bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clustering of rRNA operons inE. coliis disrupted by σH
Authors: Ho Khang , Harshey Rasika M. 
Published: September 2024

AbstractChromosomal organization inE. colias examined by Hi-C methodology indicates that long-range interactions are sparse. Yet, spatial co-localization or ‘clustering’ of 6/7 ribosomal RNA (rrn) operons distributed over half the 4.6 Mbp genome has been captured by two other methodologies - fluorescence microscopy and Mu transposition. Our current understanding of the mechanism of clustering is limited to mapping essentialciselements. To identifytranselements, we resorted to perturbing the system by chemical and physical means and observed that heat shock disrupts clustering. Levels of σHare known to rise as a cellular response to the shock. We show that elevated expression of σHalone is sufficient to disrupt clustering, independent of heat stress. The anti-clustering activity of σHdoes not depend on its transcriptional activity but requires core-RNAP interaction and DNA-binding activities. This activity of σHis suppressed by ectopic expression of σDsuggesting a competition for core-RNAP. A query of the other five known σ factors ofE. colifound that elevated expression of FecI, the ECF σ factor that controls iron citrate transport, also perturbs clustering and is also suppressed by σD. We discuss a possible scenario for how these membrane-associated σ factors participate in clustering of distantrrnloci.
Rubisco packaging and stoichiometric composition of a native β-carboxysome
Authors: Sun Yaqi , Sheng Yuewen , Ni Tao , Ge Xingwu , Sarsby Joscelyn , Brownridge Philip J. , Li Kang , Hardenbrook Nathan , Dykes Gregory F. , Rockliffe Nichola , Eyers Claire E. , Zhang Peijun , Liu Lu-Ning 
Published: September 2024

AbstractCarboxysomes are anabolic bacterial microcompartments that play an essential role in carbon fixation in cyanobacteria. This self-assembling proteinaceous organelle encapsulates the key CO2-fixing enzymes, Rubisco and carbonic anhydrase, using a polyhedral shell constructed by hundreds of shell protein paralogs. Deciphering the precise arrangement and structural organization of Rubisco enzymes within carboxysomes is crucial for understanding the formation process and overall functionality of carboxysomes. Here, we employed cryo-electron tomography and subtomogram averaging to delineate the three-dimensional packaging of Rubiscos within β-carboxysomes in the freshwater cyanobacteriumSynechococcus elongatusPCC7942 that were grown under low light. Our results revealed that Rubiscos are arranged in multiple concentric layers parallel to the shell within the β-carboxysome lumen. We also identified the binding of Rubisco with the scaffolding protein CcmM in β-carboxysomes, which is instrumental for Rubisco encapsulation and β-carboxysome assembly. Using QconCAT-based quantitative mass spectrometry, we further determined the absolute stoichiometric composition of the entire β-carboxysome. This study and recent findings on the β-carboxysome structure provide insights into the assembly principles and structural variation of β-carboxysomes, which will aid in the rational design and repurposing of carboxysome nanostructures for diverse bioengineering applications.
Differential representations for affective and informative components of reward in the striatum and hippocampus
Authors: Shen Xinxu , Wang Kainan S. , Murty Vishnu P. , Delgado Mauricio R. , Smith David V. 
Published: September 2024

AbstractReceipt of a reward is composed of affective and informative components, which are often intertwined in most reward-processing and decision-making tasks. Our previous work allowed us to identify regions that were more strongly engaged for the affective and informative components of reward upon receipt (Smith et al., 2016) and showed that the ventral striatum responds to both affective and informative components of reward processing. However, the limited spatial resolution and coarse analytical approaches made it hard to understand how these different components of reward were represented in the brain, wherein similar engagement may not necessitate similar representations. In our current study, we used high-resolution functional magnetic resonance imaging (voxel size: 1.75 mm3) and representational similarity analysis to investigate the representation of affective and informative components of reward receipt in the striatum and the hippocampus, another region that is sensitive to reward information. We found a differential representation of affective and informative components of reward receipt in the striatum and the hippocampus, with no difference in representation between the two structures. However, in the dorsal striatum, we found that representations were stronger for affective rather than the informative components of reward receipt. Finally, we observed that the ventral striatum was sensitive to the predictiveness of information, such that across-run pattern similarity in the ventral striatum increased with the predictiveness of information. In sum, our results provide evidence of how affective and informative components of rewards are represented in the striatum and the hippocampus, potentially indicating a differential coding schema for the dorsal and the ventral striatum.
Development of a protein synthesis network at the sarco/endoplasmic reticulum in adult cardiac myocytes
Authors: Sandmann Christoph , Sramek Viviana , Brandenburg Sören , Uhlenkamp Dennis , Renz Marc , Meyer Bianca , Sandmann Clara , Herzog Nicole , Groß Julia , Katus Hugo A. , Lehnart Stephan E. , Völkers Mirko , Doroudgar Shirin 
Published: September 2024

AbstractIntroductionThe endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins, which constitute a large fraction of the total protein output of a mammalian cell. Striated muscle cells contain a specialized membrane system known as the sarcoplasmic reticulum (SR) that controls calcium homeoastasis and contraction, however the biochemical and physiological relationship between the ER and SR and how both compartments participate in protein synthesis remains incompletely understood.MethodsProtein quantification and imaging of selected marker proteins for ER and SR functions was performed to characterize the relationship of the ER and SR and its individual involvement in protein synthesis in neonatal and adult cardiac myocytes. Superresolution microscopy was used to examine the interaction of ribosomes and the SR in adult cardiac myocytes.ResultsQuantification of ER and SR-associated proteins of isolated ventricular cardiac myocytes showed that relative expression of ER/SR resident protein quality elements, as well as relative ribosome levels are decreased in adult cells, whereas SR-associated Ca2+handling proteins increase. Immunocytoflourescence revealed that the membrane compartment that exists in early postpartum resembles mostly the ER and decreases in postnatal development. The SR is the main membrane network that exists in the adult cardiac myocytes, replacing the ER, in all but the perinuclear region. Immunocytoflourescence staining further indicated that both networks perform overlapping but distinct, specialized functions, such as localization of excitation-contraction coupling exclusively to the SR or initiation of secretion via the classical secretory pathway mainly from the ER. Ribosomes and mRNA were localized both in close proximity to the ER and the SR of adult ventricular cardiac myocytes. Superresolution microscopy confirmed that both the ER as well as the developed SR bind ribosomes and are direct sites of protein synthesis and protein homeostasis in adult cardiac myocytes.ConclusionOur findings suggest molecular differentiation and structural organization of the ER/SR in cardiac muscle development, resulting in the development of a protein synthesis network at the sarco/endoplasmic reticulum in adult cardiac myocytes.
Unveil the Molecular Interplay between Aminoglycosides and Pseudouridine in IRES Translation
Authors: Zhao Yu , Xu Chong , Chen Xin , Jin Hong , Li Hong 
Published: September 2024

AbstractEukaryotic ribosomes are enriched with pseudouridine, particularly at the functional centers targeted by antibiotics. Here we investigated the roles of pseudouridine in aminoglycoside-mediated translation inhibition by comparing the structural and functional properties of the wild-type ribosomes and those lacking pseudouridine (cbf5-D95A). We showed that thecbf5-D95A ribosomes have decreased thermostability and high sensitivity to aminoglycosides. When presented with an internal ribosome entry site (IRES) RNA, elongation factor eEF2, GTP, sordarin, hygromycin B preferentially binds to thecbf5-D95A ribosomes during initiation by blocking eEF2 binding and stalls the ribosomes in a non-rotated conformation, further hindering translocation. Hygromycin B binds to the inter-subunit bridge B2a that is known to be sensitive to pseudouridine, revealing a functional link between pseudouridine and aminoglycoside inhibition. Our results suggest that pseudouridine enhances both thermostability and conformational fitness of the ribosomes, thereby influencing their susceptibility to aminoglycosides.HighlightsLoss of pseudouridine increases cell sensitivity to aminoglycosidesPseudouridine enhances ribosome thermostabilityHygromycin B competes with eEF2 for the non-rotated ribosomeHygromycin B deforms the codon-anticodon duplex
Maternal adiponectin restores cholinergic vasodilation in resistance vessels from adult offspring exposed to maternal obesityin utero
Authors: Murphy Molly , Fallahi Sahand , Dumolt Jerad H. , Houck Julie A. , Vaughan Owen R. , Moore Lorna G. , Julian Colleen G. , Rosario Fredrick J. , Powell Theresa L. , Jansson Thomas , Lorca Ramón A. 
Published: September 2024

ABSTRACTMaternal obesity increases the risk of cardiovascular and metabolic disease in the offspring both during childhood and adult life. Pregnant women and mice with obesity have lower circulating levels of adiponectin (ADN) compared to lean controls. ADN is an adipokine involved in regulating energy metabolism, vascular function, and placental function. We hypothesized that offspring of obese mice have impaired resistance artery function, which can be prevented by restoration of normal circulating ADN levels in obese dams during late pregnancy. Adult female mice were fed either control or obesogenic diet and mated with control diet-fed males. Control dams received a continuous infusion of phosphate saline buffer (PBS) during late pregnancy whereas obese females received either PBS or ADN. After weaning, offspring were fed a control diet. Mesenteric arteries (MsA) were dissected from adult offspring and mounted in a wire myograph or fixed for histology. MsA responses to vasoconstrictors (phenylephrine and endothelin-1) were not different between infusion groups. However, the vasodilatory responses to acetylcholine were reduced in offspring from obese dams as compared to control-fed dams. ADN supplementation during pregnancy restored the cholinergic vasodilatory responses of resistance vessels in offspring from obese dams. These observations suggest that normalizing circulating adiponectin levels in pregnancies complicated by obesity prevents in utero programming of vascular dysfunction in the offspring.
Effects of in vitro hemolysis and repeated freeze-thaw cycles in protein abundance quantification using the SomaScan and Olink assays
Authors: Candia Julián , Fantoni Giovanna , Moaddel Ruin , Delgado-Peraza Francheska , Shehadeh Nader , Tanaka Toshiko , Ferrucci Luigi 
Published: September 2024

AbstractSomaScan and Olink are the leading aptamer- and antibody-based platforms in current proteomics research, each of them capable of measuring thousands of human proteins with a broad range of endogenous concentrations. In this study, we investigated the effects of in vitro hemolysis and repeated freeze-thaw cycles in protein abundance quantification across 10,776 (11K SomaScan) and 1,472 (Olink Explore 1536) analytes, respectively. Using SomaScan, we found two distinct groups, each one consisting of 4% of all aptamers, affected by either hemolysis or freeze-thaw cycles. Using Olink, probes impacted by freeze-thaw cycles were in line with the observations from SomaScan, with 6% of analytes affected. In dramatic contrast, however, we found that nearly half of all measured Olink probes were significantly impacted by hemolysis. Moreover, by a variety of statistical approaches, we observed that Olink probes affected by hemolysis target proteins with a larger number of annotated protein-protein interactions. Given the extent of the observed nuisance effects, we propose that unbiased, quantitative methods of evaluating hemolysis, such as the hemolysis index successfully implemented in many clinical laboratories, should be adopted in proteomics studies, particularly in those using the Olink assay. We provide detailed results for each SomaScan and Olink probe in the form of extensive Supplementary Data files to be used as resources for the growing user communities of both platforms.
Diet induced mitochondrial DNA replication instability inRad51cmutant mice drives sex-bias in anemia of inflammation
Authors: Tomaszowski Karl-Heinz , Chen Yue , Roy Sunetra , Harris Momo , Zhang Jianhua , Tsai Chi-lin , Schlacher Katharina 
Published: September 2024

AbstractAnemia of inflammation (AI) is a common comorbidity associated with obesity, diabetes, cardiac disease, aging, and during anti-cancer therapies. Mounting evidence illustrates that males are disproportionally affected by AI, but not why. Here we demonstrate a molecular cause for a sex-bias in inflammation. The data shows that mitochondrial DNA (mtDNA) instability induced by dietary stress causes anemia associated with inflamed macrophages and improper iron recycling in mice. These phenotypes are enhanced in mice with mutations inFanco/Rad51c, which predisposes to the progeroid disease Fanconi Anemia. The data reveals a striking sex-bias whereby females are protected. We find that estrogen acts as a mitochondrial antioxidant that reduces diet-induced oxidative stress, mtDNA replication instability and the distinctively mtDNA-dependent unphosphorylated STAT1 response. Consequently, treatment of maleRad51cmutant mice with estrogen or mitochondrial antioxidants suppresses the inflammation-induced anemia. Collectively, this study uncovers estrogen-responsive mtDNA replication instability as a cause for sex-specific inflammatory responses and molecular driver for AI.
Concurrent large-scale brain dynamics during the emotional face matching task and their relation to behavior and mental health
Authors: Korponay Cole , Cohen-Gilbert Julia E. , Kumar Poornima , Harnett Nathaniel G. , Medina Adrian A. , Forester Brent P. , Ressler Kerry J. , Beckmann Christian F. , Harper David G. , Nickerson Lisa D. 
Published: September 2024

AbstractPrior investigations of emotion processing’s neural underpinnings rely ona priorimodels of brain response, obscuring detection of task-relevant neurobiological processes with complex temporal dynamics. To overcome this limitation, we applied unsupervised machine learning to functional magnetic resonance imaging data acquired during the emotional face matching task (EFMT) in healthy young adults from the Human Connectome Project (n=413; n=416 replication). Tensorial independent component analysis showed that the EFMT engages 10 large-scale brain networks – each recruiting visual association cortex in distinct temporal fashions and in tandem with diverse non-visual regions – that collectively recruit 74% of cortex, posterior cerebellum, and amygdala. Despite prominent use of the EFMT to probe negative affect and related psychopathology, EFMT-recruited networks strongly reflected individual differences in cognition but not internalizing/negative affect. Overall, we characterize a richer-than-expected tapestry of concurrent EFMT-recruited brain processes, their diverse activation dynamics, and their relations to task performance and latent mental health phenotypes.
Lifetime fitness benefits of breeding site fidelity and low costs of inbreeding permit inbreeding tolerance in an avian cooperative breeder
Authors: Shah Shailee S. , Diamond Jennifer , Barve Sahas , Cosgrove Elissa J. , Bowman Reed , Fitzpatrick John W. , Chen Nancy 
Published: September 2024

AbstractInbreeding, or breeding with close relatives, often decreases individual fitness, but mate choice in many species can increase inbreeding risk. Inbreeding is more likely in species with limited dispersal, such as cooperative breeders where non-parental individuals—often offspring from previous broods—provide parental care and frequently breed close to home. We leverage 32 years of data from a population of Florida Scrub-Jays (Aphelocoma coerulescens), an avian cooperative breeder, to investigate whether mate choice, and its lifetime fitness outcomes, affects inbreeding tolerance. We find that both sexes show a stronger preference for geographically closer rather than less related mates. While female-biased dispersal mitigates inbreeding risk when pairing for the first time, limited movement away from the breeding territory by both sexes for later pairings (following mate death or divorce) results in higher relatedness between mates than expected under random mating. Males paired with close relatives and females that move longer distances experience equivalently reduced lifetime reproductive success. Fitness benefits of breeding site fidelity and relatively low fitness costs of inbreeding thus permit inbreeding tolerance in Florida Scrub-Jays. Understanding how and why mate choice contributes to inbreeding is crucial for informed conservation action for endangered species like the Florida Scrub-Jay.
Histone deacetylase 5 in prelimbic prefrontal cortex limits context-associated cocaine seeking
Authors: Barry Sarah M. , Huebschman Jessica , Devries Derek M , McCue Lauren M , Tsvetkov Evgeny , Anderson Ethan M. , Siemsen Benjamin M. , Berto Stefano , Scofield Michael D. , Taniguchi Makoto , Penrod Rachel D. , Cowan Christopher W. 
Published: September 2024

AbstractBackgroundRepeated cocaine use produces neuroadaptations that support drug craving and relapse in substance use disorders (SUDs). Powerful associations formed with drug-use environments can promote a return to active drug use in SUD patients, but the molecular mechanisms that control the formation of these prepotent drug-context associations remain unclear.MethodsIn the rat intravenous cocaine self-administration (SA) model, we examined the role and regulation of histone deacetylase 5 (HDAC5) in the prelimbic (PrL) and infralimbic (IL) cortices in context-associated drug seeking. To this end, we employed viral molecular tools, chemogenetics, RNA-sequencing, electrophysiology, and immunohistochemistry.ResultsIn the PrL, reduction of endogenous HDAC5 augmented context-associated, but not cue-or drug prime-reinstated cocaine seeking, whereas overexpression of HDAC5 in PrL, but not IL, reduced context-associated cocaine seeking, but it had no effects on sucrose seeking. In contrast, PrL HDAC5 overexpression following acquisition of cocaine SA had no effects on future cocaine seeking. We found that HDAC5 and cocaine SA altered the expression of numerous PrL genes, including many synapse-associated genes. HDAC5 significantly increased inhibitory synaptic transmission onto PrL deep-layer pyramidal neurons, and it reduced the induction of FOS-positive neurons in the cocaine SA environment.ConclusionsOur findings reveal an essential and selective role for PrL HDAC5 to limit associations formed in cocaine, but not sucrose, SA environments, and that it alters the PrL excitatory/inhibitory balance, possibly through epigenetic regulation of synaptic genes. These results further position HDAC5 as a key factor regulating reward-circuit neuroadaptations that underlie common relapse triggers in SUD.
A Cryptic Prophage Transcription Factor Drives Phenotypic Changes via Host Gene Regulation
Authors: Lally P. , Tierrafría V.H. , Gómez-Romero L. , Stringer A. , Collado-Vides J. , Wade J.T. , Galagan J.E. 
Published: September 2024

AbstractCryptic prophages (CPs) are elements of bacterial genomes acquired from bacteriophage that infect the host cell and ultimately become stably integrated within the host genome. While some proteins encoded by CPs can modulate host phenotypes, the potential for Transcription Factors (TFs) encoded by CPs to impact host physiology by regulating host genes has not been thoroughly investigated. In this work, we report hundreds of host genes regulated by DicC, a DNA-binding TF encoded in the Qin prophage ofEsherichia coli. We identified host-encoded regulatory targets of DicC that could be linked to known phenotypes of its induction. We also demonstrate that a DicC-induced growth defect is largely independent of other Qin prophage genes. Our data suggest a greater role for cryptic prophage TFs in controlling bacterial host gene expression than previously appreciated.
Thermal inactivation spectrum of influenza A H5N1 virus in raw milk
Authors: Nooruzzaman Mohammed , Covaleda Lina M. , Britto de Oliveira Pablo Sebastian , Martin Nicole H. , Koebel Katherine , Ivanek Renata , Alcaine Samuel D. , Diel Diego G. 
Published: September 2024

AbstractThe spillover of highly pathogenic avian influenza (HPAI) H5N1 virus to dairy cows and shedding of high amounts of infectious virus in milk raised public health concerns. Here, we evaluated the decay and thermal stability spectrum of HPAI H5N1 virus in raw milk. For the decay studies, HPAI H5N1 positive raw milk was incubated at different temperatures and viral titers and the thermal death time D-values were estimated. We then heat treated HPAI H5N1 virus positive milk following different thermal conditions including pasteurization and thermization conditions. Efficient inactivation of the virus was observed in all tested conditions, except for thermization at 50°C 10 min. Utilizing a submerged coil system with temperature ramp up times that resemble commercial pasteurizers, we showed that the virus was rapidly inactivated by pasteurization and most thermization conditions. These results provide important insights on the food safety measures utilized in the dairy industry.
Modulation of β-Catenin is important to promote WNT expression in macrophages and mitigate intestinal injury
Authors: Chugh Rishi Man , Bhanja Payel , Zitter Ryan , Gunewardena Sumedha , Badkul Rajeev , Saha Subhrajit 
Published: September 2024

ABSTRACTMacrophages are the major source of WNT ligands. Macrophage-derived WNT is one of the most potent regenerative signals to mitigate intestinal injury. However, regulation of WNT expression in macrophages has not been studied. In the present study, we discovered that activation of canonical β-Catenin suppresses WNT expression in macrophages. Our CHIP-seq and validation study demonstrated the involvement of β-Catenin in the transcriptional regulation of WNT expression. Genetic and pharmacological approaches to de-stabilize/inactivate β-Catenin induce WNT expression in macrophages. Extracellular vesicles (EVs) are a major career of WNT ligands. Transfusion of EVs from pre-conditioned WNT-enriched macrophages demonstrated significant regenerative benefit over native macrophage-derived EVs to mitigate radiation-induced intestinal injury. Transfusion of WNT-enriched EVs also reduces DSS-induced colitis. Our study provides substantial evidence to consider that macrophage-targeted modulation of canonical WNT signaling to induce WNT expression followed by treatment with WNT-enriched EVs can be a lead therapy against intestinal injury..SUMMARYActivation of β-Catenin suppresses WNT expression in macrophages. Macrophage-targeted pharmacological modulation of canonical WNT signaling followed by adoptive transfer mitigate radiation injury in intestine. EVs from these preconditioned macrophages mitigate chemical or radiation induced intestinal injury.