bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive Soma-Soma Plate-Like Contact Sites (Ephapses) Connect Suprachiasmatic Nucleus Neurons
Authors: Czeisler Mark É. , Shan Yongli , Schalek Richard , Berger Daniel R. , Suissa-Peleg Adi , Takahashi Joseph S. , Lichtman Jeff W. 
Published: September 2022

AbstractThe hypothalamic suprachiasmatic nucleus (SCN) is the central pacemaker for mammalian circadian rhythms. As such, this ensemble of cell-autonomous neuronal oscillators with divergent periods must maintain coordinated oscillations. To investigate ultrastructural features enabling such synchronization, 805 coronal ultrathin sections of mouse SCN tissue were imaged with electron microscopy and aligned into a volumetric stack, from which selected neurons within the SCN core were reconstructed in silica. We found that clustered SCN core neurons were physically connected to each other via multiple large soma-to-soma plate-like contacts. In some cases, a sliver of a glial process was interleaved. These contacts were large, covering on average ∼21% of apposing neuronal somata. It is possible that contacts may be the electrophysiological substrate for synchronization between SCN neurons. Such plate-like contacts may explain why synchronization of SCN neurons is maintained even when chemical synaptic transmission or electrical synaptic transmission via gap junctions is blocked. Such ephaptic contact-mediated synchronization among nearby neurons may therefore underlie the wave-like oscillations of circadian core clock genes and calcium signals observed in the SCN.SignificanceThree-dimensional reconstruction of SCN tissue via serial electron microscopy revealed a novel structural feature of SCN neurons that may account for inter-neuronal synchronization that persists even when usual mechanisms of neuronal communication are blocked. We found that SCN core neurons are connected by multiple soma-soma contact specializations, ultrastructural elements that could enable synchronization of tightly packed neurons organized in clustered networks. This extensive network of plate-like soma-soma contacts among clustered SCN neurons may provide insight into how ∼20,000 autonomous neuronal oscillators with a broad range of intrinsic periods remain synchronized in the absence of ordinary communication modalities, thereby conferring the resilience required for the SCN to function as the mammalian circadian pacemaker.
Spread the word about freshwater mussels’ conservation: Increasing awareness and willingness to support conservation-oriented policies through social media
Authors: Ferreira-Rodríguez Noé 
Published: September 2022

AbstractResearch on social media users has examined the immediate effects of popular social networking sites on vote intention, but studies have not to the potential use of these sites in conservation programs. By conducting an online survey, which included a short-term Before-After-Control-Impact experiment, the author noted an overall increase in respondents’ ecological knowledge after exposure to a dissemination campaign. More importantly, exposure to information through social media affected peoples’ willingness to change their vote intention to support conservation-oriented policies. The current study results suggest that key stakeholders in biodiversity conservation (i.e., researchers, managers, and conservationists) adopting an active role to increase biodiversity valuation may lead to a new form of ecological knowledge acquisition in modern societies.
Attenuation of neural responses in subthalamic nucleus during internally guided voluntary movements in Parkinson’s disease
Authors: Filyushkina Veronika , Belova Elena , Usova Svetlana , Tomskiy Alexey , Sedov Alexey 
Published: September 2022

AbstractThe proposed models of segregated functional loops describe the organization of motor control over externally triggered (ET) and internally guided (IG) movements. The dopamine deficiency in Parkinson’s disease (PD) is considered to cause a disturbance in the functional loop regulating IG movements. At the same time, the neural mechanisms of movement performance and the role of basal ganglia in motor control remains unclear.The aim of this study was to compare neuronal responses in subthalamic nucleus (STN) during ET and IG movements in PD. We found and analyzed 26 sensitive neurons in 12 PD patients who underwent surgery for implantation of electrodes for deep brain stimulation. We also analyzed the local field potentials (LFP) of the STN of 6 patients in the postoperative period. Patients were asked to perform voluntary movements (clenching and unclenching the fist) evoked by verbal command (ET) or self-initiated (IG).We showed heterogeneity of neuronal responses and did not find sensitive neurons associated with only one type of movement. Most cells were characterized by leading responses, indicating that the STN has an important role in movement initiation. At the same time, we found attenuation of motor responses during IG movement versus stable responses during ET movemements. LFP analysis also showed attenuation of beta desynchronization during multiple IG movements.We propose that stable neuronal response to ET movements is associated with reboot of the motor program for each movement, while attenuation of responses to IG movement is associated with single motor program launching for multiple movements.
iPSC-derived astrocytes to model phenotype-specific differential neuroinflammatory and metabolic responses in X-linked adrenoleukodystrophy
Authors: Parasar Parveen , Kaur Navtej , Poisson Laila M , Singh Jaspreet 
Published: September 2022

SUMMARYX-linked adrenoleukodystrophy (X-ALD) is an inherited progressive metabolic disorder caused by pathogenic variants in theABCD1gene, which leads to accumulation of very long chain fatty acids in body fluids and tissues including brain and spinal cord. In the absence of a clear genotype-phenotype correlation the molecular mechanisms of the severe cerebral adrenoleukodystrophy (cALD) and the milder adrenomyeloneuropathy (AMN) phenotypes remain unknown. Given our previous evidence of role of astrocytes in the neuroinflammatory response in X-ALD we investigated the metabolic and molecular profiles of astrocytes derived from induced pluripotent stem cells (iPSC). The iPSCs were in turn generated from skin fibroblasts from healthy controls and patients with AMN or cALD. AMN and cALD astrocytes exhibited lack ofABCD1and accumulation of very long chain fatty acids, a hallmark of X-ALD disease. Further, cALD astrocytes harbor significantly higher phosphorylation of STAT3, increased Toll-like receptor expression and higher chemokine and cytokine expression. In this first report of miRNA sequencing in X-ALD astrocytes, we observed that miR-9 expression was associated with increasing disease severity phenotype. CRISPR-Cas9 knock-in ofABCD1ABCD1gene expression differentially affected the expression of key molecular, metabolic and microRNA targets in AMN and cALD astrocytes. Extensive characterization of the AMN and cALD iPSC-derived astrocyte model demonstrates critical aspects of X-ALD inflammatory disease in response toABCD1ABCD1mutation and can be further utilized for exploring the contribution of astrocytes to differential inflammatory response in cALD.
Localizing the Sources of Modulations of the P3m Component by Task Difficulty
Authors: Boetzel Cindy , Kasten Florian H. , Herrmann Christoph S. 
Published: September 2022

1AbstractThe P3m is a late component of the event-related field (ERF) and is assumed to reflect the allocation of resources in various cognitive domains. The amplitude of the P3m can be affected by several task parameters, like stimulus probability, inter-stimulus interval and task difficulty. The task difficulty can alter the P3m amplitude, depending on which mechanisms are involved. The sources of the P3m are located in several brain areas, suggesting a widespread network generating the P3m. Which of these sources of the P3m give rise to the task-difficulty induced amplitude modulation are not well investigated. However, localizing these sources could pave the way for intervention studies with non-invasive brain stimulation methods, which might be suitable to modulate the pathologically altered P3m emerging in various psychiatric and neurodevelopmental disorders. We designed a MEG-study with a visual oddball-like task with two different task difficulties to 1) show decreased P3m amplitudes induced by increased task difficulty and 2) estimate the sources of this P3m modulation. Additionally, the influence of the increased task difficulty on behavioral outcomes were analyzed. The P3m amplitude decreased significantly in the hard condition compared to easy condition. Furthermore, the hit rate for standard trials decreased significantly, while the reaction times increased for both, targets and standards. For this specific visual oddball-like task, the sources of the task difficulty dependent P3m amplitude modulation are located in the centro-parietal regions.
Quantitative comparison of CRISPR-Cas9-mediated mutation efficiency between mice and MEFs using digital PCR assays
Authors: Lee Kwangjun , Lee Choogon 
Published: September 2022

AbstractThe creation of mutant mice has been invaluable for advancing biomedical science, but is too time- and resource-intensive for investigating the full range of mutations and polymorphisms. Cell culture models are therefore an invaluable complement to mouse models, especially for cell-autonomous pathways like the circadian clock. In this study, we quantitatively assessed the use of CRISPR to create cell models in MEFs as compared to mouse models. We generated two point mutations in the clock genesPer1andPer2in mice and in MEFs using the same sgRNAs and repair templates for HDR and quantified the frequency of the mutations by digital PCR. The frequency was about an order of magnitude higher in mouse zygotes compared to that in MEFs. However, the mutation frequency in MEFs was still high enough for clonal isolation by simple screening of a few dozen individual cells. ThePermutant cells that we generated provide important new insights into the role of the PAS domain in regulating PER phosphorylation, a key aspect of the circadian clock mechanism. Accurate quantification of the mutation frequency in bulk MEF populations provides a critical basis for optimizing CRISPR protocols and time/resource planning for generating cell models for further studies.
Development of a new cold hardiness prediction model for grapevine using phased integration of acclimation and deacclimation responses
Authors: Kovaleski Al P. , North Michael G. , Martinson Timothy E. , Londo Jason P. 
Published: September 2022

AbstractCold injury limits distribution of perennial agricultural crops, though replacement of plants and other management practices may allow for some damage tolerance. However, winter damage to crops such as grapevines (Vitisspp.) can result in losses in yield the following year if buds are damaged, but over many years when vines must be replaced and reach maturity before fruiting. Despite risks, grapevines are cultivated at the edge of permissible climate and rely on cold hardiness monitoring programs to determine when cold damage mitigation and management practices are required. These monitoring programs represent a critical, but laborious process for tracking cold hardiness. To reduce the need for continuous monitoring, a model (WAUS.2) using cold hardiness data collected over many years from Washington state, USA, growers was published in 2014. Although the WAUS.2 model works well regionally, it underperforms in other regions. Therefore, the objective of this work was to develop a new model (NYUS.1) that incorporates recent knowledge of cold hardiness dynamics for better prediction outcomes. Cold hardiness data fromV. labruscana‘Concord’, andV. vinifera‘Cabernet Sauvignon’ and ‘Riesling’ from Geneva, NY, USA were used. Data were separated in calibration (~2/3) and validation (~1/3) datasets. The proposed model uses three functions to describe acclimation, and two functions to describe deacclimation, with a total of nine optimized parameters. A shared chill response between acclimation and deacclimation provides a phased integration where acclimation responses decrease over the course of winter and are overcome by deacclimation. The NYUS.1 model outperforms the WAUS.2 model, reducing RMSE by up to 37% depending on cultivar. The NYUS.1 model also tends to be more conservative in its prediction, slightly underpredicting cold hardiness, as opposed to the overprediction from the WAUS.2 model. Some optimized parameters were shared between cultivars, suggesting conserved physiology was captured by the new model.Highlights-Multi-year cold hardiness data from three grapevine cultivars were used for modeling-Cold hardiness was modeled based on daily temperature and accumulated chill-Phased acclimation and deacclimation processes result in cold hardiness predictions-The new model was compared to the currently available model for grapevines-The model proposed here outperforms the currently available model
Using machine learning to predict protein-protein interactions between a zombie ant fungus and its carpenter ant host
Authors: Will Ian , Beckerson William C. , de Bekker Charissa 
Published: September 2022

AbstractParasitic fungi produce proteins that modulate virulence, alter host physiology, and trigger host responses. These proteins, classified as a type of “effector,” often act via protein-protein interactions (PPIs). The fungal parasiteOphiocordyceps camponoti-floridani(zombie ant fungus) manipulatesCamponotus floridanus(carpenter ant) behavior to promote transmission. The most striking aspect of this behavioral change is a summit disease phenotype where infected hosts ascend and attach to an elevated position. Plausibly, interspecific PPIs drive aspects ofOphiocordycepsinfection and host manipulation. Machine learning PPI predictions offer high-throughput methods to produce mechanistic hypotheses on how this behavioral manipulation occurs. Using D-SCRIPT to predict host-parasite PPIs, we found ca. 6,000 interactions involving 2,083 host proteins and 129 parasite proteins, which are encoded by genes upregulated during manipulated behavior. We identified multiple overrepresentations of functional annotations among these proteins. The strongest signals in the host highlighted neuromodulatory G-protein coupled receptors and oxidation-reduction processes. We also detectedCamponotusstructural and gene-regulatory proteins. In the parasite, we found enrichment ofOphiocordycepsproteases and frequent involvement of novel small secreted proteins with unknown functions. From these results, we provide new hypotheses on potential parasite effectors and host targets underlying zombie ant behavioral manipulation.
Cik1 and Vik1 Accessory Proteins Confer Distinct Functions to the Kinesin-14, Kar3
Authors: Bergman Zane J , Wong Jonathan J , Drubin David G , Barnes Georjana 
Published: September 2022

ABSTRACTThe budding yeast Saccharomyces cerevisiae has a closed mitosis in which the mitotic spindle and cytoplasmic microtubules (MTs) used to segregate chromosomes remain separated by the nuclear envelope throughout the cell cycle. Kar3, the yeast kinesin-14, has unique roles in both compartments and has been implicated in capturing unattached kinetochores, stabilizing crosslinked interpolar microtubules (MT), and creating intranuclear and cytoplasmic MT arrays at the spindle pole body for kinetochore capture and karyogamy, respectively. Here, we show that two proteins, Cik1 and Vik1, that form heterodimers with Kar3, regulate its localization and function within the cell and along MTs in a cell cycle-dependent manner. Using a cell cycle synchronized, yeast MT dynamics reconstitution assay in cell lysate, we found that Kar3Vik1 induces MT catastrophes in S phase and metaphase and limits MT polymerization in G1 and anaphase. In contrast, Kar3Cik1 is a catastrophe and pause promoter in G1, while increasing catastrophes in metaphase and anaphase. Adapting this assay to track single-molecules, we saw that Kar3Cik1 is necessary for tracking MT plus-ends in S phase and metaphase, but, surprisingly, not during anaphase. These experiments demonstrate how the binding partners of Kar3 modulate its diverse functions both spatially and temporally.SUMMARY STATEMENTWe show through biochemical reconstitution experiments and live-cell imaging that the functions and localization of the budding yeast kinesin-14, Kar3, are dictated by which of its two accessory protein binding partners, Cik1 or Vik1, it binds to and by the cell cycle stage.
Subcellular distribution of PP1 isoforms in holoenzyme complexes
Authors: Mehta Virja , Chamousset Delphine , Law Jennifer , Ooi Sarah , Campuzano Denise , Nguyen Vincent , Boisvert François-Michel , Moorhead Greg B. , Trinkle-Mulcahy Laura 
Published: September 2022

AbstractUnlike its counterpart Ser/Thr kinases, the predominant Ser/Thr protein phosphatase 1 (PP1) is a promiscuous enzyme that gains its subcellular localization and substrate specificity from a large panel of regulatory proteins with which it associates in predominantly dimeric complexes. Inhibition of specific PP1-mediated dephosphorylation events relies on targeting the regulatory rather than the catalytic subunit, which in turn relies on a comprehensive understanding of the holoenzyme complexes that underlie its distribution throughout the cell. Proteomic, bioinformatic and biochemical screens have assembled lists of putative regulatory proteins, which have been studied to varying degrees. We took a non-biased approach to link steady-state localization to complexes, using a combination of fluorescence imaging, cellular fractionation and quantitative affinity purification/mass spectrometry (AP/MS) to map interactomes for PP1ɑ/β/ɣ in 3 human cell lines. Comparing the distribution of each isoform between the pool of identified regulatory subunits highlighted key signaling pathways and identified c20orf27 as a novel PP1 regulatory protein. Steady-state association of a large fraction of PP1 with the evolutionarily conserved SDS22 was demonstrated, as was redistribution at the entry to mitosis. This is consistent with recent work suggesting that SDS22 acts as a PP1 sink from which it can be recruited as needed. Moving forward, this approach can be used to assess the redistribution of PP1 during other cellular processes or in response to perturbations or disease states, facilitating identification of the relevant complexes and the design of strategies to target them therapeutically.
A Programmable Model for Exploring the Functional Logic of the Drosophila Mushroom Body
Authors: Lazar Aurel A. , Turkcan Mehmet Kerem , Zhou Yiyin 
Published: September 2022

AbstractWe advance a model of the Mushroom Body of the Drosophila brain based on the recently published fruit fly brain connectome. We quantify the effect of the connectivity from antennal lobe projection neurons to Kenyon Cells (KCs) and the effect of feedback between KCs and the anterior paired lateral (APL) neuron on the representation of odorants at the KC level. We then characterize odorant representation in the mushroom body output neurons (MBONs) as a function of semantics represented by the dopaminergic neurons (DANs). Finally, we evaluate the performance of associative learning in the MB that endows pure odorants with DAN semantics.
Spectral slope and Lempel-Ziv complexity as robust markers of brain states during sleep and wakefulness
Authors: Höhn Christopher , Hahn Michael A. , Lendner Janna D. , Hoedlmoser Kerstin 
Published: September 2022

AbstractSpectral slope and Lempel-Ziv complexity are affected in many neurophysiological disorders and are modulated by sleep, anesthesia, and aging. Yet, few studies have explored the relationship between these two parameters. We evaluated the impact of sleep stage and task-engagement (resting, attention and memory) on spectral slope and Lempel-Ziv complexity in a narrow- (30 – 45Hz) and broadband (1 – 45Hz) frequency range in 28 healthy males (21.54 ± 1.90 years) over three recordings. Only in the broadband range, the slope steepens and complexity decreases continuously from wakefulness to N3. However, REM sleep is best discriminated by the narrowband slope. Importantly, slope and complexity also differentiate between tasks during wakefulness. While the narrowband complexity decreases across tasks, the slope is flattening with task engagement in both frequency ranges. In general, broadband slope and complexity are strongly positively correlated, but we observe a dissociation between them in the narrowband range. Critically, only the narrowband slope is associated with better Go/Nogo task performance. Our results demonstrate that slope and complexity are both powerful indices of sleep depth, task engagement and cognitive performance. While the broadband range is better suited to discriminate between brain states, especially the narrowband slope is a unique marker of task performance.
DipM controls multiple autolysins and mediates two regulatory feedback loops promoting cell constriction in C. crescentus
Authors: Izquierdo-Martinez Adrian , Miguel-Ruano Vega , Hernández-Tamayo Rogelio , Biboy Jacob , Batuecas María T. , Billini Maria , Glatter Timo , Vollmer Waldemar , Graumann Peter L. , Hermoso Juan A. , Thanbichler Martin 
Published: September 2022

AbstractProteins containing a catalytically inactive LytM-type endopeptidase domain have emerged as important regulators of cell wall-degrading enzymes in bacteria. Although these so-called LytM factors are wide-spread among species, the range of functions they fulfill and their precise modes of action are still incompletely understood. In this work, we study the LytM factor DipM, a protein required for proper cell division in the model species C. crescentus. We show that the LytM domain of DipM interacts directly with multiple autolysins, including the lytic transglycosylases SdpA and SdpB, the amidase AmiC and the putative carboxypeptidase CrbA, and stimulates the activities of SdpA and AmiC. The crystal structure of the LytM domain of DipM reveals conserved features, including a distinctive groove. Modeling studies suggest that this groove could represent the docking site of AmiC. The architecture of the binding interface in the DipM-AmiC complex is very similar to that observed for the LytM domain of EnvC in complex with its autoinhibitory restraining arm, suggesting a conserved role of the groove in the interaction of LytM factors with their (auto-)regulatory targets. In line with this hypothesis, a mutation in the groove abolishes DipM function. Interestingly, single-molecule tracking studies reveal that the recruitment of DipM and its regulatory targets SdpA and SdpB to the division site is mutually interdependent, with DipM establishing a self-reinforcing cycle that gradually increases lytic transglycosylase activity at the cell center as division progresses. At the same time, the DipM-dependent activation of AmiC leads to the production of denuded peptidoglycan, generating a spatial cue that attracts FtsN to the division site and thus, in turn, again promotes the recruitment of DipM. Collectively, these findings show that DipM is a central regulator that acts at the intersection of different peptidoglycan remodeling pathways and coordinates the activities of various classes of autolysins to promote cell constriction and daughter cell separation.