bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing sustained attention and fatigue across the lifespan
Authors: Hanzal S. , Learmonth G. , Thut G , Harvey M 
Published: September 2023

AbstractTrait fatigues reflects tiredness that persists throughout a prolonged period, whereas state fatigue is defined to be short term after “intense and/or prolonged effort”. We investigated the impact of prolonged sustained attention (using the SART task) on both trait and state fatigue levels in the general population. A JsPsych online version of the SART task was undertaken by 115 participants, stratified across the whole adult lifespan. While pre-task trait fatigue was a strong indicator of the initial state fatigue levels, undergoing the task itself induced an increase in reported subjective state fatigue, as well as reduced energy. Consistent with this finding, greater subjective state fatigue levels were associated with reduced accuracy. In addition, age was the best predictor of inter-participant accuracy (the older the participants, the greater the accuracy), and learning (i.e., task duration reducing reaction times). Moreover, a ceiling effect occurred where participants with higher trait fatigue did not experience greater state fatigue changes relative to those with low trait scores. In summary, we found improved accuracy in older adults, as well as a tight coupling between state fatigue and SART performance decline (in an online environment). The findings warrant further investigation into fatigue as a dynamic, task-dependent state and into SART task performance as an objective measure and inducer of fatigue.
ATF2 phosphorylation is essential for neuronal apoptosis, linking the DLK/LZK kinase cascade to JUN upregulation
Authors: Gomez-Deza Jorge , Nebiyou Matthew , Alkaslasi Mor R. , El Touny Lara H. , Slavutsky Anastasia L. , Ashby Nathan , Cheng Ken , Le Pichon Claire E. 
Published: September 2023

AbstractApoptotic neuron death is a common feature of many neurodegenerative diseases. Perhaps surprisingly, the exact mechanisms by which neurons undergo apoptosis have yet to be elucidated. We conducted an unbiased whole genome screen in human neurons to discover genes required for apoptotic neuron death, and found ATF2, MAP3K12 and JUN among top hits. We demonstrate that ATF2 is a previously unappreciated master regulator of neuron death. ATF2 is phosphorylated downstream of MAP3K12 (dual leucine zipper kinase) and MAP3K13 (leucine zipper kinase) and its phosphorylation is essential for transcriptional upregulation of JUN. We show that JUN upregulation is essential for apoptosis – but not its phosphorylation. Contrary to previous assumptions, cJun phosphorylation is therefore simply a correlate of JUN upregulation. In this study, we identify phosphorylation of ATF2 as a key event in the mechanism of neuronal apoptosis, linking the MAP3K12/13 kinase cascade to transcriptional upregulation of JUN. Since targeting members of this signaling pathway to block neuronal death has proved difficult, ATF2 offers a novel and promising alternative.
Bidirectional interaction between Protocadherin 8 and transcription factor Dbx1 regulates cerebral cortex development
Authors: Cwetsch Andrzej W , Gilabert-Juan Javier , Ferreira Sofia , Moreau Matthieu X. , Saillour Yoann , Delberghe Elodie , González Martínez Jose , Borello Ugo , Causeret Frédéric , Pierani Alessandra 
Published: September 2023

SUMMARYBrain development requires correct tissue patterning and production of appropriate cell types. Transcription factors (TFs) play essential roles in these processes, regulating the expression of target genes responsible for neuronal subtypes specific features. Cell adhesion molecules are key components of neuronal identities that control cell sorting, migration, neurite outgrowth/guidance and synaptogenesis. To date, the link between TFs and cell adhesion molecules is considered to be unidirectional. Here, we demonstrate that ectopic expression of Dbx1 leads to spatio-temporally restricted increased expression ofPcdh8and cell aggregation, together with changes in neuronal identity. Surprisingly, Pcdh8 overexpression also induces Dbx1 expression as well as a complete reorganisation of apico-basal polarity and dorso-ventral patterningviaNotch signalling. Altogether, our work therefore points to cell adhesion molecules as unexpected, yet important, players in the regulation of cell identity and, in particular, Pcdh8 through its bidirectional interaction with the Dbx1 transcription factor.
Cadherins orchestrate specific patterns of perisomatic inhibition onto distinct pyramidal cell populations
Authors: Jézéquel Julie , Condomitti Giuseppe , Kroon Tim , Hamid Fursham , Sanalidou Stella , Garces Teresa , Maeso Patricia , Balia Maddalena , Rico Beatriz 
Published: September 2023

AbstractIn the mammalian neocortex, excitatory pyramidal cells are assembled into distinct subnetworks, which project to different brain areas. GABAergic interneurons were long thought to connect promiscuously and extensively to pyramidal neurons, but recent evidence supports the existence of a cell type-specific inhibitory connectome. How and when interneurons establish such a precise connectivity pattern among intermingled populations of excitatory neurons remains enigmatic. Here, we investigated the molecular rules shaping cell type- and input-specific inhibitory connectivity in different Layer 5 (L5) pyramidal cell populations. We found that neighboring L5 intra- (L5 IT) and extra-telencephalic (L5 ET) neurons receive different combinations of inhibitory perisomatic inputs from Parvalbumin- (PV+) and Cholecystokynine-positive (CCK+) basket cells. We also identifiedCdh12andCdh13, two cadherin superfamily members, as critical mediators of L5 pyramidal cell type-specific inhibitory connectivity. Our data revealed a minimal overlap between L5 IT and L5 ET presynaptic inhibitory networks, and suggests that different populations PV+ basket cells innervate distinct L5 pyramidal cell types. Altogether, our work unravels the contribution of cadherins in shaping cortical interneuron wiring and provides new insights into the development of inhibitory microcircuits.
Patterns of Cerebellar-Cortical Structural Covariance Mirror Anatomical Connectivity of Sensorimotor and Cognitive Networks
Authors: Alasmar Zaki , Chakravarty M. Mallar , Penhune Virginia , Steele Christopher J. 
Published: September 2023

AbstractThe cortex and cerebellum are densely connected through reciprocal input/output projections that form segregated loop circuits. Anatomical studies in primates and imaging studies in humans show that anterior lobules of the cerebellum exhibit denser connections to sensorimotor and parietal cortical regions, while lobules Crus I and II are more heavily connected to prefrontal regions. The cerebellum and cortex develop in tandem in childhood, leading to the hypothesis that individual differences in structure should be related, especially for connected regions. To test this hypothesis we examined covariation between the volumes of anterior sensorimotor and lateral cognitive lobules of the cerebellum and measures of cortical thickness (CT) and surface surface area (SA) across the whole brain in a sample of 270 young, healthy adults drawn from the HCP dataset. We found that patterns of cerebellar-cortical covariance differed between sensorimotor and cognitive networks such that anterior motor lobules of the cerebellum showed greater covariance with sensorimotor regions of the cortex, while lobules Crus I and Crus II showed greater covariance with frontal and temporal regions. Interestingly, cerebellar volume showed predominantly negative relationships with CT and predominantly positive relationships with SA. Individual differences in SA are thought to be largely under genetic control while CT is thought to be more malleable by experience. This suggests that cerebellar-cortical covariation for SA may be a more stable feature, whereas covariation for CT may be more affected by development. Additionally, dissimilarity metrics revealed that the pattern of covariance showed a gradual transition between sensorimotor and cognitive lobules, consistent with evidence of functional gradients within the cerebellum. Taken together, these findings are consistent with known patterns of structural and functional connectivity between the cerebellum and cortex. They also shed new light on possibly differing relationships between cerebellar volume and cortical thickness and surface area. Finally, our findings are consistent with the interactive specialization framework which proposes that structurally and functionally connected brain regions develop in concert.
Neural Representations of Beat and Rhythm in Motor and Association Regions
Authors: Hoddinott Joshua D. , Grahn Jessica A. 
Published: September 2023

AbstractHumans perceive a pulse, or beat, underlying musical rhythm. Beat strength correlates with activity in the basal ganglia and SMA, suggesting these regions support beat perception. However, the basal ganglia and SMA make up a general timing network active during rhythm and timing perception, regardless of beat. Therefore, activity in these regions may represent basic rhythmic features, in addition to beat. Using RSA, we characterized the neural representation of rhythm in the basal ganglia, SMA, and across the whole brain. During fMRI, participants heard 12 rhythms – 4 strong-beat, 4 weak-beat, and 4 non-beat. Multi-voxel activity patterns for each rhythm, and for the mean of each condition, were tested for uniqueness. Activity patterns in beat-sensitive regions should alter as a function of beat strength, eliciting greater dissimilarities between rhythms with different beat strength than between rhythms with similar beat strength. Indeed, mean activity patterns in the putamen and SMA were significantly dissimilar for strong-beat and non-beat conditions, and dissimilarity between activity patterns across all 12 rhythms correlated with beat strength models, not basic rhythmic features. Whole-brain analyses also identified beat-sensitivity in the IFG, and inferior parietal cortex. These findings build upon univariate work suggesting that motor and association regions are beat-sensitive.
4R-Tau seeding activity unravels molecular subtypes in patients with Progressive Supranuclear Palsy
Authors: Martinez-Valbuena Ivan , Lee Seojin , Santamaria Enrique , Irigoyen Joaquin Fernandez , Forrest Shelley L. , Li Jun , Tanaka Hidetomo , Couto Blas , Reyes Nikolai Gil , Qamar Hania , Karakani Ali M. , Kim Ain , Senkevich Konstantin , Rogaeva Ekaterina , Fox Susan H. , Tartaglia M. Carmela , Visanji Naomi P. , Andrews Tallulah , Lang Anthony E. , Kovacs Gabor G. 
Published: September 2023

AbstractProgressive Supranuclear palsy (PSP) is a 4-repeat (4-R) tauopathy. We hypothesized that the molecular diversity of tau could explain the heterogeneity seen in PSP disease progression. To test this hypothesis, we performed an extensive biochemical characterisation of the high molecular weight tau species (HMW-Tau) in 20 different brain regions of 25 PSP patients. We found a correlation between the HMW-Tau species and tau seeding capacity in the primary motor cortex, where we confirmed that an elevated 4R-Tau seeding activity correlates with a shorter disease duration. To identify factors that contribute to these differences, we performed proteomic and spatial transcriptomic analysis that revealed key mechanistic pathways, in particular those involving the immune system, that defined patients demonstrating high and low tau seeding capacity. These observations suggest that differences in the tau seeding activity may contribute to the considerable heterogeneity seen in disease progression of patients suffering from PSP.
Mapping the molecular motions of 5-HT3serotonin-gated channel by Voltage-Clamp Fluorometry
Authors: Peverini Laurie , Shi Sophie , Medjebeur Karima , Corringer Pierre-Jean 
Published: September 2023

AbstractThe serotonin-gated ion channel (5-HT3R) mediates excitatory neuronal communication in the gut and the brain. It is the target for setrons, a class of competitive antagonists widely used as antiemetics, and is involved in several neurological diseases. Cryo-electron microscopy of the 5-HT3R in complex with serotonin or setrons revealed that the protein has access to a wide conformational landscape. However, assigning known high-resolution structures to actual states contributing to the physiological response remains a challenge.In the present study, we used voltage-clamp fluorometry (VCF) to measure simultaneously, for 5-HT3R expressed at a cell membrane, conformational changes by fluorescence and channel opening by electrophysiology. Four positions identified by mutational screening report motions around and outside the serotonin-binding site through incorporation of cysteine-tethered rhodamine dyes with or without a nearby quenching tryptophan. VCF recordings show that the 5-HT3R has access to four families of conformations endowed with distinct fluorescence signatures: “resting-like” without ligand, “inhibited-like” with setrons, “pre-active-like” with partial agonists and “active-like” (open channel) with partial and strong agonists. Data are remarkably consistent with cryo-EM structures, the fluorescence partners matching respectively Apo, setron-bound, 5-HT bound-closed and 5-HT-bound-open conformations. Data show that strong agonists promote a concerted motion of all fluorescently labelled sensors during activation, while partial agonists, especially when loss-of-function mutations are engineered, stabilize both active and pre-active conformations.In conclusion, VCF, though the monitoring of electrophysiologically silent conformational changes, illuminates allosteric mechanisms contributing to signal transduction and their differential regulation by important classes of physiological and clinical effectors.Significance StatementHigh-resolution structures of serotonin-gated receptors (5-HT3AR) have evidenced a wide range of conformations that are challenging to annotate to physiologically relevant states. Voltage-clamp fluorometry allows to investigate the activation of 5-HT3AR by simultaneously following molecular motions and electrophysiological states at the plasma membrane. Here, we developed four fluorescent sensors reporting conformational changes at the serotonin binding site and at the extracellular domain and transmembrane domain interface. Investigation of a series of agonists, partial agonists and antagonists show that strong agonists promote a concerted motion of the whole protein during activation, while antagonists and partial agonists stabilize distinct closed-channel conformations. Data offer insights into allosteric mechanisms, unravelling the conformational dynamics of the receptors and helping to annotate high-resolution static structures.
An amphipathic helix drives interaction of Fibrillins with plastoglobule lipid droplets
Authors: Shivaiah Kiran-Kumar , Boren Duncan M. , Tequia-Herrera Andres , Vermaas Josh , Lundquist Peter Knut 
Published: September 2023

ABSTRACTPlastoglobule lipid droplets of chloroplasts serve complex roles affecting plant development, stress tolerance and photosynthesis. They harbor a set of approximately 42 proteins that collectively dictate plastoglobule functions. Due to the monolayer structure of plastoglobules which encompass a neutral lipid core, these proteins must associate monotopically on the plastoglobule surface. However, targeting determinants have not been identified for plastoglobule proteins, and the protein-membrane interaction mechanisms that establish the plastoglobule proteome remain unclear. Here, we demonstrate that plastoglobule-localized Fibrillins harbor an amphipathic helix at the lip of their β-barrel that is necessary for proper plastoglobule association. Molecular dynamics simulations support the specific interaction of the amphipathic helix of AtFBN1a with membranes rich in lipid packing defects which are expected to be especially prevalent on the tightly curved surface of plastoglobules. Introduction of one of the amphipathic helices into stromal-or thylakoid-localized FBNs was ineffective at redirecting the proteins to plastoglobules, likely due to endogenous protein-protein interactions that override the influence of the amphipathic helix. Proteomic analyses indicate AtFBN1a influences the plastoglobule proteome through outcompeting and recruiting specific proteins. We also demonstrate that the plastoglobule-localized FBNs, AtFBN1a and AtFBN7a, bind unsaturated fatty acids, particularly C18:1, and that elimination of the amphipathic helix suppresses fatty acid binding in AtFBN1a, but promotes fatty acid binding in AtFBN7a. Predicted amphipathic helices can be identified on two-thirds of plastoglobule proteins, indicating the use of amphipathic helices may be a general mechanism by which proteins selectively associate with plastoglobules.
Potentiating NaV1.1 in Dravet syndrome patient iPSC-derived GABAergic neurons increases neuronal firing frequency and decreases network synchrony
Authors: Kelley Matt R. , Chipman Laura B. , Asano Shoh , Knott Matthew , Howard Samantha T. , Berg Allison P. 
Published: September 2023

AbstractDravet syndrome is a developmental and epileptic encephalopathy characterized by seizures, behavioral abnormalities, developmental deficits, and elevated risk of sudden unexpected death in epilepsy (SUDEP). Most patient cases are caused byde novoloss-of-function mutations in the geneSCN1A, causing a haploinsufficiency of the alpha subunit of the voltage-gated sodium channel NaV1.1. Within the brain, NaV1.1 is primarily localized to the axons of inhibitory neurons, and decreased NaV1.1 function is hypothesized to reduce GABAergic inhibitory neurotransmission within the brain, driving neuronal network hyperexcitability and subsequent pathology. We have developed a humanin vitromodel of Dravet syndrome using differentiated neurons derived from patient iPSC and enriched for GABA expressing neurons. Neurons were plated on high definition multielectrode arrays (HD-MEAs), permitting recordings from the same cultures over the 7-weeks duration of study at the network, single cell, and subcellular resolution. Using this capability, we characterized the features of axonal morphology and physiology. Neurons developed increased spiking activity and synchronous network bursting. Recordings were processed through a spike sorting pipeline for curation of single unit activity and to assess the effects of pharmacological treatments. At 7-weeks, the application of the GABAAR receptor agonist muscimol eliminated network bursting, indicating the presence of GABAergic neurotransmission. To identify the role of NaV1.1 on neuronal and network activity, cultures were treated with a dose-response of the NaV1.1 potentiator δ-theraphotoxin-Hm1a. This resulted in a strong increase in firing rates of putative GABAergic neurons, an increase in the intraburst firing rate, and eliminated network bursting. These results validate that potentiation of NaV1.1 in Dravet patient iPSC-derived neurons results in decreased firing synchrony in neuronal networks through increased GABAergic neuron activity and support the use of human neurons and HD-MEAs as viable high-throughput electrophysiological platform to enable therapeutic discovery.
Technology assisted research assessment: algorithmic bias and transparency issues
Authors: Thelwall Mike , Kousha Kayvan 
Published: September 2023

PurposeTechnology is sometimes used to support assessments of academic research in the form of automatically generated bibliometrics for reviewers to consult during their evaluations or by replacing some or all human judgements. With artificial intelligence (AI), there is increasing scope to use technology to assist research assessment processes in new ways. Since transparency and fairness are widely considered important for research assessment and AI introduces new issues, this review investigates their implications.Design/methodology/approachThis article reviews and briefly summarises transparency and fairness concerns in general terms and through the issues that they raise for various types of Technology Assisted Research Assessment (TARA).FindingsWhilst TARA can have varying levels of problems with both transparency and bias, in most contexts it is unclear whether it worsens the transparency and bias problems that are inherent in peer review.Originality/valueThis is the first analysis that focuses on algorithmic bias and transparency issues for technology assisted research assessment.
Impact of solid waste landfill proximity on residential property offer values: a case study of Pune
Authors: Abhyankar Abhijat Arun , Prakash Anand , Singla Harish Kumar 
Published: September 2023

Purpose
This study aims to examine whether or not residential properties closer to landfill sites have lower offer values by the developers. That is, by analyzing real estate data and landfill site locations, the study seeks to provide insights into whether properties situated closer to landfill sites tend to have a lower offer values than those located farther away.

Design/methodology/approach
The study is exploratory in nature, and a case study approach is applied. A landfill site named “Uruli Devachi” is selected in the region of Pune district, and data is collected from 102 developers selling residential projects within a radius of 15 km (about 9.32 mi). The gathered data is analyzed by using basic descriptive statistics, one-way ANOVA and ordinary least squares (OLS) regression. The OLS regression helps to determine whether there is a relationship between the distance of a residential property from a landfill site and its offer value.

Findings
The findings suggest that landfill sites have a detrimental impact on residential property offer values, with the negative impact increasing with proximity to a landfill site. The negative effect seems to vanish after over 10 km (about 6.21 mi). The developers provide extra facilities including a clubhouse, a children’s play area, a gym and a swimming pool in an effort to mitigate the negative effects of the landfill site on residential properties.

Practical implications
The findings of this study could have implications for property developers, real estate professionals and policymakers in understanding how landfill proximity might impact property offer values.

Originality/value
This study presents many novelties for the Indian housing market: the landfill sites do have a negative effect on the offer value of residential property; the closer the residential property to a landfill site, the higher the negative effect. Further, the developers try and mitigate the negative effect of landfill sites on residential properties by providing additional amenities such as a clubhouse, children’s play park, gym and swimming pool.