bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the motion of S2 to constrain vector clouds around Sgr A*
Authors:   GRAVITY Collaboration, Foschi A , Abuter R , Abd El Dayem K , Aimar N , Amaro Seoane P , Amorim A , Berger J P , Bonnet H , Bourdarot G , Brandner W , Davies R , de Zeeuw P T , Defrère D , Dexter J , Drescher A , Eckart A , Eisenhauer F , Förster Schreiber N M , Garcia P J V , Genzel R , Gillessen S , Gomes T , Haubois X , Heißel G , Henning Th , Jochum L , Jocou L , Kaufer A , Kreidberg L , Lacour S , Lapeyrère V , Le Bouquin J -B , Léna P , Lutz D , Mang F , Millour F , Ott T , Paumard T , Perraut K , Perrin G , Pfuhl O , Rabien S , Ribeiro D C , Sadun Bordoni M , Scheithauer S , Shangguan J , Shimizu T , Stadler J , Straubmeier C , Sturm E , Subroweit M , Tacconi L J , Vincent F , von Fellenberg S , Woillez J
Published: March 2024

The dark compact object at the centre of the Milky Way is well established to be a supermassive black hole with mass $M_{\bullet } \sim 4.3 \times 10^6 \, {\rm M}_{\odot }$, but the nature of its environment is still under debate. In this work, we used astrometric and spectroscopic measurements of the motion of the star S2, one of the closest stars to the massive black hole, to determine an upper limit on an extended mass composed of a massive vector field around Sagittarius A*. For a vector with effective mass $10^{-19} \lesssim m_\mathrm{ s} \lesssim 10^{-18} \, \rm eV$, our Markov chain Monte Carlo analysis shows no evidence for such a cloud, placing an upper bound $M_{\rm cloud} \lesssim 0.1 \% \, M_{\bullet }$ at 3σ confidence level. We show that dynamical friction exerted by the medium on S2 motion plays no role in the analysis performed in this and previous works, and can be neglected thus.
Measurement of the photometric baryon acoustic oscillations with self-calibrated redshift distribution
Authors: Song Ruiyu , Chan Kwan Chuen , Xu Haojie , Zheng Weilun
Published: March 2024

We use a galaxy sample derived from the Dark Energy Camera Legacy Survey Data Release 9 to measure the baryonic acoustic oscillations (BAO). The magnitude-limited sample consists of 10.6 million galaxies in an area of 4974 deg2 over the redshift range of [0.6, 1]. A key novelty of this work is that the true redshift distribution of the photo-z sample is derived from the self-calibration method, which determines the true redshift distribution using the clustering information of the photometric data alone. Through the angular correlation function in four tomographic bins, we constrain the BAO scale dilation parameter α to be 1.025 ± 0.033, consistent with the fiducial Planck cosmology. Alternatively, the ratio between the comoving angular diameter distance and the sound horizon, DM/rs, is constrained to be 18.94 ± 0.61 at the effective redshift of 0.749. We corroborate our results with the true redshift distribution obtained from a weighted spectroscopic sample, finding very good agreement. We have conducted a series of tests to demonstrate the robustness of the measurement. Our work demonstrates that the self-calibration method can effectively constrain the true redshift distribution in cosmological applications, especially in the context of photometric BAO measurement.
Star formation histories of dwarf lenticular galaxies
Authors: Ann Hong Bae , Seo Mira
Published: March 2024

Star formation histories (SFHs) are essential for understanding galaxy formation and evolution. We present the mean SFHs of 148 dwarf lenticular galaxies (dS0s) derived from the Sloan Digital Sky Survey spectra. These SFHs reveal two distinct periods of active star formation. The first period, concluding approximately 6 Gyr ago, witnessed the formation of predominantly old, metal-poor (Z = 0.0004) stars, accounting for approximately 60 per cent of the stellar mass and 30 per cent of the luminosity. The scarcity of extremely metal-poor (Z = 0.0001) stars suggests pre-enrichment during the reionization era. Star formation gradually waned during this initial phase. In contrast, the second period, ending around 1 Gyr ago, exhibited a peak in the middle of the period, contributing to the formation of moderately old stellar populations with intermediate metallicity. The SFHs of dS0 galaxies show a clear dependence on stellar mass, with more massive dS0s forming stars earlier. However, we find no significant correlation with morphological properties such as outer spiral arms and nucleation. The SFHs of dS0 galaxies share many similarities with those of dwarf elliptical galaxies, suggesting a common origin, mostly not primordial.
Live-cell imaging of human apurinic/apyrimidinic endonuclease 1 in the nucleus and nucleolus using a chaperone@DNA probe
Authors: Cao Xiangjian , Zheng Jinghui , Zhang Ruilan , Sun Ying , Zhao Meiping
Published: March 2024

Human apurinic/apyrimidinic endonuclease 1 (APE1) plays crucial roles in repairing DNA damage and regulating RNA in the nucleus. However, direct visualization of nuclear APE1 in live cells remains challenging. Here, we report a chaperone@DNA probe for live-cell imaging of APE1 in the nucleus and nucleolus in real time. The probe is based on an assembly of phenylboronic acid modified avidin and biotin-labeled DNA containing an abasic site (named PB-ACP), which cleverly protects DNA from being nonspecifically destroyed while enabling targeted delivery of the probe to the nucleus. The PB-ACP construct specifically detects APE1 due to the high binding affinity of APE1 for both avidin and the abasic site in DNA. It is easy to prepare, biocompatible and allowing for long-term observation of APE1 activity. This molecular tool offers a powerful means to investigate the behavior of APE1 in the nuclei of various types of live cells, particularly for the development of improved cancer therapies targeting this protein.
PbARID-associated chromatin remodeling events are essential for gametocyte development in Plasmodium
Authors: Nishi Tsubasa , Kaneko Izumi , Iwanaga Shiroh , Yuda Masao
Published: March 2024

Gametocyte development of the Plasmodium parasite is a key step for transmission of the parasite. Male and female gametocytes are produced from a subpopulation of asexual blood-stage parasites, but the mechanisms that regulate the differentiation of sexual stages are still under investigation. In this study, we investigated the role of PbARID, a putative subunit of a SWI/SNF chromatin remodeling complex, in transcriptional regulation during the gametocyte development of P. berghei. PbARID expression starts in early gametocytes before the manifestation of male and female-specific features, and disruption of its gene results in the complete loss of gametocytes with detectable male features and the production of abnormal female gametocytes. ChIP-seq analysis of PbARID showed that it forms a complex with gSNF2, an ATPase subunit of the SWI/SNF chromatin remodeling complex, associating with the male cis-regulatory element, TGTCT. Further ChIP-seq of PbARID in gsnf2-knockout parasites revealed an association of PbARID with another cis-regulatory element, TGCACA. RIME and DNA-binding assays suggested that HDP1 is the transcription factor that recruits PbARID to the TGCACA motif. Our results indicated that PbARID could function in two chromatin remodeling events and paly essential roles in both male and female gametocyte development.
RNA polymerase SI3 domain modulates global transcriptional pausing and pause-site fluctuations
Authors: Bao Yu , Cao Xinyun , Landick Robert
Published: March 2024

Transcriptional pausing aids gene regulation by cellular RNA polymerases (RNAPs). A surface-exposed domain inserted into the catalytic trigger loop (TL) of Escherichia coli RNAP, called SI3, modulates pausing and is essential for growth. Here we describe a viable E. coli strain lacking SI3 enabled by a suppressor TL substitution (β′Ala941→Thr; ΔSI3*). ΔSI3* increased transcription rate in vitro relative to ΔSI3, possibly explaining its viability, but retained both positive and negative effects of ΔSI3 on pausing. ΔSI3* inhibited pauses stabilized by nascent RNA structures (pause hairpins; PHs) but enhanced other pauses. Using NET-seq, we found that ΔSI3*-enhanced pauses resemble the consensus elemental pause sequence whereas sequences at ΔSI3*-suppressed pauses, which exhibited greater association with PHs, were more divergent. ΔSI3*-suppressed pauses also were associated with apparent pausing one nucleotide upstream from the consensus sequence, often generating tandem pause sites. These ‘–2 pauses’ were stimulated by pyrophosphate in vitro and by addition of apyrase to degrade residual NTPs during NET-seq sample processing. We propose that some pauses are readily reversible by pyrophosphorolysis or single-nucleotide cleavage. Our results document multiple ways that SI3 modulates pausing in vivo and may explain discrepancies in consensus pause sequences in some NET-seq studies.
Efficacy of probiotic supplementation and impact on fecal microbiota in patients with inflammatory bowel disease: a systematic review and meta-analysis of randomized controlled trials
Authors: Xu Mengque , Zhang Wenluo , Lin Beibei , Lei Yue , Zhang Yu , Zhang Yu , Chen Binrui , Mao Qingyi , Kim John J , Cao Qian
Published: March 2024

Context: Research regarding the treatment of inflammatory bowel disease (IBD) with probiotics has not yielded consistent results.

Objective

The aim of this meta-analysis was to evaluate the efficacy of probiotics supplementation in patients with IBD.

Data Sources

Randomized controlled trials (RCTs) evaluating the efficacy of probiotics in patients with IBD were searched in PubMed, the Google Scholar database, Web of Science, and CrossRef for the period July 2003 to June 2023.

Data Extraction

The RCTs were extracted, independently by 2 authors, according to the PICOS criteria.

Data Analysis

Seven studies, including a total of 795 patients, met the study criteria. Five end points were selected to evaluate the efficacy. Of these, 3 indicators showed a statistically significant difference in efficacy: C-reactive protein (odds ratio [OR]: –2.45, 95% confidence interval [CI]: –3.16, –1.73, P < .01), the number of fecal Bifidobacterium (OR: 3.37, 95% CI: 3.28, 3.47, P < .01), and Lactobacillus(OR: 2.00, 95% CI: 1.91, 2.09, P < .01). The other 2 indicators (disease activity for Crohn’s disease and for ulcerative colitis) showed no statistically significant difference, while the OR reflected a positive correlation.

Conclusion

Probiotics supplementation may have a positive effect on IBD by reducing clinical symptoms, reducing the serological inflammatory markers, and increasing favorable gut flora in patients with IBD. Additional RCTs are needed to evaluate the therapeutic effect of probiotics in IBD.
The Sequential Direct and Indirect Effects of Mountain Uplift, Climatic Niche, and Floral Trait Evolution on Diversification Dynamics in an Andean Plant Clade
Authors: Dellinger Agnes S , Lagomarsino Laura , Michelangeli Fabián , Dullinger Stefan , Smith Stacey D
Published: March 2024

Why and how organismal lineages radiate is commonly studied through either assessing abiotic factors (biogeography, geomorphological processes, and climate) or biotic factors (traits and interactions). Despite increasing awareness that both abiotic and biotic processes may have important joint effects on diversification dynamics, few attempts have been made to quantify the relative importance and timing of these factors, and their potentially interlinked direct and indirect effects, on lineage diversification. We here combine assessments of historical biogeography, geomorphology, climatic niche, vegetative, and floral trait evolution to test whether these factors jointly, or in isolation, explain diversification dynamics of a Neotropical plant clade (Merianieae, Melastomataceae). After estimating ancestral areas and the changes in niche and trait disparity over time, we employ Phylogenetic Path Analyses as a synthesis tool to test eleven hypotheses on the individual direct and indirect effects of these factors on diversification rates. We find strongest support for interlinked effects of colonization of the uplifting Andes during the mid-Miocene and rapid abiotic climatic niche evolution in explaining a burst in diversification rate in Merianieae. Within Andean habitats, later increases in floral disparity allowed for the exploitation of wider pollination niches (i.e., shifts from bee to vertebrate pollinators), but did not affect diversification rates. Our approach of including both vegetative and floral trait evolution, rare in assessments of plant diversification in general, highlights that the evolution of woody habit and larger flowers preceded the colonization of the Andes, but was likely critical in enabling the rapid radiation in montane environments. Overall, and in concert with the idea that ecological opportunity is a key element of evolutionary radiations, our results suggest that a combination of rapid niche evolution and trait shifts was critical for the exploitation of newly available niche space in the Andes in the mid-Miocene. Further, our results emphasize the importance of incorporating both abiotic and biotic factors into the same analytical framework if we aim to quantify the relative and interlinked effects of these processes on diversification.
Opioid-Free Analgesia is Safe and Effective in Anterior Cervical Spine Surgery
Authors: Segebarth P. Bradley , Schallmo Michael , Odum Susan , Hietpas Kayla , Michalek Caleb , Chapman T. Matthew , Leas Daniel , Milam R. Alden , Hamid Nady ,   CORE Research Group
Published: March 2024

Study Design:

Randomized controlled trial (RCT).

Objective:

Compare the efficacy of a multimodal, opioid-free (OF) pain management pathway with a traditional opioid-containing (OC) pathway in patients undergoing anterior cervical procedures.

Summary of Background Data:

Previous studies have compared opioid-based pain regimens to opioid-sparing regimens following cervical spine surgery, but have been limited by high rates of crossover, retrospective designs, reliance on indwelling pain catheters, opioid utilization for early postoperative analgesia, and/or a lack of patient-reported outcome measures.

Methods:

This is a RCT in which patients were allocated to either an OF or OC perioperative pain management protocol. Eligible study participants included adult (age up to 18 y) patients who underwent primary, 1-level or 2-level anterior cervical surgery [anterior cervical discectomy and fusion (ACDF), anterior cervical disc arthroplasty (ACDA), or hybrid (ACDF and ACDA at different levels)] for degenerative pathology. The primary outcome variable was subjective pain level at 24 hours postoperative. The final study cohort consisted of 50 patients (22 OF, 28 OC).

Results:

Patients in the OF group reported lower median postoperative pain levels at 6 hours (4 for OF vs. 7 for OC; P=0.041) and 24 hours (3 for OF vs. 5 for OC; P=0.032). At 2-week and 6-week follow-up, pain levels were similar between groups. Patients in the OF group reported greater comfort at 12 hours (9 for OF vs. 5 for OC; P=0.003) and 24 hours (9 for OF vs. 5 for OC; P=0.011) postoperatively. Notably, there were no significant differences in patients’ reported pain satisfaction, overall surgical satisfaction, or overall sense of physical and mental well-being. In addition, there were no significant differences in falls, delirium, or constipation postoperatively.

Conclusions:

A multimodal OF pain management pathway following anterior cervical surgery for degenerative disease results in statistically noninferior pain control and equivalent patient-reported outcome measures compared with a traditional OC pathway.
Corneal Reinnervation in Patients With Severe Neurotrophic Keratopathy Secondary to Herpes Zoster Ophthalmicus After Treatment With Autologous Serum Tear Drops
Authors: Abazari Azin , Abbouda Alessandro , Cruzat Andrea , Cavalcanti Bernardo , Pavan-Langston Deborah , Hamrah Pedram
Published: March 2024

Purpose:

The purpose of this study was to assess potential corneal reinnervation and recovery of corneal sensation in patients with severe neurotrophic keratopathy (NK) secondary to herpes zoster ophthalmicus (HZO) after treatment with topical autologous serum tears (AST).

Method:

Four cases of HZO with severe NK were followed clinically and by serial laser in vivo confocal microscopy (IVCM, HRT3/RCM, Heidelberg Engineering GmbH) before and during treatment with 20% AST drops 8 times a day. Two masked observers reviewed the IVCM images and assessed corneal nerve alterations.

Results:

At baseline, all patients had complete loss of corneal sensation. In addition, IVCM showed complete lack of the subbasal corneal nerve plexus in all patients. All 4 patients were refractory to conventional therapies and were treated with AST drops. All patients demonstrated significant nerve regeneration by IVCM within 3 to 7 months of treatment. The total nerve density increased to a mean ± SEM of 10,085.88 ± 2,542.74 μm/mm2 at the last follow-up. Corneal sensation measured by Cochet–Bonnet esthesiometry improved to a mean ± SEM of 3.50 ± 1.30 cm. Interestingly, 3 of 4 patients developed stromal keratitis with stromal thinning within weeks of corneal reinnervation, which was reversed by adding topical steroids.

Conclusions:

Autologous serum tears are effective in restoring corneal subbasal nerves and sensation in patients with severe NK secondary to HZO. However, this group of patients may require concurrent topical immunomodulation and antiviral therapy while on AST to prevent stromal keratitis.
GABAAR-PPT1 palmitoylation homeostasis controls synaptic transmission and circuitry oscillation in CLN1 disease
Authors: Tong Jia , Gao Jingjing , Qi Yawei , Gao Ziyan , Liu Yang , Wang Qianqian , Yuan Tiangang , Ren Minglong , Yang Guixia , Li Zhaoyue , Li Jin , Sun Hongyuan , Zhao Xing , Li Junmei , Leung Yeung-Yeung , Mu Yonghui , Xu Jiamin , Lu Chengbiao , Peng Shiyong , Ge Lihao
Published: March 2024

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis, is a fatal neurodegenerative disease caused by mutations in the CLN1 gene encoding palmitoyl protein thioesterase 1 (PPT1). To identify depalmitoylation substrate of PPT1 is crucial to understand CLN1 disease. In this study, we found that PPT1 depalmitoylates GABAAR α1 subunit at Cystein-260, while binding to Cystein-165 and −179. Mutations of PPT1 or its GABAAR α1 subunit binding site result in enhanced inhibitory synaptic transmission, strengthened and oscillation but disrupted phase coupling in CA1 region and impaired learning and memory in 1- to 2-months-old PPT1-deficient andGabra1em1mice. Our study highlights the critical role of PPT1 in maintaining GABAAR palmitoylation homeostasis and reveals a previously unknown molecular pathway in PPT1 induced diseases.
Origins of noise in both improving and degrading decision making
Authors: Shen Bo , Nguyen Duc , Wilson Jailyn , Glimcher Paul W. , Louie Kenway
Published: March 2024

Noise is a fundamental problem for information processing in neural systems. In decision-making, noise is thought to cause stochastic errors in choice. However, little is known about how noise arising from different sources may contribute differently to value coding and choice behaviors. Here, we examine how noise arising early versus late in the decision process differentially impacts context-dependent choice behavior. We find in model simulations that under early noise, contextual information enhances choice accuracy, while under late noise, context degrades choice accuracy. Furthermore, we verify these opposing predictions in experimental human choice behavior. Manipulating early and late noise – by inducing uncertainty in option values and controlling time pressure – produces dissociable positive and negative context effects. These findings reconcile controversial experimental findings in the literature, suggesting a unified mechanism for context-dependent choice. More broadly, these findings highlight how different sources of noise can interact with neural computations to differentially modulate behavior.

Significance

The current study addresses the role of noise origin in decision-making, reconciling controversies around how decision-making is impacted by context. We demonstrate that different types of noise – either arising early during evaluation or late during option comparison - leads to distinct results: with early noise, context enhances choice accuracy, while with late noise, context impairs it. Understanding these dynamics offers potential strategies for improving decision-making in noisy environments and refining existing neural computation models. Overall, our findings advance our understanding of how neural systems handle noise in essential cognitive tasks, suggest a beneficial role for contextual modulation under certain conditions, and highlight the profound implications of noise structure in decision-making.
Human visual performance for identifying letters affected by physiologically-inspired scrambling
Authors: Zhu Xingqi R , Hess Robert F , Baldwin Alex S
Published: March 2024

Abstract

In human vision, the retinal input is transformed into internal representations through a series of stages. In earlier stages, the signals from a particular visual field locus are passed in parallel from one visual processing area to the next. The connections at each stage may therefore introduce “error”, where incorrect or convergent projections result in a loss of spatial precision. Psychophysical and physiological studies have implicated spatial scrambling of this sort as a cause of the visual deficits in amblyopia. Several methods to measure scrambling (both in amblyopia and in healthy vision) have been developed in recent decades. In this work, we introduce a new approach. We consider two stages of visual processing where scrambling may occur: either at the input to or the output from the simple cell stage in V1. We refer to these as “subcortical” and “cortical” scrambling respectively. We investigated the impact of these two types of scrambling on a letter identification task. A physiologically-inspired decomposition and resynthesis algorithm was used to generate letter stimuli that simulate scrambling at each of these two stages. To establish a performance benchmark, we trained separate Convolutional Neural Networks (CNNs) to perform the task with each scrambling type. Comparing CNN performance against that of eight humans with normal healthy vision, we found humans exhibited greater resilience to subcortical scrambling compared to cortical scrambling. We further investigated performance by comparing confusion matrices. Compared to a simple template matching model, we found the human strategy to be more consistent with our CNNs. We conclude: i) the human resilience for subcortical scrambling suggests this may be the stage at which a greater degree of scrambling is introduced in the visual hierarchy, and ii) humans employ flexible strategies for identifying scrambled stimuli, more sophisticated than a simple template match to the expected target.
Deciphering the Timing and Impact of Life-extending Interventions: Temporal Efficacy Profiler Distinguishes Early, Midlife, and Senescence Phase Efficacies
Authors: Jiang Nisi , Cheng Catherine J. , Liu Qianqian , Strong Randy , Gelfond Jonathan , Nelson James F.
Published: March 2024

Evidence that life-extending interventions are not uniformly effective across the lifespan calls for an analytic tool that can estimate age-specific treatment effects on mortality hazards. Here we report such a tool, applying it to mouse data from 42 compounds tested in the NIA Interventions Testing Program. This tool identified agents that either reduced (22) or increased (15) mortality hazards or did both (2) in at least one sex, most with marked variation in the duration of efficacy and magnitude of effect size. Only 8 reduced mortality hazards after 90% mortality, when the burden of senescence is the greatest. Sex differences were common. This new analytic tool complements the commonly used log-rank test. It detects more potential life-extending candidates (22 versus 10) and indicates when during the life course they are effective. It also uncovers adverse effects.
Robust characterization of forest structure from airborne laser scanning – a systematic assessment and sample workflow for ecologists
Authors: Fischer Fabian Jörg , Jackson Toby , Vincent Grégoire , Jucker Tommaso
Published: March 2024

Forests display tremendous structural diversity, shaping carbon cycling, microclimates, and terrestrial habitats. One of the most common tools for forest structure assessments are canopy height models (CHMs): maps of canopy height obtained at high resolution and large scale from airborne laser scanning (ALS). CHMs can be computed in many ways, but little is known about the robustness of different CHM algorithms and how they affect ecological analyses.

Here, we used high-quality ALS data from nine sites in Australia, ranging from semi-arid shrublands to 90-m tall Mountain Ash canopies, to comprehensively assess CHM algorithms. This included testing their sensitivity to point cloud degradation and quantifying the propagation of errors to derived metrics of canopy structure.

We found that CHM algorithms varied widely both in their height predictions (differences up to 10 m, or 60% of canopy height) and in their sensitivity to point cloud characteristics (biases of up to ∼5 m or 40% of canopy height). Impacts of point cloud properties on CHM-derived metrics varied, from robust inference for height percentiles, to considerable errors in aboveground biomass estimates (∼50 Mg ha−1, or 10% of total), and high volatility in metrics that quantify spatial associations in canopies (e.g., gaps or spatial autocorrelation). In some cases, biases exceeded ecological variation across sites by a factor of 2. However, we also found that two CHM algorithms – a variation on a “spikefree” algorithm that adapts to local pulse densities and a simple Delaunay triangulation of first returns – allowed for robust canopy characterization and should thus create a secure foundation for ecological comparisons in space and time.

Canopy height models are a widely used tool in ecology, but their derivation is not trivial. Our study provides a best-practice guideline and a sample workflow to create robust CHMs and minimize biases and uncertainty in downstream analyses. In doing so we pave the way for global-scale comparisons of forest structural complexity from airborne laser scanning.
Design and Assembly of a Cargo-agnostic Hollow Two-lidded DNA Origami Box for Drug Delivery
Authors: Koep Abigail , Masud Nabila , Van’t Hul Jaylee , Stanley Carson , Nilsen-Hamilton Marit , Sarkar Anwesha , Schneider Ian C.
Published: March 2024

DNA origami, a method of folding DNA into precise nanostructures, has emerged as a powerful tool to design complex nanoscale shapes with movable parts. DNA origami has great potential as a drug delivery system that can encapsulate and protect a range of cargos spanning small molecules through large proteins, while remaining stable in a variety ofex vivoprocessing conditions andin vivoenvironments. DNA origami has been utilized for drug delivery applications, but the vast majority of these structures have been flexible, flat 2D or solid 3D nanostructures. There is a crucial need for a hollow and completely enclosed design capable of holding any type of cargo. In this paper, we present the design and assembly of a hollow DNA origami “box” with two actuatable lids. We characterize isothermal conditions for structural assembly in minutes that eliminates the need for a thermocycler. The stability of these structures is outstanding, remaining stable at body temperature and low pH for weeks and in the presence of solvents and biological fluids over several days. We demonstrate that passive loading of small molecules is charge dependent. We also outline an approach to design staple extensions pointing into the cavity or outside of the hollow DNA origami, allowing for either active loading of protein or the potential for decoration with passivating or targeting molecules. Future work includes fitting this hollow DNA origami structure with alternative lid opening mechanisms to release a variety of different cargos in response to environmental cues.

Graphical Abstract
ACSS2 upregulation enhances neuronal resilience to aging and tau-associated neurodegeneration
Authors: Pourshafie Naemeh , Xu Hong , Yang Kechun , Donahue Greg , Lei Xue , Zhang Shuo , Shcherbakova Oksana , Hogan Connor , Gilbert Michael , Hoxha Kevt’her , Chaboub Lesley , Lee Virginia , Adams Peter , Dani John A. , Bonini Nancy , Berger Shelley
Published: March 2024

Epigenetic mechanisms, including histone acetylation, are pivotal for learning and memory, with a role in neuronal function in Alzheimer’s disease and Related Dementia (ADRD). Acetyl-CoA synthetase 2 (ACSS2), an enzyme that generates acetyl-CoA, is central to histone acetylation and gene regulation, particularly in neurons, due to their unique metabolic demands and postmitotic state. ACSS2 can be recruited to the nucleus and chromatin, locally supplying acetyl-CoA to directly fuel histone acetyltransferase enzymes and key neuronal gene expression. This regulatory mechanism may be a promising target for therapeutic intervention in neurodegenerative diseases. Previously we showed that systemic ACSS2 deletion in mice, although largely normal in physiology, is greatly impaired in memory. Here we investigated whether increasing ACSS2 levels could protect neurons against disease and age-associated cognitive decline. Given the role of tau in ADRD, we used primary hippocampal neurons that mimic the sporadic development of tau pathology and the P301S transgenic mouse model for tau-induced memory decline. Our results show that ACSS2 upregulation mitigates tau-induced transcriptional alterations, enhances neuronal resilience against tau pathology, improves long-term potentiation, and ameliorates memory deficits. Expanding upon these findings, we reveal that increasing histone acetylation through ACSS2 upregulation improves age-associated memory decline. These findings indicate that increasing ACSS2 is highly effective in countering age- and tau-induced transcriptome changes, preserving elevated levels of synaptic genes, and safeguarding synaptic integrity. We thus highlight ACSS2 as a key player in the epigenetic regulation of cognitive aging and ADRD, providing a foundation for targeted therapeutics to enhance brain resilience and function.

ACSS2 upregulation protects neurons from disease and age-related decline by enhancing synaptic and longevity gene expression.
Vitamin C preventsS. aureusinfections of endothelial cells through its interaction with specific residues in the active site of gC1qR/p33 involved in direct entry, notably SER230, ASN345, ILE348, TYR224, ASN346, SER347, and GLU438, and its potential inhibitory effects on FnBPs, α5β1, and Protein A molecules
Authors: Miliani Maroua , Hadjidj Zeyneb , Bensefia Zakariya , Dahou Sara , Ammouche Nasreddine , Hamdoun Imane , Benammar Hadjer , Benammar Sarah , Aribi Mourad
Published: March 2024

Staphylococcus aureus(S. aureus), often perceived as an extracellular pathogenic agent, exhibits a remarkable ability to penetrate host cells, including endothelial, epithelial, and osteoblastic cells, significantly contributing to the pathogenesis of infections. A significant pathway for this invasion appears to involve the bacterium’s binding to the α5β1 integrinviaa fibronectin bridge, followed by phagocytosis. Additionally,S. aureuspresents staphylococcal protein A, a cell wall protein that binds to the Fc and Fab regions of immunoglobulins, playing a crucial role in virulence and immune evasion, and can also bind directly to the gC1qR receptor on endothelial cells. Furthermore, vitamin C is recognized for its antimicrobial and immunomodulatory properties, offering potential for reducing the risk of infection. Considering the aforementioned elements, our study focused on exploring the potential effects of vitamin C on the interactions betweenS. aureusand endothelial cells. Thus, we particularly examined two aspects: on the one hand, interactions involving fibronectin-binding proteins (FnBPs) proteins and human α5β1 integrin, and on the other hand, the interaction between vitamin C and the direct entry receptor (the globular heads of complement component 1q receptor [gC1qR/p33], also known as hyaluronic acid binding protein 1 [HABP1]). To achieve this, we utilized molecular modeling assays, primarily relying on molecular docking.
A shared genetic basis for sexually antagonistic male and female adaptations in the toothed water strider
Authors: Pruvôt Claudia , Armisen David , Roux Pascale , Arnqvist Göran , Rowe Locke , Husby Arild , Khila Abderrahman
Published: March 2024

Sexual conflict can drive the divergence of male and female phenotypes and several cross-species comparative analyses have documented patterns of correlated evolution of sex-specific traits that promote the evolutionary interests of the sexes. However, male-female coevolution can be highly dynamic. Moreover, if male and female traits do not have an entirely distinct genetic basis, this can have profound effects on their coevolutionary dynamics. Here, we use water striders, a well-studied model system for sexually antagonistic coevolution, and ask whether sex-specific phenotypic adaptations covary across populations and whether they share a common developmental genetic basis. Using comparative analyses both at the population and species levels, we document an association between a derived male mate-grasping trait and a likely female anti-grasping counteradaptation in the toothed water striderGerris odontogaster. Interestingly, in one population where males did not express their derived grasping trait, females had also regained the ancestral morphology. We then used experimental manipulation of gene expression, and show that these male and female traits are both linked to a common developmental genetic program containing Hox and sex determination genes, despite the fact that they are different structures on different segments. Our work thus suggests that the pleiotropic nature of developmental genetic programs can blur the distinction between inter- and intralocus genetic conflict.
Bayesian inference of phylogenetic distances: revisiting the eigenvalue approach
Authors: Penn Matthew J. , Scheidwasser Neil , Donnelly Christl A. , Duchêne David A. , Bhatt Samir
Published: March 2024

Using genetic data to infer evolutionary distances between molecular sequence pairs based on a Markov substitution model is a common procedure in phylogenetics, in particular for selecting a good starting tree to improve upon. Many evolutionary patterns can be accurately modelled using substitution models that are available in closed form, including the popular general time reversible model (GTR) for DNA data. For more unusual biological phenomena such as variations in lineage-specific evolutionary rates over time (heterotachy), more complex approaches uch as the GTR with rate variation (GTR+G) are required, but do not admit analytical solutions and do not automatically allow for likelihood calculations crucial for Bayesian analysis. In this paper, we derive a hybrid approach between these two methods, incorporatingG(α, α)-distributed rate variation and heterotachy into a hierarchical Bayesian GTR-style framework. Our approach is differentiable and amenable to both stochastic gradient descent for optimisation and Hamiltonian Markov chain Monte Carlo for Bayesian inference. We show the utility of our approach by studying hypotheses regarding the origins of the eukaryotic cell within the context of a universal tree of life and find evidence for a two-domain theory.
Evidence for flexible motor costs in vertical arm movements: reduced gravity-related effort minimization under high accuracy constraints
Authors: Poirier Gabriel , De Filippis Damien , Sirandre Cyril , Papaxanthis Charalambos , Gaveau Jeremie
Published: March 2024

The central nervous system (CNS) is thought to use motor strategies that minimize several criteria, such as end-point variability or effort, to plan optimal motor patterns. In the case of vertical arm movements, a large body of literature demonstrated that the brain uses a motor strategy that takes advantage of the mechanical effects of gravity to minimize muscle effort. Results from other studies suggested that the relative importance of each criterion may vary according to the task’s constraints. For example, it could be hypothesized that reduced end-point variability driven by high accuracy demands is detrimental to effort minimization. The present study probes this specific hypothesis using the framework of gravity-related effort minimization. We asked twenty young healthy participants to perform vertical arm reaching movements towards targets whose size varied across conditions. We recorded the arm kinematics and electromyographic activities of the anterior deltoid to study two well-known motor signatures of the gravity-related optimization process; i.e., directional asymmetries on velocity profiles and negative epochs on phasic muscular activities. The results showed that both indices were reduced as target size decreased, demonstrating that the gravity-related optimization process was reduced under high accuracy constraints. This phenomenon is consistent with the use of a trade-off strategy between effort and end-point variability. More generally, it suggests that the CNS is able to appropriately modulate the relative importance of varied motor costs when facing varying task demands.
Genetic diversity affects ecosystem functions across trophic levels as much as species diversity, but in an opposite direction
Authors: Fargeot Laura , Poesy Camille , Lefort Maxim , Prunier Jérôme G. , Krick Madoka , Verdonck Rik , Veyssière Charlotte , Richard Murielle , Legrand Delphine , Loot Géraldine , Blanchet Simon
Published: March 2024

Understanding the relationships between biodiversity and ecosystem functioning stands as a cornerstone in ecological research. Extensive evidence now underscores the profound impact of species loss on the stability and dynamics of ecosystem functions. However, it remains unclear whether the loss of genetic diversity within key species yield similar consequences. Here, we delve into the intricate relationship between species diversity, genetic diversity, and ecosystem functions across three trophic levels —primary producers, primary consumers, and secondary consumers— in natural aquatic ecosystems. Our investigation involves estimating species diversity and genome-wide diversity -gauged within three pivotal species-within each trophic level, evaluating seven key ecosystem functions, and analyzing the magnitude of the relationships between biodiversity and ecosystem functions (BEFs). We found that, overall, the absolute effect size of genetic diversity on ecosystem functions mirrors that of species diversity in natural ecosystems. We nonetheless unveil a striking dichotomy: while genetic diversity was positively correlated with various ecosystem functions, species diversity displays a negative correlation with these functions. These intriguing antagonist effects of species and genetic diversity persists across the three trophic levels (underscoring its systemic nature), but were apparent only when BEFs were assessed within trophic levels rather than across them. This study reveals the complexity of predicting the consequences of genetic and species diversity loss under natural conditions, and emphasizes the need for further mechanistic models integrating these two facets of biodiversity.
A novel functional gene delivery platform based on a commensal human anellovirus demonstrates transduction in multiple tissue types
Authors: Prince Cato , Bounoutas George , Zhou Bolu , Raja Waseem , Gold Isabella , Pozsgai Rianna , Thakker Parmi , Boisvert Nicole , Reardon Christopher , Thurmond Stephanie , Ozturk Erin , Boggavarapu Rajendra , Springer Simeon , Chahal Lovepreet , Nogalski Maciej , Ong Tuyen , Nawandar Dhananjay , Wright Christopher , Mackey Ashley , Parsons Geoffrey , Cabral Joseph
Published: March 2024

Anelloviridaeis a family of non-enveloped viruses with negative-sense, circular, single-stranded deoxyribonucleic acid (ssDNA) genomes that infect vertebrates and are a ubiquitous component of the human virome. Human anelloviruses evade induction of humoral immune responses and appear to be non-pathogenic. These properties, in conjunction with their enormous genomic diversity and wide tissue distribution, make anelloviruses compelling candidates as vectors for next-generation genetic medicines. Here we report the first gene delivery vector system based on a human commensal virus. This Anellovector is based on a virus of theBetatorquevirusgenus. Production is enabled by the development of the Self-Amplifying Trans-complementation of a Universal Recombinant aNellovector (SATURN) system, which relies on a self-replicating plasmid to provide viral proteins in trans that drive replication and capsid-dependent packaging of vector genomes. The SATURN system also utilizes a Cre-lox-based recombination mechanism to generate single unit-sized circular genomes inside the MOLT-4 production cell line. We demonstrate that the SATURN system can package a vector genome from a single betatorquevirus with capsids from multiple betatorquevirus species, supporting the feasibility of establishing a novel vector platform that takes advantage of the remarkable diversity of anelloviruses. The Anellovector demonstrated functionin vitroin retinal pigment epithelial (RPE) cells. The Anellovector also demonstrated durablein vivofunction in the mouse eye for 9 months after subretinal administration, and achieved comparable gene expression to dose-matched adeno-associated virus 9 (AAV9) when transduced by the intracerebroventricular (ICV) route of administration. To our knowledge, this is the first report of a functional anellovirus-based gene therapy vector. Anellovectors have great potential to deliver safe, redosable, and potent therapeutics, helping to expand the reach of programmable medicines.
Energy-ordered resource stratification as an agnostic signature of life
Authors: Goyal Akshit , Tikhonov Mikhail
Published: March 2024

The search for extraterrestrial life hinges on identifying biosignatures, often focusing on gaseous metabolic byproducts as indicators. However, most such biosignatures require assuming specific metabolic processes. It is widely recognized that life on other planets may not resemble that of Earth, but identifying biosignatures “agnostic” to such assumptions has remained a challenge. Here, we propose a novel approach by considering the generic outcome of life: the formation of competing ecosystems. We use a minimal model to argue that the presence of ecosystem-level dynamics, characterized by ecological interactions and resource competition, may yield biosignatures independent of specific metabolic activities. Specifically, we propose the emergent stratification of chemical resources in order of decreasing energy content as a candidate new biosignature. While likely inaccessible to remote sensing, this signature could be relevant for sample return missions, or for detection of ancient signatures of life on Earth itself.
Circadian control of a sex-specific behaviour in Drosophila
Authors: Riva Sabrina , Ceriani M. Fernanda , Risau-Gusman Sebastián , Franco D. Lorena
Published: March 2024

An endogenous circadian clock controls many of the behavioral traits ofDrosophila melanogaster. This “clock” relies on the activity of interconnected clusters of neurons that harbor the clock machinery. The hierarchy among clusters involved in the control of rest-activity cycles has been extensively studied. Sexually dimorphic behaviors, on the other hand, have received less attention. Even though egg-laying, a female characteristic behavior, has been shown to be rhythmic, it remains largely unexplored possibly due to metholodological constraints. The current study provides the first steps towards determining the neural substrates underlying the circadian control of egg-laying. We show that, whereas the lateral ventral neurons (LNvs) and the dorsal neurons (DNs) are dispensable, the lateral dorsal neurons (LNds) are necessary for rhythmic egg-laying. Systematically probing theDrosophilaconnectome for contacts between circadian clusters and oviposition-related neurons, we found no evidence of direct connections between LNvs or DNs and neurons recruited during oviposition. Conversely, we did find bidirectional connections between Cryptochrome (Cry) expressing LNd (Cry+ LNds) and oviposition related neurons. Taken together, these results reveal that Cry+ LNd neurons have a leading role in the control of the egg-laying rhythm inDrosophilafemales.
CORONATINE INSENSITIVE 1-mediated repression of immunity-related genes in Arabidopsis roots is overcome upon infection withVerticillium longisporum
Authors: Ulrich Louisa , Schmitz Johanna , Thurow Corinna , Gatz Christiane
Published: March 2024

Verticillium longisporumis a soil-borne fungal pathogen causing vascular disease predominantly inBrassicaceae. We have reported previously that the receptor of the plant defense hormone jasmonoyl-isoleucine (JA-Ile), CORONATINE INSENSITIVE 1 (COI1), is required in roots for efficient proliferation of the fungus in the shoot implicating a mobile root-borne signal that influences the outcome of the disease in shoots. To explore the underlying mechanism we compared the root transcriptome ofcoi1with the transcriptomes of three susceptible genotypes (wild-type, mutants deficient in JA-Ile and salicylic acid (SA) synthesis). At 10 days after infection, genes related to either xylem formation or plant immunity were induced independently of JA-Ile and SA. The biggest difference between the transcriptomes was due to 316 immunity-related genes that were pre-induced incoi1. Interfering with the expression of a subgroup of these genes partially suppressed thecoi1phenotype. We therefore hypothesize that mobile defense compounds secreted into the xylem and being transported with the transpiration stream confer tolerance to the shoot. We furthermore report that 149 of the COI1-repressed genes are induced in WT upon infection reaching similar levels as in mock-treatedcoi1. The majority of these were not further induced incoi1, indicating that COI1 is required for infection-induced expression.
Synchronization of Circadian Clock Gene Expression inArabidopsisandHyaloperonospora arabidopsidisand its Impact on Host-Pathogen Interactions
Authors: Telli Osman , Göl Deniz , Jin Weibo , Cevher-Keskin Birsen , Hong Yiguo , McDowell John M. , Studholme David J. , Tör Mahmut
Published: March 2024

Organisms across all kingdoms have an internal circadian clock running in 24h cycles. This clock affects a variety of processes, including innate immunity in plants. However, the role of pathogen circadian clocks had not been extensively explored. We previously showed that light can influence infection of the oomyceteHyaloperonospora arabidopsidis(Hpa, downy mildew disease) on its natural hostArabidopsis thaliana. Here, we identifiedHpaorthologs of known circadian clock genes (CCGs)Drosophila TIMELESS (TIM)andArabidopsis Sensitive to Red Light Reduced 1 (AtSRR1)genes. Expression of bothHpaTIMandHpaSRR1showed a circadian rhythm whenHpawas exposed to constant light. Contrastingly, these two genes were negatively regulated by constant dark exposure. Furthermore, the expression patterns ofHpaTIMandHpaSRR1correlate with those ofAtCCA1andAtLHY, indicating a synchronisation of biological clock genes between the host and the pathogen. In addition, screening mutants ofArabidopsisClock Regulated Genes (AtCRGs) with three virulentHpaisolates revealed that mutations inAtCRGsinfluencedHpaTIMandHpaSRR1expression andHpadevelopment, indicating a functional link between the plant biological clock and virulence. Moreover, sporulation ofHpawas reduced by targetingHpaTIMandHpaSRR1with short synthesized small interfering RNAs, indicating that the pathogen clock is also relevant to virulence. We propose that plant and pathogen clocks are synchronized during infection and that proper regulation of both clocks are genetically necessary for pathogen virulence.