bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic variants drive altered epigenetic regulation of endotoxin tolerance in BTBR macrophages
Authors: Ciernia Annie Vogel , Link Verena M. , Careaga Milo , LaSalle Janine , Ashwood Paul
Published: February 2020

The BTBR T+Itpr3tf/J (BTBR) mouse has been used as a complex genetic model of Autism Spectrum Disorders (ASD). While the specific mechanisms underlying BTBR behavioral phenotypes are poorly understood, prior studies have implicated profound differences in innate immune system control of pro-inflammatory cytokines. Innate immune activation and elevated pro-inflammatory cytokines are also detected in blood of children with ASD. In this study, we examined how underlying BTBR genetic variants correspond to strain-specific changes in chromatin accessibility, resulting in a pro-inflammatory response specifically in BTBR bone marrow derived macrophages (BMDM). In response to repeated lipopolysaccharide (LPS) treatments, C57BL/6J (C57) BMDM exhibited intact endotoxin tolerance. In contrast, BTBR BMDM exhibited hyper-responsive expression of genes that were normally tolerized in C57. This failure in formation of endotoxin tolerance in BTBR was mirrored at the level of chromatin accessibility. Using ATAC-seq, we specifically identified promoter and enhancer regions with strain-specific differential chromatin accessibility both at baseline and in response to LPS. Regions with strain-specific differences in chromatin accessibility were significantly enriched for BTBR genetic variants, such that an average of 22% of the differential chromatin regions had at least one variant. Together, these results demonstrate that BTBR genetic variants contribute to altered chromatin responsiveness to endotoxin challenge and a failure in formation of tolerance, resulting in a hyper-responsive innate immunity in BTBR. These findings provide evidence for an interaction between complex genetic variants and differential epigenetic regulation of innate immune responses. Our findings also provide novel mechanistic insight into the complex genetic architecture and immune abnormalities observed in ASD.
The lockdown of Hubei Province causing different transmission dynamics of the novel coronavirus (2019-nCoV) in Wuhan and Beijing
Authors: Li Xinhai , Zhao Xumao , Sun Yuehua
Published: February 2020

Background

After the outbreak of novel coronavirus (2019-nCoV) starting in late 2019, a number of researchers have reported the predicted the virus transmission dynamics. However, under the strict control policy the novel coronavirus does not spread naturally outside Hubei Province, and none of the prediction closes to the real situation.

Methods and findings

We used the traditional SEIR model, fully estimated the effect of control measures, to predict the virus transmission in Wuhan, the capital city of Hubei Province, and Beijing. We forecast that the outbreak of 2019-nCoV would reach its peak around March 6±10 in Wuhan and March 20±16 in Beijing, respectively. The infectious population in Beijing would be much less (only 0.3%) than those in Wuhan at the peak of this transmission wave. The number of confirmed cases in cities inside Hubei Province grow exponentially, whereas those in cities outside the province increase linearly.

Conclusions

The unprecedented province lockdown substantially suspends the national and global outbreak of 2019-nCoV.
The GINS complex is required for the survival of rapidly proliferating retinal and tectal progenitor cells during zebrafish development
Authors: Varga Máté , Csályi Kitti , Bertyák István , Menyhárd Dóra K. , Poole Richard J. , Cerveny Kara L. , Kövesdi Dorottya , Barátki Balázs , Rouse Hannah , Vad Zsuzsa , Hawkins Thomas A. , Stickney Heather L. , Cavodeassi Florencia , Schwarz Quenten , Young Rodrigo M. , Wilson Stephen W.
Published: February 2020

Efficient and accurate DNA replication is particularly critical in stem and progenitor cells for successful proliferation and survival. The replisome, an amalgam of protein complexes, is responsible for binding potential origins of replication, unwinding the double helix, and then synthesizing complimentary strands of DNA. According to current models, the initial steps of DNA unwinding and opening are facilitated by the CMG complex, which is composed of a GINS heterotetramer that connects Cdc45 with the mini-chromosome maintenance (Mcm) helicase. In this work, we provide evidence that in the absence of GINS function DNA replication is cell autonomously impaired, and we also show thatgins1andgins2mutants exhibit elevated levels of apoptosis restricted to actively proliferating regions of the central nervous system (CNS). Intriguingly, our results also suggest that the rapid cell cycles during early embryonic development in zebrafish may not require the function of the GINS complex as neither Gins1 nor Gins2 seem to be present during these stages.
Wnt-regulated lncRNA discovery enhanced byin vivoidentification and CRISPRi functional validation
Authors: Liu Shiyang , Harmston Nathan , Glaser Trudy Lee , Wong Yunka , Zhong Zheng , Madan Babita , Virshup David M. , Petretto Enrico
Published: February 2020

Background

Wnt signaling is an evolutionarily conserved developmental pathway that is frequently hyperactivated in cancer. While multiple protein-coding genes regulated by Wnt signaling are known, the functional lncRNAs regulated by Wnt signaling have not been systematically characterized.

Results

We comprehensively mapped lncRNAs from an orthotopic Wnt-addicted pancreatic cancer model, identifying 3,633 lncRNAs, of which 1,503 were regulated by Wnt signaling. We found lncRNAs were much more sensitive to changes in Wnt signaling in xenografts than in cultured cells. To functionally validate Wnt-regulated lncRNAs, we performed CRISPRi screens to assess their role in cancer cell proliferation. Consistent with previous genome-wide lncRNA CRISPRi screens, around 1% (13/1,503) of the Wnt-regulated lncRNAs could modify cancer cell growthin vitro. This includedCCAT1andLINC00263, previously reported to regulate cancer growth. Using anin vivoCRISPRi screen, we doubled the discovery rate, identifying twice as many Wnt-regulated lncRNAs (25/1,503) that had a functional effect on cancer cell growth.

Conclusions

Our study demonstrates the value of studying lncRNA functionsin vivo, provides a valuable resource of lncRNAs regulated by Wnt signaling and establishes a framework for systematic discovery of functional lncRNAs.
Cognitive impairments in sporadic cerebral small vessel disease (SVD): a systematic review and meta-analysis of cohorts with stroke, dementia and non-clinical presentations of SVD
Authors: Hamilton Olivia KL , Backhouse Ellen V , Janssen Esther , Jochems Angela CC , Maher Caragh , Stevenson Anna J , Ritakari Tuula E , Xia Lihua , Deary Ian J , Wardlaw Joanna M
Published: February 2020

Background

Cognitive impairment is a key clinical feature of cerebral small vessel disease (SVD), but the full range of SVD-related cognitive impairments is unclear, and little is known about how they might vary across clinical and non-clinical manifestations of SVD.

Methods

In systematic searches of OVID MEDLINE, Embase, and PsychINFO from 1st January 1985 to 6th October 2019, we identified studies reporting cognitive test results for study participants with SVD and control participants without SVD. Using standardised group-level cognitive test data, we performed random effects meta-analyses in seven cognitive domains to test whether cognitive test scores differed between SVD and control groups. We conducted meta-regression analyses to test whether differences in age, education, or vascular risk factors between SVD and control groups, or whether different clinical manifestations of SVD (e.g. stroke, cognitive impairment, or non-clinical presentations) accounted for cognitive effect sizes.

Findings

Of 8562 studies identified, we included 69 studies from six continents, published in four languages. These studies included 3229 participants with SVD and 3679 controls. Meta-analyses demonstrated that on average, control groups outperformed SVD cohorts on cognitive tests in all cognitive domains examined: executive function (estimate: -0.928; 95%CI: -1.08, -0.78); processing speed (-0.885; -1.17, -0.60); delayed memory (-0.898; -1.10, -0.69); language (-0.808; -1.01, -0.60); visuospatial ability (-0.720; -0.96, -0.48); reasoning (-0.634; -0.93, -0.34); and attention (-0.622; -0.94, -0.31; all p≤0.001). Meta-regression analyses suggested that differences in years of education between SVD and control groups may account for a proportion of the differences in performance on tests of executive function, visuospatial ability and language, and that cohorts with cognitive impairments performed more poorly on tests of executive function, delayed memory and visuospatial ability than cohorts with stroke or non-clinical presentations of SVD.

Interpretation

Participants with SVD demonstrated poorer cognitive performance relative to control groups in all cognitive domains we examined. This effect was present for all presentations of SVD, reinforcing the need to test a range of cognitive domains in both clinical and research settings. Lower levels of education in SVD versus control participants may contribute to these effects, highlighting the need to account for educational level in the assessment of SVD-related cognitive impairment.

Funding

None.
Going off the rails: Impaired coherence in the speech of patients with semantic control deficits
Authors: Hoffman Paul , Cogdell-Brooke Lucy , Thompson Hannah E
Published: February 2020

The ability to speak coherently, maintaining focus on the topic at hand, is critical for effective communication and is commonly impaired following brain damage. Recent data suggests that executive processes that regulate access to semantic knowledge (i.e., semantic control) are critical for maintaining coherence during speech. To test this hypothesis, we assessed speech coherence in a case-series of fluent stroke aphasic patients with deficits in semantic control. Patients were asked to speak about a series of topics and their responses were analysed using computational linguistic methods to derive measures of their global coherence (the degree to which they spoke about the topic given) and local coherence (the degree to which they maintained a topic from one moment to the next). Compared with age-matched controls, patients showed severe impairments to global coherence and milder impairments to local coherence, suggesting that semantic control deficits give rise to being “led up the garden path”, i.e., one sentence automatically cueing another, with the topic becoming increasingly less relevant to the original question. Global coherence was strongly correlated with the patients’ performance on tests of semantic control, with poorer ability to maintain top-down global coherence being associated with greater semantic control deficits. Other aspects of speech production were also impaired but were not correlated with semantic control deficits. This is the first study to investigate the impact of semantic control impairments within a naturalistic setting, and indicates patients with these impairments are likely to find maintaining focus in everyday conversation difficult.
Par3A and Par3B orchestrate podocyte architecture by regulating RhoA levels
Authors: Koehler Sybille , Odenthal Johanna , Jess David Unnersjö , Höhne Martin , Jüngst Christian , Grawe Ferdi , Helmstädter Martin , Hagmann H. Henning , Walz Gerd , Bloch Wilhelm , Niessen Carien , Schermer Bernhard , Wodarz Andreas , Denholm Barry , Benzing Thomas , Iden Sandra , Brinkkoetter Paul Thomas
Published: February 2020

Glomerular diseases are a major cause for chronic kidney disorders. In the majority of cases podocyte injury is causative for disease development. Cytoskeletal rearrangements and morphological changes are hallmark features of podocyte injury and result in dedifferentiation and subsequent loss of podocytes. Here, we establish a link between components of the Par3 polarity complex and actin regulators, which are necessary to establish and maintain the podocytes architecture utilizing both, mouse andDrosophilamodels. We demonstrate that the two mammalian Par3 proteins, Par3A and Par3B, share redundant functions despite differing in their ability to interact with other components of the Par complex. Only simultaneous inactivation of both Par3 proteins causes a severe disease phenotype in mouse podocytes by regulating Rho-GTP levels involving the actin regulators Synaptopodin and CD2AP in an aPKC independent manner.
Assessing thein vitroresistance development in Enterovirus 71 in the context of combination antiviral treatment
Authors: Lanko Kristina , Shi Chenyan , Patil Shivaprasad , Delang Leen , Matthijnssens Jelle , Mirabelli Carmen , Neyts Johan
Published: February 2020

There are currently no antivirals available to treat infection with enterovirus A71 (EV-A71) or any other enterovirus. The extensively studied capsid binders select rapidly for drug-resistant variants. We here explore whether the combination of two direct-acting enterovirus inhibitors with a different mechanism of action may delay or prevent resistance development to the capsid binders. To that end, the in vitro dynamics of resistance development to the capsid binder pirodavir was studied either alone or in combination with (i) a viral 2C-targeting compound (SMSK_0213), (ii) a viral 3C-protease inhibitor (rupintrivir) or (iii) a viral RNA-dependent RNA polymerase (RdRp) inhibitor [7-deaza-2’C-methyladenosine (7DMA)]. We demonstrate that combining pirodavir with either rupintrivir or the nucleoside analogue 7DMA delays the development of resistance to pirodavir and that no resistance to the protease or polymerase inhibitor develops. The combination of pirodavir with the 2C inhibitor results in a double-resistant virus population. The deep sequencing analysis of resistant populations revealed that even though resistant mutations are present in less than 30% of the population, this still provides the resistant phenotype.
Alpha-ketoamides as broad-spectrum inhibitors of coronavirus and enterovirus replication
Authors: Zhang Linlin , Lin Daizong , Kusov Yuri , Nian Yong , Ma Qingjun , Wang Jiang , von Brunn Albrecht , Leyssen Pieter , Lanko Kristina , Neyts Johan , de Wilde Adriaan , Snijder Eric J. , Liu Hong , Hilgenfeld Rolf
Published: February 2020

The main protease of coronaviruses and the 3C protease of enteroviruses share a similar active-site architecture and a unique requirement for glutamine in the P1 position of the substrate. Because of their unique specificity and essential role in viral polyprotein processing, these proteases are suitable targets for the development of antiviral drugs. In order to obtain near-equipotent, broad-spectrum antivirals against alphacoronaviruses, betacoronaviruses, and enteroviruses, we pursued structure-based design of peptidomimetic α-ketoamides as inhibitors of main and 3C proteases. Six crystal structures of protease:inhibitor complexes were determined as part of this study. Compounds synthesized were tested against the recombinant proteases as well as in viral replicons and virus-infected cell cultures; most of them were not cell-toxic. Optimization of the P2 substituent of the α-ketoamides proved crucial for achieving near-equipotency against the three virus genera. The best near-equipotent inhibitors,11u(P2 = cyclopentylmethyl) and11r(P2 = cyclohexylmethyl), display low-micromolar EC50values against enteroviruses, alphacoronaviruses, and betacoronaviruses in cell cultures. In Huh7 cells,11rexhibits three-digit picomolar activity against Middle East Respiratory Syndrome coronavirus.
Fatty Acyl Availability Modulates Cardiolipin Composition and Alters Mitochondrial Function in HeLa Cells
Authors: Oemer Gregor , Edenhofer Marie-Luise , Lackner Katharina , Leman Geraldine , Koch Jakob , Lindner Herbert H. , Dubrac Sandrine , Zschocke Johannes , Keller Markus A.
Published: February 2020

The molecular assembly of cells depends not only on their balance between anabolism and catabolism, but to a large degree also on the building blocks available in the environment. For cultivated mammalian cells, this is largely determined by the composition of the growth medium used. Here we study the impact of medium lipids on mitochondrial membrane architecture and function by combining LC-MS/MS lipidomics and functional tests with lipid supplementation experiments in an otherwise serum- and lipid-free cell culture model. We demonstrate that the composition of mitochondrial cardiolipins (CL) strongly depends on the lipid environment in cultured cells and prefers the incorporation of essential linoleic acid over other fatty acids. Simultaneously, the mitochondrial respiratory complex I activity was altered, whereas the matrix-localized enzyme citrate synthase was unaffected. This suggests a link between membrane composition and respiratory capacity. In summary, we find a strong dependency of central mitochondrial features on the type of lipids contained in the growth medium. Thus, this underlines the importance of considering these factors when using and establishing cell culture models in biomedical research.

Abstract Figure
CRISPR-Cas12a exploits R-loop asymmetry to form double-strand breaks
Authors: Cofsky Joshua C. , Karandur Deepti , Huang Carolyn J. , Witte Isaac P. , Kuriyan John , Doudna Jennifer A.
Published: February 2020

Most type V CRISPR-Cas interference proteins use a single RuvC active site to make RNA-guided breaks in double-stranded DNA substrates, an activity essential for both bacterial immunity and genome editing applications. The best-studied of these enzymes, Cas12a, initiates DNA cutting by forming a 20-nucleotide R-loop in which the guide RNA displaces one of the DNA strands of a double-helical substrate, positioning the DNase active site for first-strand cleavage. However, crystal structures and biochemical data have not explained how the second strand is cut to complete the double-strand break. Here, we show that Cas12a-mediated R-loop formation destabilizes DNA at the second-strand cleavage site, which is located outside of the R-loop structure and beyond the 3′ end of the guide RNA. Chemical and fluorescent DNA probes reveal that this destabilization is an intrinsic feature of DNA flanking the RNA-3′ side of R-loops and does not require direct protein interactions. Interestingly, DNA flanking the RNA-5′ side of R-loops is not intrinsically unstable. This asymmetry in R-loop structure may explain the uniformity of guide RNA architecture and the single-active-site cleavage mechanism that are fundamental features of all type V CRISPR-Cas systems.
Genetic predictors of participation in optional components of UK Biobank
Authors: Tyrrell Jessica , Zheng Jie , Beaumont Robin , Hinton Kathryn , Richardson Tom G , Wood Andrew R , Smith George Davey , Frayling Timothy M , Tilling Kate
Published: February 2020

Large studies (e.g. UK Biobank) are increasingly used for GWAS and Mendelian randomization (MR) studies. Selection into and dropout from studies may bias genetic and phenotypic associations. We examine genetic factors affecting participation in four optional components in up to 451,306 UK Biobank participants. We used GWAS to identify genetic variants associated with participation, MR to estimate effects of phenotypes on participation, and genetic correlations to compare participation bias across different studies. 32 variants were associated with participation in one of the optional components (P<6×10-9), including loci with known links to intelligence and Alzheimer’s disease. Genetic correlations demonstrated that participation bias was common across studies. MR showed that longer educational duration, older menarche and taller stature increased participation, whilst higher levels of adiposity, dyslipidaemia, neuroticism, Alzheimer’s and schizophrenia reduced participation. Our effect estimates can be used for sensitivity analysis to account for selective participation biases in genetic or non-genetic analyses.
Classification and characterisation of livestock production systems in northern Tanzania
Authors: de Glanville W.A. , Davis A. , Allan K.J. , Buza J. , Claxton J.R. , Crump J.A. , Halliday J.E.B. , Johnson P.C.D. , Kibona T.J. , Mmbaga B.T. , Swai E.S. , Uzzell C. , Yoder J. , Sharp J. , Cleaveland S.
Published: February 2020

Livestock keepers in sub-Saharan Africa face a growing range of pressures, including climate change, land loss, restrictive policies, and population increase. Widespread adaptation in response to such pressures can lead to the emergence of new, non-traditional typologies of livestock production.

We sought to characterise livestock production systems in northern Tanzania, a region undergoing rapid social, economic, and environmental change. Questionnaire and spatial data were collected from 404 livestock-keeping households in 21 villages in Arusha and Manyara Regions in 2016. Multiple factor analysis and hierarchical cluster analysis were used to classify households into livestock production systems based on household-level characteristics. Indicators of vulnerability, including household-level reports of hunger, illness, livestock loss, land loss and crop losses were compared between production systems.

Three distinct clusters emerged through this process. The ethnic, environmental and livestock management characteristics of households in each cluster broadly mapped onto traditional definitions of ‘pastoral’, ‘agro-pastoral’ and ‘smallholder’ livestock production in the region, suggesting that this quantitative classification system is complementary to more qualitative classification methods. Our findings also suggest that traditional systems of livestock production continue to persist in northern Tanzania. Nonetheless, we found indicators of substantial change within livestock production systems, most notably the adoption of crop agriculture in the majority of pastoral households. Smallholder households were less likely than either pastoral or agro-pastoral households to report hunger, illness, and livestock, land or crop losses.

Livelihoods that rely solely on livestock are relatively rare in northern Tanzania, which represents an important shift in production in the region, particularly among pastoralists. Policy initiatives to improve household and community well-being should recognise the continuing distinctiveness of traditional livestock production systems in the region.
Characterization of transgenic mouse lines for selectively targeting glial cells in dorsal root ganglia
Authors: Rabah Yasmine , Rubino Bruna , Moukarzel Elsie , Agulhon Cendra
Published: February 2020

The importance of glial cells in the modulation of neuronal processes is now generally accepted. In particular, enormous progress in our understanding of astrocytes and microglia physiology in the central nervous system (CNS) has been made in recent years, due to the development of genetic and molecular toolkits. However, the roles of satellite glial cells (SGCs) and macrophages – the peripheral counterparts of astrocytes and microglia – remain poorly studied despite their involvement in debilitating conditions, such as pain. Here, we characterized in dorsal root ganglia (DRGs), different genetically-modified mouse lines previously used for studying astrocytes and microglia, with the goal to implement them for investigating DRG SGC and macrophage functions. Although SGCs and astrocytes share some molecular properties, most tested transgenic lines were found to not be suitable for studying selectively a large number of SGCs within DRGs. Nevertheless, we identified and validated two mouse lines: (i) a CreERT2 recombinase-based mouse line allowing transgene expression almost exclusively in SGCs and in the vast majority of SGCs, and (ii) a GFP-expressing line allowing the selective visualization of macrophages. In conclusion, among the tools available for exploring astrocyte functions, a few can be used for studying selectively a great proportion of SGCs. Thus, efforts remain to be made to characterize other available mouse lines as well as to develop, rigorously characterize and validate new molecular tools to investigate the roles of DRG SGCs, but also macrophages, in health and disease.
Acute inhibition of centriolar satellite function and positioning reveals their functions at the primary cilium
Authors: Aydin Ozge Z. , Taflan Sevket Onur , Gurkaslar Can , Firat-Karalar Elif Nur
Published: February 2020

Centriolar satellites are dynamic, membrane-less granules composed of over 200 proteins. They store, modify, and traffic centrosome and primary cilium proteins, and help to regulate both the biogenesis and some functions of centrosomes and cilium. In most cell types, satellites cluster around the perinuclear centrosome, but their integrity and cellular distribution are dynamically remodeled in response to different stimuli, such as cell cycle cues. Dissecting the specific and temporal functions and mechanisms of satellites and how these are influenced by their cellular positioning and dynamics has been challenging using genetic approaches, particularly in ciliated and proliferating cells. To address this, we developed a chemical-based trafficking assay to rapidly and efficiently redistribute satellites to either the cell periphery or center, and fuse them into stable clusters in a temporally-controlled way. Induced satellite clustering at either the periphery or center resulted in antagonistic changes in the pericentrosomal levels of a subset of proteins, revealing a direct role for their positioning in protein targeting and sequestration. Systematic analysis of the interactome of peripheral satellite clusters revealed enrichment of proteins implicated in cilium biogenesis and mitosis. Importantly, inducible peripheral satellite targeting in ciliated cells revealed a function for satellites not just for efficient cilium assembly, but also in the maintenance of steady-state cilia and in cilia disassembly by regulating the structural integrity of the ciliary axoneme. Finally, although perturbing satellite distribution and dynamics inhibited their mitotic dissolution, it did not cause mitotic defects. Collectively, our results for the first time showed a direct link between satellite functions and their pericentrosomal clustering, and provided a new tool for probing temporal satellite functions in different contexts.
EphrinB1 modulates glutamatergic inputs into POMC neurons and controls glucose homeostasis
Authors: Gervais Manon , Picard Alexandre , Thorens Bernard , Croizier Sophie
Published: February 2020

Proopiomelanocortin (POMC) neurons are major regulators of energy balance and glucose homeostasis. In addition to being regulated by hormones and nutrients, POMC neurons are controlled by glutamatergic input originating from multiple brain regions. However, the factors involved in the formation of glutamatergic inputs and how they contribute to bodily functions remain largely unknown. Here, we show that during the development of glutamatergic inputs, POMC neurons exhibit enriched expression of theEfnb1(EphrinB1) andEfnb2(EphrinB2) genes, which are known to control excitatory synapse formation.In vitrosilencing andin vivoloss ofEfnb1orEfnb2in POMC neurons decreases the amount of glutamatergic inputs into these neurons. We found that mice lackingEfnb1in POMC neurons display impaired glucose tolerance due to blunted vagus nerve activity and decreased insulin secretion. However, mice lackingEfnb2in POMC neurons showed no deregulation of insulin secretion and only mild alterations in feeding behavior and gluconeogenesis. Collectively, our data demonstrate the role of ephrins in controlling excitatory input amount into POMC neurons and show an isotype-specific role of ephrins on the regulation of glucose homeostasis and feeding.
Transcriptional control of apical protein clustering drivesde novocell polarity establishment in the early mouse embryo
Authors: Zhu Meng , Wang Peizhe , Handford Charlotte E. , Na Jie , Zernicka-Goetz Magdalena
Published: February 2020

The establishment of cell polarityde novoin the early mammalian embryo triggers the transition from totipotency to differentiation to generate embryonic and extra-embryonic lineages. However, the molecular mechanisms governing the timing of cell polarity establishment remain unknown. Here, we identify stage-dependent transcription of Tfap2c and Tead4 as well as Rho GTPase signaling as key for the onset of cell polarization. Importantly, advancing their activity can induce precocious cell polarization and ectopic lineage differentiation in a cell-autonomous manner. Moreover, we show that the asymmetric clustering of apical proteins, regulated by Tfap2c-Tead4, and not actomyosin flow, mediates apical protein polarization. These findings identify the long-sought mechanism for the onset of polarization and the first lineage segregation in the mouse embryo.
Escargotis involved in labial and antennal imaginal disc development through two different developmental pathways
Authors: Rosales-Bravo Fernando , Sánchez-Díaz Iván , Reynaud Enrique , Narváez-Padilla Verónica
Published: February 2020

In insects, imaginal discs form the adult structures. Imaginal discs are formed by two epithelial layers, the lower disc proper columnar epithelium and the upper peripodial squamous epithelium (also known as peripodial membrane). During morphogenesis and metamorphosis there is a complex crosstalk between these two epithelia that defines the final size and form of the adult organs. In this work we found that in the antennal disc, the dosage of the transcriptional factor Escargot (Esg) regulates the extension of the peripodial epithelium. A reduction in Esg expands the peripodial domain at the expense of the antennal disc proper causing a distortion of the anteroposterior compartments resulting in malformations or duplications of antennae and maxillary palps. In the labial disc, a different morphogenetic pathway controls its development, and loss ofesgproduces a complete loss of the proboscis through a pathway that involvesdpp.

Summary statement

The geneescargotregulates proboscis, maxillary palps and antennae development inDrosophila melanogasterthrough two different developmental pathways: one involving cell adhesion proteinDE-cadherin and another through the signaling molecule decapentaplegic.
Odd-skippedcontrols neurite morphology and affect cell survival inDrosophila Melanogaster CNS
Authors: Lynn Yeoh Sue , Letzel Alina , Somerfield Clemence Bernard Hannah , Kyser Kyle , Lin Emily , Roper Amanda , Yuan Yucen , Saunders Chloe , Farag Mina , Colourous Samual , Larsen Camilla W.
Published: February 2020

The transcription factorOdd-skippedhas been implicated in many developmental processes inDrosophila melanogaster.Odd-skippedis expressed in a small cluster of neurons (Slater, Levy et al.) in the developing and adult CNS but its role in neurogenesis has so far not been addressed. Here we show thatOdd-skippedplays a pivotal role in neurite growth and arborization during development. Loss-of-Odd-skippedfunction prevents neurite outgrowth whereas over and miss-expression causes neurite growth and arborization defects. In addition, miss-expression ofOdd-skippedcan induce cell death in some neural sub types. The neurite growth and arborization defects associated withOdd-skippedover expression correlates with a reduction in the pre-synaptically targeted protein Bruchpilot in axonal arbours suggesting an overall decrease in Odd neural synapse formation. This is supported by behavioural data showing that larvae in whichOdd-skippedis overexpressed behave similarly to larvae in which Odd neurons are silenced showing that increasingOdd-skippedprotein levels affect neural function. Finally, we demonstrate that using RNAi againstOdd-skippeddoes not knock downOdd-skippedprotein but instead cause an increase in protein levels compared to control larvae. This data demonstrates that RNAi can cause up-regulation of protein levels highlighting the importance of verifying protein levels when using RNAi approaches for knock-down.
On the use of the Obara–Saika recurrence relations for the calculation of structure factors in quantum crystallography
Authors: Genoni Alessandro
Published: February 2020

Modern methods of quantum crystallography are techniques firmly rooted in quantum chemistry and, as in many quantum chemical strategies, electron densities are expressed as two-centre expansions that involve basis functions centred on atomic nuclei. Therefore, the computation of the necessary structure factors requires the evaluation of Fourier transform integrals of basis function products. Since these functions are usually Cartesian Gaussians, in this communication it is shown that the Fourier integrals can be efficiently calculated by exploiting an extension of the Obara–Saika recurrence formulas, which are successfully used by quantum chemists in the computation of molecular integrals. Implementation and future perspectives of the technique are also discussed.
Modified multiport Luo converter integrated with renewable energy sources for electric vehicle applications
Authors: Kamaraj Vibha , Nallaperumal Chellammal
Published: February 2020

Purpose

Growing concerns about the depletion of fossil fuels and global awareness about the environmental pollution motivate the automobile industries to search for an alternative transportation system such as hybrid vehicular systems, plug-in hybrid vehicular systems and electric vehicular systems. To have carbon emission-free environment, these electric vehicles use renewable sources, such as solar and fuel cell, as primary source of supply. As these renewable sources are intermittent in nature, an energy buffer such as battery or super capacitor is required for the smooth supply and regulation of load power. The current electric vehicle systems use multistage power electronic converters for energy transfer. Therefore, this paper aims to propose a modified multiport converter based on Luo topology.

Design/methodology/approach

The suggested converter is developed based on Luo topology using voltage lift technique.

Findings

Most of the research presents buck boost converter as power electronic interface in electric vehicle applications. Whereas the converter proposed in this paper is based on Luo topology. It exhibits the features of single stage conversion between the input output ports, with less ripple, high efficiency, fewer components and centralized control for effective power management.

Originality/value

The presented converter can work in all possible modes such as buck and boost modes independently or simultaneously during various operating conditions of electric vehicles. During buck/boost mode, the primary source PV (Photovoltaic) in the converter provides the required power for the vehicle and charges the secondary source, i.e. battery, whereas during boost mode the battery supplies the sufficient power to load.
Augmenting training–learning experience by design: a conceptual framework
Authors: Shree Sonal
Published: February 2020

Purpose

The purpose of this paper is to explore the possibility of designing training sessions on the basis of a dramatic structure and inclusion of contextual narrative for facilitating transfer of learning. The role of stimulating curiosity in this process has also been scanned under the lens of neurobiological insights.

Design/methodology/approach

The paper theoretically develops a framework through an integrative literature review to examine the prospect of enhanced learner engagement through structure, narrative and some interdisciplinary theories, namely, the gap theory of curiosity and the peak end theory.

Findings

A contextual story-based training method designed on the basis of a dramatic plot structure can leverage on the learners’ emotions for engaging learning sessions and retention of content. Such design offers potential to improvise and strengthen the overall training module design and delivery mechanism. The outcome is seen through enhanced peak moments of curiosity and satisfaction, thus enriching the overall training–learning process.

Research limitations/implications

The study is theory based and non-empirical which does not give it a ground to make generalised statements and conclusions. This factor, however, paves the way for future research in the allied areas such as empirical testing of the framework by identifying and testing the variables and other contextual and causal factors.

Practical implications

The suggested framework has practical implications for Learning and Development managers as well as academies. The conceptual framework provided in this work can lend some unique insights towards strengthening the training–learning process.

Originality/value

Although the concept of using stories for training is not new, this study contributes by proposing a new theoretical framework that examines together the elements of sound dramatic structure and a story-based training method. Such a design, conceived by taking into account an understanding of the working mind, can influence the overall experience of achieving positive training–learning results.
Environmental social work
Authors: Rambaree Komalsingh
Published: February 2020

Purpose

Environmental social work (ESW) is an approach and a perspective in social work focusing on ecological and environmental sustainability and justice within the context of sustainable development (SD). This study aims to analyse students’ reflective tasks on challenges for ESW education and practice from a critical theory perspective. The purpose of this study is to discuss the implications of the findings for accelerating the implementation of SD in social work curricula.

Design/methodology/approach

The research participants comprised 49 master level students from four different cohorts studying the course “Social Work and Sustainable Development” at the University of Gävle, Sweden. The sample comprised only those students who had completed at least one of the three non-mandatory reflective tasks that were set within the course. The reflective tasks of the research participants were gathered as data for this study. A qualitative methodological approach with the help of ATLAS-ti V8.4 was used to analyse the gathered data.

Findings

This study discusses three primary results, which are categorised as “Being Boxed”, “Safe and Saviour Sweden” and “Politics and Power”. Based on the results, this study argues for a transformative and emancipatory pedagogy (TEP) in the teaching and learning of ESW to accelerate the implementation of holistic SD within the social work curriculum.

Research limitations/implications

This study is mainly based on the analysis of “problematic” discourses of some of the students. The majority of the students and their respective discourses are not considered. Moreover, it would have been interesting, and probably enlightening to explore the background of the students (such as gender, ethnicity and religion) and any concomitant beliefs or prejudices (whether consciously held or otherwise) that would need to be addressed for an effective social work outcome. For ethical reasons, the background of the students was not recorded and analysed in this study.

Practical implications

Based on the results, this study argues for TEP in catalysing environmentalism within the social work curricula.

Social implications

Social workers have a political mandate from their professional ethics to work for the protection of the planet and for the well-being of all – including non-humans. This study therefore argues for ESW education within social work curricula in promoting SD through social work practice.

Originality/value

Within the context of SD, there is a global call for social work education to shift from an anthropocentric to an eco-centric paradigm. However, ESW education is still in its infancy stage and very few universities are focusing in this particular area. This study therefore brings an important and well-needed layer of empirical evidence in considering the implications for catalysing environmentalism within the social work curricula.
Local versus global food consumption: the role of brand authenticity
Authors: Riefler Petra
Published: February 2020

Purpose

This paper aims at investigating the contemporary trend toward regional consumption from the perspective of consumers’ search for brand authenticity. In particular, the paper joins literature on brand authenticity from the marketing literature and literature on the local food movement to investigate consumers’ response to authenticity claims in the competition of local and global food brands.

Design/methodology/approach

The paper engages in a series of three experimental studies; one of which uses a Becker–DeGroot–Marschak lottery to assess individuals’ willingness to pay for authenticity claims of (non)global brands.

Findings

Findings show that authenticity perceptions lead to higher brand value independent of brand globalness; while global brands can mitigate competitive disadvantages in localized consumer markets by actively authenticating their brand image.

Originality/value

This paper reveals the usefulness of authentic brand positioning for global beverage brands when competing with local beverage brands to overcome the liability of globalness. To sustainably benefit from the local food movement, local brands thus will require to build up brand images beyond associations of mere authenticity.
Mobile and stationary eye tracking comparison – package design and in-store results
Authors: Pentus Kristian , Ploom Kerli , Mehine Tanel , Koiv Madli , Tempel Age , Kuusik Andres
Published: February 2020

Purpose

This paper aims to test the similarity of the results of on-screen eye tracking compared to mobile eye tracking in the context of first fixation location on stimuli.

Design/methodology/approach

Three studies were conducted altogether with 117 participants, where the authors compared both methods: stationary eye tracking (Tobii Pro X2-60) and mobile eye tracking (Tobii Pro Glasses 2).

Findings

The studies revealed that the reported average first fixation locations from stationary and mobile eye tracking are different. Stationary eye tracking is more affected by a centre fixation bias. Based on the research, it can be concluded that stationary eye tracking is not always suitable for studying consumer perception and behaviour because of the centre viewing bias.

Research limitations/implications

When interpreting the results, researchers should take into account that stationary eye tracking results are affected by a centre fixation bias. Previous stationary eye tracking research should be interpreted with the centre fixation bias in mind. Some of this previous work should be retested using mobile eye tracking. If possible small-scale pilot studies should be included in papers to show that the more appropriate method, less affected by attention biases, was chosen.

Practical implications

Managers should trust research where the ability of package design to attract attention on a shelf is tested using mobile eye tracking. The authors suggest using mobile eye tracking to optimise store shelf planograms, point-of-purchase materials, and shelf layouts. In package design, interpretations of research using stationary eye tracking should consider its centre fixation bias. Managers should also be cautious when interpreting previous stationary eye tracking research (both applied and scientific), knowing that stationary eye tracking is more prone to a centre fixation bias.

Originality/value

While eye tracking research has become more and more popular as a marketing research method, the limitations of the method have not been fully understood by the field. This paper shows that the chosen eye tracking method can influence the results. No such comparative paper about mobile and stationary eye tracking research has been done in the marketing field.
Impact of contractors’ opportunism on construction project transaction costs
Authors: Ikuabe Matthew , Oke Ayodeji Emmanuel , Aigbavboa Clinton
Published: February 2020

Purpose

There is a growing concern of the non-balance of the final output of construction works in comparison the financial resources invested with during the course of construction projects. One propelling factor to this is the opportunistic disposition often sought out by construction contractors. This study aims to investigate the relationship between construction contractors’ opportunism and construction project transaction costs from the viewpoint of construction professionals.

Design/methodology/approach

Questionnaire survey was deployed in eliciting responses from construction professionals. A total of 337 questionnaires were distributed and 264 were retrieved and deemed fit for analysis. Methods of data analysis used for the study are Mean Item Score, Kruskal–Wallis H-test, Student Newman Kauls Post Hoc Test, Factor Analysis, Spearman Rank Correlation and Regression Analysis.

Findings

The study showed that the most-ranked factor influencing contractors’ opportunism that affects transaction cost is “Unclear scope of work”. Revealed from the study is the differing view of construction professionals of the effect of contractors’ opportunism on transaction costs. Equally revealed through Spearman correlation analysis is the potent effect that contractors’ opportunism has on transaction costs. Likewise, the study established that there is a discovered difference among construction professionals’ perceived effect of contractors’ opportunism on construction transaction costs.

Originality/value

The study establishes the nexus between construction contractors’ opportunistic disposition and construction transaction costs, which are shown to be highly correlated. The study went further to recommend that efforts should be made to ensure that issues like contract documentation should be well and appropriately carried out; roles and responsibilities of stakeholders should be well defined so as to fully keep all parties to a contract abreast with the expectations of their duties in relation to the project objectives.
Effects of high‐pressure processing on fungi spores: Factors affecting spore germination and inactivation and impact on ultrastructure
Authors: Pinto Carlos A. , Moreira Sílvia A. , Fidalgo Liliana G. , Inácio Rita S. , Barba Francisco J. , Saraiva Jorge A.
Published: February 2020

Food contamination with heat‐resistant fungi (HRF), and their spores, is a major issue among fruit processors, being frequently found in fruit juices and concentrates, among other products, leading to considerable economic losses and food safety issues. Several strategies were developed to minimize the contamination with HRF, with improvements from harvesting to the final product, including sanitizers and new processing techniques.

Considering consumers’ demands for minimally processed, fresh‐like food products, nonthermal food‐processing technologies, such as high‐pressure processing (HPP), among others, are emerging as alternatives to the conventional thermal processing techniques. As no heat is applied to foods, vitamins, proteins, aromas, and taste are better kept when compared to thermal processes. Nevertheless, HPP is only able to destroy pathogenic and spoilage vegetative microorganisms to levels of pertinence for food safety, while bacterial spores remain. Regarding HRF spores (both ascospores and conidiospores), these seem to be more pressure‐sensible than bacterial spores, despite a few cases, such as the ascospores of Byssochlamys spp., Neosartorya spp., and Talaromyces spp. that are resistant to high pressures and high temperatures, requiring the combination of both variables to be inactivated.

This review aims to cover the literature available concerning the effects of HPP at room‐like temperatures, and its combination with high temperatures, and high‐pressure cycling, to inactivate fungi spores, including the main factors affecting spores’ resistance to high‐pressure, such as pH, water activity, nutritional composition of the food matrix and ascospore age, as well as the changes in the spore ultrastructure, and the parameters to consider regarding their inactivation by HPP.