bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudomonas aeruginosauses c-di-GMP phosphodiesterases RmcA and MorA to regulate biofilm maintenance
Authors: Katharios S.L. , Whitfield G.B. , Howell P.L. , O’Toole G.A.
Published: June 2020

While the early stages of biofilm formation have been well characterized, less is known about the requirements forPseudomonas aeruginosato maintain a mature biofilm. We utilized aP. aeruginosa-phage interaction to find thatrmcAandmorA, two genes which encode for c-di-GMP-degrading phosphodiesterase (PDEs) enzymes, are important for the regulation of biofilm maintenance. Deletion of these genes initially results in an elevated biofilm phenotype characterized by increased production of c-di-GMP, Pel polysaccharide and biofilm biomass. In contrast to the wild-type strain, these mutants were unable to maintain the biofilm when exposed to carbon-limited conditions. The susceptibility to nutrient limitation, and subsequent loss of biofilm viability of these mutants, was phenotypically reproduced with a stringent response mutant (ΔrelAΔspoT), indicating that the ΔrmcAand ΔmorAmutants may be unable to appropriately respond to nutrient limitation. Genetic and biochemical data indicate that RmcA and MorA physically interact with the Pel biosynthesis machinery, supporting a model whereby unregulated Pel biosynthesis contributes to the death of the ΔrmcAand ΔmorAmutant strains in an established biofilm when nutrient-limited. These findings provide evidence that c-di-GMP-mediated regulation is required for mature biofilms ofP. aeruginosato effectively respond to changing availability of nutrients. Furthermore, the PDEs involved in biofilm maintenance are distinct from those required for establishing a biofilm, thus indicating that a wide variety of c-di-GMP metabolizing enzymes in organisms likeP. aeruginosalikely allows for discrete control over the formation, maintenance or dispersion of biofilms.

Importance

Recent advances in our understanding of c-di-GMP signaling have provided key insights into the regulation of biofilms. Despite an improved understanding of how they initially form, the processes that facilitate the long-term maintenance of these multicellular communities remain opaque. We found thatP. aeruginosarequires two phosphodiesterases, RmcA and MorA, to maintain a mature biofilm and thatP. aeruginosabiofilms lacking these PDEs succumb to nutrient limitation and die. The biofilm maintenance deficiency observed in ΔrmcAand ΔmorAmutants was also found in the stringent response defective ΔrelAΔspoTstrain, suggesting that a regulatory intersection between c-di-GMP signaling, EPS biosynthesis and the nutrient limitation response is important for persistent surface growth. We uncover components of an important regulatory system needed forP. aeruginosato persist in nutrient-poor conditions, and provide some of the first evidence that maintaining a mature biofilm is an active process.
ASSESSING THE RELATIONSHIP BETWEEN MONOALLELIC PARK2 MUTATIONS AND PARKINSON’S RISK
Authors: Lubbe Steven J , Bustos Bernabe , Hu Jing , Krainc Dimitri , Joseph Theresita , Hehir Jason , Tan Manuela , Zhang Weijia , Escott-Price Valentina , Williams Nigel M , Blauwendraat Cornelis , Singleton Andrew B , Morris Huw R ,   for International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: June 2020

Biallelic PARK2 (Parkin) mutations cause autosomal recessive Parkinson’s (PD); however, the role of monoallelic PARK2 mutations as a risk factor for PD remains unclear. We investigated the role of single heterozygous PARK2 mutations in three large independent case-control cohorts totalling 10,858 PD cases and 8,328 controls. Overall, after exclusion of biallelic carriers, single PARK2 mutations were more common in PD than controls conferring a >1.5-fold increase in risk of PD (P=0.035), with meta-analysis (19,574 PD cases and 468,488 controls) confirming increased risk (OR=1.65, P=3.69E-07). Carriers were shown to have significantly younger ages at onset compared to non-carriers (NeuroX: 56.4 vs. 61.4 years; Exome: 38.5 vs. 43.1 years). Stratifying by mutation type, we provide preliminary evidence for a more pathogenic risk profile for single PARK2 copy number variant (CNV) carriers compared to single nucleotide variant carriers. Studies that did not assess biallelic PARK2 mutations or consist of predominantly early-onset cases may be biasing these estimates, and removal of these resulted in a loss of association (OR=1.23, P=0.614; n=4). Importantly, when we looked for additional CNVs in 30% of PD cases with apparent monoallellic PARK2 mutations we found that 44% had biallelic mutations suggesting that previous estimates may be influenced by cryptic biallelic mutation status. While this study supports the association of single PARK2 mutations with PD, it highlights confounding effects therefore caution is needed when interpreting current risk estimates. Together, we demonstrate that comprehensive assessment of biallelic mutation status is essential when elucidating PD risk associated with monoallelic PARK2 mutations.
Predicting the disease outcome in COVID-19 positive patients through Machine Learning: a retrospective cohort study with Brazilian data
Authors: de Souza Fernanda Sumika Hojo , Hojo-Souza Natália Satchiko , dos Santos Edimilson Batista , da Silva Cristiano Maciel , Guidoni Daniel Ludovico
Published: June 2020

The first officially registered case of COVID-19 in Brazil was on February 26, 2020. Since then, the situation has worsened with more than 672, 000 confirmed cases and at least 36, 000 reported deaths at the time of this writing. Accurate diagnosis of patients with COVID-19 is extremely important to offer adequate treatment, and avoid overloading the healthcare system. Characteristics of patients such as age, comorbidities and varied clinical symptoms can help in classifying the level of infection severity, predict the disease outcome and the need for hospitalization. Here, we present a study to predict a poor prognosis in positive COVID-19 patients and possible outcomes using machine learning. The study dataset comprises information of 13, 690 patients concerning closed cases due to cure or death. Our experimental results show the disease outcome can be predicted with a ROC AUC of 0.92, Sensitivity of 0.88 and Specificity of 0.82 for the best prediction model. This is a preliminary retrospective study which can be improved with the inclusion of further data. Conclusion: Machine learning techniques fed with demographic and clinical data along with comorbidities of the patients can assist in the prognostic prediction and physician decision-making, allowing a faster response and contributing to the non-overload of healthcare systems.
Safe Non-opioid and Non-barbiturate containing Acute Medication Combinations in Headache: An Exhaustive Approach Based on DrugBank Database
Authors: Kaytser Victor , Zhang Pengfei
Published: June 2020

Structured Abstract

Background

Rational polypharmacy in abortive medications use is often inevitable for patients with refractory headaches.

Objective

We seek to enumerate an exhaustive list of headaches abortive medications that are without drug-drug interactions.

Methods

We updated a list of acute medications based on the widely used Jefferson Headache Manual with novel abortive medications including ubrogepant, lasmiditan, and rimegepant. Opioids and barbiturate containing products are excluded. We then conducted an exhaustive search of all pair-wise interactions for this list of medication via DrugBank API. Using this interaction list, we filtered all possible two, three, and four drug combinations of abortive medications. The resultant list of medication was then reapplied to DrugBank to verify the lack of known drug-drug interaction.

Results

There are 192 medication combinations that do not contain any drug-drug interactions. Most common elements in these combinations are ubrogepant, prochlorperazine, followed by tizanidine. There are 67 three-drug combinations that do not contain interaction. Only 2 of the four-drug combinations do not yield some form of drug-drug interactions.

Conclusion

This list of headaches abortive medications without drug-drug interactions is a useful tool for clinicians seeking to more effectively manage refractory headaches.
Health concern affects egg consumption among older adults in Tamale Metropolis, Northern Ghana
Authors: Garti Humphrey , Wemakor Anthony , Akwalpua Emmanuella , Saeed Nawaf
Published: June 2020

Background

Eggs are nutrient dense and rich source of quality protein and their consumption could significantly reduce incidence of chronic and infectious diseases especially in the elderly. This study determined egg consumption and factors that influence consumption among the elderly in Tamale metropolis.

Methods

Analytical cross-sectional study was conducted among 387 older adults 60 years and above. Data on egg consumption, nutritional knowledge and awareness of health implications of egg intake were collected using structured questionnaire. Relationships between egg consumption, nutritional knowledge and awareness of health effects of egg consumption were determined in bivariate and multivariate analysis.

Results

Respondents without awareness that egg intake increases risk of diseases were 10 times more likely to eat eggs compared to those who had awareness [Adjusted Odds Ratio 10.24; 95% Confidence Interval (CI) 4.20 – 25.00; p= 0.001]. Respondents with awareness that egg consumption was bad for health were less likely to consume eggs compared to those who thought egg intake was good for health [AOR 0.02; 95 % CI, 0.01 – 0.05, p < 0.001].

Conclusion

Egg consumption was low among the study population and was affected by health concerns: awareness that egg consumption was not good for health and exposes them to the risk of certain diseases
FMRP activates the translation of large autism/intellectual disability proteins and stimulates N-end rule E3 ligase Poe/UBR4 production within puromycin-sensitive RNP particles
Authors: Greenblatt Ethan J. , Spradling Allan C.
Published: June 2020

Mutations in Fmr1, encoding the RNA binding protein FMRP, are leading causes of intellectual disability, autism, and female infertility, but FMRP’s mechanism of action is controversial. In contrast to its previously postulated function as a translation repressor acting by stalling elongation, we recently found that FMRP activates translation initiation of large proteins in Drosophila oocytes up to ∼2-fold. We report here that FMRP’s function as a translational activator is conserved in the mammalian brain. Reanalysis of mouse cortex ribosome profiling data shows that translation of large proteins in Fmr1 mutants is down-regulated 2.0-1.2-fold; ribosome stalling appears not to influence FMRP target protein translation in either cortex or oocyte tissue. Consistent with an activator function, most FMRP targets are associated with clinical syndromes when reduced, but not when over-expressed. Fmr1-dependent translation of one target, the N-end rule E3 ligase Poe/UBR4, occurs in microscopically visible ribonucleoprotein particles. These “Poe particles” require FMRP for their formation, are distinct from P bodies, and depend on actively elongating ribosomes, as indicated by their dissolution following a brief puromycin treatment. N-end rule-mediated proteolysis via Poe/UBR4 restrains cell growth and limits MAPK signaling in nervous tissue. Thus, loss of FMRP reduces production of an important growth repressor.
RPA complexes inCaenorhabditis elegansmeiosis; unique roles in replication, meiotic recombination and apoptosis
Authors: Hefel Adam , Cronin Nicholas , Harrel Kailey , Patel Pooja , Spies Maria , Smolikove Sarit
Published: June 2020

Replication Protein A (RPA) is critical complex that acts in replication and promotes homologous recombination by allowing recombinase recruitment to processed DSB ends. Most organisms possess three RPA subunits (RPA1, RPA2, RPA3) that form a trimeric complex critical for viability. TheCaenorhabditis elegansgenome encodes for RPA-1, RPA-2 and an RPA-2 paralog RPA-4. In our analysis, we determine that RPA-2 is critical for germline replication, and normal repair of meiotic DSBs. Interestingly, RPA-1 but not RPA-2 is essential for replication, contradictory to what is seen in other organisms, that require both subunits. In the germline, both RPA-1/2 and RPA-1/4 complexes form, but RPA-1/4 is less abundant and its formation is repressed by RPA-2. While RPA-4 does not participate in replication or recombination, we find that RPA-4 inhibit RAD-51 filament formation and promotes apoptosis on a subset of damaged nuclei. Altogether these findings point to sub-functionalization and antagonistic roles of RPA complexes inC. elegans.
Small molecules exploiting structural differences within microRNA-200 precursors family members reverse a type 2 diabetes phenotype
Authors: Haniff Hafeez S. , Liu Xiaohui , Knerr Laurent , Lemurell Malin , Abegg Daniel , Adibekian Alexander , Disney Matthew D.
Published: June 2020

MicroRNA families are pervasive in the human transcriptome, but specific targeting of individual members is a challenge because of sequence homology. Many of the secondary structures of the precursors to these miRs (pre-miRs), however, are quite different. Here, we demonstrate bothin vitroandin cellulisthat design of structure-specific small molecules can inhibit specific miR family members to modulate a disease pathway. In particular, the miR-200 family consists five miRs, miR-200a, −200b, −200c, −141, and - 429, and is associated with Type II Diabetes (T2D). We designed a small molecule that potently and selectively targets pre-miR-200c’s structure. The compound reverses a pro-apoptotic effect in a pancreatic β-cell model. In contrast, oligonucleotides targeting the RNA’s sequence inhibit all family members. Global proteomics analysis further demonstrates selectivity for miR-200c. Collectively, these studies establish that miR-200c plays an important role in T2D and that small molecules targeting RNA structure can be an important complement to oligonucleotides targeting sequence.

Significance Statement

The most common way to develop medicines targeting RNA is by using oligonucleotides that target its sequence by using base pairing. Some RNAs, however, have similar sequences and thus are impossible to target selectively by using oligonucleotides. Here, we show that a class of RNAs that have similar sequences emerge from precursors that have very different structures. Exploiting these structural differences afforded a selective compound. In particular, the selective small molecule targets a member of the microRNA (miR)-200 family, the overexpression of which is linked to diabetes and pancreatic cell death. Selective inhibition of family member miR-200c alleviates pancreatic cell death, and thus the small molecule provides a path to the treatment of diabetes.
Cryo-EM Structures of Respiratorybc1-cbb3type CIII2CIV Supercomplex and Electronic Communication Between the Complexes
Authors: Steimle Stefan , VanEeuwen Trevor , Ozturk Yavuz , Kim Hee Jong , Braitbard Merav , Selamoglu Nur , Garcia Benjamin A. , Schneidman-Duhovny Dina , Murakami Kenji , Daldal Fevzi
Published: June 2020

The respiratory electron transport complexes convey electrons from nutrients to oxygen and generate a proton-motive force used for energy (ATP) production in cells. These enzymes are conserved among organisms, and organized as individual complexes or combined forming large super-complexes (SC). Bacterial electron transport pathways are more branched than those of mitochondria and contain multiple variants of such complexes depending on their growth modes. The Gram-negative species deploy a mitochondrial-like cytochromebc1(Complex III, CIII2), and may have bacteria-specificcbb3-type cytochromecoxidases (Complex IV, CIV) in addition to, or instead of, the canonicalaa3-type CIV. Electron transfer between these complexes is mediated by two different carriers: the soluble cytochromec2which is similar to mitochondrial cytochromecand the membrane-anchored cytochromecywhich is unique to bacteria. Here, we report the first cryo-EM structure of a respiratorybc1-cbb3type SC (CIII2CIV, 5.2Å resolution) and several conformers of native CIII2(3.3Å resolution) from the Gram-negative bacteriumRhodobacter capsulatus. The SC contains all catalytic subunits and cofactors of CIII2and CIV, as well as two extra transmembrane helices attributed to cytochromecyand the assembly factor CcoH. Remarkably, some of the native CIII2are structural heterodimers with different conformations of their [2Fe-2S] cluster-bearing domains. The unresolved cytochromecdomain ofcysuggests that it is mobile, and it interacts with CIII2CIV differently than cytochromec2. Distance requirements for electron transfer suggest that cytochromecyand cytochromec2donate electrons to hemecp1and hemecp2of CIV, respectively. For the first time, the CIII2CIV architecture and its electronic connections establish the structural features of two separate respiratory electron transport pathways (membrane-confined and membrane-external) between its partners in Gram-negative bacteria.
Modeling the Coronavirus Disease 2019 Incubation Period: Impact on Quarantine Policy
Authors: Pak Daewoo , Langohr Klaus , Ning Jing , Martínez Jordi Cortés , Melis Guadalupe Gómez , Shen Yu
Published: June 2020

The incubation period of coronavirus disease 2019 (COVID-19) is not always observed exactly due to uncertain onset times of infection and disease symptom. In this paper, we demonstrate how to estimate the distribution of incubation and its association with patient demographic factors when the exact dates of infection and symptoms onset may not be observed. The findings from analysis on the confirmed COVID-19 cases indicate that age could be associated with the incubation period, and an age-specific quarantine policy might be more efficient than a unified one in confining COVID-19.
SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice
Authors: Tian Jing-Hui , Patel Nita , Haupt Robert , Zhou Haixia , Weston Stuart , Hammond Holly , Lague James , Portnoff Alyse D. , Norton James , Guebre-Xabier Mimi , Zhou Bin , Jacobson Kelsey , Maciejewski Sonia , Khatoon Rafia , Wisniewska Malgorzata , Moffitt Will , Kluepfel-Stahl Stefanie , Ekechukwu Betty , Papin James , Boddapati Sarathi , Wong C. Jason , Piedra Pedro A. , Frieman Matthew B. , Massare Michael J. , Fries Louis , Lövgren Bengtsson Karin , Stertman Linda , Ellingsworth Larry , Glenn Gregory , Smith Gale
Published: July 2020

The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).
Emergence of Zika virus: Direct reversion of mutations and fitness restoration prior to spread to the Americas
Authors: Liu Jianying , Liu Yang , Shan Chao , Nunes Bruno T.D. , Yun Ruimei , Haller Sherry L. , Rafael Grace H. , Azar Sasha R. , Andersen Clark R. , Plante Kenneth , Vasilakis Nikos , Shi Pei-Yong , Weaver Scott C.
Published: July 2020

Summary Paragraph

Mosquito-borne viruses have recently spread globally, with major impacts on human health. Zika virus (ZIKV) emerged from obscurity in 2013 to spread from Asia to the South Pacific and the Americas, where millions of people were infected. For the first time, severe clinical manifestations, including Guillain Barré syndrome and defects to the fetuses of pregnant women, were detected. Phylogenetic studies have shown that ZIKV evolved in Africa and later spread to Asia, and that the Asian lineage is responsible for the recent epidemics. However, the reasons for the sudden emergence of ZIKV remain incompletely understood. Accumulating evidence on other arboviruses like chikungunya and West Nile suggest the likelihood that viral mutations could be determinants of change in ZIKV transmission efficiency responsible for efficient spread. Using evolutionary analyses, we determined that four mutations, which occurred just before ZIKV introduction to the Americas, represent direct reversions of previous mutations that accompanied spread many decades ago from ZIKV’s native Africa to Asia and early circulation there. Experimental infections of mosquitoes, human cells, and mice using ZIKV strains with and without these mutations demonstrated that the original mutations reduced fitness for urban transmission, while the reversions restored fitness, increasing epidemic risk. Overall, our findings include the three newly identified, transmission-adaptive ZIKV mutations, and demonstration that these and one identified previously restored fitness for epidemic transmission soon before introduction into the America. The initial mutations may have followed founder effects and/or drift when the virus was introduced into Asia, or could be related to changes on host or vector utilization within Asia.
Validation and Comparison of a Modified CDC Assay with two Commercially Available Assays for the Detection of SARS-CoV-2 in Respiratory Specimen
Authors: Lima Amorce , Healer Vicki , Vendrone Elaine , Silbert Suzane
Published: July 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread rapidly around the globe since it was first identified in December of 2019 in Wuhan, China. In a race to contain the infection, researchers and healthcare officials have developed several assays to help diagnose individuals with COVID-19. To help laboratories in deciding what assay to bring into testing lines, factors such as assay availability, cost, throughput, and TAT should be considered. Here we validated a modified version of the CDC assay and used it as a reference to evaluate the performance of the NeuMoDx™ SARS-CoV-2 and DiaSorin Simplexa™ Covid-19 Direct assays.In silicoanalysis and clinical sample testing showed that the primesr/probes designed by the CDC were specific to the SARS-CoV-2 as they accurately detected all reactive samples with an assay LoD of 200 copies/ml. The performance of the three assays were analyzed using 161 nasopharyngeal swabs specimen tested within 24 hours or 5 days from routine testing. A 100% agreement was observed between the commercial assays and the modified CDC SARS-CoV-2 assay. A deeper look at the Ct values showed no significant difference between NeuMoDx and the modified CDC SARS-CoV-2 assay, whereas DiaSorin had lower overall Ct values than the modified CDC SARS-CoV-2 assay. NeuMoDx and DiaSorin workflows were much easier to perform. NeuMoDx has the highest throughput and shortest TAT, whereas although the modified CDC SARS-CoV-2 assay has comparable throughput to DiaSorin, it has the longest hands-on time, and highest TAT.
Asymmetric neurogenic commitment of retinal progenitors is regulated via the Notch endocytic pathway
Authors: Nerli Elisa , Rocha-Martins Mauricio , Norden Caren
Published: July 2020

During brain development, progenitor cells need to balance proliferation and differentiation in order to generate different neurons in the correct numbers and proportions. Currently, the patterns of multipotent progenitors’ division that lead to neurogenic entry and the factors that regulate them are not fully understood. We here use the zebrafish retina to address this gap, exploiting the possibilities for quantitative live-imaging. We show that early neurogenic progenitors arise from asymmetric divisions. Notch regulates this asymmetry as when inhibited, symmetric divisions producing two neurogenic progenitors occur. Surprisingly, Notch does not act through an apicobasal activity gradient as previously suggested but through asymmetric inheritance of Sara-positive endosomes. Further, the resulting neurogenic progenitors show cell biological features different from multipotent progenitors, raising the possibility that an intermediate state of progenitors exists in the retina. Our study thus opens new insights into the regulation of proliferative and differentiative events during central nervous system development.
The genetic architecture of structural left-right asymmetry of the human brain
Authors: Sha Zhiqiang , Schijven Dick , Carrion-Castillo Amaia , Joliot Marc , Mazoyer Bernard , Fisher Simon E. , Crivello Fabrice , Francks Clyde
Published: July 2020

Left-right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and can be altered in cognitive and psychiatric disorders1-8. No mechanism has yet been identified for establishing the human brain’s left-right axis9. We performed multivariate genome-wide association scanning (mvGWAS) of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci affecting different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left-right axis determination in other organs of invertebrates and frogs10-12. Genetic variants affecting brain asymmetry overlapped with those influencing autism, educational attainment and schizophrenia.
Impact of COVID-19 related lockdown on cognition and emotion: A pilot study
Authors: Lahiri Durjoy , Dubey Souvik , Ardila Alfredo
Published: July 2020

COVID-19 pandemic has posed an unprecedented challenge in front of the world contributed mostly by social distancing and lockdown. Among several other effects this pandemic has wreaked havoc on the psychology and cognition of people across the globe. In this paper we attempted to find out the impact of lockdown and social isolation on the cognition and emotion of young healthy adults with high education (n=43) by means of a questionnaire sent through email. We found that more than 50% of the participants had some kind of emotional or cognitive (dysexecutive) symptoms, as calculated through emotional symptom index (ESI) and cognitive symptom index (CSI). The correlation between cognitive and emotional symptoms was also found to be moderately strong (0.59). Although it is a pilot study and larger samples are required to draw firm conclusion, the results argue in favor of a negative impact on the cognition and emotion of healthy educated young people caused by the COVID-19 related lockdown. It can be conjectured that, if taking an older sample with a lower education, emotional and cognitive changes would be more evident.
Developing and Validating a New Web-Based Tapping Test for Measuring Distal Bradykinesia in Parkinson’s Disease
Authors: Akram Noreen , Li Haoxuan , Ben-Joseph Aaron , Budu Caroline , Gallagher David , Bestwick Jonathan P , Noyce Alastair J , Simonet Cristina
Published: July 2020

Background

Disability in Parkinson’s disease (PD) is measured by standardised scales including the MDS-UPDRS, which are subject to high inter and intra-rater variability and fail to capture subtle motor impairment. The BRadykinesia Akinesia INcoordination (BRAIN) test is a previously validated keyboard tapping test, evaluating proximal upper-limb motor impairment. Here, a new Distal Bradykinesia Tapping (DBT) test was developed to assess distal upper-limb function. Kinetic parameters of the test include kinesia score (KS20, key taps over 20 seconds), akinesia time (AT20, mean dwell-time on each key) and incoordination score (IS20, variance of travelling time between key taps).

Objective

To develop and validate a new keyboard-tapping test to assess distal motor function in PD patients.

Methods

The DBT test was validated in 45 PD patients and 24 controls, alongside the BRAIN test. Test scores were compared between groups and correlated with MDS-UPDRS-III scores. 10 additional PD patients were recruited to assess the DBT test in monitoring motor fluctuations.

Results

All three parameters discriminated between patients and controls, with KS20 performing best, yielding 75% sensitivity for 85% specificity; area under the receiver operating characteristic curve (AUC) = 0.87. Combination of both the DBT and BRAIN tests improved discrimination (AUC=0.91). KS20 and AT20 correlated with MDS-UPDRS-III (Pearson’s r=-0.49, p<0.001 and r=0.54, p<0.001, respectively). The DBT test detected subtle changes in motor fluctuation states, which were not reflected clearly by MDS-UPDRS-III sub-scores.

Conclusion

The DBT test is a user-friendly method of assessing distal motor dysfunction in PD, possibly permitting longitudinal monitoring of PD motor complications.
BDNF overexpression in the ventral hippocampus promotes antidepressant- and anxiolytic-like activity in serotonin transporter knockout rats
Authors: Diniz Danielle M. , Calabrese Francesca , Brivio Paola , Riva Marco A. , Grandjean Joanes , Homberg Judith R.
Published: July 2020

Brain-derived neurotrophic factor is one of the most studied proteins playing a pivotal role in neuroplasticity events and vulnerability and resilience to stress-related disorders. Most importantly, BDNF is decreased in depressive patients, and increased after antidepressant treatment. Additionally, BDNF was found to be reduced in a genetic subset of depression susceptible patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT-/-) is one of the animal models used to investigate the underlying molecular mechanisms behind the genetic susceptibility to depression in humans. SERT-/-rats present decreased BDNF levels, especially BDNF exon IV, in the prefrontal cortex (PFC) and ventral hippocampus (vHIP), and display anxiety- and depression-like behavior. To investigate whether upregulating BDNF in the vHIP would meliorate the phenotype of SERT-/-rats, we overexpressed BDNF locally into the rat brain by means of stereotaxic surgery and submitted the animals to behavioral challenges, including the sucrose consumption, the open field, and forced swim tests. Additionally, we measured hypothalamus-pituitary-adrenal (HPA)-axis reactivity. The results showed that lentivirus-induced BDNF IV overexpression in the vHIP of SERT-/-rats promoted higher sucrose preference and sucrose intake, on the first day of the sucrose consumption test, indicative for decreased anhedonia-like behavior. Moreover, it decreased immobility time in the forced swim test, suggesting adaptive passive coping. Additionally, BDNF upregulation increased the time spent in the center of a novel environment, implying decreased novel-induced anxiety-like behavior. Finally, it promoted a stronger decrease in plasma corticosterone levels 60 minutes after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT-/-rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential candidate for the development new therapeutic approaches targeting the improvement of depressive symptoms.
One-Step Bacterial Artificial Chromosome (BAC) Modification: Preparation of the A Homology Arm (A-Box)
Authors: Heintz Nathaniel , Gong Shiaoching
Published: July 2020

The one-step approach to bacterial artificial chromosome (BAC) modification requires that only one homology arm be cloned into the shuttle vector (in the example presented here, we use the “A-box”). The homology arm, which in this case lies upstream of the ATG start codon, is amplified by polymerase chain reaction (PCR) using purified BAC DNA as template. The resulting amplification product is then digested with the appropriate restriction endonuclease to render it suitable for cloning into the shuttle vector.
One-Step Bacterial Artificial Chromosome (BAC) Modification: Transfer of the Reporter Vector into BAC/RecA Cells and Selection of Co-Integrates
Authors: Heintz Nathaniel , Gong Shiaoching
Published: July 2020

In one-step bacterial artificial chromosome (BAC) modification, recombination of the reporter vector with the BAC—leading to the modified BAC—is facilitated by the presence of RecA. Recombinants are selected for by growth in the presence of chloramphenicol, ampicillin, and tetracycline. Only bacteria containing correctly modified BACs and copies of pSV1.RecA will be selected. Unmodified BACs (i.e., those lacking a pLD53.SC2/A-box insert) are eliminated by exposure to ampicillin. Free reporter plasmid remaining in the BAC host bacteria will also be eliminated, because this vector requires the π protein to replicate. The co-integrates are selected by growth at high temperature, thereby eliminating the RecA plasmid. Successful modification of the BAC—formation of the co-integrate—is confirmed in separate amplification reactions.
An analytical method for spiral-wound heat exchanger: design and cost estimation considering temperature-dependent fluid properties
Authors: Hosseinian Seyed Mohsen , Mostafazade Abolmaali Ali , Afshin Hossein
Published: July 2020

Purpose

Spiral-wound heat exchangers (SWHEs) are widely used in different industries. In special applications, such as cryogenic (HEs), fluid properties may significantly depend on fluid temperature. This paper aims to present an analytical method for design and rating of SWHEs considering variable fluid properties with consistent shell geometry and single-phase fluid.

Design/methodology/approach

To consider variations of fluid properties, the HE is divided into identical segments, and the fluid properties are assumed to be constant in each segment. Validation of the analytical method is accomplished by using three-dimensional numerical simulation with shear stress transport k-ω model, and the numerical model is verified by using the experimental data. Moreover, the HE cost is selected as the main criterion in obtaining the proper design, and the most affordable geometry is selected as the proper design.

Findings

The accuracy of different heat transfer and pressure drop correlations is investigated by comparing the analytical and numerical results. The average errors in the calculation of effectiveness, shell-side pressure drop and tube-side pressure drop using the analytical method are 2.1%, 13.9% and 13.3%, respectively. Moreover, the effect of five main geometrical parameters on the SWHE cost is investigated. The results indicate that the effect of longitudinal pitch ratio on the SWHE cost can be neglected, whereas other geometrical parameters have a significant impact on the total cost of the SWHE.

Originality/value

This work contains a versatile and low-cost analytical method to design and rating the SWHEs considering the variable fluid property with consistent shell geometry. The previous studies have introduced complex methods and have not considered the consistency of shell geometry.
Use of social media for information discovery and delivery among information professionals in Pakistan
Authors: Hussain Ashfaq , Taimoor-Ul-Hassan  , Shabir Ghulam
Published: July 2020

Purpose

This study aims to examine how information professionals select a social media channel for information discovery and delivery. This analysis was focused to provide usage based ranking of social media channels for information discovery and delivery. This study has also measured the preference of social media as compared with other information and communication channels such as radio, TV, newspapers, etc., for information discovery and delivery. This study compared the global social media rank with the study rank to record the variances in the light of uses and gratification theory.

Design/methodology/approach

For this quantitative research study a self-administered survey questionnaire was used to collect data from the participants of the study. Sample of this study was 700 information professionals necessarily user of social media.

Findings

Findings of this reveals that social media is the most preferred channel for information discovery and delivery among information professionals and study validates the assumption of uses and gratification theory with a view that information professionals are independent and active users of social media and global rank of social media is significantly different from the rank developed in this study.

Research limitations/implications

The present study is limited to information professionals only and considers social media (only top 20 sites) as an information and communication channel among information professionals.

Practical implications

This study has determined the preference of social media as an information and communication channel as compared with other information and communication channels and present a ranking based on usage among information professional, which is significantly different from the existing global user based ranking.

Social implications

Social media provides versatility of information in different forms and large numbers of information professionals are the users of social media around globe. This study shall help information professional to select appropriate channels for information discovery and delivery. Usage based ranking provided in this study shall stream line the social media practices at large.

Originality/value

This study has developed a usage based rank of top social media. This study elaborated the preference of social media as an information and communication channel.
Why customers make mobile payments? Applying a means-end chain approach
Authors: Sankaran Raja , Chakraborty Shibashish
Published: July 2020

Purpose

This study aims to explore the motivational factors (or value components) using a consumer-centric view to enable consumer make mobile payments (mPayments).

Design/methodology/approach

Means-end chain (MEC) theory, an exploratory approach was employed to understand personally relevant reasons for consumer use mPayments in India. In addition, the MEC phenomenon was investigated by examining the relationships among the three layers Attribute-Consequence-Value (A-C-V).

Findings

The study revealed the most important attribute to be handling money, followed by ease of use (consequence) and convenience as value. There was a wider recognition and penetration for acceptance of mPayments in smaller amounts or micro-payments with vendors, specifically in urban cities.

Originality/value

This research is the first of its kind wherein the concept of MEC has been utilized to evaluate why consumers make mPayments and demonstrate a novel approach to explore consumer insight into this domain.
The dynamics of congressional popularity on Instagram
Authors: O'Connell David
Published: July 2020

Purpose

The purpose of this paper to understand why some members of Congress have more Instagram followers, and why some Congressional Instagram posts receive more likes and comments.

Design/methodology/approach

This study is based on a content analysis of every Instagram post shared by all members of Congress who were seated for the first six months of the 115th Congress (17,811 posts in all). Information was collected at both the account level, as well as at the level of the individual post. Variables were then created to predict a member's followers and a post's likes and comments using a series of regression models.

Findings

This paper finds that factors capturing real world influence best explain why some members have more followers on Instagram. Senators, members who have served longer in office, past or future presidential candidates, Congressional leaders and ideological extremists all had significantly more followers. This paper also shows that personal content such as family photos, personal photos, selfies and pet photos produces significantly more user responses, while impersonal content like text based posts produces fewer.

Practical implications

This paper offers a general understanding of how anyone might maximize their user engagement on Instagram.

Originality/value

Little published research has studied how politicians use Instagram. This paper expands previous work examining influence on Twitter and Facebook. Further, these findings shed light on broader issues, including how social media reinforces existing power biases, and on the increasing trend towards personalization in American politics.
Exploring the role of volunteers in social care for older adults
Authors: Cameron Ailsa , Johnson Eleanor K. , Willis Paul B. , Lloyd Liz , Smith Randall
Published: July 2020

Purpose

This paper aims to report the findings of a study that explores the contribution volunteers make to social care for older adults, identifying lessons for the social care sector and policymakers.

Design/methodology/approach

An exploratory multiple case study design was used to capture the perspectives and experiences of managers of services, volunteer co-ordinators, volunteers, paid care staff and older people. Seven diverse social care organisations took part in the study drawn from three locations in the South West of England.

Findings

This study identified three distinct models of volunteer contribution to social care services for older people. Although the contributions made by volunteers to services are valued, the study drew attention to some of the challenges related to their involvement.

Research limitations/implications

The organisations taking part in this small-scale study were all based in the South West of England, and the findings are therefore not generalisable but contribute to the growing evidence base related to this important field.

Practical implications

This study demonstrates the importance of the volunteer co-ordinator role and suggests that it is properly funded and resourced. It also confirms the importance of volunteers receiving appropriate training and support.

Originality/value

Given the increasing involvement of volunteers in the provision of social care, this paper provides lessons to ensure the role of volunteers in social care enhances rather than diminishes the quality of care provided.
“Game playing” and “docility”: youth justice in question
Authors: Creaney Sean
Published: July 2020

Purpose

The purpose of this paper is to explore young people's experiences of youth justice supervision with particular reference to the efficacy of participatory practices. This paper is based on findings from a study concerning the extent and nature of children’s participation in decision-making in youth justice. The paper uses Bourdieu’s concept of habitus, as a heuristic/practical device, to investigate children’s ability to express agency and shape or influence the content and format of interventions and approaches in youth justice.

Design/methodology/approach

The researcher’s interest in understanding the perceptions and experiences of youth justice supervision led to the adoption of the qualitative approach and specifically in-depth interviews and participant observations. The researcher interviewed front-line professionals (n = 14), operational managers (n = 6) and children under youth justice supervision (n = 20). This study involved 15 months of fieldwork undertaken between 2016 and 2017 at a youth offending service in England.

Findings

Several young people were seeking to exert minimal energy to achieve a type of passive compliance with court order requirements, adopting a “ready-to-conform” mindset. Professionals were concerned that they were also participating in this type of “game playing”.

Practical implications

A relationship-based practice that is conducive to meaningful participation can help to facilitate positive changes to lifestyles and circumstances. This paper exposes its pivotal role in bolstering children’s involvement in supervision, reducing passive compliance and preventing inauthentic transactional arrangements from forming.

Originality/value

In spite of the significant interest in the work of Pierre Bourdieu, his “thinking tools” have seldom been used to investigate the experiences, attitudes and behaviours of youth justice professionals and those under youth offending team supervision at.
Public procurement and competitiveness of women-owned businesses: a structural equation model (SEM) for gender-responsive procurement in Uganda
Authors: Oluka Pross Nagitta , Okoche Michael , Mugurusi Godfrey
Published: July 2020

Purpose

Several intergovernmental organizations claim that the involvement of women in public procurement has a direct impact on sustainable development and growth, especially in the developing world, yet we know very little of such claim. This study aims to empirically examine how public procurement can contribute to women empowerment by boosting the competitiveness of women-owned businesses (WOBs) in Uganda.

Design/methodology/approach

In this study, a cross-sectional survey method is used. Quantitative data were gathered from a sample of 371 respondents in Ministries, Departments and Agencies (MDAs) and a section of women entrepreneurs in Uganda's capital Kampala. From the literature review, six hypotheses were formulated and tested using structural equation modelling (SEM). A research model is developed and presented.

Findings

All hypotheses, except for one, were supported. Procurement policy had a significant influence on evaluation criteria, contract management and most importantly, on the competitiveness of WOBs. Within the procurement process, evaluation criteria had a significant influence on the competitiveness of WOBs, while the influence of contract management on competitiveness of WOBs was not statistically significant. We, therefore, concluded that public procurement can indeed enhance women empowerment through a gender-responsive procurement policy. Above all, pre-contract award interventions such as streamlining evaluation criteria to ease access of WOBs to public procurement contracts seem have the most significant impact to competitiveness of WOBs compared to post-ward interventions during contract management.

Originality/value

This study offers a research-based model that articulates the role of procurement policy as an enabler for competitiveness of WOBs in developing countries. The model proposes a combination of both policy (a direct influence) and interventions in the supplier selection process (an indirect influence) to boost the competitiveness of WOBs.