bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of exotic biosecurity threat ribgrass mosaic virus and novel tobamoviruses through metatranscriptomic sequencing of animal gut content
Authors: Mahar Jackie , Mifsud Jonathon C. O. , Van Brussel Kate , Lachenauer Anna E. , Harvey Erin , Turnbull Olivia M. H. , Bonat Stefanie , Newsome Thomas M. , Olsson Annabelle , Chiu-Werner Antje , Jones Menna E. , Holmes Edward C. , Maina Solomon
Published: December 2024

Ribgrass mosaic virus (RMV) and related viruses of the genusTobamovirus(Virgaviridae) are cruciferous plant pathogens that represent a threat to global horticultural systems. In Australia, they are considered exotic biosecurity threats, and an incursion of these viruses would require rapid and strict control efforts. However, current surveillance methods for these viruses are limited. We examined whether RMV and related tobamoviruses could be detected by deep sequencing of gut metatranscriptomes of vertebrate animals and ticks. Using this method, we discovered that RMV, as well as a novel relative of RMV, and two highly diverse novel tobamoviruses are present in Australia. RMV was detected in multiple sites in both the Australian Capital Territory (ACT) and Tasmania, two regions separated by approximately 700km of land and 200km of water. The novel relative of RMV was detected in the ACT and New South Wales (NSW), while the highly divergent novel tobamoviruses were each detected in a single state, NSW and Queensland (QLD). In addition, Tobacco mild green mosaic virus, which is already known to be present in Australia, was detected in QLD using this method. This work highlights the potential utility of metatranscriptomic sequencing of wild animal gut for the surveillance of biosecurity threats to native and agricultural plant species.

Importance

Plant viruses can have devastating impacts on global horticulture. Tobamoviruses (familyVirgaviridae, genusTobamovirus) are among the most damaging seed-borne viruses in horticultural crops, and Australia is free of many of the tobamoviruses that cause major crop losses in other countries. These viruses are extremely difficult to eradicate. Consequently, early detection of incursions is key to the control of these viruses in Australia, alongside rapid deployment of eradication and management plans. Current biosecurity surveillance methods in Australia rely on visual inspection, immunological assays, and molecular methods such as screening of imported seed lots. This study introduces a complementary approach that utilises unbiased metatranscriptomic sequencing of animal gut material to detect cryptic plant viruses circulating in nature. Using this approach, we detected five different tobamovirus circulating in Australia, including a virus thought to be exotic and three novel viruses. This unique approach highlights alternative options for surveillance/detection of exotic crop viruses.
Description, Development and Application of the Integrated Transport and Health Impact Modelling Tool for Global Cities (ITHIM-Global)
Authors: Khreis Haneen , Abbas Ali , Gil-Sanchez Daniel , Tatah Lambed , Schroeder Anna , Goel Rahul , Brand Christian , Johnson Rob , Woodcock James
Published: December 2024

Abstract

The Integrated Transport and Health Impact Modelling Tool for Global Cities (ITHIM-Global) was developed as an open-source tool to assess the impacts of transport mode shifts on public health and the environment in low- and middle-income countries (LMICs) where the need for such assessment is urgent and rising. The model simulates the impacts on all-cause and cause-specific mortality and years of life lost outcomes through a multi-pathway framework, specifically including physical activity, air pollution exposure, and road traffic fatalities. In addition, the model estimates changes in carbon dioxide emissions resulting from these mode shifts. ITHIM-Global employs a quasi-microsimulation approach that enables individualized exposure estimates by age, sex, and activity levels and utilises up- to-date exposure and dose-response functions that account for the non-linear relationship between physical activity levels and health. To demonstrate its functionality, document its strengths and weaknesses, and aid users, the model was applied to Bogota, Colombia, using three hypothetical scenarios, each shifting 5% of trips to one of bus, car, or cycling. Results indicate that increasing public or active transport modes enhances public health, primarily driven by gains in physical activity and to a lesser extent by reductions in traffic-related emissions. Conversely, a shift to car usage worsens health outcomes due to decreased physical activity and increased pollution exposure. ITHIM-Global serves as a flexible, detailed Health Impact Assessment (HIA) tool adaptable to urban areas across LMICs and this article delves into underlying assumptions and their influence to advance generalisable lessons on risk assessment and model development. The modular structure of ITHIM-Global, its covering of individual and population-level analyses, and extensive documentation provide an accessible, evidence-based approach for city planners and practitioners to optimize transport policies that support public health and mitigate environmental harm.

Graphical Abstract

Highlights

We describe the Integrated Transport and Health Impact Modelling Tool for Global cities (ITHIM- Global), designed for low- and middle-income country (LMIC) cities.

We apply ITHIM-Global to Bogotá, simulating impacts from three mode shift scenarios with a 5- percentage point increase in car, cycling, and bus shares.

We simulate the impacts on physical activity, air pollution, road traffic fatalities, and attributable mortalities and years of life lost.

We describe in detail the model’s elements to aid future uptake, development, and extension to other cities. We discuss strengths, weaknesses, and underlying assumptions to advance generalisable lessons on risk assessment and model development.
Significant rise ofChlamydia pneumoniaediagnoses at Marseille University Hospitals, 2024, France
Authors: Edouard Sophie , Attamna Rayane , Million Matthieu , Boschi Céline , Delerce Jeremy , Caputo Aurélia , Stoupan Didier , Diene Seydina , Kacel Idir , Andrieu Claudia , Levasseur Anthony , Chaudet Hervé , Rolain Jean-Marc , Lesage Lucile , Morand Aurélie , Fournier Pierre-Edouard , Lagier Jean-Christophe , Fenollar Florence , La Scola Bernard , Colson Philippe
Published: December 2024

We report a 19-fold increase in 2024 of qPCR diagnoses ofChlamydia pneumoniaeinfections in Marseille, Southern France, with 37 cases versus 10 between 2018-2023. These mostly affected children, and young adults. We obtained fourC. pneumoniaegenomes, all of serotype ST16, suggesting an epidemic circulation in our geographical area.
Care seeking for diarrheal illness: a systematic review and meta-analysis
Authors: Wiens Kirsten E. , Miller Marissa H. , Costello Daniel J. , Solomon Ashlynn P. , Hilbert Skye M. , Shipper Andrea G. , Lee Elizabeth C. , Azman Andrew S.
Published: December 2024

Background

Monitoring and treating diarrheal illness often rely on individuals seeking care at hospitals or clinics. Cases that seek care through pharmacies and community health workers (CHW) are frequently excluded from disease burden estimates, which are used to allocate mitigation resources. Studies on care seeking behavior can help identify these gaps but typically focus on children under five, even though diarrheal diseases like cholera and Enterotoxigenic E. coli affect all age groups. This study aimed to estimate the proportion of individuals seeking care for themselves or their children with diarrhea, considering different age groups, case definitions, and study settings.

Methods and Findings

We conducted a systematic review of population-based primary research studies published during 2000–2024 that examined care-seeking behavior for diarrhea. We included 166 studies from 62 countries. Hospitals and clinics were the most common source of care sought outside the home, with CHW and health posts rarely reported. Using a random-effects meta-analysis, we found substantial heterogeneity in care seeking between studies from low- and middle- income countries (I2= 99.3) and estimated that the proportion of diarrhea cases seeking care at a hospital or clinic was 32.8% on average (95% Confidence Interval (CI) 28.1% to 37.9%; prediction interval 3.3% to 87.5%). Although there were trends toward higher care-seeking for children compared to adults, substantial variation existed between studies, and the differences were not significant. We estimated that the adjusted odds of seeking care at a hospital or clinic were significantly higher for severe diarrhea and cholera compared to general diarrhea (Odds Ratio 3.43; 95% CI 1.71 to 6.88).

Conclusions

Our findings confirm that passive surveillance through hospitals and clinics may substantially undercount the number of people with diarrhea, particularly those with milder symptoms, although this proportion varied widely. Additionally, our findings underscore the importance of including care seeking questions across all age groups in future studies, as we cannot assume lower care seeking for adults across all settings. Our study was limited by fewer data on care- seeking from health posts, traditional healers, and CHW compared to hospitals and clinics, highlighting a need for further research on these sources of care.
Association between epidural catheter tip malposition and anesthesiologists’ experience after graduation: a cross-sectional study using postoperative CT images
Authors: Matsuo Mitsuhiro , Sakamoto Natsumi , Takebe Mariko , Takazawa Tomonori
Published: December 2024

Objectives

This study aimed to examine the incidence of epidural catheter tip malposition using postoperative CT images, and investigated its relationship with anesthesiologist and patient characteristics.

Methods

Patients who had undergone epidural anesthesia at our hospital during the previous 18 years, and who had a thorax and abdominal CT scan within 5 days after surgery were included. Malposition was defined if the tip of the catheter did not penetrate the ligamentum flavum in postoperative CT images.

Results

Among 189 eligible patients (median age 71 years, range 15-89), 78 (41%) were female. The median number of years of postgraduate experience of the physicians inserting the epidural catheter was 5.7 years (range 2.0-35.4). All epidural catheters were inserted using the paramedian approach in the left lateral decubitus position. The puncture site was the middle (48%) or lower (49%) thoracic spine. Epidural catheter malposition was observed in 24 patients (12.7%, 95% confidence interval [CI] 8.3-18.3). Among these cases, catheter tips were located at the vertebrae (vertebral arches: 9, transverse processes: 2, spinous process: 1), in superficial soft tissue (erector spinae: 5, subcutaneous: 4), and in deep soft tissue (intervertebral foramina: 2, subpleural space: 1). Anesthesiologists in the malposition group had significantly more experience since graduation (median 10.1 years vs. 5.6 years, P=0.010). No other characteristics showed an association with catheter malposition.

Conclusions

Analysis of postoperative CT images revealed that the epidural catheter tip did not penetrate the ligamentum flavum in approximately 13% of cases. Our results suggest that even experienced anesthesiologists should be vigilant regarding proper catheter tip positioning.
Repeated net-tDCS of the hypothalamus appetite-control network reduces inhibitory control and sweet food intake in persons with overweight or obesity
Authors: Ester-Nacke Theresa , Veit Ralf , Thomanek Julia , Book Magdalena , Tamble Lukas , Beermann Marie , Löffler Dorina , Salvador Ricardo , Ruffini Giulio , Heni Martin , Birkenfeld Andreas L. , Plewnia Christian , Preissl Hubert , Kullmann Stephanie
Published: December 2024

Background

Reduced inhibitory control is associated with obesity and neuroimaging studies indicate that diminished prefrontal cortex activity influence eating behavior and metabolism. The hypothalamus regulates energy homeostasis and is functionally connected to cortical and subcortical regions especially the frontal areas.

Objectives

We tested network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in appetite control.

Methods

In a randomized, double-blind parallel group design, 44 adults with overweight or obesity (BMI 30.6 kg/m2, 52.3 % female) received active (anodal or cathodal) or sham 12-channel net-tDCS on the hypothalamus appetite-control network for 25 minutes on three consecutive days while performing a Stop-Signal-Task to measure response inhibition. Before and after stimulation, state questionnaires assessed changes in desire to eat and food craving. Directly after stimulation, participants received a breakfast buffet to evaluatead-libitumfood intake. An oral glucose tolerance test was conducted at follow-up. Resting-state functional MRI was obtained at baseline and follow-up.

Results

The Stop-Signal Reaction Time (SSRT) was shorter in both active groups versus sham, indicating improved response inhibition. Additionally, a stronger increase in hypothalamic functional connectivity was associated with shorter SSRT. Caloric intake of sweet food was lower in the anodal group versus sham, but no main effects between groups were observed on total and macronutrient intake, food craving ratings and desire to eat. At follow-up, no differences were observed between groups on peripheral metabolism.

Conclusion

Our study suggests that modulating hypothalamic functional network connectivity patterns via net-tDCS may improve food choice and inhibitory control.

Graphical Abstract

Highlights

Active net-tDCS groups showed better inhibitory control compared to the sham group.

Stronger increase in hypothalamic functional connectivity associated with better inhibitory control after active net-tDCS.

No differences were found between the active net-tDCS and sham groups for total kilocaloric intake.

Anodal net-tDCS showed lower sweet food intake compared to the sham group.
Programming the elongation of mammalian cell aggregates with synthetic gene circuits
Authors: Courte Josquin , Chung Christian , Jain Naisargee , Salazar Catcher , Phuchane Neo , Grosser Steffen , Lam Calvin , Morsut Leonardo
Published: December 2024

A key goal of synthetic morphogenesis is the identification and implementation of methods to control morphogenesis. One line of research is the use of synthetic genetic circuits guiding the self-organization of cell ensembles. This approach has led to several recent successes, including control of cellular rearrangements in 3D via control of cell-cell adhesion by user-designed artificial genetic circuits. However, the methods employed to reach such achievements can still be optimized along three lines: identification of circuits happens by hand, 3D structures are spherical, and effectors are limited to cell-cell adhesion. Here we show the identification, in a computational framework, of genetic circuits for volumetric axial elongation via control of proliferation, tissue fluidity, and cell-cell signaling. We then seek to implement this design in mammalian cell aggregatesin vitro.We start by identifying effectors to control tissue growth and fluidityin vitro. We then combine these new modules to construct complete circuits that control cell behaviors of interest in space and time, resulting in measurable tissue deformation along an axis that depends on the engineered signaling modules. Finally, we contextualizein vitroandin silicoimplementations within a unified morphospace to suggest further elaboration of this initial family of circuits towards more robust programmed axial elongation. These results and integratedin vitro/in silicopipeline demonstrate a promising method for designing, screening, and implementing synthetic genetic circuits of morphogenesis, opening the way to the programming of various user-defined tissue shapes.
Self-organizing human heart assembloids with autologous and developmentally relevant cardiac neural crest-derived tissues
Authors: Kostina Aleksandra , Kiselev Artem , Huang Amanda , Lankerd Haley , Caywood Sammantha , Jurado-Fernandez Ariadna , Volmert Brett , O’Hern Colin , Juhong Aniwat , Liu Yifan , Qiu Zhen , Park Sangbum , Aguirre Aitor
Published: December 2024

Neural crest cells (NCCs) are a multipotent embryonic cell population of ectodermal origin that extensively migrate during early development and contribute to the formation of multiple tissues. Cardiac NCCs play a critical role in heart development by orchestrating outflow tract septation, valve formation, aortic arch artery patterning, parasympathetic innervation, and maturation of the cardiac conduction system. Abnormal migration, proliferation, or differentiation of cardiac NCCs can lead to severe congenital cardiovascular malformations. However, the complexity and timing of early embryonic heart development pose significant challenges to studying the molecular mechanisms underlying NCC-related cardiac pathologies. Here, we present a sophisticated functional model of human heart assembloids derived from induced pluripotent stem cells, which, for the first time, recapitulates cardiac NCC integration into the human embryonic heartin vitro. NCCs successfully integrated at developmentally relevant stages into heart organoids, and followed developmental trajectories known to occur in the human heart. They demonstrated extensive migration, differentiated into cholinergic neurons capable of generating nerve impulses, and formed mature glial cells. Additionally, they contributed to the mesenchymal populations of the developing outflow tract. Through transcriptomic analysis, we revealed that NCCs acquire molecular features of their cardiac derivatives as heart assembloids develop. NCC-derived parasympathetic neurons formed functional connections with cardiomyocytes, promoting the maturation of the cardiac conduction system. Leveraging this model’s cellular complexity and functional maturity, we uncovered that early exposure of NCCs to antidepressants harms the development of NCC derivatives in the context of the developing heart. The commonly prescribed antidepressant Paroxetine disrupted the expression of a critical early neuronal transcription factor, resulting in impaired parasympathetic innervation and functional deficits in cardiac tissue. This advanced heart assembloid model holds great promise for high-throughput drug screening and unraveling the molecular mechanisms underlying NCC-related cardiac formation and congenital heart defects.

IN BRIEF

Human neural crest heart assembloids resembling the major directions of neural crest differentiation in the human embryonic heart, including parasympathetic innervation and the mesenchymal component of the outflow tract, provide a human-relevant embryonic platform for studying congenital heart defects and drug safety.
spotPCR: A Rapid and Efficient Approach for Indexing Individual Template Molecules using Unique Molecular Identifiers
Authors: Limberis Jason D , Nagel Roland J , Chakravorty Soumitesh , Block Dena , Dewell Scot , Nalyvayko Alina , Metcalfe John Z
Published: December 2024

Low-frequency mutations provide valuable insights in various fields, including drug resistance identification, cancer and infectious disease research. One promising strategy to enhance the sensitivity and specificity of mutation detection is the incorporation of unique molecular identifiers (UMIs) during polymerase chain reaction (PCR) amplification and before deep sequencing. However, conventional methods for UMI incorporation oRen necessitate multiple labor-intensive steps. spotPCR (Specific Primer Limited Unique Molecular Identifier Tagging PCR) overcomes these challenges, streamlining the UMI tagging process.
STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis
Authors: Olatoke Tasnim , Zhang Erik Y. , Wagner Andrew , He Quan , Li Siru , Astreinidis Aristotelis , McCormack Francis X. , Xu Yan , Yu Jane J.
Published: December 2024

Lymphangioleiomyomatosis (LAM) is a cystic lung disease that primarily affects women. LAM is caused by the invasion of metastatic smooth muscle-like cells into the lung parenchyma, leading to abnormal cell proliferation, lung remodeling and progressive respiratory failure. LAM cells have TSC gene mutations, which occur sporadically or in people with Tuberous Sclerosis Complex. Although it is known that hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) due to TSC2 gene mutations contributes to aberrant cell growth in LAM lung, tumor origin and invasive mechanism remain unclear. To determine molecular drivers responsible for aberrant LAM cell growth, we performed integrative single-cell transcriptomic analysis and predicted that STAT1 interacts with Pre-B cell leukemia transcription factor (PBX1) to regulate LAM cell survival. Here, we show activation of STAT1 and STAT3 proteins in TSC2- deficient LAM models. Fludarabine, a potent STAT1 inhibitor, induced the death of TSC2- deficient cells, increased caspase-3 cleavage, and phosphorylation of necroptosis marker RIP1. Fludarabine treatment impeded lung colonization of TSC2-deficient cells and uterine tumor progression, associated with reduced percentage of PCNA-positive cells in vivo. Interestingly, IFN-γ treatment increased STAT1 phosphorylation and PD-L1 expression, indicating that STAT1 aids TSC2-deficient tumor cells in evading immune surveillance in LAM. Our findings indicate that STAT1 signaling is critical for LAM cell survival and could be targeted to treat LAM and other mTORC1 hyperactive tumors.
Sneezing in response to bright light exposure: A case study in a photic sneezer
Authors: Bickerstaff Lucien , Trinkl Josef , Munkwitz Stephan , Spitschan Manuel
Published: December 2024

Background

The photic sneeze reflex (PSR) is a widespread, yet understudied phenomenon characterised by sneezing in response to bright-light exposure, reportedly affecting around 30% of the general population. Our goals were to collect real-world data to characterise PSR-inducing naturalistic light conditions, and to develop an indoor protocol to reliably induce the PSR in affected individuals using parametric stimuli.

Methods

This study was carried out on one male adult affected by photic sneezing (n=1). To characterise naturalistic light conditions eliciting photic sneezing, real-world light exposure was measured over a 30-day period, while logging PSR events. To study photic sneezing in response to artificial stimuli, a setup including a multi-primary LED source and an integrating sphere was used to present 30-second light stimuli to the participant while collecting pupillometric data with an eye-tracker.

Results

82 photic sneeze events were recorded, with an average of 2.73 sneezes per day and a range of 1 to 6 sneezes per event. At a sneeze event, illuminance is on average ten times bigger than five minutes before the sneeze event. A significant increase in illuminance is observed around 2 minutes before the sneeze event. Light levels go back down to pre-sneeze levels within 10 minutes after sneezing. Despite exposure to more than 150 stimuli, no sneeze could be artificially induced in the participant. However, a strong tickling sensation was consistently reported, especially for high illuminance settings.

Conclusions

Real-world light data confirmed that a sudden increase in environmental lighting conditions can induce photic sneezing. Further analysis could be relevant on instances of illuminance increments not eliciting a photic sneeze. The experimental setup only elicited tickling sensations, but with further testing and optimisation, it is reasonable to assume that it would reliably induce photic sneezes, thereby opening further mechanistic study of this intriguing phenomenon.
Exclusive cataloging of near-complete genomes unveils novel functional insights into the human gut microbiome
Authors: Ma Junyeong , Kim Nayeon , Cha Jun Hyung , Kim Wonjong , Kim Chan Yeong , Yang Sunmo , Beck Samuel , Lee Insuk
Published: December 2024

Understanding the human gut microbiome requires comprehensive genomic catalogs, yet many existing ones lack geographic diversity and include numerous medium-quality metagenome-assembled genomes (MAGs) missing up to 50% of genomic regions, potentially leading to inaccurate functional insights into the microbiome. To address these limitations, we developed an enhanced Human Reference Gut Microbiome (HRGM2), a catalog of near-complete (NC) MAGs (completeness ≥90% and contamination ≤5%) and isolate genomes (collectively ‘NC genomes’) with extensive geographic sampling. HRGM2 comprises 155,211 non-redundant NC genomes from 4,824 prokaryotic species across 41 countries, representing a 66% increase in genome count and a 50% boost in species diversity over the NC genome-based Unified Human Gastrointestinal Genome catalog. Extensive sampling from Africa revealed previously undetectable Africa-associated phyla, highlighting microbial links between humans and the environment. Given the high species complexity of the human gut microbiota, DNA-based species profiling using HRGM2 outperforms marker-based profiling in accuracy. Profiling genomes with enhanced protein functional annotations provides reliable insights into the microbiome. Notably, with exclusive use of NC genomes, HRGM2 enhances assessments of microbiota metabolic capacities and supports genome-scale metabolic models (GEMs) of entire gut microbiota. These findings offer novel functional perspectives on the human gut microbiome, achievable only through high-quality genome cataloging.
Calibration-free estimation of field dependent aberrations for single molecule localization microscopy across large fields of view
Authors: Droste Isabel , Schuitema Erik , Khan Sajjad , Heldens Stijn , van Werkhoven Ben , Lidke Keith A. , Stallinga Sjoerd , Rieger Bernd
Published: December 2024

Image quality in single molecule localization microscopy (SMLM) depends largely on the accuracy and precision of the localizations. While under ideal imaging conditions the theoretically obtainable precision and accuracy are achieved, in practice this changes if (field dependent) aberrations are present. Currently there is no simple way to measure and incorporate these aberrations into the Point Spread Function (PSF) fitting, therefore the aberrations are often taken constant or neglected all together. Here we introduce a model-based approach to estimate the field-dependent aberration directly from single molecule data without a calibration step. This is made possible by using nodal aberration theory to incorporate the field-dependency of aberrations into our fully vectorial PSF model. This results in a limited set of aberration fit parameters that can be extracted from the raw frames without a bead calibration measurement, also in retrospect. The software implementation is computationally efficient, enabling fitting of a full 2D or 3D dataset within a few minutes. We demonstrate our method on 2D and 3D localization data of microtubuli and nuclear pore complexes over fields of view (FOV) of up to 180 μm and compare it with spline-based fitting and a deep learning based approach.
Gene flow can reveal ghost lineages
Authors: Tricou Théo , Marsot Enzo , Boussau Bastien , Tannier Éric , de Vienne Damien M.
Published: December 2024

Ghost species, encompassing extinct, unknown, and unsampled taxa, vastly outnumber those typically included in phylogenetic analyses. This hidden diversity has been shown to influence the study of horizontal gene flow (e.g., introgression and horizontal gene transfer) by complicating the phylogenetic signals commonly used for their detection.

In this work, we explore the potential of horizontal gene transfer (HGT) detection methods based on phylogenies (i.e., reconciliation methods) to reveal and quantify ghost diversity along the branches of a species phylogeny. We succinctly present the theoretical framework for this approach, and we demonstrate, using simple simulations, that HGT signals, as interpreted by a reconciliation method, can reveal the presence and phylogenetic position of ghost clades, despite the absence of genomic data for these taxa. We anticipate possible limitations and difficulties in using HGT detection to explore ghost diversity and suggest promising approaches to address or circumvent them. Altogether, this proof of concept opens new lines of research for the future: a scarce fossil record and a large proportion of unknown lineages, especially in Archaea and Bacteria, does not equate to an absence of information for evolutionary studies.
Mapping neuropeptide sigaling in the human brain
Authors: Ceballos Eric G , Farahani Asa , Liu Zhen-Qi , Milisav Filip , Hansen Justine Y , Dagher Alain , Misic Bratislav
Published: December 2024

Neuropeptides are functionally diverse signaling molecules in the brain, regulating a wide range of basal bodily and cognitive processes. Despite their importance, the distribution and function of neuropeptides in the human brain remains underexplored. Here we comprehensively map the organization of human whole-brain neuropeptide receptors across multiple levels of description; from molecular and cellular embedding to mesoscale connectivity and macroscale cognitive specialization. Using gene transcription as a proxy, we reconstruct a topographic cortical and subcortical atlas of neuropeptide receptors for 38 neuropeptide receptors, across 14 different neuropeptide families. We find that most neuropeptide receptors are highly expressed either in cortex or subcortex, delineating an anatomical cortical-subcortical gradient. Neuropeptides preferentially co-localize with metabotropic neurotransmitters, suggesting a system-wide correspondence between slow-acting molecular signaling mechanisms. Mapping neuropeptide receptors and their cognate ligands onto white-matter connectomes, we demonstrate that specific neuropeptides families shape electrophysiological and haemodynamic inter-regional connectivity. To investigate the behavioural consequences of distributed neuropeptide systems, we apply meta-analytic decoding to neuropeptide maps and show a gradient of functions, from sensory-cognitive to reward and bodily functions. Finally, evolutionary analysis indicates extended positive selection for neuropeptides in early mammals, suggesting that refinement of neuropeptides coincides with the emergence of neocortex and higher cognitive function. Collectively, these results show that the neuropeptide receptors are highly organized across the human brain and closely intertwined with multiple features of brain structure and function.
Age-related decline in neural phase-locking to envelope and temporal fine structure revealed by frequency following responses: A potential signature of cochlear synaptopathy impairing speech intelligibility
Authors: Ponsot Emmanuel , Devolder Pauline , Dhooge Ingeborg , Verhulst Sarah
Published: December 2024

Assessing the contribution of cochlear synaptopathy (CS) to the variability in speech-in-noise intelligibility among individuals remains a challenge. While several studies have proposed biomarkers for CS based on neural phase-locking to the temporal envelope (ENV), fewer have investigated how CS affects the coding of temporal fine structure (TFS), despite its crucial role in speech-in-noise perception. In this study, we specifically examined whether TFS-based markers of CS could be derived from electrophysiological responses and psychophysical detection thresholds of spectral modulation (SM) in a complex tone, which serves as a parametric model of speech. We employed an integrated approach, combining psychophysical testing with frequency-following response (FFR) measurements in three groups of participants: young normal-hearing (yNH), older normal-hearing (oNH), and older hearing-impaired (oHI) individuals. We expanded on previous work by assessing phase-locking to both ENV, using a 4 kHz rectangular amplitude-modulated (RAM) tone, and TFS, using a low-frequency (<1.5 kHz) SM complex tone. Overall, FFR results showed significant reductions in neural phase-locking to both ENV and TFS components with age and hearing loss. Specifically, the strength of TFS-related FFRs, particularly the component corresponding to the harmonic closest to the peak of the spectral envelope (∼500 Hz), was negatively correlated with age, even after adjusting for audiometric thresholds. This TFS marker also correlated with ENV-related FFRs derived from the RAM tone, suggesting a shared decline in phase-locking capacity across low and high cochlear frequencies. Computational simulations of the auditory periphery indicated that the observed FFR strength reduction with age is consistent with approximately 50% loss of auditory nerve fibers, aligning with histopathological data. However, the TFS-based FFR marker did not account for variability in speech intelligibility observed in the same participants. Psychophysical measurements showed no age-related effects and were unrelated to the TFS-based FFR marker, highlighting the need for further psychophysical research to establish a behavioral counterpart. Altogether, our results demonstrate that FFRs to vowel-like stimuli can serve as a complementary electrophysiological marker for assessing neural coding fidelity to stimulus TFS. This approach could provide a valuable tool for better understanding the impact of CS on an important coding dimension for speech-in-noise perception.
Effects of an auxin antagonist, PEO-IAA, and an auxin transport inhibitor, NPA, on gametophore development inPhyscomitrium patens(Hedw.) Mitt
Authors: Robinson Shawn R , Ashton Neil W
Published: December 2024

Auxin sensing and polar auxin transport (PAT) are required for normal growth and development of stem internodes and leaves of gametophores ofPhyscomitrium(formerlyPhyscomitrella)patens. Auxin is required for the formation of leaf apical cells, and NPA-driven elevation of the intracellular auxin/cytokinin ratio stimulates bifurcation at the leaf margin. Auxin is implicated in the differentiation of the leaf midrib. Auxin sensing and PAT appear not to be needed for the transition of gametophore buds into leafy shoots.
Estimating changes in life expectancy in Hong Kong during the COVID-19 pandemic
Authors: Law Alexandra H. T. , Presanis Anne M. , Cheung Justin K. , Wu Peng , Schooling C. Mary , Cowling Benjamin J. , Wong Jessica Y.
Published: December 2024

Background

Hong Kong has one of the longest life expectancies in the world but was heavily impacted by COVID-19 in 2022.

Methods

We constructed sex-specific life tables from 1998-2023 using parametric bootstrapping to account for statistical uncertainty in mortality rates. We used Arriaga’s decomposition method to estimate age-specific contributions to overall changes in life expectancy over this period. We also estimated cause-specific mortality rates.

Results

Hong Kong reported 50666 deaths in 2020, 51354 in 2021, 63692 in 2022, and 54731 in 2023. Estimates of life expectancy in males and females in 2020 and 2021 were similar to the pre-pandemic trend from 1998-2019 but declined significantly in 2022. Life expectancy for males was 82.3 years in 2021 and 80.4 years in 2022, and for females it was 87.9 in 2021 and 86.4 years in 2022. Compared to the pre-pandemic trend, the 2022 values corresponded to reductions by 2.22 (95% CI: 2.08, 2.36) years in males and 2.30 (95% CI: 2.17, 2.43) years in females. The loss in life expectancy in 2022 was mainly attributed to increased respiratory mortality rates in adults aged 65 or above. In 2023 life expectancy increased by 0.60 (95% CI: 0.46, 0.75) years in males and by 1.10 (95% CI: 0.95, 1.26) years in females.

Conclusions

In 2022 a very high respiratory mortality rate in older adults in Hong Kong during the COVID-19 pandemic was associated with a reduction in life expectancy by more than 2 years. In 2023 life expectancy increased towards the pre-pandemic trend.
Decreased interleukin-8 levels in the peripheral blood of Alzheimer’s patients
Authors: Ros Francisco , Martínez Lozano María Dolores , Arnau Javier , Martínez Jacobo , Vericat Alejandro , Sánchez Rafael , Burgos Javier S.
Published: December 2024

Introduction

Multiple studies have reported variations in inflammatory levels in blood of Alzheimer’s disease (AD), although further research is needed to identify discriminatory biomarkers for AD diagnosis.

Methods

A prospective comparative paired study of a group of AD patients compared to normal controls (NC) was carried out in a multicenter study, where age and sex ratio were homogenized to avoid bias. The cohort comprised 39 patients with a diagnosis of AD (64.1% women; mean age 74.8±0.8 years) and 27 matched NC (66.7% women; 74.8±0.8 years). The diagnosis of AD was performed by neurologists using the Mini-Mental State Examination test (MMSE) and classical markers in cerebrospinal fluid (CSF) and/or amyloid-PET. We investigated the discriminatory potential of 13 serological parameters in blood, consisting of seven interleukins (IL-3, IL-4, IL-5, IL-6, IL-8, IL-12p40, and IL-15) and other 6 serological inflammatory markers (EGF, GM-CSF, IP-10, sCD40L, PDGF-AB/BB, and RANTES). Additionally, six sociodemographic variables were examined. Apolipoprotein E (APOE) genotype was also determined.

Results

The results revealed an inverse association between educational level, number of languages spoken, and physical activity, with the risk of AD. An enrichment of the APOE4 isoform was observed in AD (28 out of 39 AD vs 3 out of 24 NC). All circulating inflammation markers were lower in AD patients than in NC (except for IP-10 and sCD40L, while Il-3 and GM-CSF were undetectable in both groups), with statistically significant differences detected in IL-8, IL-12p40, and PDGF-AB/BB (AD/NC ratios of 0.56, 0.59, and 0.81, respectively). IL-8 was decreased specifically in APOE4 carriers (carriers/non-carriers ratio of 0.73), and in amyloid-positive cases (positives/NC ratio of 0.46), whereas IL-12p40 and PDGF-AB/BB showed positives/NC ratios of 0.56 and 0.83, respectively.

Discussion

Serum levels of IL-8, IL-12p40, and PDGF-AB/BB were significantly reduced in AD patients. Additionally, IL-8 decrease was associated with APOE4-carriers and amyloid-positive cases.
The avoidable health burden and healthcare costs related to alcohol consumption in Australia: multistate life table modelling
Authors: Wanjau Mary Njeri , Cobiac Linda , Shahid Mishel , Malawige Amila , Aminde Leopold , Subhi Moosa Al , Nguyen Phuong , Angeles Mary Rose , Ananthapavan Jaithri , Veerman Lennert
Published: December 2024

Background and Aims

Excessive use of alcohol is one of the leading risks for mortality and disability globally. In Australia, alcohol was the fifth-highest risk factor contributing to disease burden in 2019. Estimates of the avoidable (future) alcohol related burden can help make the case for investment in preventive measures. This analysis aims to estimate the avoidable burden related to alcohol consumption in Australia.

Design, setting, participants and intervention

The Alcohol Policy model (TAP),a proportional multi-state lifetable model was developed and used to estimate the avoidable alcohol-related disease, injury and healthcare cost burden by comparing a scenario where the Australian adult population (aged ≥ 15 years) continues to drink alcohol at current rates to an identical population that consumes no alcohol. Taking 2020 as the base year, an open cohort was modelled over a 60-year time horizon.

Measurements

Changes in population alcohol consumption are modelled to lead to changes in 1) incident cases and mortality from alcohol-related diseases and injuries, 2) long-term health outcomes summarised as health adjusted life years (HALYs) and 3) healthcare costs. Results are reported in single years, over 25 years and 60 years (for HALYs and healthcare costs). No discounting was applied.

Findings

Over the first 25 years, elimination of alcohol consumption at the population level could prevent over 25.9 million incident cases of alcohol-related diseases and injuries (89% acute causes, 1% cancers and 10% other modelled chronic diseases). This translates to 5.1 (95% uncertainty interval [UI] 4.0 to 6.2) million HALYs gained and AUD 55 (95% UI 36 to 75) billion saved in healthcare costs. Over a 60-year period, the potential health benefits increase to 17 (95%UI 14 to 21) million HALYs and is associated with AUD 68 (95%UI 9.6 to 130) billion in healthcare cost-savings.

Conclusion

Our findings show that the avoidable alcohol-related disease, injury and healthcare cost burden in Australia is substantial. These findings reinforce the need for investment in effective and cost-effective polices that reduce alcohol consumption.
Deep profiling of plant stress biomarkers following bacterial pathogen infection with protein corona based nano-omics
Authors: Coreas Roxana , Sridhar Nikitha , Lin Teng-Jui , Squire Henry J. , Voke Elizabeth , Landry Markita P.
Published: December 2024

Detection and remediation of stress in crops is vital to ensure agricultural productivity. Conventional forms of assessing stress in plants are limited by feasibility, delayed phenotypic responses, inadequate specificity, and lack of sensitivity during initial phases of stress. While mass spectrometry is remarkably precise and achieves high-resolution, complex samples, such as plant tissues, require time-consuming and biased depletion strategies to effectively identify low-abundant stress biomarkers. Here, we bypassed these reduction methods via a nano-omics approach, where gold nanoparticles were used to enrich time- and temperature-dependent stress-related proteins through biomolecular corona formation that were subsequently analyzed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). This nano-omic approach was more effective than a conventional proteomic analysis using UHPLC- MS/MS for resolving biotic-stress induced responses at early stages of pathogen infection inArabidopsis thaliana, well before the development of visible phenotypic symptoms, as well as in distal tissues of pathogen infected plants at early timepoints. The enhanced sensitivity of this nano-omic approach enables the identification of stress-related proteins at early critical timepoints, providing a more nuanced understanding of plant-pathogen interactions that can be leveraged for the development of early intervention strategies for sustainable agriculture.
Habitat filtering but not microbiota origin controls microbiome transplant outcomes in soil
Authors: Causevic Senka , Tackmann Janko , Sentchilo Vladimir , Malfertheiner Lukas , von Mering Christian , van der Meer Jan Roelof
Published: December 2024

Human activities cause global losses of soil microbiome diversity and functionality. Microbiota transplants offer a potential solution, but the factors influencing transplant success remain unclear. We investigated how microbiota origin affects microbiome mergers, hypothesizing that native strains through niche preference are better adapted to their habitat and will outcompete non-native ones. To test this, we contrasted transplants between soil microcosm-cultured topsoil or lakewater communities with a community of 21 soil bacteria (SynCom). In both cases, SynCom transplant increased resident productivity but permanently shifted compositions, although its abundance dropped from an initial 50-80% to <1% within two months. Both merged and non-merged communities resembled natural soil microbiota in comparisons with over 81,000 soil, sediment and lake compositional data. Our results show that habitat filtering and niche competition, more than microbiota origin, determine transplant outcomes. Despite the limited proliferation of SynCom transplants, their capacity to instill lasting community trajectory changes opens new paths for microbiome engineering.

TEASER

Even transiently present microbiota transplants can alter resident microbiome composition through processes governed by habitat filtering.
Enhanced Yield and Gentle Purification of HIV for Cryo-Electron Tomography Analysis of Virion Maturation
Authors: Preece Benjamin , Peppel Wiley , Gallegos Rodrigo , Yassasi Gillian , Clinger Gabe , Bohn Nicole , Adhikary Broti , Mendonça Luiza , Belnap David , Vershinin Michael , Saffarian Saveez
Published: December 2024

HIV is a lentivirus characterized by the formation of its mature core. Visualization and structural examination of HIV requires purification of virions to high concentrations. The yield and integrity of these virions are crucial for ensuring a uniform representation of all viral particles in subsequent analyses. In this study, we present a method for purification of HIV virions which minimizes forces applied to virions while maximizing the efficiency of collection. This method allows us to capture between 1,000 and 5,000 HIV virions released from individual HEK293 cells after transfection with the NL4.3 HIV backbone, a 10 fold advantage over other methods. We utilized this approach to investigate HIV core formation from several constructs: pNL4-3(RT:D185A&D186A) with an inactive reverse transcriptase, NL4.3(IN: V165A&R166A) with a type-II integrase mutation, and NL4.3(Ѱ: Δ(105-278)&Δ(301-332)) featuring an edited Ѱ packaging signal. Notably, virions from NL4.3(Ѱ: Δ(105-278)&Δ(301-332)) displayed a mixed population, comprising immature virions, empty cores, and cores with detectable internal density. Conversely, virions derived from NL4.3(IN: V165A&R166A) exhibited a type II integrase mutant phenotype characterized by empty cores and RNP density localized around the cores, consistent with previous studies. In contrast, virions released from pNL4-3(RT:D185A&D186A) displayed mature cores containing detectable RNP density. We suggest that the purification methods developed in this study can significantly facilitate the characterization of enveloped viruses.
A Novel Method for Testing Antifungal Interactions: Assessing Synergy and Antagonism inCandida albicansClinical Isolates
Authors: Lundvik Hanna , Santini Ramona , Unalan Altintop Tugce , Özenci Volkan , Andersson Dan I. , Fatsis-Kavalopoulos Nikos
Published: December 2024

The rise in antifungal resistance has limited treatment options for serious fungal infections, emphasizing the need for effective combination therapies. However, low-cost and rapid systems to evaluate synergy and antagonism in antifungal combinations are lacking. Here, we introduce a novel in vitro testing method for assessing antifungal interactions in C.albicans, enabling the simultaneous testing of three antifungal agents in a single agar plate with overnight results. This method, validated against the checkerboard assay, provides consistent fractional inhibitory concentration (FICi) measurements with reduced variability and workload. We applied this method in a comprehensive screen of 92 clinical C.albicansisolates for three antifungals—amphotericin B, fluconazole, and anidulafungin—yielding assessments of a total of 276 distinct combinations of antifungals and isolates. Results revealed isolate-specific interaction patterns, with amphotericin B and fluconazole showing synergy in 1% of isolates, anidulafungin and fluconazole in 19.5%, and amphotericin B and anidulafungin in 23.9%. These findings underscore the need for isolate-specific testing in clinical settings, which this scalable, high-throughput assay can facilitate effectively.