bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2
Authors: Caiola Hanna O. , Wu Qian , Soni Shaili , Wang Xue-Feng , Monahan Kevin , Pang Zhiping P. , Wagner George C. , Zhang Huaye
Published: December 2023

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer’s disease. Nonetheless, the molecular mechanisms underlying aberrant neuronal connectivity remains unclear. We previously found that the serine/threonine kinase Microtubule Affinity Regulating Kinase 2 (MARK2), also known as Partitioning Defective 1b (Par1b), is important for the formation of dendritic spinesin vitro.However, despite its genetic association with several neurological disorders, thein vivoimpact of MARK2 on neuronal connectivity and cognitive functions remains unclear. Here, we demonstrate that loss of MARK2in vivoresults in changes to dendritic spine morphology, which in turn leads to a decrease in excitatory synaptic transmission. Additionally, loss of MARK2 produces substantial impairments in learning and memory, anxiety, and social behavior. Notably, MARK2 deficiency results in heightened seizure susceptibility. Consistent with this observation, RNAseq analysis reveals transcriptional changes in genes regulating synaptic transmission and ion homeostasis. These findings underscore thein vivorole of MARK2 in governing synaptic connectivity, cognitive functions, and seizure susceptibility.
Imputing Single-Cell Protein Abundance in Multiplex Tissue Imaging
Authors: Kirchgaessner Raphael , Watson Cameron , Creason Allison , Keutler Kaya , Goecks Jeremy
Published: December 2023

Multiplex tissue imaging are a collection of increasingly popular single-cell spatial proteomics and transcriptomics assays for characterizing biological tissues both compositionally and spatially. However, several technical issues limit the utility of multiplex tissue imaging, including the limited number of molecules (proteins and RNAs) that can be assayed, tissue loss, and protein probe failure. In this work, we demonstrate how machine learning methods can address these limitations by imputing protein abundance at the single-cell level using multiplex tissue imaging datasets from a breast cancer cohort. We first compared machine learning methods’ strengths and weaknesses for imputing single-cell protein abundance. Machine learning methods used in this work include regularized linear regression, gradient-boosted regression trees, and deep learning autoencoders. We also incorporated cellular spatial information to improve imputation performance. Using machine learning, single-cell protein expression can be imputed with mean absolute error ranging between 0.05-0.3 on a [0,1] scale. Finally, we used imputed data to predict whether single cells were more likely to come from pre-treatment or post-treatment biopsies. Our results demonstrate (1) the feasibility of imputing single-cell abundance levels for many proteins using machine learning; (2) how including cellular spatial information can substantially enhance imputation results; and (3) the use of single-cell protein abundance levels in a use case to demonstrate biological relevance.
Aperiodic EEG predicts variability of visual temporal processing
Authors: Deodato Michele , Melcher David
Published: December 2023

The human brain exhibits both oscillatory and aperiodic, or 1/f, activity. Although a large body of research has focused on the relationship between brain rhythms and sensory processes, aperiodic activity has often been dismissed as noise and functionally irrelevant. Prompted by recent findings linking aperiodic activity to the balance between neural excitation and inhibition, we investigated its effects on the temporal resolution of perception. We recorded EEG from participants during resting state and a task in which they detected the presence of two flashes separated by variable inter-stimulus intervals. Two-flash discrimination accuracy typically follows a sigmoid function whose steepness reflects perceptual variability or inconsistent integration/segregation of the stimuli. We found that individual differences in the steepness of the psychometric function correlated with EEG aperiodic exponents over posterior scalp sites. In other words, participants with higher levels of aperiodic activity (i.e., neural excitation) exhibited increased sensory noise, resulting in shallower psychometric curves. Our finding suggest that aperiodic EEG is linked to sensory integration processes usually attributed to the rhythmic inhibition of neural oscillations. Overall, this correspondence between aperiodic neural excitation and behavioral measures of sensory noise provides a more comprehensive explanation of the relationship between brain activity and sensory integration and represents an important extension to theories of how the brain samples sensory input over time.
Loss of PV interneurons in the BLA contributes to altered network and behavioral states in chronically epileptic mice
Authors: Colmers Phillip L.W. , Antonoudiou Pantelis , Basu Trina , Scapa Garrett , Fuller Patrick , Maguire Jamie
Published: December 2023

Psychiatric disorders, including anxiety and depression, are highly comorbid in people with epilepsy. However, the mechanisms mediating the shared pathophysiology are currently unknown. There is considerable evidence implicating the basolateral amygdala (BLA) in the network communication of anxiety and fear, a process demonstrated to involve parvalbumin-positive (PV) interneurons. The loss of PV interneurons has been well described in the hippocampus of chronically epileptic mice and in postmortem human tissue of patients with temporal lobe epilepsy (TLE). We hypothesize that a loss of PV interneurons in the BLA may contribute to comorbid mood disorders in epilepsy. To test this hypothesis, we employed a ventral intrahippocampal kainic acid (vIHKA) model of chronic epilepsy in mice, which exhibits profound behavioral deficits associated with chronic epilepsy. We demonstrate a loss of PV interneurons and dysfunction of remaining PV interneurons in the BLA of chronically epileptic mice. Further, we demonstrate altered principal neuron function and impaired coordination of BLA network and behavioral states in chronically epileptic mice. To determine whether these altered network and behavioral states were due to the loss of PV interneurons, we ablated a similar percentage of PV interneurons observed in chronically epileptic mice by stereotaxically injecting AAV-Flex-DTA into the BLA of PV-Cre mice. Loss of PV interneurons in the BLA is sufficient to alter behavioral states, inducing deficits in fear learning and recall of fear memories. These data suggest that compromised inhibition in the BLA in chronically epileptic mice contributes to behavioral deficits, suggesting a novel mechanism contributing to comorbid anxiety and epilepsy.

Significance Statement

Psychiatric illnesses and epilepsy are highly comorbid and negatively impact the quality of life of people with epilepsy. The pathophysiological mechanisms mediating the bidirectional relationship between mood disorders and epilepsy remain unknown and, therefore, treatment options remain inadequate. Here we demonstrate a novel mechanism, involving the loss of PV interneurons in the BLA, leading to a corruption of network and behavioral states in mice. These findings pinpoint a critical node and demonstrate a novel cellular and circuit mechanism involved in the comorbidity of psychiatric illnesses and epilepsy.
GeneExt: a gene model extension tool for enhanced single-cell RNA-seq analysis
Authors: Zolotarov Grygoriy , Grau-Bové Xavier , Sebé-Pedrós Arnau
Published: December 2023

Incomplete gene models negatively impact single-cell gene expression quantification. This is particularly true in non-model species where often gene 3′ ends are inaccurately annotated, while most scRNA-seq methods only capture the 3′ transcript region. This results in many genes being incorrectly quantified or not detected. GeneExt leverages scRNA-seq data to refine gene annotations, enhancing biological interpretation and cross-species comparisons of cell type expression atlases.
Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma
Authors: Manoharan Varsha Thoppey , Abdelkareem Aly , Brown Samuel , Gillmor Aaron , Hall Courtney , Seo Heewon , Narta Kiran , Grewal Sean , Dang Ngoc Ha , Ahn Bo Young , Otz Kata , Lun Xueqing , Mah Laura , Zemp Franz , Mahoney Douglas , Senger Donna L. , Chan Jennifer A. , Morrissy A. Sorana
Published: December 2023

Diffuse invasion of glioblastoma cells through normal brain tissue is a key contributor to tumor aggressiveness, resistance to conventional therapies, and dismal prognosis in patients. A deeper understanding of how components of the tumor microenvironment (TME) contribute to overall tumor organization and to programs of invasion may reveal opportunities for improved therapeutic strategies. Towards this goal, we applied a novel computational workflow to a spatiotemporally profiled GBM xenograft cohort, leveraging the ability to distinguish human tumor from mouse TME to overcome previous limitations in analysis of diffuse invasion. Our analytic approach, based on unsupervised deconvolution, performs reference-free discovery of cell types and cell activities within the complete GBM ecosystem. We present a comprehensive catalogue of 15 tumor cell programs set within the spatiotemporal context of 90 mouse brain and TME cell types, cell activities, and anatomic structures. Distinct tumor programs related to invasion were aligned with routes of perivascular, white matter, and parenchymal invasion. Furthermore, sub-modules of genes serving as program network hubs were highly prognostic in GBM patients. The compendium of programs presented here provides a basis for rational targeting of tumor and/or TME components. We anticipate that our approach will facilitate an ecosystem-level understanding of immediate and long-term consequences of such perturbations, including identification of compensatory programs that will inform improved combinatorial therapies.
Historical contingency influences the diversity of feather nanostructures in cuckoos
Authors: Nordén Klara K. , Cooney Christopher R. , Babarović Frane , Stoddard Mary Caswell
Published: December 2023

Structural coloration is widespread in animals, yet we know relatively little about its evolution and development. While previous studies have explored adaptive functions of structural color, a key gap is our lack of understanding of how historical contingency (path-dependency of biological processes) influences the loss and gain of this complex trait. We shed light on this question by describing feather nanostructures responsible for plumage colors in the cuckoos (family Cuculidae), a group with widespread occurrence of shiny, metallic plumage (metallic luster). The melanosomes found in feathers with metallic luster have specialized shapes: hollow rods, thin solid rods, hollow platelets, or solid platelets. In contrast, it is generally assumed that drably colored feathers possess thick, rod-shaped melanosomes. However, we uncover that this assumption is unfounded in cuckoos. We describe metallic luster in the plumages of 126 cuckoo species and map its phylogenetic distribution. This reveals that metallic luster is widespread in cuckoos but has likely been lost several times. We then use transmission electron microscopy to describe the feather nanostructures of 21 cuckoo species. Surprisingly, the drab feathers of many cuckoo species contain melanosomes with specialized shapes. We propose that historical contingency greatly influences nanostructure diversity in cuckoos. Specialized melanosome shapes can be retained in the plumages of drab species, potentially making it easier for metallic luster to evolve again in the future. This discovery supports the idea that historical contingency plays a key role in shaping the evolution of plumage color diversity.
Intra-horn insemination in the alpacaVicugna pacos: Copulatory wounding and deep sperm deposition
Authors: Brennan Patricia LR , Purdy Stephen , Bacon Sarah J
Published: December 2023

Alpacas (Vicugna pacos) are reported to be the rare mammal in which the penis enters the uterus in mating. To date, however, only circumstantial evidence supports this assertion. Using female alpacas culled for meat, we determined that the alpaca penis penetrates to the very tips of the uterine horns, abrading the tract and breaking fine blood vessels. All female alpacas sacrificed one hour or 24 hours after mating showed conspicuous bleeding in the epithelium of some region of their reproductive tract, including the hymen, cervix and the tips of each uterine horn, but typically not in the vagina. Unmated females showed no evidence of conspicuous bleeding. Histological examination of mated females revealed widespread abrasion of the cervical and endometrial epithelium, injuries absent in unmated females. Within one hour of mating, sperm were already present in the oviduct. The male alpaca’s cartilaginous penis tip with a hardened urethral process is likely responsible for the copulatory abrasion. The entire female reproductive tract interacts with the penis, functioning like a vagina. Alpacas are induced ovulators, and wounding may hasten delivery of the seminal ovulation-inducing factor beta-NGF into the female’s blood stream. There is no evidence of sexual conflict in copulation in alpaca, and thus wounding may also be one of a variety of mechanisms devised by mammals to induce a beneficial, short-term inflammatory response that stimulates blastocyst implantation, the uterine remodeling associated with placental development, and thus the success of early pregnancy.
Insect Detect: An open-source DIY camera trap for automated insect monitoring
Authors: Sittinger Maximilian , Uhler Johannes , Pink Maximilian , Herz Annette
Published: December 2023

Insect monitoring is essential to design effective conservation strategies, which are indispensable to mitigate worldwide declines and biodiversity loss. For this purpose, traditional monitoring methods are widely established and can provide data with a high taxonomic resolution. However, processing of captured insect samples is often time-consuming and expensive, which limits the number of potential replicates. Automated monitoring methods can facilitate data collection at a higher spatiotemporal resolution with a comparatively lower effort and cost. Here, we present the Insect Detect DIY (do-it-yourself) camera trap for non-invasive automated monitoring of flower-visiting insects, which is based on low-cost off-the-shelf hardware components combined with open-source software. Custom trained deep learning models detect and track insects landing on an artificial flower platform in real time on-device and subsequently classify the cropped detections on a local computer. Field deployment of the solar-powered camera trap confirmed its resistance to high temperatures and humidity, which enables autonomous deployment during a whole season. On-device detection and tracking reliably estimated insect activity/abundance after metadata post-processing. Our insect classification model achieved a high top-1 accuracy on the test dataset and generalized well on a real-world dataset with captured insect images. The camera trap design and open-source software are highly customizable and can be adapted to different use cases. With custom trained detection and classification models, as well as accessible software programming, many possible applications surpassing our proposed deployment method can be realized.
Biomechanical effects of adding an articulating toe joint to a passive foot prosthesis for incline and decline walking
Authors: Teater Rachel H. , Zelik Karl E. , McDonald Kirsty A.
Published: December 2023

Walking on sloped surfaces is challenging for many lower limb prosthesis users, in part due to the limited ankle range of motion provided by typical prosthetic ankle-foot devices. Adding a toe joint could potentially benefit users by providing an additional degree of flexibility to adapt to sloped surfaces, but this remains untested. The objective of this study was to characterize the effect of a prosthesis with an articulating toe joint on the preferences and gait biomechanics of individuals with unilateral below-knee limb loss walking on slopes. Nine active prosthesis users walked on an instrumented treadmill at a +5° incline and −5° decline while wearing an experimental foot prosthesis with two configurations: a Flexible toe joint and a Locked-out toe joint. Three participants preferred the Flexible toe joint over the Locked-out toe joint for incline and decline walking. Eight of nine participants went on to participate in a biomechanical data collection. The Flexible toe joint decreased prosthesis Push-off work by 2 J during both incline and decline walking (p=0.008). During incline walking, prosthetic limb knee flexion at toe-off was 3° greater in the Flexible configuration compared to the Locked (p=0.008). Overall, these results indicate that adding a toe joint to a passive foot prosthesis has relatively small effects on joint kinematics and kinetics during sloped walking. This study is part of a larger body of work that also assessed the impact of a prosthetic toe joint for level and uneven terrain walking and stair ascent/descent. Collectively, toe joints do not appear to substantially or consistently alter lower limb mechanics for active unilateral below-knee prosthesis users. Our findings also demonstrate that user preference for passive prosthetic technology may be both subject-specific and task-specific. Future work could investigate the inter-individual preferences and potential benefits of a prosthetic toe joint for lower-mobility individuals.
Can upwelling regions be potential thermal refugia for marine species during climate warming? The case of Mexico
Authors: Angeles-Gonzalez Luis Enrique , Torrejón-Magallanes Josymar , Osorio-Olvera Luis , Avendaño Otilio , Díaz Fernando , Rosas Carlos
Published: December 2023

Anthropogenic climate warming will change the thermal habitats of marine species worldwide. Species are expected to migrate to higher latitudes as warming intensifies since behavioral and physiological mechanisms have been adapted to maximize fitness under a specific range of temperatures. However, given the possible intensification of upwelling ecosystems, they may act as potential thermal refugia under climate warming, which could protect the diversity of the marine ecosystems, making them important regions for marine resource management. This research aimed to predict the effects of climate warming on commercial and non-commercial marine species (vertebrate and invertebrates) reported in official Mexican documents (> 300 species) based on a thermal niche characterization with the objective to observe if the upwelling regions can act as potential thermal refugia. For this, we considered Representative Concentration Pathway (6.0 and 8.5) scenarios for the present and the future (2040-2050 and 2090-2100). Current and future patterns of suitability, species distribution, richness, and turnover were calculated via ecological niche models using the minimum volume ellipsoids as an algorithm. The results in this study highlight that beyond migration to higher latitudes, some upwelling regions (not all) could be potentially used as some type of “oasis” by marine species refuging from environmental pressure or zones of higher stability of species. Specifically, the upwelling systems in western Baja California and north of Yucatan may be essential regions for future management in Mexico. Nevertheless, it is important to note that climate change acts on numerous ecosystem features, such as trophic relationships, phenology, and other environmental variables not considered here. Future research could test our hypothesis under more realistic simulations. However, migration toward upwelling regions seems to be the most logical selection from all the available ecosystems as climate refugia for marine species beyond movement to higher latitudes or depths.
In Silico Therapeutic Intervention on Cytokine Storm in COVID-19
Authors: Bakshi Abhisek , Gangopadhyay Kaustav , Basak Sujit , Chakrabarti Amlan , Dasgupta Abhijit , De Rajat K.
Published: December 2023

The recent global COVID-19 outbreak, attributed by the World Health Organization to the rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), underscores the need for an extensive exploration of virological intricacies, fundamental pathophysiology, and immune responses. This investigation is vital to unearth potential therapeutic avenues and preventive strategies. Our study delves into the intricate interaction between SARS-CoV-2 and the immune system, coupled with exploring therapeutic interventions to counteract dysfunctional immune responses like the ‘cytokine storm’ (CS), a driver of disease progression. Understanding these immunological dimensions informs the design of precise multiepitopetargeted peptide vaccines using advanced immunoinformatics and equips us with tools to confront the cytokine storm. Employing a control theory-based approach, we scrutinize the perturbed behavior of key proteins associated with cytokine storm during COVID-19 infection. Our findings support ACE2 activation as a potential drug target for CS control and confirm AT1R inhibition as an alternative strategy. Leveraging deep learning, we identify potential drugs to individually target ACE2 and AT1R, with Lomefloxacin and Fostamatinib emerging as standout options due to their close interaction with ACE2. Their stability within the protein-drug complex suggests superior efficacy among many drugs from our deep-learning analysis. Moreover, there is a significant scope for optimization in fine-tuning protein-drug interactions. Strong binding alone may not be the sole determining factor for potential drugs; precise adjustments are essential. The application of advanced computational power offers novel solutions, circumventing time-consuming lab work. In scenarios necessitating both ACE2 and AT1R targeting, optimal drug combinations can be derived from our analysis of drug-drug interactions, as detailed in the manuscript.
An explainable machine learning data analytics method using TIGIT-linked genes for identifying biomarker signatures to clinical outcomes
Authors: Soorya G , Agrawal Divya , Bhat Shilpa , Mandal Tirtha , Kashipathi Shalini , Madhusudhan M. S. , Rodrigues Golding , Ghosh Maloy , Chirmule Narendra
Published: December 2023

In the last decade, immunotherapies targeting immune checkpoint inhibitors have been extremely effective in eliminating subsets of some cancers in some patients. Multi-modal immune and non-immune factors that contribute to clinical outcomes have been utilized for predicting response to therapies and developing diagnostics. However, these data analytic methods involve a combination of complex mathematical data analytics, and even-more complex biological mechanistic pathways. In order to develop a method for data analytics of transcriptomics data sets, we have utilized an explainable machine learning (ML) model to investigate the genes involved in the signaling pathway of T-cell-immunoreceptor with immunoglobulin and ITIM domain (TIGIT). TIGIT is a receptor on T, NK, and T-regulatory cells, that has been classified as a checkpoint inhibitor due to its ability to inhibit innate and adaptive immune responses. We extracted gene whole genome sequencing data of 1029 early breast cancer patient tumors, and adjacent normal tissues from the TCGA and UCSC Xena Data Hub public databases. We followed a workflow which involved the following steps: i) data acquisition, processing, and visualization followed by ii) developed of a predictive prognostic model using input (gene expression data) and output (survival time) parameters iii) model interpretation was performed by calculating SHAP (Shapely-Additive-exPlanations); iv) the application of the model involved a Cox-regression model, trained with L-2 regularization and optimization using 5 fold cross validation. The model identified gene signatures associated with TIGIT that predicted survival outcome with a test set with a score of 0.601. In summary, we have utilized this case study of TIGIT-mediated signaling pathways to develop a roadmap for biologists to harness ML methods effectively.
Deciphering the actin structure-dependent preferential cooperative binding of cofilin
Authors: Ngo Kien Xuan , Vu Huong T , Umeda Kenichi , Trinh Minh-Nhat , Kodera Noriyuki , Uyeda Taro Q.P.
Published: December 2023

The mechanism underlying the preferential and cooperative binding of cofilin and the expansion of clusters toward the pointed-end side of actin filaments remains poorly understood. To address this, we conducted a principal component analysis based on available filamentous actin (F-actin) and C-actin (cofilins were excluded from cofilactin) structures and compared to monomeric G-actin. The results strongly suggest that C-actin, rather than F-ADP-actin, represented the favourable structure for binding preference of cofilin. High-speed atomic force microscopy explored that the shortened bare half helix adjacent to the cofilin clusters on the pointed end side included fewer actin protomers than normal helices. The mean axial distance (MAD) between two adjacent actin protomers along the same long-pitch strand within shortened bare half helices was longer (5.0–6.3 nm) than the MAD within typical helices (4.3–5.6 nm). The inhibition of torsional motion during helical twisting, achieved through stronger attachment to the lipid membrane, led to more pronounced inhibition of cofilin binding and cluster formation than the presence of inorganic phosphate (Pi) in solution. F-ADP-actin exhibited more naturally supertwisted half helices than F-ADP.Pi-actin, explaining how Pi inhibits cofilin binding to F-actin with variable helical twists. We propose that protomers within the shorter bare helical twists, either influenced by thermal fluctuation or induced allosterically by cofilin clusters, exhibit characteristics of C-actin-like structures with an elongated MAD, leading to preferential and cooperative binding of cofilin.
Spatial organization and stochastic fluctuations of immune cells impact clinical responsiveness to immune checkpoint inhibitors in patients with melanoma
Authors: Giuliani Giuseppe , Stewart William , Li Zihai , Jayaprakash Ciriyam , Das Jayajit
Published: December 2023

High-dimensional, spatial single-cell technologies such as CyTOF imaging mass cytometry (IMC) provide detailed information regarding locations of a large variety of cancer and immune cells in microscopic scales in tumor microarray (TMA) slides obtained from patients prior to immune checkpoint inhibitor (ICI) therapy. An important question is how the initial spatial organization of these cells in the tumor microenvironment (TME) change with time, regulate tumor growth and eventually outcomes as patients undergo ICI therapy. Utilizing IMC data of melanomas of patients who later underwent ICI therapy, we develop a spatially resolved interacting cell systems model that is calibrated against patient response data to address the above question. We find that the tumor fate in these patients is determined by the spatial organization of activated CD8+ T cells, macrophages, and melanoma cells and the interplay between these cells that regulate exhaustion of CD8+ T cells. We find that fencing of tumor cell boundaries by exhausted CD8+T cells is dynamically generated from the initial conditions that can play a pro-tumor role. Furthermore, we find that specific spatial features such as co-clustering of activated CD8+ T cells and macrophages in the pre-treatment samples determine the fate of the tumor progression, despite stochastic fluctuations and changes over the treatment course. Our framework enables determination of mechanisms of interplay between a key subset of tumor and immune cells in the TME that regulate clinical response to ICIs.

Significance

Recent advances in single cell technologies allows for spatial imaging a wide variety of cancer and immune cells in tissue samples obtained from solid tumors. This detailed snapshot data of microscale organization of tumor and immune cells could provide valuable insights into underlying biology and clinical responsiveness to cancer immunotherapy. By combining published data from imaging mass-cytometry and patient response against ICI drugs with data analysis rooted in statistical physics and statistical inference theory, we developed and studied the dynamics of mechanistic spatially resolved models: we show that tumor growth during ICI treatment is regulated by non-intuitive interplay between CD8+ T cells and tumor associated macrophages, formation of a pro-tumor fencing of exhausted CD8+ T cells around melanoma cells, specific features of spatial organization of these cells prior to treatment, and stochastic fluctuations in the dynamics. The mechanisms unveiled in our studies are general and can pertain to the response of other solid tumors to ICI therapy.
Spatial ecology and population dynamics of brown troutSalmo truttaL. in reservoirs and headwater tributaries
Authors: Dodd Jamie R. , Noble Richard A.A. , Nunn Andy D. , Owen Holly , Moccetti Paolo , Harvey Jonathan P. , Wallace Liam , Gillespie Ben , Joyce Domino A. , Bolland Jonathan D.
Published: December 2023

This investigation compared the spatial ecology and population dynamics of brown troutSalmo trutta L. between reservoirs with (impact; Langsett Reservoir) and without (control; Grimwith Reservoir) barriers to fish movements into afferent headwater tributaries, including the effectiveness of a fish pass to remediate connectivity. Passive Integrated Transponder (PIT) telemetry revealed fish that emigrated from Langsett and Grimwith reservoirs were 1-3 and 0-2 years old, respectively, and predominantly did so in March-May and October-December in both. Weirs at Langsett Reservoir (emigration rate = 26%) appeared to thwart emigration relative to Grimwith Reservoir (emigration rate = 85%). Acoustic telemetry (2D positions) in the impact reservoir revealed the largest home range was in October – December (monthly K95 ± S.D. up to 26.9 ± 6.69 ha in November), activity was influenced by both month and time of day, and fish occupied shallow water depths (relative to reservoir depth), especially at night. Large proportions of brown trout tagged in Grimwith and Langsett reservoirs (42.9% and 64.1%, respectively) and fish that emigrated (37.2% and 27.7%, respectively) were detected moving upstream into tributaries. At both reservoirs, peak immigration for 3- and ≥4-year-old fish occurred in October-December, although upstream movements occurred throughout the year and by all age classes. Three brown trout passed upstream of each of the weirs on River Little Don (prior to fish pass construction; 3% of those that approached from downstream) and Thickwoods Brook (throughout the study; 2%). Overall fish pass solution passage efficiency was 14% but was higher for 2- and 3-year-old fish (32%), which was comparable to fish translocated from upstream (33%). Passage predominantly occurred at lower river levels than fish pass entrance / attraction, which was also lower than during approaches to the weir. A Before-After Control-Impact (BACI) design found that although juvenile (0+, but not >0+) brown trout densities were lower after fish pass construction, the reduction was significantly less than at control sites, i.e., the fish pass had a positive effect. Overall, this investigation significantly furthers our understanding of brown trout spatial ecology and population dynamics in reservoirs and headwater tributaries.
Biological characteristics and metabolic phenotypes of different anastomosis groups ofRhizoctonia solanistrains
Authors: Sun Meili , Wang Hancheng
Published: December 2023

Rhizoctonia solaniis an important plant pathogen worldwide, and causes serious target spot disease in tobacco in the last five years. This research studied the biological characteristics of four different anastomosis groups (R. solaniAG-3,R. solaniAG-5,R. solaniAG-6,R. solaniAG-1-IB) ofR. solanifrom tobacco, and analyzed the metabolic phenotype differences of these strains using metabolic phenotype technology. The results showed that the suitable temperature for mycelial growth of four anastomosis group strains were all from 20 to 30 °C, and for sclerotia formation were from 20 to 25 °C. Under different lighting conditions,R. solaniAG-6 strains produced the most sclerotium, followed byR. solaniAG-3,R. solaniAG-5 andR. solaniAG-1-IB. All strains had strong oligotrophic survivability, and can grow on water agar medium without any nitrutions. They exhibited three types of sclerotia distribution form, including dispersed type (R. solaniAG-5 andR. solaniAG-6), peripheral type (R. solaniAG-1-IB), and central type (R. solaniAG-3). They all presented different pathogenicities in tobacco leaves, with the most virulent was noted byR. solaniAG-6, followed byR. solaniAG-5 and AG-1-IB, finally wasR. solaniAG-3.R. solaniAG-1-IB strains firstly present symbtom about inoculation. Metabolic fingerprints of four anastomosis groups were different to each other.R. solaniAG-3, AG-6, AG-5 and AG-1-IB strains efficiently metabolized 88, 94, 71 and 92 carbon substrates, respectively. Nitrogen substrates of amino acids and peptides were the significant utilization patterns forR. solaniAG-3.R. solaniAG-3 and AG-6 showed a large range of adaptabilities and were still able to metabolize substrates in the presence of the osmolytes, including up to 8% sodium lactate. Four anastomosis groups all showed active metabolism in environments with pH values from 4 to 6 and exhibited decarboxylase activities.

One-sentence summary

Rhizoctonia solanistrains from different anastomosis groups have a different adaptability to habitats.
Apoplastic barrier establishment in roots and nodules of Lotus japonicus is essential for root-shoot signaling and N-fixation
Authors: Shen Defeng , Venado Rafael E. , Neumann Ulla , Dyballa-Rukes Nadine , Mahiwal Swati , Metzger Sabine , Nakano Ryohei Thomas , Marín Macarena , Andersen Tonni Grube
Published: December 2023

The molecular framework underlying apoplastic root barrier formation has been unveiled in the model speciesArabidopsis thalianawhere establishment of Casparian strips occurs at an early stage of root development. In legumes, this region overlaps with the area where nitrogen-fixing bacteria can induce nodule formation, termed the susceptible zone. Moreover, while nodules themselves also contain an endodermis spanning their vascular bundles, it is current unknown if Casparian strips serve as a filter for transport across this specialized organ. Here we establish barrier mutants in the symbiosis modelLotus japonicus.We find that the while genetic network controlling Casparian strip formation is conserved in this legume species, formation of functional barriers is crucial for establishment of N-fixing nodules. By probing this in detail, we establish a model where the Casparian strip, via its linked Schengen pathway, converge with long distance N signaling and systemic regulation of nodulation. Moreover, this also reveal that the genetic system for barrier establishment in the root endodermis is shared in nodule vascular endodermis and required for nodule function. Combined, our findings uncover a novel role of apoplastic root barriers and establishes a mutant collection suitable to probe the role of root barriers in symbiotic plant-microbe relationships.
Biases of Principal Component Analysis (PCA) in Physical Anthropology Studies Require a Reevaluation of Evolutionary Insights
Authors: Mohseni Nima , Elhaik Eran
Published: December 2023

Evolutionary biologists, primarily palaeoanthropologists, anatomists and ontogenists, employ modern geometric morphometrics to quantitatively analyse physical forms (e.g., skull morphology) and explore relationships, variations, and differences between samples and taxa using landmark coordinates. The standard approach comprises two steps: Generalised Procrustes Analysis (GPA) followed by Principal Component Analysis (PCA). PCA projects the superimposed data produced by GPA onto a set of uncorrelated variables, which can be visualised on scatterplots and used to draw phenetic, evolutionary, and ontogenetic conclusions. Recently, the use of PCA in genetic studies has been challenged. Due to PCA’s central role in morphometrics, we sought to evaluate the standard approach and claims based on PCA outcomes. To test PCA’s accuracy, robustness, and reproducibility using benchmark data of the crania of five papionin genera, we developed MORPHIX, a Python package for processing superimposed landmark data with classifier and outlier detection methods, which can be further visualised using various plots. Throughout this manuscript, we address the recent and contentious use of PCA in physical anthropology and phylogenetic inference, such as the case ofHomo Nesher Ramla, an archaic hominin with a questionable taxonomy. We found that PCA outcomes are artefacts of the input data and are neither reliable, robust, nor reproducible as field members may assume. We also found that supervised machine learning classifiers are more accurate both for classification and detecting new taxa. Our findings raise concerns about PCA-based findings applied in 18,400 to 35,200 Physical anthropology studies. Our work can be used to evaluate prior and novel claims concerning the origins and relatedness of inter- and intra-species and improve phylogenetic and taxonomic reconstructions.
The Role of Attention in Multi Attribute Decision Making
Authors: Sampson Aaron , Yang You-Ping , Usher Marius , Levy Dino , Niebur Ernst , Stuphorn Veit
Published: December 2023

Real-life decisions typically involve multiple options, each with multiple attributes affecting value. In such complex cases, sequential shifts of attention to specific options and attributes are thought to guide the decision process. We designed a task that allowed us to monitor attention in monkeys engaged in such multi-attribute decisions. We recorded pre-supplementary motor area neurons encoding action value signals reflecting the decision process. Attention guides this process through two mechanisms. First, attention enhances the activity of neurons representing the currently sampled option, independent of the attended option value. Second, attention up-regulates the gain of information integration towards the evolving value estimate for the attended option. In contrast, we found no evidence for a third suggested mechanism, in which only the attended option is represented. Instead, attention influences the ongoing information accumulation and competition between the options by modulating the strength of the value information that drives this circuit.
Time-dependent thermodynamic relationships for a Brownian particle that walks in a complex network
Authors: Taye Mesfin Asfaw
Published: December 2023

The thermodynamics feature of systems that are driven out of equilibrium is explored forMBrownian ratchets that are arranged in a complex network. The exact time-dependent solution depicts that as the network size increases, the entropyS, entropy productionep(t), and entropy extractionhd(t) of the system step up which is feasible since these thermodynamic quantities exhibit an extensive property. In other words, as the number of lattice size increases, the entropyS, entropy productionep(t), and entropy extractionhd(t) step up revealing that these complex networks can not be reduced into the corresponding one-dimensional lattice. On the contrary, the rate for thermodynamic relations such as the velocity V, entropy production rateėp(t) and entropy extraction ratebecome independent of the network size in the long time limit. The exact analytic result also shows that the free energy decreases with the system size. The model system is further analyzed by including heat transfer via kinetic energy. Since the heat exchange via kinetic energy does not affect the energy extraction rate, the heat dumped to the cold reservoirs contributes only to the internal entropy production. As the result, such systems exhibit a higher degree of irreversibility. The thermodynamic features of a system that operates between hot and cold baths are also compared and contrasted with a system that operates in a heat bath where its temperature varies linearly along the reaction coordinate. Regardless of the network arrangements, the entropy, entropy production, and extraction rates are considerably larger for the linearly varying temperature case than a system that operates between hot and cold baths.

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A two-step mechanism for creating stable, condensed chromatin by the Polycomb complex PRC1
Authors: Seif Elias , Francis Nicole J.
Published: December 2023

TheDrosophilaPRC1 complex regulates gene expression by modifying histone proteins and chromatin architecture. Two PRC1 subunits, PSC and Ph, are most implicated in chromatin architecture. In vitro, PRC1 compacts chromatin and inhibits transcription and nucleosome remodeling. The long disordered C-terminal region of PSC (PSC-CTR) is important for these activities, while Ph has little effect. In cells, Ph is important for condensate formation, long range chromatin interactions, and gene regulation, and its polymerizing Sterile alpha motif (SAM) is implicated in these activities. In vitro, truncated Ph containing the SAM and two other conserved domains (mini-Ph) undergoes phase separation with chromatin, suggesting a mechanism for SAM-dependent condensate formation in vivo. How the distinct activities of PSC and Ph on chromatin function together in PRC1 is not known. To address this question, we analyzed structures formed with large chromatin templates and PRC1 in vitro. PRC1 bridges chromatin into extensive fibrillar networks. Ph, its SAM, and SAM polymerization activity have little effect on these structures. Instead, the PSC-CTR controls their growth, and is sufficient for their formation. To understand how phase separation driven by Ph SAM intersects with the chromatin bridging activity of the PSC-CTR, we used mini-Ph to form condensates with chromatin and then challenged them with PRC1 lacking Ph (PRC1ΔPh). PRC1ΔPh converts mini-Ph chromatin condensates into clusters of small non-fusing condensates and bridged fibers. These condensates retain a high level of chromatin compaction and do not intermix. Thus, phase separation of chromatin by mini-Ph, followed by the action of the PSC-CTR creates a unique chromatin organization with regions of high nucleosome density and extraordinary stability. We discuss how this coordinated sequential activity of two proteins found in the same complex may occur and the possible implications of stable chromatin architectures in maintaining transcription states.
Stimulus selection influences prediction of individual phenotypes in naturalistic conditions
Authors: Li Xuan , Eickhoff Simon B. , Weis Susanne
Published: December 2023

Understanding individual differences and brain-behaviour relationships is an essential goal of human neuroscience. Recent studies have shown the great potential of naturalistic stimuli, e.g., movie clips, in advancing this pursuit. While the use of naturalistic stimuli attracts increasing interest, the influence of stimulus selection remains largely unclear. In this study, we show that brain activity is generally sensitive to the choice of movie stimuli at both group and individual subject levels. Using sex classification as an example, we demonstrate that brain activity elicited by different stimuli can lead to distinct prediction performance and unique predictive features. The stimuli that yield better classification performance often elicit stronger synchrony of brain activity across all subjects and are mostly derived from Hollywood films with rich social content and cohesive narratives. Our results highlight the importance of stimulus selection and provide practical guidance for choosing appropriate stimuli, opening up new avenues for future studies on individual differences and brain-behaviour relationships.
Carbon usage in yellow-fleshedManihot esculentastorage roots shifts from starch biosynthesis to cell wall and raffinose biosynthesis via themyo-inositol pathway
Authors: Gutschker Sindy , Ruescher David , Rabbi Ismail Y. , Rosado-Souza Laise , Pommerrenig Benjamin , van Doorn Anna M. , Schlereth Armin , Neuhaus H. Ekkehard , Fernie Alisdair R. , Reinert Stephan , Sonnewald Uwe , Zierer Wolfgang
Published: December 2023

Cassava is a crucial staple crop for smallholder farmers in tropical Asia and Sub-Saharan Africa. Although high yield remains the top priority for farmers, the significance of nutritional values has increased in cassava breeding programs. A notable negative correlation between provitamin A and starch accumulation poses a significant challenge for breeding efforts. The negative correlation between starch and carotenoid levels in conventional and genetically modified cassava plants implies the absence of a direct genomic connection between the two traits. The competition among various carbon pathways seems to account for this relationship. In this study, we conducted a thorough analysis of 49 African cassava genotypes with varying levels of starch and provitamin A. Our goal was to identify factors contributing to differential starch accumulation. With the carotenoid levels of the varieties considered as a confounding effect on starch production, we found that yellow and white-fleshed storage roots did not differ significantly in most measured components of starch or de novo fatty acid biosynthesis. However, genes and metabolites associated with myo-inositol synthesis and cell wall component production were substantially enriched in high provitamin A genotypes. These results indicate that yellow-fleshed cultivars, in comparison to their white-fleshed counterparts, direct more carbon towards the synthesis of raffinose and cell wall components, a finding that is supported by a significant rise in the starch-free residue to total dry yield ratio in yellow storage roots versus white storage roots. Our findings enhance comprehension of the biosynthesis of starch and carotenoids in the storage roots of cassava.
Brain-wide topographic coordination of traveling spiral waves
Authors: Ye Zhiwen , Bull Matthew S. , Li Anna , Birman Daniel , Daigle Tanya L. , Tasic Bosiljka , Zeng Hongkui , Steinmetz Nicholas A.
Published: December 2023

Traveling waves of activity are a prevalent phenomenon within neural networks of diverse brain regions and species1–4, and have been implicated in myriad brain functions including sensory perception5–8, memory9, spatial navigation10–12and motor control13,14. However, the anatomical basis for these waves, and whether they are locally confined versus distributed across the brain, remains unclear. Here we use cortex-wide imaging and large-scale electrophysiology in awake mice to reveal the organization of traveling waves across spatial scales. Traveling waves formed spiral patterns predominantly centered on somatosensory cortex. Strikingly, the local axonal architecture of neurons in sensory cortex exhibited a matching circular arrangement. At the cortex-wide scale, these spiral waves were mirrored between hemispheres and between sensory and motor cortex, reflecting topographic long-range axons. Finally, at the brain-wide scale, cortical spiral waves were coordinated with subcortical spiking patterns in the thalamus, striatum and midbrain. These results establish that traveling waves are structured by axonal pathways and globally impact neural activity across diverse brain systems.