bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractHigher 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

AbstractDendritic 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

AbstractThe 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.Teaser3D 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

AbstractReprogramming 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

ABSTRACTThe 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.
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

AbstractUnderstanding 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

AbstractPattern 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 SummaryLipid 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

AbstractThe 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

AbstractAcetylcholine 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 StatementMuscarinic 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

AbstractGenome-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

AbstractProtecting 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.TeaserRestrictions 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

AbstractTarakihi (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

ABSTRACTThe 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.Abstract Graphic