bluuebunny/crossref_metadata_2025 huggingface dataset:
Before and after delisting: population dynamics of North Atlantic humpback whales over two decades in the Gulf of Maine
Authors: Robbins Jooke , Bérubé Martine , Clapham Phillip J. , Mattila David K. , Palsbøll Per J. , Asmutis-Silvia Regina , Hill Alex , Howes Laura J. , Landry Scott , Lonergan Shelley , Schulte Dianna , Tackaberry Jennifer E. , Weinrich Mason T. , Pace Richard M.
Published: February 2024

Whales are long-lived, slow-reproducing species that were decimated by commercial whaling. Although some populations seem close to recovery, others are challenging to assess. We studied humpback whales (Megaptera novaeangliae) in the Gulf of Maine, an area of the North Atlantic (NA) with well-documented threats. Long-term studies and mark-recapture data were used to estimate humpback whale apparent survival, abundance and population growth from 2000 through 2019. Estimates were derived from a hierarchical, Bayesian state-space model with sex, age, and random time effects on survival while accounting for individual capture probability. Abundance increased from 744 (95% CI: 726-762) in 2000 to 1,706 (95% CI: 1,639-1,771) in 2019, with 4.6% mean annual growth. However, adult males exhibited higher survival and outnumbered adult females by the end of the study. Over time, fewer calves were observed, calf survival varied and the juvenile class declined. These are rare insights into the dynamics underlying whale abundance trends and they revealed similarities to an endangered species that is declining due to environmental and human impacts. The results inform a listing change under the U.S. Endangered Species Act, a mortality event of unprecedented magnitude off the U.S and humpback whale recovery from historical whaling in the NA.
TMEM16 and OSCA/TMEM63 proteins share a conserved potential to permeate ions and phospholipids
Authors: Lowry Augustus J. , Liang Pengfei , Song Mo , Wan Y.C. Serena , Pei Zhen-Ming , Yang Huanghe , Zhang Yang
Published: February 2024

The calcium-activated TMEM16 proteins and the mechanosensitive/osmolarity-activated OSCA/TMEM63 proteins belong to the Transmembrane Channel/Scramblase (TCS) superfamily. Within the superfamily, OSCA/TMEM63 proteins, as well as TMEM16A and TMEM16B, are thought to function solely as ion channels. However, most TMEM16 members, including TMEM16F, maintain an additional function as scramblases, rapidly exchanging phospholipids between leaflets of the membrane. Although recent studies have advanced our understanding of TCS structure-function relationships, the molecular determinants of TCS ion and lipid permeation remain unclear. Here we show that single mutations along the transmembrane helix (TM) 4/6 interface allow non-scrambling TCS members to permeate phospholipids. In particular, this study highlights the key role of TM 4 in controlling TCS ion and lipid permeation and offers novel insights into the evolution of the TCS superfamily, suggesting that, like TMEM16s, the OSCA/TMEM63 family maintains a conserved potential to permeate ions and phospholipids.
Enhanced Antibody Response to the Conformational Non-RBD RegionviaDNA Prime-Protein Boost Elicits Broad Cross-Neutralization Against SARS-CoV-2 Variants
Authors: Ma Yun-Fei , Chen Kun , Xie Bowen , Zhu Jiayi , He Xuan , Chen Chunying , Yang Yuhe Renee , Liu Ye
Published: February 2024

Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice. Mice with enhanced antibody responses targeting conformational non-RBD region show better performance in cross-neutralization against the Wuhan-01, Delta, and Omicron subvariants.Viaanalyzing the distribution of conformational epitopes, and quantifying epitope-specific binding antibodies, we verified a positive correlation between the proportion of binding antibodies against the N-terminal domain (NTD) supersite (a conformational non-RBD epitope) and SARS-CoV-2 neutralization potency. The current work highlights the importance of high ratio of conformational non-RBD-specific binding antibodies in mediating viral cross-neutralization and provides new insight into overcoming the immune escape of SARS-CoV-2 variants.
Evaluating a Motor Progression Connectivity Model Across Parkinson’s Disease Stages
Authors: Hacker Mallory L. , Isaacs David A. , Rajamani Nanditha , Pazira Kian , Abdou Eli , Sharp Sheffield , Davis Thomas L. , Hedera Peter , Phibbs Fenna T. , Charles David , Horn Andreas
Published: February 2024

Background

Stimulation of a specific site in the dorsolateral subthalamic nucleus (STN) was recently associated with slower motor progression in Parkinson’s Disease (PD), based on the deep brain stimulation (DBS) in early-stage PD pilot trial.

Objective

To test whether stimulation of this site is associated with improvements of long-term motor outcomes in advanced-stage PD.

Methods

Active contacts of the early DBS cohort (N=14) were analyzed. Sweet spot and connectivity models derived from this cohort were then used to estimate long-term motor outcomes in an independent DBS cohort of advanced-stage PD patients (N=29).

Results

In early-stage PD, proximity of stimulation to the dorsolateral STN associated with slower motor progression. In advanced-stage PD, stimulation proximity to the same site associated with better long-term motor outcomes (R=0.60, P<0.001).

Conclusions

Results suggest stimulation of a specific site in the dorsolateral STN associates with both slower motor progression and long-term motor improvements in PD.
Preconception indicators and associations with health outcomes reported in UK routine primary care data: a systematic review
Authors: Schoenaker Danielle , Lovegrove Elizabeth M , Cassinelli Emma H , Hall Jennifer , McGranahan Majel , McGowan Laura , Carr Helen , Alwan Nisreen A , Stephenson Judith , Godfrey Keith M
Published: February 2024

Background

Routine primary care data may be a valuable resource for preconception health research and informing provision of preconception care.

Aim

To review how primary care data could provide information on the prevalence of preconception indicators and examine associations with maternal and offspring health outcomes.

Design and Setting

Systematic review of observational studies using UK routine primary care data.

Method

Literature searches were conducted in five databases (March 2023) to identify observational studies that used national primary care data from individuals aged 15-49 years. Preconception indicators were defined as medical, behavioural and social factors that may impact future pregnancies. Health outcomes included those that may occur during and after pregnancy. Screening, data extraction and quality assessment were conducted by two reviewers.

Results

From 5,259 records screened, 42 articles were included. The prevalence of 30 preconception indicators was described for female patients, ranging from 0.01% for sickle cell disease to >20% for each of advanced maternal age, previous caesarean section (among those with a recorded pregnancy), overweight, obesity, smoking, depression and anxiety (irrespective of pregnancy). Few studies reported indicators for male patients (n=3) or associations with outcomes (n=5). Most studies had low risk of bias, but missing data may limit generalisability.

Conclusion

Findings demonstrate that routinely collected UK primary care data can be used to identify patients’ preconception care needs. Linking primary care data with health outcomes collected in other datasets is underutilised but could help quantify how optimising preconception health and care can reduce adverse outcomes for mothers and children.

How this fits in

Provision of preconception care is not currently embedded into routine clinical practice but may be informed by routinely collected primary care data.

This systematic review demonstrates that UK primary care data can provide information on the prevalence of a range of medical, behavioural and social factors among female patients of reproductive age, while limited research has examined male preconception health or associations with maternal and offspring health outcomes.

Routinely recorded electronic patient record data can be used by primary healthcare professionals to search for preconception risk factors and thereby support individualised preconception care, while aggregate data can be used by public health agencies to promote population-level preconception health.

Further data quality improvements and linkage of routine health datasets are needed to support the provision of preconception care and future research on its benefits for maternal and offspring health outcomes.
Acute kidney injury outcomes of COVID-19 confirmed patients in a Philippine tertiary hospital: A retrospective study
Authors: Sayson Joberly , Kalaw Reginald , Ordona Bernadette Ecunar , Lim Marissa Elizabeth
Published: February 2024

The novel coronavirus (COVID-19) is known to be the fifth pandemic causing massive deaths worldwide. This virus has not only been deeply associated with acute respiratory distress, but also acute kidney injury (AKI). This study describes the baseline characteristics and various outcomes of AKI based on the KDIGO 2012 Clinical Practice Guidelines in patients hospitalized with COVID-19 at a Philippine tertiary hospital. A total of 195 patient records were retrospectively reviewed for the study. Of the 195 patients, 81(42%) patients developed AKI. Significant baseline characteristics included older age (56.28 + 14.12), presence of hypertension (p=0.004), diabetes mellitus (p=0.002), and cardiovascular disease (p=0.003). Also, the use of diuretics, inotropes and antibiotics were more prevalent in patients who developed AKI. Most of the patients who had AKI were categorized as stage 1 (49.38%). Mechanical ventilation was significantly (p<0.001) more prevalent in patients with AKI (20.99%) compared to patients without AKI (5.26%). There was significantly higher rates (p<0.001) of renal replacement therapy in patients with AKI (30.86%). Lastly, higher mortality rates were observed in patients with AKI (50.62%) versus patients without AKI (12.28%). Our study demonstrated that patients with COVID-19 can develop AKI and tend to have a poorer prognosis.
[ICoN: Integration using Co-attention across Biological Networks
Authors: Tasnina Nure , Murali T. M.
Published: February 2024

Motivation

Molecular interaction networks are powerful tools for studying cellular functions. Integrating diverse types of networks enhances performance in downstream tasks such as gene module detection and protein function prediction. The challenge lies in extracting meaningful protein feature representations due to varying levels of sparsity and noise across these heterogeneous networks.

Results

We propose ICoN, a novel ‘co-attention’-based, denoising, unsupervised graph neural network model that takes multiple protein-protein association networks as inputs and generates an integrated single network by computing a unified feature representation for each protein. A key contribution of ICoN is a novel approach that enables cross-network communication through co-attention during training. The model also incorporates a denoising training technique, introducing perturbations to each input network and training the model to reconstruct the original network from its corrupted version, a method previously unexplored in network integration.

Our experimental results demonstrate that ICoN surpasses individual networks across three downstream tasks: gene module detection, gene coannotation prediction, and protein function prediction. Compared to existing unsupervised network integration models, ICoN exhibits superior performance across the majority of downstream tasks and exhibits enhanced robustness against noise. This work introduces a promising approach for effectively integrating diverse protein-protein association networks, aiming to achieve a biologically meaningful unified representation of proteins.

Availability

The ICoN software is available under the GNU Public License v3 athttps://github.com/Murali-group/ICoN.
Plastid phylogenomics reveals evolutionary relationships in the mycoheterotrophic orchid genusDipodiumand provides insights into plastid gene degeneration
Authors: Goedderz Stephanie , Clements Mark A. , Bent Stephen J. , Nicholls James A. , Patel Vidushi S. , Crayn Darren M. , Schlüter Philipp M. , Nargar Katharina
Published: February 2024

The orchid genusDipodiumR.Br. (Epidendroideae) comprises leafy autotrophic and leafless mycoheterotrophic species, the latter confined to sect.Dipodium. This study examined plastome degeneration inDipodiumin a phylogenomic and temporal context. Whole plastomes were reconstructed and annotated for 24Dipodiumsamples representing 14 species and two putatively new species, encompassing over 80% of species diversity in sect.Dipodium. Phylogenomic analysis based on 68 plastid loci including a broad outgroup sampling across Orchidaceae found sect.Leopardanthusas sister lineage to sect.Dipodium. Dipodium ensifolium, the only leafy autotrophic species in sect.Dipodiumwas found sister to all leafless, mycoheterotrophic species, supporting a single evolutionary origin of mycoheterotrophy in the genus. Divergence time estimations found thatDipodiumarose ca. 33.3 Ma near the lower boundary of the Oligocene and crown diversification commenced in the late Miocene, ca. 11.3 Ma. Mycoheterotrophy in the genus was estimated to have evolved in the late Miocene, ca. 7.3 Ma, in sect.Dipodium. The comparative assessment of plastome structure and gene degradation inDipodiumrevealed that plastidndhgenes were pseudogenised or physically lost in allDipodiumspecies, including in leafy autotrophic species of bothDipodiumsections. Levels of plastidndhgene degradation were found to vary among species as well as within species, providing evidence of relaxed selection for retention of the NADH dehydrogenase complex within the genus.Dipodiumexhibits an early stage of plastid genome degradation as all species were found to have retained a full set of functional photosynthesis-related genes and housekeeping genes. This study provides important insights into plastid genome degradation along the transition from autotrophy to mycoheterotrophy in a phylogenomic and temporal context.
Trophic niche partitioning in symbiotic marine invertebrates
Authors: Guibert Isis , Conti-Jerpe Inga Elizabeth , Pons Leonard , Tayaban Kuselah , Sayco Sherry Lyn , Cabaitan Patrick , Conaco Cecilia , Baker David Michael
Published: February 2024

Fierce competition for food and space underpins coral reefs’ biodiversity - supported by photosymbiotic foundational species. In contrast to other ecosystems, there is scant evidence that competition is mitigated by niche partitioning. Indeed, the dynamic evolutionary lineages of symbiotic partners and their syntrophy create layers of nutritional complexity that obfuscate patterns that structurn reef communities. As conspicuous members of Indo-Pacific reefs - giant clams co-occur with reef-building corals and similarly associate with algal symbionts. Using a common garden experiment, we analyzed stable isotope values from six giant clam species in the Philippines. These data, along with published data from ten sympatric corals, were used to calculate a novel metric - the Host Evaluation: Reliance on Symbionts (HERS) index - to assess variations in relative trophic strategies. Consistent with trophic niche partitioning – all species fell along an autotrophy-heterotrophy gradient with little overlap. We found a significant phylogenetic signal in clam HERS score, highlighting the role of selection in their nutritional ecology. We conclude that niche partitioning comes with tradeoffs, where predominantly autotrophic species showed higher growth rates but higher susceptibility to stress and consequently - greater conservation concern.

Teaser

Trophic niche partitioning plays a role in symbiotic marine invertebrate evolution with benefits and costs.
Building Blocks of Understanding: Constructing a Reverse Genetics Platform for studying determinants of SARS-CoV-2 replication
Authors: Olguin-Nava Marco , Bohn Patrick , Hennig Thomas , Börtlein Charlene , Gribling-Burrer Anne-Sophie , Schmidt Nora , Caliskan Neva , Dölken Lars , Munschauer Mathias , Smyth Redmond P.
Published: February 2024

To better understand viral pathogenesis, host-virus interactions, and potential therapeutic interventions, the development of robust reverse genetics systems for SARS-CoV-2 is crucial. Here, we present a reverse genetics platform that enables the efficient manipulation, assembly, and rescue of recombinant SARS-CoV-2. The versatility of our reverse genetics system was demonstrated by generating recombinant SARS-CoV-2 viruses. We used this system to generate N501Y and Y453F spike protein mutants. Characterization studies revealed distinct phenotypic effects, impact on viral fitness, cell binding, and replication kinetics. We also investigated a recently discovered priming site for NSP9, which is postulated to produce a short RNA antisense leader sequence. By introducing the U76G mutation into the 5’UTR, we show that this priming site is necessary for the correct production of genomic and subgenomic RNAs, and also for efficient viral replication. In conclusion, our developed reverse genetics system provides a robust and adaptable platform for the efficient generation of recombinant SARS-CoV-2 viruses for their comprehensive characterization.

Significance statement

In this study, we present a versatile reverse genetics platform facilitating the efficient manipulation, assembly, and rescue of recombinant SARS-CoV-2. Demonstrating its adaptability, we successfully engineered N501Y and Y453F spike protein mutants, each exhibiting distinct phenotypic effects on viral fitness, cell binding, and replication kinetics. We also investigated a novel negative sense priming site for NSP9, demonstrating a role in RNA production and viral replication. This straightforward reverse genetic system is therefore a powerful tool to generate recombinant viruses for advancing our understanding of SARS-CoV-2 biology.
Genome-wide CRISPR screen identifies AC9 as a key regulator of ER Ca2+homeostasis involved in neuronal differentiation
Authors: Wang Liuqing , Li Jia , Wang Yiping , Zhong Ziyi , Wang Yuqing , Huang Rui , Zhang Bingwei , Liu Panpan , Ye Erkejiang , Cao Ruotong , Ali Sher , Ke Yuepeng , Yang Junjie , Yokoyama Tatsushi , Liu Jin , Zhang Xiaoyan , Sakamoto Masayuki , Sun Lin , Zhou Yubin , Wang Youjun
Published: February 2024

Endoplasmic reticulum (ER) calcium (Ca2+) homeostasis is essential for maintaining normal cellular physiological functions. Its disturbance is strongly linked to the onset and progression of human diseases, including cancer, developmental defects, and neurodegenerative disorders. The lack of sensitive ratiometric ER Ca2+indicators, nevertheless, hinders systematic investigation of ER Ca2+modulators and the underlying mechanisms. Capitalizing on two ultra-sensitive ER Ca2+indicators and CRISPR-based genome-wide screening, we identified a set of proteins capable of reducing the ER Ca2+content. Further comparative analysis and qPCR validation pinpointed adenylate cyclase 9 (AC9), which is upregulated during neuronal differentiation, as a key ER-Ca2+-reducing regulator. Mechanistically, AC9-mediated production of cAMP is not essential for its ability to reduce ER Ca2+content. Instead, AC9 inhibits store operated calcium entry (SOCE) by acting on Orai1, ultimately causing attenuation of ER Ca2+level. More physiologically relevant, upregulation of AC9 in neurons is essential for reducing ER Ca2+levels duringDrosophilabrain development. Collectively, this study lays a solid groundwork for further in-depth exploration of the regulatory mechanisms dictating ER Ca2+homeostasis during neuronal differentiation and brain development.
Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex
Authors: Quave Cana B. , Vasquez Andres M. , Aquino-Miranda Guillermo , Marín Milagros , Bora Esha P. , Chidomere Chinenye L. , Zhang Xu O. , Engelke Douglas S. , Do-Monte Fabricio H.
Published: February 2024

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of cat odor (Risk-Takers) or exhibited increased avoidance (Risk-Avoiders), as revealed by K-means clustering. Single-unit recordings from the prelimbic cortex (PL) demonstrated decreased neuronal activity upon acute morphine exposure in both Risk-Takers and Risk-Avoiders, but this firing rate suppression was absent after repeated morphine administration. Risk-Avoiders also displayed distinct post-morphine excitation in PL which persisted across conditioning. During the preference test, subpopulations of PL neurons in all groups were either excited or inhibited when rats entered the paired side. Interestingly, the inhibition in PL activity was lost during the subsequent conflict test in both saline and Risk-Avoider groups, but persisted in Risk-Takers. Additionally, Risk-Takers showed an increase in the proportion of PL neurons displaying location-specific firing in the drug-paired side from the preference to the conflict test. Together, our results suggest that persistent PL inhibitory signaling in the drug-associated context during motivational conflict may underlie increased risk-taking behavior following opioid exposure.

SIGNIFICANCE STATEMENT

Risky opioid use is well established in opioid use disorder, but the underlying neural correlates are poorly understood. In this study, we present findings from a novel behavioral task in which rats face a motivational conflict between contextual opioid reward memory and a naturalistic predator threat. Performing neuronal recordings in the prelimbic prefrontal cortex (PL), a brain region critical for executive decision-making, we demonstrate enhanced representation of drug-associated context and persistent inhibitory signaling by PL neurons that occur alongside opioid-induced risk-taking behavior. Our findings refine a preclinical model for studying addiction, establish PL as a prime region for investigating drug-environment interactions, and positions the prefrontal cortex as a candidate region for translational studies targeting risky opioid use.
Depression Attenuates Caudate and Dorsolateral Prefrontal Cortex Alpha and Beta Power Response to Reward
Authors: Qian Helen , Johnson Graham W , Hughes Natasha C , Paulo Danika L , Zhao Zixiang , Subramanian Deeptha , Dhima Kaltra , Bick Sarah K
Published: February 2024

Depression is a prevalent psychiatric condition and a common comorbidity across neurological disorders. Common symptoms include anhedonia, negative emotional biases, and cognitive dysfunction. Beta (15-30 Hz) neural oscillations have been shown to increase during reward-based learning within fronto-striatal reward networks. Corticostriatal beta oscillations have also been implicated in cognitive functions including working memory. However, the relationship between beta oscillations and depression remains unknown. Using intracranial recordings, we aimed to investigate how depression modulates the spectral power of neural oscillations in corticostriatal structures during reward feedback in a working memory task. Thirty movement disorder patients undergoing awake deep brain stimulation surgery with electrode trajectories traversing the caudate or dorsolateral prefrontal cortex (DLPFC) participated in this study. We recorded local field potential data intraoperatively as subjects completed a 2-back verbal working memory task where they identified whether a word matched the word presented two trials prior. Subjects received reward in the form of visual feedback for correct answers. Word stimuli had either a positive, negative, or neutral emotional valence. Subjects completed the Beck Depression Inventory-II preoperatively, and we used a cut-off score of 14 to identify patients with depression. We found that caudate and DLPFC power increased in the alpha (8-15 Hz) and beta range during reward feedback and that this increase was significantly greater for subjects without depression compared to depressed subjects. In non-depressed patients, positive feedback stimuli evoked significantly higher beta power in the caudate during reward compared to neutral and negative stimuli. In depressed patients, emotional valence did not affect reward-related caudate spectral power, while DLPFC alpha power was significantly higher following positive emotional stimuli in comparison to neutral but not negative stimuli. We additionally found that anti-depressant medications (ADMs) generally blunted alpha and beta reward signaling processes in the DLPFC. This blunting effect on reward-related alpha power in the DLPFC, however, was reversed in depressed patients, indicating that the effects of ADMs on reward signaling processes may depend on whether a patient is exhibiting depression symptoms. Our findings suggest that depression suppresses the alpha and beta power response to both reward and emotional stimuli during working memory, indicating power attenuation in these frequency bands may contribute to emotional and cognitive depression symptoms.
The Optimization of High-Protein Duckweed Cultivation in Eutrophicated Water with Mutualistic Bacteria
Authors: Akkarajeerawat Sunyapat , Chauvanasmith Thanatkorn , Keatsirisart Chanan
Published: February 2024

The exponential increase in the human population is the leading cause of a global food crisis and the rise of humanity’s carbon footprint level. One such approach to resolve these issues is the cultivation of duckweed (Wolffia globosa) for consumption in the Northern and Northeastern provinces of Thailand. In particular, duckweed has drawn increasing attention due to its rapid growth rate, adaptability to extreme conditions, and potential as a protein alternative; however, their properties can be greatly enhanced. Our research investigates two optimizations for the cultivation of duckweeds: in the medium’s nitrogen-phosphorus concentration and the use of plant growth-promoting bacteria (PGPB). We hypothesized that using phosphorus-rich water and PGPB would significantly increase duckweed biomass production, while nitrogen-rich water would increase protein content. This was based on evidence from past research showing that aquatic plants have high nitrogen and phosphorus uptake and that PGPB can support the growth of plants by nitrogen fixation. We found that the phosphorus-rich group boosted biomass greatly, while the nitrogen-rich group significantly enhanced their protein value. Furthermore, PGPB yielded the highest increase in biomass, but had an insignificant impact on protein. Based on our results, we recommend the use of nitrogen and phosphorus-rich water and PGPB to optimize duckweed cultivation, addressing the global food crisis and environmental impact.
Stability of influenza A virus in droplets and aerosols is heightened by the presence of commensal respiratory bacteria
Authors: David Shannon C. , Schaub Aline , Terrettaz Céline , Motos Ghislain , Costa Laura J. , Nolan Daniel S. , Augugliaro Marta , Glas Irina , Pohl Marie O. , Klein Liviana K. , Luo Beiping , Bluvshtein Nir , Violaki Kalliopi , Hugentobler Walter , Krieger Ulrich K. , Peter Thomas , Stertz Silke , Nenes Athanasios , Kohn Tamar
Published: February 2024

Aerosol transmission remains a major challenge for the control of respiratory viruses, particularly for those that cause recurrent epidemics, like influenza A virus (IAV). These viruses are rarely expelled alone, but instead are embedded in a consortium of microorganisms that populate the respiratory tract. The impact of microbial communities and inter-pathogen interactions upon the stability of transmitted viruses is well-characterised for pathogens of the gut, but is particularly under-studied in the respiratory niche. Here, we assessed whether the presence of 5 different species of common commensal respiratory bacteria could influence the stability of IAV within droplets deposited on surfaces and within airborne aerosol particles at typical indoor air humidity. It was found that bacterial presence within stationary droplets, either a mixed community or individual strains, resulted in 10- to 100-fold more infectious IAV remaining after 1 hour. Bacterial viability was not required for this viral stabilisation, though maintained bacterial morphology seemed to be essential. Additionally, non-respiratory bacteria tested here had little stabilising effect, indicating this phenomenon was respiratory-specific. The protective bacteria stabilised IAV in droplets via induction of early efflorescence due to flattened droplet morphology during drying. Even when no efflorescence occurred at high humidity or the bacteria-induced changes in droplet morphology were abolished by aerosolization instead of deposition on a well-plate, the bacteria remained protective. This indicates an additional stabilisation mechanism that is currently unknown. Notably, respiratory bacteria at equivalent density offered varying degrees of protection in droplets, with the Gram-positive speciesStaphylococcus aureusandStreptococcus pneumoniaebeing the most robustly stabilising. This suggests that the composition of an individual’s respiratory microbiota could be a previously un-considered host-specific factor influencing the efficacy of expelled viral spread. Identifying novel host-specific factors such as the commensal microbiota that can influence viral stability in the environment will further increase our understanding of individual transmission risks, and will provide novel opportunities to limit the spread of respiratory infections within our populations.

Synopsis

Our findings have significant environmental and health relevance, as they identify the host respiratory microbiota as a novel factor potentially contributing to environmental viral stability within indoor environments.
Nuclear pores safeguard the integrity of the nuclear envelope
Authors: Taniguchi Reiya , Orniacki Clarisse , Kreysing Jan Philipp , Zila Vojtech , Zimmerli Christian E. , Böhm Stefanie , Turoňová Beata , Kräusslich Hans-Georg , Doye Valérie , Beck Martin
Published: February 2024

Nuclear pore complexes (NPCs) constitute giant channels within the nuclear envelope that mediate nucleocytoplasmic exchange. NPC diameter is thought to be regulated by nuclear envelope tension, but how such diameter changes are physiologically linked to cell differentiation, where mechanical properties of nuclei are remodeled and nuclear mechanosensing occurs, remains unstudied. Here we used cryo-electron tomography to show that NPCs dilate during differentiation of mouse embryonic stem cells into neural progenitors. In Nup133-deficient cells, which are known to display impaired neural differentiation, NPCs however fail to dilate. By analyzing the architectures of individual NPCs with template matching, we revealed that the Nup133-deficient NPCs are structurally heterogeneous and frequently disintegrate, resulting in the formation of large nuclear envelope openings. We propose that the elasticity of the NPC scaffold mechanically safeguards the nuclear envelope. Our studies provide a molecular explanation for how genetic perturbation of scaffolding components of macromolecular complexes causes tissue-specific phenotypes.
Intact Somatosensory Temporal Sensitivity in Adults on the Autism Spectrum: A High-Density Electrophysiological Mapping Study Using the Mismatch Negativity (MMN) Sensory Memory Paradigm
Authors: Isenstein Emily L. , Freedman Edward G. , Molholm Sophie , Foxe John J.
Published: February 2024

Atypical reactivity to somatosensory inputs is common in autism spectrum disorder and carries considerable impact on downstream social communication and quality of life. While behavioral and survey work have established differences in the perception of somatosensory information, little has been done to elucidate the underlying neurophysiological processes that drive these characteristics. Here, we implemented a duration-based somatosensory mismatch negativity paradigm to examine the role of temporal sensitivity and sensory memory in the processing of vibrotactile information in autistic (n=30) and neurotypical (n=30) adults. To capture the variability in responses between groups across a range of duration discrepancies, we compared the electrophysiological responses to frequent standard vibrations (100 ms) and four infrequent deviant vibrations (115, 130, 145, and 160 ms). The same stimuli were used in a follow-up behavioral task to determine active detection of the infrequent vibrations. We found no differences between the two groups with regard to discrimination between standard and deviant vibrations, demonstrating comparable neurologic and behavioral temporal somatosensory perception. However, exploratory analyses yielded subtle differences in amplitude at the N1 and P220 time points. Together, these results indicate that the temporal mechanisms of somatosensory discrimination are conserved in adults on the autism spectrum, though more general somatosensory processing may be affected. We discuss these findings in the broader context of the MMN literature in autism, as well as the potential role of cortical maturity in somatosensory mechanisms.
Ca2+-driven cytoplasmic backflow secures spindle position in fertilized mouse eggs
Authors: Totsuka Takaya , Ohsugi Miho
Published: February 2024

Abstract

Fertilization triggers hours-long Ca2+oscillations in mammalian eggs, but the effects of repeated Ca2+surges remain unclear. Here, we investigate spindle dynamics and its relationship with cytoplasmic streaming in fertilized mouse eggs. The spindle, initially parallel to the plasma membrane, rotates vertically, in accordance with previously reported results using artificially activated eggs. Intriguingly, it transiently reverses its rotation direction in synchrony with Ca2+oscillations, regardless of artificially altered frequency. This effect results from cytoplasmic streaming, initially moving from spindle to egg center, displaying a Ca2+-dependent backflow. Streaming also impacts spindle positioning, balancing spindle rotation and cortical localization maintenance. We provide evidence that Ca2+-dependent cortical myosin II activation causes actomyosin contraction, leading to transient streaming towards non-contracting actin cap regions overlaying chromosomes. Our findings underscore the role of Ca2+oscillations in maintaining spindle position in fertilized eggs, thereby ensuring highly asymmetric division and preservation of maternal stores in zygotes.
Insights into the role of glycerophospholipids on the iron export function of SLC40A1 and the molecular mechanisms of ferroportin disease
Authors: Debbiche Rim , Elbahnsi Ahmad , Uguen Kévin , Ka Chandran , Callebaut Isabelle , Le Gac Gérald
Published: February 2024

SLC40A1 is the sole iron export protein reported in mammals. In humans, its dysfunction is responsible for ferroportin disease, an inborn error of iron metabolism transmitted as an autosomal dominant trait and observed in different ethnic groups. As a member of the major facilitator superfamily, SLC40A1 requires a series of conformational changes to enable iron translocation across the plasma membrane. The influence of lipids on these conformational changes has been little investigated to date. Here, we combine molecular dynamics simulations of SLC40A1 embedded in bilayers with experimental alanine scanning mutagenesis to analyze the specific role of glycerophospholipids. We identify four basic residues (Lys90, Arg365, Lys366 and Arg371) that are located at the membrane-cytosol interface and consistently interact with POPC and POPE lipid molecules. These residues surround a network of salt bridges and hydrogens bonds that play a critical role in stabilizing SLC40A1 in its basal outward-facing conformation. More deeply embedded in the plasma membrane, we identify Arg179 as a charged amino acid residue also tightly interacting with lipid phosphates. This result into a local deformation of the lipid bilayer. Interestingly, Arg179 is adjacent to Arg178, which forms a functionally important salt-bridge with Asp473 and is a recurrently associated with ferroportin disease when mutated to glutamine. We demonstrate that the two p.Arg178Gln and p.Arg179Thr missense variants have similar functional behaviors. These observations provide insights into the role of phospholipids in the formation/disruption of the SLC40A1 inner gate, and give a better understanding of the diversity of molecular mechanisms of ferroportin disease.
Establishment of terminal selector combinations in optic lobe neurons
Authors: Simon Félix , Holguera Isabel , Chen Yen-Chung , Malin Jennifer , Valentino Priscilla , Njoo-Deplante Claire , El-Danaf Rana Naja , Kapuralin Katarina , Erclik Ted , Konstantinides Nikolaos , Özel Mehmet Neset , Desplan Claude
Published: February 2024

The medulla is the part of the Drosophila optic lobe with the greatest neuronal diversity, in which the identity of each neuronal type is specified in progenitors and newborn neurons via the integration of temporal, spatial, and Notch-driven patterning mechanisms. This identity is maintained in differentiating and adult neurons by the expression of neuronal type-specific combinations of terminal selectors, which are transcription factors expressed continuously during development and in the adult that are thought to control all neuronal type-specific gene expression. However, how the patterning mechanisms establish terminal selector expression is unknown. We have previously characterized the temporal and Notch origin of medulla neurons. Here we have used single-cell mRNA-sequencing to characterize their spatial origins and identified two new spatial subdomains. Together, this makes the medulla the first complex brain structure for which the patterning mechanisms specifying the identity of each neuronal type are known. This knowledge allowed us to identify correlations between patterning information, terminal selector expression and neuronal features. Our results suggest that different subsets of the patterning information accessible to a given neuronal type control the expression of each of its terminal selectors and of modules of terminal features, including neurotransmitter identity. Therefore, the evolution of new neuronal types could rely on the acquisition of modules of neuronal features pre-determined by their developmental origin.
High-throughput nanopore DNA sequencing of large insert fosmid clones directly from bacterial colonies
Authors: Chuzel Léa , Sinha Amit , Cunningham Caileigh V. , Taron Christopher H.
Published: February 2024

Fosmids and cosmids are vectors frequently used in functional metagenomic studies. With a large insert capacity (around 30 kb) they can encode dozens of cloned genes or in some cases, entire biochemical pathways. Fosmids with cloned inserts can be transferred to heterologous hosts and propagated to enable screening for new enzymes and metabolites. After screening, fosmids from clones with an activity of interest must bede novosequenced, a critical step towards identification of the gene(s) of interest. In this work, we present a new approach for rapid and high-throughput fosmid sequencing directly fromEscherichia colicolonies without liquid culturing or fosmid purification. Our sample preparation involves fosmid amplification with phi29 polymerase and then direct nanopore sequencing using the Oxford Nanopore Technologies system. We also present a bioinformatics pipeline termed “phiXXer” that facilitates bothde novoread assembly and vector trimming to generate a linear sequence of the fosmid insert. Finally, we demonstrate accurate sequencing of 96 fosmids in a single run and validate the method using two fosmid libraries that contain cloned large insert (∼30-40 kb) genomic or metagenomic DNA.

Importance

Large-insert clone (fosmids or cosmids) sequencing is challenging and arguably the most limiting step of functional metagenomic screening workflows. Our study establishes a new method for high-throughput nanopore sequencing of fosmid clones directly from lysedE. colicells. It also describes a companion bioinformatic pipeline that enablesde novoassembly of fosmid DNA insert sequences. The devised method widens the potential of functional metagenomic screening by providing a simple, high-throughput approach to fosmid clone sequencing that dramatically speeds the pace of discovery.
Distinct dynamics and intrinsic properties in ventral tegmental area populations mediate reward association and motivation
Authors: Elum Jordan E , Szelenyi Eric R , Juarez Barbara , Murry Alexandria D , Loginov Grigory , Zamorano Catalina A , Gao Pan , Wu Ginny , Ng-Evans Scott , Xu Xiangmin , Golden Sam A , Zweifel Larry S
Published: February 2024

Ventral tegmental area (VTA) dopamine neurons regulate reward-related associative learning and reward-driven motivated behaviors, but how these processes are coordinated by distinct VTA neuronal subpopulations remains unresolved. Here we examine the neural correlates of reward-related prediction-error, action, cue, and outcome encoding as well as effort exertion and reward anticipation during reward-seeking behaviors. We compare the contribution of two primarily dopaminergic and largely non-overlapping VTA subpopulations, all VTA dopamine neurons, and VTA GABAergic neurons of the mouse midbrain to these processes. The dopamine subpopulation that projects to the nucleus accumbens (NAc) core preferentially encodes prediction-error and reward-predictive cues. In contrast, the dopamine subpopulation that projects to the NAc shell preferentially encodes goal-directed actions and reflects relative reward anticipation. VTA GABA neuron activity strongly contrasts VTA dopamine population activity and preferentially encodes reward outcome and retrieval. Electrophysiology, targeted optogenetics, and whole-brain input mapping reveal heterogeneity among VTA dopamine subpopulations. Our results demonstrate that VTA subpopulations carry distinct reward-related learning and motivation signals and reveal a striking pattern of functional heterogeneity among projection-defined VTA dopamine neuron populations.
Mountable miniature microphones to identify and assign mouse ultrasonic vocalizations
Authors: Waidmann Elena N. , Yang Victor H.Y. , Doyle William C. , Jarvis Erich D.
Published: February 2024

Vocal communication is a major component of animal social behavior. Vocalizations can be learned or innate, and can convey a variety of signals, including territorial limits, the presence of predators, or courtship intent. Mouse ultrasonic vocalizations (USVs) are a promising model in which to study mammalian vocal production circuits. While mouse USVs are innate, mice still show complex vocal behavior, including production of structured song composed of multiple syllable types and the ability to modify their vocal rate and syllable repertoire based on social conditions. Though in courtship interactions male mice produce the majority of the emitted USVs, female mice are capable of emitting USVs. In order to study the underlying mechanisms of vocal production in freely behaving pairs of mice, it is necessary to identify the individual responsible for each syllable in group settings. Previous methods to identify the source of an individual USVs have used high-density microphone arrays and triangulation methods, which involve the use of multiple costly microphones and require implementation of complex computational methods. Here we identified, developed, and used an inexpensive, mountable, ultrasound-sensitive miniature-microphone system to record and identify USVs from individual mice during dual socializing behavior. Our system includes custom circuit boards that can be fitted to individual mice and connected to a variety of existing USV recording systems. We found that these miniature microphones reliably detected mouse USVs, and that a high percentage (90%) of vocalizations could be attributed to a specific animal in a vocalizing pair based on the relative amplitude differences alone. This simple readout method avoids the implementation of complicated triangulation methods. By pairing this method with simultaneous video recording and automated animal body part and identity tracking, we were able to study and describe the broader courtship behavioral landscape, in which USV production is one component. These results offer a promising, low-cost, and simple method that researchers can implement to study the social vocal communication between at least pairs of vocalizing mice.
Hibiscus bullseyes reveal mechanisms controlling petal pattern proportions that influence plant-pollinator interactions
Authors: Riglet Lucie , Zardilis Argyris , Fairnie Alice L. , Yeo May T. , Jönsson Henrik , Moyroud Edwige
Published: February 2024

Colourful patterns on flower corollas are key signals to attract pollinators. The formation of such motifs relies on the establishment of developmental boundaries that partition the growing petal epidermis into different subdomains, where cells can produce specific pigments and acquire distinctive cell shapes and textures. While some of the transcription factors and biosynthetic pathways producing these characteristics as cell differentiate have been extensively studied, the upstream processes restricting the activities of molecular players to specific regions of the petal epidermis remain enigmatic. Here, we unveil that the petal surface ofHibiscus trionum, an emerging model system featuring a bullseye on its corolla, is pre-patterned as the position of the bullseye boundary is specified long before the motif becomes visible to the human eye. Using a 1-D computational model, we explore how a boundary established at such an early stage can be maintained throughout development. Reciprocally, by exploiting transgenic lines and natural variants, we show that plants can regulate the relative position of the boundary during the pre-patterning phase or modulate division and growth on either side of this boundary at later developmental stages to yield variations in final bullseye proportions. Finally, we provide evidence that such modifications in bullseye size have functional significance as buff-tailed bumblebees (Bombus terrestris) can reliably identify a food source based on the size of its bullseye. Notably, we found that individuals exhibit a clear preference for the larger bullseye ofH. trionumover the smaller pattern of its close relative,H. richardsonii.