bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional network analysis of the sub-regions of the primary motor cortex during rest
Authors: Alahmadi Adnan A.S.
Published: May 2020

The cytoarchitectonic properties of the primary motor cortex have shown two distinct sub-regions: Anterior Broadmann area 4 (BA4a) and Posterior Broadmann area 4 (BA4p). Some previous studies have suggested that these two sub-regions are functionally different and showed that in few fMRI experiments, these sub-regions may have different roles in brain functions. Resting-state fMRI (rsfMRI) is advanced technique that allows investigating in detail the functional connectivity and provides a greater understanding of the physiological behavior of different brain regions. In this study, 198 healthy subjects were examined using a region-based rsfMRI analysis to investigate whether BA4a and BA4p have similar or different connections to other brain networks. The finding shows that indeed these two sub-regions have distinct connectivity to different brain networks. BA4a has a greater connection to motor-related areas while BA4p has connections to nonmotor-related areas (such as sensory, attentional, and higher order regions), suggesting that these two sub-regions should be considered as two separate regions of interests.
Digital interventions in adult mental healthcare settings: recent evidence and future directions
Authors: Dülsen Patrick , Bendig Eileen , Küchler Ann-Marie , Christensen Helen , Baumeister Harald
Published: May 2020

Purpose of review

Internet and mobile-based interventions (IMI) can be used as online delivered forms of psychotherapeutic mental health treatments. These interventions can be an effective as well as time and cost-efficient treatment with the potential to scale up mental healthcare. In this review, we map implementation possibilities into routine mental healthcare settings and provide the most recent evidence.

Recent findings

Fourteen articles on digital mental healthcare approaches published in the last 18 months were included. Despite the limited number, the studies provide evidence for the effectiveness of IMI in treating inpatients and outpatients with various disorders in different mental healthcare settings. IMI were investigated as stand-alone interventions, in combination with other treatment forms (blended-care), or as aftercare.

Although there is encouraging evidence for the effectiveness of IMI in mental healthcare settings, several limitations have to be considered. The small number of studies conducted within the healthcare system, especially with inpatient samples, calls for more collaboration between researchers and clinical practitioners to unravel barriers and develop efficient protocols for the integration into routine care. Nonetheless, IMI are a promising tool for the endeavour of closing the treatment gap and should, therefore, be further explored in varying settings.
The rise and rise of mitochondrial DNA mutations
Authors: Lawless Conor , Greaves Laura , Reeve Amy K. , Turnbull Doug M. , Vincent Amy E.
Published: May 2020

How mitochondrial DNA mutations clonally expand in an individual cell is a question that has perplexed mitochondrial biologists for decades. A growing body of literature indicates that mitochondrial DNA mutations play a major role in ageing, metabolic diseases, neurodegenerative diseases, neuromuscular disorders and cancers. Importantly, this process of clonal expansion occurs for both inherited and somatic mitochondrial DNA mutations. To complicate matters further there are fundamental differences between mitochondrial DNA point mutations and deletions, and between mitotic and post-mitotic cells, that impact this pathogenic process. These differences, along with the challenges of investigating a longitudinal process occurring over decades in humans, have so far hindered progress towards understanding clonal expansion. Here we summarize our current understanding of the clonal expansion of mitochondrial DNA mutations in different tissues and highlight key unanswered questions. We then discuss the various existing biological models, along with their advantages and disadvantages. Finally, we explore what has been achieved with mathematical modelling so far and suggest future work to advance this important area of research.
Decoding and encoding models reveal the role of mental simulation in the brain representation of meaning
Authors: Soto David , Sheikh Usman Ayub , Mei Ning , Santana Roberto
Published: May 2020

How the brain representation of conceptual knowledge varies as a function of processing goals, strategies and task-factors remains a key unresolved question in cognitive neuroscience. In the present functional magnetic resonance imaging study, participants were presented with visual words during functional magnetic resonance imaging (fMRI). During shallow processing, participants had to read the items. During deep processing, they had to mentally simulate the features associated with the words. Multivariate classification, informational connectivity and encoding models were used to reveal how the depth of processing determines the brain representation of word meaning. Decoding accuracy in putative substrates of the semantic network was enhanced when the depth processing was high, and the brain representations were more generalizable in semantic space relative to shallow processing contexts. This pattern was observed even in association areas in inferior frontal and parietal cortex. Deep information processing during mental simulation also increased the informational connectivity within key substrates of the semantic network. To further examine the properties of the words encoded in brain activity, we compared computer vision models—associated with the image referents of the words—and word embedding. Computer vision models explained more variance of the brain responses across multiple areas of the semantic network. These results indicate that the brain representation of word meaning is highly malleable by the depth of processing imposed by the task, relies on access to visual representations and is highly distributed, including prefrontal areas previously implicated in semantic control.
Was the Devonian placoderm
Titanichthys
a suspension feeder?
Authors: Coatham Samuel J. , Vinther Jakob , Rayfield Emily J. , Klug Christian
Published: May 2020

Large nektonic suspension feeders have evolved multiple times. The apparent trend among apex predators for some evolving into feeding on small zooplankton is of interest for understanding the associated shifts in anatomy and behaviour, while the spatial and temporal distribution gives clues to an inherent relationship with ocean primary productivity and how past and future perturbations to these may impact on the different tiers of the food web. The evolution of large nektonic suspension feeders—‘gentle giants’—occurred four times among chondrichthyan fishes (e.g. whale sharks, basking sharks and manta rays), as well as in baleen whales (mysticetes), the Mesozoic pachycormid fishes and at least twice in radiodontan stem group arthropods (Anomalocaridids) during the Cambrian explosion. The Late Devonian placoderm
Titanichthys
has tentatively been considered to have been a megaplanktivore, primarily due to its gigantic size and narrow, edentulous jaws while no suspension-feeding apparatus have ever been reported. Here, the potential for microphagy and other feeding behaviours in
Titanichthys
is assessed via a comparative study of jaw mechanics in
Titanichthys
and other placoderms with presumably differing feeding habits (macrophagy and durophagy). Finite-element models of the lower jaws of
Titanichthys termieri
in comparison to
Dunkleosteus terrelli
and
Tafilalichthys lavocati
reveal considerably less resistance to von Mises stress in this taxon. Comparisons with a selection of large-bodied extant taxa of similar ecological diversity reveal similar disparities in jaw stress resistance. Our results, therefore, conform to the hypothesis that
Titanichthys
was a suspension feeder with jaws ill-suited for biting and crushing but well suited for gaping ram feeding.
Realigning science, society and policy in uncertain times
Authors: Mehta Goverdhan , Hopf Henning , Krief Alain , Matlin Stephen A.
Published: May 2020

Against a backdrop of rapidly changing social, economic and geopolitical settings and ideologies, the world is facing a wide range of challenges, including in biodiversity, climate, energy, the environment, food, health and water. These can only be addressed by fully harnessing key capacities that science offers. However, there is a crisis of trust in science which affects some sections of society and some policy-makers, impairing the capacity of science to deliver its essential roles. This damaged relationship between science, society and policy has immense health, economic and social consequences and implications for sustainability of the entire planet. Scientists must strive collectively to re-establish trust by society and politicians where it is damaged, and reinforce conviction of science's central importance in underpinning policy. Science's roles must in turn be acknowledged by policies that sustain innovation and freedom to work without political interference or constraints. A well-functioning and trusting relationship between science, society and policy-makers offers a potent means to thwart and mitigate emergent global challenges.
Exosomes promote caprine parainfluenza virus type 3 infection by inhibiting autophagy
Authors: Mao Li , Liang Panhong , Li Wenliang , Zhang Shaohua , Liu Maojun , Yang Leilei , Li Jizong , Li Huixia , Hao Fei , Sun Min , Zhang Wenwen , Wang Liqun , Cai Xuepeng , Luo Xuenong
Published: May 2020

Caprine parainfluenza virus type 3 (CPIV3) is a novel important pathogen causing respiratory disease in goats, but the pathogenic mechanism is not clear yet. Evidence suggests that exosomes transfer biologically active molecules between cells. Viral infections can cause profound changes in exosome components, and exosomes have been involved in viral transmission and pathogenicity. In this study, we explored the characteristics and functions of exosomes purified from the supernatant of Madin–Darby bovine kidney (MDBK) cells inoculated with CPIV3. Infection of CPIV3 showed increased exosome secretion and the loading of viral proteins and RNA into exosomes. These exosomes were capable of transferring CPIV3 genetic materials to recipient cells to establish a productive infection and promote the viral replication. To explore the potential mechanism, small RNA deep sequencing revealed that CPIV3 exosomes contained a diverse range of RNA species, including miRNA and piRNA, in proportions different from exosomes isolated from mock-infected cells. Expression patterns of 11 differentially expressed miRNAs were subsequently validated by quantitative reverse transcriptase PCR (qRT-PCR). Targets of miRNAs were predicted and functional annotation analysis showed that the main pathways involved were autophagy signalling ways. Autophagy inhibited by the CPIV3-exosome was further verified, and miR-126–3 p_2 packaged in the vesicles was an important regulation factor in this process. Inhibition of autophagy may be one of the responsible reasons for promoting efficient replication of exosome-mediated CPIV3 infection. The study suggests that exosomes are key in pathogenesis or protection against CPIV3. Further understating of their role in CPIV3 infection may bring novel insight to the development of protection measures.
COVID-19 Pandemic: Is Chronic Inflammation a Major Cause of Death?
Authors: Tskhay Albina , Yezhova Alena , Alibek Kenneth
Published: May 2020

Background

Today humanity is facing another infectious threat: a newly emerging virus SARS-CoV-2 causing COVID-19. It was already described that COVID-19 mortality among elderly people and people with such underlying conditions as obesity, cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes s increased. Dysregulation of the immune responses vital for antiviral defense, which are typical for chronic inflammation, led us to a hypothesis that chronic inflammation is the main risk factor for increased susceptibility and mortality from COVID-19.

Method

Based on the available information for 126 countries, statistical analysis to find out whether the difference in incidence and mortality within countries can be explained by the existing chronic inflammation among the countries’ population, was conducted.

Results

A positive correlation between the percentage of people dying from chronic noncommunicable diseases and COVID-19 incidence (p<0.001) and mortality (p<0.001) within countries.

Conclusion

The problem of COVID-19-caused high mortality rate may be a consequence of the high number of people having chronic low-grade inflammation as a precondition, and thus, one of the potential ways to reduce risk of morbidity and mortality is to focus on this widespread health problem, mainly occurring in developed countries and to take corresponding diagnostic, preventative, and treatment measures.
Comprehensive analyses of the cysteine thiol oxidation of PKM2 reveals the effects of multiple oxidation on cellular oxidative stress response
Authors: Irokawa Hayato , Numasaki Satoshi , Kato Shin , Iwai Kenta , Inose-Maruyama Atsushi , Ohdate Takumi , Hwang Gi-Wook , Toyama Takashi , Watanabe Toshihiko , Kuge Shusuke
Published: May 2020

Redox regulation of proteins via cysteine residue oxidation is known to be involved in the control of various cellular signal pathways. Pyruvate kinase M2 (PKM2), a rate-limiting enzyme in glycolysis, is critical for the metabolic shift from glycolysis to the pentose phosphate pathway under oxidative stress in cancer cell growth. The PKM2 tetramer acts as pyruvate kinase (PK), whereas the PKM2 dimer, which is induced by Cys358 oxidation, has reduced PK activity. Here, we identified four oxidation-sensitive cysteine residues (Cys152, Cys358, Cys423, and Cys424) responsible for three different oxidation forms. Possibly due to obstruction of the dimer-dimer interface, sulfenylation (-SOH) at Cys424 inhibited tetramer formation and PK activity. Cys423 is responsible for intermolecular disulfide bonds with heterologous proteins. In addition, intramolecular polysulfide linkage (–Sn–, n≧3) possible between Cys152 and Cys358 also is induced. We found that cells expressing the oxidation-resistant, constitutive-tetramer PKM2 (PKM2C358,424A) show a higher intracellular reactive oxygen species (ROS) and greater sensitivity to ROS-generating reagents and ROS-inducible anti-cancer drugs. These results highlight the possibility that PKM2 inhibition via Cys358 and Cys424 oxidation contributes to the elimination of excess ROS and oxidative stress.
Rapid estimation of excess mortality in times of COVID-19 in Portugal - Beyond reported deaths
Authors: Vieira Andre , Peixoto Vasco Ricoca , Aguiar Pedro , Abrantes Alexandre
Published: May 2020

Background: One month after the first COVID-19 infection was recorded, Portugal counted 18 051 cases and 599 deaths from COVID-19. To understand the overall impact on mortality of the pandemic of COVID-19, we estimated the excess mortality registered in Portugal during the first month of the epidemic, from March 16 until April 14 using two different methods.
Methods: We compared the observed and expected daily deaths (historical average number from daily death registrations in the past 10 years) and used 2 standard deviations confidence limit for all-cause mortality by age and specific mortality cause, considering the last 6 years. An adapted ARIMA model was also tested to validate the estimated number of all-cause deaths during the study period.
Results: Between March 16 and April 14, there was an excess of 1,255 all-cause deaths, 14% more than expected. The number of daily deaths often surpassed the 2 standard deviations confidence limit. The excess mortality occurred mostly in people aged 75+. Forty-nine percent (49%) of the estimated excess deaths were registered as due to COVID-19, The other 51% registered as other natural causes.
Conclusion: Even though Portugal took early containment measures against COVID-19, and the population complied massively with those measures, there was significant excess mortality during the first month of the pandemic, mostly among people aged 75+. Only half of the excess mortality was registered as directly due do COVID-19.
Estimation of COVID-19 transmission rates in California and the U.S. with reporting delays
Authors: Worden Lee , Wannier Rae , Neus Micaela , Kwan Jennifer C. , Ge Alex Y. , Richardson Eugene T. , Porco Travis C.
Published: May 2020

We estimated time-varying reproduction numbers of COVID-19 transmission in counties and regions of California and in states of the United States, using the Wallinga-Teunis method of estimations applied to publicly available data. The serial interval distribution assumed incorporates wide uncertainty in delays from symptom onset to case reporting. This assumption contributes smoothing and a small but meaningful increase in numerical estimates of reproduction numbers due to the likely existence of secondary cases not yet reported. Transmission in many areas of the U.S. may not yet be controlled, including areas in which case counts appear to be stable or slowly declining.
Risk factors for hospital admission related to COVID-19 in inflammatory rheumatic diseases
Authors: Freites Dalifer , Leon Leticia , Mucientes Arkaitz , Rodriguez-Rodriguez Luis , Font Judit , Madrid Alfredo , Colomer Jose Ignacio , Jover Juan Angel , Fernandez-Gutierrez Benjamin , Abasolo Lydia
Published: May 2020

OBJECTIVES: To describe patients with inflammatory rheumatic diseases (IRD) who had COVID-19; to compare patients who need hospital admission versus those that did not and assess risk factors of hospital admission related to COVID-19.
METHODS: We performed a prospective observational study, from 1st March 2020 until the 24th of April. All patients being attended at the rheumatology outpatient clinic of a tertiary hospital of Madrid, with medical diagnosis of inflammatory rheumatic disease, and with symptomatic COVID-19 disease were included. Main variable was the hospital admission related to COVID-19. Covariates: sociodemographic, clinical and treatments. We performed a multivariate logistic regression model to assess risk factors of hospital admission.
RESULTS: 123 patients with IRD and COVID-19 disease were identified and included. We found 54 patients that need hospital admission, 59.2% were women, with a mean age at hospital admission of 69.7 (15.7) years, and a median lag time from symptoms onset to hospital admission of 5 (3-10) days. The median length of stay was 9 (6-14) days. A total of 12 patients died (22%) during their hospital admission. Factors independently associated with hospital admission were being older (OR 1.08; p=0.00), and type of diagnosis (OR 3.55; p=0.01), compared to those who were ambulatory. DMARDs dropped from the model. Male sex, associated comorbidities and glucocorticoids use showed a tendency risk (p<0.2)
CONCLUSION: Our results suggests that age, comorbidities and having an autoimmune systemic condition increased the risk of hospital admission, whereas disease modifying agents were not associated with hospital admission.
Simulating SARS-CoV-2 epidemics by region-specific variables and modeling contact tracing app containment
Authors: Ferrari Alberto , Santus Enrico , Cirillo Davide , Ponce-de-Leon Miguel , Marino Nicola , Ferretti Maria Teresa , Chadha Antonella Santuccione , Mavridis Nikolaos , Valencia Alfonso
Published: May 2020

Targeted contact-tracing through mobile phone apps has been proposed as an instrument to help contain the spread of COVID-19 and manage the lifting of nation-wide lockdowns currently in place in USA and Europe. However, there is an ongoing debate on its potential efficacy, especially in the light of region-specific demographics.

We built an expanded SIR model of COVID-19 epidemics that accounts for region-specific population densities, and we used it to test the impact of a contact-tracing app in a number of scenarios. Using demographic and mobility data from Italy and Spain, we used the model to simulate scenarios that vary in baseline contact rates, population densities and fraction of app users in the population.

Our results show that, in support of efficient isolation of symptomatic cases, app-mediated contact-tracing can successfully mitigate the epidemic even with a relatively small fraction of users, and even suppress altogether with a larger fraction of users. However, when regional differences in population density are taken into consideration, the epidemic can be significantly harder to contain in higher density areas, highlighting potential limitations of this intervention in specific contexts.

This work corroborates previous results in favor of app-mediated contact-tracing as mitigation measure for COVID-19, and draws attention on the importance of region-specific demographic and mobility factors to achieve maximum efficacy in containment policies.
Black/African American Communities are at Highest Risk of COVID-19: Spatial Modeling of New York City ZIP Code-Level Testing Results
Authors: DiMaggio Charles , Klein Michael , Berry Cherisse , Frangos Spiros
Published: May 2020

Introduction

The population and spatial characteristics of COVID-19 infections are poorly understood, but there is increasing evidence that in addition to individual clinical factors, demographic, socioeconomic and racial characteristics play an important role.

Methods

We analyzed positive COVID-19 testing results counts within New York City ZIP Code Tabulation Areas (ZCTA) with Bayesian hierarchical Poisson spatial models using integrated nested Laplace approximations.

Results

Spatial clustering accounted for approximately 32% of the variation in the data. For every one unit increase in a scaled standardized measure of Chronic Obstructive Pulmonary Disease (COPD) in a community, there was an approximate 8-fold increase in the risk of a positive COVID-19 test in a ZCTA (Incidence Density Ratio = 8.2, 95% Credible Interval 3.7, 18.3). There was a nearly five-fold increase in the risk of a positive COVID-19 test. (IDR = 4.8, 95% Cr I 2.4, 9.7) associated with the proportion of Black / African American residents. Increases in the proportion of residents older than 65, housing density and the proportion of residents with heart disease were each associated with an approximate doubling of risk. In a multivariable model including estimates for age, COPD, heart disease, housing density and Black/African American race, the only variables that remained associated with positive COVID-19 testing with a probability greater than chance were the proportion of Black/African American residents and proportion of older persons.

Conclusions

Areas with large proportions of Black/African American residents are at markedly higher risk that is not fully explained by characteristics of the environment and pre-existing conditions in the population.
Hydroxychloroquine in COVID-19: An updated systematic review with meta-analysis
Authors: Chacko Jose , Brar Gagan , Premkumar Robert
Published: May 2020

Background

Hydroxychloroquine is being administered among patients with COVID-19 infection in many healthcare systems across the world, considering its in vitro effect against the SARS-CoV-2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID-19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID-19 infection.

Methods

We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until August 1, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was administered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity.

Results

We included 23 studies, including seven randomized controlled trials and 16 observational studies. Among these, 11,029 patients received hydroxychloroquine alone or in combination, while 12063 did not. Mortality was reported at different points in time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 0.94, 95% CI: 0.72–1.22; p = 0.63). Clinical worsening did not differ between patients who received hydroxychloroquine compared to those who did not (OR 0.93, 95% CI: 0.57–1.52; p = 0.77). Negative conversion, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 0.67, CI: 0.21–2.11; p = 0.49). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1–6.55; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 5.95, CI: 2.56–13.83; p < 0.00001).

Conclusions

Our meta-analysis does not suggest improvement in mortality, clinical progression, or negative conversion by RT-PCR among patients with COVID-19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.
Obesity and COVID-19: The role of visceral adipose tissue
Authors: Petersen Antonia , Bressem Keno , Albrecht Jakob , Thiess Hans-Martin , Vahldiek Janis , Hamm Bernd , Makowski Marcus , Niehues Alexandra , Niehues Stefan , Adams Lisa Christine
Published: May 2020

INTRODUCTION: During the unprecedented health crisis of the COVID-19 pandemic it was
suggested that obesity might aggravate severe acute respiratory syndrome coronavirus-2 (SARS
CoV-2). Therefore, this study aims to investigate the association between Compute Tomography
(CT)-based measurements of visceral and subcutaneous fat as measures of obesity and COVID-19
severity.
METHODS: 30 patients with laboratory-confirmed COVID-19 and a mean age of 65.59 plus/minus 13.06
years from a level one medical center in Berlin, Germany, were retrospectively analyzed and
included in the present analysis. SARS-CoV-2 was confirmed by polymerase chain reaction from
throat swaps or deep nasal swabs on the day of admission. Severe clinical courses of COVID-19
were defined by hospitalization in intensive care unit (ICU) and invasive mechanical ventilation.
All patients received low-dose chest CT-based fat measurements at the level of the first lumbar
vertebra.
RESULTS: An increase in visceral fat area (VFA) by one square decimeter was associated with a
22.53-fold increased risk for ICU treatment and a 16.11-fold increased risk for mechanical
ventilation (adjusted for age and sex). For upper abdominal circumference, each additional
centimeter of circumference showed a 1.13-fold increased risk for ICU treatment and a 1.25-fold
increased risk for mechanical ventilation. There was no significant correlation of subcutaneous fat
area (SFA) or body mass index (BMI) with severe clinical courses of COVID-19.
CONCLUSIONS: Our results suggest that visceral adipose tissue and upper abdominal
circumference specifically increasing the risk of COVID-19 severity. CT-based quantification of
visceral adipose tissue and upper abdominal circumference in routinely acquired chest CTs may
therefore be a simple tool for risk assessment in SARS-CoV-2-patients.
Thiazoline-related TRPA1 agonist odorants orchestrate survival fate in mice
Authors: Matsuo Tomohiko , Isosaka Tomoko , Tang Lijun , Soga Tomoyoshi , Kobayakawa Reiko , Kobayakawa Ko
Published: May 2020

Therapeutic hypothermia protects the brain after cardiopulmonary arrest. Innate fear has evolved to orchestrate protective effects in life-threatening situations. Thus, strong fear perception may induce a specialized life-protective metabolism based on hypothermia/hypometabolism; however, such phenomena and their inducers are yet to be elucidated. Here, we report that thiazoline-related fear odors (tFOs), which are TRPA1 agonists and induce robust innate fear in mice, induced hibernation-like systemic hypothermia/hypometabolism, accelerated glucose uptake in the brain, and suppressed aerobic metabolism via phosphorylation of pyruvate dehydrogenase, thereby enabling long-term survival in a lethal hypoxic environment. In contrast to hibernation, during which immune functions are generally suppressed, tFO-stimulation induced a crisis-response immune state characterized by potentiated innate immune functions but suppressed inflammation with anti-hypoxic ability. Collectively, these responses exerted potent therapeutic effects in cutaneous and cerebral ischemia/reperfusion injury models. Whole brain mapping and chemogenetic activation revealed that sensory representation of tFOs orchestrate survival fate via brain stem Sp5/NST to midbrain PBN pathway. TFO-induced strong crisis perception maximizes latent life-protective effects by shifting metabolism to a crisis response mode characterized by hypothermia, hypometabolism and crisis immunity.
Mrr1 regulation of methylglyoxal catabolism and methylglyoxal-induced fluconazole resistance inCandida lusitaniae
Authors: Biermann Amy R. , Demers Elora G. , Hogan Deborah A.
Published: May 2020

InCandidaspecies, the transcription factor Mrr1 regulates azole resistance genes in addition to the expression of a suite of other genes including known and putative methylglyoxal reductases. Methylglyoxal (MG) is a toxic metabolic byproduct that is significantly elevated in certain disease states that frequently accompany candidiasis, including diabetes, kidney failure, sepsis, and inflammation. Through the genetic analysis ofCandida lusitaniae(syn.Clavispora lusitaniae) strains with different Mrr1 variants with high and low basal activity, we showed that Mrr1 regulates basal and/or induced expression of two highly similar MG reductases,MGD1andMGD2, and that both participate in MG detoxification and growth on MG as a sole carbon source. We found that exogenous MG increases Mrr1-dependent expression ofMGD1andMGD2inC. lusitaniaesuggesting that Mrr1 is part of the natural response to MG. MG also induced expression ofMDR1, which encodes a major facilitator protein involved in fluconazole resistance, in a partially Mrr1-dependent manner. MG significantly improved growth ofC. lusitaniaein the presence of fluconazole and strains with hyperactive Mrr1 variants showed greater increases in growth in the presence of fluconazole by MG. In addition to the effects of exogenous MG, we found knocking outGLO1, which encodes another MG detoxification enzyme, led to increased fluconazole resistance inC. lusitaniae. Analysis of isolates otherCandidaspecies found heterogeneity in MG resistance and MG stimulation of growth in the presence of fluconazole. Given the frequent presence of MG in human disease, we propose that induction ofMDR1in response to MG is a novel contributor toin vivoresistance of azole antifungals in multipleCandidaspecies.

Author Summary

InCandidaspecies, constitutively active variants of the transcription factor Mrr1 confer resistance to fluconazole, a commonly used antifungal agent. However, the natural role of Mrr1 as well as how its activity is modulatedin vivoremain poorly understood. Here, we have shown that, in the opportunistic pathogenCandida lusitaniae, Mrr1 regulates expression and induction of two enzymes that detoxify methylglyoxal, a toxic metabolic byproduct. Importantly, serum methylglyoxal is elevated in conditions that are also associated with increased risk of colonization and infection byCandidaspecies, such as diabetes and kidney failure. We discovered that methylglyoxal causes increased expression of these two Mrr1-regulated detoxification enzymes as well as an efflux pump that causes fluconazole resistance. Likewise, methylglyoxal increased the ability of multipleC. lusitaniaestrains to grow in the presence of fluconazole. Several otherCandidastrains that we tested also exhibited stimulation of growth on fluconazole by methylglyoxal. Given the physiological relevance of methylglyoxal in human disease, we posit that the induction of fluconazole resistance in response to methylglyoxal may contribute to treatment failure.
Large domain movements through lipid bilayer mediate substrate release and inhibition of glutamate transporters
Authors: Wang Xiaoyu , Boudker Olga
Published: May 2020

Glutamate transporters are essential players in glutamatergic neurotransmission in the brain, where they maintain extracellular glutamate below cytotoxic levels and allow for rounds of transmission. The structural bases of their function are well established, particularly within a model archaeal homologue, sodium and aspartate symporter GltPh. However, the mechanism of gating on the cytoplasmic side of the membrane remains ambiguous. We report Cryo-EM structures of GltPhreconstituted into nanodiscs, including those structurally constrained in the cytoplasm-facing state and either apo, bound to sodium ions only, substrate, or blockers. The structures show that both substrate translocation and release involve movements of the bulky transport domain through the lipid bilayer. They further reveal a novel mode of inhibitor binding and show how solutes release is coupled to protein conformational changes. Finally, we describe how domain movements are associated with the displacement of bound lipids and significant membrane deformations, highlighting the potential regulatory role of the bilayer.
Development of an X-ray imaging detector for high-energy X-ray microtomography
Authors: Hoshino Masato , Uesugi Kentaro , Yagi Naoto
Published: May 2020

A dedicated X-ray imaging detector for 200 keV high-energy X-ray microtomography was developed. The novelty of the detector is a large-format camera lens employed for a wide field of view. Several scintillators were evaluated in terms of the degree of efficiency of detection for high-energy X-ray photons and the modulation transfer function. For tomographic measurement, a high-definition CMOS camera was incorporated in the detector to achieve a high spatial resolution while keeping the field of view wide. Rocks with fossil inclusions were imaged to demonstrate the applicability of the detector to high-energy X-ray microtomography.
Generic skills in accounting education in Saudi Arabia: students’ perceptions
Authors: Al Mallak Mohammed Ali , Tan Lin Mei , Laswad Fawzi
Published: May 2020

Purpose

The purpose of this exploratory study is to examine the perceptions of Saudi university accounting students of the importance of developing generic skills in their accounting education, the levels of competence they should acquire and expect to achieve during the academic study, and the constraints that may hinder the development of generic skills in accounting education.

Design/methodology/approach

The study uses the skills outlined in the IFAC’s International Education Standards (IES) 3 (intellectual, personal, organizational and business management, and interpersonal and communication) and IES 4 (ethics in accounting/business). A survey questionnaire was used to collect the data.

Findings

The findings show that students perceived all five generic skill categories to be important, with ethical skills rated as the most important. However, the students expected that they would achieve a somewhat lower level of generic skill by the end of their studies in all areas, and they perceived a number of constraints that impede their skill development. The results indicate the importance of developing generic skills in accounting education and suggest that the Saudi accounting education system could do more to provide students with opportunities to develop generic skills to enable them to succeed in their future careers.

Originality/value

As little of the current literature has focused on generic skills in accounting education in a non-Western country, this research contributes to the literature on generic skills in a developing nation.
Tourist experience on traditional pastries in UNESCO heritage city
Authors: Tan Cheng Ling , Yeo Sook Fern
Published: May 2020

Purpose

In recent years, the traditional pastries industry has gained popularity among tourists due to the advantage of the pastries location at UNESCO Heritage city, Penang. However, the little research focussed on this particular industry, and there is lack of evidence of the tourists' experience with the traditional pastries and how these attributes affect their revisit decision.

Design/methodology/approach

The study utilizes a qualitative research design to gain in-depth understanding on tourists' thought and their repurchase decision. Secondary data were collected via TripAdvisor with 68 tourists who visited the most popular three pastries shops namely, Him Heang, Ghee Hiang and Min Xiang Tai, which are later analysed using qualitative content analysis.

Findings

The findings revealed that tourists generally concerned about the service quality, value, brand image and atmospherics that could affect their repurchasing decision. Particularly, the staff service quality has been viewed as the upmost important attribute to influence the tourists' decision. Therefore, the pastries shops shall ensure that the staff who serve the tourists shall be well trained to satisfy the tourists' enquiry.

Research limitations/implications

The limitation concerning the interpretation of the secondary data based on the feedbacks and comments of the tourists may derive the bias possibility. Future research might consider the large-scale primary data to extend the findings.

Originality/value

Limited research exists on the tourists' experience which affects the repurchasing decision in pastries industry. This study provides valuable information for pastries shops and researchers interested in this area.
FinTech and household finance: a review of the empirical literature
Authors: Agarwal Sumit , Chua Yeow Hwee
Published: May 2020

Purpose

This paper reviews recent advances in the empirical literature of FinTech and household finance.

Design/methodology/approach

We survey the effects of FinTech on three different aspects of household finance: payments, lending and portfolio decisions. Specifically, we examine the impact of digital payments, mobile money, FinTech lending, marketplace lending, robo-advising and crowd-funding.

Findings

Studies suggest that FinTech has positively benefited households by increasing consumption and borrowing. This allows them to smoothen their consumption across time. Furthermore, there is an improvement in their portfolio diversification. Nonetheless, there is also evidence that certain households overconsume and borrow beyond their means.

Originality/value

Despite the importance of this topic, there has been a lack of empirical evidence until recently. In this paper, we take stock of the empirical evidence in the literature through the lens of household finance
Implicit and explicit norms and tools of safety net management
Authors: Kane Edward
Published: May 2020

Purpose

This paper explains the value of interpreting the design of a country's financial safety net as an exercise in incomplete social contracting.

Design/methodology/approach

Safety net contracts unlucky financial institutions and customers to transfer some or all of what would otherwise be ruinous losses to taxpayers in other sectors. Their capacity to do this is based on a series of unspoken and slowly varying cultural norms that govern when government support is supplied to an insolvent bank, in what forms, on what terms and under what limitations. Identifying these norms is the purpose of this paper. Identifying similarities in the norms that hold sway in the United States and China is the main contribution this paper has to offer.

Findings

Regulators do not want to face the consequences of challenging large insolvent banks' claims that funding problems that their managers know to be hopeless reflect a spate of reversible bad luck and a temporary shortfall in liquidity. In hopes of shifting the problem forward to their successors, regulators forbear from meaningful intervention until and unless crisis-driven depositor runs force them into action.

Research limitations/implications

This means that much like US rescue arrangements, one can demonstrate that the Chinese safety net is incomplete in four ways. It does not fully delineate the events that trigger a loss transfer. It sets formal but imperfectly enforceable limits on the size of potential loss transfers. The political obligations that actually persuade state actors to bail out major banks in a crisis are largely implicit and optional in timing, magnitude and transparency. Finally, the identity of the citizens who will be forced to absorb the costs of crisis bailouts is also optional. Who pays and how they do so will be determined in part during the crisis but will not be finalized until well after the crisis has blown over.

Originality/value

The analysis makes it clear that authorities, express commitment to fair and efficient modes of financial supervision is destined to break down under crisis pressure unless the disadvantaged equity stake that the safety net assigns to taxpayers is rebalanced to record and collect taxpayers' deserved share of the profits a country's megabanks book during booms.
Dichotomous impacts on social and environmental sustainability: competitiveness and development levels matter
Authors: Doyle Eleanor , Perez Alaniz Mauricio
Published: May 2020

Purpose

Whereas in developed countries, sustainability primarily focuses on environmental topics, in developing countries the issues of poverty, development and equity are equally, if not more, important. The purpose of this paper is to apply measures of social and environmental sustainability to assess sustainable development for the period 2005–2015 across a sample of 94 countries for which relevant data are available. Countries include two groups: developed and developing countries.

Design/methodology/approach

Using the index-based approach introduced by the World Economic Forum in its Global Competitiveness Project, a range of indicators are collected for estimating trends in both social and environmental sustainability. For the panel of data identified, a dynamic panel data estimator method is applied to the data set constructed. This paper presents the empirical results identifying key competitiveness factors related to social and environmental sustainability (separately and combining both aspects in a comprehensive sustainability framework).

Findings

This study explores how sustainable competitiveness offers a comprehensive assessment of the inter-related dynamics of the social, the environmental and economic building blocks of sustainable development simultaneously. Performance impacts are found to differ substantially across two groups of countries depending on their development level. This highlights the challenges in shaping and achieving sustainable development goals.

Originality/value

To the best of the authors’ knowledge, this research is novel in examining the intersections between economic competitiveness and environmental and social sustainability addressing an identified research gap. In addition, the paper investigates the most important competitiveness pillars focusing on both strengths and weaknesses in sustainable competitiveness across developed and developing countries.
Exploring SMEs’ qualitative growth and networking through formalization
Authors: Milanesi Matilde , Guercini Simone , Tunisini Annalisa
Published: May 2020

Purpose

This paper aims to analyze the role of networking through formalization, namely, the adoption of specific contractual forms, in triggering small- and medium-sized enterprises (SMEs’) qualitative growth. The paper adopts an approach to SMEs’ growth that stresses the multi-dimensionality nature of the concept, which includes not only size but also relationship and capability growth.

Design/methodology/approach

A qualitative methodology is used, based on the study of cases of SMEs from an Italian fashion district, connected by a specific contractual form – the so-called “network contract” (NC) – promoted by the national government. Two cases of NCs are presented, a vertical and a horizontal network.

Findings

The paper highlighted the positive influence of NCs, intended as a managerial strategy not only aimed at collaboration, on the growth paths of SMEs but also stressed that the influence of NCs cannot be isolated, but acts virtuously together with other variables. Such variables include entrepreneurs’ and managers’ individual traits, the context – industrial district in the two cases under study – in which SMEs operate, the presence of an external actor that stimulates the adoption of NCs.

Originality/value

The focus on qualitative growth, which can be triggered by the formalization of business relationships through contractual forms, contributes to the debate on the nature and content of SMEs’ growth. The awareness of the variables that contribute to SMEs’ growth is crucial for both entrepreneurs and institutional actors who want to create the conditions to undertake paths of qualitative growth.
A different approach to the network method: continuity equation in flow through porous media under retaining structures
Authors: Martínez-Moreno Encarnación , Garcia-Ros Gonzalo , Alhama Ivan
Published: May 2020

Purpose

This study aims to present a new numerical model for the simulation of water flow through porous media of anisotropic character, based on the network simulation method and with the use of the free code Ngspice.

Design/methodology/approach

For its design, it starts directly from the flow conservation equation, which presents several advantages in relation to the numerical simulation of the governing equation in terms of the potential head. The model provides very precise solutions of streamlines and potential patterns in all cases, with relatively small meshes and acceptable calculation times, both essential characteristics when developing a computational tool for engineering purposes. The model has been successfully verified with analytical results for non-penetrating dams in isotropic media.

Findings

Applications of the model are presented for the construction of the flow nets, calculation of uplift pressures, infiltrated flow and average exit gradient in anisotropic scenarios with penetrating dams with and without sheet piles, being all this output information part of the decision process in ground engineering problems involving these retaining structures.

Originality/value

This study presents, for the first time, a numerical network model for seepage problems that is not obtained from the Laplace's governing equation, but from the water flow conservation continuity equation.
Quality initiatives in public health and other health-related fields
Authors: MacVane Phipps Fiona
Published: May 2020

Purpose

The purpose of the International Journal of Health Governance (IJHG) review is to present a synopsis of the accepted articles in each issue, thus allowing readers to identify articles of particular interest to themselves.

Design/methodology/approach

The review editor reads all the submissions for each issue and then prepares an overview presenting the major themes with reference to supporting literature

Findings

The findings from all articles are presented in a succinct format.

Originality/value

The value of the IJHG review lies in the fact that no other Emerald publication includes a review section of this type. This unique contribution to this particular journal enhances usability and reader satisfaction.