our understanding of the differences in freezing tolerance among zoysiagrass germplasm.
Schizophrenia Polygenic Risk Score and 20-Year Course of Illness in Psychotic Disorders
Authors: Jonas Katherine G. , Lencz Todd , Li Kaiqiao , Malhotra Anil K. , Perlman Greg , Fochtmann Laura J. , Bromet Evelyn J. , Kotov Roman
Published: March 2019

Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnostics and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β= 0.21), lower GAF (β= −0.28), and worse cognition (β= −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a powerful tool for diagnosis and treatment planning.
Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle
Authors: Santos-Lopez Alfonso , Marshall Christopher W. , Scribner Michelle R. , Snyder Daniel , Cooper Vaughn S.
Published: March 2019

Bacterial populations vary in their stress tolerance and population structure depending upon whether growth occurs in well-mixed or structured environments. We hypothesized that evolution in biofilms would generate greater genetic diversity than well-mixed environments and lead to different pathways of antibiotic resistance. We used experimental evolution and whole genome sequencing to test how the biofilm lifestyle influenced the rate, genetic mechanisms, and pleiotropic effects of resistance to ciprofloxacin inAcinetobacter baumanniipopulations. Both evolutionary dynamics and the identities of mutations differed between lifestyle. Planktonic populations experienced selective sweeps of mutations including the primary topoisomerase drug targets, whereas biofilm-adapted populations acquired mutations in regulators of efflux pumps. An overall trade-off between fitness and resistance level emerged, wherein biofilm-adapted clones were less resistant than planktonic but more fit in the absence of drug. However, biofilm populations developed collateral sensitivity to cephalosporins, demonstrating the clinical relevance of lifestyle on the evolution of resistance.
PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers
Authors: Aakula Anna , Isomursu Aleksi , Rupp Christian , Erickson Andrew , Kauko Otto , Shah Pragya , Padzik Artur , Pokharel Yuba Raj , Kaur Amanpreet , Li Song-Ping , Trotman Lloyd , Taimen Pekka , Rannikko Antti , Lammerding Jan , Paatero Ilkka , Mirtti Tuomas , Ivaska Johanna , Westermarck Jukka
Published: March 2019

While organ-confined PCa is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities. Here, we discover that PCa tumors with concomitantly compromised function of two tumor suppressor phosphatases, PP2A and PTEN, are particularly aggressive, having less than 50% 5-year secondary-therapy free patient survival. Functionally, overexpression of PME-1, a PP2A inhibitor protein, inhibits anoikis in PTEN-deficient PCa cells. In vivo, PME-1 inhibition increased apoptosis in in ovo PCa tumor xenografts, and attenuated PCa cell survival in zebrafish circulation. Molecularly, PME-1 deficient PCa cells display increased trimethylation at lysines 9 and 27 of histone H3 (H3K9me3 and H3K27me3), a phenotype corresponding to increased apoptosis sensitivity. In summary, we discover that PME-1 overexpression supports anoikis resistance in PTEN-deficient PCa cells. Clinically, the results identify PME-1 as a candidate biomarker for a subset of particularly aggressive PTEN-deficient PCa.
Multiplatform Biomarker Identification using a Data-driven Approach Enables Single-sample Classification
Authors: Zhang Ling , Thapa Ishwor , Haas Christian , Bastola Dhundy
Published: March 2019

High-throughput gene expression profiles have allowed discovery of potential biomarkers enabling early diagnosis, prognosis and developing individualized treatment. However, it remains a challenge to identify a set of reliable and reproducible biomarkers across various gene expression platforms and laboratories for single sample diagnosis and prognosis. We address this need with our Data-Driven Reference (DDR) approach, which employs stably expressed housekeeping genes as references to eliminate platform-specific biases and non-biological variabilities. Our method identifies biomarkers with “built-in” features, and these features can be interpreted consistently regardless of profiling technology, which enable classification of single-sample independent of platforms. Validation with RNA-seq data of blood platelets shows that DDR achieves the superior performance in classification of six different tumor types as well as molecular target statuses (such asMETorHER2-positive, and mutantKRAS, EGFRorPIK3CA) with smaller sets of biomarkers. We demonstrate on the three microarray datasets that our method is capable of identifying robust biomarkers for subgrouping medulloblastoma samples with data perturbation due to different microarray platforms. In addition to identifying the majority of subgroup-specific biomarkers in Code-Set of nanoString, some potential new biomarkers for subgrouping medulloblastoma were detected by our method. Our results show that the DDR method contributes significantly to single-sample classification of disease and shed light on personalized medicine.
Insight into dynamics of APOBEC3G protein in complexes with DNA assessed by high speed AFM
Authors: Pan Yangang , Shlyakhtenko Luda S. , Lyubchenko Yuri L.
Published: March 2019

APOBEC3G (A3G) is a single-stranded DNA (ssDNA) binding protein that restricts the HIV virus by deamination of dC to dU during reverse transcription of the viral genome. A3G has two zing-binding domains: the N-terminal domain (NTD), which efficiently binds ssDNA, and the C-terminal catalytic domain (CTD), which supports deaminase activity of A3G. Until now, structural information on A3G has lacked, preventing elucidation of the molecular mechanisms underlying its interaction with ssDNA and deaminase activity. We have recently built computational model for the full-length A3G monomer and validated its structure by data obtained from time-lapse High-Speed Atomic Force Microscopy (HS AFM). Here time-lapse HS AFM was applied to directly visualize the structure and dynamics of A3G in complexes with ssDNA. Our results demonstrate a highly dynamic structure of A3G, where two domains of the protein fluctuate between compact globular and extended dumbbell structures. Quantitative analysis of our data revealed a substantial increase in the number of A3G dumbbell structures in the presence of the DNA substrate, suggesting the interaction of A3G with the ssDNA substrate stabilizes this dumbbell structure. Based on these data, we developed a model explaining the interaction of globular and dumbbell structures of A3G with ssDNA and suggested a possible role of the dumbbell structure in A3G function.
Plasticity at the DNA recognition site of the MeCP2 mCG-binding domain
Authors: Lei Ming , Tempel Wolfram , Liu Ke , Min Jinrong
Published: March 2019

MeCP2 is an abundant protein, involved in transcriptional repression by binding to CG and non-CG methylated DNA. However, MeCP2 might also function as a transcription activator as MeCP2 is found bound to sparsely methylated promoters of actively expressed genes. Furthermore, Attachment Region Binding Protein (ARBP), the chicken ortholog of MeCP2, has been reported to bind to Matrix/scaffold attachment regions (MARs/SARs) DNA with an unmethylated 5’-CAC/GTG-3’ consensus sequence. In this study, we investigated how MeCP2 recognizes unmethylated 5’-CAC/GTG-3’ motif containing DNA by binding and structural studies. We found that MeCP2-MBD binds to MARs DNA with a comparable binding affinity to mCG DNA, and the MeCP2-CAC/GTG complex structure revealed that MeCP2 residues R111 and R133 form base-specific interactions with the GTG motif. For comparison, we also determined crystal structures of the MeCP2-MBD bound to mCG and mCAC/GTG DNA, respectively. Together, these crystal structures illustrate the adaptability of the MeCP2-MBD toward the GTG motif as well as the mCG DNA, and also provide structural basis of a biological role of MeCP2 as a transcription activator and its disease implications in Rett syndrome.
An event-related potential study of decision making and feedback utilization in female college students who binge drink
Authors: Na Eun-Chan , Jang Kyoung-Mi , Kim Myung-Sun
Published: March 2019

This study investigated the ability to use feedback for decision making in female college students who binge drink (BD) using the Iowa Gambling Task (IGT) and event-related potentials (ERPs). Twenty-seven binge drinkers and 23 non-binge drinkers (non-BD) were identified based on scores on the Korean version of the Alcohol Use Disorder Test and the Alcohol Use Questionnaire. The IGT consists of four cards, including two cards that result in a net loss, with large immediate gains but greater losses in the long term, and two cards that result in a net gain, with small immediate gains but reduced losses in the long term. Participants were required to choose one card at a time to maximize profit until the end of the task while avoiding losses. The BD group showed a significantly lower total net score than the non-BD group, indicating that the BD group chose more disadvantageous cards. The BD group showed significantly smaller ΔFRN amplitudes (difference in amplitudes of feedback-related negativity [FRN] between gain and loss feedback) except in P3. Additionally, ΔFRN amplitudes in the fronto-central area were positively correlated with the total net score and net scores for sectors 4 and 5. Thus, total net scores and later performance on the IGT increased as ΔFRN amplitudes from the fronto-central area increased. FRN is known to reflect early feedback evaluation employing a bottom-up mechanism, whereas P3 is known to reflect late feedback processing and allocation of attentional resources using a top-down mechanism. These results indicate that college students who binge drink have deficits in early evaluation of positive or negative feedback and that this deficit may be related to decision making deficits.
Experimental 3D coherent diffractive imaging from photon-sparse random projections
Authors: Giewekemeyer K. , Aquila A. , Loh N.-T. D. , Chushkin Y. , Shanks K. S. , Weiss J.T. , Tate M. W. , Philipp H. T. , Stern S. , Vagovic P. , Mehrjoo M. , Teo C. , Barthelmess M. , Zontone F. , Chang C. , Tiberio R. C. , Sakdinawat A. , Williams G. J. , Gruner S. M. , Mancuso A. P.
Published: March 2019

The routine atomic resolution structure determination of single particles is expected to have profound implications for probing structure–function relationships in systems ranging from energy-storage materials to biological molecules. Extremely bright ultrashort-pulse X-ray sources – X-ray free-electron lasers (XFELs) – provide X-rays that can be used to probe ensembles of nearly identical nanoscale particles. When combined with coherent diffractive imaging, these objects can be imaged; however, as the resolution of the images approaches the atomic scale, the measured data are increasingly difficult to obtain and, during an X-ray pulse, the number of photons incident on the 2D detector is much smaller than the number of pixels. This latter concern, the signal `sparsity', materially impedes the application of the method. An experimental analog using a conventional X-ray source is demonstrated and yields signal levels comparable with those expected from single biomolecules illuminated by focused XFEL pulses. The analog experiment provides an invaluable cross check on the fidelity of the reconstructed data that is not available during XFEL experiments. Using these experimental data, it is established that a sparsity of order 1.3 × 10−3 photons per pixel per frame can be overcome, lending vital insight to the solution of the atomic resolution XFEL single-particle imaging problem by experimentally demonstrating 3D coherent diffractive imaging from photon-sparse random projections.
Anti-disturbance iterative learning tracking control for space manipulators with repetitive reference trajectory
Authors: Qiao Jian Zhong , Wu Hao , Zhu Yukai , Xu Jianwei , Li Wenshuo
Published: March 2019

Purpose

This paper is concerned with the repetitive trajectory tracking control for space manipulators under model uncertainties and vibration disturbances.

Design/methodology/approach

The model uncertainties and link vibration of manipulators will degrade the tracking performance of space manipulators; in this paper, a new hybrid control scheme that consists of a composite hierarchical anti-disturbance controller and an iterative learning controller is developed to solve this problem.

Findings

The composite hierarchical controller can effectively attenuate model uncertainties and reject vibration disturbances, whereas the iterative learning controller is able to improve the tracking accuracy for repetitive reference trajectory.

Originality/value

The proposed scheme compensates for the shortcomings of iterative learning control which can only deal with repetitive disturbances, ensuring the accuracy and repeatability of space manipulators under model uncertainties and random disturbances.
Distributed adaptive fuzzy tracking algorithms for multiple uncertain mechanical systems
Authors: Sun Yanchao , Chen Liangliang , Qin Hongde
Published: March 2019

Purpose

This paper aims to investigate the distributed coordinated fuzzy tracking problems for multiple mechanical systems with nonlinear model uncertainties under a directed communication topology.

Design/methodology/approach

The dynamic leader case is considered while only a subset of the follower mechanical systems can obtain the leader information. First, this paper approximates the system uncertainties with finite fuzzy rules and proposes a distributed adaptive tracking control scheme. Then, this paper makes a detailed classification of the system uncertainties and uses different fuzzy systems to approximate different kinds of uncertainties. Further, an improved distributed tracking strategy is proposed. Closed-loop systems are investigated using graph theory and Lyapunov theory. Numerical simulations are performed to verify the effectiveness of the proposed methods.

Findings

Based on fuzzy control and adaptive control theories, the desired distributed coordinated tracking control strategies for multiple uncertain mechanical systems are developed.

Originality/value

Compared with most existing literature, the proposed distributed tracking algorithms use fuzzy control and adaptive control techniques to cope with system nonlinear uncertainties of multiple mechanical systems. Moreover, the improved control strategy not only reduces fuzzy rules but also has higher control accuracy.
E-university delivery model: handling the evaluation process
Authors: Ismail Rasha , Safieddine Fadi , Jaradat Ashraf
Published: March 2019

Purpose

The setting up of e-university has been slow-going. Much of e-university slow progress has been attributed to poor business models, branding, disruptive technologies, lack of organisational structure that accommodates such challenges, and failure to integrate a blended approach. One of the stumbling blocks, among many, is the handling of evaluation process. E-university models do not provide much automation compared to the original brick-and-mortar classroom model of delivery. The underlining technologies may not have been supportive; however, the conditions are changing, and more evaluation tools are becoming available for academics. The paper aims to discuss these issues.

Design/methodology/approach

This paper identifies the extent of current online evaluation processes. In this process, the team reviews the case study of a UK E-University using Adobe Connect learning model that mirrors much of the physical processes as well as online exams and evaluation tools. Using the Riva model, the paper compares the physical with the online evaluation processes for e-universities to identify differences in these processes to evaluate the benefits of e-learning. As a result, the models can help us to identify the processes where improvements can take place for automating the process and evaluate the impact of this change.

Findings

The paper concludes that this process can be significantly shortened and provide a fairer outcome but there remain some challenges for e-university processes to overcome.

Originality/value

This paper examines the vital quality assurance processes in academia as more universities move towards process automation, blended or e-university business models. Using the case study of Arden University online distance learning, the paper demonstrates, through modelling and analysis that the process of online automation of the evaluation process is achieved with significant efficiency.
The mediating role of overall fairness perception: a structural equation modelling assessment
Authors: Mohammad Jihad , Quoquab Farzana , Idris Fazli , Al Jabari Mohammad , Wishah Raed
Published: March 2019

Purpose

Most of the past studies related to organisational justice focussed on different types of justice, such as procedural justice, distributive justice and interactional justice either separately or collectively. Still, further investigation on the overall concept of fairness is required to extend theoretical generalisability. Moreover, researchers argued that overall fairness rather than a specific type represents more concrete situation about employees’ perception of fairness within an organisation. Considering this, the purpose of this paper is to examine the mediating effect of overall fairness perception (OFP) in relation to workplace outcome as well as its predictive ability on employees’ attitude and behaviour in term of psychological ownership and citizenship behaviour.

Design/methodology/approach

A total of 250 questionnaires were distributed among the employees of financial institutions in Malaysia, which yielded 150 completed usable responses. Smart PLS (version 3) software and SPSS were utilised in order to analyse the data.

Findings

The results revealed that overall fairness plays a crucial role as a mediator as well as a predictor. Limitations and future research directions are also discussed.

Practical implications

This study provides useful insights for the mangers of financial institutions. It also suggests strategies about how to manage justice and workplace outcomes at workplace.

Originality/value

This paper is among the pioneers to address the mediating role of OFP in relations to workplace attitude and behaviour in non-western context.
Training effects on subsistence entrepreneurs’ hope and goal attainment
Authors: Barrios Andres , Reficco Ezequiel , Taborda Rodrigo
Published: March 2019

Purpose

The purpose of this paper is to explore the extent to which hope and perceived goal attainment can be developed in subsistence entrepreneurs through the right training tools.

Design/methodology/approach

A longitudinal study of a subsistence entrepreneurship training program in three Central American countries was carried out. Participants were divided on the basis of their exposure to training (yes, no), and of the type of training received (none, business plan, business model). The authors carried out three assessments (just before the program, six months and one year after the program) of participants’ business goals and their hope of attaining them. Information was analyzed using linear regression.

Findings

Participants exposed to training reported significant increases in perceived goal attainment and in their hope levels. Training based on the business plan affected hope agency in the short term, as predicted by the logic of causation theory. Training based on the business canvas affected hope pathways, as predicted by the logic of effectuation theory.

Research limitations/implications

Given the data collection process (a non-random sample and selection of participants), the findings are not generalizable without stringent procedures and further replication.

Practical implications

If hope is a reliable predictor of goal attainment, it should be promoted and measured. Given the limited means of gathering data and making reliable projections that most entrepreneurs endure, the business canvas’ contribution to entrepreneurs’ “emotional equipment” ceteris paribus should be more valuable for subsistence entrepreneurs.

Originality/value

This is the first study comparing the short- and long-term effects of two entrepreneurial learning devices on entrepreneurs’ hope and business goal attainment.
An inherent differentiation and system level assessment approach to inventory management
Authors: Jonsson Patrik , Mattsson Stig-Arne
Published: March 2019

Purpose

The purpose of this paper is to explain the effects of inherent differentiation and system level performance assessment in inventory management. This is done by comparing the performance of two common safety stock methods, by considering the methods’ inherent differentiation and item group-level performance effects.

Design/methodology/approach

Due to the lack of analytical relationships between the two methods, the analysis is based on event-driven simulations. Data are collected from eight different case companies. Findings explain the importance of assessing safety stock performance for groups of items and not for individual items, as is common in academic studies. It explains how the methods’ inherent differentiation and planning environment characteristics affect the relative performances of the two safety stock methods.

Findings

The study explains the importance of assessing performance of safety stock methods on a system-level, rather than on item-level measures. It explains why the demand fill-rate method has a negative impact on the performance for groups of items, while the number-of-days method has a positive impact. The study also explains how the group-level safety stock performance is affected by five demand data characteristics.

Research limitations/implications

The study explains the importance of assessing performance of safety stock methods on a system-level, rather than on item-level measures. It explains why the demand fill-rate method has a negative impact on the performance for groups of items, while the number-of-days method has a positive impact. The study also explains how the group-level safety stock performance is affected by five demand data characteristics.

Practical implications

Understanding the necessity of system level assessment of safety stock performance, how methods inherently differentiate service levels, and how demand characteristics affect methods’ performance can guide the choice of safety stock methods in companies.

Originality/value

No research on the characteristics of the number-of-days safety stock method, any assessment of differentiation characteristics of and comparison with the demand fill-rate method, has been published. The variable “inherent differentiation” is also introduced and defined.