bluuebunny/crossref_metadata_2025 huggingface dataset:
Woody species with high wood density are more vulnerable to global change in South China
Authors: Li Guolin C , Veresoglou Stavros D
Published: November 2023

To cope with global change, plants shift their distributions. Distribution shifts tend to be more dramatic across rare species. We here questioned how the distribution range of eight rare woody species is changing and how effectively the plants cope with the shift. We further addressed whether plant traits that could predict those parameters. We carried out Maxent Distribution Modelling on species observation records before 1980 under present climatic conditions and four future (CMIP5) scenarios. To assess how effectively plants cope with migration we assessed species observations after 1980. We finally collated plant trait data on three traits. Most distribution ranges expanded northwards. Temperature driven rather than precipitation driven variables described distribution shifts best. Wood density summarized well the susceptibility of those plants to climate change. There are many woody species in tropical and subtropical areas for which we have very little information available. We identified, subject to our small pool of species, a plant trait, wood density, that could summarize responses to global change that could potentially be used as a tool in conservation ecology to prioritize conservation efforts.
The superior colliculus response space has globally high– and locally low-dimensionality
Authors: Schwartz Ole S. , Yonehara Keisuke
Published: November 2023

An understanding of cell types is essential for understanding neural circuits, but only when the response of each type is clearly defined and predictable, as has been observed in the retina1. Recent work has shown that neural responses in the visual cortex are of high dimensionality, questioning the validity of defining cell types in the deeper visual system2–4. Here we investigate the dimensionality of neural responses in the midbrain using two-photon calcium imaging in superficial layers of the mouse superior colliculus (SC). Responses of individual neurons to closely related stimuli, such as ON and OFF light signals, were mutually dependent such that the response to one stimulus could be predicted from the response to the other. In contrast, individual neurons responded to brightness and motion in a statistically independent manner, maximizing functional diversity but preventing traditional cell type classification. To capture the globally high, locally low dimensionality of neural responses, we propose a multidimensional response model, in which classification of cellular responses is meaningful only in local low-dimensional structures. Our study provides a framework to investigate the processing of visual information by the SC, which likely requires a high-dimensional response space structure5,6to perform higher-order cognitive tasks7–12.
Divergent reward cue representations in prefrontal cortex underlie differences in reward motivation between adolescents and adults
Authors: Manzano Nieves Gabriela , Rahn Rachel M , Baskoylu Saba N , Liston Conor M
Published: November 2023

A prevailing view on postnatal brain development is that brain regions gradually acquire adult functions as they mature. The medial prefrontal cortex (mPFC) regulates reward learning, motivation, and behavioral inhibition, and undergoes a protracted postnatal maturation. During adolescence, reward-seeking behavior is heightened compared to adulthood — a developmental difference that may be driven by a hypoactive mPFC, with decreased top-down control of impulsive reward-seeking. However, this hypothesis has been difficult to test directly, due in part to technical challenges of recording neuronal activityin vivoacross this developmental period. Here, using a novel 2-photon imaging-compatible platform for recording mPFC activity during an operant reward conditioning task beginning early in life, we show that the adolescent mPFC is hyper-responsive to reward cues. Distinct populations of mPFC neurons encode reward-predictive cues across development, but representations of no-reward cues and unrewarded outcomes are relatively muted in adolescence. Chemogenetic inhibition of GABAergic neurons decreased motivation in adolescence but not in adulthood. Together, our findings indicate that reward-related activity in the adolescent mPFC does not gradually increase across development. On the contrary, adolescent mPFC neurons are hyper-responsive to reward-related stimuli and encode reward-predictive cues and outcomes through qualitatively different mechanisms relative to the adult mPFC, opening avenues to developing distinct, developmentally informed strategies for modulating reward-seeking behavior in adolescence and adulthood.
Insectivorous birds and bats outperform ants in the top-down regulation of arthropods across strata of a Japanese temperate forest
Authors: Sivault Elise , Kollross Jan , Jorge Leonardo Re , Finnie Sam , Diez-Méndez David , Garzon Sara Fernandez , Maraia Heveakore , Lenc Jan , Libra Martin , Murakami Masashi , Nakaji Tatsuro , Nakamura Masahiro , Sreekar Rachakonda , Sam Legi , Abe Tomokazu , Weiss Matthias , Sam Katerina
Published: November 2023

Birds, bats, and ants are recognized as significant arthropod predators. However, empirical studies reveal inconsistent trends in their relative roles in top-down control across strata. Here, we describe the differences between forest strata in the separate effects of birds, bats, and ants on arthropod communities and their cascading effects on plant damage.

We implemented a factorial design to exclude vertebrates and ants in both the canopy and understory. Additionally, we separately excluded birds and bats from the understory using diurnal and nocturnal exclosures. At the end of the experiments, we collected all arthropods and assessed herbivory damage.

Arthropods responded similarly to predator exclusion across forest strata, with a density increase of 81% on trees without vertebrates and 53% without both vertebrates and ants. Additionally, bird exclusion alone led to an 89% increase in arthropod density, while bat exclusion resulted in a 63% increase. Herbivory increased by 42% when vertebrates were excluded and by 35% when both vertebrates and ants were excluded. Bird exclusion alone increased herbivory damage by 28%, while the exclusion of bats showed a detectable but non-significant increase (by 22%). In contrast, ant exclusion had no significant effect on arthropod density or herbivory damage across strata.

Our results reveal that the effects of birds and bats on arthropod density and herbivory damage are similar between the forest canopy and understory in this temperate forest. In addition, ants were not found to be significant predators in our system. Furthermore, birds, bats, and ants appeared to exhibit antagonistic relationships in influencing arthropod density. These findings highlight, unprecedentedly, the equal importance of birds and bats in maintaining ecological balance across different strata of a temperate forest.
Emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence
Authors: Mellado Susana , Morillo-Bargues María José , Perpiñá-Clérigues Carla , Touahri Najoua , García-García Francisco , Moreno-Manzano Victoria , Guerri Consuelo , Pascual María
Published: November 2023

NOD-like receptors are innate immunity sensors that provide an early and effective response to pathogenic or injury conditions. However, abnormalities in these receptors may cause excessive inflammation. Our studies have reported that an activation of the NLRP3-inflammasome complex in ethanol-treated astrocytes and in chronic alcohol-fed mice could be associated with neuroinflammation and brain damage. Considering the therapeutic role of the molecules contained in the extracellular vesicles (EVs) derived by mesenchymal stem cells (MSC-EVs), the present study aims to evaluate whether the intravenous administration of MSC-EVs from adipose tissue, through inhibiting the NLRP3 inflammasome activation, is capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking. We demonstrate that MSC-EVs ameliorate the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes (e.g., NLRP1, NLRC4 and AIM2), as well as the alterations of inflammatory genes (IL-1β, IL-18, iNOS, NF-κB, MCP-1 and CX3CL1) and miRNAs (miR-21a-5p, miR-146a-5p and miR-141-5p) induced by binge-like ethanol treatment in adolescent mice. Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways. Taken together, these findings provide, for the first time, evidence of the therapeutic potential of MSC-derived EVs to restore the hippocampal neuroinflammatory response through the NLRP3 inflammasome activation induced by binge drinking in adolescence.
Anti-inflammatory immunomodulation for the treatment of Congenital Diaphragmatic Hernia
Authors: Vallejo-Cremades Mayte , Merino Javier , Carmona Rita , Córdoba Laura , Salvador Beatriz , Martínez Leopoldo , Tovar Juan. Antonio , Llamas Miguel Ángel , Muñoz-Chápuli Ramon , Fresno Manuel
Published: November 2023

Congenital diaphragmatic hernia (CDH) is a rare disease where the diaphragm does not develop properly altering lung development with no established therapy. We have analyzed the effect of anti-inflammatory immunomodulators that influence macrophage activation in animal CDH models. In the widely-used nitrofen-induced model of CDH in pregnant rats, administration of a single dose of atypical Toll-like Receptors TLR2/4 dual ligands (CS1 and CS2), 3 days after nitrofen, cured diaphragmatic hernia in 73 % of the fetuses, repaired the lesion with complete diaphragm closure. Moreover, they also improve pulmonary hypoplasia and vessel hypertrophy, enhancing pulmonary maturity of fetuses. CS1 treatment also rescued the CDH phenotype in the G2-GATA4Cre;Wt1fl/flCDH genetic mice model. Only 1 out 11 mutant embryos showed CDH after CS1 administration, whereas CDH prevalence was 70% in untreated mutant embryos. Mechanistically, CS1 stimulated the infiltration of repairing M2 macrophages (CD206+ and Arg1+) into the damaged diaphragm and reduced T cell infiltration. Alteration in retinoic acid pathways a have been also implicated in the etiology of CDH. TLR2/4 dual ligands also induced retinol pathway genes, including RBP1, RALDH2, RARα and RARβ, in the affected lungs and the diaphragm and in macrophagesin vitro. The present results place atypical TLR2/4 ligands as a promising solution for CDH, where the own immune system of the fetus is responsible for repairing the hernia/damage in the diaphragm, ensuring the correct positioning and development of all organs.
Conformational diversity in class C GPCR positive allosteric modulation
Authors: Cannone Giuseppe , Berto Ludovic , Malhaire Fanny , Ferguson Gavin , Foullien Aurelien , Balor Stéphanie , Font-Ingles Joan , Llebaria Amadeu , Goudet Cyril , Kotecha Abhay , Vinothkumar Kutti R. , Lebon Guillaume
Published: November 2023

The metabotropic glutamate receptors (mGlus) are class C G protein coupled receptors (GPCR) that form obligate dimers activated by the major excitatory neurotransmitter L-glutamate1,2. The architecture of mGlu receptor comprises an extracellular Venus-Fly Trap domain (VFT) connected to a transmembrane domain (7TM) through a Cysteine-Rich Domain (CRD). The binding of L-glutamate in the VFTs and subsequent conformational change results in the signal being transmitted to the 7TM inducing G-protein binding and activation3–6. The mGlu receptors signal transduction can be allosterically potentiated by positive allosteric modulators (PAMs) binding to the 7TMs, which are of therapeutic interest in various neurological disorders7–9. Here, we report the cryoEM structures of metabotropic glutamate receptor 5 (mGlu5) purified with three chemically and pharmacologically distinct PAMs. We find that PAMs modulate the receptor equilibrium through their different binding modes, revealing how their interactions in the 7TMs impact the mGlu5receptor conformational landscape and function. In addition, we identified a PAM-free but agonist-bound intermediate state that is stabilised by interactions mediated by intracellular loop 2. The activation of mGlu5receptor is a multi-step sequential process in which the binding of the PAMs in the 7TM modulates the equilibrium towards the active state.
SELENOT regulates endoplasmic reticulum calcium flux via SERCA2 and maintains dopaminergic DAT to protect against attention deficit hyperactivity disorder in mice
Authors: Guo Qing , Li Zhao-Feng , Hu Dong-Yan , Li Pei-Jun , Wu Kai-Nian , Fan Hui-Hui , Deng Jie , Wu Hong-Mei , Zhang Xiong , Zhu Jian-Hong
Published: November 2023

Attention deficit and hyperactivity disorder (ADHD) is a prevalent developmental disorder. SELENOT is an endoplasmic reticulum-resident selenocysteine-containing protein. We aimed to investigate the role of SELENOT in dopaminergic neurons. Results fromSelenotfl/fl;Dat-cremice showed that SELENOT deficiency in dopaminergic neurons resulted in ADHD-like behaviors including hyperlocomotion, recognition memory deficit, repetitive movement, and impulsivity. Dopamine metabolism, extrasynaptic dopamine, spontaneous excitatory postsynaptic currents in the striatum and electroencephalogram theta power were enhanced inSelenotfl/fl;Dat-cremice, whereas dopaminergic neurons in the substantia nigra were slightly reduced but exhibited normal neuronal firing and little cellular stress. Among dopamine- associated proteins, dopamine transporter (DAT) level was remarkably reduced and monoamine oxidase A increased mildly in the striatum and/or midbrain ofSelenotfl/fl;Dat-cremice. The ADHD-like phenotype and DAT ablation were corroborated inSelenotfl/fl;Nestin- cremice, but not inSelenotfl/fl;Gfap-cremice. In vitro overexpression and knockdown analyses and RNA-sequencing data revealed that SELENOT causatively regulated DAT mRNA and protein expression through Ca2+signaling and NURR1. SELENOT maintained cellular Ca2+levels via interaction with endoplasmic reticulum SERCA2, but not IP3Rs and RYRs, as demonstrated by Ca2+imaging, co-immunoprecipitation coupled with mass spectrometry, and colocalization analyses. Treatment with psychostimulants, amphetamine or methylphenidate, rescued the hyperactivity inSelenotfl/fl;Dat-cremice. In conclusion, SELENOT in dopaminergic neurons is indispensable to maintain proper dopamine signaling in the midbrain against ADHD.
Decoding Remapped Spatial Information in the Peri-Saccadic Period
Authors: Moran Caoimhe , Johnson Philippa A. , Landau Ayelet N. , Hogendoorn Hinze
Published: November 2023

It has been suggested that, prior to a saccade, visual neurons predictively respond to stimuli that will fall in their receptive fields after completion of the saccade. This saccadic remapping process is thought to compensate for the shift of the visual world across the retina caused by eye movements. To map the timing of this predictive process in the brain, we recorded neural activity using electroencephalography (EEG) during a saccade task. Participants made saccades between two fixation points while covertly attending to oriented gratings briefly presented at various locations on the screen. Data recorded during trials in which participants maintained fixation were used to train classifiers on stimuli in different positions. Subsequently, data collected during saccade trials were used to test for the presence of remapped stimulus information at the post-saccadic retinotopic location in the peri-saccadic period, providing unique insight intowhenremapped information becomes available. We found that the stimulus could be decoded at the remapped location ∼180 ms post-stimulus onset, but only when the stimulus was presented 100-200 ms before saccade onset. Within this range, we found that the timing of remapping was dictated by stimulus onset rather than saccade onset. We conclude that presenting the stimulus immediately before the saccade allows for optimal integration of the corollary discharge signal with the incoming peripheral visual information, resulting in a remapping of activation to the relevant post-saccadic retinotopic neurons.

Significance Statement

Each eye movement leads to a shift of the visual world across the retina, such that the visual input before and after the eye movement do not match. Despite this, we perceive the visual world as stable. A predictive mechanism known as saccadic remapping is thought to contribute to this stability. We use a saccade task with time-resolved EEG decoding to obtain a fine-grained analysis of the temporal dynamics of the saccadic remapping process. Probing different stimulus-saccade latencies and an array of stimulus locations, we identify when remapped information becomes available in the visual cortex. We describe a critical window in which feedforward visual information and the preparatory motor signals interact to allow for predictive remapping of a stimulus.
Hot spots in a cold river synchronize temporarily separated salmon runs in their offspring’s development
Authors: Negishi JN , Morisaki N , Song YY , Aruga N , Urabe H , Nakamura F
Published: November 2023

The identification of thermal heterogeneity in the environment and its inclusion in adaptive strategies are key to habitat management of cold-water fish, including salmonid species. This study tested the hypothesis that upwelling of groundwater (GW) from a tributary catchment through a relatively deep aquifer (tributary GW) affects salmon redds selection in an urbanized gravel-bed river, and that the spawning preference of such areas depends on the seasonal context. The field study was conducted between 2001 and 2015 in an approximately 6-km long segment of the Toyohira River, Northern Japan. Chum salmon redds distribution data over 15 years (2001-2015) were combined with spatial distribution data of hyporheic water affected by tributary GW in the riverbed to examine seasonally variable redds site selection in relation to the presence of unique GW. Furthermore, models that predicted the hyporheic water thermal regime were coupled with redds count data to estimate the approximate timing of fry emergence from the riverbed. The redds site selection was seasonally variable, with a higher dependence on tributary-GW-affected areas with a decrease in water temperature. The time until fry emergence from spawning was shortened when the tributary-GW area was chosen during the cold winter. Overall, the present study identified hotspots for salmon spawning redds in winter with a disproportionately high level of site selection because of their warmer temperature compared to surface river water in winter. Thermally diverse spawning habitats allow the diversification of spawner strains in synchronized descents to the sea. Signs of tributary-GW pollution was suggested, and thus the conservation of the groundwater pathway and its sources, followed by improvements in quality, can be beneficial to the Chum salmon populations in the Toyohira River.
Environmental DNA is more effective than hand sorting in evaluating earthworm biodiversity recovery under regenerative agriculture
Authors: Llanos J. , Hipperson H. , Horsburgh G. , Lappage M.G. , Maher K.H. , Burke T. , Leake J.R. , Watt P. J.
Published: November 2023

Regenerating soil biodiversity is vital to help reverse declines in the health of agricultural soils caused by intensification, and to support sustainable food production and agro-ecosystem services. Earthworms are key functional components of soil biodiversity, with different ecotypes and species delivering specific beneficial soil functions. However, conventional monitoring by hand-sorting from soil pits is highly labour intensive, can reliably identify only adults to species, and may under-record anecics (deep-burrowing ecotypes). Here, we compare soil environmental DNA (eDNA) metabarcoding using two different primer sets and next-generation sequencing, with hand-sorting from standard soil-pits. The experiment comprised four conventionally managed arable fields into which strips of grass-clover ley had been introduced three years earlier. Earthworm population responses had been recorded by hand-sorting for the first two years and our goal was to assess these in the third year and to compare them both by hand and with the use of eDNA. The eDNA method found the same 8 species as hand-sorting, but had greater power for detecting anecic earthworms and quantifying local species richness. Earthworm abundance increased by over 55% into the third year of the leys, surpassing abundances in adjacent permanent grasslands, helping to explain the observed soil health regeneration. Both overall relative abundances and site occupancy proportions of earthworm eDNA were found to have potential as proxies for abundance, and the performance of each of these measures and the implications for further work are discussed. We demonstrate that eDNA can overcome some of the significant barriers and limitations to monitoring earthworm diversity and recommend its wider use both to better understand the earthworm population benefits of different soil management practices, and to guide agricultural policy and practice decisions affecting soil health.
ABCal: a Python package for Author Bias Computation and Scientometric Plotting for Reviews and Meta-Analyses
Authors: Le Clercq L.S.
Published: November 2023

Systematic reviews are critical summaries of the exiting literature on a given subject and, when combined with meta-analysis, provides a quantitative synthesis of evidence to direct and inform future research. Such reviews must, however, account for complex sources of between study heterogeneity and possible sources of bias, such as publication bias. This paper presents the methods and results of a research study using a newly developed software tool called ABCal (version 1.0.2) to compute and assess author bias in the literature, providing a quantitative measure for the possible effect of overrepresented authors introducing bias to the overall interpretation of the literature. ABCal includes a new metric referred to as author bias, which is a measure of potential biases per paper when the frequency or proportions of contributions from specific authors are considered. The metric is able to account for a significant portion of the observed heterogeneity between studies included in meta-analyses. A meta-regression between observed effect measures and author bias values revealed that higher levels of author bias were associated with higher effect measures while lower author bias was evident for studies with lower effect measures. Furthermore, the software’s capabilities to analyse authorship contributions and produce scientometric plots was able to reveal distinct patterns in both the temporal and geographic distributions of publications, which may relate to any evident publication bias. Thus, ABCal can aid researchers in gaining a deeper understanding of the research landscape and assist in identifying both key contributors and holistic research trends.
Protein thiol alterations drive aberrant phase separation in aging
Authors: Vignane Thibaut , Hugo Martín , Hoffmann Christian , Katsouda Antionia , Petric Jovan , Wang Han , Miler Marko , Comas Ferran , Petrovic Dunja , Chen Suyuan , Miljkovic Jan Lj. , Morris Jordan L , Chowdhury Suvagata Roy , Prudent Julien , Polovic Natalija , Murphy Michael P. , Papapetropoulos Andreas , Milovanovic Dragomir , Filipovic Milos R.
Published: November 2023

Cellular homeostasis relies on precise regulation through chemical processes, such as protein posttranslational modifications (PTM) and physical processes, such as biomolecular condensation. Aging disrupts this balance, increasing susceptibility to diseases and death. However, the mechanisms behind age-related pathogenesis remain elusive. In this study, we dissected various cysteine PTMs and their impact on protein-mediated biomolecular condensation in aging brain. Our findings reveal that aging is associated with significant remodeling of cysteine PTMs, which impacts protein ability to participate in liquid-liquid phase separation (LLPS). Specifically, aging leads to an increase in protein sulfenylation and sulfonylation, which promotes LLPS and through conformational change increases the propensity of proteins to aggregate. Protein persulfidation, a protective thiol modification, prevents this by causing condensate dissolution. We demonstrate that age-induced alterations in cysteine PTMs influence the LLPS properties of synapsin-1 and G3BP2, resulting in disruptions in neurotransmitter release and stress granule formation, respectively. Additionally, our study uncovers that GAPDH is susceptible to LLPS and cysteine sulfonylation exacerbates its transition from condensates to aggregates. Mice deficient in cystathionine gamma-lyase, a pro-longevity gene that regulates intracellular persulfide levels, exhibit a shorter lifespan and spontaneous development of neurofibrillary tangles.
Disuse-driven plasticity in the human thalamus and putamen
Authors: Chauvin Roselyne J. , Newbold Dillan J. , Nielsen Ashley N. , Miller Ryland L. , Krimmel Samuel R. , Metoki Athanasia , Wang Anxu , Van Andrew N. , Montez David F. , Marek Scott , Suljic Vahdeta , Baden Noah J. , Ramirez-Perez Nadeshka , Scheidter Kristen M. , Monk Julia S. , Whiting Forrest I. , Adeyemo Babatunde , Snyder Abraham Z. , Kay Benjamin P. , Raichle Marcus E. , Laumann Timothy O. , Gordon Evan M. , Dosenbach Nico U.F.
Published: November 2023

Motor adaptation in cortico-striato-thalamo-cortical loops has been studied mainly in animals using invasive electrophysiology. Here, we leverage functional neuroimaging in humans to study motor circuit plasticity in the human subcortex. We employed an experimental paradigm that combined two weeks of upper-extremity immobilization with daily resting-state and motor task fMRI before, during, and after the casting period. We previously showed that limb disuse leads to decreased functional connectivity (FC) of the contralateral somatomotor cortex (SM1) with the ipsilateral somatomotor cortex, increased FC with the cingulo-opercular network (CON) as well as the emergence of high amplitude, fMRI signal pulses localized in the contralateral SM1, supplementary motor area and the cerebellum. From our prior observations, it remains unclear whether the disuse plasticity affects the thalamus and striatum. We extended our analysis to include these subcortical regions and found that both exhibit strengthened cortical FC and spontaneous fMRI signal pulses induced by limb disuse. The dorsal posterior putamen and the central thalamus, mainly CM, VLP and VIM nuclei, showed disuse pulses and FC changes that lined up with fmri task activations from the Human connectome project motor system localizer, acquired before casting for each participant. Our findings provide a novel understanding of the role of the cortico-striato-thalamo-cortical loops in human motor plasticity and a potential link with the physiology of sleep regulation. Additionally, similarities with FC observation from Parkinson Disease (PD) questions a pathophysiological link with limb disuse.
Dissection of figured wood trait in curly birch (Betula pendula var. carelica) using high-throughput genotyping
Authors: Gubaev Rim , Karzhaev Dmitry , Grigoreva Elizaveta , Lytkin Kirill , Safronycheva Elizaveta , Volkov Vladimir , Nesterchuk Veronika , Vetchinnikova Lidiya , Zhigunov Anatoly , Potokina Elena
Published: November 2023

Curly (Karelian) birch is a special variety ofBetula penduladistributed in the northwestern part of Europe. Karelian birch is well-known for its valuable figured curly wood also known as “wooden marble”. The genetic basis underlying curly wood formation has been debated since last century, however, there was no data about loci responsible for the curly wood trait. In the present study, we analyzed two full-sibs populations derived from experimental crosses of curly birches and segregating for the trait. RADseq genotyping was applied to reveal how many loci are involved in ‘curliness’ formation and to search for genetic variants associated with this trait. One single interval on chromosome 10 was detected containing possible candidate genes. InDel marker BpCW1 was suggested for the first time for marker-assisted selection of trees with curly wood at their earliest stages of development.
Microdosing ketamine inDrosophiladoes not inhibit SERT like SSRIs, but causes behavioral changes mediated by glutamate and serotonin receptors
Authors: Dunham Kelly E. , Khaled Kani H. , Weizman Leah , Venton B. Jill
Published: November 2023

Recently, the FDA approved microdosing ketamine for treatment resistant depression. Traditional antidepressants, like serotonin selective reuptake inhibitors (SSRIs), block serotonin reuptake, but it is not clear if ketamine blocks serotonin reuptake. Here, we tested the effects of feeding ketamine and SSRIs toDrosophila melanogasterlarvae, which has a similar serotonin system to mammals, and is a good model to track depression behaviors, such as locomotion and feeding. Fast-scan cyclic voltammetry (FSCV) was used to measure optogenetically-stimulated serotonin changes, and locomotion tracking software and blue dye feeding to monitor behavior. We fed larvae various doses (1-100 mM) of antidepressants for 24 hours and found that 1 mM ketamine did not affect serotonin, but increased locomotion and feeding. Low doses (≤ 10 mM) of escitalopram and fluoxetine inhibited dSERT and also increased feeding and locomotion behaviors. At 100 mM, ketamine inhibited dSERT and increased serotonin concentrations, but decreased locomotion and feeding due to its anesthetic properties. Since microdosing ketamine causes behavioral effects, we also investigated behavior changes with low doses of other NMDA receptor antagonists and 5-HT1Aand2agonists, which are other possible sites for ketamine action. NMDA receptor antagonism increased feeding, while serotonin receptor agonism increased locomotion, which could explain these effects with ketamine. Ultimately, this work shows thatDrosophilais a good model to discern antidepressant mechanisms, and that ketamine does not work on dSERT like SSRIs at microdoses, but affects behavior with other mechanisms.

Graphical abstract

Microdosing ketamine is a novel depression treatment, but it is not clear how it changes serotonin in real-time.Drosophila melanogaster(fruit fly) is a good model to study depression behaviors. Here, we used fast-scan cyclic voltammetry, video tracking, and feeding assays to measure serotonin and behavior after feeding ketamine and SSRIs to larvae. At microdoses, ketamine did not affect serotonin, which was different from SSRIs. However, higher doses inhibited dSERT. Locomotion and feeding changes were also dose-dependent, and we saw separate effects with NMDA and serotonin receptor drugs. This work facilitates future behavioral and pharmacological testing with ketamine usingDrosophila.
Sleep disturbances as risk factors for neurodegeneration later in life
Authors: Simmonds Emily , Levine Kristin S , Han Jun , Iwaki Hirotaka , Koretsky Mathew J , Kuznetsov Nicole , Faghri Faraz , Solsberg Caroline Warly , Schuh Artur , Jones Lietsel , Bandres-Ciga Sara , Blauwendraat Cornelis , Singleton Andrew , Escott-Price Valentina , Leonard Hampton L , Nalls Mike A
Published: November 2023

The relationship between sleep disorders and neurodegeneration is complex and multi-faceted. Using over one million electronic health records (EHRs) from Wales, UK, and Finland, we mined biobank data to identify the relationships between sleep disorders and the subsequent manifestation of neurodegenerative diseases (NDDs) later in life. We then examined how these sleep disorders’ severity impacts neurodegeneration risk. Additionally, we investigated how sleep attributed risk may compensate for the lack of genetic risk factors (i.e. a lower polygenic risk score) in NDD manifestation.

We found that sleep disorders such as sleep apnea were associated with the risk of Alzheimer’s disease (AD), amyotrophic lateral sclerosis, dementia, Parkinson’s disease (PD), and vascular dementia in three national scale biobanks, with hazard ratios (HRs) ranging from 1.31 for PD to 5.11 for dementia. These sleep disorders imparted significant risk up to 15 years before the onset of an NDD. Cumulative number of sleep disorders in the EHRs were associated with a higher risk of neurodegeneration for dementia and vascular dementia. Sleep related risk factors were independent of genetic risk for Alzheimer’s and Parkinson’s, potentially compensating for low genetic risk in overall disease etiology. There is a significant multiplicative interaction regarding the combined risk of sleep disorders and Parkinson’s disease.

Poor sleep hygiene and sleep apnea are relatively modifiable risk factors with several treatment options, including CPAP and surgery, that could potentially reduce the risk of neurodegeneration. This is particularly interesting in how sleep related risk factors are significantly and independently enriched in manifesting NDD patients with low levels of genetic risk factors for these diseases.

HIGHLIGHTS

Sleep disorders, particularly sleep apnea, are associated with the risk of Alzheimer’s disease, amyotrophic lateral sclerosis, dementia, Parkinson’s disease, and vascular dementia in national scale biobanks.

These sleep disorders imparted significant risk up to 15 years before the onset of a neurodegenerative disease.

The cumulative number of sleep disorders in the electronic health records were associated with a higher risk of neurodegeneration related to dementia and vascular dementia.

Sleep related risk factors are independent of genetic risk for Alzheimer’s and Parkinson’s, potentially compensating for low genetic risk in overall disease etiology.

Significant multiplicative interaction exists regarding the combined risk of sleep disorders and Parkinson’s disease.
Mapping the Middle East Respiratory Syndrome (MERS) related Research – A Scoping Review (2012-2023)
Authors: Hassan Maya , Yarow Halima , Mccabe Ruth , Dobschuetz Sophie Von , Khan Wasiq , Barakat Amal , Van Kerkhove Maria D. , Bakar Abdinasir Abu , Naja Hala Abou El
Published: November 2023

Background

Middle East respiratory syndrome (MERS), is a zoonotic disease caused by MERS coronavirus (MERS-CoV). The purpose of this scoping review was to take stock of the empirical research evidence for MERSDCoV, map the information to priority research areas as set out in existing MERS-CoV research roadmaps, identify technical areas that received less attention and set recommendations for the advancement of MERS-CoV research.

Methods

We undertook a scoping review for MERS-CoV, comprehensively searching the three databases PubMed, EMBASE, and CINAHL for studies published between 1 January 2012 and 24 January 2023. Two reviewers screened studies and extracted data using a pilot-tested screening form. We categorized studies into priority research areas outlined in existing roadmaps and summarized the evidence available for each category.

Results

A total of 1,264 records were included in the review, assigned into pre-defined categories. 33% of the included records were molecular genetics studies, followed by therapeutic studies (17.6%) and pathogenesis studies (15.6%). We found that, while there has been a substantial research effort on MERS-CoV, many technical themes pertaining to the areas of animal, human, animal-human interface, and environmental research identified by FAO, WHO, and WOAH in the past have not sufficiently been addressed to date. This includes asymptomatic human cases role in transmission, human exposure risk from dromedary products, reinfection, analyses of camel value chain and production systems, and anthropological studies characterizing interactions at the animal-human interface, in addition to studies highlighting the role of environmental factors in MERS-CoV transmission.

Conclusion

Our study highlights the continued need for coordinated action to better prepare for, prevent, detect, and respond to MERS-CoV. Examples include the need for enhancing collaborative surveillance, accelerating the development of MERS-CoV medical countermeasures, strengthening community protection, reducing MERS-CoV transmission at healthcare facility level and reinforcing multi-sectoral coordination using the One Health approach.
Serum proteomics revealsAPOEdependent and independent protein signatures in Alzheimer’s disease
Authors: Frick Elisabet A. , Emilsson Valur , Jonmundsson Thorarinn , Steindorsdottir Anna E. , Johnson Erik C. B. , Puerta Raquel , Dammer Eric B. , Shantaraman Anantharaman , Cano Amanda , Boada Mercè , Valero Sergi , García-González Pablo , Gudmundsson Elias F. , Gudjonsson Alexander , Loureiro Joseph J. , Orth Anthony P. , Seyfried Nicholas T. , Levey Allan I. , Ruiz Agustin , Aspelund Thor , Jennings Lori L. , Launer Lenore J. , Gudmundsdottir Valborg , Gudnason Vilmundur
Published: November 2023

The current demand for early intervention, prevention, and treatment of late onset Alzheimer’s disease (LOAD) warrants deeper understanding of the underlying molecular processes which could contribute to biomarker and drug target discovery. Utilizing high-throughput proteomic measurements in serum from a prospective population-based cohort of older adults (n=5,294), we identified 303 unique proteins associated with incident LOAD (median follow-up 12.8 years). Over 40% of these proteins were associated with LOADindependentlyofAPOE-ε4carrier status. These proteins were implicated in neuronal processes and overlapped with protein signatures of LOAD in brain and cerebrospinal fluid. We found 17 proteins which LOAD-association was stronglydependentonAPOE-ε4carrier status. Most of them showed consistent associations with LOAD in cerebrospinal fluid and a third had brain-specific gene expression. Remarkably, four proteins in this group (TBCA, ARL2, S100A13 and IRF6) were downregulated byAPOE-ε4yet upregulated as a consequence of LOAD as determined in a bi-directional Mendelian randomization analysis, reflecting a potential response to the disease onset. Accordingly, the direct association of these proteins to LOAD was reversed uponAPOE-ε4genotype adjustment, a finding which we replicate in an external cohort (n=719). Our findings provide an insight into the dysregulated pathways that may lead to the development and early detection of LOAD, including those both independent and dependent onAPOE-ε4. Importantly, many of the LOAD-associated proteins we find in the circulation have been found to be expressed - and have a direct link with AD - in brain tissue. Thus, the proteins identified here, and their upstream modulating pathways, provide a new source of circulating biomarker and therapeutic target candidates for LOAD.
The association of diet quality and physical activity with cardiovascular disease and mortality in 85,545 older Australians: A longitudinal study
Authors: Ding Ding , Van Buskirk Joe , Partridge Stephanie , Clare Philip , Giovannucci Edward , Bauman Adrian , Freene Nicole , Gallagher Robyn , Nguyen Binh
Published: November 2023

Background

A quality diet and an active lifestyle are both important cornerstones of cardiovascular disease (CVD) prevention. However, despite their interlinked effects on metabolic health, the two behaviours are rarely jointly considered, particularly within the context of CVD prevention. We examined the independent, interactive and joint associations of diet and physical activity with CVD hospitalisation, CVD mortality and all-cause mortality.

Methods

CVD-free Australian participants aged 45-74 years reported physical activity, diet and sociodemographic and lifestyle characteristics at baseline (2006-09) and follow-up (2012-15), and data were linked to hospitalisation and death registries (31/03/2019 for CVD hospitalisation and all-cause mortality and 08/12/2017 for CVD mortality). Diet quality was categorised as low, medium and high based on meeting dietary recommendations. Physical activity was operationalised as 1) total moderate-to-vigorous physical activity (MVPA) as per guidelines and 2) the composition of MVPA as the ratio of vigorous-intensity physical activity (VPA) to total MVPA. We used a left-truncated cause-specific Cox proportional hazards model using time-varying covariates.

Results

During a median of 10.7 years of follow-up, 6,581 participants were admitted to the hospital for CVD and 6,586 died from all causes (879 from CVD during 9.3 years). A high-quality diet was associated with a 17% lower risk of all-cause mortality than low-quality, and the highest MVPA category (compared with the lowest) was associated with 44% and 48% lower risks of CVD and all-cause mortality. Multiplicative interactions between diet and physical activity were non-significant. For all outcomes, the lowest risk combinations involved a high-quality diet and the highest MVPA categories. Accounting for total MVPA, some VPA was associated with further risk reduction of CVD hospitalisation and all-cause mortality.

Conclusion

For CVD prevention and longevity, one should adhere to both a healthy diet and an active lifestyle and incorporate some VPA when possible.
Experience in the validation of a rapid test for NS1 and IgM for early diagnosis during a dengue epidemic in Colombia
Authors: Ramírez Rosa-Margarita Gélvez , Consuegra Mónika Patricia , Estupiñan María Isabel , Rangel Adriana Torres , Herrera Víctor Mauricio , de Lamballerie Xavier , Centeno Luis Ángel Villar
Published: November 2023

Dengue has a broad spectrum of syndromic presentations, making clinical diagnosis difficult in regions where acute febrile syndrome has multiple etiologies. Rapid tests for detecting NS1 and IgM are broadly proposed for the early diagnosis of dengue; however, their implementation in primary care settings is inconsistent, and the relevance of IgM detection in this context has not been firmly established. Our study aimed to describe the experience of validating an NS1-IgM rapid test in primary care settings in Bucaramanga, Colombia, during a dengue epidemic (2018 to 2020). We tested blood samples from 568 patients with a clinical diagnosis of dengue using the Bioline Dengue Duo rapid test and RT-PCR as a reference to estimate sensitivity, specificity, and positive and negative predictive values (SE, SP, PPV, and NPV, respectively). The prevalence of infection was 32.9% (95%CI: 29.1, 36.8), whereas SE and SP were 83.4% and 72.7% for NS1 without statistical heterogeneity across disease duration. NS1’s PPV and NPV were 60.0% and 89.9% at the observed prevalence. Our results show that NS1 and IgM rapid tests (POCT) are feasible in the primary care setting. The contribution of the NS1 test was indisputable, with high-performance levels far superior to those of the IgM test. The NS1+IgM combination did not offer a significant advantage over NS1 alone.
Highly amine-reactive graphene-oxide EM grids for biochemical surface modification in aqueous buffer
Authors: Brown Simon H.J. , Bouwer James C. , Cohen Scott B.
Published: November 2023

Graphene oxide (GO), an oxidized derivative of graphene, has found application in cryo-electron microscopy (cryo-EM) as a hydrophilic and transparent solid support on which to adsorb biological macromolecules, providing an alternative to traditional aqueous films. Current applications generally adsorb the macromolecule directly onto unmodified GO or modify the GO surface with polyethylene glycol-amine reagents. This nucleophilic amine reaction must be performed in an aprotic organic solvent and therefore precludes the use of biological samples such as nucleic acids and peptides. The utility of GO could be expanded by the ability to covalently modify its surface with biochemical affinity reagents such as small- molecule metabolites, peptides, or nucleic acids, in aqueous buffer at neutral pH. Presented here is a chemical procedure that converts all oxygen functionalities of GO to highly amine- reactive glycidyl epoxide groups, achieved without the need of specialized laboratory equipment. We show that single sheets of glycidyl epoxide-modified GO react on the EM grid with primary amines at micromolar concentrations in minutes at room temperature in aqueous buffer. Given the ease of derivatizing biochemical reagents with amines, the chemistry described here will enable imaging of macromolecules immobilized on GO through specific biochemical and biologically relevant binding interactions.
Effect of sleeve gastrectomy on sperm quality and fertility on non-obese diabetes diet model rat
Authors: Tumentemur Gamze , Titiz Mustafa , Bobus Ors Alev
Published: November 2023

Background

In people with diabetes, the effect of sleeve gastrectomy on impaired sperm parameters, hormonal profile and testis tissue remains controversial to some extent.

The context and purpose of the study

Effects of sleeve gastrectomy on hormonal profile, sperm parameters, and testis tissue in infertile men with type II diabetes mellitus (TIIDM). This study included thirty two TIIDM that were scheduled with and without sleeve gastrectomy. All rats were taken a sperm analysis, a testis tissue and a serum hormone profile before, 8 weeks after surgery.

Results

There was a significant correlation between weight loss after sleeve gastrectomy and decreased in glucose profile (p < 0.05). As regards the hormonal profile, testosterone improved significantly after 8 weeks following sleeve gastrectomy. There was a significant increase in sperm count (p < 0.05), and improved sperm morphology during the follow-up after sleeve gastrectomy, also showed that significant changes as improved in testis tissue after surgery.

Conclusion

Sleeve gastrectomy significantly improves testosterone deficiency, testis tissue and sperm count in TIIDM rats. More prospective clinical studies are needed to show how bariatric surgery affects infertility affected by TIIDM patients.