bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual impact of PTEN mutation on CSF dynamics and cortical networks via the dysregulation of neural precursors and their interneuron descendants
Authors: DeSpenza Tyrone , Kiziltug Emre , Allington Garrett , Barson Daniel G. , O’Connor David , Robert Stephanie M. , Mekbib Kedous Y. , Nanda Pranav , Greenberg Ana , Singh Amrita , Duy Phan Q. , Mandino Francesca , Zhao Shujuan , Lynn Anna , Reeves Benjamin C. , Marlier Arnaud , Getz Stephanie A. , Nelson-Williams Carol , Shimelis Hermela , Walsh Lauren K. , Zhang Jinhui , Wang Wei , OuYang Annaliese , Smith Hannah , Butler William , Carter Bob S. , Deniz Engin , Lake Evelyn M. R. , Constable Todd , Gûnel Murat , Lifton Richard P. , Alper Seth L. , Chih Jin Sheng , Crair Michael C. , Moreno-De-Luca Andres , Luikart Bryan W. , Kahle Kristopher T. 
Published: March 2023

SUMMARYExpansion of the cerebrospinal fluid (CSF)-filled cerebral ventricles (ventriculomegaly) is the quintessential feature of congenital hydrocephalus (CH) but also seen in autism spectrum disorder (ASD) and several neuropsychiatric diseases.PTENis frequently mutated in ASD; here, we showPTENis abona fiderisk gene for the development of ventriculomegaly, including neurosurgically-treated CH.Pten-mutant hydrocephalus is associated with aqueductal stenosis due to the hyperproliferation of periventricularNkx2.1+neural precursors (NPCs) and CSF hypersecretion from inflammation-dependent choroid plexus hyperplasia. The hydrocephalicPten-mutant cortex exhibits ASD-like network dysfunction due to impaired activity ofNkx2.1+NPC-derived inhibitory interneurons.Raptordeletion or post-natal Everolimus corrects ventriculomegaly, rescues cortical deficits, and increases survival by antagonizing mTORC1-dependentNkx2.1+cell pathology. These results implicate a dual impact of PTEN mutation on CSF dynamics and cortical networks via the dysregulation of NPCs and their interneuron descendants. These data identify a non-surgical treatment target for hydrocephalus and have implications for other developmental brain disorders.HIGHLIGHTSPTEN de novomutations are associated with cerebral ventriculomegaly in autism spectrum disorder (ASD) and congenital hydrocephalus (CH).Pten-mutant hydrocephalus is associated with aqueductal stenosis due to the hyperproliferation of medial ganglionic eminenceNkx2.1+neural precursors and CSF hypersecretion from inflammation-induced choroid plexus hyperplasia.The hydrocephalicPten-mutant cortex exhibits ASD-like network dysfunction due to impaired activity ofNkx2.1+NPC-derived inhibitory interneurons.mTORC1 inhibition viaRaptordeletion or early post-natal treatment with rapamycin or everolimus increases survival and amelioratesPten-mutant ventriculomegaly and cortical pathology.
Generalizing biological surround suppression based on center surround similarity via deep neural network models
Authors: Pan Xu , DeForge Annie , Schwartz Odelia 
Published: March 2023

AbstractSensory perception is dramatically influenced by the context. Models of contextual neural surround effects in vision have mostly accounted for Primary Visual Cortex (V1) data, via nonlinear computations such as divisive normalization. However, surround effects are not well understood within a hierarchy, for neurons with more complex stimulus selectivity beyond V1. We utilized feedforward deep convolutional neural networks and developed a gradient-based technique to visualize the most suppressive and excitatory surround. We found that deep neural networks exhibited a key signature of surround effects in V1, highlighting center stimuli that visually stand out from the surround and suppressing responses when the surround stimulus is similar to the center. We found that in some neurons, especially in late layers, when the center stimulus was altered, the most suppressive surround surprisingly can follow the change. Through the visualization approach, we generalized previous understanding of surround effects to more complex stimuli, in ways that have not been revealed in visual cortices. In contrast, the suppression based on center surround similarity was not observed in an untrained network. We identified further successes and mismatches of the feedforward CNNs to the biology. Our results provide a testable hypothesis of surround effects in higher visual cortices, and the visualization approach could be adopted in future biological experimental designs.Author summaryNeural responses and perception of a visual stimulus are influenced by the context, such as what spatially surrounds a given feature. Contextual surround effects have been extensively studied in the early visual cortex. But the brain processes visual inputs hierarchically, from simple features up to complex objects in higher visual areas. Contextual effects are not well understood for higher areas of cortex and for more complex stimuli. Utilizing artificial deep neural networks and a visualization technique we developed, we found that deep networks exhibited a key signature of surround effects in the early visual cortex, highlighting center stimuli that visually stand out from the surround and suppressing responses when the surround stimulus is similar to the center. We found in some neurons, especially in late layers, when the center stimulus was altered, the most suppressive surround could surprisingly follow. This is a generalization of known surround effects for more complex stimuli that has not been revealed in the visual cortex. Our findings relate to notions of efficient coding and salience perception, and emerged without incorporating specialized nonlinear computations typically used to explain contextual effects in the early cortex. Our visualization approach provides a new experimental paradigm and a testable hypothesis of surround effects for more complex stimuli in higher cortical areas; the visualization approach could be adopted in biological experimental designs.
Vessel Density Mapping of Cerebral Small Vessels on 3D High Resolution Black Blood MRI
Authors: Sarabi Mona Sharifi , Ma Samantha J. , Jann Kay , Ringman John M. , Wang Danny J.J. , Shi Yonggang 
Published: March 2023

AbstractCerebral small vessels are largely inaccessible to existing clinical in vivo imaging technologies. This study aims to present a novel analysis pipeline for vessel density mapping of cerebral small vessels from high-resolution 3D black-blood MRI at 3T. Twenty-eight subjects (10 under 35 years old, 18 over 60 years old) were imaged with the T1-weighted turbo spin-echo with variable flip angles (T1w TSE-VFA) sequence optimized for black-blood small vessel imaging with iso-0.5mm spatial resolution at 3T. Hessian-based vessel segmentation methods (Jerman, Frangi and Sato filter) were evaluated by vessel landmarks and manual annotation of lenticulostriate arteries (LSAs). Using optimized vessel segmentation, large vessel pruning and non-linear registration, a semiautomatic pipeline was proposed for quantification of small vessel density across brain regions and further for localized detection of small vessel changes across populations. Voxel-level statistics was performed to compare vessel density between two age groups. Additionally, local vessel density of aged subjects was correlated with their corresponding gross cognitive and executive function (EF) scores using Montreal Cognitive Assessment (MoCA) and EF composite scores compiled with Item Response Theory (IRT). Jerman filter showed better performance for vessel segmentation than Frangi and Sato filter which was employed in our pipeline. Cerebral small vessels on the order of a few hundred microns can be delineated using the proposed analysis pipeline on 3D black-blood MRI at 3T. The mean vessel density across brain regions was significantly higher in young subjects compared to aged subjects. In the aged subjects, localized vessel density was positively correlated with MoCA and IRT EF scores. The proposed pipeline is able to segment, quantify, and detect localized differences in vessel density of cerebral small vessels based on 3D high-resolution black-blood MRI. This framework may serve as a tool for localized detection of small vessel density changes in normal aging and cerebral small vessel disease.
Pyruvate dehydrogenase dependent metabolic program affects oligodendrocyte maturation and remyelination
Authors: Sajjad M , Zahoor Insha , Rashid Faraz , Rattan Ramandeep , Giri Shailendra 
Published: March 2023

AbstractThe metabolic need of the premature oligodendrocytes (Pre-OLs) and mature oligodendrocytes (OLs) are distinct. The metabolic control of oligodendrocyte maturation is not fully understood. Here we show that the terminal maturation and higher mitochondrial respiration in the oligodendrocyte is an integrated process controlled through pyruvate dehydrogenase (Pdh). Combined bioenergetics and metabolic studies show that mature oligodendrocytes show elevated TCA cycle activity than the premature oligodendrocytes. Our signaling studies show that the increased TCA cycle activity is mediated by the activation of Pdh due to inhibition of pyruvate dehydrogenases isoform-1 (Pdhk1) that phosphorylates and inhibits Pdh. Accordingly, when Pdhk1 is directly expressed in the premature oligodendrocytes, they fail to mature. While Pdh converts pyruvate into the acetyl-CoA by its oxidative decarboxylation, our study shows that Pdh also activates a unique molecular switch required for oligodendrocyte maturation by acetylating the bHLH family transcription factor Olig1. Pdh inhibition via Pdhk1 blocks the Olig1-acetylation and hence, oligodendrocyte maturation. Using the cuprizone model of demyelination, we show that Pdh is deactivated during the demyelination phase, which is reversed in the remyelination phase upon cuprizone withdrawal. In addition, Pdh activity status correlates with the Olig1-acetylation status. Hence, the Pdh metabolic node activation allows a robust mitochondrial respiration and activation of a molecular program necessary for the terminal maturation of oligodendrocytes. Our findings open a new dialogue in the developmental biology that links cellular development and metabolism. These findings have far-reaching implications for the development of therapies for a variety of demyelinating disorders including multiple sclerosis.
Astrocytes control cocaine-induced synaptic plasticity and reward through the matricellular protein hevin
Authors: Mongrédien Raphaële , Anesio Augusto , Fernandes Gustavo J. D. , Eagle Andrew L. , Maldera Steeve , Pham Cuong , Vilette Adèle , Bianchi Paula , Franco Clara , Louis Franck , Gruszczynski Carole , Betancur Catalina , Erdozain Amaia M. , Robison Alfred J. , Boucard Antony A. , Li Dongdong , Cruz Fabio C. , Gautron Sophie , Heck Nicolas , Vialou Vincent 
Published: March 2023

ABSTRACTDrug addiction involves profound modifications of neuronal plasticity in the nucleus accumbens, which may engage various cell types. Here, we report prominent effects of cocaine on calcium signals in astrocytes characterized byin vivofiber photometry. Astrocyte calcium signals in the nucleus accumbens are sufficient and necessary for the acquisition of cocaine seeking behavior. We identify the astrocyte-secreted matricellular protein hevin as an effector of the action of cocaine and calcium signals on reward and neuronal plasticity.
Seed Longevity is Controlled by Metacaspases
Authors: Liu Chen , Hatzianestis Ioannis H. , Pfirrmann Thorsten , Reza Salim H. , Minina Elena A. , Moazzami Ali , Stael Simon , Gutierrez-Beltran Emilio , Pitsili Evgenia , Dörmann Peter , D’ Andrea Sabine , Gevaert Kris , Romero-Campero Francisco , Ding Pingtao , Nowack Moritz K. , Van Breusegem Frank , Jones Jonathan D. G. , Bozhkov Peter V , Moschou Panagiotis N. 
Published: March 2023

AbstractTo survive extreme desiccation, seeds enter dormancy that can last millennia. This dormancy involves the accumulation of protective but structurally disordered storage proteins through unknown adjustments of proteolytic surveillance mechanisms. Mutation of all six types II metacaspases (MCAs)-II in the model plant Arabidopsis revealed their essential role in modulating these proteolytic mechanisms. MCA-II mutant seeds fail to properly target at the endoplasmic reticulum (ER) the AAA ATPase Cell Division Cycle 48 (CDC48) to dispose of misfolded proteins. MCA-IIs cleave a CDC48 adaptor, the ubiquitination regulatory X domain-containing (PUX) responsible for localizing CDC48 to the lipid droplets. When cleaved, CDC48-PUX is inactivated and allows a lipid droplet-to-ER shuttling of CDC48, an important step in the regulation of seeds’ lifespan. In sum, we uncover antagonism between proteolytic pathways bestowing longevity.One-Sentence SummaryMetacaspase proteases confer seed longevity by antagonizing CDC48 activity.
EndogenousStaphylococcus aureusCRISPR-cassystem limits phage proliferation and efficiently excises from the genome as part of the SCCmeccassette
Authors: Mikkelsen Kasper , Bowring Janine Zara , Ng Yong Kai , Frisinger Frida Svanberg , Maglegaard Julie Kjærsgaard , Li Qiuchun , Sieber Raphael N. , Petersen Andreas , Andersen Paal Skytt , Rostøl Jakob T. , Høyland-Kroghsbo Nina Molin , Ingmer Hanne 
Published: March 2023

AbstractCRISPR-Cas is an adaptive immune system that allows bacteria to inactivate mobile genetic elements. Approximately 50% of bacteria harbor CRISPR-cas, however in the human pathogenStaphylococcus aureus, CRISPR-casloci are less common and often studied in heterologous systems. We analyzed the prevalence of CRISPR-casin genomes of methicillin resistantStaphylococcus aureus(MRSA) isolated in Denmark. Only 2.9 % of the strains carried CRISPR-cassystems, but for strains of sequence type ST630 over half were positive. All CRISPR-casloci were type III-A and located within the staphylococcal chromosomal cassette (SCCmec) type V(5C2&5) conferring β-lactam resistance. Curiously, only 23 different CRISPR spacers were identified in 69 CRISPR-positive strains and almost identical SCCmeccassettes, CRISPR arrays andcasgenes, are present in staphylococcal species other thanaureus, suggesting that these were transferred horizontally. For the ST630 strain 110900, we demonstrate that the SCCmeccassette containing CRISPR-casexcises from the chromosome at high frequency. However, the cassette was not transferable under the conditions investigated. One of the CRISPR spacers targets a late gene in the lytic bacteriophage (phage) virus philPLA-RODI, and we show that the system protects against phage infection by reducing phage burst size. However, CRISPR-Cas can be overloaded or bypassed by CRISPR escape mutants. Our results imply that the endogenous type III-A CRISPR-Cas system inS. aureusis active against targeted phages, albeit with low efficacy. This suggests nativeS. aureusCRISPR-Cas offers only partial immunity, and in nature may work in tandem with other defense systems.ImportanceCRISPR-Cas is an adaptive immune system enabling bacteria and archaea to protect themselves against mobile genetic elements such as phages. In strains ofStaphylococcus aureus, CRISPR-casis rare, but when present, it is located within the SCCmecelement encoding resistance to methicillin and other β-lactam antibiotics. We show that the entire module is excisable, with almost identical versions found in different species ofnon-aureusstaphylococci suggesting that the system only rarely acquires new spacers inS. aureus. Additionally, we show that in its endogenous form, theS. aureusCRISPR-Cas is active but inefficient against lytic phages, with phages being able to form escape mutants or overload the system. This leads us to propose that CRISPR-Cas inS. aureusoffers only partial immunity in native systems, and so may work together with other defense systems to prevent phage-mediated killing.
Schlafen14 Regulates Gene Expression Depending on Codon Usage
Authors: Valenzuela Carlos , Saucedo Sergio , Llano Manuel 
Published: March 2023

ABSTRACTSchlafen (SLFN) is a family of proteins upregulated by type I interferons with a regulatory role in translation. Intriguingly, SLFN14 associates with the ribosome and can degrade rRNA, tRNA, and mRNAin vitro, but a role in translation is still unknown. Ribosomes are important regulatory hubs during translation elongation of mRNAs rich in rare codons. Therefore, we evaluated the potential role of SLFN14 in the expression of mRNAs enriched in rare codons, using HIV-1 genes as a model. We found that SLFN14 regulates in a variety of cell types, including primary immune cells, the expression of HIV-1 and non-viral genes based on their codon adaptation index, a measurement of the synonymous codon usage bias; consequently, SLFN14 inhibited the replication of HIV-1. The potent inhibitory effect of SLFN14 on the expression of the rare codon-rich transcript HIV-1 Gag was minimized by codon optimization. Mechanistically, we found that the endoribonuclease activity of SLFN14 is required, and that ribosomal, but not messenger, RNA degradation is associated with the transcript selectivity of SLFN14. Therefore, we propose that SLFN14 impairs the expression of transcripts rich in rare codons, in a catalytic-dependent manner.
Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: a systematic review and meta-analysis
Authors: Almulla Abbas F. , Thipakorn Yanin , Abo Algon Ali Abbas , Tunvirachaisakul Chavit , Al-Hakeim Hussein K. , Maes Michael 
Published: March 2023

AbstractBackgroundMajor depression (MDD) and bipolar disorder (BD) are linked to immune activation, increased oxidative stress, and lower antioxidant defenses.ObjectivesTo systematically review and meta-analyze all data concerning biomarkers of reverse cholesterol transport (RCT), lipid-associated antioxidants, lipid peroxidation products, and autoimmune responses to oxidatively modified lipid epitopes in MDD and BD.MethodsDatabases including PubMed, Google scholar and SciFinder were searched to identify eligible studies from inception to January 10th, 2023. Guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.ResultsThe current meta-analysis included 176 studies (60 BD and 116 MDD) and examined 34,051 participants, namely 17,094 with affective disorders and 16,957 healthy controls. Patients with MDD and BD showed a) significantly decreases in RCT (mainly lowered high-density lipoprotein cholesterol and paraoxonase 1); b) lowered lipid soluble vitamins (including vitamin A, D, and coenzyme Q10); c) increased lipid peroxidation and aldehyde formation, mainly increased malondialdehyde (MDA), 4-hydroxynonenal, peroxides, and 8-isoprostanes; and d) Immunoglobulin (Ig)G responses to oxidized low-density lipoprotein and IgM responses to MDA. The ratio of all lipid peroxidation biomarkers / all lipid-associated antioxidant defenses was significantly increased in MDD (standardized mean difference or SMD=0.433; 95% confidence intervals (CI): 0.312; 0.554) and BD (SMD=0.653; CI: 0.501-0.806). This ratio was significantly greater in BD than MDD (p=0.027).ConclusionIn MDD/BD, lowered RCT, a key antioxidant and anti-inflammatory pathway, may drive increased lipid peroxidation, aldehyde formation, and autoimmune responses to oxidative specific epitopes, which all together cause increased immune-inflammatory responses and neurotoxicity.
Earnings quality and firm valuation: evidence from several European countries
Authors: Fassas Athanasios , Nerantzidis Michail , Tsakalos Ioannis , Asimakopoulos Ioannis 
Published: March 2023

Purpose
This study aims to investigate the association between firm valuation and earnings quality in several European countries. Also, it examines if country-level governance and market development are important determinants of firm valuation.

Design/methodology/approach
Using a sample of 5,002 non-financial firms in 37 European countries over the years 2004 to 2019, the authors evaluate the research question using regression models.

Findings
The authors find a significant positive relationship between firm valuation and a multi-factor earnings quality measure based on four components (accruals, cash flows, operating efficiency and exclusions). The authors further show that stock market development is also a driver of firm value, while country-level governance is significant only in the case of a firm fixed effect model with time effects. The results are robust to alternative model specifications that control for endogeneity, sample heterogeneity and alternative proxies for firm valuation.

Practical implications
Policy makers and market participants could benefit from the findings, by exploiting the advantages of earnings quality in terms of high-ranking stocks whose earnings are backed by cash flows and other sustainable sources.

Originality/value
To the best of the authors’ knowledge, this study is the first to empirically test the relationship between earnings quality and firm value in the European setting during a period that incorporates the adoption of IFRS. This is quite interesting as it permits cross-border comparability in terms of financial reporting and provides deeper and more representative evidence.
The nexus between tourism development, environmental quality and economic growth. Does renewable energy help in achieving carbon neutrality goal?
Authors: Banga Cathrine , Deka Abraham , Ringim Salim Hamza , Mustapha Abubakar Sadiq , Özdeşer Hüseyin , Kilic Hasan 
Published: March 2023

Purpose
The current study aims to ascertain the association between tourism development, economic growth and environmental quality by using the short-run and long-run autoregressive distributive lag model.

Design/methodology/approach
Tourism development has a major role to play in improving a nation’s economic growth. However, it is also blamed for exacerbating environmental pollution because of its massive use of energy (non-renewable energy).

Findings
The major findings of this research show that renewable energy (RE) use and gross domestic product (GDP) negatively impact carbon dioxide (CO2) emissions in South Africa. Tourism arrivals and CO2 emissions negatively impact GDP, while capital positively impacts GDP in the long run.

Practical implications
This research recommends the use of RE, since it reduces carbon emissions, and capital, as it remains the major driver of economic growth.

Originality/value
The originality of the current research is that it uses long-period annual time series data from 1971 to 2019 of South Africa, one of the largest tourist nations in Africa. To the best of the authors’ knowledge, no studies have examined South Africa in this context and minimal research has been conducted to ascertain the impact of the tourism industry on the environment, despite the accusations directed toward it.