bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes
Authors: Rivosecchi Julieta , Jost Daniel , Vachez Laetitia , Gautier François , Bernard Pascal , Vanoosthuyse Vincent
Published: November 2020

The mechanisms leading to the accumulation of the SMC complexes condensins around specific transcription units remain unclear. Observations made in bacteria suggested that RNA polymerases (RNAP) constitute an obstacle to SMC translocation, particularly when RNAP and SMC travel in opposite directions. Here we show in fission yeast that gene termini harbour intrinsic condensin-accumulating features whatever the orientation of transcription, which we attribute to the frequent backtracking of RNAP at gene ends. Consistent with this, to relocate backtracked RNAP2 from gene termini to gene bodies was sufficient to cancel the accumulation of condensin at gene ends and to redistribute it evenly within transcription units, indicating that RNAP backtracking may play a key role in positioning condensin. Formalization of this hypothesis in a mathematical model suggests that the inclusion of a sub-population of RNAP with longer dwell-times is essential to fully recapitulate the distribution profiles of condensin around active genes. Taken together, our data strengthen the idea that dense arrays of proteins tightly-bound to DNA alter the distribution of condensin on chromosomes.
Metagenomic characterization of a harmful algal bloom using nanopore sequencing
Authors: Schafran Peter W. , Cai Victor , Yang Hsiao-Pei , Li Fay-Wei
Published: November 2020

Water bodies around the world are increasingly threatened by harmful algal blooms (HABs) under current trends of rising water temperature and nutrient load. Metagenomic characterization of HABs can be combined with water quality and environmental data to better understand and predict the occurrence of toxic events. However, standard short-read sequencing typically yields highly fragmented metagenomes, preventing direct connection of genes to a single genome. Using Oxford Nanopore long-read sequencing, we were able to obtain high quality metagenome-assembled genomes, and show that dominant organisms in a HAB are readily identified, though different analyses disagreed on the identity of rare taxa. Genes from diverse functional categories were found not only in the most dominant genera, but also in several less common ones. Using simulated datasets, we show that the Flongle flowcell may provide an option for HAB monitoring with less data, at the expense of failing to detect rarer organisms and increasing fragmentation of the metagenome. Based on these results, we believe that Nanopore sequencing provides a fast, portable, and affordable method for studying HABs.
Differential expression between African-ancestry and White patients diagnosed with Triple-Negative Breast Cancer: EGFR, Myc, Bcl2 and β-Catenin as ancestry-associated markers
Authors: Matias Ana T. , Jacinta-Fernandes Ana , Maia Ana-Teresa , Braga Sofia , Jacinto António , Cabral M. Guadalupe , Brito Patrícia H.
Published: November 2020

Purpose

Triple-negative breast cancer (TNBC) has a higher incidence, a younger age of onset, and a more aggressive behavior in African-ancestry women. Biological disparities have been suggested as an important factor influencing the ancestry-associated TNBC discrepancy. In this study, we sought to identify ancestry-associated differential gene and protein expression between African-ancestry and White TNBC patients, controlling for patients’ menopause status and pathological staging at diagnosis.

Methods

Differential gene expression analyses (DGEA) were performed using RNA-sequencing data from The Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GSEA) and Ingenuity Pathway Analysis (IPA), with focus on network design, were performed to highlight candidate genes for further validation through immunohistochemistry of TNBC samples from patients followed in Portugal.

Results

With 52 African-American and 90 White TNBC patients included, TCGA’s data corroborate that African-American patients have a higher TNBC incidence (28.42% vs 11.89%, p<0.0001). Particularly, premenopausal and stage II disease African-American patients also have significantly lower survival probability, comparing with White patients (log-rank p=0.019 and 0.0038, respectively). DGEA results suggest that expression profile differences are more associated with TNBC staging than with patient’s menopause status. Hippo pathway and cellular community gene sets are downregulated, while breast cancer gene set is upregulated in African-Americans, comparing with White TNBC patients. Furthermore, MAPK pathway gene set is upregulated when controlling for stage II disease. Due to their central role in highly scored networks resulted from IPA’s network design, EGFR, Myc and Bcl2 genes were selected for further validation through immunohistochemistry. We also included β-Catenin in the validation study as it is consensually reported to be required in TNBC tumorigenesis. Although patients used in the DGEA and in the immunohistochemistry experiments are geographically and culturally distinct, both groups of African-ancestry patients are mostly of western-African ancestry and, interesting, differential gene and protein expression matched.

Conclusions

We found ancestry-associated gene expression patterns between African-ancestry and White TNBCs, particularly when controlling for menopause status or staging. EGFR, Myc, Bcl2 and β-catenin gene and protein differential expression matching results in distinct populations suggest these markers as being important indicators of TNBC’s ancestry-associated development.
A high-quality, chromosome-level genome assembly of the Black Soldier Fly (Hermetia IllucensL.)
Authors: Generalovic Tomas N. , McCarthy Shane A. , Warren Ian A. , Wood Jonathan M.D. , Torrance James , Sims Ying , Quail Michael , Howe Kerstin , Pipan Miha , Durbin Richard , Jiggins Chris D.
Published: November 2020

Background

Hermetia illucensL. (Diptera: Stratiomyidae), the Black Soldier Fly (BSF) is an increasingly important mass reared entomological resource for bioconversion of organic material into animal feed.

Results

We generated a high-quality chromosome-scale genome assembly of the BSF using Pacific Bioscience, 10X Genomics linked read and high-throughput chromosome conformation capture sequencing technology. Scaffolding the final assembly with Hi-C data produced a highly contiguous 1.01 Gb genome with 99.75% of scaffolds assembled into pseudo-chromosomes representing seven chromosomes with 16.01 Mb contig and 180.46 Mb scaffold N50 values. The highly complete genome obtained a BUSCO completeness of 98.6%. We masked 67.32% of the genome as repetitive sequences and annotated a total of 17,664 protein-coding genes using the BRAKER2 pipeline. We analysed an established lab population to investigate the genomic variation and architecture of the BSF revealing six autosomes and the identification of an X chromosome. Additionally, we estimated the inbreeding coefficient (1.9%) of a lab population by assessing runs of homozygosity. This revealed a plethora of inbreeding events including recent long runs of homozygosity on chromosome five.

Conclusions

Release of this novel chromosome-scale BSF genome assembly will provide an improved platform for further genomic studies and functional characterisation of candidate regions of artificial selection. This reference sequence will provide an essential tool for future genetic modifications, functional and population genomics.
The Nuclear Pore Complex consists of two independent scaffolds
Authors: Regmi Saroj G. , Lee Hangnoh , Kaufhold Ross , Fichtman Boris , Chen Shane , Aksenova Vasilisa , Turcotte Elizabeth , Harel Amnon , Arnaoutov Alexei , Dasso Mary
Published: November 2020

Macromolecular transport between the nucleus and cytoplasm is mediated through Nuclear Pore Complexes (NPCs), which are built from multiple copies of roughly 34 distinct proteins, called nucleoporins1–3. Models of the NPC depict it as a composite of several sub-domains that have been named the outer rings, inner ring, cytoplasmic fibrils and nuclear basket. While the NPC has been extensively studied, the roles of individual nucleoporins within NPCs and their functional interactions remain poorly understood. Here, we applied a rapid degron system to systematically investigate how individual nucleoporins contribute toward NPC architecture. We find that acute depletion of outer ring components (NUP96 or NUP107) disperses the outer ring and cytoplasmic fibrils without disassembly of inner ring members. Conversely, rapid degradation of the inner ring complex component NUP188 disrupts the inner ring without dislodging outer ring members. We also found that depletion of NUP93 destabilized all NPC domains, indicating that it has a unique role as a lynchpin of NPC structure. Our data highlight the modular nature of NPC organization, suggesting that the outer and inner ring complexes do not extensively rely on each other for structural stability after NPC assembly is complete. This dynamic assessment provides new insights regarding the remarkable structural independence of domains within the NPC.
Identification of root rot resistance QTLs in pea usingFusarium solanif. sp.pisi-responsive differentially expressed genes
Authors: Williamson-Benavides Bruce A. , Sharpe Richard , Nelson Grant , Bodah Eliane T. , Porter Lyndon D. , Dhingra Amit
Published: November 2020

Pisum sativum(pea) yields have declined significantly over the last decades, predominantly due to susceptibility to root rot diseases. One of the main causal agents of root rot is the fungusFusarium solanif. sp.pisi(Fsp), leading to yield losses ranging from 15 to 60%. Determining and subsequently incorporating the genetic basis for resistance in new cultivars offers one of the best solutions to control this pathogen; however, no green-seeded pea cultivars with complete resistance toFsphave been identified. To date, only partial levels of resistance toFsphas been identified among pea genotypes. SNPs mined fromFsp-responsive differentially expressed genes (DEGs) identified in a preceding study were utilized to identify QTLs associated withFspresistance using composite interval mapping in two recombinant inbred line (RIL) populations segregating for partial root rot resistance. A total of 769 DEGs with single nucleotide polymorphisms (SNPs) were identified, and the putative SNPs were evaluated for being polymorphic across four partially resistant and four susceptibleP. sativumgenotypes. The SNPs with validated polymorphisms were used to screen two RIL populations using two phenotypic criteria: root disease severity and plant height. One QTL,WB.Fsp-Ps5.1 that mapped to chromosome V explained 14.76 % of the variance with a confidence interval of 10.36 cM. The other four QTLs located on chromosomes II, III, and V, explained 5.26–8.05 % of the variance. The use of SNPs derived fromFsp-responsive DEGs for QTL mapping proved to be an efficient way to identify molecular markers associated withFspresistance in pea. These QTLs are potential candidates for marker-assisted selection and gene pyramiding to obtain high levels of partial resistance in pea cultivars to combat root rot caused byFsp.
Andean uplift, drainage basin formation, and the evolution of riverweeds(Marathrum,Podostemaceae)in northern South America
Authors: Bedoya Ana M. , Leaché Adam D. , Olmstead Richard G.
Published: November 2020

Northern South America is a geologically dynamic and species-rich region. While fossil and stratigraphic data show that reconfiguration of river drainages resulted from mountain uplift in the tropical Andes, investigations of the impact of landscape change on the evolution of the flora in the region have been restricted to terrestrial taxa.

We explore the role of landscape change on the evolution of plants living strictly in rivers across drainage basins in northern South America by conducting population structure, phylogenomic, phylogenetic networks, and divergence-dating analyses for populations of riverweeds (Marathrum, Podostemaceae).

We show that mountain uplift and drainage basin formation isolated populations ofMarathrumand created barriers to gene flow across rivers drainages. Sympatric species hybridize and the hybrids show the phenotype of one parental line. We propose that the pattern of divergence of populations reflect the formation of river drainages, which was not complete until <4 Ma

Our study provides a clear picture of the role of landscape change in shaping the evolution of riverweeds in northern South America, advances our understanding of the reproductive biology of this remarkable group of plants, and spotlights the impact of hybridization in phylogenetic inference.
Single-femtosecond atomic-resolution observation of a protein traversing a conical intersection
Authors: Hosseinizadeh A. , Breckwoldt N. , Fung R. , Sepehr R. , Schmidt M. , Schwander P. , Santra R. , Ourmazd A.
Published: November 2020

The structural dynamics of a molecule are determined by the underlying potential energy landscape. Conical intersections are funnels connecting otherwise separate energy surfaces. Posited almost a century ago1, conical intersections remain the subject of intense scientific investigation2–4. In biology, they play a pivotal role in vision, photosynthesis, and DNA stability5,6. In ultrafast radiationless de-excitation1,7, they are vital to ameliorating photon-induced damage. In chemistry, they tightly couple the normally separable nuclear and electronic degrees of freedom, precluding the Born-Oppenheimer approximation8. In physics, they manifest a Berry phase, giving rise to destructive interference between clockwise and anti-clockwise trajectories around the conical intersection9. Accurate theoretical methods for examining conical intersections are at present limited to small molecules. Experimental investigations are challenged by the required time resolution and sensitivity. Current structure-dynamical understanding of conical intersections is thus limited to simple molecules with around 10 atoms, on timescales of about 100 fs or longer10. Spectroscopy can achieve better time resolution, but provides only indirect structural information. Here, we present single-femtosecond, atomic-resolution movies of a 2,000-atom protein passing through a conical intersection. These movies, extracted from experimental data by geometric machine learning, reveal the dynamical trajectories of de-excitation via a conical intersection, yield the key parameters of the conical intersection controlling the de-excitation process, and elucidate the topography of the electronic potential energy surfaces involved.
The primary cilium is required for MC4R control of food intake and body weight
Authors: Wang Yi , Bernard Adelaide , Comblain Fanny , Yue Xinyu , Paillart Christophe , Zhang Sumei , Reiter Jeremy F. , Vaisse Christian
Published: November 2020

The Melanocortin-4 Receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis and mutations in MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R expressing neurons are unknown. We recently reported that MC4R localizes to primary cilia, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether MC4R functions there. Here, using mouse genetic approaches, we found that cilia are required specifically on MC4R-expressing neurons to restrain feeding behavior. Moreover, these cilia were critical for pharmacological activators of MC4R to exert an anorexigenic effect. MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus (PVN) of the hypothalamus are essential to restrict food intake. MC4R activation increases adenylyl cyclase activity. Like removing cilia, inhibiting adenylyl cyclase activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, MC4R signals via cilia of PVN neurons to control food intake and body weight. We propose that defects in ciliary localization of MC4R cause obesity in human inherited obesity syndromes and ciliopathies.
Directional phyllotactic bias in calatheas (Goeppertia, Marantaceae): a citizen science approach
Authors: Durrington Benjamin , Chong Fiona , Chitwood Daniel H. ,   Twitter Calathea Poll Participants
Published: November 2020

Lateral organs arranged in spiral phyllotaxy are separated by the golden angle, ≈137.5°, leading to handedness: either clockwise or counter-clockwise. In some species, leaves are asymmetric such that they are smaller and curved towards the side ascending the phyllotactic spiral. As such, these asymmetries lead to mirroring of leaf shapes in plants of opposite phyllotactic handedness. Previous reports had suggested that the pin-stripe calathea (Goeppertia ornata) may be exclusively of one phyllotactic direction, counter-clockwise, but had limited sampling to a single population. Here, we use a citizen science approach leveraging a social media poll, internet image searches, and in-person verification at nurseries in four countries and two continents to demonstrate that calatheas (Goeppertia spp.) around the world are biased towards counter-clockwise phyllotaxy. The possibility that this bias is genetic and its implications for models of phyllotaxy that assume handedness is stochastically specified in equal proportions is discussed.
Hidden cell diversity in Placozoa: Ultrastructural Insights fromHoilungia hongkongensis
Authors: Romanova Daria Y. , Varoqueaux Frederique , Daraspe Jean , Nikitin Mikhail A. , Eitel Michael , Fasshauer Dirk , Moroz Leonid L.
Published: November 2020

From a morphological point of view, placozoans are among the most simple free-living animals. This enigmatic phylum is critical for our understanding of the evolution of animals and their cell types. Their millimeter-sized, disc-like bodies consist of only three cell layers that are shaped by roughly six major cell types. Placozoans lack muscle cells and neurons but are able to move using their ciliated lower surface and take up food in a highly coordinated manner. Intriguingly, the genome ofTrichoplax adhaerens, the founding member of the enigmatic phylum, has disclosed a surprising level of genetic complexity. Moreover, recent molecular and functional investigations have uncovered a much larger, so-far hidden cell-type diversity. Here, we have extended the microanatomical characterization of a recently described placozoan species –Hoilungia hongkongensis. InH. hongkongensis, we recognized the established canonical three-layered placozoan body plan but also came across several morphologically distinct and potentially novel cell types, among them novel gland cells and “shiny spheres”-bearing cells at the upper epithelium. Thus, the diversity of cell types in placozoans is indeed higher than anticipated.
Predicting future from past: The genomic basis of recurrent and rapid stickleback evolution
Authors: Roberts Kingman Garrett A , Vyas Deven N , Jones Felicity C , Brady Shannon D , Chen Heidi I , Reid Kerry , Milhaven Mark , Bertino Thomas S , Aguirre Windsor E , Heins David C , von Hippel Frank A , Park Peter J , Kirch Melanie , Absher Devin M , Myers Richard M , Di Palma Federica , Bell Michael A , Kingsley David M , Veeramah Krishna R
Published: November 2020

Similar forms often evolve repeatedly in nature, raising longstanding questions about the underlying mechanisms. Here we use repeated evolution in sticklebacks to identify a large set of genomic loci that change recurrently during colonization of new freshwater habitats by marine fish. The same loci used repeatedly in extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors. Dramatic genotypic and phenotypic changes arise within 5-7 years, facilitated by standing genetic variation and linkage between adaptive regions. Both the speed and location of changes can be predicted using empirical observations of recurrence in natural populations or fundamental genomic features like allelic age, recombination rates, density of divergent loci, and overlap with mapped traits. A composite model trained on these stickleback features can also predict the location of key evolutionary loci in Darwin’s finches, suggesting similar features are important for evolution across diverse taxa.
Degradation ofboscalid, pyraclostrobin, fenbuconazole, andglyphosateresidues by an advanced oxidative process utilizing ultraviolet light and hydrogen peroxide
Authors: Skanes Blake , Ho Jordan , Warriner Keith , Prosser Ryan S.
Published: November 2020

Recently an advanced oxidative process (AOP) combining H2O2and UV-C light was observed to be effective at controllingListeria monocytogens(Murray et al., 2018) andEscherichia coliO157:H7 and degrading chlorpyrifos residues on the surface of apples (Ho et al., 2020). Little is known about the application of AOP for the degradation of other pesticide residues. This study examined degradation of boscalid, pyraclostrobin, fenbuconazole and glyphosate by 3% (w/v) H2O2, UV-C (254 nm) irradiation and their combination on apple skin and glass. The extent of degradation was not significantly different between the AOP and optimal individual treatment. However, treatment susceptibility was different with glyphosate most effectively degraded by H2O2exposure (up to 98% on apple, 3% (w/v) H2O2at 30□C for 15 min) while boscalid, pyraclostrobin and fenbuconazole were more effectively degraded by UV-C (up to 88%, 100% and 70% degradation after ~11,000 mJ/cm2). Suggestions for possible causes of degradation are proposed.
Can a nick promote partial genome re-replication?
Authors: Johansson Erik , Diffley John F.X
Published: November 2020

Single-stranded DNA breaks, including simple nicks, are amongst the most common forms of DNA damage in cells. They can be readily repaired by ligation; however, if a nick occurs just ahead of an approaching replisome, the outcome is a ‘collapsed’ replication fork in which the nick is converted into a single-ended double-strand DNA break. Attention has largely focused on the processes by which this broken end is used to prime replication restart. We realized that in eukaryotic cells, where replication initiates from multiple replication origins, a second fork converging on the collapsed fork offers additional opportunities for repair, but also generates a substrate that can promote localized re-replication. We have modelled this with purified proteinsin vitroand have found that there is, indeed, an additional hazard that eukaryotic replisomes face. We discuss how this problem might be mitigated.
GABAergic signaling promotes early-life seizures in epileptic SYNGAP1+/-mice
Authors: Sullivan Brennan J. , Kipnis Pavel A. , Ammanuel Simon G. , Kadam Shilpa D.
Published: November 2020

Objective

SYNGAP1encephalopathy is a developmental and epileptic encephalopathy caused by pathogenic loss of function variants.Syngap1-heterozygous (Het+/-) mice demonstrate progressive epilepsy with multiple seizure phenotypes in adulthood. Here, we investigate early-life seizures in Het+/-pups and explore ofSyngap1encephalopathy during development.

Methods

Post-natal day 7 (P7) and P12 mice were investigated by tethered video-electroencephalographic (vEEG). The effects of GABAergic drugs phenobarbital (PB) and pentylenetetrazol (PTZ) were investigated at P7 and P12, respectively. 24h tethered vEEG was performed at P24, and telemetric 24h vEEG with 6h sleep deprivation was performed at P35. The effect of perampanel (PMP), an AMPA receptor antagonist, was investigated at P24.

Results

Het+/-mice have spontaneous early-life seizures that lack an overt behavioral phenotype. These subclinical seizures are refractory to PB, but the GABAAreceptor (GABAAR) antagonist PTZ significantly reduced seizure frequency suggesting that GABAergic signaling may promote seizure generation in Het+/-pups. At juvenile ages, Het+/-pups recapitulated the early emergence of high gamma (35-50Hz) during NREM and disruption of behavioral-state gamma homeostasis. This biomarker was significantly exacerbated in Het+/-pups after increasing sleep pressure with sleep deprivation.

Significance

Seizures during development have adverse effects on cognitive function. Therefore, an improved understanding of theSYNGAP1epilepsy during developmental ages is necessary to delineate the deleterious interactions between aberrant synaptic function and recurrent seizures. The development of evidence-based therapies for early-life intervention will benefit from these insights.
Preferred auditory temporal processing regimes and auditory-motor interactions
Authors: Kern Pius , Assaneo M. Florencia , Endres Dominik , Poeppel David , Rimmele Johanna M.
Published: November 2020

Decoding the rich temporal dynamics of complex sounds such as speech is constrained by the underlying neuronal processing mechanisms. Oscillatory theories suggest the existence of one optimal perceptual performance regime at auditory stimulation rates in the delta to theta range (<10 Hz), but reduced performance in the alpha range (10-14 Hz) is controversial. Additionally, the widely discussed motor system contribution to timing remains unclear. We measured rate discrimination thresholds between 4-15 Hz, and auditory-motor coupling strength was estimated through auditory-motor synchronization. In a Bayesian model comparison, high auditory-motor synchronizers showed a larger range of constant optimal temporal judgments than low synchronizers, with performance decreasing in the alpha range. This evidence for optimal auditory processing in the theta range is consistent with preferred oscillatory regimes in auditory cortex that compartmentalize stimulus encoding and processing. The findings suggest, remarkably, that increased auditory-motor interaction might extend such an optimal range towards faster rates.
Genome-wide Identification of the Genetic Basis of Amyotrophic Lateral Sclerosis
Authors: Zhang Sai , Cooper-Knock Johnathan , Weimer Annika K. , Shi Minyi , Moll Tobias , Harvey Calum , Nezhad Helia Ghahremani , Franklin John , dos Santos Souza Cleide , Wang Cheng , Li Jingjing , Elhaik Eran , Eitan Chen , Hornstein Eran , Kenna Kevin P. ,   Project MinE Sequencing Consortium, Veldink Jan , Ferraiuolo Laura , Shaw Pamela J. , Snyder Michael P.
Published: November 2020

Amyotrophic lateral sclerosis (ALS) is an archetypal complex disease centered on progressive death of motor neurons. Despite heritability estimates of 52%, GWAS studies have discovered only seven genome-wide significant hits, which are relevant to <10% of ALS patients. To increase the power of gene discovery, we integrated motor neuron functional genomics with ALS genetics in a hierarchical Bayesian model called RefMap. Comprehensive transcriptomic and epigenetic profiling of iPSC-derived motor neurons enabled RefMap to systematically fine-map genes and pathways associated with ALS. As a significant extension of the known genetic architecture of ALS, we identified a group of 690 candidate ALS genes, which is enriched with previously discovered risk genes. Extensive conservation, transcriptome and network analyses demonstrated the functional significance of these candidate genes in motor neurons and disease progression. In particular, we observed a genetic convergence on the distal axon, which supports the prevailing view of ALS as a distal axonopathy. Of the new ALS genes we discovered, we further characterizedKANK1that is enriched with coding and noncoding, common and rare ALS-associated genetic variation. Modelling patient mutations in human neurons reducedKANK1expression and produced neurotoxicity with disruption of the distal axon. RefMap can be applied broadly to increase the discovery power in genetic association studies of human complex traits and diseases.
Insulin Resistance Mediates Crosstalk between Skeletal Muscle and the Heart to Prevent Cardiac Dysfunction
Authors: Jia Dandan , Zhang Jun , Liu Xueling , Anderson John-Paul , Tian Zhenjun , Nie Jia , Shi Yuguang
Published: November 2020

Obesity and type 2 diabetes milieus (T2DM) are the leading causes of cardiovascular morbidity and mortality. Although insulin resistance is believed to underlie these disorders, a paradox exists that obese patients with cardiovascular diseases have better prognoses relative to leaner patients with the same diagnoses, whereas improvement of insulin sensitivity by thiazolidines significantly increases the risk of heart failure in T2DM patients. Using mice with skeletal muscle-specific deletion of the insulin receptor gene (MIRKO), we resolved this dilemma by demonstrating that insulin resistance in the skeletal muscle prevents myocardial hypertrophy and dysfunction in response to diet-induced obesity. In spite of aggregating obesity, insulin resistance selectively protected the heart, but not other metabolic tissues, from mitochondrial dysfunction and insulin resistance in MIRKO mice, leading to significant attenuation of inflammation and apoptosis of cardiomyocytes. Together, our findings revealed an unexpected role of insulin resistance as a double edge sword, calling for reevaluation of ongoing efforts for targeting insulin resistance for the treatment of metabolic diseases.

Significance statement

Insulin resistance is commonly recognized as one of the major causes of T2DM and other aging-related chronic diseases. However, cumulative efforts in targeting insulin resistance for the treatment of T2DM and other metabolic disorders have not met with great success due to unwanted side effects on heart failure. Here we report that insulin resistance in skeletal muscle is a double edge sword. On one hand, insulin resistance in skeletal muscle aggregates obesity and its related metabolic syndromes, and on the other it protects the heart from the development of myocardial hypertrophy, dysfunction, and apoptosis in response to DIO. Our findings call for reevaluation of the ongoing strategies in targeting insulin resistance as a novel treatment for T2DM and other metabolic diseases.
osr1couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation
Authors: Perens Elliot A. , Diaz Jessyka T. , Quesnel Agathe , Askary Amjad , Crump J. Gage , Yelon Deborah
Published: November 2020

Transcriptional regulatory networks refine gene expression boundaries throughout embryonic development to define the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and its neighboring vessel progenitors are poorly understood. Here, we delineate new roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafishosr1mutants display decreased IM formation and premature emergence of neighboring lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss ofhand2partially suppresses theosr1mutant phenotypes.hand2andosr1are both expressed in the posterior lateral mesoderm, butosr1expression decreases dramatically prior to LVP emergence. Overexpressingosr1inhibits LVP development while enhancing IM formation. Together, our data demonstrate thatosr1modulates both the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels ofosr1andhand2expression is essential to demarcate the dimensions of kidney and vessel progenitor territories.

SUMMARY STATEMENT

Analysis of theosr1mutant phenotype reveals roles in determining the extent of intermediate mesoderm formation while inhibiting premature differentiation of neighboring vessel progenitors.
Neurexins play a crucial role in cerebellar granule cell survival by organizing autocrine machinery for neurotrophins
Authors: Uemura Takeshi , Suzuki Emi , Kawase Shiori , Kurihara Taiga , Yasumura Misato , Yoshida Tomoyuki , Fukai Shuya , Yamazaki Maya , Fei Peng , Abe Manabu , Watanabe Masahiko , Sakimura Kenji , Mishina Masayoshi , Tabuchi Katsuhiko
Published: November 2020

Neurexins (NRXNs) are among the key presynaptic cell adhesion molecules that regulate synapse function and formation via trans-synaptic interaction with postsynaptic ligands. Here, we generated cerebellar granule cell (CGC)-specificNrxntriple-knockout (TKO) mice to allow the deletion of all NRXNs. Unexpectedly, most CGCs died in these mice. The requirement of NRNXs for cell survival was reproduced in cultured CGCs. We showed that the axons of culturedNrxnTKO CGCs that were not in contact with the postsynaptic structure had defects in the formation of presynaptic protein cluster and action potential-induced Ca2+influx. Additionally, these cells were impaired in the secretion from axons of depolarization-induced fluorescence-tagged brain-derived neurotrophic factor (BDNF), and the cell-survival defect was rescued by the application of BDNF. Our results suggest that CGC survival is maintained by autocrine neurotrophic factors, and that NRXNs organize the presynaptic protein clusters and the autocrine neurotrophic factor secretory machinery independent of contact with postsynaptic ligands.
The integration of Tgfβ and Egfr signaling programs confers the ability to lead heterogeneous collective invasion
Authors: Nasir Apsra , Camacho Sharon , McIntosh Alec T. , Graham Garrett T. , Rahhal Raneen , Huysman Molly E. , Alsharief Fahda , Riegel Anna T. , Pearson Gray W.
Published: November 2020

Phenotypic heterogeneity promotes tumor evolution and confounds treatment. Minority subpopulations of trailblazer cells enhance the heterogeneity of invading populations by creating paths in extracellular matrix (ECM) that permit the invasion of phenotypically diverse siblings. The regulatory programs that induce a trailblazer state are poorly understood. Here, we define a new Tgfβ induced trailblazer population that is more aggressive than previously characterized Keratin 14 expressing trailblazer cells. Rather than triggering a binary switch to a single trailblazer state, Tgfβ induced multiple unique states that were distinguished by their expression of regulatory transcription factors, genes involved in ECM reorganization and capacity to initiate collective invasion. The integration of a parallel Egfr signaling program was necessary to induce pro-motility genes and could be targeted with clinically approved drugs to prevent trailblazer invasion. Surprisingly, Egfr pathway activity also had the collateral consequence of antagonizing the expression of a cohort of Tgfβ induced genes, including a subset involved in ECM remodeling. Together, our results reveal a new compromise mode of signal integration that promotes a trailblazer state and can be therapeutically targeted to prevent collective invasion.
Nonlinear ultrasonic waves in a magneto-flexo-thermally actuated single walled armchair carbon nanotube embedded on polymer matrix
Authors: Selvamani Rajendran , Jayan M. Mahaveer Sree , Ebrahimi Farzad
Published: November 2020

Purpose

The purpose of this paper is concerned with the study of nonlinear ultrasonic waves in a magneto-flexo-thermo (MFT) elastic armchair single-walled carbon nanotube (ASWCNT) resting on polymer matrix.

Design/methodology/approach

A mathematical model is developed for the analytical study of nonlinear ultrasonic waves in a MFT elastic armchair single walled carbon nanotube rested on polymer matrix using Euler beam theory. The analytical formulation is developed based on Eringen’s nonlocal elasticity theory to account small scale effect. After developing the formal solution of the mathematical model consisting of partial differential equations, the frequency equations have been analysed numerically by using the nonlinear foundations supported by Winkler-Pasternak model. The solution is obtained by ultrasonic wave dispersion relations.

Findings

From the literature survey, it is evident that the analytical formulation of nonlinear ultrasonic waves in an MFT elastic ASWCNT embedded on polymer matrix is not discussed by any researchers. So, in this paper the analytical solutions of nonlinear ultrasonic waves in an MFT elastic ASWCNT embedded on polymer matrix are studied. Parametric studies is carried out to scrutinize the influence of the nonlocal scaling, magneto-electro-mechanical loadings, foundation parameters, various boundary condition and length on the dimensionless frequency of nanotube. It is noticed that the boundary conditions, nonlocal parameter and tube geometrical parameters have significant effects on dimensionless frequency of nanotubes.

Originality/value

This paper contributes the analytical model to find the solution of nonlinear ultrasonic waves in an MFT elastic ASWCNT embedded on polymer matrix. It is observed that the increase in the foundation constants raises the stiffness of the medium and the structure is able to attain higher frequency once the edge condition is C-C followed by S-S. Further, it is noticed that the natural frequency is arrived below 1% in both local and nonlocal boundary conditions in the presence of temperature coefficients. Also, it is found that the density and Poisson ratio variation affects the natural frequency with below 2%. The results presented in this study can provide mechanism for the study and design of the nano devices such as component of nano oscillators, micro wave absorbing, nano-electron technology and nano-electro--magneto-mechanical systems that make use of the wave propagation properties of ASWCNTs embedded on polymer matrix.
Cacao Capitalism and Extended Urbanization: On the Contradictory Origins of Bounded Urbanism in Nineteenth‐century Coastal Ecuador
Authors: Fenton Robert Priessman
Published: November 2020

This article challenges both contemporary and classic urban theory by analyzing the historical case of coastal Ecuador. Working from primary and secondary sources, I track the urbanization of coastal Ecuador during the long nineteenth century, when cacao exports determined not only the economic wellbeing of the city of Guayaquil, but of the entire tropical lowland region. I argue that this extended urban geography was both experienced and practiced as an unbounded economic and cultural region. As the value of cacao exports skyrocketed, capitalists in the city invested in infrastructural projects and financial instruments, divorcing money‐making from cacao production. After the Gran Incendio (great fire) of 1896, the city was rebuilt according to the ideals of modern liberal planning that further separated the city from the country symbolically, despite their continued material interconnection. This work suggests that long histories of capitalist urbanization provide material and theoretical support for critiquing bounded urban theory both past and present, by moving beyond the city and highlighting the processes undergirding spatial production under capitalist social relations. Likewise, this historical case study argues that city‐centrism, rather than being constituted epistemologically, was tied to liberal notions of the urban based on nineteenth‐century ideologies of modernization and progress.
The Effect of Land Fragmentation on the Technical Inefficiency of Dairy Farms
Authors: Bradfield Tracy , Butler Robert , Dillon Emma , Hennessy Thia , Kilgarriff Paul
Published: November 2020

Exploiting the link between land identification and farm accountancy data, we use a uniquely detailed database to conduct a robust analysis of land fragmentation and its effect on technical inefficiency on dairy farms in Ireland. Using a stochastic production frontier model, our results show that the number of parcels, the average distance between parcels and the main farm, and the portion of land separate from the main farm all increase technical inefficiency. Such inefficiency can be reduced through increased parcel area, reduced travel distances, advisory services contact, intensive practices and hired labour. Our findings support the need for policy to improve land and labour mobility, providing evidence to support incentives to promote the transfer and long‐term leasing of agricultural land.
High‐pressure processing of meat: Molecular impacts and industrial applications
Authors: Bolumar Tomas , Orlien Vibeke , Sikes Anita , Aganovic Kemal , Bak Kathrine H. , Guyon Claire , Stübler Anna‐Sophie , de Lamballerie Marie , Hertel Christian , Brüggemann Dagmar A.
Published: November 2020

High‐pressure processing (HPP) has been the most adopted nonthermal processing technology in the food industry with a current ever‐growing implementation, and meat products represent about a quarter of the HPP foods. The intensive research conducted in the last decades has described the molecular impacts of HPP on microorganisms and endogenous meat components such as structural proteins, enzyme activities, myoglobin and meat color chemistry, and lipids, resulting in the characterization of the mechanisms responsible for most of the texture, color, and oxidative changes observed when meat is submitted to HPP. These molecular mechanisms with major effect on the safety and quality of muscle foods are comprehensively reviewed. The understanding of the high pressure–induced molecular impacts has permitted a directed use of the HPP technology, and nowadays, HPP is applied as a cold pasteurization method to inactive vegetative spoilage and pathogenic microorganisms in ready‐to‐eat cold cuts and to extend shelf life, allowing the reduction of food waste and the gain of market boundaries in a globalized economy. Yet, other applications of HPP have been explored in detail, namely, its use for meat tenderization and for structure formation in the manufacturing of processed meats, though these two practices have scarcely been taken up by industry. This review condenses the most pertinent‐related knowledge that can unlock the utilization of these two mainstream transformation processes of meat and facilitate the development of healthier clean label processed meats and a rapid method for achieving sous vide tenderness. Finally, scientific and technological challenges still to be overcome are discussed in order to leverage the development of innovative applications using HPP technology for the future meat industry.
Habitat components and population density drive plant litter consumption byEudrilus eugeniae(Oligochaeta) under tropical conditions
Authors: KAMDEM Michel Mathurin , NGAKOU Albert , YANOU NJINTANG Nicolas , VOUA OTOMO Patricks
Published: November 2020

The ingestion of organic and mineral materials by earthworms is a prominent functional role that has profound consequences for the decomposition and stabilization of soil organic matter. To investigate the litter consumption of the African nightcrawler earthwormEudrilus eugeniaeunder different tropical conditions, we used DNA barcoding to identify specimens ofE. eugeniaecollected from sites across the Adamawa region in Cameroon, and studied the influence of habitat suitability (soil properties), soil moisture, litter type, and population density on litter consumption. A total of four litter consumption experiments were carried out using soils collected from refuse disposal sites, agricultural lands, and savannahs dominated by the Mexican sunflowerTithonia diversifolia. The results revealed that litter consumption significantly increased in the refuse disposal and agricultural soils as opposed to the Mexican sunflower (T. diversifolia) soil, a cow dung enriched substrate, and a sterile soil horizon from the savannah (P< 0.05). The optimum moistures for litter consumption were between 24% and 50%. Litter type did not affect the consumption rate of the earthworms (P> 0.05). We observed a general positive density‐dependent consumption with litter mass loss increasing with increasing density. Our results suggest thatE. eugeniaehas a strong direct effect on the decomposition of plant materials than expected from previous estimations, and that litter consumption rates are determined by several habitat components and population density.
Preparation and antioxidant activities of polysaccharides obtained from abalone viscera by combination of enzymolysis and multiple separation methods
Authors: Guo Shu , Wang Jiao , He Chuanbo , Wei Haocheng , Ma Ying , Xiong Hejian
Published: November 2020

Abalone viscera were byproducts of the abalone processing and usually discarded as wastes. In this study, we tried to obtain functional polysaccharides from abalone viscera by a combination of enzymatic hydrolysis, membrane separation, anion exchange chromatography, and gel filtration techniques. Abalone viscera underwent successive hydrolyzation with alcalase and flavourzyme. Each enzymolysis was followed by deproteinization via membrane separation. The final yield of crude abalone viscera polysaccharide (CAVP) was 19.72%; the polysaccharide content of CAVP was 51.75%. Furthermore, three fractions of polysaccharides (AVP1, AVP2, and AVP3) were isolated from the CAVP by anion exchange chromatography and gel filtration. The molecular weights of each AVP were 14.99 kDa, 58.48 kDa, and 39.63 kDa, with a carbohydrate content of 62.75, 23.09, and 44.67%, respectively. These AVPs showed excellent antioxidant activities in vitro. Our results provide a scientific basis for the further utilization of polysaccharides from abalone viscera.

Practical Application

This study demonstrated an eco‐friendly approach for industrial production of high purity animal‐derived polysaccharides without any environmental pollution caused by the viscera waste of abalone and promoting the comprehensive utilization of abalone resources.
Investigation of sugars, organic acids, phenolic compounds, antioxidant activity and the aroma fingerprint of small white apricots grown in Xinjiang
Authors: Su Congyan , Zheng Xiaochun , Zhang Dandan , Chen Yu , Xiao Jing , He Yi , He Jingren , Wang Bin , Shi Xuewei
Published: November 2020

Small white apricot is well known as a famous fresh fruit and even a folk medicine in Xinjiang. To investigate nutritive value, antioxidant activity, and flavor of small white apricot, sugars, organic acids, total flavonoids, phenolic compounds, antioxidant activities, and volatile compounds in five apricot cultivars were examined by high‐performance liquid chromatography (HPLC) and headspace solid‐phase microextraction coupled with gas chromatography–mass spectrometry (HS‐SPME‐GC‐MS). The results showed that sucrose (32.94% to 42.49%), malic acid (69.21% to 76.75%), and quercetin‐3‐rutinoside (72.84% to 74.05%) were the dominant sugar, organic acid, and phenolic compounds in small white apricot, respectively. The antioxidant activity reached up to 61.72 to 135.52 mg TEs 100 g−1. Furthermore, the aroma fingerprint of the small white apricot consisted of 1‐octen‐3‐ol, 1‐dodecanol, pentanal, hexanal, (E)‐2‐hexenal, (E)‐2‐heptenal, 6‐methyl‐5‐hepten‐2‐one, (E)‐2‐nonenal, 1‐octen‐3‐one, β‐myrcene, and linalool, providing clear green, grassy, and fatty notes. Apricots from different cultivars possessed a similar flavor, while linalool and (E)‐2‐hexenal had been identified as the characteristic aroma compounds in small white apricot. The results provide a complete chemical characterization of the taste, functional ingredients and aroma of the small white apricot.

Practical Application

The nutritive value, antioxidant activity and flavor of small white apricot were investigated in this study. The results will provide a theoretical basis for developing characteristic variety aroma, nutritive value, and medicinal value of small white apricot.