bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic identification of the interactome of stalled ribosome nascent chain complexes translating the thylakoid membrane protein D1
Authors: Stolle Dominique S. , Treimer Paul , Lambertz Jan , Osterhoff Lena , Bischoff Annika , Dünschede Beatrix , Rödiger Anja , Herrmann Christian , Baginsky Sacha , Nowaczyk Marc M. , Schünemann Danja
Published: March 2022

The synthesis of multi-span thylakoid membrane proteins initiates at ribosomes off the membrane. Subsequently, the ribosome nascent chain complexes (RNCs) are transferred to the translocase machinery in the thylakoid membrane for cotranslational protein insertion. These steps require finely tuned mechanisms for protein processing, quality control, and targeting to prevent misfolding or aggregation and to ensure efficient transfer of the nascent chain to the insertion machinery. However, little is known about the regulatory network underlying these processes. To identify factors specifically involved in the cotranslational biogenesis of the reaction center protein D1 of photosystem II we established a chloroplast-derived in vitro translation method that allows the production and affinity purification of stalled RNCs bearing nascent chains of D1 of different defined lengths. Stalled RNCs translating the soluble ribosomal subunit uS2c were affinity-purified for comparison. Quantitative tandem-mass spectrometry revealed a set of about 120 proteins specifically associated with D1 RNCs. The interactome includes proteins with broad functions in protein processing, biogenesis and metabolic pathways, such as chlorophyll biosynthesis. We identified STIC2 as a new factor specifically associated with D1 RNCs. Furthermore, our results demonstrated that the interaction of STIC2 with the thylakoid insertase Alb3 and its homologue Alb4 is mediated by the conserved motif III within the C-terminal regions of Alb3 and Alb4. Our data suggest that STIC2 is involved in cotranslational substrate delivery at the thylakoid membrane by coordinating the binding of the D1 RNCs to the insertase machinery.
GBScleanR: Robust genotyping error correction using hidden Markov model with error pattern recognition
Authors: Furuta Tomoyuki , Yamamoto Toshio , Ashikari Motoyuki
Published: March 2022

Reduced-representation sequencing (RRS) provides cost-effective and time-saving genotyping platforms. Although the outstanding advantage of RRS in throughput, the obtained genotype data usually contains a large number of errors. Several error correction methods employing hidden Morkov model (HMM) have been developed to overcome these issues. Those methods assume that markers have a uniform error rate with no bias in the allele read ratio. However, bias does occur because of uneven amplification of genomic fragments and read mismapping. In this paper we introduce an error correction tool, GBScleanR, which enables robust and precise error correction for noisy RRS-based genotype data by incorporating marker-specific error rates into the HMM. The results indicate that GBScleanR improves the accuracy by more than 25 percentage points at maximum as compared to the existing tools in simulation datasets and achieves the most reliable genotype estimation in real data even with error prone markers.
Structural and functional insight into the plant unique multimodular triphosphosphate tunnel metalloenzymes of Arabidopsis thaliana
Authors: Pesquera Marta , Martinez Jacobo , Wang Kai , Hofmann Manuel , Loubéry Sylvain , Steensma Priscille , Hothorn Michael , Fitzpatrick Teresa B.
Published: March 2022

Triphosphate tunnel metalloenzymes (TTMs) are found in all biological kingdoms and have been characterized in microorganisms and animals. Members of the TTM family already characterized have divergent biological functions and act on a range of triphosphorylated substrates (RNA, thiamine triphosphate, inorganic polyphosphate). TTM proteins in plants have received considerably less attention and are unique in that some homologs harbor additional domains including a P-loop kinase and transmembrane domain. Here we report on structural and functional aspects of the multimodular TTM1 and TTM2 of Arabidopsis thaliana. Tissue and cellular microscopy studies show that both AtTTM1 and AtTTM2 are expressed in actively dividing (meristem) tissue and are tail-anchored proteins at the outer mitochondrial membrane - mediated by the single transmembrane domain at the C-terminus, supporting earlier studies. Crystal structures of AtTTM1 in the presence and absence of a non-hydrolyzable ATP analog reveal a catalytically incompetent TTM tunnel domain tightly interacting with the P-loop kinase domain that is locked in an inactive conformation. Structural comparison reveals that a helical hairpin may facilitate movement of the TTM domain thereby activating the kinase. Genetic studies show that AtTTM2 is important for the developmental transition from the vegetative to the reproductive phase in Arabidopsis, whereas its closest paralog AtTTM1 is not. Rational design of mutations based on the 3D structure demonstrates that both the P-loop kinase and TTM tunnel modules of AtTTM2 are required for the developmental switch.
Informative and adaptive distances and summary statistics in sequential approximate Bayesian computation
Authors: Schälte Yannik , Hasenauer Jan
Published: March 2022

Calibrating model parameters on heterogeneous data can be challenging and inefficient. This holds especially for likelihood-free methods such as approximate Bayesian computation (ABC), which rely on the comparison of relevant features in simulated and observed data and are popular for otherwise intractable problems. To address this problem, methods have been developed to scale-normalize data, and to derive informative low-dimensional summary statistics using inverse regression models of parameters on data. However, while approaches only correcting for scale can be inefficient on partly uninformative data, the use of summary statistics can lead to information loss and relies on the accuracy of employed methods.

In this work, we first show that the combination of adaptive scale normalization with regression-based summary statistics is advantageous on heterogeneous parameter scales. Second, we present an approach employing regression models not to transform data, but to inform sensitivity weights quantifying data informativeness. Third, we discuss problems for regression models under non-identifiability, and present a solution using target augmentation. We demonstrate improved accuracy and efficiency of the presented approach on various problems, in particular robustness and wide applicability of the sensitivity weights. Our findings demonstrate the potential of the adaptive approach. The developed algorithms have been made available in the open-source Python toolbox pyABC.
Sequence-structure-function relationships in the microbial protein universe
Authors: Koehler Leman Julia , Szczerbiak Pawel , Renfrew P. Douglas , Gligorijevic Vladimir , Berenberg Daniel , Vatanen Tommi , Taylor Bryn C. , Chandler Chris , Janssen Stefan , Pataki Andras , Carriero Nick , Fisk Ian , Xavier Ramnik J. , Knight Rob , Bonneau Richard , Kosciolek Tomasz
Published: March 2022

Abstract / Summary

For the past half-century, structural biologists relied on the notion that similar protein sequences give rise to similar structures and functions. While this assumption has driven research to explore certain parts of the protein universe, it disregards spaces that don’t rely on this assumption. Here we explore areas of the protein universe where similar protein functions can be achieved by different sequences and different structures. We predict ∼200,000 structures for diverse protein sequences from 1,003 representative genomes1across the microbial tree of life, and annotate them functionally on a per-residue basis. Structure prediction is accomplished using the World Community Grid, a large-scale citizen science initiative. The resulting database of structural models is complementary to the AlphaFold database, with regards to domains of life as well as sequence diversity and sequence length. We identify 148 novel folds and describe examples where we map specific functions to structural motifs. We also show that the structural space is continuous and largely saturated, highlighting the need for shifting the focus from obtaining structures to putting them into context, to transform all branches of biology, including a shift from sequence-based to sequence-structure-function based meta-omics analyses.
Universal dynamics of biological pattern formation in spatio-temporal morphogen variations
Authors: Dalwadi Mohit P. , Pearce Philip
Published: March 2022

In biological systems, chemical signals termed morphogens self-organise into patterns that are vital for many physiological processes. As observed by Turing in 1952, these patterns are in a state of continual development, and are usually transitioning from one pattern into another. How do cells robustly decode these spatio-temporal patterns into signals in the presence of confounding effects caused by unpredictable or heterogeneous environments? Here, we answer this question by developing a general theory of pattern formation in spatio-temporal variations of ‘pre-pattern’ morphogens, which determine gene-regulatory network parameters. Through mathematical analysis, we identify universal dynamical regimes that apply to wide classes of biological systems. We apply our theory to two paradigmatic pattern-forming systems, and predict that they are robust with respect to non-physiological morphogen variations. More broadly, our theoretical framework provides a general approach to classify the emergent dynamics of pattern-forming systems based on how the bifurcations in their governing equations are traversed.
Genetic Analysis Suggests a Surface of PAT-4 (ILK) that Interacts with UNC-112 (kindlin)
Authors: Qadota Hiroshi , McPherson Annie , Corbitt Rachel , Dackowski Evan Kelton , Matsunaga Yohei , Oberhauser Andres , Benian Guy M.
Published: March 2022

The transmembrane protein integrin plays a crucial role in the attachment of cells to the extracellular matrix. Integrin recruits many proteins intracellularly, including a four protein complex (Kindlin, Integrin linked kinase (ILK), PINCH, and parvin). C. elegans muscle provides an excellent model to study integrin adhesion complexes. In C. elegans, UNC-112 (Kindlin) binds to the cytoplasmic tail of PAT-3 (β-integrin) and to PAT-4 (ILK). We previously reported that PAT-4 binding to UNC-112 is essential for the binding of UNC-112 to PAT-3. Although there are crystal structures for ILK and a kindlin, there is no co-crystal structure available. To understand the molecular interaction between PAT-4 (ILK) and UNC-112 (Kindlin), we took a genetic approach. First, we isolated mutant PAT-4 proteins that cannot bind to UNC-112. Then, we isolated suppressor mutant UNC-112 proteins that restore interaction with mutant PAT-4 proteins. Second, these mutant PAT-4 proteins cannot localize to attachment structures in nematode muscle, but upon co-expression of an UNC-112 suppressor mutant protein, the mutant PAT-4 protein could localize to attachment structures. Third, overexpression of a mutant PAT-4 protein results in disorganization of the adhesion plaques at muscle cell boundaries, and co-expression of the UNC-112 supressor mutant protein alleviates this defect. Thus, we demonstrate that UNC-112 binding to PAT-4 is required for the localization and function of PAT-4 in integrin adhesion complexes in vivo. The missense mutations were mapped onto homology models of PAT-4 and UNC-112, and taking into account previously isolated mutations, we suggest a surface of PAT-4 that binds to UNC-112.
Meta-analysis of the autism gut microbiome identifies factors influencing study discrepancies and machine learning classification
Authors: Chavira Aries , Wang Eric Hou-Jen , Mills Robert H.
Published: March 2022

Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder and accumulating evidence has suggested that dysbiosis of the gut microbiome plays an essential role. However, a body of research has investigated the ASD gut microbiome without consensus as to whether or how the ASD microbiome differs from neurotypical children. Here, we evaluate the underlying factors leading to study discrepancies by performing a meta-analysis on reprocessed 16S ribosomal RNA gene amplicon (16S) sequencing data. We compile a total of 1,740 samples across 13 carefully selected published studies together with samples from the American Gut Project, and analyze the data in aggregate and from a per-study perspective. We observed increased Bifidobacterium, Actinobacteria, and Prevotella among ASD individuals across cohorts. We further identified associations to Desulfovibrionales, Deltaproteobacteria and Prevotella that were dependent upon which 16S variable regions were sequenced. Utilizing machine learning (ML), we obtained increased accuracy in ASD classification using data collected from certain territories, on younger subjects, on unrelated age-matched rather than related controls, on samples with increased sequencing depth and when accounting for sex differences. Our work provides compelling evidence that the gut microbiome is altered in ASD patients, and highlights novel factors that are important considerations for future studies.
Transcriptional analysis identifies overlapping and tissue-distinct profiles between Kaposi sarcoma tumors of the skin and gastrointestinal tract
Authors: Ramaswami Ramya , Tagawa Takanobu , Mahesh Guruswamy , Serquina Anna , Koparde Vishal , Lurain Kathryn , Dremel Sarah , Li Xiaofan , Mungale Ameera , Beran Alex , Ohler Zoe Weaver , Bassel Laura , Warner Andrew , Mangusan Ralph , Widell Anaida , Ekwede Irene , Krug Laurie T. , Uldrick Thomas S. , Yarchoan Robert , Ziegelbauer Joseph M.
Published: March 2022

Kaposi sarcoma (KS), caused by Kaposi sarcoma herpesvirus (KSHV), is a multicentric tumor characterized by abnormal vasculature and proliferation of KSHV-infected spindle cells. KS commonly involves the skin but in severe cases KS can also involve the gastrointestinal tract (GI). Here, we sought to compare the cellular and KSHV gene expression signatures of skin and GI KS lesions. Skin and GI KS were compared to normal matched samples using bulk RNA sequencing.Twenty-two paired samples of KS and normal tissue were obtained (skin (10 pairs) and GI (12 pairs)) from 19 patients with KS of whom 17 had concurrent HIV infection. Seven paired samples were from patients who had received prior KS therapy. Three patients provided both skin and GI samples at the same timepoint. These analyses identified 370 differentially expressed genes unique to cutaneous KS and 58 DEGs unique to GI KS compared to normal skin or GI tissues. Twenty-six differentially expressed genes overlapped between skin and GI KS, which included FLT4, which encodes for a VEGF-C and VEGF-D receptor, and STC1. KSHV infection of primary lymphatic endothelial cells (LECs) resulted in increased angiogenesis, and repression of STC1 or FLT4 inhibited angiogenesis. The analyses of KSHV expression from KS lesions identified certain lytic genes, specifically ORF75, that were consistently expressed, and these expression patterns differed from laboratory infection of LECs with KSHV and KSHV gene expression in PEL cell lines. This study demonstrates that complex patterns of gene expression are found in KS tissue that differ from the canonical latent/lytic programs seen in KSHV cell lines and also demonstrates differences in viral gene and clinically relevant host gene expression in skin and GI KS that may offer insights into the pathogenesis of these forms of KS.

One sentence summary

Kaposi sarcoma that manifests in the skin and gastrointestinal tracts differ by human and viral gene expression.
Evidence that conserved essential genes are enriched for pro-longevity factors
Authors: Oz Naci , Vayndorf Elena , Tsuchiya Mitsuhiro , McLean Samantha , Turcios-Hernandez Lesly , Pitt Jason N. , Blue Ben W. , Muir Michael , Kiflezghi Michael G. , Tyshkovskiy Alexander , Mendenhall Alexander , Kaeberlein Matt , Kaya Alaattin
Published: March 2022

At the cellular level, many aspects of aging are conserved across species. This has been demonstrated by numerous studies in simple model organisms like Saccharomyces cerevisiae, Caenorhabdits elegans, and Drosophila melanogaster. Because most genetic screens examine loss of function mutations or decreased expression of genes through reverse genetics, essential genes have often been overlooked as potential modulators of the aging process. By taking the approach of increasing the expression level of a subset of conserved essential genes, we found that 25% of these genes resulted in increased replicative lifespan in S. cerevisiae. This is greater than the ∼3.5% of genes found to affect lifespan upon deletion, suggesting that activation of essential genes may have a relatively disproportionate effect on increasing lifespan. The results of our experiments demonstrate that essential gene overexpression is a rich, relatively unexplored means of increasing eukaryotic lifespan.
Modeling the Evolution of Rates of Continuous Trait Evolution
Authors: Martin B. S. , Bradburd G. S. , Harmon L. J. , Weber M. G.
Published: March 2022

Abstract

Rates of phenotypic evolution vary markedly across the tree of life, from the accelerated evolution apparent in adaptive radiations to the remarkable evolutionary stasis exhibited by so-called “living fossils”. Such rate variation has important consequences for large-scale evolutionary dynamics, generating vast disparities in phenotypic diversity across space, time, and taxa. Despite this, most methods for estimating trait evolution rates assume rates vary deterministically with respect to some variable of interest or change infrequently during a clade’s history. These assumptions may cause underfitting of trait evolution models and mislead hypothesis testing. Here, we develop a new trait evolution model that allows rates to vary gradually and stochastically across a clade. Further, we extend this model to accommodate generally decreasing or increasing rates over time, allowing for flexible modeling of “early/late bursts” of trait evolution. We implement a Bayesian method, termed “evolving rates” (evorates for short), to efficiently fit this model to comparative data. Through simulation, we demonstrate that evorates can reliably infer both how and in which lineages trait evolution rates varied during a clade’s history. We apply this method to body size evolution in cetaceans, recovering substantial support for an overall slowdown in body size evolution over time with recent bursts among some oceanic dolphins and relative stasis among beaked whales of the genus Mesoplodon. These results unify and expand on previous research, demonstrating the empirical utility of evorates.
AlphaFold encodes the principles to identify high affinity peptide binders
Authors: Chang Liwei , Perez Alberto
Published: March 2022

Machine learning has revolutionized structural biology by solving the problem of predicting structures from sequence information. The community is pushing the limits of interpretability and application of these algorithms beyond their original objective. Already, AlphaFold’s ability to predict bound conformations for complexes has surpassed the performance of docking methods, especially for protein-peptide binding. A key question is the ability of these methods to differentiate binding affinities between several peptides that bind the same receptor. We show a novel application of AlphaFold for competitive binding of different peptides to the same receptor. For systems in which the individual structures of the peptides are well predicted, predictions in which both peptides are introduced capture the stronger binder in the bound state, and the other peptide in the unbound form. The speed and robustness of the method will be a game changer to screen large libraries of peptide sequences to prioritize for detailed experimental characterization.
Low-Toxin Clostridioides difficile RT027 Strains Exhibit Robust Virulence
Authors: Anwar Farhan , Roxas Bryan Angelo P. , Shehab Kareem W. , Ampel Neil , Viswanathan VK , Vedantam Gayatri
Published: March 2022

Clostridioides difficile is a leading cause of healthcare-associated infections worldwide. Currently, there is lack of consensus on a single optimal diagnostic method for C. difficile infection (CDI). Nucleic acid amplification tests (NAAT) that detect toxin genes are highly sensitive, but their specificity limitations could inflate CDI rates. Alternate multi-step diagnostic algorithms emphasize the detection of C. difficile toxins TcdA/TcdB, and are premised on the rationale that stool toxin-negative (Tox-) CDI patients have less severe disease, shorter diarrhea duration, and fewer disease complications. There have been no systematic assessments, however, of the virulence of C. difficile strains from Tox-/NAAT+ (discrepant) specimens. In our prospective analysis of 1243 C. difficile-positive patient stool specimens from three Southern Arizona hospitals, 31% were discrepant. Ribotype 027 (RT027) strains were recovered from 221 specimens; of these, 23% were discrepant. Post-culture, RT027 strains produced a range of toxin amounts including levels lower than that of the non-epidemic strain CD630. These low-toxin RT027 (LT-027) strains harbored both tcdA and tcdB genes, and their culture supernatants were cytotoxic to cultured fibroblasts. We confirmed robust colonization and virulence of a subset of LT-027 strains using multiple rodent models; lethality in animals infected with LT-027 strains was comparable to that potentiated by a high-toxin RT027 strain. Comparative genomics and proteomics analyses of several LT-027 strains identified unique genes and altered protein abundances relative to closely-related high-toxin strains. Collectively our data highlight the robust virulence and clinical relevance of low-toxin-producing, RT027 C. difficile isolates.
Coenzyme Q regulates UCP1 expression and thermogenesis through the integrated stress responses
Authors: Chang Ching-Fang , Gunawan Amanda L. , Zushin Peter-James H. , Timblin Greg A. , Bertholet Ambre M. , Wang Biao , Sajio Kaoru , Kirichok Yuriy , Stahl Andreas
Published: March 2022

Coenzyme Q (CoQ) is an essential component of mitochondrial respiration1 and required for thermogenic activity in brown adipose tissues2 (BAT). CoQ deficiency leads to a wide range of pathological manifestations3 but mechanistic consequences of CoQ deficiency in specific tissues such as BAT remain poorly understood. Here we show that pharmacological or genetic CoQ deficiency (50-75% reduction) in BAT leads to accumulation of cytosolic mitochondrial RNAs (mtRNAs) and activation of the eIF2α kinase PKR resulting in the induction of the integrated stress response (ISR) and suppression of UCP1 expression in an ATF4-dependent fashion. Surprisingly, despite diminished UCP1 levels, BAT CoQ deficiency increases whole-body metabolic rates at room temperature and thermoneutrality resulting in decreased weight gain on high fat diets (HFD). This mitohormesis like effect of BAT CoQ insufficiency is dependent on the ATF4-FGF21 axis in BAT revealing an unexpected role for CoQ in the modulation of whole-body energy expenditure with wide-ranging implications for primary and secondary CoQ deficiencies.
A South American mouse morbillivirus sheds light into a clade of rodent-borne morbilliviruses
Authors: Debat Humberto J.
Published: March 2022

Morbilliviruses are negative sense single stranded monosegmented RNA viruses in the family Paramyxoviridae (order Mononegavirales). Morbilliviruses infect diverse mammals including humans, dogs, cats, small ruminants, seals, and cetaceans, which serve as natural hosts. Here, I report the identification and characterization of novel viruses associated with South American long-haired and olive field mice. The divergent viruses dubbed Ratón oliváceo morbillivirus (RoMV) detected in renal samples from mice collected from Chile and Argentina are characterized by an unusually large genome including long intergenic regions and the presence of an accessory protein between the F and H genes redounding in a genome architecture consisting in 3’-N-P/V/C-M-F-hp-H-L-5’. Structural and functional annotation, genetic distance and evolutionary insights suggest that RoMV is a member of a novel species within genus Morbillivirus tentatively dubbed South American mouse morbillivirus. Phylogenetic analysis suggests that this mouse morbillivirus is closely related to, and clusters into a monophyletic group of novel rodent-borne morbilliviruses. This subclade of divergent viruses expands the host range, redefines the genomic organization and provides insights on the evolutionary history of genus Morbillivirus.
A Biological Signature for the Inhibition of Outer Membrane Lipoprotein Biogenesis
Authors: Lehman Kelly M. , Smith Hannah C. , Grabowicz Marcin
Published: March 2022

The outer membrane (OM) of Gram-negative bacteria is an essential organelle that acts as a formidable barrier to antibiotics. Increasingly prevalent resistance to existing drugs has exacerbated the need for antibiotic discovery efforts targeting the OM. Acylated proteins, known as lipoproteins, are essential in every pathway needed to build the OM. The central role of OM lipoproteins makes their biogenesis a uniquely attractive therapeutic target, but it also complicates in vivo identification of on-pathway inhibitors, as inhibition of OM lipoprotein biogenesis broadly disrupts OM assembly. Here, we use genetics to probe the eight essential proteins involved in OM lipoprotein biogenesis. We define a biological signature consisting of three simple assays that can characteristically identify OM lipoprotein biogenesis defects in vivo. The few known chemical inhibitors of OM lipoprotein biogenesis conform to the biological signature. We also examine MAC13243, a proposed inhibitor of OM lipoprotein biogenesis, and find that it fails to conform to the biological signature. Indeed, we demonstrate that MAC13243 activity relies entirely on a target outside of the OM lipoprotein biogenesis pathway. Hence, our signature offers simple tools to easily assess whether antibiotic lead compounds target an essential pathway that is the hub of OM assembly.

IMPORTANCE

Gram-negative bacteria have an outer membrane, which acts as a protective barrier and excludes many antibiotics. The limited number of antibiotics active against Gram-negative bacteria, along with rising rates of antibiotic resistance, highlights the need for efficient antibiotic discovery efforts. Unfortunately, finding the target of lead compounds, especially ones targeting outer membrane construction, remains difficult. The hub of outer membrane construction is the lipoprotein biogenesis pathway. We show that defects in this pathway result in a signature cellular response that can be used to quickly and accurately validate pathway inhibitors. Indeed, we found that MAC13243, a compound previously proposed to target outer membrane lipoprotein biogenesis, does not fit the signature, and we show that it instead targets an entirely different cellular pathway. Our findings offer a streamlined approach to discovery and validation of lead antibiotics against a conserved and essential pathway in Gram-negative bacteria.
TheVerticillium longisporumphospholipase VlsPLA2is a virulence factor targets host nuclei and modulates plant immunity
Authors: Rafiei Vahideh , Vélëz Heriberto , Piombo Edoardo , Dubey Mukesh , Tzelepis Georgios
Published: March 2022

Phospholipases A2(PLA2) are lipolytic enzymes, responsible for phospholipids hydrolysis. The role of PLA2in various aspects of cell physiology has been shown, but their involvement in host-microbe interactions remains to be elucidated. The present study investigated the biological function of the secreted VIsPLA2phospholipase in the phytopathogenic fungusVerticillium longisporumwith emphasis on its role in host-microbe interactions. TheVlsPLA2was highly induced inV. longisporumduring interaction with host plantBrassica napus, encoding an active phospholipase A2. VlsPLA2-overexpressionV. longisporumstrain showed an increased virulence onArabidopsisplants, plausibly by inducing virulence factors. Furthermore, VIsPLA2are transported to the nucleus, by hijacking VAMPA proteins, causing suppression of PTI-induced hypersensitive response, possibly by modulating the expression of genes involved in plant immunity. In summary, VlsPLA2acts as a virulence factor by hydrolyzing the hosts nuclear envelope phospholipids, an action that induces signaling cascade, suppressing basal plant immunity responses.
Shallow environmental gradients can cause range margins to form
Authors: Tomasini Matteo , Eriksson Martin , Johannesson Kerstin , Rafajlović Marina
Published: March 2022

One hypothesis invoked to explain limits to species’ ranges is a mismatch in environmental conditions between the central and marginal areas of species’ ranges. Low population size at the margins causes genetic drift to outplay selection locally, and limits the accumulation of genetic variance, so that adaptation is hindered locally. Earlier theoretical work shows that, for a population expanding over a spatially heterogeneous environment without any geographical barriers, adaptation will fail abruptly and sharp range margins will establish only when the underlying environmental conditions change more and more severely across space, whereas an environment changing constantly will result either in infinite expansion or rapid global extinction. Here, we extend this “steepening-gradient hypothesis” to encompass situations when multiple (up to three) environmental factors impose selection on separate adaptive traits. We show that multiple selection gradients steepen each other and that it is sufficient that just one of the gradients steepen in space for sharp range margins to form. This is true even if this gradient is shallow throughout the realised range. Thus, despite its detrimental role in forming range margins, it could be overlooked in field studies. Finally, by decomposing an environmental gradient to selection on two (or three) adaptive traits, we show that a population can withstand harsher environmental conditions than when selection acts on one adaptive trait alone. This finding argues for the evolution of novel traits in harsh environments.
The genome wide analysis deciphered virulence factors and secondary metabolites of Chryseobacterium and description of Chryseobacterium indicum sp. nov
Authors: Victor Manish Prakash , Das Lipika , Das Subrata K.
Published: March 2022

This study describes a novel bacterium, Chryseobacterium strain PS-8, isolated from the skin of freshwater pufferfish (Tetraodon cutcutia). Cells are Gram-negative. The genome size is 4.72 Mb, and the G+C content is 36.4%. The in silico DDH homology, ANI, and AAI were below the cutoff value, 70% and 95% to 96%, respectively, as required for novel species delineation. The phylogenomic analysis using core and non-recombinant core genes, the strain PS-8 showed clustering with Chryseobacterium gambrini DSM 18014T. Generally, Chryseobacterium species are considered opportunistic pathogens. Prediction of the virulence genes revealed genes for adherence, biofilm and stability (glf, lpxD, clpE, cps0, clpE, IlpA), proliferation (tufA, cap8E, galE, kfic, bioB, clpP, kdtB, csgD, carB), resistance to immune response (htpB, katA, wbtl, sodB, kpsF), and host-defense evasion system (kpst, clpE, kfic, ybtQ, cap8G, clpP). The cladogram based upon the virulence genes showed a similar phylogeny amongst the Chryseobacterium species. Additionally, secondary metabolites producing gene clusters were identified, including microviridin, resorcinol and polyene, terpene, etc. Our study showed that strain PS-8 constitute a novel species for which Chryseobacterium indicum sp. nov. is proposed. The type strain is PS-8T (= TBRC 15233T = NBRC 115235T).
Multifaceted Atlases of the Human Brain in its Infancy
Authors: Ahmad Sahar , Wu Ye , Wu Zhengwang , Thung Kim-Han , Lin Weili , Li Gang , Wang Li , Yap Pew-Thian
Published: March 2022

Brain atlases agglomerate structural and functional features of a population of individuals in a standard coordinate space. Here, we introduce for the first time a collection of atlases that charts postnatal development of the human brain in a spatio-temporally dense manner from two weeks to two years of age. Atlases capturing month-to-month changes of the human brain are essentially nonexistent for the first two years of life — the critical developmental period during which the brain is evolving in virtually all facets at an exponential pace. This unmet need is compounded by the lack of atlases that provide a unified and holistic picture of the brain from both the perspectives of cortical surface convolutions and tissue volumetric characteristics. Existing surface and volumetric atlases are typically constructed independently in different coordinate spaces, causing discrepancies and complications in multifaceted analyses. Our month-specific conjoint surface and volumetric atlases chart normative patterns and capture key traits of early brain development and are therefore critical for identifying aberrations from normal developmental trajectories. Our atlases represent a major advance toward providing the neuroscience community an invaluable resource to facilitate the understanding of early structural and functional development by mapping multiple measurements of infant brains in a common reference frame for precise spatio-temporal quantification of cortical and subcortical changes.
Accurate Protein Domain Structure Annotation with DomainMapper
Authors: Manriquez-Sandoval Edgar , Fried Stephen D.
Published: March 2022

Automated domain annotation plays a number of important roles in structural informatics and typically involves searching query sequences against Hidden Markov Model (HMM) profiles. This process can be ambiguous or inaccurate when proteins contain domains with non-contiguous residue ranges, and especially when insertional domains are hosted within them. Here we present DomainMapper, an algorithm that accurately assigns a unique domain structure annotation to any query sequence, including those with complex topologies. We validate our domain assignments using the AlphaFold database and confirm that non-contiguity is pervasive (6.5% of all domains in yeast and 2.5% in human). Using this resource, we find that certain folds have strong propensities to be non-contiguous or insertional across the Tree of Life, likely underlying evolutionary preferences for domain topology. DomainMapper is freely available and can be run as a single command line function.

HIGHLIGHTS

DomainMapper generates a unique domain structure annotation, including non-contiguous and insertional domains

Automated annotations of non-contiguous domains are validated against the AlphaFold database

DomainMapper can be easily installed and used by non-experts

Certain folds have strong preferences to be non-contiguous or insertional

GRAPHICAL ABSTRACT
ASD modelling in organoids reveals imbalance of excitatory cortical neuron subtypes during early neurogenesis
Authors: Jourdon Alexandre , Wu Feinan , Mariani Jessica , Capauto Davide , Norton Scott , Tomasini Livia , Amiri Anahita , Suvakov Milovan , Schreiner Jeremy D. , Jang Yeongjun , Panda Arijit , Nguyen Cindy Khanh , Cummings Elise M. , Han Gloria , Powell Kelly , Szekely Anna , McPartland James C. , Pelphrey Kevin , Chawarska Katarzyna , Ventola Pamela , Abyzov Alexej , Vaccarino Flora M.
Published: March 2022

There is no clear genetic etiology or convergent pathophysiology for autism spectrum disorders (ASD). Using cortical organoids and single-cell transcriptomics, we modeled alterations in the formation of the forebrain between sons with idiopathic ASD and their unaffected fathers in thirteen families. Alterations in the transcriptome suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between the excitatory neurons of the dorsal cortical plate and other lineages such as the early-generated neurons from the putative preplate. The imbalance stemmed from a divergent expression of transcription factors driving cell fate during early cortical development. While we did not find probands’ genomic variants explaining the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and developmental transcriptome in idiopathic ASD.
Persistent postnatal migration of interneurons into the human entorhinal cortex
Authors: Nascimento Marcos Assis , Biagiotti Sean , Herranz-Pérez Vicente , Bueno Raymund , Ye Chun J. , Abel Taylor , Rubio-Moll Juan S. , Garcia-Verdugo Jose Manuel , Huang Eric J. , Alvarez-Buylla Arturo , Sorrells Shawn F.
Published: March 2022

The entorhinal cortex (EC) is a highly-interconnected hub for multisensory integration and memory processing1–3, containing diverse neuronal subtypes4,5 including subpopulations that are uniquely spatially-tuned6,7. Although many spatial and memory functions develop in infancy, it is considered that neurogenesis and neuronal migration to the EC occurs prenatally. Here we show that the postnatal human temporal lobe contains a prominent stream with large chains of young migrating neurons and many individual neurons breaking away directed into the EC. The EC stream forms between the second and third trimesters of prenatal development when the lateral ventricle walls in the temporal lobe collapse, displacing the subventricular zone (SVZ) and dividing radial glia. At birth, the EC stream follows a path of radial glial ﬁbers in the site of the collapsed ventricle. Migratory chains persist up to 11 months postnatally; however, many individually migrating young neurons can still be detected in the EC at 2 years of age and a few isolated cells at 3 years of age. Within the EC at birth, immature neurons are a mixed population expressing markers of the medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE), but postnatally rapidly become primarily CGE-derived. Using single-nuclei RNAseq we identified these lineages and found that the MGE-derived neurons matured at earlier postnatal ages compared to those derived from the CGE. The CGE interneurons arriving and maturing the latest included subtypes expressing calretinin (CR), reelin (RELN), and vasoactive intestinal protein (VIP) many of which settle in layer II of the entorhinal cortex. This study reveals that the human EC is still being constructed during the first years of life revealing the largest known postnatal stream of migratory neurons in humans. The protracted postnatal arrival of a diverse population of interneurons could contribute to plasticity8,9 and proper excitation-inhibition balance10,11 within these highly connected brain circuits.
Attracting the millennial customer: the case of food trucks
Authors: Kraus Sascha , Sen Sandipan , Savitskie Katrina , Kumar Sampath K. , Brooks John
Published: March 2022

Purpose

The purpose of this paper is to examine millennial customer perceptions of food trucks and to identify factors that can foster their behavioral intentions pertaining to food trucks.

Design/methodology/approach

The study is based on a sample of 247 millennial customers of various food truck vendors in the United States and was assessed using ordinary least squares regression analysis.

Findings

Food truck image and employee friendliness were found to impact both customer satisfaction and word of mouth behavior; however, the other hypotheses were not supported.

Research limitations/implications

There were two limitations. The first was that one of the constructs did not achieve the minimum average variance extracted. The second was that data collection was done in a single city in the United States; therefore, future research could overcome these limitations through a refinement of the construct’s items and targeting more cities.

Originality/value

There has been limited academic research on the millennial customer perceptions of the food truck phenomenon. This research addresses that gap through a field study that examines factors that contributed to the growth and popularity of food trucks among millennials
Potential role of general practice in reducing emergency department demand: A qualitative study
Authors: Willson Katie A , Lim David , Toloo Ghasem‐Sam , FitzGerald Gerry , Kinnear Frances B , Morel Douglas G
Published: March 2022

Objective

To inform local, state and national strategies intended to reduce demand for ED care, the present study aimed to identify key factors influencing the current provision of acute care within primary healthcare (PHC) and explore the policy and system changes potentially required.

Methods

Semi‐structured interviews with key stakeholders were audio‐recorded, transcribed verbatim and analysed through content and thematic approaches incorporating the Walt and Gilson health policy framework.

Results

Eleven interviews were conducted. Five key considerations were highlighted, namely the barriers and enablers for general practitioners (GPs) in providing acute care, barriers to patient use of PHC instead of ED, suggestions for new PHC models and improvements for current ED models. Additionally, economic issues relating to clinic funding and GP remuneration, complexities of state or federal funding and management of urgent care centres (UCC) were identified. Potential policy changes included GP clinics incorporating emergency appointments, GP triage, further patient streaming and changes to the ED medical workforce model, as well as linking hospitals with PHC clinics. Suggested system changes included improving rapid access to non‐GP specialists, offering qualifications for urgent care within PHC, developing integrated information technology systems and educating patients regarding appropriate healthcare system pathways.

Conclusion

The present study suggested that while PHC has the potential to attenuate the demands for ED services, a whole‐of‐system approach focusing on realignment of priorities and integrated changes are needed.
Relative contribution of genetic and environmental factors to determination of wing morphs of the brown planthopper Nilaparvata lugens
Authors: Zhang Chao , Mao Meng‐Sha , Liu Xiang‐Dong
Published: March 2022

Wing dimorphism is a fascinating feature of the ability of insects to adapt to environments. The brown planthopper (BPH) Nilaparvata lugens, a serious pest of rice, can switch between the long‐ and short‐winged morphs. It has been known that environmental factors can affect the wing morph of BPH. However, it is still unclear whether the effect of environment is dependent on BPH genetic backgrounds or not. In the present study, we established the pure‐bred lineages of short‐ and long‐winged BPHs via multigenerational selection, and we found that survival and fecundity were similar between these 2 lineages. Wing morphs of the pure‐bred lineages were almost fully dependent on genetics, but independent of the environmental factors, nymphal density and rice plant stage, 2 key factors affecting BPH wing morphs. In the unselected BPH population, short‐ and long‐winged morphs were produced depending on those 2 environmental factors, indicating the contribution of environment to wing morph. In the wing‐selected lineages, 4 developmental regulated genes of wing, NlInR1, NlInR2, NlAkt, and NlFoxo were expressed stably in the short‐winged adults, but almost silenced in the long‐winged adults. However, all these genes were expressed normally with a similar level in both the short‐ and long‐winged adults in an unselected population except NlFoxo. The pure‐bred lineages of long‐ and short‐winged morphs exhibited different expression patterns of wing development‐regulated genes, suggesting the genetic determination of wing morphs. Effects of environmental factors on wing morphs occurred only in the genetic mix population.
From being sacked to being unwell: A conservation of resources view on the effects of psychological contract violation on layoff victims' wellbeing
Authors: Asante Eric Adom , Oduro Frederick , Danquah Barbara , Dei Mensah Rebecca , Dartey‐Baah Kwasi , Affum‐Osei Emmanuel
Published: March 2022

Although there is a consensus in the literature that layoff can be viewed as a form of psychological contract (PC) violation, research is yet to examine how such violation impacts layoff victims' well‐being outcomes including life satisfaction, sleep quality and psychological distress. Integrating psychological contract theory and the conservation of resource theory, we hypothesized a dual‐stage moderated mediation model in which PC violation resulting from layoff is associated with three dimensions of layoff victims' well‐being via worry. This indirect effect is proposed to be conditional on the level of social support received. Based on a sample of 252 layoff victims, we found support for the dual‐stage moderated mediation model in which the association between PC violation and the three dimensions of well‐being via worry was weak for layoff victims reporting high levels of social support. Findings contribute to our understanding of how PC violation is associated with nonwork outcomes.
Giving sleep position advice in pregnancy: Will we make women anxious?
Authors: Warland Jane , Footner Sarah , Beaufoy Georgie , Stocker Jade , Agostini Alex , Dorrian Jillian
Published: March 2022

Background

There is now robust evidence that when women settle to sleep on their back in late pregnancy (>28 weeks) they are at increased risk of stillbirth. Therefore, there are several stillbirth prevention programs worldwide that have begun advising pregnant women to adopt a side position when settling to sleep in late pregnancy. However, some hold concerns that giving women information about sleep position and stillbirth risk may make them anxious.

Aim

This study aimed to determine what influences how ‘safe sleep’ messages are perceived by pregnant women and if there is anxiety associated with receiving this message.

Materials and Methods

An online survey of 537 Australian women (n = 97 were ‘currently pregnant’). The survey examined participant’s views regarding sleep position messages, type of information source as well as participant characteristics such as general anxiety and their fetal health locus of control (FHLC).

Results

Our findings suggest that the FHLC may influence how health messaging regarding sleep in pregnancy is perceived and acted upon. We have also shown a subset of pregnant women may feel anxiety associated with the sleep position in pregnancy message. This may not be related to history of anxiety, but rather to their higher ‘internal’ FHLC, ie those who reflect a greater sense of personal agency over fetal health.

Conclusions

Our findings suggest most women will perceive information about settling into sleep position as informative rather than anxiety provoking. Therefore, maternity care providers should not be overly concerned about provoking anxiety when providing this information.