bluuebunny/crossref_metadata_2025 huggingface dataset:
Photosynthetic CO2response characteristics in canopy ofLarix principis-rupprechtiiMayr. tree and practicability of three Models
Authors: Ma Xuemei , Wu Chaofeng , Liu Qiang , Huang Xuanrui
Published: June 2023

Accurately predicting the crown photosynthesis of trees is important to understand the tree growth status and carbon circle in terrestrial ecosystem. However, modeling the photosynthetic carbon dioxide (CO2) response curves for individual tree are still challenging due to the complex canopy structure and changeable environmental conditions. Therefore, taking 16-old yearLarix principis-rupprechtii Mayr. as the research material, the dynamic CO2response models of photosynthesis, including rectangular hyperbolic model (RHM), the non-rectangular hyperbolic model (NRHM) and the modified rectangular hyperbolic model (MRHM), were used to simulate CO2response curves of the crown. The fitting accuracy of the models depend on the comparison of determinants coefficients (R2), mean square errors (MSE) and Akaike information criterion (AIC). The results showed that the mean value ofR2(R2=0.9939 ∼ 0.9964) of MRHM was the highest, whereasMSEvalue (MSE=0.2185∼0.2627) andAICvalue (AIC=-13.18∼-8.03) were the lowest. The CO2-saturated gross photosynthetic rate (Amax) and the saturation point (CiSP) obtained by MRHM were closest to the measured value respectively. Therefore, the MRHM fitted the CO2response data well, and calculated the photosynthetic parameters directly and accurately, the fitted result showed α,Amax,CiSP, CiCPandRPwere 0.04, 7.51 μmol·m-2s-1, 938.97 μmol·m-2, 67.54 μmol·m-2and 0.60 μmol·m-2s-1, respectively. In addition, the difference on the photosynthetic CO2response parameters values showed somewhat among different layers and orientations. In all, all data suggested that the modified rectangular hyperbolic model (MRHM) was an ideal model to fit the crown photosynthetic CO2response curve ofLarix principis-rupprechtiiMayr. These results are of great significance for parameter calibration of photosynthetic model and robust prediction of photosynthetic response in forest.
Investigating miRNA signatures in metastatic breast cancer: Anin-silicoanalysis
Authors: Harini Lakshminarasimhan , Madhav Lekshmi , Srivastava Sweta , Ramaswamy Gopalakrishna , Ramesh Rakesh
Published: June 2023

miRNAs are small non-coding RNAs that regulate most cellular processes. Tumorigenesis disrupts the normal balance in the cell, which leads to changes in the cell cycle, cell signalling, activation of growth factors, miRNA deregulation, etc. Thus, the variations in miRNA expression between normal and tumor stages can be used to predict, diagnose, detect and identify different cancer stages, thereby suggesting the potential use of the miRNAs as biomarkers or potential therapeutic targets for cancer.

In this study we aim to identify differentially expressed miRNAs which could serve as potential biomarkers or therapeutic targets for breast cancer.

Microarray-based expression analysis was performed on tissue samples from patients with early and locally advanced breast cancer and nCounter analysis was performed to detect differentially expressed miRNA. Additionally, functional enrichment analysis, miRNA linked gene prediction, and in silico analysis for miRNA expression in cancer databases were carried out. This analysis revealed increased expression of Hsa-miR-199a and b. Further these miRs had increased expression levels across various cancer. Importantly, genes such as CALR, SSR2, and YWHAZ predicted as miR’s target were highly expressed in breast cancer. However, these genes lack therapeutic drugs targeting them. Overall, our study identified previously unexplored miRNAs and their gene targets, which could be exploited as potential targets for future therapeutic interventions.
Large vessel occlusions of milder severity show better collaterals and reduced harm from thrombectomy transfer delays
Authors: Rowling Hannah , Italiano Dominic , Churilov Leonid , Palanikumar Logesh , Harvey Jackson , Kleinig Timothy , Parsons Mark , Mitchell Peter , Davis Stephen , Kruyt Nyika , Campbell Bruce , Zhao Henry
Published: June 2023

Background and Purpose

Patients with large vessel occlusion (LVO) stroke of milder baseline clinical severity are often missed by pre-hospital severity-based triage tools. We examined whether these patients had differences in 1) markers of collateral circulation and 2) the relative harm of transfer delays on outcome, compared to patients with clinically more severe baseline deficits.

Methods

Registry data from two large Australian thrombectomy centers was used to identify all directly presenting and transferred LVO patients undergoing endovascular thrombectomy, divided into those with milder baseline deficits (NIHSS <10) and severe baseline deficits (NIHSS ≥10). Baseline CT-perfusion markers of collateral circulation and the association between transfer status and functional outcome (using the 90-day modified Rankin Scale) were compared.

Results

Of 1210 included LVO patients, 273 (22.6%) had milder severity. Milder LVO patients showed smaller median ischemic core volumes (12.6 [IQR 0.0-17.9] vs 27.5 [IQR 6.5-37.1] mL, p<0.001)), higher median perfusion mismatch ratio (148.3 [IQR 5.0-500.0] vs 66.2 [IQR 3.6-17.2], p<0.001) and lower median hypoperfusion intensity ratio (0.25 [IQR 0.18-0.38] vs 0.40 [IQR 0.22-0.57], p<0.001). Transferred patients had a lower odd of excellent outcome than primary presenters, when deficits were severe deficits (aOR 0.759 [95% CI 0.576-0.999]) but not when deficits were milder (aOR 1.357 [95% CI 0.764-2.409], pinteraction=0.122).

Conclusions

Patients with LVO stroke of milder clinical severity have significantly better imaging markers of collateral circulation compared to high-severity patients. Despite high rates of thrombolytics, secondary transfer to thrombectomy-center was only associated with poorer 90-day functional outcomes in higher-severity patients. Failure of pre-hospital screening tools to detect lower-severity LVO patients for immediate pre-hospital bypass to a thrombectomy center may not deleteriously affect their outcome.
Lesion network localization of a stable personality trait
Authors: Palm Stephan T. , Khosravani Sanaz , Campanella Fabio , Cohen Alexander L. , Drew William , Fabbro Franco , Pottanat Roger , Urgesi Cosimo , Ferguson Michael A. , Siddiqi Shan H.
Published: June 2023

Objective

To identify a convergent neuroanatomical substrate for novelty seeking (NS), a stable personality trait, which could serve as a therapeutic target for transcranial magnetic stimulation (TMS).

Methods

We analyzed two independent datasets (total n=136) in which the Temperament and Character Inventory (TCI) was used to document alterations across 7 stable personality traits before and after brain lesions surgically induced by glioma resection. Using lesion network mapping, we examined whether alterations in NS were causally associated with lesions to specific brain networks. We assessed for strength of replication across datasets and specificity against other personality traits.

Results

Lesion locations that are linked to NS map to a common brain with its largest cluster in the dorsal cingulate. This map was specific to NS relative to other personality traits and overlapped with prior published neuroimaging findings related to the term “novelty”. Utilizing a pre-computed connectome, we also derived a map highlighting potential targets for non-invasive brain stimulation that may alter this stable personality trait.

Conclusions

We derived and cross-validated a brain network that is functionally connected to lesions that are causally responsible for the stable personality trait “novelty seeking”. Lesions to this network were associated with changes in NS. This includes a superficial node within the dorsolateral prefrontal cortex that may serve as a promising TMS target to modulate or protect against abnormal NS.
Differential usage of DNA modifications in neurons, astrocytes, and microglia
Authors: Tooley Kyla B. , Chucair-Elliott Ana J. , Ocañas Sarah R. , Machalinski Adeline H. , Pham Kevin D. , Stanford David R. , Freeman Willard M.
Published: June 2023

Background

Cellular identity is determined partly by cell type-specific epigenomic profiles that regulate gene expression. In neuroscience, there is a pressing need to isolate and characterize the epigenomes of specific CNS cell types in health and disease. This is especially true as for DNA modifications where most data are derived from bisulfite sequencing that cannot differentiate between DNA methylation and hydroxymethylation. In this study, we developed anin vivotagging mouse model (Camk2a-NuTRAP) for paired isolation of neuronal DNA and RNA without cell sorting and then used this model to assess epigenomic regulation of gene expression between neurons and glia.

Results

After validating the cell-specificity of the Camk2a-NuTRAP model, we performed TRAP-RNA-Seq and INTACT whole genome oxidative bisulfite sequencing to assess the neuronal translatome and epigenome in the hippocampus of young mice (3 months old). These data were then compared to microglial and astrocytic data from NuTRAP models. When comparing the different cell types, microglia had the highest global mCG levels followed by astrocytes and then neurons, with the opposite pattern observed for hmCG and mCH. Differentially modified regions between cell types were predominantly found within gene bodies and distal intergenic regions, with limited differences occurring within proximal promoters. Across cell types there was a negative correlation between DNA modifications (mCG, mCH, hmCG) and gene expression at proximal promoters. In contrast, a negative correlation of mCG with gene expression within the gene body while a positive relationship between distal promoter and gene body hmCG and gene expression was observed. Furthermore, we identified a neuron-specific inverse relationship between mCH and gene expression across promoter and gene body regions.

Conclusions

In this study, we identified differential usage of DNA modifications across CNS cell types, and assessed the relationship between DNA modifications and gene expression in neurons and glia. Despite having different global levels, the general modification-gene expression relationship was conserved across cell types. The enrichment of differential modifications in gene bodies and distal regulatory elements, but not proximal promoters, across cell types highlights epigenomic patterning in these regions as potentially greater determinants of cell identity.
DanioCTC: Injection of circulating tumor cells from metastatic breast cancer patients in zebrafish xenografts for analysis of metastasis
Authors: Reinhardt Florian , Coen Luisa , Rivandi Mahdi , Franken André , Sawitning Ayu Setyono Eunike , Lindenberg Tobias , Eberhardt Jens , Fehm Tanja , Niederacher Dieter , Knopf Franziska , Neubauer Hans
Published: June 2023

Circulating tumor cells (CTCs) are considered as metastatic precursor cells, and zebrafish xenografts provide anin vivomodel to study cancer cell spread. Currently, the low number of patient-derived CTCs limits their analysis in animal models. We present DanioCTC, a xenograft workflow for injecting CTCs from metastatic breast cancer (MBC) patients into zebrafish embryos to study cell disseminationin vivo. The study successfully adapts existing workflows and combines diagnostic leukapheresis (DLA), the Parsortix microfluidic system, flow cytometry, and the automated cell micromanipulator CellCelector setup to enrich and isolate MBC-derived CTCs and to finally inject them into Zebrafish embryos, where their dissemination was tracked up to 3 days post-injection. MDA-MB-231 cells were used as a standard xenotransplantation control, and these cells were frequently found in the head and blood-forming regions of the tail. Using DLA aliquots spiked with MBA-MB-231 cells, the newly established DanioCTC workflow confirmed the dissemination of MDA-MB-231 cells into these regions. CTCs from an MBC patient were then enriched by DLA, Parsortix, and flow cytometry, isolated with the CellCelectorTM and xenografted into zebrafish embryos. CTCs were mainly detected in the head and trunk, unlike MDA-MB-231 cells, which were present in the head and tail. DanioCTC presents a significant breakthrough in the use of zebrafish embryos as a model to study CTC disseminationin vivo, which can be used for patient-derived CTCs instead of cell culture-derived cancer cells as a crucial step towards understanding the biology of metastatic breast cancer.

Statement of significance

DanioCTC is a novel workflow to inject patient-derived CTCs into zebrafish, enabling studies on CTC dissemination and personalized treatmentin vivo, therefore advancing our toolkit to fight metastatic cancer.
Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition
Authors: Alegre-Zurano Laia , Caceres-Rodriguez Alba , Berbegal-Sáez Paula , Lassalle Olivier , Manzoni Olivier , Valverde Olga
Published: June 2023

Background

A single usage of a drug of abuse can have lasting effects on both the brain and behavior, continuing even after the drug has been metabolized and eliminated from the body. A single dose of cocaine can abolish endocannabinoid-mediated long-term depression (eCB-LTD) in the nucleus accumbens (NAc) within 24 hours of administration. However, it is uncertain whether this altered neuroplasticity entails a behavioral deficit.

Methods

Our study employed adult male mice to investigate the effects of a single dose of cocaine (20 mg/kg) on eCB-LTD, saccharin preference, and social interactions 24 hours after administration. We also examined the gene expression in components of the eCB system. The pharmacological increase of anandamide was evaluated using the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 mg/kg).

Results

After a single dose of cocaine, mice displayed altered plasticity, social interactions, and preference for saccharin and a reduction in mRNA levels of the anandamide-catabolizing enzyme NAPE-PLD. We discovered that the FAAH inhibitor URB597 (1 mg/kg) successfully reversed the cocaine-induced loss of eCB-LTD in the NAc and restored normal social interaction in cocaine-exposed mice, but it did not affect their saccharin preference.

Conclusions

Overall, this research underlines the neuroplastic changes and subsequent behavioral alterations that occur after the initial use of cocaine, while also suggesting a potential role for anandamide in the early impairments caused by cocaine. The findings highlight the importance of understanding the mechanisms underlying the initiation of drug use and offer a potential therapeutic target.
Mediating Effect of Physical Activity on Relation between Cardio-respiratory Fitness and Physical Function Capacity of Older Adults
Authors: Aloko Eric A. , Ansah Edward W. , Apaak Daniel , Sarpong Emmanuel O. , Seibu Munkaila , Sorkpor Stephen R.
Published: June 2023

The ageing process is normally accompanied by several physiological changes like a decline in physical function and increased risk of chronic health conditions. In older adults, maintaining physical function and cardiovascular health is essential for maintaining independence and quality of life. Cardio-respiratory fitness and physical functional capacity (PFC) are two important indicators of physical health in older adults. This study aims to investigate the mediating effect of physical activity (PA) on the relationship between CRF and PFC in older adults. Using quantitative cross-sectional design, we employed a multistage sampling strategy to recruit 998 older adults from Navrongo for this study. The senior fitness test battery, international physical activity questionnaire (IPAQ) short form for elderly, weighing scale and tape measure were used to collect the data. The findings revealed that, 53.4% and 53.9% of these older adults had reduced PFC and CRF respectively. It was also found that PA partially mediates the relationship between CRF and PFC of the older adults with an indirect effect of CRF on PFC as β = .0030, t = 1.579 p < .05, with a direct effect of CRF on PFC, β = .867, t = 42.954, p < .05, and the total effect, β = .872, t = 43.110, p < .05. We concluded that physical activity partially mediates the relationship between CRF and PFC among older adults in Navrongo. Therefore, there is the need for evidenced-based intervention to promote PA among these older adults to improve their PFC and quality of life.
Labour Care Guide implementation as a decision-making tool for monitoring labour among health care providers in Southwestern Uganda: A protocol for a multisite Effectiveness-Implementation study
Authors: Mugyenyi GR , Mulogo EM , Tumuhimbise W , Atukunda EC , Kayondo M , Ngonzi J , Byamugisha J , Yarine F
Published: June 2023

Background

The new WHO Labour Care Guide, also regarded as the “next-generation partograph” basing on recent evidence has been recorded as a core component of the 2018 consolidated set of guidelines on intrapartum care for positive child birth experience. The Ugandan Ministry of Health is in the process of adopting the new WHO Labour Care Guide (LCG) with no local context specific data to inform this transition. This study will employ evidence-based research frameworks to identify challenges, and potential opportunities that would inform and refine the implementation strategy and scale-up of this highly promising LCG. We will also seek to utilize best practices to evaluate implementation effectiveness of the new LCG, through employing measurable implementation matrices (implementation, service, patient outcomes).

Methods

This study will be a multisite effectiveness-implementation study across all basic and comprehensive emergency obstetric and newborn care facilities in Mbarara district and Mbarara City in Southwestern Uganda. We will employ both quantitative and qualitative methods to evaluate the use of the newly recommended WHO Labor Care Guide in monitoring labor among all health care providers actively engaged in deliverying women across all public maternity health facilities in Mbarara district and Mbarara City. No participant has been recruited at hie point in time

Results and Discussion

This study will offer an opportunity to ascertain whether the new WHO Labour Care Guide tool is an effective decision-making tool to monitor labor among healthcare providers conducting routine deliveries in publicly funded facilities in Southwestern Uganda. We will also identify practical, context-specific and actionable strategies for achieving optimal implementation effectiveness in a rural low resource setting.
Clinical utility of measuring CD4+T follicular cells in patients with immune dysregulation
Authors: LaBere Brenna , Nguyen Alan A. , Habiballah Saddiq B. , Elkins Megan , Imperial Juliet , Li Betty , Devana Sridevi , Timilsina Suraj , Stubbs Spencer B. , Joerger Jill , Chou Janet , Platt Craig D.
Published: June 2023

Mechanistic studies of autoimmune disorders have identified circulating T follicular helper (cTfh) cells as drivers of autoimmunity. However, the quantification of cTfh cells is not yet used in clinical practice due to the lack of age-stratified normal ranges and the unknown sensitivity and specificity of this test for autoimmunity. We enrolled 238 healthy participants and 130 patients with common and rare disorders of autoimmunity or autoinflammation. Patients with infections, active malignancy, or any history of transplantation were excluded. In 238 healthy controls, median cTfh percentages (range 4.8% – 6.2%) were comparable among age groups, sexes, races, and ethnicities, apart from a significantly lower percentages in children less than 1 year of age (median 2.1%, CI: 0.4% – 6.8,p<0.0001). Among 130 patients with over 40 immune regulatory disorders, a cTfh percentage exceeding 12% had 88% sensitivity and 94% specificity for differentiating disorders with adaptive immune cell dysregulation from those with predominantly innate cell defects. This threshold had a sensitivity of 86% and specificity of 100% for active autoimmunity and normalized with effective treatment. cTfh percentages exceeding 12% distinguish autoimmunity from autoinflammation, thereby differentiating two endotypes of immune dysregulation with overlapping symptoms and different therapies.
Evaluation of abstract rule-based associations in the human premotor cortex during passive observation
Authors: Gharesi Niloofar , Luneau Lucie , Kalaska John F. , Baillet Sylvain
Published: June 2023

Decision-making often manifests in behavior, typically yielding overt motor actions. This complex process requires the registration of sensory information with one’s internal representation of the current context, before a categorical judgment of the most appropriate motor behavior can be issued. The construct concept of embodied decision-making encapsulates this sequence of complex processes, whereby behaviorally salient information from the environment is represented in an abstracted space of potential motor actions rather than only in an abstract cognitive “decision” space. Theoretical foundations and some empirical evidence account for support the involvement of premotor cortical circuits in embodied cognitive functions. Animal models show that premotor circuits participate in the registration and evaluation of actions performed by peers in social situations, that is, prior to controlling one’s voluntary movements guided by arbitrary stimulus-response rules. However, such evidence from human data is currently limited. Here we used time-resolved magnetoencephalography imaging to characterize activations of the premotor cortex as human participants observed arbitrary, non-biological visual stimuli that either respected or violated a simple stimulus-response association rule. The participants had learned this rule previously, either actively, by performing a motor task (active learning), or passively, by observing a computer perform the same task (passive learning). We discovered that the human premotor cortex is activated during the passive observation of the correct execution of a sequence of events according to a rule learned previously. Premotor activation also differs when the subjects observe incorrect stimulus sequences. These premotor effects are present even when the observed events are of a non-motor, abstract nature, and even when the stimulus-response association rule was learned via passive observations of a computer agent performing the task, without requiring overt motor actions from the human participant. We found evidence of these phenomena by tracking cortical beta-band signaling in temporal alignment with the observation of task events and behavior. We conclude that premotor cortical circuits that are typically engaged during voluntary motor behavior are also involved in the interpretation of events of a non-ecological, unfamiliar nature but related to a learned abstract rule. As such, the present study provides the first evidence of neurophysiological processes of embodied decision-making in human premotor circuits when the observed events do not involve motor actions of a third party.
Localized and global representation of prior value, sensory evidence, and choice in male mouse cerebral cortex
Authors: Ishizu Kotaro , Nishimoto Shosuke , Ueoka Yutaro , Funamizu Akihiro
Published: June 2023

Adaptive behavior requires integrating prior knowledge of action outcomes and sensory evidence for making decisions while maintaining prior knowledge for future actions. As outcome- and sensory-based decisions are often tested separately, it is unclear how these processes are integrated in the brain. In a tone frequency discrimination task with two sound durations and asymmetric reward blocks, we found that neurons in the medial prefrontal cortex of male mice represented the additive combination of prior reward expectations and choices. The sensory inputs and choices were selectively decoded from the auditory cortex irrespective of reward priors and the secondary motor cortex, respectively, suggesting localized computations of task variables are required within single trials. In contrast, all the recorded regions represented prior values that needed to be maintained across trials. We propose localized and global computations of task variables in different time scales in the cerebral cortex.
Whole Genome Sequencing Reveals Autooctoploidy in the Chinese Sturgeon and its Evolutionary Trajectories
Authors: Wang Binzhong , Wu Bin , Liu Xueqing , Hu Yacheng , Ming Yao , Bai Mingzhou , Liu Juanjuan , Xiao Kan , Zeng Qingkai , Yang Jing , Wang Hongqi , Guo Baifu , Tan Chun , Hu Zixuan , Zhao Xun , Li Yanhong , Yue Zhen , Mei Junpu , Jiang Wei , Yang Yuanjin , Li Zhiyuan , Gao Yong , Chen Lei , Jian Jianbo , Du Hejun
Published: June 2023

The Order Acipenseriformes, which include sturgeons and paddlefishes, represent “living fossils” with complex genomes that are good models for understanding whole genome duplication (WGD) and ploidy evolution in fishes. Here we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploidAcipenser sinensis(Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show thatA. sinensisis a complex autooctoploid species containing four kinds of octovalents (8 n), a hexavalent (6 n), two tetravalents (4 n), and a divalent (2 n). We propose based on an analysis taking into account delayed rediploidization that its octoploid genome composition results from two rounds of homologous whole genome duplications (WGDs), and further provide insight into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy composition and evolutionary trajectories of polyploidy fishes.
TheToxoplasmamonocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival
Authors: Dong Hui , Yang Jiong , He Kai , Zheng Wen-Bin , Lai De-Hua , Liu Jing , Ding Hui-Yong , Wu Rui-Bin , Brown Kevin M. , Hide Geoff , Lun Zhao-Rong , Zhu Xing-Quan , Long Shaojun
Published: June 2023

The apicoplast is a four-membrane plastid found in the apicomplexans, which harbors biosynthesis and organelle housekeeping activities in the matrix. However, the mechanism driving the flux of metabolites, in and out, remains unknown. Here we used TurboID and genome engineering to identify apicoplast transporters inToxoplasma gondii. Among the many novel transporters, we show that one pair of apicomplexan monocarboxylate transporters (AMTs) appears to have evolved from a putative host cell that engulfed a red alga. Protein depletion showed that AMT1 and AMT2 are critical for parasite growth. Metabolite analyses supported the notion that AMT1 and AMT2 are associated with biosynthesis of isoprenoids and fatty acids. However, stronger phenotypic defects were observed for AMT2, including in the inability to establishT. gondiiparasite virulence in mice. This study clarifies, significantly, the mystery of apicoplast transporter composition and reveals the importance of the pair of AMTs in maintaining the apicoplast activity in apicomplexans.
Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures
Authors: Schiffmann Andrea , Ahlswede Lena , Gimpl Gerald
Published: June 2023

The enzyme acyl-CoA:cholesterol acyltransferase (ACAT) is normally localized in the endoplasmic reticulum (ER) where it can esterify cholesterol for storage in lipid droplets and/or the formation of lipoproteins. Here, we report that ACAT can translocate from the ER into vesicular structures in response to different ACAT inhibitors. The translocation was fast (within minutes), reversible and occurred in different cell types. Interestingly, oleic acid was able to fasten the re-translocation from vesicles back into the reticular ER network. The process of ACAT translocation could also be induced by cyclodextrins, cholesterol, lanosterol (but not 4-cholestene-3 one), 25-hydroxycholesterol, and by certain stress stimuli such as hyperosmolarity (sucrose treatment), temperature change, or high-density cultivation.In vitroesterification showed that ACAT remains fully active after it has been translocated to vesicles in response to hyperosmotic sucrose treatment of the cells. The translocation process was not accompanied by changes in the electrophoretic mobility of ACAT, even after chemical crosslinking. Interestingly, the protein synthesis inhibitor cycloheximide showed a stimulating effect on ACAT activity and prevented the translocation of ACAT from the ER into vesicles. The translocation process of ACAT may provide a new way to regulate cholesterol esterification in cells, by altering the accessibility of the enzyme to its substrate.
The acidic intrinsically disordered region of the inflammatory mediator HMGB1 mediates fuzzy interactions with chemokine CXCL12
Authors: Mantonico Malisa Vittoria , Leo Federica De , Quilici Giacomo , Colley Liam , Marchis Francesco De , Crippa Massimo , Schulte Tim , Zucchelli Chiara , Ricagno Stefano , Giachin Gabriele , Ghitti Michela , Bianchi Marco , Musco Giovanna
Published: June 2023

Chemokines engage in heterodimeric interactions to activate or dampen their cognate receptors in inflammatory conditions. The chemokine CXCL12 forms with the alarmin HMGB1 a patho-physiologically relevant heterocomplex (HMGB1●CXCL12), whose formation synergically promotes the inflammatory response elicited by the G-protein coupled receptor CXCR4. However, the molecular details of complex formation were still elusive. Through an integrative structural approach (NMR, AUC, ITC, MST, SAXS) we show that HMGB1●CXCL12 represents the firstfuzzychemokines heterocomplex reported so far. HMGB1 and CXCL12 form a dynamic equimolar assembly, rather than involving one HMGB1 and two CXCL12 molecules as previously assumed, with structured and unstructured HMGB1 regions recognizing the dimerization surface of CXCL12. We uncover an unexpected role of the acidic intrinsically disordered region (IDR) in heterocomplex formation and provide the first evidence that the acidic IDR facilitates the ternary HMGB1•CXCL12•CXCR4 interaction on the cell surface. Thus, the interaction of HMGB1 with CXCL12 diverges radically from the classical rigid heterophilic chemokine-chemokine dimerization. Simultaneous interference with the multiple interactions within HMGB1●CXCL12 complex formation might offer novel pharmacological strategies to inhibit its detrimental activity in inflammatory conditions.
Distinct subtypes of grey matter heterotopia show subtype-specific morpho-electric neuronal properties and dynamics of epileptiform activity in mice
Authors: Vermoyal Jean-Christophe , Hardy Delphine , Goirand-Lopez Lucas , Vinck Antonin , Silvagnoli Lucas , Fortoul Aurélien , Francis Fiona , Cappello Silvia , Bureau Ingrid , Represa Alfonso , Cardoso Carlos , Watrin Françoise , Marissal Thomas , Manent Jean-Bernard
Published: June 2023

Grey matter heterotopia (GMH) are neurodevelopmental disorders associated with abnormal cortical function and epilepsy. Subcortical band heterotopia (SBH) and periventricular nodular heterotopia (PVNH) are two well-recognized GMH subtypes in which neurons are misplaced, either forming nodules lining the ventricles in PVNH, or forming bands in the white matter in SBH. Although both PVNH and SBH are commonly associated with epilepsy, it is unclear whether these two GMH subtypes differ in terms of pathological consequences or, on the contrary, share common altered mechanisms. Here, we studied two robust preclinical models of SBH and PVNH, and performed a systematic comparative assessment of the physiological and morphological diversity of heterotopia neurons, as well as the dynamics of epileptiform activity and input connectivity. We uncovered a complex set of altered properties, including both common and distinct physiological and morphological features across heterotopia subtypes, and associated with specific dynamics of epileptiform activity. Taken together, these results suggest that pro-epileptic circuits in GMH are, at least in part, composed of neurons with distinct, subtype-specific, physiological and morphological properties depending on the heterotopia subtype. Our work supports the notion that GMH represent a complex set of disorders, associating both shared and diverging pathological consequences, and contributing to forming epileptogenic networks with specific properties. A deeper understanding of these properties may help to refine current GMH classification schemes by identifying morpho-electric signatures of GMH subtypes, to potentially inform new treatment strategies.
New viruses ofCladosporiumsp. expand considerably the taxonomic structure ofGammapartitivirusgenus
Authors: Jaccard Augustine , Dubuis Nathalie , Kellenberger Isabelle , Brodard Justine , Schnee Sylvain , Gindro Katia , Schumpp Olivier
Published: June 2023

Despite the fact thatCladosporiumsp. are ubiquitous fungi, their viromes have been little studied. By analysing a collection of Cladosporium fungi, two new partitiviruses named Cladosporium cladosporioides partitivirus 1 (CcPV1) and Cladosporium cladosporioides partitivirus 2 (CcPV2) co-infecting a strain ofCladosporium cladosporioideswere identified. Their complete genome consists in two monocistronic dsRNA segments (RNA1 and RNA2) with a high percentage of pairwise identity on 5’ and 3’ end. The RNA dependant RNA polymerase (RdRp) of both viruses and the capsid protein (CP) of CcPV1 display the classic characteristics required for their assignment to theGammapartitivirusgenus. In contrast, CcPV2 RNA2 encodes for a 41 KDa CP that is unusually small with a low percentage of amino acid identity as compared to CPs of other viruses classified in this genus. This sequence was used to annotate fifteen similar viral sequences with unconfirmed function. The phylogeny of the CP was highly consistent with the phylogeny of their corresponding RdRp, supporting the organization of gammapartitiviruses into three distinct clades despite stretching the current demarcation criteria.
When Neural Activity Fails to Reveal Causal Contributions
Authors: Fakhar Kayson , Dixit Shrey , Hadaeghi Fatemeh , Kording Konrad P. , Hilgetag Claus C.
Published: June 2023

Neuroscientists rely on distributed spatio-temporal patterns of neural activity to understand how neural units contribute to cognitive functions and behavior. However, the extent to which neural activity reliably indicates a unit’s causal contribution to the behavior is not well understood. To address this issue, we provide a systematic multi-site perturbation framework that captures time-varying causal contributions of elements to a collectively produced outcome. Applying our framework to intuitive toy examples and artificial neuronal networks revealed that recorded activity patterns of neural elements may not be generally informative of their causal contribution due to activity transformations within a network. Overall, our findings emphasize the limitations of inferring causal mechanisms from neural activities and offer a rigorous lesioning framework for elucidating causal neural contributions.
The Time-Course of Food Representation in the Human Brain
Authors: Moerel Denise , Psihoyos James , Carlson Thomas A.
Published: June 2023

Humans make decisions about food every day. The visual system provides important information that forms a basis for these food decisions. Although previous research has focused on visual object and category representations in the brain, it is still unclear how visually presented food is encoded by the brain. Here, we investigate the time-course of food representations in the brain. We used time-resolved multivariate analyses of electroencephalography (EEG) data, obtained from human participants (both sexes), to determine which food features are represented in the brain, and whether focused attention is needed for this. We recorded EEG while participants engaged in one of two tasks. In one task the stimuli were task relevant, whereas in the other task the stimuli were not task relevant. Our findings indicate that the brain can differentiate between food and non-food items from approximately 112 milliseconds after stimulus onset. The neural signal at later latencies contained information about food naturalness, how much the food was transformed, as well as the perceived caloric content. This information was present regardless of the task. Information about whether food is immediately ready to eat, however, was only present when the food was task relevant and presented at a slow presentation rate. Furthermore, the recorded brain activity correlated with the behavioural responses in an odd-item-out task. The fast representation of these food features, along with the finding that this information is used to guide food categorisation decision-making, suggests that these features are important dimensions along which the representation of foods is organised.
Maturation-dependent changes in cortical and thalamic activity during slow waves of light sleep: insights from a combined EEG-fMRI study
Authors: Bergamo Damiana , Handjaras Giacomo , Petruso Flavia , Talami Francesca , Ricciardi Emiliano , Benuzzi Francesca , Vaudano Anna Elisabetta , Meletti Stefano , Bernardi Giulio , Betta Monica
Published: June 2023

INTRODUCTION

Studies using scalp EEG have shown that slow waves (0.5-4 Hz), the most prominent hallmark of NREM sleep, undergo relevant changes from childhood to adulthood, mirroring brain structural modifications and the acquisition of cognitive skills. Here we used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes.

METHODS

We analyzed data from 14 school-age children with self-limited focal epilepsy of childhood who fell asleep during EEG-fMRI recordings. Brain regions associated with slow-wave occurrence were identified using a voxel-wise regression that also modeled interictal epileptic discharges and sleep spindles. At the group level, a mixed-effects linear model was used. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults.

RESULTS

Slow waves were associated with hemodynamic-signal decreases in bilateral somatomotor areas. Such changes extended more posteriorly relative to those in adults. Moreover, the involvement of areas belonging to the default mode network changes as a function of age. No significant hemodynamic responses were observed in subcortical structures. However, we identified a significant correlation between age and thalamic hemodynamic changes.

CONCLUSIONS

Present findings indicate that the somatomotor cortex may have a key role in slow-wave expression throughout the lifespan. At the same time, they are consistent with a posterior-to-anterior shift in slow-wave distribution mirroring brain maturational changes. Finally, our results suggest that slow-wave changes may not reflect only neocortical modifications but also the maturation of subcortical structures, including the thalamus.

Statement of significance

Low spatial resolution of conventional EEG has widely limited the possibility of accurately determining in humans the role of different brain structures in the expression of sleep slow waves throughout development. Here, for the first time, we took advantage of a simultaneous EEG-fMRI approach to accurately describe the cortical and subcortical hemodynamic correlates of sleep slow waves in a sample of 14 school-aged children. In order to elucidate age-dependent changes, we qualitatively compared present findings with those previously obtained in a group of adults. Overall our results have important implications for the understanding of how cortico-cortical and subcortico-cortical interactions shape sleep slow waves across development.
Epsilon tubulin is an essential determinant of microtubule-based structures in male germ cells
Authors: Stathatos G. Gemma , Merriner D. Jo , O’Connor Anne E. , Zenker Jennifer , Dunleavy Jessica E.M. , O’Bryan Moira K.
Published: June 2023

Alpha, beta and gamma tubulins are essential building blocks for all eukaryotic cells. The functions of the non-canonical tubulins, delta, epsilon and zeta, however, remain poorly understood and their requirement in mammalian development untested. Herein we have used a spermatogenesis model to define epsilon tubulin (TUBE1) function in mice. We show that TUBE1 is essential for the function of multiple complex microtubule arrays, including the meiotic spindle, axoneme and manchette and in its absence, there is a dramatic loss of germ cells and male sterility. Through examining axoneme structure, we identify differences in TUBE1 function between somatic and germ cells and potentially between species. Moreover, we provide evidence for the interplay between TUBE1 and katanin-mediated microtubule severing, and for the sub-specialization of individual katanin paralogs in the regulation of specific microtubule arrays.
A Simulation Study on High Spatio-Temporal Resolution Acousto-Electrophysiological Neuroimaging
Authors: Schoeters Ruben , Tarnaud Thomas , Martens Luc , Tanghe Emmeric
Published: June 2023

Acousto-electrophysiological neuroimaging is a technique hypothesized to record electrophysiological activity of the brain with millimeter spatial and sub-millisecond temporal resolution. This improvement is obtained by tagging areas with focused ultrasound (fUS). Due to mechanical vibration with respect to the measuring electrodes, the electrical activity of the marked region will be modulated onto the ultrasonic frequency. The region’s electrical activity can subsequently be retrieved via demodulation of the measured signal. In this study, the feasibility of this hypothesized technique is tested. This is done by calculating the forward electroencephalography (EEG) response under quasi-static assumptions. The head is simplified as a set of concentric spheres. Two sizes are evaluated representing human and mouse brains. Moreover, feasibility is assessed for wet and dry transcranial, and for cortically placed electrodes. The activity sources are modeled by dipoles, with their current intensity profile drawn from a power-law power spectral density. It is shown that mechanical vibration modulates the endogenous activity onto the ultrasonic frequency. The signal strength depends non-linearly on the alignment between dipole orientation, vibration direction and recording point. The strongest signal is measured when these three dependencies are perfectly aligned. The signal strengths are in the pV-range for a dipole moment of 5 nAm and ultrasonic pressures within FDA-limits. The endogenous activity can then be accurately reconstructed via demodulation. Two interference types are investigated: vibrational and static. Depending on the vibrational interference, it is shown that millimeter resolution signal detection is possible also for deep brain regions. Subsequently, successful demodulation depends on the static interference, that at MHz-range has to be sub-picovolt.
Glucocorticoid stress hormones stimulate vesicle-free Tau secretion and spreading in the brain
Authors: Yu Qing , Du Fang , Belli Irla , Gomes Patricia A. , Sotiropoulos Ioannis , Waites Clarissa L.
Published: June 2023

Chronic stress and elevated levels of glucocorticoids (GCs), the main stress hormones, accelerate Alzheimer’s disease (AD) onset and progression. A major driver of AD progression is the spreading of pathogenic Tau protein between brain regions, precipitated by neuronal Tau secretion. While stress and high GC levels are known to induce intraneuronal Tau pathology (i.e.hyperphosphorylation, oligomerization) in animal models, their role in trans-neuronal Tau spreading is unexplored. Here, we find that GCs promote secretion of full-length, vesicle-free, phosphorylated Tau from murine hippocampal neurons andex vivobrain slices. This process occurs via type 1 unconventional protein secretion (UPS) and requires neuronal activity and the kinase GSK3β. GCs also dramatically enhance trans-neuronal Tau spreadingin vivo, and this effect is blocked by an inhibitor of Tau oligomerization and type 1 UPS. These findings uncover a potential mechanism by which stress/GCs stimulate Tau propagation in AD.
Learning and memory in hybrid migratory songbirds - cognition as a reproductive isolating barrier across seasons
Authors: Alario Ashley , Trevino Marlene , Justen Hannah , Woodman Constance J. , Roth Timothy C. , Delmore Kira E.
Published: June 2023

Hybrid zones can be used to identify traits that maintain reproductive isolation and contribute to speciation. Cognitive traits may serve as post-mating reproductive isolating barriers, reducing the fitness of hybrids if, for example, misexpression occurs in hybrids and disrupts important neurological mechanisms. We tested this hypothesis in a hybrid zone between two subspecies of Swainson’s thrushes (Catharus ustulatus) using two cognitive tests – an associative learning spatial test and neophobia test. We included comparisons across the sexes and seasons (spring migration and winter), testing if hybrid females performed worse than males (as per Haldane’s rule) and if birds (regardless of ancestry or sex) performed better during migration, when they are building navigational maps and encountering new environments. We documented reduced cognitive abilities in hybrids, but this result was limited to males and winter. Hybrid females did not perform worse than males in either season. Although season was a significant predictor of performance, contrary to our prediction, all birds learned faster during the winter. The hypothesis that cognitive traits could serve as post-mating isolating barriers is relatively new; this is one of the first tests in a natural hybrid zone and non-food-caching species. We also provide one of the first comparisons of cognitive abilities between seasons. Future neurostructural and neurophysiological work should be used to examine mechanisms underlying our behavioral observations.
Determinants of overall user success in an academic digital library environment: validation of the integrated digital library user success (IDLUS) model
Authors: Iqbal Memoona , Rafiq Muhammad
Published: June 2023

Purpose

Digital Libraries are complex, and this complexity is a motive to study user success on the behalf of appropriate user success models. These models comprise the factors which play a part between people, technology and organizations. The purpose of this study was to specify and examine an integrated digital library user success (IDLUS) model within the context of digital library settings, Higher Education Commission National Digital Library (HEC-NDL) of Pakistan, by adopting and reusing the existing digital library and Web success models.

Design/methodology/approach

Stratified random sampling technique was used to choose the sample from the University of the Punjab, a highly ranked public sector university in Pakistan. Participants were asked to complete an adapted survey questionnaire. A total of 355 completed and usable questionnaires were obtained. Data analyses through confirmatory factor analyses and structural equation modeling produced the results that have supported the proposed IDLUS model. The proposed IDLUS model was tested and supported through model fit statistics in the academic computing environment of the HEC-NDL of Pakistan.

Findings

Findings revealed that relationships between the latent variables hypothesized in the model were confirmed.

Research limitations/implications

The study has both theoretical and practical ramifications for academicians and information system designers and developers.

Originality/value

The IDLUS model is recommended first time in the history of librarianship in Pakistan as an overall user success model in the digital library information system computing environment. That made numerous recommendations for future research in the field of information management, particularly for digital library development at national and international levels.