bluuebunny/crossref_metadata_2025 huggingface dataset:
Collagenous colitis in a child induced by chronic respiratory allergy
Authors: Wan Xue-Meng , Wang Zhi-Ling , Wang Li-Yuan , Cai Xiao-Tang , Wan Chao-Min , Xie Yong-Mei
Published: August 2020

Introduction:

Collagen colitis (CC) is a microscopic colitis diagnosed by mucosal biopsy and is extremely rare in children.

Patient concerns:

We reported a child with severe persistent diarrhea that could not be relieved with traditional diarrheal treatment. No abnormalities were found after multiple colonoscopies.

Diagnoses:

A significant increase in total IgE levels was found in the patient's blood. He had a history of mild chronic allergic rhinitis and slightly intermittent wheezing. However, we found that the child had a hyperallergic reaction to multiple respiratory antigens and had mild pulmonary dysfunction. Finally, colonoscopy with biopsy identified the diagnosis of CC.

Intervention:

Considering that a respiratory allergic reaction was one of the causes of diarrhea, anti-allergic treatment was given to the child, and his severe diarrhea was soon relieved. Corticosteroid treatment was suggested to the patient, but his parents firmly refused steroid therapy. According to the patient's specific allergic reaction to mites, desensitization treatment was finally chosen for him.

Outcomes:

After 1 year of desensitization for dust mites, the patient's respiratory symptoms improved, total IgE levels decreased, autoantibodies declined, and diarrhea did not reoccur. Colonoscopy with biopsy showed a significant improvement in pathology.

Conclusion:

CC in children is rare, and childhood CC induced by a respiratory allergic reaction has not been previously reported. Therefore, this is a special case of CC in a patient who was cured with anti-allergy treatments and desensitization instead of steroid therapy.
Relationship of pulmonary function with myocardial microdamage and oxidative stress in the Japanese population without a history of cardiopulmonary disease
Authors: Sugiura Tomonori , Dohi Yasuaki , Takase Hiroyuki , Fujii Satoshi , Seo Yoshihiro , Ohte Nobuyuki
Published: August 2020

An association between pulmonary and cardiovascular impairment has been reported, but studies are lacking that focus on individuals without advanced impairment in the pulmonary or cardiovascular system. We aimed to investigate the relationship between myocardial microdamage and reduced pulmonary function in the Japanese population without a history of cardiopulmonary disease and to assess whether oxidative stress links the 2 features.

We enrolled patients undergoing an annual health check-up and measured serum high-sensitivity cardiac troponin I (hs-cTnI) and derivatives of reactive oxygen metabolites (d-ROM) to evaluate myocardial microdamage and oxidative stress. To assess pulmonary function, we calculated forced vital capacity as a percentage of predicted value, forced expiratory volume in 1 second as a percentage of predicted value, and the ratio of forced expiratory volume in 1 second to forced vital capacity. Possible associations between each parameter of pulmonary function, hs-cTnI, and d-ROM were cross-sectionally investigated.

The study included 1265 participants (57 ± 12 years). In multivariate regression analysis, the forced vital capacity as a percentage of predicted value was inversely associated with hs-cTnI levels after adjustment for possible confounders. In another multivariate model, all indices of pulmonary function were inversely correlated with d-ROM levels. We observed similar relationships in a multivariate regression model that included hs-cTnI and d-ROM simultaneously as independent variables. Levels of d-ROM and hs-cTnI also were significantly associated.

These results highlight an inverse association of pulmonary function with hs-cTnI and d-ROM in the Japanese population without a history of cardiopulmonary disease. The findings suggest that in individuals without obvious cardiovascular and pulmonary diseases, reduced pulmonary function could reflect myocardial microdamage, at least in part through increased oxidative stress.
A fluid mechanic’s analysis of the teacup singularity
Authors: Barkley Dwight
Published: August 2020

The mechanism for singularity formation in an inviscid wall-bounded fluid flow is investigated. The incompressible Euler equations are numerically simulated in a cylindrical container. The flow is axisymmetric with the swirl. The simulations reproduce and corroborate aspects of prior studies reporting strong evidence for a finite-time singularity. The analysis here focuses on the interplay between inertia and pressure, rather than on vorticity. The linearity of the pressure Poisson equation is exploited to decompose the pressure field into independent contributions arising from the meridional flow and from the swirl, and enforcing incompressibility and enforcing flow confinement. The key pressure field driving the blowup of velocity gradients is that confining the fluid within the cylinder walls. A model is presented based on a primitive-variables formulation of the Euler equations on the cylinder wall, with closure coming from how pressure is determined from velocity. The model captures key features in the mechanics of the blowup scenario.
Cost-effectiveness of combining drug and environmental treatments for environmentally transmitted diseases
Authors: Castonguay François M. , Sokolow Susanne H. , De Leo Giulio A. , Sanchirico James N.
Published: August 2020

Control of neglected tropical diseases (NTDs) via mass drug administration (MDA) has increased considerably over the past decade, but strategies focused exclusively on human treatment show limited efficacy. This paper investigated trade-offs between drug and environmental treatments in the fight against NTDs by using schistosomiasis as a case study. We use optimal control techniques where the planner’s objective is to treat the disease over a time horizon at the lowest possible total cost, where the total costs include treatment, transportation and damages (reduction in human health). We show that combining environmental treatments and drug treatments reduces the dependency on MDAs and that this reduction increases when the planners take a longer-run perspective on the fight to reduce NTDs. Our results suggest that NTDs with environmental reservoirs require moving away from a reliance solely on MDA to integrated treatment involving investment in both drug and environmental controls.
Sheep in wolves’ clothing: prey rely on proactive defences when predator and non-predator cues are similar
Authors: Symes Laurel B. , Martinson Sharon J. , Kernan Ciara E. , ter Hofstede Hannah M.
Published: August 2020

Predation produces intense selection and a diversity of defences. Reactive defences are triggered by predator cues, whereas proactive defences are always in effect. We assess whether prey rely on proactive defences when predator cues do not correlate well with predation risk. Many bats use echolocation to hunt insects, and many insects have evolved to hear bats. However, in species-rich environments like Neotropical forests, bats have extremely diverse foraging strategies, and the presence of echolocation corresponds only weakly to the presence of predators. We assess whether katydids that live in habitats with many non-dangerous bat species stop calling when exposed to echolocation. For 11 species of katydids, we quantified behavioural and neural responses to predator cues, and katydid signalling activity over 24 h periods. Despite having the sensory capacity to detect predators, many Neotropical forest katydids continued calling in the presence of predator cues, displaying proactive defences instead (short, infrequent calls totalling less than 2 cumulative seconds of sound per 24 h). Neotropical katydid signalling illustrates a fascinating case where trophic interactions are probably mediated by a third group: bats with alternative foraging strategies (e.g. frugivory). Although these co-occurring bats are not trophically connected, their mere presence disrupts the correlation between cue and predation risk.
Help or flight? Increased threat imminence promotes defensive helping in humans
Authors: Vieira Joana B. , Schellhaas Sabine , Enström Erik , Olsson Andreas
Published: August 2020

In humans and other mammals, defensive responses to danger vary with threat imminence, but it is unknown how those responses affect decisions to help conspecifics. Here, we manipulated threat imminence to investigate the impact of different defensive states on human helping behaviour. Ninety-eight healthy adult participants made trial-by-trial decisions about whether to help a co-participant avoid an aversive shock, at the risk of receiving a shock themselves. Helping decisions were prompted under imminent or distal threat, based on temporal distance to the moment of shock administration to the co-participant. Results showed that, regardless of how likely participants were to also receive a shock, they helped the co-participant more under imminent than distal threat. Reaction times and cardiac changes during the task supported the efficacy of the threat imminence manipulation in eliciting dissociable defensive states, with faster responses and increased heart rate during imminent compared to distal threats. Individual differences in empathic concern were specifically correlated with helping during imminent threats. These results suggest that defensive states driving active escape from immediate danger may also facilitate decisions to help others, potentially by engaging neurocognitive systems implicated in caregiving across mammals.
Does Accreditation Symbolize Quality in Public Healthcare Delivery? An Investigation of Hospitals in Kerala
Authors: Joseph Sindhu
Published: August 2020

Accreditation has become an important benchmark for healthcare organisations, and accordingly, many government hospitals in Kerala got accredited with national level (NABH) and state level (KASH) accreditation programmes. This study examined the quality of public healthcare delivery in these accredited hospitals while having a comparison with the non-accredited hospitals. It also compared the impact of national and state-level accreditation programmes in Kerala public healthcare settings. This cross-sectional study conducted between July 2017 and July 2018, employing a positivist approach using stratified random sampling. In total, 621 samples were collected from in-patients of both accredited (NABH and KASH) (312) and nonaccredited (309) public healthcare institutions in Kerala. Nine constructs overarching the quality of healthcare delivery and patient satisfaction construct are used in the study. The study found that patient satisfaction is identical in both accredited and nonaccredited hospitals (M=4.28). Patient satisfaction in NABH accredited hospital (M=4.27±0.67874) is lower than that of KASH accredited hospital (M=4.30±1.25417). The mean score of six constructs of quality healthcare delivery of KASH accredited hospitals is higher than NABH accredited. Thus, the study concluded that accreditation, regardless of its type, has no impact on patient satisfaction even though the accreditation process slightly improved different dimensions of quality healthcare delivery.
COVID-19 and heart medications: What’s the connection?
Authors: Saleknezhad Nafiseh , Khosravi Bardia , Anushiravani Amir , Eslahi Masoud , Radmard Amir Reza , Sirusbakht Azin , Pourabbas Seyed Mohammad , Abdollahi Mohammad , Kasaeian Amir , Sorouri Majid , Sima Ali Reza
Published: August 2020

Aim

To determine association between clinical outcome of COVID-19 and prior usage of cardiovascular and metabolic drugs, including, Aspirin, ACEIs, ARBs, Clopidogrel, metformin, and Statins.

Methods

Statistical examination of the demographic, clinical, laboratory and imaging features of 353 patients with SARS-CoV-2 disease admitted from February to April 2020.

Result

Minor discrepancies were observed in the clinical presentations, radiologic involvement and laboratory results across groups of patients under treatment with specific drugs. Aspirin-users had better clinical outcome with lower need of ventilation support, whereas, metformin- users had increased chance of intubation and of mortality.

Conclusion

Although not being conclusive, our findings suggest the possibility of the effect of previous drug usages on the various presentations and clinical course of COVID-19 infection.
Ethnic differences in SERPINA1 allele frequencies may partially explain national differences in COVID-19 fatality rates
Authors: Shapira Guy , Shomron Noam , Gurwitz David
Published: August 2020

COVID-19 infection and fatality rates vary considerably between countries. We present preliminary evidence that these variations may in part reflect ethnic differences in the frequencies of polymorphic alleles of SERPINA1, coding for alpha-1 antitrypsin, the major blood serine protease inhibitor.
Monitoring COVID-19 related public Interest and population Health Literacy in South Asia: An Internet Search-Interest Based Model
Authors: Symum Hasan , Sagor Kh Mohammed Ali
Published: August 2020

Background

Information epidemiology based on internet search data can be used to model COVID-19 pandemic progressions and monitor population health literacy. However, the applicability of internet searches to monitor COVID-19 infections and public health awareness in South Asian countries are unclear.

Objectives

To assess the association of public interest and health literacy in COVID-19 with the actual number of infected cases for countries in South Asia.

Methods

Google Trends data from January to March 2020 were used to correlate public interest and health literacy with official data on COVID-19 cases using the relative search volume (RSV) index. Public interest in COVID-19 was retrieved in RSV indices with the search term “Coronavirus (Virus)”. Similarly, an OR combination of search terms “hand wash”, “face mask”, “hand sanitizer”, “face shield” and “gloves” were used to retrieve RSV indices as a surrogate of population health literacy in COVID-19. Daily confirmed COVID-19 cases were obtained from the COVID-19 data repository managed by the Johns Hopkins University. Country-level time-lag correlation analyses were performed for a time lag between 30 and +30 days.

Results

COVID-19-related worldwide public interest reached a peak on March 16, 2020, right after the WHO announcement of coronavirus outbreak as a pandemic. COVID-19 related public interest reached the highest peak in South Asian countries a few days after each county reported 100th confirmed cases. There were significant positive correlations between COVID-19 related public interest and daily laboratory confirmed cases in countries expect Nepal, Bhutan, and Sri Lanka. The highest public interest in South Asian Countries was on average 12 days before the local maximum of new confirmed cases. Similarly, web searches related to personal hygiene and COVID-19 preventive measures in south Asia correlated to the number of confirmed cases as well as national restriction measures.

Conclusion

Public interest indicated by RSV indices can help to monitor the progression of an outbreak such as the current COVID-19 pandemic particularly in countries with a lack of diagnostic and surveillance capacity, and thereby distribute appropriate health information to the general public.
Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies
Authors: Han Namshik , Hwang Woochang , Tzelepis Konstantinos , Schmerer Patrick , Yankova Eliza , MacMahon Méabh , Lei Winnie , Katritsis Nicholas M , Liu Anika , Schuldt Alison , Harris Rebecca , Chapman Kathryn , McCaughan Frank , Weber Friedemann , Kouzarides Tony
Published: August 2020

The global outbreak of SARS-CoV-2 necessitates the rapid development of new therapies against COVID-19 infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2-induced protein (SIP) network, based on disease signatures defined by COVID-19 multi-omic datasets(Bojkova et al., 2020; Gordon et al., 2020), and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2-induced pathways, 40 of which are already in COVID-19 clinical trials(Clinicaltrials.gov, 2020) testifying to the validity of the approach. Using artificial neural network analysis we classified these 200 drugs into 9 distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (130) and immune response (70). A subset of drugs implicated in viral replication were tested in cellular assays and two (proguanil and sulfasalazine) were shown to inhibit replication. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials.
Highly potent anti-SARS-CoV-2 multivalent DARPin therapeutic candidates
Authors: Walser Marcel , Rothenberger Sylvia , Hurdiss Daniel L. , Schlegel Anja , Calabro Valérie , Fontaine Simon , Villemagne Denis , Paladino Maria , Hospodarsch Tanja , Neculcea Alexandra , Cornelius Andreas , Schildknecht Patricia , Matzner Mirela , Hänggi Martin , Franchini Marco , Kaufmann Yvonne , Schaible Doris , Schlegel Iris , Iss Chloe , Looser Thamar , Mangold Susanne , Herzog Christel , Schiegg Dieter , Reichen Christian , Radom Filip , Bosshart Andreas , Lehmann Andreas , Haeuptle Micha A. , Zürcher Alexander , Vagt Toni , Sigrist Gabriel , Straumann Marcel , Proba Karl , Veitonmäki Niina , Dawson Keith M. , Zitt Christof , Mayor Jennifer , Ryter Sarah , Lyoo Heyrhyoung , Wang Chunyan , Li Wentao , Drulyte Ieva , Du Wenjuan , Binz H. Kaspar , de Waal Leon , Stittelaar Koert J. , Taplin Sarah , Lewis Seth , Steiner Daniel , van Kuppeveld Frank J.M. , Engler Olivier , Bosch Berend-Jan , Stumpp Michael T. , Amstutz Patrick
Published: August 2020

Globally accessible therapeutics against SARS-CoV-2 are urgently needed. Here, we report the generation of the first anti-SARS-CoV-2 DARPin molecules with therapeutic potential as well as rapid large-scale production capabilities. Highly potent multivalent DARPin molecules with low picomolar virus neutralization efficacies were generated by molecular linkage of three different monovalent DARPin molecules. These multivalent DARPin molecules target various domains of the SARS-CoV-2 spike protein, thereby limiting possible viral escape. Cryo-EM analysis of individual monovalent DARPin molecules provided structural explanations for the mode of action. Analysis of the protective efficacy of one multivalent DARPin molecule in a hamster SARS-CoV-2 infection model demonstrated a significant reduction of pathogenesis. Taken together, the multivalent DARPin molecules reported here, one of which has entered clinical studies, constitute promising therapeutics against the COVID-19 pandemic.
Quantification of iPSC-derived vascular networks in novel phototunable angiogenic hydrogels
Authors: Crosby Cody O. , Hillsley Alex , Kumar Sachin , Parekh Sapun H. , Rosales Adrianne , Zoldan Janet
Published: August 2020

Vascularization of engineered scaffolds remains a critical obstacle hindering the translation of tissue engineering from the bench to the clinic. Previously, we demonstrated the robust micro-vascularization of collagen hydrogels with induced pluripotent stem cell (iPSC)-derived endothelial progenitors; however, physically cross-linked collagen hydrogels compact rapidly and exhibit limited strength. To address these challenges, we synthesized an interpenetrating polymer network (IPN) hydrogel comprised of collagen and norbornene-modified hyaluronic acid (NorHA). This dual-network hydrogel combines the natural cues presented by collagen’s binding sites and extracellular matrix (ECM)-mimicking fibrous architecture with thein situmodularity and chemical cross-linking of NorHA. We modulated the stiffness and degradability of this novel IPN hydrogel by varying the concentration and sequence, respectively, of the NorHA peptide cross-linker. Rheological characterization of the photo-mediated gelation process revealed that the stiffness of the IPN hydrogel increased with cross-linker concentration and was decoupled from the bulk NorHA content. Conversely, the swelling of the IPN hydrogel decreased linearly with increasing cross-linker concentration. Collagen microarchitecture remained relatively unchanged across cross-linking conditions, although the mere addition of NorHA delayed collagen fibrillogenesis. Upon iPSC-derived endothelial progenitor encapsulation, robust, lumenized microvascular networks developed in IPN hydrogels over two weeks. Subsequent computational analysis showed that an initial rise in stiffness increased the number of branch points and vessels, but vascular growth was suppressed in high stiffness IPN hydrogels. These results suggest that an IPN hydrogel consisting of collagen and NorHA is highly tunable, compaction resistant, and capable of stimulating angiogenesis.

STATEMENT OF SIGNIFICANCE

We have synthesized the first tunable collagen and norbornene functionalized hyaluronic acid (NorHA) interpenetrating polymer network hydrogel. This unique biomaterial allows for control over hydrogel stiffness, independent of the total polymer concentration, by varying the concentration of a peptide cross-linker and was specifically designed to produce a biomimetic vasculogenic microenvironment. Using the system, we performed a detailed study of the vasculogenesis of induced pluripotent stem cell-derived (iPSC) endothelial progenitors, a poorly studied cell source with considerable therapeutic potential. Our results show that vascular growth can be tuned by altering the stiffness and degradability of the scaffolds independently. Finally, we improved upon our open-source computational pipeline programmed in ImageJ and MATLAB to further quantify vascular topologies in three dimensions.

Graphical abstract
Cell line-specific network models of ER+ breast cancer identify PI3Kα inhibitor sensitivity factors and drug combinations
Authors: Tejeda Zañudo Jorge Gómez , Mao Pingping , Alcon Clara , Kowalski Kailey J. , Johnson Gabriela N. , Xu Guotai , Baselga José , Scaltriti Maurizio , Letai Anthony , Montero Joan , Albert Reka , Wagle Nikhil
Published: August 2020

Durable control of invasive solid tumors necessitates identifying therapeutic resistance mechanisms and effective drug combinations. A promising approach to tackle the cancer drug resistance problem is to build mechanistic mathematical models of the signaling network of cancer cells, and explicitly model the dynamics of information flow through this network under distinct genetic conditions and in response to perturbations.

In this work, we used a network-based mathematical model to identify sensitivity factors and drug combinations for the PI3Kα inhibitor alpelisib, which was recently approved for ER+PIK3CAmutant breast cancer. We experimentally validated the model-predicted efficacious combination of alpelisib and BH3 mimetics (e.g. MCL1 inhibitors) in ER+ breast cancer cell lines. We also experimentally validated the reduced sensitivity to alpelisib caused by FOXO3 knockdown, which is a novel potential resistance mechanism. Our experimental results showed cell line-specific sensitivity to the combination of alpelisib and BH3 mimetics, which was driven by the choice of BH3 mimetics. We find that cell lines were sensitive to the addition of either MCL1 inhibitor s63845 alone or in combination with BCL-XL/BCL-2 inhibitor navitoclax, and that the need for the combination of both BH3 mimetics was predicted by the expression of BCL-XL. Based on these results, we developed cell line-specific network models that are able to recapitulate the observed differential response to alpelisib and BH3 mimetics, and also incorporate the most recent knowledge on resistance and response to PI3Kα inhibitors.

Overall, we present an approach for the development, experimental testing, and refining of mathematical models, which we apply to the context of PI3Kα inhibitor drug resistance in breast cancer. Our approach predicted and validated PI3Kα inhibitor sensitivity factors (FOXO3 knockdown) and drug combinations (BH3 mimetics), and illustrates that network-based mathematical models can contribute to overcoming the challenge of cancer drug resistance.
Assessing distribution changes of selected native and alien invasive plant species under changing climatic conditions in Nyeri County, Kenya
Authors: Waititu Julius Maina , Mundia Charles Ndegwa , Sichangi Arthur W
Published: August 2020

Changes in climatic conditions increases the risks of native and alien taxa expanding in geographical range and causing habitat transformations. The role of climate change in enhancing bio-invasions in local natural environments need to be assessed to guide on effective species management policy formulations. In this present study, we used species presence records, predictor variables and an ensemble of General Circulation Models data to predict suitable ecological niches for five of the selected invasive plant species within Nyeri County, Kenya. We predicted species distributions under RCP2.6, RCP4.5, and RCP8.5 emission scenarios for the years 2050 and 2070. We analysed species distribution changes to identify invasive species requiring immediate management action. Our analysis indicated that three of the five study species were suitable in ~50% of the study area while the other two were suitable in ~30% under the current climate.Lantana camara L.andSolanum campylacanthum Hochst. ex A. Richspecies would experience the largest range shift distance of ~6 – 10km and the largest habitat gain of ~12 – 33% in the future.Caesalpinia decapetala (Roth) Alston, Opuntia stricta (Haw.) Haw.andSenna didymobotrya (Fresen.) H.S. Irwin & Barnebyspecies on the other hand would have a decline in habitat range under future climate change scenarios. Although,S. didymobotryais considered a native species, it would lose half of its current suitable habitat in the future. Range shift analysis showed all study species would generally shift to the north west direction or towards the Aberdare ranges. From this study we conclude thatinvasive species management programs for smaller geographical areas ought to consider projecting species distributions under climate change scenarios to identify areas with high possible biodiversity changes. This would be important to conservationists when prioritizing management actions of invasive species in the region where data on invasive species is still limited.
Resveratrol induces H2A.X phosphorylation and H4K16 de-acetylation inToxoplasma gondii
Authors: Contreras Susana M. , Ganuza Agustina , Corvi María M. , Angel Sergio O.
Published: August 2020

Resveratrol (RSV) is a multi-target drug that demonstrated activity againstToxoplasma gondiiin macrophage and HFF cell line infection models. In addition to modulate redox homeostasis, RSV is also an activator of Sir2, a type III HDAC. RSV inhibited intracellularT. gondiitachyzoite growth at concentrations below the toxic effect on host cells. The IC50value in a 24-hours treatment was 53 μM. After 96 hours of treatment the maximum non-toxic concentration for host cell, 20 μM, only inhibitedT. gondiigrowth a 50%. RSV induced a reduction in H4K16 acetylation (H4K16ac), a mark associated to transcription, DNA replication and homologous recombination repair, without any effect on H3 acetylation (H3ac). RSV also enhanced the SQE motif phosphorylation onT. gondiiH2A.X (termed γH2A.X), a DNA damage associated PTM. Sirtinol, a specific Sir2 inhibitor also inhibitedT. gondiibut did not altered the acetylation status of H3 and H4K16 as well as H2A.X phosphorylation. Our findings suggest a possible link between RSV and DNA damage or DNA repair process maybe due to DNA replication stress and/or another undetermined mechanism.
Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron
Authors: Liu Xinhuai , Yeo Shel-Hwa , McQuillan H. James , Herde Michel K. , Hessler Sabine , Cheong Isaiah , Porteous Robert , Herbison Allan E.
Published: August 2020

The necessity and functional significance of neurotransmitter co-transmission remains unclear. The glutamatergic “KNDy” neurons co-express kisspeptin, neurokinin B (NKB) and dynorphin and exhibit a highly stereotyped synchronized behavior that reads out to the gonadotropin-releasing hormone (GnRH) neuron dendrons to drive episodic hormone secretion. Using expansion microscopy, we show that KNDy neurons make abundant close but non-synaptic appositions with the GnRH neuron dendron. Confocal GCaMP6 calcium imaging demonstrated that, of the neurotransmitters co-expressed by KNDy neurons, only kisspeptin was able to activate the GnRH neuron dendron. The selective deletion of kisspeptin from KNDy neurons resulted in mice in which the synchronized behavior of the KNDy neurons was maintained but their ability to drive episodic hormone secretion was abolished. This indicates that KNDy neurons drive episodic hormone secretion through converse modes of highly redundant neuropeptide co-transmission orchestrated by differential postsynaptic neuropeptide receptor expression at their two target sites.
Frequent lineage-specific substitution rate changes support an episodic model for protein evolution
Authors: Prabh Neel , Tautz Diethard
Published: August 2020

Since the inception of the molecular clock model for sequence evolution, the investigation of protein divergence has revolved around the question of a more or less constant rate of overall sequence information change. Although anomalies in clock-like divergence are described for some proteins, nowadays, the assumption of a constant decay rate for a given protein family is taken as the null model for protein evolution. Still, so far, a systematic test of this null model has not been done at a genome-wide scale despite the databases’ enormous growth. We focus here on divergence rate comparisons between closely related lineages, since this allows clear orthology assignments by synteny and unequivocal alignments, which are crucial for the determination of substitution rate changes. Thus, we generated a high-confidence dataset of syntenic orthologs from four ape species, including humans. Further analysis revealed that despite the appearance of an overall clock-like substitution pattern, a substantial number of proteins show lineage-specific acceleration and deceleration in divergence rates, or combinations of both in different lineages. Interestingly, when aggregated, even the families showing large lineage-specific rate perturbations can show overall rate equality. Our analysis uncovers a much more dynamic history of substitution rate changes in protein families. Which invalidates a pan-genome null model of constant decay, on the one hand, but remains compatible with the existing notion that aggregated data can be reliably used to estimate species splitting time. Ultimately, our data shows that a null model of constant change is not suitable to predict the evolutionary trajectories of individual proteins.
RDC complex executes a dynamic piRNA program duringDrosophilaspermatogenesis to safeguard male fertility
Authors: Chen Peiwei , Luo Yicheng , Aravin Alexei A.
Published: August 2020

piRNAs are small non-coding RNAs that guide the silencing of transposons and other targets in animal gonads. InDrosophilafemale germline, many piRNA source loci dubbed ‘piRNA clusters’ lack hallmarks of active genes and exploit an alternative path for transcription, which relies on the Rhino-Deadlock-Cutoff (RDC) complex. It remains to date unknown how piRNA cluster transcription is regulated in the male germline. We found that components of RDC complex are expressed in male germ cells during early spermatogenesis, from germline stem cells (GSCs) to early spermatocytes. RDC is essential for expression of dual-strand piRNA clusters and transposon silencing in testis; however, it is dispensable for expression of Y-linkedSuppressor of StellatepiRNAs and thereforeStellatesilencing. Despite intactStellaterepression,rhimutant males exhibited compromised fertility accompanied by germline DNA damage and GSC loss. Thus, piRNA-guided repression is essential for normal spermatogenesis beyondStellatesilencing. While RDC associates with multiple piRNA clusters in GSCs and early spermatogonia, its localization changes in later stages as RDC concentrates on a single X-linked locus,AT-chX. Dynamic RDC localization is paralleled by changes in piRNA cluster expression, indicating that RDC executes a fluid piRNA program during different stages of spermatogenesis.
Global historic pandemics caused by the FAM-1 genotype of the Irish potato pathogenPhytophthora infestans
Authors: Saville Amanda C. , Ristaino Jean B.
Published: August 2020

The FAM-1 genotype ofPhytophthora infestanscaused late blight in the 1840s in the US and Europe and was responsible for the Irish famine. We examined 140 herbarium specimens collected between 1845 and 1991 from six continents and used 12-plex microsatellite genotyping (SSR) to identify FAM-1 and the mtDNA lineage (Herb-1/ Ia) present in historic samples. FAM-1 was detected in approximately 73% of the historic specimens and was found on 6 continents. The US-1 genotype was found in only 27% of the samples and was found later on all continents except Australia/Oceania. FAM-1 was the first genotype detected in almost all the former British colonies from which samples were available. The data from historic samples suggest the FAM-1 genotype was widespread, diverse, and spread more widely than US-1. The famine lineage spread to six continents over 140 years, and likely spread during global colonization from Europe.
BAX is necessary for neuronal death following exposure to isoflurane during the neonatal period
Authors: Slupe Andrew M. , Villasana Laura , Wright Kevin M.
Published: August 2020

Exposure to volatile anesthetics during the neonatal period results in acute neuronal death in rodent and non-human primate models, potentially leading to lasting cognitive deficits. We usedBax-/-mice to show that neuronal death following neonatal exposure to isoflurane is mediated by the apoptotic pathway, and that GABAergic interneurons are selectively vulnerable. NeonatalBax-/-mice also showed attenuated microglial activation after exposure to isoflurane, indicating that neuroinflammatory response is secondary to neuronal apoptosis. Isoflurane-induced neuronal apoptosis in neonates appeared to have little effect on seizure threshold or cognitive function later in life. Collectively, these findings define the acute injury mechanism of volatile anesthetics during the neonatal period.
Longitudinal changes in brain metabolites in healthy subjects and patients with first episode psychosis (FEP): a 7-Tesla MRS study
Authors: Wang Min , Barker Peter B. , Cascella Nicola , Coughlin Jennifer M. , Nestadt Gerald , Nucifora Frederick C. , Sedlak Thomas W. , Kelly Alexandra , Younes Laurent , Geman Donald , Sawa Akira , Yang Kun
Published: August 2020

Objective

7 Tesla (T) longitudinal magnetic resonance spectroscopy (MRS) offers a precise measurment of metabolic levels in human brain via a non-invasive approach. Studying longitudinal changes in neurometabolites could help identify trait and state markers for diseases and understand inconsistent findings from different researchers due to differences in the age of study participants and duration of illness. This study is the first to report novel longitudinal patterns in young adulthood from both physiological and pathological viewpoints using 7T MRS.

Methods

Utilizing a four-year longitudinal cohort with 38 first episode psychosis (FEP) patients (onset within 2 years) and 48 healthy controls (HC), the authors examined the annual percentage changes of 9 neurometabolites in 5 brain regions.

Results

Both FEP patients and HC subjects were found to have significant longitudinal reductions in glutamate (Glu) in the anterior cingulate cortex (ACC). Only FEP patients were found to have a significant decrease over time in γ-aminobutyric acid (GABA), N-acetyl aspartate (NAA), myo-inositol (mI), and total choline (tCho: phosphocholine plus glycerophosphocholine) in the ACC. Uniquely, glutathione (GSH) was found to have a near zero annual percentage change in both FEP patients and HC subjects in all 5 brain regions over a four-year timespan in young adulthood.

Conclusions

GSH could be a trait marker for diagnostic applications at least in young adulthood. Glu, GABA, NAA, mI, and tCho in the ACC are associated with the patient’s status and could be state markers for mechanistic studies of psychotic disorders, including those for progressive pathological changes and medication effects in young adulthood.
Genome-wide haplotype association study in imaging genetics using whole-brain sulcal openings of 16,304 UK Biobank subjects
Authors: Karkar Slim , Dandine-Roulland Claire , Mangin Jean-François , Guen Yann Le , Philippe Cathy , Deleuze Jean-François , Pierre-Jean Morgane , Floch Edith Le , Frouin Vincent
Published: August 2020

Neuroimaging-genetics cohorts gather two types of data: brain imaging and genetic data. They allow the discovery of associations between genetic variants and brain imaging features. They are invaluable resources to study the influence of genetics and environment in the brain features variance observed in normal and pathological populations. This study presents a genome wide haplotype analysis for 123 brain sulcus opening value (a measure of sulcal width) across the whole brain that include 16,304 subjects from UK Biobank. Using genetic maps, we defined 119,548 blocks of low recombination rate distributed along the 22 autosomal chromosomes, and analyzed 1,051,316 haplotypes. To test associations between haplotypes and complex traits, we designed three statistical approaches. Two of them use a model that includes all the haplotypes for a sin gle block, while the last approach considers one model by haplotype. All the statistics produced were assessed as rigorously as possible. Thanks to the rich imaging dataset at hand, we used resampling techniques to assess False Positive Rate for each statistical approach in a genome-wide and brain-wide context. The results on real data show that genome-wide haplotype analyses are more sensitive than single-SNP approach and account for local complex Linkage Disequilibrium (LD) structure, which makes genome-wide haplotype analysis an interesting and statistically sound alternative to the single-SNP counterpart.
Autophagy Compensates for Lkb1 Loss to Maintain Adult Mice Homeostasis and Survival
Authors: Khayati Khoosheh , Bhatt Vrushank , Hu Zhixian Sherrie , Fahumy Sajid , Luo Xuefei , Guo Jessie Yanxiang
Published: August 2020

Liver Kinase B1 (LKB1) is the major energy sensor for cells to respond to metabolic stress. Autophagy degrades and recycles proteins, macromolecules, and organelles for cells to survive starvation. To access the role and cross-talk between autophagy and Lkb1 in normal tissue homeostasis, we generated genetically engineered mouse models where we can conditionally deleteLkb1and autophagy essential gene,Atg7, respectively or simultaneously, throughout the adult mice. We found that Lkb1 was essential for the survival of adult mice, and autophagy activation could temporarily compensate for the acute loss of Lkb1 and extend mouse life span. We further found that acute deletion of Lkb1 in adult mice led to impaired intestinal barrier function, hypoglycemia, and abnormal serum metabolism, which was partly rescued by the Lkb1 loss-induced autophagy upregulation via inhibiting p53 induction. Taken together, we demonstrated that autophagy and Lkb1 work synergistically to maintain adult mouse homeostasis and survival.
The effect of online learning on communication between instructors and students during Covid-19 pandemic
Authors: Alawamleh Mohammad , Al-Twait Lana Mohannad , Al-Saht Gharam Raafat
Published: August 2020

Purpose

This study aims to explore whether online learning has an effect on communication between instructors and students in a negative way, whether online learning affects students' productivity levels and to evaluate and suggest ways of improving effective online communication between instructors and students.

Design/methodology/approach

This study used is a quantitative research study which was conducted through a semi-structured online survey through a random sample technique.

Findings

Results revealed that the vast majority agree with the questions of the study. Students still prefer classroom classes over online classes due to many problems they face when taking online classes, such as lack of motivation, understanding of the material, decrease in communication levels between the students and their instructors and their feeling of isolation caused by online classes.

Research limitations/implications

This research studied the impact from students' perspective only as the sample was selected only from students.

Originality/value

This research reached the students’ point of view in a broader way which will help understanding the issues and provide effective solutions. This research suggested that instructors must communicate with their students and vice versa in more informal channels (instant messages online chat groups, audio calls, private video calls …) in parallel with the formal channels (online platforms, email …). Finally, instructors should encourage students to participate and study more by providing different kind of incentives.
Service quality assessment model for academic libraries
Authors: Alam Md. Jahangir , Mezbah-ul-Islam Muhammad
Published: August 2020

Purpose

The purpose of this paper is to develop a service quality assessment model for academic libraries using SERVQUAL and validate the model surveying teachers, students and researchers.

Design/methodology/approach

A model was developed, including 28 statements of five dimensions using the SERVQUAL instrument. It incorporated three segments, i.e. minimum service expectation, desired service expectation and actual service performance with a seven-point Likert scale. The minimum service expectation and desired service expectation appear at both ends of the tolerance zone, which represents the range of satisfactory service performance. A performance level upper tolerance zone could delight users, or service performance below the tolerance zone would cause dissatisfaction. A survey was conducted among 552 respondents from ten private university libraries of Bangladesh to validate the model.

Findings

Several statistical methods like Cronbach’s alpha (0.986), Bartlett’s test (0.001), rotation sums of squared loadings (74.26) in factor analysis, item loading (0.671‐0.839), commonalities (0.579‐0.859), Kaiser–Meyer–Olkin value (0.971), construct reliability (0.862‐0.910) and AVE value (0.510‐0.660) supported reliability and validity of the model. The actual service performance of all dimensions existed within the tolerance zone of the respective dimensions. Besides, the overall service performance (5.11) resided within the tolerance zone (4.73‐5.84), indicating the users were satisfied with the service provided by their libraries.

Originality/value

The model was developed in the current context of university libraries, which produced appropriate results. It will prompt further research on service quality assessment in academic libraries globally.
Thematic analysis of destination images for social media engagement marketing
Authors: Song Seobgyu , Park Seunghyun “Brian” , Park Kwangsoo
Published: August 2020

Purpose

This study assessed the effect of photo themes to facilitate social media user engagement in Facebook brand pages and emphasized the important role of designing images for developing destination marketing strategies.

Design/methodology/approach

This study analyzed 8,900 posts that were published by official tourism destination marketers for each destination (Hong Kong, Japan, South Korea). Text mining analysis, image thematic coding analysis and two-way ANOVA were applied to examine the significant differences across proposed determinants for the following engagements: the numbers of likes, comments and shares.

Findings

The results indicated that photographs on social media of three tourism destinations can be explored based on 11 categories of image themes. The themes' significant and distinct effects on three indicators of social media engagement were verified.

Originality/value

This research presented methodological insights by integrating thematic and statistical analyses with social media analytics. The findings of this study provided theoretical evidence of the importance of image themes in the context of social media engagement marketing. Based on the implications of this study, practitioners would enhance the effectiveness of social media marketing.
The three pillars of institutional theory and IFRS implementation in Nigeria
Authors: Osinubi Igbekele Sunday
Published: August 2020

Purpose

This study explores the effects of the three pillars of institutional theory in shaping the activities of institutional entrepreneurs and other social actors during International Financial Reporting Standards (IFRS) implementation in Nigeria.

Design/methodology/approach

This study uses a document analysis method to achieve the objectives of the study.

Findings

This study finds that IFRS implementation in Nigeria witnessed some progression from regulative to normative to cognitive pillar building. The regulation on IFRS implementation was initiated top-down rather than through lobbying from professional accounting bodies and the public. Changes in the regulatory framework brought some improvement to corporate financial reporting practices such as the timing of corporate filings of audited financial reports. However, the implementation process is laden with conflicts and power struggle among institutional actors. These conflicts and power struggles led the President of Nigeria to sack the Board of the Financial Reporting Council of Nigeria (FRC), the reconstitution of the Board and appointment of a Chairman for the Board of the FRC.

Practical implications

IFRS implementation process resulted in power redistribution among institutional actors, which led to resistance, tensions and conflicts among institutional actors. The conflicts arise from the need of actors to legitimate their activities and secure their positions. The three institutional pillars are key components of a change process and the actor's social position affects their capability to act as an institutional entrepreneur.

Originality/value

This finding should provide foundational knowledge that will inform practitioners, researchers and regulators in developing countries on how institutional actors shape the approach to corporate reporting regulations.