bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutant huntingtin exon-1 impaired GTPCH and DHFR expression in plants and mice
Authors: Hung Chiu-Yueh , Zhu Chuanshu , Kittur Farooqahmed S. , He Maotao , Arning Erland , Zhang Jianhui , Johnson Asia J. , Jawa Gurpreet S. , Thomas Michelle D. , Ding Tomas T. , Xie Jiahua
Published: May 2022

Pathophysiology associated with Huntington’s disease (HD) has been studied extensively in various cell and animal models since the 1993 discovery of the mutant huntingtin (mHtt) with abnormally expanded polyglutamine (polyQ) tracts as the causative factor. However, the sequence of early pathophysiological events leading to HD still remains elusive. To gain new insights into the polyQ-induced early pathogenic events, we expressed Htt exon1 (Httex1) with a normal (21), or an extended (42 or 63) number of polyQ in tobacco plants, which lack an Htt ortholog to avoid any associated effects from endogenous Htt. Here, we show that transgenic plants accumulated Httex1 proteins with corresponding polyQ tracts, and that mHttex1 induced protein aggregation and affected plant growth, especially root and root hair development, in a polyQ length-dependent manner. Quantitative proteomic analysis of young roots from severely affected Httex1Q63 and unaffected Httex1Q21 plants showed that the most impaired protein by polyQ63 is a GTP cyclohydrolase I (GTPCH) along with many its related one-carbon (C1) metabolic pathway enzymes. GTPCH is a key enzyme involved in folate biosynthesis in plants and tetrahydrobiopterin (BH4) biosynthesis in mammals. Validating studies in 4-week-old R6/2 HD mice expressing a mHttex1 showed reduced levels of GTPCH and dihydrofolate reductase (DHFR, a key folate utilization/alternate BH4 biosynthesis enzyme), and impaired C1 and BH4 metabolisms. Our findings from mHttex1 plants and mice reveal impaired expressions of GTPCH and DHFR and contribute to a better understanding of mHtt-altered C1 metabolism and C1 interconnected BH4 metabolism leading to the pathogenesis of HD.
Effect of pressure insole sampling frequency on peak force accuracy during running
Authors: Elstub L.J. , Grohowski L.M. , Wolf D.N. , Owen M.K. , Noehren B. , Zelik K.E.
Published: May 2022

Pressure sensing insoles enable us to estimate forces under the feet during activities such as running, which can provide valuable insight into human movement. Pressure insoles also afford the opportunity to collect more data in more representative environments than can be achieved in laboratory studies. One key challenge with real-world use of pressure insoles is limited battery life which restricts the amount of data that can be collected on a single charge. Reducing sampling frequency is one way to prolong battery life, at the cost of decreased measurement accuracy, but this trade-off has not been quantified, which hinders decision-making by researchers and developers. Therefore, we characterized the effect of decreasing sampling frequency on peak force estimates from pressure insoles (Novel Pedar, 100 Hz) across a range of running speeds and slopes. Data were downsampled to 50, 33, 25, 20, 16 and 10 Hz. Force peaks were extracted due to their importance in biomechanical algorithms trained to estimate musculoskeletal forces and were compared with the reference sampling frequency of 100 Hz to compute relative errors. Peak force errors increased exponentially from 0.7% (50 Hz) to 9% (10 Hz). However, peak force errors were <3% for all sampling frequencies down to 20 Hz. For some pressure insoles, sampling rate is inversely proportional to battery life. Therefore, these findings suggest that battery life could be increased up to 5x at the expense of 3% errors. These results are encouraging for researchers aiming to deploy pressure insoles for remote monitoring or in longitudinal studies.
Genetic, vocal, and body size divergence across the Northern Peruvian Low supports two species within the Masked Flowerpiercer (Diglossa cyanea)
Authors: Martínez-Gómez Silvia C. , Lara Carlos Esteban , Remsen J. V. , Brumfield Robb T. , Cuervo Andrés M.
Published: May 2022

Populations that become genetically isolated by geographical barriers may express phenotypic divergence more strongly in some traits than in others. Even when genetic differentiation among isolated populations accumulates at a rapid rate, this may not be reflected in phenotypic differentiation. This decoupling of trait divergence from genetic divergence has been found in multiple Andean bird lineages that occupy latitudinally long, linear ranges that are fragmented by ecological and topographic barriers. One of these montane birds is Diglossa cyanea (Thraupidae; Masked Flowerpiercer), a species with a distribution bisected by valleys and lowlands. Across these dispersal barriers one finds subspecies that differ only in subtle but diagnostic phenotypic differences. We evaluated genetic and phenotypic divergence throughout its distribution and found support for two distinct lineages sharply separated by the Maraňón River valley at the Northern Peruvian Low (NPL). Specifically, we found that the two populations from the opposite sides of the NPL show deep divergence in mitochondrial DNA (mtDNA; ~6.7% uncorrected p distance, n = 122), in song structure (exclusive final notes in southern populations, n = 88), and in wing length (longer wings in the southern population, n = 364). No genetic variation or song structure was observed within the large range of the southern group (from the NPL to central Bolivia) or within all northern populations (from the NPL to Venezuela). Moreover, these two lineages are possibly paraphyletic with respect to D. caerulescens (Bluish Flowerpiercer). Our results suggest that the southern taxon, D. c. melanopis, should be recognized as a species-level taxon, distinct from a redefined D. cyanea. We highlight the need to continue amassing complementary suites of datasets from field observations and experiments, laboratory analyses, and collection-based assessments, to better characterize the evolutionary history and taxonomic diversity of Neotropical montane birds.
mRNA-based vaccines against SARS-CoV-2 do not stimulate interferon stimulatory gene expression in individuals affected by Aicardi Goutières Syndrome
Authors: Takanohashi Asako , Alameh Mohamad-Gabriel , Woidill Sarah , Hacker Julia , Davis Benjamin , Helman Guy , Gavazzi Francesco , Adang Laura , D’Aiello Russell , Winters Patrick , Cordova Devon , Khandaker Taibeen , Ni Houping , Tam Ying , Lin Paulo , Weissman Drew , Shults Justine , Vanderver Adeline
Published: May 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses threats to individuals with rare disease, in part because so little is known about the impact of COVID-19 infection and vaccination safety in rare disease populations. Of particular concern, given the overlap in disease manifestations and interferon dysregulation, are a group of heritable autoinflammatory conditions called type I interferonopathies. The most common of these, Aicardi Goutières Syndrome (AGS), is caused by altered nucleic acid metabolism and sensing, resulting in additional concerns surrounding the use of mRNA vaccination approaches. To determine whether mRNA vaccines induce an interferon response in AGS, we applied mRNA SARS-CoV-2 vaccines to whole blood samples and assessed internalization and interferon signaling gene expression responses to the mRNA. In all cases (11 AGS and 11 control samples), interferon signatures did not significantly increase from baseline, regardless of baricitinib treatment status in the AGS subjects, and were even decreased, when using codon optimized SARS-CoV-2 di-proline modified spike sequence (S2P). Internalization of S2P in human dendritic cells was verified by Western Blot, and in control and AGS blood cells was verified by Luciferase activity. Although numbers of tested samples in this rare disease are small, based on these findings, we suggest that COVID vaccination is unlikely to directly stimulate the interferon signaling gene expression in AGS patients via response to mRNA internalization. The in vitro nature of this study cannot exclude an exaggerated interferon response to spike protein production at a systemic level in individuals with a primary heritable interferonopathy. In the context of continued SARS-CoV-2 spread in the community, we do not recommend withholding vaccination in this rare disease group. However, we recommend that vaccinations for AGS patients are provided in a controlled setting with appropriate observation and used with caution in individuals with prior vaccine associated adverse events.
The regulatory landscapes of human ovarian ageing
Authors: Jin Chen , Wang Xizhe , Hudgins Adam D. , Gamliel Amir , Pei Mingzhuo , Kim Seungsoo , Contreras Daniela , Hoeijmakers Jan , Campisi Judith , Lobo Rogerio , Williams Zev , Rosenfeld Michael G. , Suh Yousin
Published: May 2022

Summary paragraph

The ovary is the first organ to age in the human body, affecting both fertility and overall health in women1-8. However, the biological mechanisms underlying human ovarian ageing remain poorly understood. Here we performed single-nuclei multi-omics analysis of young and reproductively aged human ovaries to understand the molecular and cellular basis of ovarian ageing in humans. Our analysis reveals coordinated changes in transcriptomic output and chromatin accessibility across cell types during ageing, including elevated mTOR and MAPK signaling, decreased activity of the oxidative phosphorylation and DNA damage repair pathways, and an increased signature of cellular senescence. By constructing cell type-specific regulatory networks, we uncover enhanced activity of the transcription factor CEBPD across cell types in the aged ovary, with a corresponding significant loss of activity of most cell identity-associated transcription factors. Moreover, by performing integrative analyses of our single-nuclei multi-omics data with common genetic variants associated with age at natural menopause (ANM) from genome-wide association studies, we demonstrate a global impact of functional variants on changes in gene regulatory networks across ovarian cell types. Finally, we nominate about a dozen of functional non-coding variants, their target genes and cell types and regulatory mechanisms that underlie genetic association with ANM. This work provides a comprehensive multimodal landscape of human ovarian ageing and mechanistic insights into inherited variation of ANM.
Metadata retrieval from sequence databases with ffq
Authors: Gálvez-Merchán Ángel , Min Kyung Hoi (Joseph) , Pachter Lior , Booeshaghi A. Sina
Published: May 2022

We present a command-line tool, called ffq, for querying user-generated data and metadata from sequence databases. The code can be found here: https://github.com/pachterlab/ffq.
A binocular perception deficit characterizes prey pursuit in developing mice
Authors: Allen Kelsey , Gonzalez-Olvera Rocio , Kumar Milen , Feng Ting , Pieraut Simon , Hoy Jennifer L.
Published: May 2022

The mouse continues to be one of the most powerful models in which to address the molecular and cellular mechanisms underlying mammalian visual system development. In particular, integration of binocular information at the cellular level has long been studied in specific regions of the mouse visual cortex to gain mechanistic insight into the development of vision. However, we lack an understanding of the development of the visual perceptions themselves in mice and other species that might rely on successful binocular integration. Further, the superior colliculus also processes binocular input and it remains unclear how early visual experience differentially impacts activity in this brain area during behavior. To address these major outstanding questions, we quantified the natural visually-guided behavior of postnatal day 21 (P21) and adult mice using a live prey capture assay and a computerized-spontaneous perception of visual objects tasks (C-SPOT). Analysis of both behavioral assays revealed robust and specific binocular visual field processing deficits in P21 mice as compared to adults. In addition, c-Fos expression in the anterior region of the superior colliculus (SC), the region that would process stimuli located in the binocular visual field, was highly different between P21 mice and adults after C-SPOT. We thus exploited a natural visual pursuit behavior and C-SPOT to provide the first demonstration of a specific visual perception deficit related to binocular integration in developing mice.

Highlights

Juvenile (P21) mice robustly investigate live insects

Insect pursuit behavior relying on binocular vision is immature in P21 mice

Visually-induced arrest responses are similar between P21 and adult mice.

Ethologically-relevant visual experience differentially increases c-Fos expression in the superior colliculus of juveniles versus adults.
Distinct types of multicellular aggregates in Pseudomonas aeruginosa liquid cultures
Authors: Melaugh Gavin , Martinez Vincent , Baker Perrin , Hill Preston , Howell P. Lynne , Wozniak Daniel J. , Allen Rosalind J.
Published: May 2022

Pseudomonas aeruginosa forms suspended multicellular aggregates when cultured in liquid media. Such aggregates may be important in disease, and/or as a pathway to biofilm formation. The polysaccharide Psl and extracellular DNA (eDNA) have both been implicated in aggregation, but previous results depend strongly on the experimental conditions. Here we develop a quantitative microscopy-based method for assessing changes in the size distribution of suspended aggregates over time in growing cultures. For exponentially growing cultures of P. aeruginosa PAO1, we find that aggregation is mediated by cell-associated Psl, rather than by either eDNA or se-creted Psl. These aggregates arise de novo within the culture via a growth process that involves both collisions and clonal growth. They are “non-cheatable” since Psl non-producing cells do not aggregate with producers. In contrast, we find that stationary phase (overnight) cultures contain a different type of multicelullar aggregate, in which both eDNA and Psl mediate cohesion. Our findings suggest that the physical and bi-ological properties of multicellular aggregates may be very different in early-stage vs late-stage bacterial cultures.
Museum specimens of a landlocked pinniped reveal recent loss of genetic diversity and unexpected population connections
Authors: Heino Matti T. , Nyman Tommi , Palo Jukka U. , Harmoinen Jenni , Valtonen Mia , Pilot Małgorzata , Översti Sanni , Salmela Elina , Kunnasranta Mervi , Hoelzel A. Rus , Ruokonen Minna , Aspi Jouni
Published: May 2022

Aim

The Saimaa ringed seal (Pusa hispida saimensis) is endemic to Lake Saimaa in Finland. The subspecies is thought to have originated when parts of the ringed seal population of the Baltic region were trapped in lakes emerging due to post-glacial bedrock rebound around 9,000 years ago. During the 20th century, the population experienced a drastic human-induced bottleneck. Today encompassing a little over 400 seals with extremely low genetic diversity, it is classified as endangered. Our main aim was to evaluate the role of the 20th century bottleneck in the erosion of genetic diversity in the Saimaa seal population. We also evaluated connections with other ringed seals from the Baltic Sea, Lake Ladoga, North America, Svalbard and the White Sea.

Location

Lake Saimaa, Finland, together with the Baltic Sea and the Arctic Ocean.

Methods

We sequenced sections of the mitochondrial control region from 60 up to 125 years old museum specimens of the Saimaa ringed seal. The generated dataset was combined with publicly available sequences. We studied how genetic variation has changed through time in this subspecies, and how it is phylogenetically related to other ringed seal populations.

Results

We observed temporal fluctuations in haplotype frequencies and loss of haplotypes accompanied by a recent reduction in female effective population size. In apparent contrast with the traditionally held view of the Baltic origin of the population, the Saimaa ringed seal mtDNA variation shows also affinities to North American ringed seals.

Main conclusions

Our results suggest that the Saimaa ringed seal has experienced recent genetic drift associated with small population size. The results further suggest that extant Baltic ringed seals do not represent well the ancestral population of the Saimaa ringed seal, which calls for re-evaluation of the deep history of this subspecies.
In-situ lipid profiling of insect pheromone glands by Direct Analysis in Real Time Mass Spectrometry
Authors: Cetraro Nicolas , Yew Joanne Y.
Published: May 2022

Lipid pheromones play a significant role in the behavior and ecology of many insects. The characterization of pheromone structures is a significant challenge due to their low abundance and ephemeral nature. Here we present a method for the analysis of lipid molecules from single pheromone glands of Drosophila melanogaster (fruit fly) using Direct Analysis in Real Time mass spectrometry (DART MS). Our results reveal that DART MS analysis of single tissues generates reproducible, species-specific lipid profiles comprised of fatty acids, wax esters, diacylglycerides and triacylglycerides. In addition, the ion source temperature and application of a solvent wash can cause significant qualitative and quantitative changes in the mass spectral profile. Lastly, we show that untargeted chemical fingerprinting of the gland can be used to accurately categorize species according to phylogenetic subgroup or genotype. Collectively, our findings indicate that DART MS is a rapid and powerful method for characterizing a broad range of lipids in tissues with minimal preparation. The application of direct tissue DART MS will expand the “secretome” of molecules produced by pheromone glands. In addition to its direct relevance to chemical ecology, the method could potentially be used in pharmaceutical studies for the screening and detection of tissue-specific drug metabolites.
Basic Leucine Zippers: Aureochromes Versus the Rest
Authors: Khamaru Madhurima , Deb Anwesha , Mitra Devrani
Published: May 2022

The photoreceptor cum transcription factors, Aureochromes, is present exclusively in marine photosynthetic algae. Co-existence of Light-Oxygen-Voltage (LOV) sensor and basic leucine zipper (bZIP) effector in aureochromes is unique -- no other photoreceptors barring aureochromes are known to possess bZIP as effector. The ability of aureochromes to participate in diverse biological activities, inverse topological arrangement make them a model protein not only to study light-dependent gene expression or transcriptional regulation but also as potential optogenetic scaffold. While detailed structural information is available for the LOV sensor, 3D structural information is absent for bZIP/bZIP+linker+LOV module. This study therefore aims for a thorough investigation of the bZIP domains from aureochromes and others, and their interaction with substrate DNA using tools from sequence/structural bioinformatics and network theory. With an in-depth comparison between 26 aureochrome subtypes and 147 plant/ophistokont bZIPs, we explore important residues at basic region and zipper - necessary for dimerization stability and DNA binding specificity. Perhaps the most notable finding is the unique histidine substitution at the DNA binding signature sequence of aureochromes, completely absent in any other bZIPs. Not only is this residue important for DNA binding, this can serve as a potential switch point in aureochrome/bZIP evolution. An all-atom network analysis on representative bZIP-DNA co-crystal structures, especially the measurement of eigenvector centrality, further adds importance to hydrophobic interactions in the zipper region to stabilize bZIP dimer and facilitate DNA binding.
Ectodermal Wnt signalling, cell fate determination and polarity of the skate gill arch skeleton
Authors: Rees Jenaid M. , Sleight Victoria A. , Clark Stephen J. , Nakamura Tetsuya , Gillis J. Andrew
Published: May 2022

The gill skeleton of cartilaginous fishes (sharks, skates, rays and holocephalans) exhibits a striking anterior–posterior polarity, with a series of fine appendages called branchial rays projecting from the posterior margin of the gill arch cartilages. We previously demonstrated in the skate (Leucoraja erinacea) that branchial rays derive from a posterior domain of pharyngeal arch mesenchyme that is responsive to Shh signalling from a distal gill arch epithelial ridge (GAER) signalling centre. However, how branchial ray progenitors are specified exclusively within posterior gill arch mesenchyme is not known. Here we show that genes encoding several Wnt ligands are expressed in the ectoderm immediately adjacent to the skate GAER, and that these Wnt signals are transduced largely in the anterior arch environment. Using pharmacological manipulation, we show that inhibition of Wnt signalling results in an anterior expansion of Shh signal transduction in developing skate gill arches, and in the formation of ectopic anterior branchial ray cartilages. Our findings demonstrate that ectodermal Wnt signalling contributes to gill arch skeletal polarity in skate by restricting Shh signal transduction and chondrogenesis to the posterior arch environment and highlights the importance of signalling interactions at embryonic tissue boundaries for cell fate determination in vertebrate pharyngeal arches.
A type IV Autotaxin inhibitor ameliorates acute liver injury and non-alcoholic steatohepatitis in mice
Authors: Booijink Richell , Salgado-Polo Fernando , Jamieson Craig , Perrakis Anastassis , Bansal Ruchi
Published: May 2022

An important but rather underexplored pathway implicated in liver disease is the lysophosphatidic acid (LPA) signaling axis. LPA acts through G-protein coupled receptors inducing downstream signaling pathways related to cell proliferation, differentiation, and migration, and is predominantly produced by the extracellular phosphodiesterase, Autotaxin (ATX). ATX has gained significant attention lately with an impressive number of ATX inhibitors (type I-IV) reported. Here, we aim to evaluate the therapeutic potential of a (yet unexplored) type IV ATX inhibitor, Cpd17, in liver injury. In this study, we first confirmed the involvement of the ATX/LPA signaling axis in human and murine diseased livers. Thereafter, we evaluated the effects of Cpd17, in comparison with the classic type I ATX inhibitor PF8380, in vitro. While both inhibitors attenuated induced cell injury phenotypes as assessed using various assays and specific readout parameters in hepatocytes, macrophages, and hepatic stellate cells (HSCs), Cpd17 appeared more effective. This prompted us to characterize the mechanism of action of both inhibitors in situ and in vitro in macrophages and HSCs, demonstrating that Cpd17 was more potent in inhibiting relevant signaling pathways, namely RhoA-mediated cytoskeletal remodeling, and phosphorylation of MAPK/ERK and AKT/PKB. Finally, we investigated the therapeutic potential of Cpd17 in two liver disease mouse models, CCl4-induced acute liver injury and diet-induced non-alcoholic steatohepatitis. We demonstrate that Cpd17 has an excellent potential for reducing liver injury in both disease models in vivo. We conclude that ATX inhibition, by type IV inhibitor in particular, has an excellent potential for clinical application in liver diseases.
Membrane Bound O-Acyltransferase 7 (MBOAT7)-Driven Lysophosphatidylinositol (LPI) Acylation in Adipocytes Contributes to Systemic Glucose Homeostasis
Authors: Massey William , Varadharajan Venkateshwari , Banerjee Rakhee , Brown Amanda L. , Horak Anthony J. , Hohe Rachel C. , Chan E. Ricky , Pan Calvin , Zhang Renliang , Allende Daniela S. , Lusis Aldons J. , Brown J. Mark
Published: May 2022

Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly common and is a leading cause of end stage liver diseases such as cirrhosis and hepatocellular carcinoma. The rise in NAFLD closely parallels the global epidemic of obesity and type 2 diabetes mellitus (T2DM), and there is a clear interrelationship between abnormal lipid metabolism, insulin resistance, and NAFLD progression. Several genetic loci have been identified as contributors to NAFLD progression, all of which are consistently linked to abnormal lipid metabolic processes in the liver. The common loss-of-function variant rs641738 (C>T) near the gene encoding Membrane-Bound O-Acyltransferase 7 (MBOAT7) is associated with increased susceptibility to NAFLD as well as the entire spectrum of NAFLD progression. The MBOAT7 gene encodes a lipid metabolic enzyme that is capable of esterifying polyunsaturated fatty acyl-CoAs to LPI substrates to generate phosphatidylinositol (PI) lipids. We previously showed that antisense oligonucleotide (ASO)-mediated knockdown of Mboat7 in mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance (Helsley et al., 2019). Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ∼100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, adipocyte-specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid (AA)-containing PI pools, Mboat7 is the major source of AA-containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.
QTL mapping for seed morphology using the instance segmentation neural network inLactucaspp
Authors: Seki Kousuke , Toda Yosuke
Published: May 2022

Wild species of lettuce (Lactucasp.) are thought to have first been domesticated for oilseed contents to provide seed oil for human consumption. Although seed morphology is an important trait contributing to oilseed in lettuce, the underlying genetic mechanisms remain elusive. Since lettuce seeds are small, a manual phenotypic determination required for a genetic dissection of such traits is challenging. In this study, we built and applied an instance segmentation-based seed morphology quantification pipeline to measure traits in seeds generated from a cross between the domesticated oilseed type cultivar ‘Oilseed’ and the wild species ‘UenoyamaMaruba’ in an automated manner. Quantitative trait locus (QTL) mapping following ddRAD-seq revealed 11 QTLs linked to 7 seed traits (area, width, length, length-to-width ratio, eccentricity, perimeter length, and circularity). Remarkably, the three QTLs with the highest LOD scores,qLWR-3.1, qECC-3.1, andqCIR-3.1, for length-to-width ratio, eccentricity, and circularity, respectively, mapped to linkage group 3 (LG3) around 161.5 to 214.6 Mb, a region previously reported to be associated with domestication traits from wild species. These results suggest that the oilseed cultivar harbors genes acquired during domestication to control seed shape in this genomic region. This study also provides genetic evidence that domestication arose, at least in part, by selection for the oilseed type from wild species and demonstrates the effectiveness of image-based phenotyping to accelerate discoveries of the genetic basis for small morphological features such as seed size and shape.
Single molecule multi-omics reveals context-dependent regulation of enhancers by DNA methylation
Authors: Kreibich Elisa , Kleinendorst Rozemarijn , Barzaghi Guido , Kaspar Sarah , Krebs Arnaud R
Published: May 2022

Enhancers are cis-regulatory elements that control the establishment of cell identities during development. In mammals, enhancer activation is tightly coupled with local DNA demethylation. Yet, whether this epigenetic remodelling is necessary for enhancer activation is unknown. Here, we developed a single molecule multi-omics approach to measure chromatin accessibility and transcription factor binding as a function of the presence of methylation on the same DNA molecules. We leveraged natural epigenetic heterogeneity at active enhancers to test the impact of DNA methylation on their activity in multiple cell lineages. While reduction of DNA methylation appears dispensable for the activity of most enhancers, we identify a class of cell-type-specific enhancers where presence of DNA methylation antagonises the binding of transcription factors. Genetic perturbations reveal that chromatin accessibility and transcription factor binding are a direct function of active demethylation at these loci. Thus, in addition to safeguarding the genome from spurious activation, DNA methylation directly controls transcription factor occupancy at cell-type-specific active enhancers.
Expanded Distribution and Predicted Suitable Habitat for the Critically Endangered Yellow-tailed Woolly Monkey (Lagothrix flavicauda) in Peru
Authors: Zarate Melissa A. , Shanee Sam , Charpentier Elvis , Sarmiento Yeissy , Schmitt Christopher A.
Published: May 2022

The Tropical Andes Biodiversity Hotspot holds a remarkable number of species at risk of extinction due to anthropogenic habitat loss, hunting and climate change. One of these species, the Critically Endangered yellow-tailed woolly monkey (Lagothrix flavicauda), was recently sighted in Junín region, 206 kilometres south of its previously known distribution. The range extension, combined with continued habitat loss, calls for a re-evaluation of the species’ distribution and available suitable habitat. Here, we present novel data from surveys at 53 sites in the regions of Junín, Cerro de Pasco, Ayacucho and Cusco. We encounteredL. flavicaudaat 9 sites, all in Junín, and the congenericL. l. tschudiiat 20 sites, but never in sympatry. Using these new localities along with all previous geographic localities for the species, we made predictive Species Distribution Models based on Ecological Niche Modelling using a generalized linear model and maximum entropy. Each model incorporated bioclimatic variables, forest cover, vegetation measurements, and elevation as predictor variables. Model evaluation showed >80% accuracy for all measures. Precipitation was the strongest predictor of species presence. Habitat suitability maps illustrate potential corridors for gene flow between the southern and northern populations, although much of this area is inhabited byL. l. tschudii. An analysis of the current protected area (PA) network showed ∼47% of remaining suitable habitat is unprotected. With this, we suggest priority areas for new protected areas or expansions to existing reserves that would conserve potential corridors betweenL. flavicaudapopulations. Further surveys and characterization of the distribution in intermediate areas, combined with studies on genetic flow, are still needed to protect this species.
A comparison between Mini-loop mediated isothermal amplification and polymerase spiral reaction for selective amplification of short template DNA
Authors: Allsopp RC , Alexandrou G , Toumazou C , Ali S , Charles Coombes R , Kalofonou M , Shaw J A
Published: May 2022

Isothermal amplification of circulating tumour-derived DNA (ctDNA) in the blood plasma could provide a rapid and cost effective alternative to PCR and NGS approaches for real-time cancer monitoring. Several variations of isothermal technologies exist, typically designed over unconstrained template length. Here, we compared the amplification efficiency of a compact loop mediated isothermal amplification reaction (termed AS-Mini-LAMP) with polymerase spiral reaction (PSR) suitable for analysis of ctDNA. Utilising 4-primers and targeting a 155 bp template encompassing the estrogen receptor (ESR1) c.1138G>C (p.E380Q) missense mutation.

Using synthetic E380Q template DNA and Bst2.0 polymerase, results demonstrate that AS-Mini-LAMP was capable of selective mutant allele DNA amplification to a limit of 1,000 mutant copies, whereas no specific amplification was observed by PSR. The alternative use of Bst3.0 polymerase for either AS-Mini-LAMP or PSR revealed non-canonical events that underpin potentially misleading results when employing isothermal chemistries. In conclusion, AS-Mini-LAMP is more suited to mutation detection than PSR.
Host adaptation drives genetic diversity in a vector-borne disease system
Authors: Combs Matthew A. , Tufts Danielle M. , Adams Ben , Lin Yi-Pin , Kolokotronis Sergios-Orestis , Diuk-Wasser Maria A.
Published: May 2022

The range of hosts a pathogen can infect is a key trait influencing human disease risk and reservoir host infection dynamics. Borrelia burgdorferi sensu stricto (Bb), an emerging zoonotic pathogen, causes Lyme disease and is widely considered a host generalist, commonly infecting mammals and birds. Yet the extent of intraspecific variation in Bb host breadth, its role in determining host competence and potential implications to human infection remain unclear. We conducted a long-term study of Bb diversity, defined by the polymorphic ospC locus, across white-footed mice, passerine birds, and tick vectors leveraging long-read amplicon sequencing. Our results reveal strong variation in host breadth across Bb genotypes, exposing a spectrum of genotype-specific host-adapted phenotypes. We found support for multiple niche polymorphism maintaining Bb diversity in nature and little evidence of temporal shifts in genotype dominance, as would be expected under negative frequency-dependent selection. Passerine birds support the circulation of several human invasive strains in the local tick population and harbor greater Bb genotypic diversity compared to white-footed mice. Mouse-adapted Bb genotypes exhibited longer persistence in individual mice compared to non-adapted genotypes and infection communities infecting individual mice preferentially became dominated by mouse-adapted genotypes over time. We posit that intraspecific variation in Bb host breadth and specificity helps maintain overall species fitness in response to transmission by a generalist vector. Because pathogen genotypes vary in host breadth and result in diverse human disease manifestations, our findings indicate that a more nuanced definition of ‘host competence’ incorporating local genotype frequency is warranted.

Significance

Lyme disease is the most common vector-borne disease in the US with a causative agent (Borrelia burgdorferi) exhibiting high genetic diversity that partially correlates with human disease manifestations. Understanding the extent of host specificity in pathogens is critical for evaluating disease risk, but host specificity and mechanisms maintaining genetic diversity in Bb are unknown. We show that Bb genotypes exhibit variable host adaptation to white-footed mice and passerine birds, two common reservoir hosts, which appears to promote high intraspecific pathogen diversity. Conversely, we find limited evidence of negative frequency-dependent selection, an alternative mechanism for diversity maintenance. Our results reveal cryptic intraspecies host breadth variation and suggest that evaluating host competence depends on the frequency of host-adapted genotypes in local environments.
Overexpression screen of chromosome 21 genes reveals modulators of Sonic hedgehog signaling relevant to Down syndrome
Authors: Moyer Anna J. , Fernandez Fabian-Xosé , Li Yicong , Klinedinst Donna K. , Florea Liliana D. , Kazuki Yasuhiro , Oshimura Mitsuo , Reeves Roger H.
Published: May 2022

Dysregulation of Sonic hedgehog (SHH) signaling may contribute to multiple Down syndrome-associated phenotypes, including cerebellar hypoplasia, congenital heart defects, craniofacial and skeletal dysmorphologies, and Hirschsprung disease. Granule cell precursors isolated from the developing cerebellum of Ts65Dn mice are less responsive to the mitogenic effects of SHH than euploid cells, and a single postnatal dose of the SHH pathway agonist SAG rescues cerebellar morphology and performance on learning and memory tasks in Ts65Dn mice. SAG treatment also normalizes expression levels of OLIG2 in neural progenitor cells derived from human trisomy 21 iPSCs. However, despite evidence that activating SHH signaling can ameliorate some Down syndrome-associated phenotypes, chromosome 21 does not encode any components of the canonical SHH pathway. Here, we screened 163 chromosome 21 cDNAs in a series of SHH-responsive cell lines to identify chromosome 21 genes that modulate SHH signaling. We confirmed overexpression of trisomic candidate genes using RNA-seq in Ts65Dn and TcMAC21 cerebellum. Our study indicates that some chromosome 21 genes, including DYRK1A, upregulate SHH signaling while others, such as HMGN1 and MIS18A, inhibit SHH signaling. Overexpression of genes involved in chromatin structure and mitosis, but not genes previously implicated in ciliogenesis, regulate the SHH pathway. Our data suggest that cerebellar hypoplasia and other phenotypes related to aberrant SHH signaling arise from the net effect of trisomy for multiple chromosome 21 genes rather than the overexpression of a single trisomic gene. Identifying which chromosome 21 genes modulate SHH signaling may suggest new therapeutic avenues for ameliorating Down syndrome phenotypes.

One Sentence Summary

Multiple chromosome 21 genes modulate Sonic hedgehog signaling, which is dysregulated in Down syndrome.
Effect of Na2SiO3 concentration on microstructure and corrosion resistance of MAO coatings prepared on Al-Mg-Sc alloys
Authors: Wu Mingjin , Jiang Feng , Jiang Jingyu
Published: May 2022

Purpose

The purpose of this paper is to investigate the effect of Na2SiO3 concentration on the microstructure and corrosive properties of microarc oxidation (MAO) coating on Al-Mg-Sc alloy and explore microstructure evolution rule of Al substrate in the contact area.

Design/methodology/approach

The Na2SiO3 concentration in electrolytes influenced the microstructure and corrosion behavior of MAO coatings. Instantaneous high temperature and high pressure due to microarc discharge caused annealing treatment. The corrosive behavior of the MAO coating was featured with polarization curves and electrochemical impedance spectrum in 3.5 Wt.% NaCl solution.

Findings

The substrate in the contact area existed the instantaneous annealing treatment, which caused obvious recrystallization. The coating prepared in electrolyte containing 7 g/L Na2SiO3 exhibited the highest protective properties in 3.5 Wt.% NaCl solution.

Originality/value

MAO treatment could increase the corrosion resistance by producing a protective layer on the Al-Mg-Sc alloy surface at a suitable Na2SiO3 concentration and microstructure evolution rule of Al substrate in the contact area was obtained.
Territorial servitisation in Italian industrial districts: the role of technological and professional KIBS
Authors: Baldoni Edoardo , De Propris Lisa , Storai Dimitri
Published: May 2022

Purpose

This paper aims to analyse to what extent Italian industrial districts (IDs), with their traditional manufacturing specialization, experimented a territorial servitisation process in terms of spread of specifically professional and technological knowledge-intensive business services’ activities over the period 2012–2018.

Design/methodology/approach

This paper articulates knowledge-intensive business services activities in two types, technological knowledge-intensive business services and professional knowledge-intensive business services. It tracks their growth and their co-location with manufacturing sectors in Italian IDs by means of firm employment data and location quotients. Firm employment data is extracted from Statistical Archive of Active firms (ASIA) data set provided by Italian National Institute for Statistics (ISTAT). ASIA data is matched with ISTAT territorial identification of Italian local labour systems and IDs.

Findings

In 2018, Italian IDs featured, next to their traditional over-specialisation in manufacturing activities, an under-specialisation in knowledge-intensive business services’ activities. Nevertheless, the dynamic analysis carried out over the period 2012–2018 shows that IDs firm employment in technological knowledge-intensive business services and professional knowledge-intensive business services grew at a higher rate than the national average.

Originality/value

The novelty of this paper is to distinguish between technological knowledge-intensive business services and professional knowledge-intensive business services and to measure the presence and the growth of these two different types of knowledge-intensive business services in Italian IDs.
Natural convection process endorsed in coaxial duct with Soret/Dufour effect
Authors: Shah Syed Saqib , Öztop Hakan F. , Ul-Haq Rizwan , Abu-Hamdeh Nidal
Published: May 2022

Purpose

The purpose of this paper is to analyse the buoyancy flow, mass and heat transfer in coaxial duct under Soret and Dufour effect. The combined effects of the thermal-diffusion and diffusion-thermo coefficients, as well as the Schmidt number, on natural convection in a heated lower coaxial curve were explored using the proposed physical model. The Dufour and Soret effects are taken into consideration in the energy and concentration equations, respectively.

Design/methodology/approach

The dominating mathematical models are converted into a set of non-linear coupled partial differential equations, which are solved using a numerical approach. The controlling non-linear boundary value problem is numerically solved using the penalty finite element method with Galerkin’s weighted residual scheme over the entire variety of essential parameters.

Findings

It was observed that different parameters were tested such as heat generation or absorption coefficient, buoyancy ratio, Soret coefficient, Dufour coefficient, Lewis number and Rayleigh number. Effect of Rayleigh number, absorption/generation and Dufour coefficient on isotherm are significantly reported. For greater values of Lewis number, maximum mass transfer in duct in the form of molecular particles is produced. Buoyancy ratio parameter decreases the average rate of heat flow and increases its mass transfer.

Originality/value

The main originality of this work is to make an application of Soret and Dufour effects in a coaxial duct in the presence of source sink.
Enhancing food production to prevent households from food insecurity in rural Burkina Faso: does land ownership matter?
Authors: Séogo Windinkonté
Published: May 2022

Purpose

This paper assesses the effect of land ownership on household food security through its productivity enhancement effect in rural Burkina Faso.

Design/methodology/approach

As the link between land tenure security and productivity is indirect, the study relies on a complex mixed process regression model with robustness to assess the effect of land ownership on household productivity. Then, an instrumental variable (IV) approach is followed to investigate the association between household productivity and food security. The rural development program survey data collected from 1,892 households in 2017 are used.

Findings

The complex mixed process estimation results are robust and show that land ownership has a positive effect on household productivity. From the IV results, it is found that productive households spend more on food, have a low share of expenditures on food and are less likely to experience severe food shortages, implying an improvement in their food security status. This highlights a positive association between land ownership and food security.

Originality/value

Unlike previous studies that only focused on the effect of land ownership on land-related investments and agricultural productivity, this study deepens the analysis and sheds light on how land ownership, agricultural production and food security are related. It gives empirical evidence on the importance of land policies in the struggle against food insecurity in agrarian economies.

Peer review

The peer review history for this article is available at https://publons.com/publon/10.1108/IJSE-11-2021-0658.
Examining the interstate variations and interlinkage between water poverty and multidimensional poverty in India: evidence from household-level data
Authors: Pandey Suchitra , Mohapatra Geetilaxmi , Arora Rahul
Published: May 2022

Purpose

The purpose of the present study is to examine the inter-relationship between the multi-dimensional poverty and water poverty using household level data for Indian states.

Design/methodology/approach

A modified water poverty index (MWPI) for both rural and urban households was created using the five components approach and various quantifiable proxies. Principal component analysis (PCA) has been used for the construction of MWPI. Multidimensionality of poverty (MPI) is measured using the Alkire and Foster methodology. Further, the study has utilized correlation and Tobit regression analysis to show the relationship between MWPI and MPI.

Findings

The empirical findings suggest that there is a positive and significant relationship between multidimensional poverty and water poverty, with the extent of relationship being greater in rural areas. The results show that in rural areas all the components of water poverty has significant impact on multidimensional poverty, whereas in urban areas except use component all others have significant impact on multidimensional poverty. Further, components of multidimensional poverty were also found to be significantly impacting water poverty.

Practical implications

The study suggests that policymakers cannot treat both forms of poverty in isolation. If India aims to reduce poverty, then it needs to pay significant attention to improving water conditions.

Originality/value

This is a pioneering attempt to construct water poverty index at the household level while accounting for micro-level differences for Indian economy. It highlights that water poverty leads to multi-dimensional poverty and vice-versa.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-12-2021-0731.
Machining of titanium alloys using phosphonium-based halogen-free ionic liquid as lubricant additives
Authors: Bambam Arun Kumar , Dhanola Anil , Gajrani Kishor Kumar
Published: May 2022

Purpose

Nowadays, ionic liquids (ILs) are used as lubricant additives because of their ability to improve tribological characteristics. However, majority of the ILs contains halogen-based anions. They are extremely sensitive to moisture and produce detrimental halides and halogen acids when reacted with moisture and water. These halides and halogen acids are harmful to the health and environment of the operator’s. This paper aims to study four different lubricants including two halogen-based ILs blended in canola oil and two phosphonium-based halogen-free ILs blended in canola oil and in pure canola oil.

Design/methodology/approach

Viscosity and contact angle were measured by using rheometer and contact angle goniometer, respectively. Machining experiments were performed using turning centre with four different lubricants at two different cutting speeds and temperatures, and the machining forces, tool morphology and roughness of the machined surface were analysed.

Findings

The results showed that the inclusion of 1% phosphonium-based halogen-free ILs blended in canola oil increased the viscosity by 44.8% and reduced the cutting and thrust force by 21.7% and 26.8%, respectively, compared to pure canola oil lubricant. Microscopic analysis of tool showed lower adhesive and abrasive wear when machined with phosphonium-based halogen-free ILs blended in canola oil. The workpiece surface roughness reduced by 32% for phosphonium-based halogen-free ILs blended in canola oil compared with pure canola oil.

Originality/value

Halogen-free ILs are possible green lubricants, as they do not contain harmful elements such as F, S, B and Cl like halogen-based ILs. To the best of the authors’ knowledge, this is presumably the first work which shows machining performance of halogen-free ILs as lubricant additives.