bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rich dynamics and functional organization on topographically designed neuronal networksin vitro
Authors: Montalà-Flaquer Marc , López-León Clara F. , Tornero Daniel , Fardet Tanguy , Monceau Pascal , Bottani Samuel , Soriano Jordi 
Published: September 2022

SUMMARYNeuronal cultures are a prominent experimental tool to understand complex functional organization in neuronal assemblies. However, neurons grown on flat surfaces exhibit a strongly coherent bursting behavior with limited functionality. To approach the functional richness of naturally formed neuronal circuits, here we studied neuronal networks grown on polydimethylsiloxane (PDMS) topographical patterns shaped as either parallel tracks or square valleys. We followed the evolution of spontaneous activity in these cultures along 20 daysin vitrousing fluorescence calcium imaging. The networks were characterized by rich spatiotemporal activity patterns that comprised from small regions of the culture to its whole extent. Effective connectivity analysis revealed the emergence of spatially compact functional modules that were associated to both the underpinned topographical features and predominant spatiotemporal activity fronts. Our results show the capacity of spatial constraints to mold activity and functional organization, bringing new opportunities to comprehend the structure-function relationship in living neuronal circuits.
Novelty detection and multiple timescale integration drive Drosophila orientation dynamics in temporally diverse olfactory environments
Authors: Sehdev Aarti , Jayaram Viraaj , Kadakia Nirag , Brown Ethan , Emonet Thierry 
Published: September 2022

ABSTRACTTo survive, insects must effectively navigate odors plumes to their source. In natural plumes, turbulent winds break up smooth odor regions into disconnected patches, so navigators encounter brief bursts of odor interrupted by bouts of clean air. The timing of these encounters plays a critical role in navigation, determining the direction, rate, and magnitude of insects’ orientation and speed dynamics. Still, disambiguating the specific role of odor timing from other cues, such as spatial structure, is challenging due to natural correlations between plumes’ temporal and spatial features. Here, we use optogenetics to isolate temporal features of odor signals, examining how the frequency and duration of odor encounters shape the navigational decisions of freely-walking Drosophila. We find that fly angular velocity depends on signal frequency and intermittency – fraction of time signal can be detected – but not directly on durations. Rather than switching strategies when signal statistics change, flies smoothly transition between signal regimes, by combining an odor offset response with a frequency-dependent novelty-like response. In the latter, flies are more likely to turn in response to each odor hit only when the hits are sparse. Finally, the upwind bias of individual turns relies on a filtering scheme with two distinct timescales, allowing rapid and sustained responses in a variety of signal statistics. A quantitative model incorporating these ingredients recapitulates fly orientation dynamics across a wide range of environments.
The transcriptional landscape of glycosylation-related genes in cancer
Authors: Rodriguez Ernesto , Lindijer Dimitri , van Vliet Sandra J. , Garcia Vallejo Juan J. , van Kooyk Yvette 
Published: September 2022

AbstractChanges in glycosylation patterns have been associated with malignant transformation and clinical outcome in several types of cancer, although no comprehensive analysis has been performed in a pan-cancer setting. Here, we performed an extensive transcriptomic analysis of glycosylation related genes (such as enzymes involved in synthesis and degradation of glycoconjugates, transporters, mucins and galectins), using publicly available bulk and single cell transcriptomic data sets from tumor samples and cancer cell lines. We identified genes and pathways associated with different tumor types, which may represent novel diagnostic biomarkers as α2-3 sialylation for Melanoma, MUC21 for Lung adenocarcinoma and Galectin-7 for Squamous cell carcinomas (SCC). Accordingly, serum levels of Galectin-7 in patients with lung cancer were elevated in SCC respect to adenocarcinomas, supporting its biomarker potential. Moreover, we characterized the contribution of different cell types to the overall glycosylation profiles observed by performing the integration and analysis of 14 single cell RNA-seq datasets. This led us to identify that cancer cells are responsible for the specific tumor glyco-codes identified in bulk transcriptomics, while stromal and immune cells contribute in a conserved manner across various malignancies. Furthermore, our results suggest that the glycosylation-related genes and pathways expressed by cancer cells are influenced by the cell of origin and the oncogenic pathways that led to malignant transformation. Lastly, we described the association of different glycosylation-related genes and pathways with the clinical outcome of patients. Interestingly, while the expression of genes associated to some pathways (as proteoglycan biosynthesis) are consistently associated with a more aggressive disease, the correlation of others pathways with the survival of patients depends on the particular tumor type. Remarkably, the expression of genes associated with the synthesis of CMP-sialic acid was correlated with lower survival of patients in Uveal Melanoma and PDAC, while the opposite was observed for colorectal cancer. The extensive transcriptomic analysis of glycosylation pathways in cancer that we report here can serve as a resource for future research aimed to unravel the glyco-code in cancer related to clinical outcome or biomarker development.
Uncovering the contributions of charge regulation to the stability of single alpha helices
Authors: Fossat Martin J. , Posey Ammon E. , Pappu Rohit V. 
Published: September 2022

ABSTRACTThe single alpha helix (SAH) is a recurring motif in biology. The consensus sequence has a di-block architecture that includes repeats of four consecutive glutamate residues followed by four consecutive lysine residues. Measurements show that the overall helicity of sequences with consensus E4K4repeats is insensitive to a wide range of pH values. Here, we use the recently introducedq-canonical ensemble, which allows us to decouple measurements of charge state and conformation, to explain the observed insensitivity of SAH helicity to pH. We couple the outputs from separate measurements of charge and conformation with atomistic simulations to derive residue-specific quantifications of preferences for being in an alpha helix and for the ionizable residues to be charged vs. uncharged. We find a clear preference for accommodating uncharged Glu residues within internal positions of SAH-forming sequences. The stabilities of alpha helical conformations increase with the number of E4K4repeats and so do the numbers of accessible charge states that are compatible with forming conformations of high helical content. There is conformational buffering whereby charge state heterogeneity buffers against large-scale conformational changes thus making the overall helicity insensitive to large changes in pH. Further, the results clearly argue against a single, rod-like alpha helical conformation being the only or even dominant conformation in the ensembles of so-called SAH sequences.
Divergent expression of aristaless1 and aristaless2 is associated with embryonic appendage and pupal wing development in butterflies
Authors: Bayala Erick X. , Cisneros Isabella , Massardo Darli , VanKuren Nicholas W. , Kronforst Marcus R. 
Published: September 2022

AbstractAristaless is a major regulator of developmental processes. It is well known for its role during appendage specification and extension across animals. Butterflies and moths have two copies of aristaless, aristaless1 (al1) and aristaless2 (al2), as a result of a gene duplication event. Previous work in Heliconius has shown that both copies appear to have novel functions related to wing color patterning. Here we expand our knowledge on the expression profiles associated with both ancestral and novel functions of Al1 across embryogenesis and wing pigmentation. Furthermore, we characterize Al2 expression, providing a comparative framework for understanding the role of gene duplicates in novel and ancestral roles. Our work shows that both Al1 and Al2 expression are associated with developing sensory appendages (leg, mouth, spines, and eyes) in embryos. Interestingly, Al1 appears to show higher expression earlier in embryogenesis while the highest levels of Al2 expression are shifted to later stages of embryonic development. Furthermore, Al1 localization appears extranuclear while Al2 co-localizes tightly with nuclei earlier, and then also expands outside the nucleus later in development. We observed similar cellular expression patterns for Al1 and Al2 in pupal wings when examining their roles in pigmentation. We also describe, for the first time, how Al1 localization appear to correlates with zones of Anterior/Posterior elongation of the body during embryonic growth, showcasing a possible new function related to Aristaless’ previously described role in appendage extension. Overall, these data suggest similar developmental roles associated with the extension/formation of specific appendages for both duplicates. However, we describe that such functions might be regulated by spatially and temporally complex patterns of expression for al1 and al2. This work expands our knowledge of Aristaless function and expression following gene duplication and the implications of the duplication on butterfly development. Finally, and more fundamentally, our study helps clarify principles behind sub-functionalization and gene expression evolution associated with developmental functions following gene duplication events.
Neural mechanisms of emotional health in traumatic brain injury patients undergoing rTMS treatment
Authors: Sultana T. , Hasan M.A. , Kang X , Liou-Johnson V. , Adamson M.M. , Razi A. 
Published: September 2022

AbstractEmotional dysregulation such as that seen in depression, are a long-term consequence of mild traumatic brain injury (TBI), that can be improved by using neuromodulation treatments such as repetitive transcranial magnetic stimulation (rTMS). Previous studies provide insights into the changes in functional connectivity related to general emotional health after the application of rTMS procedures in patients with TBI. However, these studies provide little understanding of the underlying neuronal mechanisms that drive the improvement of the emotional health in these patients.The current study focuses on inferring the effective (causal) connectivity changes and their association with emotional health, after rTMS treatment of cognitive problems in TBI patients (N=32). Specifically, we used resting state functional magnetic resonance imaging together with spectral dynamic causal model to investigate changes in brain effective connectivity, before and after the application of high frequency (10 Hz) rTMS over left dorsolateral prefrontal cortex. We investigated the effective connectivity of the cortico-limbic network comprised of 11 regions of interest which are part of the default mode, salience and executive control networks, known to be implicated in emotional processing.The results indicate that overall, among extrinsic connections, the strength of excitatory connections decreased while that of inhibitory connections increased indicating reduction in the activity of all the inspected brain regions after the neuromodulation. The cardinal region in the analysis was dorsal anterior cingulate cortex which is considered to be the most influenced during emotional health disorders.Our findings implicate the altered connectivity of dorsal anterior cingulate cortex with left anterior insula and medial prefrontal cortex, after the application of rTMS, as a potential neural mechanism underlying improvement of emotional health. Our investigation highlights the importance of these brain regions as treatment targets in emotional processing in TBI.
Global patterns and correlates in the emergence of antimicrobial resistance in humans
Authors: Mendelsohn Emma , Ross Noam , Zambrana-Torrelio Carlos , Van Boeckel T. P. , Laxminarayan Ramanan , Daszak Peter 
Published: September 2022

AbstractAntimicrobial resistance (AMR) is a critical global health threat, and drivers of the emergence of novel strains of antibiotic-resistant bacteria in humans are poorly understood at the global scale. We examined correlates of AMR emergence in humans using global data on the origins of novel strains of AMR bacteria from 2006 to 2017, human and livestock antibiotic use, country economic activity, and reporting bias indicators. We found that AMR emergence is positively correlated with antibiotic consumption in humans, whereas the relationship with antibiotic consumption in livestock is modified by gross domestic product (GDP), with only higher GDP countries showing a slight positive association. We also found that human travel may play a role in AMR emergence, likely driving the spread of novel AMR strains into countries where they are subsequently detected for the first time. Finally, we produced predictive models and country-level maps of the global distribution of AMR risk. We assessed these against spatial patterns of reported AMR emergence, to identify gaps in surveillance that can be used to direct prevention and intervention policies.
Detecting mild traumatic brain injury with MEG, normative modelling and machine learning
Authors: Itälinna Veera , Kaltiainen Hanna , Forss Nina , Liljeström Mia , Parkkonen Lauri 
Published: September 2022

AbstractDiagnosis of mild traumatic brain injury (mTBI) is challenging, as the symptoms are diverse and nonspecific. Electrophysiological studies have discovered several promising indicators of mTBI that could serve as objective markers of brain injury, but we are still lacking a diagnostic tool that could translate these findings into a real clinical application.Here, we used a multivariate machine-learning approach to detect mTBI from resting-state magnetoencephalography (MEG) measurements. To address the heterogeneity of the condition, we employed a normative modeling approach and modeled MEG signal features of individual mTBI patients as deviations with respect to the normal variation. To this end, a normative dataset comprising 621 healthy participants was used to determine the variation in power spectra across the cortex. In addition, we constructed normative datasets based on age-matched subsets of the full normative data. To discriminate patients from healthy control subjects, we trained support vector machine classifiers on the quantitative deviation maps for 25 mTBI patients and 20 controls not included in the normative dataset.The best performing classifier made use of the full normative data across the entire age range. This classifier was able to distinguish patients from controls with an accuracy of 79%, which is high enough to substantially contribute to clinical decision making. Inspection of the trained model revealed that low-frequency activity in the theta frequency band (4–8 Hz) is a significant indicator of mTBI, consistent with earlier studies. The method holds promise to advance diagnosis of mTBI and identify patients for treatment and rehabilitation.Significance statementMild traumatic brain injury is extremely common, but no definite diagnostic method is yet available. Objective markers for detecting brain injury are needed to direct care to those who would best benefit from it. We present a new approach based on MEG recordings that first explicitly addresses the variability in brain dynamics within the population through normative modeling, and then applies supervised machine-learning to detect pathological deviations related to mTBI. The approach can easily be adapted to other brain disorders as well and could thus provide a basis for an automated tool for analysis of MEG/EEG towards disease-specific biomarkers.
Cortical somatostatin interneuron subtypes form cell-type specific circuits
Authors: Wu Sherry Jingjing , Sevier Elaine , Saldi Giuseppe-Antonio , Yu Sabrina , Abbott Lydia , Choi Da Hae , Sherer Mia , Qiu Yanjie , Shinde Ashwini , Rizzo Daniella , Xu Qing , Barrera Irving , Kumar Vipin , Marrero Giovanni , Prönneke Alvar , Huang Shuhan , Rudy Bernardo , Stafford David A. , Macosko Evan , Chen Fei , Fishell Gord 
Published: September 2022

SUMMARYThe cardinal interneuron classes are a useful simplification of cortical interneuron diversity, but such broad subgroupings glosses over the molecular, morphological, and circuit specificity of interneuron subtypes, most notably among the somatostatin interneuron class. The organizing principles by which the connectivity of these subtypes is specified are unknown. To address this knowledge gap, we designed a series of genetic strategies to target the breadth of somatostatin interneuron subtypes. Using these strategies to target three subtypes that span the entire cortical column, we examined their afferent and efferent connectivity. Our data demonstrated that each of these possesses remarkable reciprocal connectivity with the intracortical or corticofugal pyramidal classes, as well as parvalbumin interneurons. Even when two interneuron subtypes shared the same efferent target, their synaptic targeting proved selective for particular dendritic compartments. We thus provide evidence that subtypes of somatostatin cortical interneurons form cell-type specific cortical circuits.
Effect of Physical Activity on Olfactory Acuity: A Systematic Review
Authors: Cournoyer Mathieu , Gauthier Alexandre-Charles , Maldera Alice , Maso Fabien Dal , Mathieu Marie-Eve 
Published: September 2022

AbstractOlfactory acuity, which includes detection thresholds, identification and appreciation/intensity, seems to decline with aging, obesity, and various neurological disorders. Knowing that the sense of smell influences energy intake, the interest in protecting this sense is constantly increasing. Physical activity might be a key intervention to counteract the loss of olfactory function. This systematic review aims to explore the literature on the effect of physical activity on olfactory acuity. The search strategy consisted of using index terms and keywords in MEDLINE, EMBASE, EBM Reviews – Cochrane Central Register of Controlled Trials, CINAHL, SPORTDiscus, and Web of Science search engine. Data from 17 studies that include 10 861 participants revealed that physical activity has improved olfactory thresholds, identification, and intensity. More precisely, chronic physical activity seemed to have better effects on olfactory components than acute practice. Even though this review clarified evidence about the effect of physical activity on the sense of smell, better methodological consistency is needed across studies such as standardized experimental conditions, the time of the day data are collected, and similar relative energy intake between participants to produce more robust results.
Exploring the challenges and possibilities of critical literacy pedagogy: K-8 teacher discussions about race in a virtual professional development course
Authors: Lucero Audrey , Avelar Janette Dalila 
Published: September 2022

PurposeThe purpose of this study is to better understand the ways in which K-8 teachers from a semirural, predominantly white district perceive their responsibilities to work toward anti-racism, as well as to learn more about how the teachers can be supported as they work to overcome the challenges facing teachers in these fraught times in this country’s history.Design/methodology/approachThe authors use a reconstructive approach to critical discourse analytic methods (Bartlett, 2012; Hughes, 2018; Luke, 2002, 2004; Martin, 2004) to analyze an online discussion that took place among participants in a virtual anti-racist critical professional development course (Kohli, 2019; Kohliet al., 2015) as they grappled with what it means to confront their own racial identities, positionalities and responsibilities.FindingsThree primary tensions emerged in teachers’ discussion: between geographic and professional identities; between individual and institutional responsibility; and between literacy instruction and critical literacy instruction. In all three cases, teachers expressed the difficulties associated with enacting anti-racist critical literacy pedagogy in their school context, while also leaving space for possibility.Practical implicationsThe findings from this study add to the field’s understanding about how teachers in various contexts approach the work of anti-racist critical literacy pedagogy at different stages in their careers and how teacher educators might support them in doing so.Originality/valueThis study is important in its focus on professional development for in-service teachers, as much of the work has focused on preservice teachers and those who have been in classrooms for varying lengths of time have different levels of experience and different professional needs (Hambacher and Ginn, 2021). It is also notable that these teachers worked in a semirural, predominantly white district, as teachers working in such geographic locations often do not receive education about engaging with diversity (Anthony-Stevenset al., 2017; Anthony-Stevens and Langford, 2020) and it is essential that teachers and students in these districts are engaged if we are going to make headway in challenging whiteness in schools.
COVID-19 and entrepreneurship courses in Latin American universities: an analysis of satisfaction comparing students' and lecturers' perspectives
Authors: Barrera-Verdugo Gustavo , Romaní Gianni , Cadena-Echeverría Jaime Luis , Carrero-Morales Gisela I. , Padín-Zamot Gerardo 
Published: September 2022

PurposeThis study aims to investigate how the disruptive change from a face-to-face to an online teaching/learning modality due to COVID-19 has been perceived by students and lecturers of entrepreneurship courses in universities in six Latin American countries by evaluating the conditions that affect their satisfaction.Design/methodology/approachTwo online surveys were distributed to lecturers and students of entrepreneurship courses. A total of 559 responses were received from students and 270 lecturers from six Latin American countries. The information was analysed through principal component analysis (PCA), correlations and the Mann–Whitney–Wilcoxon test.FindingsThis research provides new information about the factors that are relevant to student and lecturer satisfaction when moving from mandatory face-to-face to online classes. The results show that overall satisfaction is lower among students than among teachers. Besides, that student communication with the lecturer and technology-supported access to lectures are two important aspects that affect student satisfaction. Regarding lecturers' satisfaction, the participation and attitude of their students in online classes are important conditions that affect their intention to teach online courses in the future.Practical implicationsThis study has allowed us to reflect on online education and teaching methodologies in Latin-American universities after the COVID-19 pandemic, as well as to recognise opportunities for improvement to increase student and lecturer satisfaction in this new reality.Originality/valueThis study provides new evidence by comparing the satisfaction between lecturers and students in entrepreneurship courses and factors that affect their satisfaction in several Latin American countries, after change to an online modality due to COVID-19.