bluuebunny/crossref_metadata_2025 huggingface dataset:
Using a real-world network to model the tradeoff between stay-at-home restriction, vaccination, social distancing and working hours on COVID-19 dynamics
Authors: Nashebi Ramin , Sari Murat , Kotil Seyfullah
Published: April 2022

Background

Human behavior, economic activity, vaccination, and social distancing are inseparably entangled in epidemic management. This study aims to investigate the effects of various parameters such as stay-at-home restrictions, work hours, vaccination and social distance on the containment of pandemics such as COVID-19.

Methods

To achieve this, we developed an agent-based model based on a time-dynamic graph with stochastic transmission events. The graph is constructed from a real-world social network. The graph’s edges have been categorized into three categories: home, workplaces, and social environment. The conditions needed to mitigate the spread of wild-type (WT) COVID-19 and the delta variant have been analyzed. Our purposeful agent-based model has carefully executed tens of thousands of individual-based simulations. We propose simple relationships for the trade-offs between effective reproduction number (Re), transmission rate, work hours, vaccination, and stay at home restrictions.

Results

For the WT, it has been found that a 13% increase in vaccination impacts the reproduction number, like the magnitude of decreasing nine hours of work to four and a single day of stay-at-home order. For the delta, 16% vaccination has the same effect. Also, since we can keep track of household and non-household infections, we observed that the change in household transmission rate does not significantly alter theRe. Household infections are not limited by transmission rate due to the high frequency of connections. For COVID-19’s specifications, theRedepends on the non-household transmissions rate.

Conclusions

All measures are worth considering. Vaccination and transmission reduction are almost interchangeable. Without vaccination or teaching people how to lower their transmission probability significantly, changing work hours or weekend restrictions will only make people more frustrated
Effectiveness of ChAdOx1 nCoV-19 Corona Virus Vaccine (Covishield™) in preventing SARS-CoV2 infection, Chennai, Tamil Nadu, India, 2021
Authors: Murali Sharan , Sakthivel Manikandanesan , P Kamaraj , Venkataswamy Vettrichelvan , Thangaraj Jeromie Wesley Vivian , Shete Anita , John Alby , Arjun Jaganathan , C P Girish Kumar , Yadav Pragya D , Sahay Rima , Majumdar Triparna , Dhudhmal Manisha , Sivalingam Azhagendran , D Sudha Rani , D Augustine , R Vijayaprabha , M Murali Mohan , A Suresh , M Punita , G Elavarasu , C Prabhakaran , S Dhana Priya Vadhani , M Prakash , P Ezhil , Parasuraman Ganeshkumar , M Jagadeesan , Narnaware Manish S , Bedi Gagandeep Singh , Kaur Prabhdeep , Murhekar Manoj V
Published: April 2022

Background

India experienced the second wave of the COVID-19 pandemic in March 2021, driven by the delta variant. Apprehensions around the usefulness of vaccines against delta variant posed a risk to the vaccination program. Therefore, we estimated the effectiveness of two doses of the ChAdOx1 nCoV-19 (Covishield) vaccine against COVID-19 infection among individuals ≥45 years in Chennai, India.

Methods

A community-based cohort study was conducted from May to September 2021 in a selected geographic area in Chennai, Tamil Nadu. The estimated sample size was 10,232. We enumerated individuals from all eligible households and periodically updated vaccination and COVID-19 infection data. We computed vaccine effectiveness with its 95% confidence interval for two doses of the Covishield vaccine against any COVID-19 infection.

Results

We enrolled 69,435 individuals, of which 21,793 were above 45 years. Two dose coverage of Covishield in the 18+ and 45+ age group was 18% and 31%, respectively. The overall incidence of COVID-19 infection was 1099 per 100,000 population. The vaccine effectiveness against COVID-19 disease in the ≥45 age group was 61.3% (95% CI: 43.6 - 73.4) at least two weeks after receiving the second dose of Covishield. Genomic analysis of 74 (28 with two doses, 15 with one dose, and 31 with zero dose) out of the 90 aliquots collected from the 303 COVID-19 positive individuals in the 45+ age group showed delta variants and their sub-lineages.

Conclusion

We demonstrated the effectiveness of two doses of the ChAdOx1 vaccine against the delta variant in the general population of Chennai. We recommend similar future studies considering emerging variants and newer vaccines. Two-dose vaccine coverage could be ensured to protect against COVID-19 infection.
A needle in a haystack: metagenomic DNA sequencing to quantify Mycobacterium tuberculosis DNA and diagnose tuberculosis
Authors: Chang Adrienne , Mzava Omary , Kounatse Liz-Audrey Djomnang , Lenz Joan , Burnham Philip , Kaplinsky Peter , Andama Alfred , Connelly John , Bachman Christine M. , Cattamanchi Adithya , Steadman Amy , De Vlaminck Iwijn
Published: April 2022

Background

Tuberculosis (TB) remains a significant cause of mortality worldwide. Metagenomic next-generation sequencing has the potential to reveal biomarkers of active disease, identify coinfection, and improve detection for sputum-scarce or culture-negative cases.

Methods

We conducted a large-scale comparative study of 427 plasma, urine, and oral swab samples from 334 individuals from TB endemic and non-endemic regions to evaluate the utility of a shotgun metagenomic DNA sequencing assay for tuberculosis diagnosis.

Findings

We found that the choice of a negative, non-TB control cohort had a strong impact on the measured performance of the diagnostic test: the use of a control patient cohort from a nonendemic region led to a test with nearly 100% specificity and sensitivity, whereas controls from TB endemic regions exhibited a high background of nontuberculous mycobacterial DNA, limiting the diagnostic performance of the test. Using mathematical modeling and quantitative comparisons to matched qPCR data, we found that the burden of Mycobacterium tuberculosis DNA constitutes a very small fraction (0.04 or less) of the total abundance of DNA originating from mycobacteria in samples from TB endemic regions.

Interpretation

Our findings suggest that the utility of a metagenomic sequencing assay for tuberculosis diagnostics is limited by the low burden of M. tuberculosis in extrapulmonary sites and an overwhelming biological background of nontuberculous mycobacterial DNA.

Funding

This work was supported by the National Institutes of Health, the Rainin Foundation, the National Science Foundation, and the Bill and Melinda Gates Foundation.
Effectiveness of COVID-19 mRNA vaccine booster dose relative to primary series during a period of Omicron circulation
Authors: Petrie Joshua G. , King Jennifer P. , McClure David L. , Rolfes Melissa A. , Meece Jennifer K. , Belongia Edward A. , McLean Huong Q.
Published: April 2022

During a period of Omicron variant circulation, we estimated relative VE of COVID-19 mRNA booster vaccination versus primary two-dose series in an ongoing community cohort. Relative VE was 66% (95% CI: 46%, 79%) favoring the booster dose compared to primary series vaccination. Our results support current booster recommendations.
COVID-19 relevant genetic variants confirmed in an admixed population
Authors: Texis Tomas , Luis Cruz-Jaramilllo José , García-Muñoz Willebaldo , Anzures-Cortés Lourdes , Haddad-Talancón Lorenza , Sánchez-García Sergio , del Carmen Jiménez Martínez María , Pérez Barragán Edgar , Nieto-Patlán Alejandro , Martínez-Ezquerro José D. , Rubio-Carrasco Kenneth , Rodríguez-Dorantes Mauricio , Cortés-Ramírez Sergio , Mellado-Sánchez Gabriela , Pérez-Tapia Sonia Mayra , Gonzalez-Covarrubias Vanessa
Published: April 2022

The dissection of factors that contribute to COVID-19 infection and severity has overwhelmed the scientific community for almost 2 years. Current reports highlight the role of in disease incidence, progression, and severity. Here, we aimed to confirm the presence of previously reported genetic variants in an admixed population. Allele frequencies were assessed and compared between the general population (N=3079) for which at least 30% have not been infected with SARS-CoV2 as per July 2021 versus COVID-19 patients (N=106).

Genotyping data from the Illumina GSA array was used to impute genetic variation for 14 COVID-relevant genes, using the 1000G phase 3 as reference based on the human genome assembly hg19, following current standard protocols and recommendations for genetic imputation. Bioinformatic and statistical analyses were performed using MACH v1.0, R, and PLINK.

A total of 7953 variants were imputed on, ABO, CCR2, CCR9, CXCR6, DPP9, FYCO1, IL10RB/IFNAR2, LZTFL1, OAS1, OAS2, OAS3, SLC6A20, TYK2, and XCR1. Statistically significant allele differences were reported for 10 and 7 previously identified and confirmed variants, ABO rs657152, DPP9 rs2109069, LZTFL1 rs11385942, OAS1 rs10774671, OAS1 rs2660, OAS2 rs1293767, and OAS3 rs1859330 p<0.03. In addition, we identified 842 variants in these COVID-related genes with significant allele frequency differences between COVID patients and the general population (p-value <E-2 – E-179).

Our observations confirm the presence of genetic differences in COVID-19 patients in an admixed population and prompts for the investigation of the statistical relevance of additional variants on these and other genes that could identify local and geographical patterns of COVID-19.
Estimation of cochlear frequency selectivity using a convolution model of forward-masked compound action potentials
Authors: Deloche François , Parida Satyabrata , Sivaprakasam Andrew , Heinz Michael G.
Published: April 2022

Frequency selectivity is a fundamental property of the peripheral auditory system; however, the invasiveness of auditory nerve (AN) experiments limits its study in the human ear. Compound action potentials (CAPs) associated with forward-masking have been suggested as an alternative means to assess cochlear frequency selectivity. Previous methods relied on an empirical comparison of AN and CAP tuning curves in animal models, arguably not taking full advantage of the information contained in forward-masked CAPs. In this work, we seek to provide a direct estimate of the quality factor characterizing AN frequency tuning using many forward-masked CAP responses. The method is based on a convolution model of the CAP that takes into account the masking of AN populations induced by notched-noise maskers with various notch widths and attenuations. The model produces masking patterns that, once convolved by a unitary response, predict forward-masked CAP waveforms. Model parameters, including those characterizing frequency selectivity, are fine-tuned by minimizing waveform prediction errors across the different masking conditions, yielding robust estimates. The method was applied to click-evoked CAPs at the round window of anesthetized chinchillas. The estimated quality factor Q10 as a function of center frequency is shown to closely match the average quality factor obtained from AN-fiber tuning curves, without the need for an empirical correction factor. Beyond the estimation of frequency selectivity, the proposed model proves to be accurate in predicting forward-masked CAP responses, and therefore could be extended to study more complex aspects of cochlear signal processing using a similar experimental approach.
Odorant representations indicate nonlinear processing across the olfactory system
Authors: Olivares Jesús , Orio Patricio , Sadílek Viktor , Schmachtenberg Oliver , Canales-Johnson Andrés
Published: April 2022

The brain’s recurrent connectivity supports both oscillatory and non-oscillatory neural activities that coordinate temporally across regions. Understanding how these dynamics contribute to the processing and transmission of olfactory information remains unclear, especially across distributed networks in the olfactory system. In this study, we investigate whether odorant identity can be distinguished through nonlinear interactions in the local field potentials (LFPs) of the olfactory bulb and telencephalic regions (Vv and Dp) in rainbow trout. Our results show that odorant identity modulates complex information-theoretic metrics, specifically information sharing and redundancy, across these brain areas, indicating nonlinear processing. In contrast, traditional linear connectivity measures, such as coherence and phase synchrony, showed little or no significant modulation by odorants. These findings suggest that nonlinear interactions encoded by olfactory oscillations carry crucial odor information across the teleost olfactory system, offering insights into the broader role of nonlinear dynamics in sensory processing.
Immediate neural network impact after the loss of a semantic hub
Authors: Kocsis Zsuzsanna , Jenison Rick L. , Cope Thomas E. , Taylor Peter N. , Calmus Ryan M. , McMurray Bob , Rhone Ariane E. , Sarrett McCall E. , Kikuchi Yukiko , Gander Phillip E. , Berger Joel I. , Kovach Christopher K. , Choi Inyong , Greenlee Jeremy D. , Kawasaki Hiroto , Griffiths Timothy D. , Howard Matthew A. , Petkov Christopher I.
Published: April 2022

The human brain extracts meaning from the world using an extensive neural system for semantic knowledge. Whether such broadly distributed systems1–3crucially depend on or can compensate for the loss of one of their highly interconnected hubs4–6is controversial4. The strongest level of causal evidence for the role of a brain hub is to evaluate its acute network-level impact following disconnection and any rapid functional compensation that ensues. We report rare neurophysiological data from two patients who underwent awake intracranial recordings during a speech prediction task immediately before and after neurosurgical treatment that required disconnection of the left anterior temporal lobe (ATL), a crucial hub for semantic knowledge4–6. Informed by a predictive coding framework, we tested three sets of hypotheses includingdiaschisiscausing disruption in interconnected sites7andincompleteorcomplete compensationby other language-critical and speech processing sites8–10. Immediately after ATL disconnection, we observed highly specific neurophysiological alterations in the recorded fronto-temporal network, including abnormally magnified high gamma responses to the speech sounds in auditory cortex. We also observed evidence for rapid compensation, seen as focal increases in effective connectivity involving language-critical sites in the inferior frontal gyrus and speech processing sites in auditory cortex. However, compensation was incomplete, in part because after ATL disconnection speech prediction signals were depleted in auditory cortex. This study provides direct causal evidence for a semantic hub in the human brain and shows striking neural impact and a rapid attempt at compensation in a neural network after the loss of one of its hubs.
Structure of the Dengue Virus RNA Promoter
Authors: Sun Yi-Ting , Varani Gabriele
Published: April 2022

Dengue virus, a single-stranded positive sense RNA virus, is the most prevalent mosquito-borne pathogen in the world. Like all RNA viruses, it uses conserved structural elements within its genome to control essential replicative steps. A 70 nucleotides stem-loop RNA structure (called SLA) found at the 5’-end of the genome of all flaviviruses, functions as the promoter for viral replication. This highly conserved structure interacts with the viral polymerase NS5 to initiate RNA synthesis. Here we report the NMR structure of a monomeric SLA from Dengue virus serotype 1, assembled to high-resolution from independently folded structural elements. The DENV1 SLA has an L-shape structure, where the top and side helices are coaxially-stacked and the bottom helix is roughly perpendicular to them. Because the sequence is highly conserved among different flavivirus genomes, it is likely that the three-dimensional fold and local structure of SLA are also conserved among flaviviruses and required for efficient replication. This work provides structural insight into the Dengue promoter and provides the foundation for the discovery of new antiviral drugs that target this essential replicative step.
The rhizodynamics robot: Automated imaging system for studying long-term dynamic root growth
Authors: McCaskey Erin , Taylor Isaiah , Pierce Christopher , Ligon Jason , Aydin Enes , Hunner Carrie , Carmichael Amanda , Eserman Lauren , Coffey Emily E.D. , Benfey Philip N , Goldman Daniel I
Published: April 2022

The study of plant root growth in real time has been difficult to achieve in an automated, high-throughput, and systematic fashion. Dynamic imaging of plant roots is important in order to discover novel root growth behaviors and to deepen our understanding of how roots interact with their environments. We designed and implemented the Generating Rhizodynamic Observations Over Time (GROOT) robot, an automated, high-throughput imaging system that enables time-lapse imaging of 90 containers of plants and their roots growing in a clear gel medium over the duration of weeks to months. The system uses low-cost, widely available materials. As a proof of concept, we employed GROOT to collect images of orchid root growth of multiple species over six months. Beyond imaging plant roots, our system is highly customizable and can be used to collect time-lapse image data of different container sizes and configurations regardless of what is being imaged, making it applicable to many fields that require longitudinal time-lapse recording.
Triglyceride lipolysis driven by glucose restriction triggers liquid-crystalline phase transitions and proteome remodeling of lipid droplets
Authors: Rogers Sean , Gui Long , Kovalenko Anastasiia , Zoni Valeria , Carpentier Maxime , Ramji Kamran , Ben Mbarek Kalthoum , Bacle Amelie , Fuchs Patrick , Campomanes Pablo , Reetz Evan , Speer Natalie Ortiz , Reynolds Emma , Thiam Abdou Rachid , Vanni Stefano , Nicastro Daniela , Henne W. Mike
Published: April 2022

Lipid droplets (LDs) are reservoirs for triglycerides (TGs) and sterol-esters (SEs), but how these lipids are organized within LDs and influence its proteome remains unclear. Using in situ cryoelectron tomography, we show that glucose restriction triggers lipid phase transitions within LDs generating liquid-crystalline lattices inside them. Mechanistically this requires TG lipolysis, which decreases the LD TG:SE ratio, promoting SE transition to a liquid-crystalline phase. Molecular dynamics simulations reveal TG depletion promotes spontaneous TG and SE de-mixing in LDs, additionally altering the lipid packing of the phospholipid monolayer surface. Fluorescence imaging and proteomics further reveal that liquid-crystalline phases are associated with selective remodeling of the LD proteome. Some canonical LD proteins including Erg6 re-localize to the ER network, whereas others remain LD-associated. Model peptide LiveDrop also redistributes from LDs to the ER, suggesting liquid-crystalline-phases influence ER-LD inter organelle transport. Our data suggests glucose restriction drives TG mobilization, which alters the phase properties of LD lipids and selectively remodels the LD proteome.
Humoral signaling-mediated effects of unilateral brain injury: differences in the left-right sided afferent responses
Authors: Watanabe Hiroyuki , Kobikov Yaromir , Sarkisyan Daniil , Lavrov Igor , Schouenborg Jens , Zhang Mengliang , Bakalkin Georgy
Published: April 2022

Disruption of neural tracts descending from the brain to the spinal cord after brain trauma and stroke causes postural and sensorimotor deficits. We previously showed that unilateral lesion to the sensorimotor cortex in rats with completely transected thoracic spinal cord produced asymmetry in hindlimb posture and withdrawal reflexes. Supraspinal signals to hindlimb muscles may be transmitted through the paravertebral chain of sympathetic ganglia that remain intact after the transection. We here demonstrated that prior transection of the spinal cord at the cervical level that was rostrally to segments with preganglionic sympathetic neurons, did not abolish formation of asymmetry in hindlimb posture and musculo-articular resistance to stretch after unilateral brain injury. Thus not the sympathetic system but humoral signals may mediate the effects of brain injury on the lumbar spinal circuits. The asymmetric responses in rats with transected spinal cords were eliminated by bilateral lumbar dorsal rhizotomy after the left-side brain injury, but resistant to deafferentation after the right-side brain lesion. Two mechanisms, one dependent on and one independent of afferent input may account for asymmetric hindlimb motor responses. Resistance to deafferentation may be due to sustained stretch- and effort-unrelated muscle contractions that is often observed in patients with central lesions. Left-right asymmetry is unusual feature of these mechanisms that both are activated by humoral signals.

Graphical Abstract
A python-based package for long-lasting video acquisition and semi-automated detection of convulsive seizures in rodents
Authors: Diaz-Arce Daniel , Ghouma Anis , Scalmani Paolo , Mantegazza Massimo , Duprat Fabrice
Published: April 2022

Background

Epilepsy is a very invalidating pathology characterized by the unpredictable appearance of abnormal cerebral activity leading to seizures and co-morbidities. The ability to detect and even predict seizures is a major challenge and many research laboratories are using rodents’ models of epilepsy to unravel possible mechanisms. The gold standard to record and detect seizures is electroencephalography, but it is very invasive. For rodents used in research, video analysis is a very interesting approach but the major disadvantages are that it is time consuming, prone to human error, and not very reproducible. Commercial solutions for detailed phenotyping analysis on humans or rodents exist but they are costly. Some open source software programs are also available, they provide very interesting and precise behavior data, but none of them are made for high throughput analysis of a large number of video files generated by long lasting recordings.

New method

We developed an open-source python-based package of two software programs that enable automated video acquisition and simple motion analysis associated with a spectral power analysis, which enable a semi-automated identification of convulsive seizures. The method needs cheap webcams and a computer or a server.

Results

Using two murine epilepsy models (Nav1.1 mutations), we have compared our motion analysis software to human visual inspection and found an 88.8% accuracy in convulsive seizures detection. We then compare our method to the gold standard electrocorticogram analysis and found a 93.2% accuracy. The motion analysis is also interesting to get a readout of the animal activity without the invasiveness of electromyogram recordings.

Conclusions

This new method is easy to use, cost-effective and allows: 1) detection of convulsive seizures in a noninvasive way, 2) high speed analysis of a large number of video files with a good accuracy, and 3) automated acquisition and semi-automated analysis of a very large number of files.

Highlights

Noninvasive semi-automated detection of convulsive seizures from videos

High speed of analysis with a good accuracy

Ability to acquire and analyze a very large number of files

Easy to use graphical interfaces

Cost-effective setup
Resource sharing leads to the emergence of division of labour
Authors: Kreider Jan J. , Janzen Thijs , Bernadou Abel , Elsner Daniel , Kramer Boris H. , Weissing Franz J.
Published: April 2022

Division of labour occurs in a broad range of organisms. Yet, how division of labour can emerge in the absence of pre-existing interindividual differences is poorly understood. Using a simple but realistic model, we show that in a group of initially identical individuals, division of labour emerges spontaneously if returning foragers share part of their resources with other group members. In the absence of resource sharing, individuals follow an activity schedule of alternating between foraging and other tasks. If non-foraging individuals are fed by other individuals, their alternating activity schedule becomes interrupted, leading to task specialisation and the emergence of division of labour. Furthermore, nutritional differences between individuals reinforce division of labour. Such differences can be caused by increased metabolic rates during foraging or by dominance interactions during resource sharing. Our model proposes a plausible mechanism for the self-organised emergence of division of labour in animal groups of initially identical individuals. This mechanism could also play a role for the emergence of division of labour during the major evolutionary transitions to eusociality and multicellularity.
Loss of PRMT2 in myeloid cells in normoglycemic mice phenocopies impaired regression of atherosclerosis in diabetic mice
Authors: Vurusaner Beyza , Thevkar-Nages Prashanth , Kaur Ravneet , Giannarelli Chiara , Garabedian Michael J. , Fisher Edward A.
Published: April 2022

Regression of atherosclerosis is impaired in diabetes. However, the factors mediating this effect remain incomplete. We identified Protein Arginine Methyltransferase 2 (PRMT2) as a protein whose expression in macrophages is reduced in hyperglycemia and diabetes. PRMT2 catalyzes arginine methylation to target proteins to modulate gene expression. Because PRMT2 expression is reduced in cells in hyperglycemia, we wanted to determine whether PRMT2 plays a causal role in the impairment of atherosclerosis regression in diabetes. We therefore examined the consequence of deleting PRMT2 in myeloid cells during regression of atherosclerosis in normal and diabetic mice. Remarkably, we found a significant impairment of atherosclerosis regression under normoglycemic conditions in mice lacking PRMT2 (Prmt2-/-) in myeloid cells that mimics the decrease in regression of atherosclerosis in WT mice under diabetic conditions. This was associated with increased plaque macrophage retention, as well as increased apoptosis and necrosis. PRMT2-deficient plaque CD68+ cells under normoglycemic conditions showed increased expression of genes involved in cytokine signaling and inflammation compared to WT. Consistently Prmt2-/- bone marrow derived macrophages (BMDMs) showed an increased response of pro-inflammatory genes to LPS, and a decreased response of inflammation resolving genes to IL-4. This increased response to LPS in Prmt2-/- BMDMs is via enhanced NF-kappa B activity. Thus, the loss of PRMT2 is causally linked to impaired atherosclerosis regression via a heightened inflammatory response in macrophages. That PRMT2 expression was lower in myeloid cells in plaques from human subjects with diabetes supports the relevance of our findings to human atherosclerosis.
Bayesian interpolation for power laws in neural data analysis
Authors: Davidovich Iván A. , Roudi Yasser
Published: April 2022

Power laws arise in a variety of phenomena ranging from matter undergoing phase transition to the distribution of word frequencies in the English language. Usually, their presence is only apparent when data is abundant, and accurately determining their exponents often requires even larger amounts of data. As the scale of recordings in neuroscience becomes larger, an increasing number of studies attempt to characterise potential power-law relationships in neural data. In this paper, we aim to discuss the potential pitfalls that one faces in such efforts and to promote a Bayesian interpolation framework for this purpose. We apply this framework to synthetic data and to data from a recent study of large-scale recordings in mouse primary visual cortex (V1), where the exponent of a powerlaw scaling in the data played an important role: its value was argued to determine whether the population’s stimulus-response relationship is smooth, and experimental data was provided to confirm that this is indeed so. Our analysis shows that with such data types and sizes as we consider here, the best-fit values found for the parameters of the power law and the uncertainty for these estimates are heavily dependent on the noise model assumed for the estimation, the range of the data chosen, and (with all other things being equal) the particular recordings. It is thus challenging to offer a reliable statement about the exponents of the power law. Our analysis, however, shows that this does not affect the conclusions regarding the smoothness of the population response to low-dimensional stimuli but casts doubt on those to natural images. We discuss the implications of this result for the neural code in the V1 and offer the approach discussed here as a framework that future studies, perhaps exploring larger ranges of data, can employ as their starting point to examine power-law scalings in neural data.
Prescribed fire selects for a pyrophilous soil subcommunity in a northern California mixed conifer forest
Authors: Fischer Monika S. , Patel Neem J. , de Lorimier Phillip J. , Traxler Matthew F.
Published: April 2022

Low intensity prescribed fire is a critical strategy for mitigating the effects of catastrophic wildfires. The above-ground response to fire has been well-documented, including many ecosystem benefits associated with prescribed burning, but fewer studies have directly addressed the effect of prescribed fire on soil organisms. We aimed to understand how soil microbial communities respond to prescribed fire and to determine the ecological processes driving their dynamics. We extensively sampled four plots for 17 months in a mixed conifer forest in northern California, USA; immediately following a low-intensity prescribed fire, a higher-intensity prescribed fire, and two no-burn control plots. We found that prescribed fire significantly altered the community structure for both fungi (ITS) and bacteria (16S), which was sustained throughout the time-series. By comparing our community profiling results with a model of neutral community assembly, we found that the presence of most taxa across all experimental conditions could be explained by neutral processes. However, combining threshold indicator taxa analysis and correlation network analysis with the neutral model identified a cohort of taxa that responded deterministically to prescribed fire. The subcommunity identified through this series of analyses includes both known and new pyrophilous taxa. Beyond this, our analyses revealed network modules within postfire communities which were responsive to fire-intensity. Taken together, these results lay the foundation for building a process-driven understanding of microbial community assembly in the context of the classical disturbance regime of fire.
Visual working memory recruits two functionally distinct alpha rhythms in posterior cortex
Authors: Rodriguez-Larios Julio , ElShafei Alma , Wiehe Melanie , Haegens Saskia
Published: April 2022

Oscillatory activity in the human brain is dominated by posterior alpha oscillations (8-14 Hz), which have been shown to be functionally relevant in a wide variety of cognitive tasks. Although posterior alpha oscillations are commonly considered a single oscillator anchored at an individual alpha frequency (IAF; ∼10 Hz), previous work suggests that IAF reflects a spatial mixture of different brain rhythms. In this study, we assess whether Independent Component Analysis (ICA) can disentangle functionally distinct posterior alpha rhythms in the context of visual short-term memory retention. Magnetoencephalography (MEG) was recorded in 33 subjects while performing a visual working memory task. Group analysis at sensor level suggested the existence of a single posterior alpha oscillator that increases in power and decreases in frequency during memory retention. Conversely, single-subject analysis of independent components revealed the existence of two dissociable alpha rhythms: one that increases in power during memory retention (Alpha1) and another one that decreases in power (Alpha2). Alpha1 and Alpha2 rhythms were differentially modulated by the presence of visual distractors (Alpha1 increased in power while Alpha2 decreased) and had an opposite relationship with accuracy (positive for Alpha1 and negative for Alpha2). In addition, Alpha1 rhythms showed a lower peak frequency, a narrower peak width, a greater relative peak amplitude and a more central source than Alpha2 rhythms. Together, our results demonstrate that modulations in posterior alpha oscillations during short-term memory retention reflect the dynamics of at least two distinct brain rhythms with different functions and spatiospectral characteristics.

Significance statement

Alpha oscillations are the most prominent feature of the human brain’s electrical activity, and consist of rhythmic neuronal activity in posterior parts of the cortex. Alpha is usually considered a single brain rhythm that changes in power and frequency to support cognitive operations. We here show that posterior alpha entails at least two dissociable rhythms with distinct functions and characteristics. These findings could solve previous inconsistencies in the literature regarding the direction of task-related alpha power/frequency modulations and their relation to cognitive performance. In addition, the existence of two distinct posterior alpha rhythms could have important consequences for the design of neurostimulation protocols aimed at modulating alpha oscillations and subsequently cognition.
Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation
Authors: Alavattam Kris G , Mitzelfelt Katie A , Bonora Giancarlo , Fields Paul A , Yang Xiulan , Chiu Han Sheng , Pabon Lil , Bertero Alessandro , Palpant Nathan J , Noble William S , Murry Charles E
Published: April 2022

Background

Vascular endothelial cells are a mesoderm-derived lineage with many essential functions, including angiogenesis and coagulation. However, the gene regulatory mechanisms that underpin endothelial specialization are largely unknown, as are the roles of 3D chromatin organization in regulating endothelial cell transcription.

Methods

To investigate the relationships between 3D chromatin organization and gene expression in endothelial cell differentiation, we induced endothelial cell differentiation from human pluripotent stem cells and performed Hi-C and RNA-seq assays at specific timepoints in differentiation.

Results

Our analyses reveal that long-range intrachromosomal contacts increase over the course of endothelial cell differentiation, as do genomic compartment transitions between active and inactive states. These compartmental states are tightly associated with endothelial transcription. Dynamic topologically associating domain (TAD) boundaries strengthen and converge on an endothelial cell state, and nascent TAD boundaries are linked to the expression of genes that support endothelial cell specification. Relatedly, chromatin pairwise point interactions (DNA loops) increase in frequency during differentiation and are linked to the expression of genes with essential roles in vascular biology, includingMECOM, TFPI, andKDR. To identify forms of regulation specific to endothelial cell differentiation, we compared the functional chromatin dynamics of endothelial cells with those of developing cardiomyocytes. Cardiomyocytes exhibit greater long-rangecisinteractions than endothelial cells, whereas endothelial cells have increased local intra-TAD interactions and much more abundant pairwise point interactions.

Conclusions

Genome topology changes dynamically during endothelial differentiation, including acquisition of long-rangecisinteractions and new TAD boundaries, interconversion of hetero- and euchromatin, and formation of DNA loops. These chromatin dynamics guide transcription in the development of endothelial cells and promote the divergence of endothelial cells from related cell types such as cardiomyocytes.
A Deep SE(3)-Equivariant Model for Learning Inverse Protein Folding
Authors: McPartlon Matt , Lai Ben , Xu Jinbo
Published: April 2022

In this work, we establish a framework to tackle the inverse protein design problem; the task of predicting a protein’s primary sequence given its backbone conformation. To this end, we develop a generative SE(3)-equivariant model which significantly improves upon existing autoregressive methods. Conditioned on backbone structure, and trained with our novel partial masking scheme and side-chain conformation loss, we achieve state-of-the-art native sequence recovery on structurally independent CASP13, CASP14, CATH4.2, and TS50 test sets. On top of accurately recovering native sequences, we demonstrate that our model captures functional aspects of the underlying protein by accurately predicting the effects of point mutations through testing on Deep Mutational Scanning datasets. We further verify the efficacy of our approach by comparing with recently proposed inverse protein folding methods and by rigorous ablation studies.
Theory of spontaneous persistent activity and inactivity in vivo reveals differential cortico-entorhinal functional connectivity
Authors: Choudhary Krishna , Berberich Sven , Hahn Thomas T. G. , Mehta Mayank R.
Published: April 2022

Persistent activity is thought to mediate working memory. While such stimulus evoked persistence is well studied, mechanisms of internally generated or spontaneous persistence in vivo are unknown. Further, current theories based on attractor dynamics focus on elevated activity as a memory substrate, while little attention has focused on the role of inactivity attractors. Here, we present a mean field model of functional interaction between large cortical networks that predicts both spontaneous persistent activity (SPA) and inactivity (SPI); the latter has never been seen before in experiments or models. We confirm these predictions using simultaneously recorded neocortical local field potential (LFP) and the membrane potential (Vm) of identified excitatory neurons from several brain areas in vivo during slow oscillations, especially from layer 3 of the medial (MECIII) and lateral entorhinal cortex (LECIII), which show SPA and SPI. By matching model and experimental statistics, we predict the relative strength of internal and external excitation in the LECIII and MECIII networks. Our predictions match anatomical data. Further, the model predicts, and the experiments confirm, that SPA and SPI are quantized by cortical UDS and follow the statistics of a history dependent Bernoulli process. These convergent, theory-experiment results thus reveal the differential nature of cortico-entorhinal functional connectivity, resulting in a unique pattern of persistent activity and persistent inactivity, a novel and energetically efficient memory substrate.
Deterministic Early Endosomal Maturations Emerge From a Stochastic Trigger-and-Convert Mechanism
Authors: York Harrison M , Joshi Kunaal , Wright Charles S , Kreplin Laura Z , Rodgers Samuel , Moorthi Ullhas K , Gandhi Hetvi , Patil Abhishek , Mitchell Christina , Iyer-Biswas Srividya , Arumugam Senthil
Published: April 2022

Endosomal maturation is critical for robust and timely cargo transport to specific cellular compartments. The most prominent model of early endosomal maturation involves phosphoinositide-driven gain or loss of specific proteins on individual endosomes, emphasising an autonomous and stochastic description. However, limitations in fast, volumetric imaging long hindered direct whole-cell measurements of absolute numbers of maturation events. Here, we use lattice light-sheet imaging and bespoke automated analysis to track individual very early (APPL1-positive) and early (EEA1-positive) endosomes over the entire population, demonstrating that direct interendosomal contact drives maturation. Using fluorescence lifetime, we show that this interaction is underpinned by asymmetric EEA1 binding to very early and early endosomes through its N- and C-termini, respectively. In combination with agent-based simulation that confirms a ‘trigger-and-convert’ model, our findings indicate that APPL1-to EEA1-positive maturation is driven not by autonomous events but by heterotypic EEA1-mediated interactions, providing a mechanism for temporal and population-level control of maturation.
Resilience to anxiety and anhedonia after predator scent stress is accompanied by increased nucleus accumbens mGlu5 in female rats
Authors: Blount H.L. , Dee J. , Wu L. , Schwendt M. , Knackstedt L.A.
Published: April 2022

Despite the higher prevalence of post-traumatic stress disorder (PTSD) in women, the majority of preclinical neuroscience research has been conducted utilizing male subjects. We have found that male rats exposed to the predator scent 2,4,5-trimethyl-3-thiazoline (TMT) show heterogenous development of long-term anxiety-like behavior and conditioned fear to the TMT environment. Stress-Resilient males exhibit increased mGlu5 mRNA expression in the basolateral amygdala (BLA) and prefrontal cortex. Here we sought to determine whether the same behavioral and genetic responses would be observed in female rats exposed to TMT. Sprague-Dawley rats were exposed to TMT for ten minutes, while Controls were exposed to an unscented environment. Anxiety and anhedonia were assessed 7-14 days later with elevated plus maze (EPM), acoustic startle response (ASR), light/dark box, and sucrose preference test. TMT-exposed females spent less time in the EPM open arms and exhibited greater startle amplitude, and reduced sucrose intake compared to Controls. Median split analyses conducted on EPM and sucrose intake yielded phenotypes that displayed behavior in the light/dark box consistent with EPM and sucrose testing. Unlike male Susceptible rats, female Susceptible rats showed no freezing when re-exposed to the TMT context, nor did Resilient female rats present elevated BLA mGlu5 mRNA levels. Instead, Susceptible females had greater BLA mGlu5 than Resilient or Control rats. This work indicates that, as in humans, rats exhibit sex-dependent responses to stress. This translational animal model may provide insight into how females are uniquely affected by PTSD.
Genomic underpinnings of population persistence in Isle Royale moose
Authors: Kyriazis Christopher C. , Beichman Annabel C. , Brzeski Kristin E. , Hoy Sarah R. , Peterson Rolf O. , Vucetich John A. , Vucetich Leah M. , Lohmueller Kirk E. , Wayne Robert K.
Published: April 2022

Island ecosystems provide models to assess the impacts of isolation on population persistence. However, most studies of persistence have focused on a single species, without comparisons to other organisms they interact with in the ecosystem. The simple predator-prey system of moose and gray wolves on Isle Royale provides allows a direct contrast of genetic variation in a prey species with their natural predator. Wolves on Isle Royale exhibited signs of severe inbreeding depression, which nearly drove the population to extinction in 2019. In the relative absence of wolves, the moose population has thrived and exhibits no obvious signs of inbreeding depression despite being isolated for ∼120 years and having low genetic diversity. Here, we examine the genomic underpinnings of population persistence in the Isle Royale moose population. We document high levels of inbreeding in the population, roughly as high as the wolf population at the time of its decline. However, inbreeding in the moose population manifests in the form of intermediate-length runs of homozygosity indicative of gradual inbreeding, contrasting with the severe recent inbreeding observed in the wolf population. Using simulations, we demonstrate that this more gradual inbreeding in the moose population has resulted in an estimated 50% purging of the inbreeding load, helping to explain the continued persistence of the population. However, we also document notable increases in genetic load, which could eventually threaten population viability over the long term. Finally, we document low diversity in mainland North American moose populations due to a severe founder event occurring near the end of the Holocene. Overall, our results demonstrate a complex relationship between inbreeding, genetic diversity, and population viability that highlights the importance of maintaining isolated populations at moderate size to avert extinction from genetic factors.

Significance statement

Isolated wildlife populations face a high risk of extinction due in part to the deleterious consequences of inbreeding. Whether purifying natural selection can overcome these negative impacts by “purging” harmful recessive mutations is a topic of active debate. We characterized the extent of purging in an isolated moose population. Our results demonstrate signatures of gradual inbreeding in the population, ideal circumstances to facilitate purging. Using simulations, we demonstrate substantial potential for purging in the population, though we also show that fitness is reduced by small population size and inbreeding. Our findings provide insight into the mechanisms enabling persistence in isolated populations, with implications for conserving the growing number of isolated populations worldwide.
Evaluation of Nav1.8 as a therapeutic target for Pitt Hopkins Syndrome
Authors: Martinowich Keri , Das Debamitra , Sripathy Srinidhi Rao , Maher Brady J.
Published: April 2022

Pitt Hopkins Syndrome (PTHS) is a rare syndromic form of autism spectrum disorder (ASD) caused by autosomal dominant mutations in the Transcription Factor 4 (TCF4) gene. TCF4 is a basic helix-loop-helix transcription factor that is critical for neurodevelopment and brain function through its binding to cis-regulatory elements of target genes. One potential therapeutic strategy for PTHS is to identify dysregulated target genes and normalize their dysfunction. Here, we propose that SCN10A is an important target gene of TCF4 that is an applicable therapeutic approach for PTHS. Scn10a encodes the voltage-gated sodium channel Nav1.8 and is consistently shown to be upregulated in PTHS mouse models. In this perspective, we review prior literature and present novel data that suggests inhibiting Nav1.8 in PTHS mouse models is effective at normalizing neuron function, brain circuit activity and behavioral abnormalities and posit this therapeutic approach as a treatment for PTHS.
A general framework for species-abundance distributions: linking traits and dispersal to explain commonness and rarity
Authors: Koffel Thomas , Umemura Kaito , Litchman Elena , Klausmeier Christopher A.
Published: April 2022

Species-abundance distributions (SADs) describe the spectrum of commonness and rarity in a community. Beyond the universal observation that most species are rare and only a few common, more-precise description of SAD shape is controversial. Furthermore, the mechanisms behind SADs and how they vary along environmental gradients remain unresolved. We lack a general non-neutral theory of SADs. Here we develop a trait-based framework, focusing on a local community coupled to the region by dispersal. The balance of immigration and exclusion determines abundances, which vary over orders-of-magnitude. Under stabilizing selection, the local trait-abundance distribution (TAD) reflects a transformation of the regional TAD. The left-tail of the SAD depends on scaling exponents of the exclusion function and the regional species pool. More-complex local dynamics can lead to multimodal TADs and SADs. Connecting SADs with trait-based ecological theory provides a way to generate more-testable hypotheses on the controls over commonness and rarity in communities.