bluuebunny/crossref_metadata_2025 huggingface dataset:
Convolutional networks can model the functional modulation of the MEG responses associated with feed-forward processes during visual word recognition
Authors: van Vliet Marijn , Rinkinen Oona , Shimizu Takao , Niskanen Anni-Mari , Devereux Barry , Salmelin Riitta
Published: February 2022

Neuroimaging studies have provided a wealth of information about when and where changes in brain activity might be expected during reading. We sought to better understand the computational steps that give rise to such task-related modulations of neural activity by using a convolutional neural network to model the macro-scale computations necessary to perform single-word recognition. We presented the model with stimuli that had been shown to human volunteers in an earlier magnetoencephalography (MEG) experiment and evaluated whether the same experimental effects could be observed in both brain activity and model. In a direct comparison between model and MEG recordings, the model accurately predicted the amplitude changes of three evoked MEG response components commonly observed during single-word reading. In contrast to traditional models of reading, our model directly operates on the pixel values of an image containing text. This allowed us to simulate the whole gamut of processing from the detection and segmentation of letter shapes to word-form identification, with the deep learning architecture facilitating inclusion of a large vocabulary of 10k Finnish words. Interestingly, the key to achieving the desired behavior was to use a noisy activation function for the units in the model as well as to obey word frequency statistics when repeating stimuli during training. We conclude that the deep learning techniques that revolutionized models of object recognition can also create models of reading that can be straightforwardly compared to neuroimaging data, which will greatly facilitate testing and refining theories on language processing in the brain.
Assessing agreement between different polygenic risk scores in the UK Biobank
Authors: Clifton Lei , Collister Jennifer A , Liu Xiaonan , Littlejohns Tom J , Hunter David J
Published: February 2022

1.

Polygenic risk scores (PRS) are proposed to be used in clinical and research settings for risk stratification. However, there are limited investigations on how different PRS diverge from each other for risk prediction of individuals.

We compared two recently published PRS for each of three conditions, breast cancer, hypertension and dementia, to assess the stability of running these algorithms for risk prediction in a single large population. We used imputed genotyping data from the UK Biobank (UKB) prospective cohort, limited to the White British subset.

We found that:

Only 65%-79% of SNPs in the first PRS were represented in the more recent PRS for all three diseases, after having taken linkage disequilibrium (LD) into account (R2 >0.8).

Although the difference in the area under the received operator curve (AUC) obtained using the two PRS is hardly appreciable for all three diseases, there were large differences in individual risk prediction between the two PRS.

We found substantial discordance between different PRS for the same disease, indicating that individuals could receive different medical advice depending on which PRS is used to assess their genetic susceptibility. It is desirable to resolve this uncertainty before using PRS for risk stratification in clinical settings.
Exon variants associated with asthma and allergy1
Authors: Wjst Matthias
Published: February 2022

Recent biobank based exon sequencing studies included thousands of traits while the mutational spectrum of asthma and allergy associated genes is still unknown.

Methods

Meta-analysis of exome data from 281,104 UK Biobank samples that were analyzed for association of mostly rare variants with asthma, allergic rhinitis and atopic dermatitis. Variants of interest (VOI) were tabulated, shared genes annotated and compared to earlier GWAS, WGBS, WES and selected candidate gene studies.

Results

354 VOI were significantly associated with the traits examined. They cluster mainly in two large regions on chromosome 6 and 17 while there is basically no overlap of atopic dermatitis with both other diseases. After exclusion of the two atopic dermatitis variants, 321 unique VOI remain in 122 unique genes. 30 genes are shared by the group of 87 genes with increased and the group of 65 genes with decreased risk for allergic disease. 85% of genes identified earlier by common SNPs in GWAS can not be replicated.

Discussion

Most identified genes are involved in interferon γ and IL33 signaling pathway. They highlight already known but also new pharmacological targets, including the IL33 receptor ST2/IL1RL1, TLR1, ALOX15, GSDMA, BTNL2, IL13 and IKZF3. Future pharmacological studies will need to included these VOI for stratification of the study population.
Motor cortical influence relies on task-specific activity covariation
Authors: Warriner Claire L. , Fageiry Samaher , Saxena Shreya , Costa Rui M. , Miri Andrew
Published: February 2022

During limb movement, spinal circuits facilitate the alternating activation of antagonistic flexor and extensor muscles. Yet antagonist cocontraction is often required to stabilize joints, like when loads are handled. Previous results suggest that these different muscle activation patterns are mediated by separate flexion- and extension-related motor cortical output populations, while others suggest recruitment of task-specific populations. To distinguish between hypotheses, we developed a paradigm in which mice toggle between forelimb tasks requiring antagonist alternation or cocontraction and measured activity in motor cortical layer 5b. Our results conformed to neither hypothesis: consistent flexion- and extension-related activity was not observed across tasks, and no task-specific populations were observed. Instead, activity covariation among motor cortical neurons dramatically changed between tasks, thereby altering the relation between neural and muscle activity. This was also observed specifically for corticospinal neurons. Collectively, our findings indicate that motor cortex drives different muscle activation patterns via task-specific activity covariation.

HIGHLIGHTS

Mice perform two forelimb tasks involving distinct antagonist muscle activity in a novel paradigm

L5b motor cortical neurons are not organized by task-specific activity

L5b motor cortical neurons do not encode muscle activity consistently across tasks

Task-specific muscle activity is driven by a change in motor cortical activity covariation

eTOC BLURB

Warriner et al. simultaneously measured muscle and motor cortical activity in mouse during antagonist forelimb muscle alternation and cocontraction, revealing that these distinct muscle activation patterns are not driven through consistent flexion and extension programs nor through the activity of discrete, task-specific neuronal subsets. Instead, distinct patterns involve task-specific changes in firing pattern covariation among layer 5b neurons, and corticospinal neurons in particular, which change their relationship to muscle activity across tasks.
Quantitative live-cell imaging of secretion activity reveals dynamic immune responses
Authors: Yamagishi Mai , Miyata Kaede , Kamatani Takashi , Kabata Hiroki , Baba Rie , Tanaka Yumiko , Suzuki Nobutake , Matsusaka Masako , Motomura Yasutaka , Kiniwa Tsuyoshi , Koga Satoshi , Goda Keisuke , Ohara Osamu , Funatsu Takashi , Fukunaga Koichi , Moro Kazuyo , Uemura Sotaro , Shirasaki Yoshitaka
Published: February 2022

The measurement of cytokine secretions has contributed to the development of immunology; however, new methods that enable highly sensitive and efficient analysis are required for the precise characterisation of dynamic secretion activity when using rare cells or limited human specimens. Here, we report a new technology for quantitative live-cell imaging of secretion activity (qLCI-S), that enables high-throughput and dual-colour detection of prolonged secretion activity at the single-cell level, followed by transcriptome analysis for individual cells based on their phenotype. The power of the qLCI-S was demonstrated by visualising the individual and longitudinal cytokine secretion patterns of group 2 innate lymphoid cells, which comprised <0.01% human peripheral blood mononuclear cells, and identifying their minor subpopulations. This new technology will provide new insights into the spatiotemporal dynamic nature of various secretory functions and the development of fundamental tools for phenotypic drug discovery and regenerative and precision medicine.
Recapitulation of Human Pathophysiology and Identification of Forensic Biomarkers in a Translational Swine Model of Chlorine Inhalation Injury
Authors: Achanta Satyanarayana , Gentile Michael A. , Albert Carolyn J. , Schulte Kevin A. , Pantazides Brooke G. , Crow Brian S. , Quiñones-González Jennifer , Perez Jonas W. , Ford David A. , Patel Rakesh P. , Blake Thomas A. , Gunn Michael D. , Jordt Sven E.
Published: February 2022

Rationale

Chlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2exposures frequently occur in domestic and occupational environments, and in transportation accidents. There is a knowledge gap in large animal models of Cl2-induced acute lung injury (ALI) required to accurately model human etiology and for the development of targeted countermeasures

Objective

To develop a translational model of Cl2-induced ALI in swine to study toxico-pathophysiology and identify biomarkers useful for forensic analysis.

Methods

Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl2gas (≤ 240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation.

Results

Exposure to Cl2resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Chlorine exposure resulted in increased total BALF and neutrophil counts, vascular leakage, and edema compared to the control group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-L-tyrosine and 3,5-dichloro-L-tyrosine) were detected in plasma and lung after Cl2-exposure.

Conclusions

The translational model developed in this study replicates key features of humans exposed to Cl2and is suitable to test medical countermeasures. Specific biomarkers of Cl2exposure have been identified in plasma and lung tissue samples.

Take home message

We developed a swine model of chlorine gas-induced acute lung injury that exhibits several features of human acute respiratory distress syndrome. We validated chlorinated fatty acids and protein adducts in plasma and lung samples as forensic biomarkers.
Ontogeny of learning and visual discrimination in zebrafish
Authors: Santacà Maria , Dadda Marco , Valle Luisa Dalla , Fontana Camilla , Gjinaj Gabriela , Bisazza Angelo
Published: February 2022

With the exception of humans, early cognitive development has been thoroughly investigated only in precocial species, well developed at birth and with a broad behavioural and cognitive repertoire. We investigated another highly altricial species, the zebrafish, Danio rerio, whose embryonic development is very rapid: 72 hours. The nervous system of hatchlings is poorly developed, and their cognitive capacities are largely unknown. Larvae trained at 8 days post-fertilisation rapidly learned to associate a visual pattern with a food reward, showing significant performance at 10 days post-fertilisation. We exploited this capacity to study hatchlings’ discrimination learning capacities. Larval zebrafish rapidly and accurately learned colour and shape discriminations. They also discriminated a figure from its mirror image and from its 90°-rotated version, although with lower performance. Our study revealed impressive similarities in learning and visual discrimination capacities between newborn and adult zebrafish despite their enormous differences in brain size and degree of development.
Interaural time difference sensitivity under binaural cochlear implant stimulation persists at high pulse rates up to 900 pps
Authors: Buck Alexa N. , Buchholz Sarah , Schnupp Jan W. , Rosskothen-Kuhl Nicole
Published: February 2022

Background

Spatial hearing remains one of the major challenges for bilateral cochlear implant (biCI) users, and early deaf patients in particular are often completely insensitive to interaural time differences (ITDs) delivered through biCIs. One popular hypothesis is that this may be due to a lack of early binaural experience. However, we have recently shown that neonatally deafened rats fitted with biCIs in adulthood quickly learn to discriminate ITDs as well as their normal hearing litter mates, and perform an order of magnitude better than human biCI users.

Methods

Our unique behaving biCI rat model allows us to investigate other possible limiting factors of prosthetic binaural hearing, such as the effect of stimulus pulse rate and envelope shape. Previous work has indicated that ITD sensitivity may decline substantially at the high pulse rates often used in clinical practice. We therefore measured behavioral ITD thresholds in neonatally deafened, adult implanted biCI rats to pulse trains of 50, 300, 900 and 1800 pulses per second (pps), with either rectangular or Hanning window envelopes.

Results

Our rats exhibited very high sensitivity to ITDs at pulse rates up to 900 pps for both envelope shapes, similar to those in common clinical use. However, ITD sensitivity declined to near zero at 1800 pps, for both Hanning and rectangular windowed pulse trains.

Conclusions

Current clinical cochlear implant (CI) processors are often set to pulse rates ≥900 pps, but ITD sensitivity in human CI listeners has been reported to decline sharply above ∼300 pps. Our results suggest that the relatively poor ITD sensitivity seen at >300 pps in human CI users may not reflect the hard upper limit of biCI ITD performance in the mammalian auditory pathway. Perhaps with training or better CI strategies good binaural hearing may be achievable at pulse rates high enough to allow good sampling of speech envelopes while delivering usable ITDs.
TORC1, BORC, ARL-8 cycling, and kinesin-1 drive vesiculation of cell corpse phagolysosomes
Authors: Fazeli Gholamreza , Levin-Konigsberg Roni , Bassik Michael C , Stigloher Christian , Wehman Ann M
Published: February 2022

The dynamics of phagolysosomes leading to cargo clearance are important to provide cells with metabolites and avoid auto-immune responses, but little is known about how phagolysosomes finally resolve cell corpses and cell debris. We previously discovered that polar body phagolysosomes tubulate into small vesicles to facilitate corpse clearance within 1.5 hours in C. elegans. Here, we show that vesiculation depends on activating TORC1 through amino acid release by the solute transporter SLC-36.1. Downstream of TORC1, BLOC-1-related complex (BORC) recruits the Arf-like GTPase ARL-8 to the phagolysosome for tubulation by kinesin-1. We find that disrupting the regulated GTP-GDP cycle of ARL-8 reduces tubulation, delays corpse clearance, and mislocalizes ARL-8 away from lysosomes. We also demonstrate that mammalian phagocytes use BORC to promote phagolysosomal degradation, confirming the conserved importance of this pathway. Finally, we show that HOPS is required for rapid degradation of the small phagolysosomal vesicles. Thus, by observing single phagolysosomes over time, we identified the molecular pathway regulating phagolysosome vesiculation that promotes efficient resolution.
Brain aging differs with cognitive ability regardless of education
Authors: Walhovd Kristine B. , Nyberg Lars , Lindenberger Ulman , Magnussen Fredrik , Amlien Inge K. , Sørensen Øystein , Wang Yunpeng , Mowinckel Athanasia M. , Kievit Rogier A. , Ebmeier Klaus. P. , Bartrés-Faz David , Kühn Simone , Boraxbekk Carl-Johan , Ghisletta Paolo , Madsen Kathrine Skak , Baaré Willliam F.C. , Zsoldos Enikő , Penninx Brenda , Fjell Anders M.
Published: February 2022

Higher general cognitive ability (GCA) is associated with lower risk of neurodegenerative disorders, but neural mechanisms are unknown. GCA could be associated with more cortical tissue, from young age, i.e. brain reserve, or less cortical atrophy in adulthood, i.e. brain maintenance. Controlling for education, we investigated the relative association of GCA with reserve and maintenance of cortical volume, -area and -thickness through the adult lifespan, using multiple longitudinal brain imaging cohorts (n = 3327, 7002 MRI scans, baseline age 20-88 years, followed-up up to 11 years). There were widespread positive relationships between GCA and cortical characteristics (level-level associations). In select regions, higher baseline GCA was associated with less atrophy over time (level-change associations). Relationships remained when controlling for polygenic scores for both GCA and education. Our findings suggest that higher GCA is associated with cortical volumes by both brain reserve and -maintenance mechanisms through the adult lifespan.
Functional specialization of specific DC subsets in the synovial fluid of JIA patients
Authors: Boltjes Arjan , Kumar Samat Anoushka Ashok , Plantinga Maud , Mokry Michal , Castelijns Bas , Swart Joost F. , Vastert Bas J. , Creyghton Menno , Nierkens Stefan , van Loosdregt Jorg , van Wijk Femke
Published: February 2022

Dendritic cells (DC) are crucial for initiating and shaping immune responses. So far, little is known about heterogeneity and functional specialization of human DC subsets in (local) inflammatory conditions. We profiled conventional (c)DC1, cDC2 and monocytes based on phenotype, transcriptome and function from a local inflammatory site, namely synovial fluid (SF) from patients suffering from a chronic inflammatory condition, Juvenile Idiopathic Arthritis (JIA). cDC1, a relatively small dendritic cell subset in blood, are strongly enriched in SF. SF cDC1 showed a quiescent immune signature without a clear inflammatory profile low expression of PRR, chemokine, and cytokine receptors, and poor induction of T cell proliferation and cytokine production, but selective production of IFNλ upon polyinosinic:polycytidylic acid exposure. In stark contrast, cDC2 and monocytes from the same environment, showed a pro-inflammatory transcriptional profile, high levels of (spontaneous) pro-inflammatory cytokine production, and strong induction of T cell proliferation and cytokine production, including IL-17. Although the cDC2 and monocytes showed an overlapping transcriptional core profile, there were clear differences in the transcriptional landscape and functional features, indicating that these cell types retain their lineage identity in chronic inflammatory conditions. In conclusion, our findings suggest that at the site of inflammation, there is specific functional programming of human DC subsets, especially cDC2. In contrast, the enriched subset of cDC1 remains relatively quiescent and seemingly unchanged under inflammatory conditions, pointing to a more regulatory role.
A simple DLP-bioprinting strategy produces cell-laden crypt-villous structures for an advanced 3D gut model
Authors: Torras Núria , Zabalo Jon , Abril Eduardo , Carré Albane , García-Díaz María , Martínez Elena
Published: February 2022

The intestine is a complex tissue with a characteristic three-dimensional (3D) crypt-villous architecture, which plays a key role in the intestinal function. This function is also regulated by the intestinal stroma that actively supports the intestinal epithelium, maintaining homeostasis. Efforts to account for the 3D complex structure of the intestinal tissue have been focused mainly in mimicking the epithelial barrier, while solutions to include the stromal compartment are scarce and unpractical to be used in routine experiments. Here we demonstrate that by employing an optimized bioink formulation and the suitable printing parameters it is possible to produce fibroblast-laden crypt-villous structures by means of digital light processing (DLP) stereolithography. This process provides excellent cell viability, accurate spatial resolution and high printing throughput, resulting in a robust biofabrication approach that yields functional gut mucosa tissues compatible with conventional testing techniques.

Teaser

3D bioprinting approach for the direct fabrication of advanced cell-laden tissue constructs by means of visible-light photopolymerization.
Termination factor Rho mediates transcriptional reprogramming ofBacillus subtilisstationary phase
Authors: Bidnenko Vladimir , Nicolas Pierre , Guérin Cyprien , Dérozier Sandra , Chastanet Arnaud , Dairou Julien , Redko-Hamel Yulia , Jules Matthieu , Bidnenko Elena
Published: February 2022

Reprogramming of gene expression during transition from exponential growth to stationary phase is crucial for bacterial survival. In the model Gram-positive bacteriumBacillus subtilis, this process is mainly governed by the activity of the global transcription regulators AbrB, CodY and Spo0A. We recently showed that the transcription termination factor Rho, known for its ubiquitous role in the inhibition of antisense transcription, is involved in Spo0A-mediated regulation of differentiation programs specific to the stationary phase inB. subtilis. To identify other aspects of the regulatory role of Rho during adaptation to starvation, we have constructed aB. subtilisstrain that expressesrhoat a relatively stable high level in order to circumvent its decrease occurring in the wild-type cells entering the stationary phase. We show thatB. subtiliscells stably expressing Rho fail to sporulate and to develop genetic competence, which is largely, but not exclusively, due to abnormally low expression of the master regulator Spo0A. Moreover, in addition to a global decrease of antisense transcription, these cells exhibit genome-wide alterations of sense transcription. A significant part of these alterations affects genes from global regulatory networks of cellular adaptation to the stationary phase and reflects the attenuated de-repression of the AbrB and CodY regulons and the weakened stringent response. Accordingly, stabilization of Rho level reprograms stationary phase-specific physiology ofB. subtiliscells, negatively affects cellular adaptation to nutrient limitations and alters cell-fate decision-making to such an extent that it blocks development of genetic competence and sporulation. Taken together, these results indicate that the activity of termination factor Rho constitutes a previously unknown layer of control over the stationary phase and post-exponential adaptive strategies inB. subtilis, from the adjustment of cellular metabolism to the activation of survival programs.
Transcriptional changes in Plasmodium falciparum upon conditional knock down of mitochondrial ribosomal proteins RSM22 and L23
Authors: Dass Swati , Mather Michael W. , Ling Liqin , Vaidya Akhil B. , Ke Hangjun
Published: February 2022

The mitochondrion of malaria parasites is an attractive antimalarial drug target, which require mitoribosomes to translate genes encoded in the mitochondrial (mt) DNA. Plasmodium mitoribosomes are composed of highly fragmented ribosomal RNA (rRNA) encoded in the mtDNA. All mitoribosomal proteins (MRPs) and other assembly factors are encoded in the nuclear genome. Here, we have studied one small subunit (SSU) MRP, RSM22 (Pf3D7_1027200) and one large subunit (LSU) MRP, L23 (Pf3D7_1239100) in Plasmodium falciparum. We show that both proteins localize to the mitochondrion and are essential for parasite survival. However, the parasites survive conditional knock down (KD) of PfRSM22 for two days longer than PfMRPL23 KD. RNA sequencing revealed transcriptomic changes of the nuclear and mitochondrial genomes upon KD of these MRPs. In the early phase following KD, while most mt rRNAs and transcripts of putative MRPs were downregulated in the absence of PfRSM22, several mt rRNAs and MRPs were upregulated after KD of PfMRPL23. At the late time points of KD, loss of PfRSM22 and PfMRPL23 caused defects in many essential metabolic pathways, leading to parasite death. There was a significant overlap among the mitochondrial related transcripts downregulated in the late phase of PfRSM22 and PfMRPL23 KDs. We have also identified a list of mitochondrial proteins of unknown function that are likely Plasmodium MRPs based on their structural similarity to known MRPs as well as their expression profiles in KD parasites.
Ceramide-Rich Microdomains Facilitate Nuclear Envelope Budding during the Biogenesis of LTB4-containing Exosomes
Authors: Arya Subhash B. , Chen Song , Javed Fatima , Parent Carole A.
Published: February 2022

Neutrophils migrating towards chemoattractant gradients amplify their recruitment range by releasing the secondary chemoattractant leukotriene B4(LTB4)1,2. We previously demonstrated that LTB4and its synthesizing enzymes, the 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP), and leukotriene A4hydrolase (LTA4H), are packaged and released in exosomes3. We now report that the biogenesis of the LTB4-containing exosomes is initiated at the nuclear envelope (NE) of activated neutrophils. We show that the neutral sphingomyelinase 1 (nSMase1)-mediated generation of ceramide enriched lipid-ordered microdomains initiates the clustering of the LTB4-synthesizing enzymes on the NE. We isolated and analyzed exosomes from activated neutrophils and established that the FLAP/5-LO-positive exosome population is distinct from that of the CD63-positive exosome population. Furthermore, we observed a strong co-localization between ALIX and FLAP at the periphery of nuclei and within cytosolic vesicles. We propose that the initiation of NE curvature and bud formation is mediated by nSMase1-dependent ceramide generation, which leads to FLAP and ALIX recruitment. Together, these observations elucidate the mechanism for LTB4secretion and identify a novel pathway for exosome generation.
Global determinants of insect mitochondrial genetic diversity
Authors: French Connor M , Bertola Laura D , Carnaval Ana C , Economo Evan P , Kass Jamie M , Lohman David J , Marske Katharine A , Meier Rudolf , Overcast Isaac , Rominger Andrew J. , Staniczenko Phillip , Hickerson Michael J
Published: February 2022

Understanding global patterns of genetic diversity (GD) is essential for describing, monitoring, and preserving life on Earth. To date, efforts to map macrogenetic patterns have been restricted to vertebrates, which comprise only a small fraction of Earth’s biodiversity. Here, we construct the first global map of predicted insect mitochondrial (COI) GD, derived from publicly available data. We calculate the mitochondrial GD mean (GDM) and evenness (GDE) of insect assemblages across the globe, identify their environmental correlates, and make predictions of mitochondrial GD levels in unsampled areas based on environmental data. Using the largest single-locus genetic dataset yet assembled, we find that mitochondrial GDE follows a quadratic latitudinal gradient peaking in the subtropics. Both mitochondrial GDM and GDE positively correlate with seasonally hot temperatures, as well as climate stability since the last glacial maximum. Our models explain 27.9% and 24.0% of the observed variation in mitochondrial GDM and GDE in insects, respectively, making an important step towards understanding global biodiversity patterns in the most diverse animal taxon.
CD36 homologs determine microbial resistance to the Lyme disease spirochete
Authors: O’Neal Anya J. , Singh Nisha , Forrest Iain S. , Rolandelli Agustin , Wang Xiaowei , Shaw Dana K. , Young Brianna D. , Narasimhan Sukanya , Dutta Shraboni , Snyder Greg A. , Marnin Liron , Butler L. Rainer , Samaddar Sourabh , Mendes M. Tays , Paz Francy E. Cabrera , Valencia Luisa M. , Sundberg Eric J. , Fikrig Erol , Pal Utpal , Weber David J. , Do Ron , Pedra Joao H.F.
Published: February 2022

Pattern recognition receptors sense pathogens in arthropods and mammals through distinct immune processes. Whether these molecules share a similar function and recognize the same microbe in evolutionarily distant species remain ill-defined. Here, we establish that the CD36 superfamily is required forBorrelia burgdorferiresistance in both the arthropod vector and humans. Using the blacklegged tickIxodes scapularisand an electronic health record-linked biobank, we demonstrate that CD36 members elicit immunity to the Lyme disease spirochete. In ticks, the CD36-like protein Croquemort recognizes lipids and initiates the immune deficiency and jun N-terminal kinase pathways againstB. burgdorferi. In humans, exome sequencing and clinical information reveal that individuals withCD36loss-of-function variants have increased prevalence of Lyme disease. Altogether, we discovered a conserved mechanism of anti-bacterial immunity.

One Sentence Summary

Lipid receptors belonging to the CD36 superfamily exhibit a shared immune function in both ticks and humans.
Multistep loading of PCNA onto DNA by RFC
Authors: Schrecker Marina , Castaneda Juan C. , Devbhandari Sujan , Kumar Charanya , Remus Dirk , Hite Richard K.
Published: February 2022

The DNA sliding clamp proliferating cell nuclear antigen (PCNA) is an essential co-factor for many eukaryotic DNA metabolic enzymes. PCNA is loaded around DNA by the ATP-dependent clamp loader replication factor C (RFC), which acts at single-stranded/double-stranded DNA junctions harboring a recessed 3’ end (3’ ss/dsDNA junctions) and at DNA nicks. To illuminate the loading mechanism we have investigated the structure of RFC:PCNA bound to ATPγS and 3’ ss/dsDNA junctions or nicked DNA using cryogenic electron microscopy. Unexpectedly, we observe open and closed PCNA conformations in the RFC:PCNA:DNA complex, revealing that PCNA can adopt an open, planar conformation that allows direct insertion of dsDNA, and indicating that PCNA ring-closure is not mechanistically coupled to ATP-hydrolysis. By resolving multiple DNA-bound states of RFC:PCNA we observe that partial melting facilitates lateral insertion into the central channel formed by RFC:PCNA. We also resolve the Rfc1 N-terminal domain and demonstrate that its single BRCT domain participates in coordinating DNA prior to insertion into the central RFC channel, which promotes PCNA loading on the lagging strand of replication forks in vitro. Combined, our data suggest a comprehensive and fundamentally revised model for the RFC-catalyzed loading of PCNA onto DNA.
M2 receptors are required for spatiotemporal sequence learning in mouse primary visual cortex
Authors: Sarkar Susrita , Reyes Catalina Martinez , Jensen Cambria M. , Gavornik Jeffrey P.
Published: February 2022

Acetylcholine is a neurotransmitter that plays a variety of roles in the central nervous system. It was previously shown that blocking muscarinic receptors with a non-selective antagonist prevents a form of experience-dependent plasticity termed “spatiotemporal sequence learning” in the mouse primary visual cortex (V1). Muscarinic signaling is a complex process involving the combined activities of five different G-protein coupled receptors, M1-M5, all of which are expressed in the murine brain but differ from each other functionally and in anatomical localization. Here we present electrophysiological evidence that M2, but not M1, receptors are required for spatiotemporal sequence learning in mouse V1. We show in male mice that M2 is highly expressed in the neuropil in V1, especially in thalamorecipient layer 4, and co-localizes with the soma in a subset of somatostatin expressing neurons in deep layers. We also show that expression of M2 receptors is higher in the monocular region of V1 than it is in the binocular region, but that the amount of experience-dependent sequence potentiation is similar in both regions, and that blocking muscarinic signaling after visual stimulation does not prevent plasticity. This work establishes a new functional role for M2-type receptors in processing temporal information and demonstrates that monocular circuits are modified by experience in a manner similar to binocular circuits.

Significance Statement

Muscarinic acetylcholine receptors are required for multiple forms of plasticity in the brain and support perceptual functions, but the precise role of the five subtypes (M1-M5) are unclear. Here we show that the M2 receptor is specifically required to encode experience-dependent representations of spatiotemporal relationships in both monocular and binocular regions of mouse V1. Muscarinic receptors are metabotropic in nature and have complex downstream signaling effects that can be difficult to isolate experimentally. In addition to identifying a novel functional role for M2 receptors, this work also suggests that V1 circuits can be used as an in-vivo model to understand the relationship between cholinergic signaling and coding of complex temporal relationships in cortical circuits.
Conditional GWAS of non-CG transposon methylation inArabidopsis thalianareveals major polymorphisms in five genes
Authors: Sasaki Eriko , Gunis Joanna , Reichardt-Gomez Ilka , Nizhynska Viktoria , Nordborg Magnus
Published: February 2022

Genome-wide association studies (GWAS) have revealed that the striking natural variation for DNA CHH-methylation (mCHH; H is A, T, or C) of transposons has oligogenic architecture involving major alleles at a handful of known methylation regulators. Here we use a conditional GWAS approach to show that CHG-methylation (mCHG) has a similar genetic architecture — once mCHH is statistically controlled for. We identify five keytrans-regulators that appear to modulate mCHG levels, and show that they interact with a previously identified modifier of mCHH in regulating natural transposon mobilization.
Protecting seabed sediment carbon for climate mitigation: a UK case study
Authors: Epstein Graham , Roberts Callum M.
Published: February 2022

Protecting areas of seabed sediment would appear to be an important climate mitigation strategy, however carbon has not been considered in national management plans. Using spatial analyses we show, in the UK Exclusive Economic Zone (EEZ), high potential organic carbon loss due to mobile bottom fishing is likely to be geographically restricted. Currently designated seabed marine protected areas (MPAs) cover 32.9% of the EEZ, 30.0% of carbon stocks, but only 12.9% of fishing disturbance. If all MPAs were closed to mobile bottom fishing, we estimate a prevention of only 6.9% of potential organic carbon losses due to fishing disturbance across the EEZ. In contrast, areas identified as having largest climate change mitigation potential cover just 16.5% of the EEZ, contain 24.7% of OC stocks and closing these areas to mobile fishing could save 29.6% of potential carbon losses. We must re-evaluate current seabed management plans and incorporate evidence-based carbon considerations.

Teaser

Restrictions on bottom trawling and dredging outside of MPA networks may be necessary to derive a climate mitigation benefit.
Genomic stock structure of the marine teleost tarakihi (Nemadactylus macropterus) provides evidence of fine-scale adaptation and a temperature-associated cline amid panmixia
Authors: Papa Yvan , Morrison Mark A. , Wellenreuther Maren , Ritchie Peter A.
Published: February 2022

Tarakihi (Nemadactylus macropterus) is an important fishery species with widespread distribution around New Zealand and off the southern coasts of Australia. However, little is known about whether the populations are locally adapted or genetically structured. To address this, we conducted whole-genome resequencing of 175 tarakihi from around New Zealand and Tasmania (Australia) to obtain a dataset of 7.5 million genome-wide and high-quality single nucleotide polymorphisms (SNPs). Variant filtering,FST-outlier analysis, and redundancy analysis (RDA) were used to evaluate population structure, adaptive structure, and locus-environment associations. A weak but significant level of neutral genetic differentiation was found between tarakihi from New Zealand and Tasmania (FST= 0.0054–0.0073,P≤ 0.05), supporting the existence of at least two separate reproductive stocks. No clustering was detected among the New Zealand populations (ФST< 0.001,P= 0.77). Outlier-based, presumably adaptive variation suggests fine-scale adaptive structure between locations around central New Zealand off the east (Wairarapa, Cape Campbell, and Hawke’s Bay) and the west coast (Tasman Bay/Golden Bay and Upper West Coast of South Island). Allele frequencies from 55 loci were associated with at least one of six environmental variables, of which 47 correlated strongly with yearly mean water temperature. Although genes associated with these loci are linked to various functions, the most common functions were integral components of membrane and cilium assembly. Projection of the RDA indicates the existence of a latitudinal temperature cline. Our work provides the first genomic insights supporting panmixia of tarakihi in New Zealand and evidence of a genomic cline that appears to be driven by the temperature gradients, together providing crucial information to inform the stock assessment of this species, and to widen the insights of the ecological drivers of adaptive variation in a marine species.
Simple and efficient modification of Golden Gate design standards and parts using oligo stitching
Authors: De Saeger Jonas , Vermeersch Mattias , Gaillochet Christophe , Jacobs Thomas B.
Published: February 2022

The assembly of DNA parts is a critical aspect of contemporary biological research. Gibson assembly and Golden Gate cloning are two popular options. Here, we explore the use of single stranded DNA oligos with Gibson assembly to augment Golden Gate cloning workflows in a process called “oligo stitching”. Our results show that oligo stitching can efficiently convert Golden Gate parts between different assembly standards and directly assemble incompatible Golden Gate parts without PCR amplification. Building on previous reports, we show that it can also be used to assemblede novosequences. As a final application, we show that restriction enzyme recognition sites can be removed from plasmids and utilize the same concept to perform saturation mutagenesis. Given oligo stitching’s versatility and high efficiency, we expect that it will be a useful addition to the molecular biologist’s toolbox.

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Study on diamond temperature stability during long-duration growth via MPCVD under the influence of thermal contact resistance
Authors: Yang Bo , Shen Shengnan , Zhang Libin , Shen Qiao , Zhang Rongjun , Zhang Yanyan , Gan Zhiyin , Liu Sheng
Published: February 2022

During the process of growing diamond crystals via microwave plasma chemical vapor deposition (MPCVD), the substrate temperature will gradually increase with increasing growth time. At present, the commonly used method to compensate for the temperature increase is to reduce the deposition parameters (gas pressure and input power) or adjust the height of the susceptor. However, according to previous studies, reducing the substrate parameters will reduce the growth rate. In addition, adjusting the height of the susceptor may cause secondary plasma, which could damage the equipment. Therefore, it is necessary to find the reason for the substrate temperature increase with the growth time and eliminate it. Firstly, the effect of substrate size change on the substrate temperature was simulated dynamically, which indicated that the substrate size change was not the main reason for the continuous increase of the substrate temperature. Subsequent analysis showed that non-diamond carbon formed at the bottom of the grown diamond, which may cause a change of the thermal contact resistance. Therefore, a thermal contact resistance component was introduced into the existing model of diamond growth, and it was found that the substrate temperature increased with the roughness of the bottom of the substrate. In order to eliminate the influence of thermal contact resistance, a welding growth method was proposed with the aim of avoiding the accumulation of the non-diamond carbon at the bottom of the substrate. The growth with different welding materials showed that the grown diamond's internal stress distribution after welding growth was similar to that without welding growth, but the non-diamond carbon at the bottom was obviously restrained. However, the selection of welding materials needs to be further optimized with respect to the welding stability and growth rate.
Non-destructive characterization of the spatial variation of γ/γ′ lattice misfit in a single-crystal Ni-based superalloy by energy-resolved neutron imaging
Authors: Malamud Florencia , Santisteban Javier Roberto , Gao Yan , Shinohara Takenao , Oikawa Kenichi , Tremsin Anton
Published: February 2022

Lattice misfit in nickel-based superalloys is one of the important microstructural parameters that control their mechanical properties, such as creep behaviour at high temperatures. Here, energy-resolved neutron imaging experiments are performed at a spallation neutron source to determine the spatial variation of lattice misfit on a second-generation nickel-based single-crystal superalloy specimen produced from a failed low-cycle fatigue specimen. The wavelength spectrum of the neutrons scattered by the specimen displays a large number of peaks, each corresponding to a spot in traditional Laue diffraction experiments. An analysis of the position and width of those Laue peaks in the transmission spectra allows determination of the lattice parameters of the γ and γ′ phases that compose the specimen, as well as the strain misfit and the misorientation between them. An analytical model is developed to describe the full wavelength pattern of Laue peaks arising from a specimen composed of two single crystals, and this model is used to perform least-squares refinements of the spectra measured at different positions of the specimen, with a spatial resolution of ∼500 × 500 µm. The local variations of the lattice parameter across the sample area were less than 4 mÅ for both phases, and the lattice misfit remains essentially constant at a value of 0.30 ± 0.03%, whilst the misorientation between the two phases is always smaller than 10′. By contrast, the relative misorientation between different parts of the specimen varies locally up to 1.5° on a scale of millimetres.
Combined angular and energy dispersive diffraction: optimized data acquisition, normalization and reduction
Authors: King A. , Guignot N. , Henry L. , Morard G. , Clark A. , Le Godec Y. , Itié J.-P.
Published: February 2022

Combined angular and energy dispersive diffraction is particularly well suited to experiments at high pressures in large-volume presses, and to the study of liquid or amorphous systems. This work describes the data acquisition, correction and reduction approach developed at the PSICHE beamline of the SOLEIL synchrotron. The measured data were normalized for both the scattering volume and the effective incident energy spectrum. By optimizing the acquisition strategy, the measurement time and radiation dose are greatly reduced. The correction and reduction protocol outputs normalized scattering profiles that are suitable for pair distribution function or liquid structure analysis. These processes are demostrated with examples from a number of real experimental data sets.
Crystal structure of tris(4,7-diphenyl-1,10-phenanthroline-κ2
N,N′)cobalt(III) tris(hexafluorophosphate) monohydrate
Authors: Mani Asma , Belgaied Jamel Eddine , Gasser Gilles , Blacque Olivier
Published: February 2022

The title compound, [Co(C72H48N6)](PF6)3·H2O, crystallizes with one tripositive complex molecule, three hexafluorophosphate anions and one solvent molecule of water in the asymmetric unit. The N6 coordination set around the central CoIII atom defines a distorted octahedral environment. Four fluorine atoms of one hexafluorophosphate anion are disordered over two sets of positions with site-occupancy factors of 0.697 (5) and 0.303 (5). In the crystal, intermolecular π–π stacking interactions, C—H...π, C—H...F and O—H...F and interactions are present.
The social psychology of work engagement: state of the field
Authors: Bakker Arnold B.
Published: February 2022

Purpose

Research on work engagement is flourishing and shows important links between work engagement and career success. However, a systematic account of the social-psychological origins of engagement is largely lacking. In the paper, the author develops a theoretical model and discusses how employees actively influence and are influenced by employees' leader's, colleagues' and partner's work engagement.

Design/methodology/approach

The author integrates literatures on emotional contagion, team work engagement, leadership, proactive work behavior and work-to-family spillover. This results in a model of the social-psychological processes involved in work engagement.

Findings

Work engagement is the result of various social-psychological processes. First, work engagement is contagious – colleagues, leaders and the intimate partner can be important causes of engagement. Second, work engagement emerges at the team-level when team members collectively experience high levels of vigor, dedication and absorption. Team members of engaged teams synchronize their activities well and perform better. Third, leaders may influence employee work engagement through fast (unconscious) and slow (conscious) influence processes. Fourth, employees may use social forms of proactive behavior to stay engaged in their work, including job crafting and playful work design. Finally, work engagement may spill over and enrich the family domain. The social-psychological model of work engagement shows how leaders, followers and family members provide, craft and receive (i.e. exchange) resources and facilitate each other's work and family engagement.

Practical implications

Organizations may increase work engagement by using social-psychological interventions, including training sessions that foster fast and slow leadership, team-boosting behaviors and (team-level) job crafting and playful work design.

Originality/value

Whereas most previous studies have focused on job demands and resources as possible causes of work engagement, the present article outlines the state of the field regarding the social-psychological processes involved in engagement.
The interplay of perceived risk, perceive benefit and generation cohort in digital finance adoption
Authors: Jain Niyati , Raman T.V.
Published: February 2022

Purpose

Financial service providers are facing challenges in the acceptance of digital financial services. The study, therefore, intends to identify factors contributing towards the adoption of digital finance. It has worked on the influencers and demotivators of digital finance adoption by individuals. These influencers are labelled as perceived benefits and demotivators as perceived risks. In addition to perceived benefit and risk, the study has also included the difference in perception on the basis of generation cohort.

Design/methodology/approach

The data have been collected through a structured questionnaire from 411 respondents. Partial least squares structured equation modelling (PLS-SEM) has been used to analyse the proposed model on SmartPLS.

Findings

The findings suggested that the benefits were more influential in adoption behaviour than perceived risk. In addition to perceived benefit and risk, the study has also included the difference in perception on the basis of generation cohort. The results summarised that benefits had a more significant impact in Generation Z (Gen Z) than in Millennials.

Research limitations/implications

The evaluation and categorisation of perceived risk and benefits into meaningful dimensions generate value to the adoption behaviour of digital finance. Thus, the findings are useful for the policymakers and researchers to contemplate the perception of individuals in digital finance based on the generation cohort.

Originality/value

The empirical findings of the present research contribute to limited evidence of a relationship between perceived risk, perceived benefit and digital finance adoption on the basis of generation cohort.