bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Risk and the Somatic Cell Lineage Tree
Authors: Derényi Imre , Demeter Márton C. , Szöllősi Gergely J.
Published: July 2020

All the cells of a multicellular organism are the product of cell divisions that trace out a single binary tree, the so-called cell lineage tree. Because cell divisions are accompanied by replication errors, the shape of the cell lineage tree is one of the key determinants of how somatic evolution, which can potentially lead to cancer, proceeds. Cancer initiation usually requires the accumulation of a certain number of driver mutations. By mapping the accumulation of driver mutations into a graph theoretical problem, we show that in leading order of the mutation rate the probability of collecting a given number of driver mutations depends only on the distribution of the lineage lengths (irrespective of any other details of the cell lineage tree), and we derive a simple analytical formula for this probability. Our results are crucial in understanding how natural selection can shape the cell lineage trees of multicellular organisms in order to reduce their lifetime risk of cancer. In particular, our results highlight the significance of the longest cell lineages. Our analytical formula also provides a tool to quantify cancer susceptibility in theoretical models of tissue development and maintenance, as well as for empirical data on cell linage trees.

Significance Statement

A series of cell divisions starting from a single cell produce and maintain tissues of multicellular organisms. Somatic evolution, including the development of cancer, takes place along thecell lineage treetraced out by these cell divisions. A fundamental question in cancer research is how the lifetime risk of cancer depends on the properties of an arbitrary cell lineage tree. Here we show that for small mutation rates (which is the case in reality) the distribution of the lineage lengths alone determines cancer risk, and that this risk can be described by a simple analytical formula. Our results have far-reaching implications not only for cancer research, but also for evolutionary biology in general.
A CRISPR-based genome-wide screen for adipogenesis reveals new insights into mitotic expansion and lipogenesis
Authors: Turn Rachel E. , Hilgendorf Keren I. , Johnson Carl T. , Han Kyuho , Rabiee Atefeh , Demeter Janos , Aziz-Zanjani Mohammad Ovais , Domizi Pablo , Cheng Ran , Zhu Yingdi , Jiang Zewen , Svensson Katrin J. , Bassik Michael C. , Jackson Peter K.
Published: July 2020

In response to excess nutrients, white adipose tissue expands by both generating new adipocytes and by upregulating lipogenesis in existing adipocytes. Here, we performed a genome-wide functional genomics screen to identify regulators of adipogenesis in the mouse 3T3-L1 preadipocyte model. The pooled screening strategy utilized FACS to isolate populations based on lipid content by gating for fluorescence intensity of the lipophilic, green fluorescent BODIPY dye. Additionally, the approach categorized if genes functioned during mitotic expansion or lipogenesis. Cellular mechanisms regulating the rate of protein translation and protein stability were found critical for adipogenesis and lipogenesis. These protein-directed mechanisms were further supported by proteomic analyses, which demonstrated that essential changes in protein abundance driving 3T3-L1 adipogenesis were not driven by transcription. We exemplify this theme by showing that the hypusination pathway, a conserved regulator of translation initiation, is critical to translate adipogenic inducers of mitotic expansion and that the neddylation/ubiquitin pathway modulates insulin sensitivity to regulate lipogenesis.
Transient receptor potential canonical 5 (TRPC5) mediates inflammatory mechanical pain
Authors: Sadler Katelyn E. , Moehring Francie , Shiers Stephanie I. , Laskowski Lauren J. , Mikesell Alexander R. , Plautz Zakary R. , Mecca Christina M. , Dussor Gregory , Price Theodore J. , McCorvy John D. , Stucky Cheryl L.
Published: July 2020

Persistent tactile pain is a poorly managed symptom of inflammatory and neuropathic injury. To develop therapies for this maladaptive sensation, the underlying molecular mediators must be identified. Using knockout mice and pharmacological inhibitors, we identified transient receptor canonical 5 (TRPC5) as a key contributor to the persistent tactile pain that occurs in many inflammatory and neuropathic preclinical rodent models. TRPC5 inhibition was effective in injuries associated with elevated levels of the bioactive phospholipid lysophosphatidylcholine (LPC). Exogenous application of LPC induced TRPC5-dependent behavioral mechanical allodynia, neuronal mechanical hypersensitivity, and spontaneous pain.In vitro, LPC activated both homomeric mouse and human TRPC5 channels, which upon examination of human dorsal root ganglia tissue, were expressed in 75% of human sensory neurons. Based on these results, TRPC5 inhibitors should be pursued as personalized therapy for spontaneous and tactile pain in conditions where elevated LPC is a biomarker.
Structural basis of αE-catenin–F-actin catch bond behavior
Authors: Xu Xiao-Ping , Pokutta Sabine , Torres Miguel , Swift Mark F. , Hanein Dorit , Volkmann Niels , Weis William I.
Published: July 2020

Cell-cell and cell-matrix junctions transmit mechanical forces during tissue morphogenesis and homeostasis. α-Catenin links cell-cell adhesion complexes to the actin cytoskeleton, and mechanical load strengthens its binding to F-actin in a direction-sensitive manner. This so-called catch bond behavior is described by a model in which force promotes a transition between weak and strong actin-bound states. We describe the cryo-electron microscopy structure of the F-actin-bound αE-catenin actin-binding domain, which in solution forms a 5-helix bundle. Upon binding to actin, the first helix of the bundle dissociates and the remaining four helices and connecting loops rearrange to form the interface with actin. Deletion of the N-terminal helix produces strong actin binding in the absence of force. Our analysis explains how mechanical force applied to αE-catenin or its homolog vinculin favors the strongly bound state, and the dependence of catch bond strength on the direction of applied force.
Persistent intestinal abnormalities and symptoms in cystic fibrosis: The underpinning mechanisms impacting gut health and motility. Protocol for a systematic review
Authors: Marsh R.J. , Ng C. , Major G. , Rivett D.W. , Smyth A. , van der Gast C.J.
Published: July 2020

Background

Patients with cystic fibrosis (CF) are characterised by abnormalities of the intestinal tract relating to gut motility and physiological issues, with daily symptoms of disease including abdominal pain, flatulence, bloating, and constipation. With improvements in respiratory outcomes, a shift in disease manifestations has highlighted the prevalence of the gastrointestinal-related problems associated with CF, yet most therapies currently in clinical use for the gut symptoms of CF have been repurposed from other disease indications and have not been developed with a knowledge of the mechanisms underpinning gastrointestinal disease in CF. Increased attention towards the role of intestinal inflammation and microbial dysbiosis in the CF population warrants a comprehensive knowledge of these aspects alongside the increased luminal fat content, dysmotility, and small intestinal bacterial overgrowth (SIBO) resultant of the primary consequences of CFTR dysfunction (disrupted fluid secretion and pancreatic insufficiency), and how they contribute towards the intestinal complications of CF disease.

Methods and Study Design

We will conduct a systematic review to comprehensively address our current understanding of the primary consequences of CFTR dysfunction, and their subsequent secondary effects that contribute towards the disruption of gut motility, health, and associated symptoms in the CF intestine. Databases searched will include PubMed, CINAHL, MEDLINE and the Cochrane library from 1939 until a specified date of last search, alongside clinical trial databases for ongoing studies. Search strategies will include various terminology that relates to the primary mechanistic defects of CF, postulated secondary effects of such defects, and symptoms experienced in patients. A full search strategy is outlined in appendix B. One reviewer will apply an inclusion criterion to obtained abstracts. Following agreement from a second reviewer, full-text articles will be sought, and data will be extracted from relevant articles. Disagreements will be resolved with a third reviewer. The quality of data will be assessed by the GRADE criteria. Data will be used to present a narrative, and where possible, quantitative synthesis.

Discussion

This systematic review will discuss our current understanding of the underpinning mechanisms of the persisting abnormalities in gut health and motility within CF, addressing potential intricate relationships that further contribute to disease progression within the intestinal tract. Furthermore, we will identify current gaps in the literature to propose directions for future research. A comprehensive understanding of these aspects in relation to intestinal abnormalities will aid future clinical directions.
Modelling theWolbachiaIncompatible Insect Technique: strategies for effective mosquito population elimination
Authors: Pagendam D.E. , Trewin B.J. , Snoad N. , Ritchie S.A. , Hoffmann A.A. , Staunton K.M. , Paton C. , Beebe N.
Published: July 2020

TheWolbachiaIncompatible Insect Technique (IIT) shows promise as a method for eliminating invasive mosquitoes such asAedes aegypti(Linnaeus)(Diptera: Culicidae) and reducing the incidence of vector-borne diseases such as dengue, chikungunya and Zika. Successful implementation of this biological control strategy relies on high-fidelity separation of male from female insects in mass production systems for inundative release into landscapes. Processes for sex-separating mosquitoes are typically error prone, laborious and IIT programs run the risk of releasingWolbachiainfected females and replacing wild mosquito populations. We introduce a simple Markov Population Process (MPP) model for studying mosquito populations subjected to aWolbachia-IIT program which exhibit an unstable equilibrium threshold. The model is used to study,in silico, scenarios that are likely to yield a successful elimination result. Our results suggest that elimination is best achieved by releasing males at rates that adapt to the ever-decreasing wild population, thus reducing the risk of releasingWolbachia-infected females while reducing costs. While very high-fidelity sex-separation is required to avoid establishment, release programs tend to be robust to the release of a small number ofWolbachia-infected females. These findings will inform and enhance the next generation ofWolbachia-IIT control strategies that are already showing great promise in field trials.
Development of a severity of disease score and classification model by machine learning for hospitalized COVID-19 patients
Authors: Marcos Miguel , Belhassen-García Moncef , Sánchez-Puente Antonio , Sampedro-Gomez Jesús , Azibeiro Raúl , Dorado-Díaz P-Ignacio , Marcano-Millán Edgar , García-Vidal Carolina , Moreiro-Barroso Maria-Teresa , Cubino-Bóveda Noelia , Pérez-García María-Luisa , Rodríguez-Alonso Beatriz , Encinas-Sánchez Daniel , Peña-Balbuena Sonia , Sobejano-Fuertes Eduardo , Inés Sandra , Carbonell Cristina , Lopez-Parra Miriam , Andrade-Meira Fernanda , López-Bernús Amparo , Lorenzo Catalina , Carpio Adela , Polo-San-Ricardo David , Sánchez-Hernández Miguel-Vicente , Borrás Rafael , Sagredo-Meneses Víctor , Sanchez Pedro-L , Soriano Alex , Martín-Oterino José-Ángel
Published: July 2020

BACKGROUND

Efficient and early triage of hospitalized Covid-19 patients to detect those with higher risk of severe disease is essential for appropriate case management.

METHODS

We trained, validated, and externally tested a machine-learning model to early identify patients who will die or require mechanical ventilation during hospitalization from clinical and laboratory features obtained at admission. A development cohort with 918 Covid-19 patients was used for training and internal validation, and 352 patients from another hospital were used for external testing. Performance of the model was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity and specificity.

RESULTS

A total of 363 of 918 (39.5%) and 128 of 352 (36.4%) Covid-19 patients from the development and external testing cohort, respectively, required mechanical ventilation or died during hospitalization. In the development cohort, the model obtained an AUC of 0.85 (95% confidence interval [CI], 0.82 to 0.87) for predicting severity of disease progression. Variables ranked according to their contribution to the model were the peripheral blood oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio, age, estimated glomerular filtration rate, procalcitonin, C-reactive protein, updated Charlson comorbidity index and lymphocytes. In the external testing cohort, the model performed an AUC of 0.83 (95% CI, 0.81 to 0.85). This model is deployed in an open source calculator, in which Covid-19 patients at admission are individually stratified as being at high or non-high risk for severe disease progression.

CONCLUSIONS

This machine-learning model, applied at hospital admission, predicts risk of severe disease progression in Covid-19 patients.
MIND diet associated with later onset of Parkinson’s disease
Authors: Metcalfe-Roach A , Yu AC , Golz E , Sundvick K , Cirstea MS , Kliger D , Foulger LH , Mackenzie M , Finlay BB , Appel-Cresswell S
Published: July 2020

Background

The MIND diet has been linked with prevention of Alzheimer’s disease and cognitive decline but has not been fully assessed in the context of Parkinson’s disease (PD).

Objective

To determine whether MIND diet adherence is associated with the age of Parkinson’s disease onset in a manner superior to that of the Mediterranean diet.

Methods

Food Frequency Questionnaires from 167 participants with PD and 119 controls were scored for MIND and two versions of Mediterranean diet adherence. Scores were compared between sex and disease subgroups, and PD diet adherence was correlated with age of onset using univariate and multivariate linear models.

Results

The female subgroup adhered more closely to the MIND diet than the males, and diet scores were not modified by disease status. Later age of onset correlated most strongly with MIND diet adherence in the female subgroup, corresponding to differences of up to 17.4 years (p<0.001) between low and high dietary tertiles. Greek Mediterranean adherence was also significantly associated with later PD onset across all models (p=0.05-0.03). Conversely, only Greek Mediterranean adherence remained correlated with later onset across all models in men, with differences of up to 8.4 years (p=0.002).

Conclusions

This cross-sectional study finds a strong correlation of age of onset of PD with dietary habits, suggesting that nutritional strategies may be an effective tool to delay PD onset. Further studies may help to elucidate potential nutrition-related sex-specific pathophysiological mechanisms and differential prevalence rates in PD.
An exact method for quantifying the reliability of end-of-epidemic declarations in real time
Authors: Parag Kris V , Donnelly Christl A , Jha Rahul , Thompson Robin N
Published: July 2020

We derive and validate a novel and analytic method for estimating the probability that an epidemic has been eliminated (i.e. that no future local cases will emerge) in real time. When this probability crosses 0.95 an outbreak can be declared over with 95% confidence. Our method is easy to compute, only requires knowledge of the incidence curve and the serial interval distribution, and evaluates the statistical lifetime of the outbreak of interest. Using this approach, we rigorously show how the time-varying under-reporting of infected cases will artificially inflate the inferred probability of elimination and hence lead to early (false-positive) end-of-epidemic declarations. Contrastingly, we prove that incorrectly identifying imported cases as local will deceptively decrease this probability, resulting in late (false-negative) declarations. Failing to sustain intensive surveillance during the later phases of an epidemic can therefore substantially mislead policymakers on when it is safe to remove travel bans or relax quarantine and social distancing advisories. World Health Organisation guidelines recommend fixed (though disease-specific) waiting times for end-of-epidemic declarations that cannot accommodate these variations. Consequently, there is an unequivocal need for more active and specialised metrics for reliably identifying the conclusion of an epidemic.
The natural history of symptomatic COVID-19 in Catalonia, Spain: a multi-state model including 109,367 outpatient diagnoses, 18,019 hospitalisations, and 5,585 COVID-19 deaths among 5,627,520 people
Authors: Burn Edward , Tebé Cristian , Fernandez-Bertolin Sergio , Aragon Maria , Recalde Martina , Roel Elena , Prats-Uribe Albert , Prieto-Alhambra Daniel , Duarte-Salles Talita
Published: July 2020

Background

The natural history of Coronavirus Disease 2019 (COVID-19) has yet to be fully described, with most previous reports focusing on hospitalised patients. Using linked patient-level data, we set out to describe the associations between age, gender, and comorbidities and the risk of outpatient COVID-19 diagnosis, hospitalisation, and/or related mortality.

Methods

A population-based cohort study including all individuals registered in Information System for Research in Primary Care (SIDIAP). SIDIAP includes primary care records covering > 80% of the population of Catalonia, Spain, and was linked to region-wide testing, hospital and mortality records. Outpatient diagnoses of COVID-19, hospitalisations with COVID-19, and deaths with COVID-19 were identified between 1st March and 6th May 2020. A multi-state model was used, with cause-specific Cox survival models estimated for each transition.

Findings

A total of 5,627,520 individuals were included. Of these, 109,367 had an outpatient diagnosis of COVID-19, 18,019 were hospitalised with COVID-19, and 5,585 died after either being diagnosed or hospitalised with COVID-19. Half of those who died were not admitted to hospital prior to their death. Risk of a diagnosis with COVID-19 peaked first in middle-age and then again for oldest ages, risk for hospitalisation after diagnosis peaked around 70 years old, with all other risks highest at oldest ages. Male gender was associated with an increased risk for all outcomes other than outpatient diagnosis. The comorbidities studied (autoimmune condition, chronic kidney disease, chronic obstructive pulmonary disease, dementia, heart disease, hyperlipidemia, hypertension, malignant neoplasm, obesity, and type 2 diabetes) were all associated with worse outcomes.

Interpretation

There is a continued need to protect those at high risk of poor outcomes, particularly the elderly, from COVID-19 and provide appropriate care for those who develop symptomatic disease. While risks of hospitalisation and death are lower for younger populations, there is a need to limit their role in community transmission. These findings should inform public health strategies, including future vaccination campaigns.
PROJECTING A MATURE EPIDEMIC: A SIMPLE TOOL WITH AN APPLICATION TO COVID-19 DEATHS
Authors: Artzrouni Marc , Wykoff Randy
Published: July 2020

We describe a new statistical model for the spread of a mature epidemic, i.e. one characterized by an exponentially decaying growth rate of the cumulative number of cases/deaths – the speed of this decay being measured by the growth rate’s half-life. If such a pattern is observed during the recent past, then it can be extrapolated. A spreadsheet is made available that allows users to input weekly cumulative numbers of deaths and obtain an estimate of the growth rate’s baseline half-life and the corresponding projections. These projections can be compared to those with a larger half-life (if a protracted epidemic is expected, e.g. due to second wave), or with a smaller one (if successful therapies or mitigation efforts reduce transmission). The model is applied to deaths due to COVID-19 in California in May-June 2020.
Staff testing for COVID-19 via an online pre-registration form
Authors: Moolla M. Saadiq , Parker Arifa , Parker M. Aslam , Sithole Sthembiso , Amien Leila , Chiecktey Rubeena , Bawa Tasneem , Mowlana Abdurasiet
Published: July 2020

Structured Abstract

Background

Healthcare workers are at increased risk of contracting SARS-CoV-2 and potentially causing institutional outbreaks. Staff testing is critical in identifying and isolating infected individuals while also reducing unnecessary workforce depletion. Tygerberg Hospital implemented an online pre-registration system to expedite staff and cluster testing.

Objectives

We aimed to identify (1) specific presentations associated with a positive or negative result for SARS-CoV-2 and (2) staff sectors where enhanced strategies for testing might be required.

Methods

Retrospective descriptive study involving all clients making use of the hospital’s pre-registration system during May 2020.

Results

Of 799 clients, most were young and female with few comorbidities. The most common occupation was nurses followed by administrative staff, doctors and general assistants. Doctors tested earlier compared to other staff (median: 1.5 vs 4 days). The most frequent presenting symptoms were headache, sore throat, cough and myalgia. Amongst those testing positive (n=105), fever, altered smell, altered taste sensation, chills and history of fever were the most common symptoms. Three or more symptoms was more predictive of a positive test, but 12/145 asymptomatic clients also tested positive.

Conclusion

Staff coronavirus testing using an online pre-registration form is a viable and acceptable strategy. While some presentations are less likely to be associated with SARS-CoV-2 infection, no symptom can completely exclude it. Staff testing should form part of a bundle of strategies to protect staff including wearing masks, regular hand washing, buddy screening, physical distancing, availability of PPE and special dispensation for COVID-19-related leave.

Unstructured Abstract

Hospital staff testing is critical to identify and isolate SARS-CoV-2 infected individuals while reducing unnecessary workforce depletion. Tygerberg Hospital implemented an online pre-registration system to expedite staff testing. In a retrospective descriptive study of all clients registering during May 2020 (N=799), we found rapid and sustained uptake of the system. The most frequent presenting symptoms were headache, sore throat, cough and myalgia. Amongst those testing positive (n=105), fever, altered smell, altered taste sensation and chills were the most likely symptoms, but 12/145 asymptomatic clients also tested positive. Staff testing should form part of a bundle of strategies to protect staff.
Fluorescentin vivoediting reporter (FIVER): A novel multispectral reporter ofin vivogenome editing
Authors: Tennant Peter A. , Foster Robert G. , Dodd Daniel O. , Sou Ieng Fong , McPhie Fraser , Younger Nicholas , Murphy Laura C. , Pearson Matthew , Vernay Bertrand , Keighren Margaret A. , Budd Peter , Hart Stephen L. , Megaw Roly , Boulter Luke , Mill Pleasantine
Published: July 2020

Advances in genome editing technologies have created opportunities to treat rare genetic diseases, which are often overlooked in terms of therapeutic development. Nonetheless, substantial challenges remain: namely, achieving therapeutically beneficial levels and kinds of editing in the right cell type(s). Here we describe the development of FIVER (fluorescentin vivoediting reporter) — a modular toolkit forin vivodetection of genome editing with distinct fluorescent read-outs for non-homologous end-joining (NHEJ), homology-directed repair (HDR) and homology-independent targeted integration (HITI). We demonstrate that fluorescent outcomes reliably report genetic changes following editing with diverse genome editors in primary cells, organoids andin vivo. We show the potential of FIVER for high-throughput unbiased screens, from small molecule modulators of genome editing outcomes in primary cells through to genome-widein vivoCRISPR cancer screens. Importantly, we demonstrate itsin vivoapplication in postnatal organ systems of interest for genetic therapies — retina and liver. FIVER will broadly help expedite the development of therapeutic genome surgery for many genetic disorders.
Direct visualization of four diffusive LexA states controlling SOS response strength during antibiotic treatment
Authors: Schärfen Leonard , Tišma Miloš , Hartmann Andreas , Schlierf Michael
Published: July 2020

In bacteria, the key mechanism governing mutation, adaptation and survival upon DNA damage is the SOS response. Through autoproteolytic digestion triggered by single-stranded DNA caused by most antibiotics, the transcriptional repressor LexA controls over 50 SOS genes including DNA repair pathways and drivers of mutagenesis. Efforts to inhibit this response and thereby combat antibiotic resistance rely on a broad understanding of its behaviorin vivo, which is still limited. Here, we develop a single-molecule localization microscopy assay to directly visualize LexA mobility inEscherichia coliand monitor the SOS response on the level of transcription factor activity. We identify four diffusive populations and monitor their temporal evolution upon ciprofloxacin-induced continuous DNA damage. With LexA mutants, we assign target bound, non-specifically DNA bound, freely diffusing and cleaved repressors. We develop a strategy to count LexA in fixed cells at different time points after antibiotic stress and combine the time-evolution of LexA sub-populations and the repressor’s overall abundance. Through fitting a detailed kinetic model we obtainin vivosynthesis, cleavage and binding rates and determined that the regulatory feedback system reaches a new equilibrium in ∼100 min. LexA concentrations showed non-constant heterogeneity during SOS response and designate LexA expression, and thereby regulation of downstream SOS proteins, as drivers of evolutionary adaptation. Even under low antibiotic stress, we observed a strong SOS response on the LexA level, suggestion that small amounts of antibiotics can trigger adaptation inE. coli.
Improving vaccine efficacy based on non-covalent photoinactivation of microorganisms - sources vaccine antigens (MSVA)
Authors: Martynov Artur , Farber Boris , Osolodchenko Tatyana , Klein Ilya
Published: July 2020

One of the most promising methods for non-covalent inactivation of vaccine-producing microorganisms is the use of photoinactivation using riboflavin derivatives. The study used a dynamic combinatorial derivative of riboflavin - succinyl-maleinyl riboflavin. Corpuscular vaccines are divided into the following groups: from 2AB to 5AB - bacteria were inactivated by riboflavin derivative and blue light, and groups from 6AB to 9AB were inactivated by formalin (0.1% formalin in 9 log CFU was kept for 2 weeks in an thermostat and then sterility was determined - bacterial growth was not observed). A dynamic derivative of riboflavin at a final concentration of 0.02% can photo inactivate 6 time more bacteria P. Aeruginosa and E. coli than riboflavin. The minimum effective blue light emitter power (450 nm) for the photodynamic inactivation of both P. aeruginosa and E. coli is 1024.2 mW / cm2. In groups of mice pre-vaccinated intraperitoneally with corpuscular photo inactivated vaccines based on suspensions of and E. coli at doses of 0.5-1.0 ml 4 log (CFU) / mL, 100% survival of all animals was observed, whereas in control group with the same type of vaccines but formalin-treated vaccines, it failed to achieve a 100% protective effect.
Lox’d in translation: Contradictions in the nomenclature surrounding common lox site mutants and their implications in experiments
Authors: Shaw Daniel , Serrano Luis , Lluch-Senar Maria
Published: July 2020

The Cre-Lox system is a highly versatile and powerful DNA recombinase mechanism, mainly used in genetic engineering to insert or remove desired DNA sequences. It is widely utilised across multiple fields of biology, with applications ranging from plants, to mammals, to microbes. A key feature of this system is its ability to allow recombination between mutant lox sites, traditionally named lox66 and lox71, to create a functionally inactive double mutant lox72 site. However, a large portion of the published literature has incorrectly annotated these mutant lox sites, which in turn can lead to difficulties in replication of methods, design of proper vectors, and confusion over the proper nomenclature. Here, we demonstrate common errors in annotations, the impacts they can have on experimental viability, and a standardised naming convention. We also show an example of how this incorrect annotation can induce toxic effects in bacteria that lack optimal DNA repair systems, exemplified byMycoplasma pneumoniae.

Data Summary

The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
The imprinted lncRNA Peg13 regulates sexual preference and the gender-specific brain transcriptome in mice
Authors: Keshavarz Maryam , Tautz Diethard
Published: July 2020

The authors have withdrawn their manuscript because of concerns about the data. Reanalysis of the original transcriptome data files did not confirm the analysis reported in the paper. The conclusions based on the gene sets that are regulated by Peg13 cannot be supported. In addition, original data files recovered for the behavioral data described in Table 2 show several inconsistencies with respect to the values reported in the corresponding supplemental data file S2. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Hippocampal dentate gyrus coordinates brain-wide communication and memory updating through an inhibitory gating
Authors: Caramés José María , Pérez-Montoyo Elena , Garcia-Hernandez Raquel , Canals Santiago
Published: July 2020

Distinct forms of memory processing are often causally identified with specific brain regions, but a key facet of memory processing includes linking separated neuronal populations. Using cell-specific manipulations of inhibitory neuronal activity, we discovered a key role of the dentate gyrus (DG) in coordinating dispersed neuronal populations during memory formation. In whole-brain fMRI and electrophysiological experiments, we found that parvalbumin (PV) interneurons in the DG control the functional coupling of the hippocampus within a wider network of neocortical and subcortical structures including the prefrontal cortex (PFC) and the nucleus accumbens (NAc). In a novel object-location task, regulation of PV interneuron activity enhanced or prevented memory encoding and, without effect upon the total number of task activated c-Fos+ cells, revealed a correlation between activated neuronal populations in the hippocampus-PFC-NAc network. These data suggest a critical regulatory role of PV interneurons in the dentate gyrus in brain-wide polysynaptic communication channels and the association of cell assemblies across multiple brain regions.
A ray-tracing algorithm for ab initio calculation of thermal load in undulator-based synchrotron beamlines
Authors: Rebuffi Luca , Shi Xianbo , Sanchez del Rio Manuel , Reininger Ruben
Published: July 2020

The OASYS suite and its powerful integration features are used to implement a ray-tracing algorithm to accurately calculate the thermal load in any component of an undulator-based synchrotron beamline. This is achieved by sampling and converting the SRW source of a given energy into a Shadow source and using the latter code to ray trace the full beamline. The accuracy of the algorithm is proved by reconstructing the full undulator radiation distribution through an aperture and comparing the result with direct calculaton of the total power using SRW. The algorithm is particularly suited to analyze cases with complex beamline layouts and optical elements, such as crystals, multilayers, and compound refractive lenses. Examples of its use to calculate the power load on elements of two of the feature beamlines at the Advanced Photon Source Upgrade Project and a comparison of the results with analytical calculations are presented.
The role of national culture in the relationship between microfinance outreach and sustainability: a correlated random effects approach
Authors: Zainuddin Mohammad , Mahi Masnun , Akter Shabiha , Yasin Ida Md.
Published: July 2020

Purpose

This study investigates the role of national culture between outreach and sustainability of microfinance institutions (MFIs). Despite microfinance's deep embeddedness in cultural contexts, research on the influence of national culture on MFI performance is rather sparse. This paper seeks to fill this gap and, based on cross-country microfinance data, attempts to explain the outreach-sustainability relationship in reference to cultural factors.

Design/methodology/approach

An unbalanced panel, consisting of 5,741 MFI-year observations of 1,232 MFIs from 43 countries in six regions, is drawn from the Microfinance Information Exchange (MIX) Market database. Two different econometric models are tested. Model 1 estimates the direct effect of outreach on sustainability, using a fixed-effects estimator. Model 2 examines the moderation effect of national culture on outreach-sustainability relationship, employing correlated random effects approach.

Findings

The results show that depth of outreach and financial sustainability of MFIs are negatively related, and the relationship is moderated by national culture. Power distance and uncertainty avoidance positively moderate the outreach-sustainability relationship, whereas individualism and masculinity negatively moderate the relationship.

Originality/value

The findings suggest that the national culture where MFIs are located plays an important contingent role in their performance and that the magnitude of the trade-off effect varies from culture to culture. The research thus provides further insight in the trade-off debate and contributes to literatures of both microfinance and cross-cultural management.
Hardware simulation of lane keeping assist based on sensor fusion
Authors: Cholis Basjaruddin Noor , Rakhman Edi , Adinugraha Fazrin
Published: July 2020

Purpose

Safety is one of the most crucial factors in transportation due to so many factors, including human-error, that might result in various small to fatal accidents. This is why lane keeping assist (LKA) is an important system that needs to be developed. LKA will prevent the vehicle from moving to another lane because the driver is negligent to maintain the direction of the vehicle.

Design/methodology/approach

In this study, LKA works using camera and ultrasonic sensors. The data coming from these two types of sensors are then fused to determine how should the car reacts to some certain situation so that it stays on the lane. The sensor fusion method was used to further ensure the car's safety.

Findings

The results of the hardware simulation show that LKA can successfully avoid the car from getting off the lane with safety index of 95% for high-speed mode and 100% for medium and low-speed mode; meanwhile on the use of ultrasonic sensor, the speed of the car is adjusted to the distance of the car's side disturbance.

Originality/value

This research has succeeded in simulating a sensor fusion–based LKA system.
Teacher trainees' understandings of mentoring within a Middle Eastern BEd program
Authors: Pattisson Joy
Published: July 2020

Purpos

The purpose of this study was to explore young Arab women's understandings of mentoring as part of a pre-service teacher training program both before and after an extended internship throughout which a collaborative approach to mentoring was practiced. It aimed to identify the opportunities and challenges such an approach would bring in the quest to support trainee teachers' professional development.

Design/methodology/approach

Data for this small-scale qualitative study were collected using a brainstorming class-based activity, semi-structured interviews and reflective journals. Data were analyzed using word clouds, and the identification of themes through the coding of transcripts.

Findings

The dominant findings in this study were that mentoring was perceived as emotional support, pedagogic and professional support, evaluation and relationship. While understandings of mentoring amongst participants did shift as a result of mentors adopting a collaborative approach, data indicated that the strength of cultural assumptions held by the participants hindered the rate of change, creating an obstacle to the desired outcome of increasing trainees' agency.

Originality/value

While perceptions of mentoring reported within this study indicate considerable overlap with those in other geographical and cultural contexts, closer examination of the data identified differences also. Without an understanding of the nature and influence of the social assumptions that underlie these differences, mentors who participate in culturally diverse mentor–trainee pairings can misinterpret an unwillingness of trainees to fully engage with the mentoring process and thus fail to provide the required scaffolding and support needed to maximize professional development.
The effects of indoor plants on customers' shopping decisions in a restaurant environment
Authors: Yildirim Kemal , Yildirim Kaya Nazlı Nazende , Olmus Ferdi
Published: July 2020

Purpose

The purpose of this paper is to focus on the effects of indoor plants on customers' shopping decisions in the restaurant environment.

Design/methodology/approach

The assumption of the research is that there is a relationship between restaurants where indoor plants are used and the customers' shopping decisions (restaurant entry and purchase). A hypothetical study was performed to test this assumption that was based on the digital images of two different restaurants (restaurant with and restaurant without indoor plants) modelled in a virtual environment. The Likert scale questionnaire used in this study was completed by 335 participants.

Findings

Results indicated that restaurants designed with indoor plants had a more positive effect on the shopping decisions of participants than restaurants designed without indoor plants. The statistically significant results between evaluations of customers and their demographic backgrounds were determined. The male participants with a 26–35 age range showed more positive opinions about the plant designed restaurants than female participants with a 36–55 age range. Also, higher education graduate participants showed more positive opinions about the plant designed restaurant than secondary education graduate participants.

Originality/value

This paper reveals a significant relationship between restaurant design and shopping decisions. Results of the study suggest that retailers and designers may be able to make easily stores more appealing for customers by designing them with indoor plants.
Characteristics of asynchronous online discussions in a graduate course: an exploratory study
Authors: Li Xiaofeng , Yu Yawen
Published: July 2020

Purpose

This paper aims to investigate the following questions: What are the types of discussion prompts in a fully online graduate course? What are the key characteristics of students’ discussion initial posts and replies in a fully online graduate course? In what ways, if any, do discussion prompts influence the types of initial posts and replies in discussion threads?

Design/methodology/approach

This study adopted a qualitative approach to explore the dynamics of students’ knowledge construction through using asynchronous discussion boards. A total of 20 discussion prompts and 115 discussion threads from nine archival discussion boards in a fully online library science course were collected and analyzed.

Findings

The findings identified open-ended, explanatory and reflective prompts in discussion boards. Students engaged in simply stating, paraphrasing, elaborating, extending, reflecting, socializing and sharing emotions in discussion posts. These findings highlighted the interconnectedness of reflection and socio-emotional interactions in a community of inquiry and pointed out their important roles to support richer and deeper online discussions. The study further observed linkages between the types of discussion prompts and the types of discussion posts.

Originality/value

This study addressed an urgent need to understand the use of online discussion boards in an emergency remote teaching condition in a pandemic. The findings of this study offered educators insights into evidence-based design recommendations for prompts to support students’ knowledge construction and deep learning through using discussion boards.
Correlation analysis between expectancy-value and achievement goals in MOOCs on energy sustainability: profiles with higher engagement
Authors: Romero-Rodríguez Luis M. , Ramírez-Montoya María Soledad , Valenzuela González Jaime Ricardo
Published: July 2020

Purpose

This paper aims to analyze the interrelationship that exists between expectancy-value and achievement goals as factors that are decisive for participants’ higher engagement in 12 massive open online courses (MOOCs) on energy sustainability and to determine the profile of participants achieving higher success rates.

Design/methodology/approach

A qualitative–quantitative study of correlational and descriptive scope is carried out on two instruments based on pre- and post-tests of 6,029 participants, which is followed by a qualitative data analysis distributed by code families to identify participants’ main motivations to take MOOCs.

Findings

The results showed a positive moderate-high correlation between expectancy-value and achievement goals, which means in a practical sense that the participants’ subjective estimates of the possibility of reaching their goals prior to the beginning of the course were fulfilled, as the intentionality of the subjects-participants was positive with respect to the contents imparted.

Practical implications

The profiles of participants with a higher tendency to successfully finish the course and with high rates of engagement share the following characteristics: having previously and successfully finished more than one MOOC; taking the MOOC for work purposes (promotion, seeking better job opportunities, etc.); and having intrinsic motivation, that is, not depending on external factors such as obligations and certifications.

Originality/value

This research suggests that there are pre-educational factors that define the trend of successful completion of MOOCs, based on expectancy-value (e.g. previous experiences with other MOOCs) and achievement goals (e.g. job improvement), with external motivational issues such as completion certificates being less prevalent in the learning intention.
Energy consumption analysis of glass house using electrochromic window in the subtropical region
Authors: Wang Yang , Lin Misheng , Xu Ke , Zhang Shuyang , Ma Hongwei
Published: July 2020

Purpose

Electrochromic window (ECW) has been gradually applied to building engineering in recent years. However, empirical study of this technology used in green building design is still lacking. This study aims to verify the lighting and energy-saving performance of ECW under a specific geographical environment.

Design/methodology/approach

The meditation pavilion of Jinwan new materials research institute in Zhuhai is taken for research object. Three kinds of sun-shading techniques, namely, ECW, Low-E window and ordinary glass window, with same specifications are selected as the building facade structure for simulation. Day lighting analysis, sun-shading performance and annual energy consumption are separately simulated in the same environment by the Autodesk Ecotect Analysis software. The energy-saving performance of ECW is obtained by comparisons.

Findings

Result shows that the shading performance of ECW is much better than ordinary window and Low-E window. When ECW is used in the east, west or top lighting interfaces of a building, about 40% of the total solar radiation can be reduced during daytime in summer. Taking the ordinary glass window as a basic reference, ECW can save about 90% of the annual energy consumption of the glass house. ECW can effectively reduce the annual refrigeration energy consumption of buildings in the subtropical region.

Practical implications

Reasonable use of ECW in the subtropical region can effectively reduce the annual energy consumption of buildings.

Originality/value

It is a precedent study to analyze the lighting performance and energy consumption of a glass house with ECW. The energy-saving characteristics and beautiful appearance of ECW shall make it a future green building technology.
The use of photovoice in evaluating a community-based rehabilitation (CBR) program: experiences from CBR volunteers in Namibia
Authors: Shumba Tonderai Washington , Haufiku Desderius , Amukugo Hans
Published: July 2020

Purpose

Qualitative participatory methods are needed to measure the effectiveness of the community-based rehabilitation (CBR) program in Namibia. The study explored the experiences of CBR volunteers in evaluating CBR program in Namibia through the use of photovoice. Further the study assessed the strengths and limitations of utilizing photovoice method as an assessment tool for CBR evaluation.

Design/methodology/approach

The study employed a qualitative, explorative, descriptive and contextual design. Data was collected through the photovoice method. Two CBR sites and 16 participants who were CBR volunteers were purposively selected. Data was collected and analysis was conducted simultaneously utilizing the photovoice method and themes were determined using WHO CBR matrix.

Findings

Various experiences were elicited regarding participants' experiences in line with the five components of the CBR matrix. Most experiences were reported regarding the health component, and the education component had the least experiences reported. Methodological strength and weaknesses as well as implications for practice are revealed. Further research can explore the benefits of combining photovoice with other data collection methods.

Research limitations/implications

The use of purposive sampling in selecting both CBR sites and participants limited wider representation of CBR program sites and persons with all disabilities in Namibia, respectively.

Originality/value

Sustainability of CBR programs depends on community ownership, empowerment and government funding. Photovoice is participatory and hence gives community ownership and empowerment. Evidence from photovoice can enable persons with disabilities to formulate action plans that can advocate their concerns with policymakers and justify more funding for CBR programs.