bluuebunny/crossref_metadata_2025 huggingface dataset:
Intimate partner homicide: Risk constellations in separation conflicts and points of intervention for the police
Authors: Horn Stefanie , Vogt Catharina , Wüller Chiara , Görgen Thomas
Published: April 2024

The escalation of conflicts in intimate relationships to potentially fatal partner violence poses a massive safety risk for victims involved. In addition, separations represent a particularly vulnerable phase for the dynamics of violent escalation. Based on an analysis of court records of three cases of attempted or completed homicides in the course of intimate partner separation in Germany, we outline the conditions under which the separation process is to be assessed by the police as a high-risk phase for the escalation of violence. The study's findings suggest that police work would be more effective if measures were implemented to focus on the overall history of violence rather than on isolated cases, and if these measures were aimed directly at the perpetrators. Moreover, inter-institutional cooperation would support the police in identifying perpetrators at an early stage and carrying out valid risk assessments, rather than working in isolation. The study presents starting points and options for police prevention measures.
Examining the relationship between officer attitudes and behaviour in a multi-site trial of procedural justice training
Authors: Telep Cody W , Weisburd David , Jonathan-Zamir Tal , Zastrow Taryn
Published: April 2024

While reformers view police training as an important means for improving performance, the training evidence base has historically been weak. Little research has focussed on how training impacts both attitudes and behaviour in the field, and the extent to which changes in attitudes following a training program are linked to officer behaviour in the field. This paper uses data from a multi-site randomized trial of procedural justice training in hot spots to assess the attitude–behaviour link. We ask to what extent do officers’ attitudes about procedural justice impact their behaviour in the field? We find no support for officer baseline attitudes being predictive of their use of procedural justice with the public. But for trained officers, we do find evidence that attitudes following training are related to behaviour in observed interactions in the field. We conclude with a discussion of the implications for police training and training evaluation studies.
The irrational failure to act
Authors: Heeney Matthew
Published: April 2024

I defend against a salient objection the thesis that practical rationality requires us to perform intentional actions. The objection is that if rationality requires the performance of intentional actions, then agents are irrational for failing to succeed in what they intend to do. I reply to this objection by hewing closely to the principle that the rational ‘ought’ implies ‘can’. We are rationally required not to successfully realize the content of our intentions but to exercise the fallible abilities in our possession. Taking this line permits us to agree that we are not irrational for failing to succeed, while also endorsing the anti-Internalist claim that practical rationality embraces intentional actions themselves, rather than merely the beliefs and intentions that prompt and sustain them.
Glymphatic System Dysfunction Underlying Schizophrenia Is Associated With Cognitive Impairment
Authors: Tu Ye , Fang Yan , Li Guohui , Xiong Fei , Gao Feng
Published: April 2024

Background and Hypothesis

Despite the well-documented structural and functional brain changes in schizophrenia, the potential role of glymphatic dysfunction remains largely unexplored. This study investigates the glymphatic system’s function in schizophrenia, utilizing diffusion tensor imaging (DTI) to analyze water diffusion along the perivascular space (ALPS), and examines its correlation with clinical symptoms.

Study Design

A cohort consisting of 43 people with schizophrenia and 108 healthy controls was examined. We quantified water diffusion metrics along the x-, y-, and z-axis in both projection and association fibers to derive the DTI-ALPS index, a proxy for glymphatic activity. The differences in the ALPS index between groups were analyzed using a 2-way ANCOVA controlling for age and sex, while partial correlations assessed the association between the ALPS index and clinical variables.

Study Results

People with schizophrenia showed a significantly reduced DTI-ALPS index across the whole brain and within both hemispheres (F = 9.001, P = .011; F = 10.024, P = .011; F = 5.927, P = .044; false discovery rate corrected), indicating potential glymphatic dysfunction in schizophrenia. The group by cognitive performance interaction effects on the ALPS index were not observed. Moreover, a lower ALPS index was associated with poorer cognitive performance on specific neuropsychological tests in people with schizophrenia.

Conclusion

Our study highlights a lower ALPS index in schizophrenia, correlated with more pronounced cognitive impairments. This suggests that glymphatic dysfunction may contribute to the pathophysiology of schizophrenia, offering new insights into its underlying mechanisms.
Familial hemiplegic migraine in Indian children—a tertiary center experience
Authors: Saini Lokesh , Gunasekaran Pradeep Kumar , Tiwari Sarbesh , Choudhary Bharat , Manjunathan Sujatha , Kumar Ashna
Published: April 2024

Familial hemiplegic migraine (FHM), an autosomal dominant subtype of hemiplegic migraine, is a channelopathy presenting with severe headache, visual field defect, paresthesia, unilateral motor deficit, encephalopathy, seizures and aphasia. This cross-sectional study was conducted over 10 months in children aged 1–18 years suspected of hemiplegic migraine at a tertiary care pediatric hospital. Fourteen children were screened and five children with genetically confirmed FHM were included. The symptoms in the study population were paroxysmal hemiparesis (5/5), headache (5/5) and focal seizures (1/5). The hemiplegia episodes lasted from 4 h to 7 days. The mean age at the onset of neurological symptoms was 6.8 ± 0.7 years and the mean age at diagnosis was 12.8 ± 1.7 years, with a mean delay of 6.1 ± 1.9 years for the diagnosis. Neuroimaging during acute episodes revealed accentuated gray, white differentiation in the contralateral cerebral hemisphere with mild effacement of sulcal spaces in T2/fluid-attenuated inversion recovery (FLAIR) images. Genetic testing revealed ATP1A2 mutations (FHM2) in 4/5 and SCN1A (FHM3) in 1/5 patients. All of them (5/5) were initiated on oral topiramate and had favorable treatment responses with a mean follow-up duration of 7 ± 1.4 months. Diagnosis of FHM is mainly clinical and can be confirmed by genetic analysis. Perfusion and diffusion-weighted MRI should be considered during acute headache episodes, as it is mostly normal in symptom-free periods. Routine MRI sequences like T1 weighted, T2 weighted, FLAIR and contrast remain normal even during acute attacks.
CircTHBS1 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR‐136‐3p/IGF2R axis
Authors: Guo Yanyan , Huang Chuyi , Qiu Liyan , Fu Jiahui , Xu Cailing , Yang Fang
Published: April 2024

The precise molecular mechanism behind fetal growth restriction (FGR) is still unclear, although there is a strong connection between placental dysfunction, inadequate trophoblast invasion, and its etiology and pathogenesis. As a new type of non‐coding RNA, circRNA has been shown to play a crucial role in the development of FGR. This investigation identified the downregulation of hsa_circ_0034533 (circTHBS1) in FGR placentas through high‐sequencing analysis and confirmed this finding in 25 clinical placenta samples using qRT‐PCR. Subsequent in vitro functional assays demonstrated that silencing circTHBS1 inhibited trophoblast proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression and promoted apoptosis. Furthermore, when circTHBS1 was overexpressed, cell function experiments showed the opposite result. Analysis using fluorescence in situ hybridization revealed that circTHBS1 was primarily found in the cytoplasmic region. Through bioinformatics analysis, we anticipated the involvement of miR‐136‐3p and IGF2R in downstream processes, which was subsequently validated through qRT‐PCR and dual‐luciferase assays. Moreover, the inhibition of miR‐136‐3p or the overexpression of IGF2R partially reinstated proliferation, migration, and invasion abilities following the silencing of circTHBS1. In summary, the circTHBS1/miR‐136‐3p/IGF2R axis plays a crucial role in the progression and development of FGR, offering potential avenues for the exploration of biological indicators and treatment targets.
Defective CAPSL function causes impaired retinal angiogenesis through the MYC axis and is associated with familial exudative vitreoretinopathy
Authors: Liu Wenjing , Li Shujin , Yang Mu , Ma Jie , Liu Lu , Fei Ping , Xiang Qianchun , Huang Lulin , Zhao Peiquan , Yang Zhenglin , Zhu Xianjun
Published: April 2024

Familial exudative vitreoretinopathy (FEVR) is a severe genetic disorder characterized by incomplete vascularization of the peripheral retina and associated symptoms that can lead to vision loss. However, the underlying genetic causes of approximately 50% of FEVR cases remain unknown. Here, we report two heterozygous variants, c.88C > T (p.Arg30Ter) and c.247C > T (p.Leu83Phe), in calcyphosine like (CAPSL), from four patients in two unrelated FEVR-affected families. Both variants exhibited compromised CAPSL protein expression. Vascular endothelial cell-specific inactivation ofCapslin postnatal mice resulted in defective sprouting, delayed radial/vertical vascular progression, compromised endothelial proliferation, and impaired cell migration, recapitulating the human FEVR phenotypes.CAPSL-depleted human retinal microvascular endothelial cells (HRECs) exhibited impaired tube formation, decreased cell proliferation, disrupted cell polarity establishment and filopodia/lamellipodia formation, as well as disrupted collective cell migrationin vitro. Transcriptomic and proteomic profiling ofCAPSL-depleted HRECs revealed thatCAPSLabolition inhibited the MYC signaling axis, in which the expression of core MYC targeted genes were profoundly decreased. Furthermore, a combined analysis ofCAPSL-depleted HRECs andc-MYC-depleted human umbilical vein endothelial cells (HUVECs) uncovered similar transcription patterns. Collectively, this study reports a novel FEVR-associated candidate gene,CAPSL, which provides valuable information for genetic counseling and prenatal diagnosis of FEVR. This study also reveals that compromised CAPSL function may causes FEVR through MYC axis, shedding light on the potential involvement of MYC signaling in the pathogenesis of FEVR.
Comparison of spatial transcriptomics technologies using tumor cryosections
Authors: Rademacher Anne , Huseynov Alik , Bortolomeazzi Michele , Wille Sina Jasmin , Schumacher Sabrina , Sant Pooja , Keitel Denise , Okonechnikov Konstantin , Ghasemi David R. , Pajtler Kristian W. , Mallm Jan-Philipp , Rippe Karsten
Published: April 2024

Background

Spatial transcriptomics (ST) technologies are revolutionizing our understanding of intra-tumor heterogeneity and the tumor microenvironment by revealing single-cell molecular profiles within their spatial tissue context. The rapid evolution ofSTmethods, each with unique features, presents a challenge in selecting the most appropriate technology for specific research objectives. Here, we compare four imaging-basedSTmethods – RNAscope HiPlex, Molecular Cartography, MERFISH/Merscope, and Xenium – together with sequencing-basedST(Visium). These technologies were used to study cryosections of medulloblastoma with extensive nodularity (MBEN), a tumor chosen for its distinct microanatomical features.

Results

Our analysis reveals that automated imaging-basedSTmethods are well suited to delineating the intricate MBEN microanatomy, capturing cell-type-specific transcriptome profiles. We devise approaches to compare the sensitivity and specificity of the different methods together with their unique attributes to guide method selection based on the research aim. Furthermore, we demonstrate how reimaging of slides after theSTanalysis can markedly improve cell segmentation accuracy and integrate additional transcript and protein readouts to expand the analytical possibilities and depth of insights.

Conclusions

This study highlights key distinctions between variousSTtechnologies and provides a set of parameters for evaluating their performance. Our findings aid in the informed choice ofSTmethods and delineate approaches for enhancing the resolution and breadth of spatial transcriptomic analyses, thereby contributing to advancingSTapplications in solid tumor research.
Predicting drug combination response surfaces
Authors: Huusari Riikka , Wang Tianduanyi , Szedmak Sandor , Aittokallio Tero , Rousu Juho
Published: April 2024

Prediction of drug combination responses is a research question of growing importance for cancer and other complex diseases. Current machine learning approaches generally consider predicting either drug combination synergy summaries or single combination dose-response values, which fail to appropriately model the continuous nature of the underlying dose-response combination surface and can lead to inconsistencies when a synergy score or a dose-response matrix is reconstructed from separate predictions. We propose a structured prediction method, comboKR, that directly predicts the drug combination response surface for a drug combination. The method is based on a powerful input-output kernel regression technique and functional modeling of the response surface. As an important part of our approach, we develop a novel normalisation between response surfaces that standardizes the heterogeneous experimental designs used to measure the dose-responses, and thus allows training the method with data measured in different laboratories. Our experiments on two predictive scenarios highlight the suitability of the proposed approach especially in the traditionally challenging setting of predicting combination responses for new drugs not available in the training data.
Comparative Analysis of Structural Alignment Algorithms for Protein-Protein Interfaces in Template-Based Docking Studies
Authors: Cankara Fatma , Tuncbag Nurcan , Gursoy Attila , Keskin Ozlem
Published: April 2024

Protein-protein interactions are pivotal for various functions within living organisms. Understanding their underlying mechanisms holds significant potential for unraveling cellular processes. There are several methods to identify protein-protein interactions, including but not limited to template-based docking. The power of template docking lies in the template library selection and the quality of structural alignment. Within the scope of our investigation, we specifically delve into the performance of four structural alignment algorithms on one protein interface and four protein structure benchmark sets. This study places particular emphasis on assessing these tools on protein interfaces, composed of non-continuous structure segments, as these interfaces play a crucial role in protein interactions, especially in the context of template-based docking. Notably, our findings indicate that TM-align, despite not being explicitly designed for sequence-order independent alignment, exhibits comparable performance to tools tailored for this purpose while executing in a considerably shorter time frame. Therefore, TM-align emerges as a promising candidate for the crucial structural alignment step in template-docking pipelines.
GαolfRegulates Biochemical Signaling in Neurons Associated with Movement Control and Initiation
Authors: Millett Michael , Heuberger Anika , Castosa Elisabeth Martin , Comite Allison , Wagner Preston , Hall Dominic , Gallardo Ignacio , Chambers Nicole E , Wagner Lloyd , Moehle Mark S
Published: April 2024

The heterotrimeric G-protein α subunit, Gαolf, acts to transduce extracellular signals through G-protein coupled receptors (GPCRs) and stimulates adenylyl cyclase mediated production of the second messenger cyclic adenosine monophosphate. Numerous mutations in theGNALgene, which encodes Gαolf, have been identified as causative for an adult-onset dystonia. These mutations disrupt GPCR signaling cascades inin vitroassays through several mechanisms, and this disrupted signaling is hypothesized to lead to dystonic motor symptoms in patients. However, the cells and circuits that mutations inGNALcorrupt are not well understood. Published patterns of Gαolfexpression outside the context of the striatum are sparse, conflicting, often lack cell type specificity, and may be confounded by expression of the closeGNALhomolog ofGNAS. Here, we use RNAScope in-situ hybridization to quantitatively characterizeGnalmRNA expression in brain tissue from wildtype C57BL/6J adult mice. We observed widespread expression ofGnalpuncta throughout the brain, suggesting Gαolfis expressed in more brain structures and neuron types than previously accounted for. We quantify transcripts at a single cell level, and use neuron type specific markers to further classify and understand patterns ofGNALexpression. Our data suggests that brain regions classically associated with motor control, initiation, and regulation show the highest expression ofGNAL, with Purkinje Cells of the cerebellum showing the highest expression of any neuron type examined. Subsequent conditionalGnalknockout in Purkinje cells led to markedly decreased intracellular cAMP levels and downstream cAMP-dependent enzyme activation. Our work provides a detailed characterization ofGnalexpression throughout the brain and the biochemical consequences of loss of Gαolfsignalingin vivoin neurons that highly expressGnal.
Hearing in categories aids speech streaming at the “cocktail party”
Authors: Bidelman Gavin M. , Bernard Fallon , Skubic Kimberly
Published: April 2024

Our perceptual system bins elements of the speech signal into categories to make speech perception manageable. Here, we aimed to test whether hearing speech in categories (as opposed to a continuous/gradient fashion) affords yet another benefit to speech recognition: parsing noisy speech at the “cocktail party.” We measured speech recognition in a simulated 3D cocktail party environment. We manipulated task difficulty by varying the number of additional maskers presented at other spatial locations in the horizontal soundfield (1-4 talkers) and via forward vs. time-reversed maskers, promoting more and less informational masking (IM), respectively. In separate tasks, we measured isolated phoneme categorization using two-alternative forced choice (2AFC) and visual analog scaling (VAS) tasks designed to promote more/less categorical hearing and thus test putative links between categorization and real-world speech-in-noise skills. We first show that listeners can only monitor up to ∼3 talkers despite up to 5 in the soundscape and streaming is not related to extended high-frequency hearing thresholds (though QuickSIN scores are). We then confirm speech streaming accuracy and speed decline with additional competing talkers and amidst forward compared to reverse maskers with added IM. Dividing listeners into “discrete” vs. “continuous” categorizers based on their VAS labeling (i.e., whether responses were binary or continuous judgments), we then show the degree of IM experienced at the cocktail party is predicted by their degree of categoricity in phoneme labeling; more discrete listeners are less susceptible to IM than their gradient responding peers. Our results establish a link between speech categorization skills and cocktail party processing, with a categorical (rather than gradient) listening strategy benefiting degraded speech perception. These findings imply figure-ground deficits common in many disorders might arise through a surprisingly simple mechanism: a failure to properly bin sounds into categories.
Heterologous HSPC transplantation rescues neuroinflammation and ameliorates peripheral manifestations in the mouse model of lysosomal transmembrane enzyme deficiency, MPS IIIC
Authors: Pan Xuefang , Caillon Antoine , Fan Shuxian , Khan Shaukat , Tomatsu Shunji , Pshezhetsky Alexey V.
Published: April 2024

Mucopolysaccharidosis III type C (MPS IIIC) is an untreatable neuropathic lysosomal storage disease caused by a genetic deficiency of the lysosomal N-acetyltransferase, HGSNAT, catalyzing a transmembrane acetylation of heparan sulfate. HGSNAT is a transmembrane enzyme uncapable of free diffusion between the cells and their cross-correction which limits development of therapies based on the enzyme replacement and gene correction. Since our previous work identified neuroinflammation as a hallmark of the CNS pathology in MPS IIIC, we tested whether it can be corrected by replacement of activated brain microglia with neuroprotective macrophages/microglia derived from a heterologous HSPC transplant.

Eight-week-old MPS IIIC (HgsnatP304L) mice were transplanted with HSPC from congenic wild type mice after myeloablation with Busulfan and studied by behaviour test battery staring from the age of 6 months. At the age of ∼8 months, mice were sacrificed to study pathological changes in the brain, heparan sulfate storage and other biomarkers of the disease. We found that the treatment corrected several behaviour deficits including hyperactivity and reduction of socialization, but not a memory decline. It also improved several features of CNS pathology such as microastroglyosis, expression of pro-inflammatory cytokine IL-1β, and accumulation of misfolded amyloid aggregates in cortical neurons. At the periphery, the treatment delayed development of terminal urinary retention, potentially increasing longevity, and reduced blood levels of heparan sulfate. However, we did not observe correction of lysosomal storage phenotype in neurons and heparan sulfate brain levels.

Together, our results demonstrate that neuroinflammation in a neurological lysosomal storage disease, caused by defects in a transmembrane enzyme, can be effectively ameliorated by replacement of microglia bearing the genetic defect with the cells from normal healthy donor. They also suggest, that heterologous HSPC transplant, if used together with other methods, such as chaperone therapy or substrate reduction therapy, may constitute an effective combination therapy for MPS IIIC and other disorders with a similar etiology.
The first example of extreme and independent host plant shifts mediated by parasitic plants in insects
Authors: Zelvelder B. , Kergoat G.J. , Benoit L. , Tsuchida T. , Haran J. , Allio R.
Published: April 2024

Abstract

Phytophagous insects have specialized on virtually every plant lineage. Parasitic plants, however, are uncommon hosts. Among insects, only a single lineage of weevils, the Smicronychini, has successfully radiated on both parasitic and non-parasitic plants in a large panel of distantly related Asterid families. This unusual pattern suggests that major host plant shifts have occurred over the course of their diversification. Through the analysis of a phylogenomic dataset, we reconstruct for the first time their evolutionary history and ancestral host plant associations. Our results show that independent host plant shifts occurred both from parasitic to non-parasitic hosts and between distinct parasitic lineages. These results suggest that host shift mechanisms can be driven by ecological opportunities provided by plant-plant interactions. This first evidence of extreme insect host plant shifts mediated by parasitic plant-plant interactions emphasizes the core importance of ecological interactions as driving forces behind insect host plant shifts.
Selective engagement of prefrontal VIP neurons in reversal learning
Authors: Yi Jee Hyun , Yoon Young Ju , Jeong Huijeong , Choe Seo Yeon , Jung Min Whan
Published: April 2024

To gain insights into neural mechanisms enabling behavioral adaptations to complex and multidimensional environmental dynamics, we examined roles of VIP neurons in mouse medial prefrontal cortex (mPFC) in probabilistic reversal learning. Behaviorally, manipulating VIP neuronal activity left probabilistic classical conditioning unaffected but severely impaired reversal learning. Physiologically, conditioned cue-associated VIP neuronal responses changed abruptly after encountering an unexpected reward. They also conveyed strong reward prediction error signals during behavioral reversal, but not before or after, unlike pyramidal neurons which consistently conveyed error signals throughout all phases. Furthermore, the signal’s persistence across trials correlated with reversal learning duration. These results suggest that mPFC VIP neurons play crucial roles in rapid reversal learning, but not in incremental cue-outcome association learning, by monitoring significant deviations from ongoing environmental contingency and imposing error-correction signals during behavioral adjustments. These findings shed light on the intricate cortical circuit dynamics underpinning behavioral flexibility in complex, multifaceted environments.
Atypical epigenetic and small RNA control of degenerated transposons and their fragments in clonally reproducingSpirodela polyrhiza
Authors: Dombey Rodolphe , Buendía-Ávila Daniel , Barragán-Borrero Verónica , Diezma-Navas Laura , Ponce-Mañe Arturo , Vargas-Guerrero José Mario , Elias Rana , Marí-Ordóñez Arturo
Published: April 2024

A handful of model plants have provided insight into silencing of transposable elements (TEs) through RNA-directed DNA methylation (RdDM). Guided by 24-nt long small-interfering RNAs (siRNAs), this epigenetic regulation installs DNA methylation and histone modifications like H3K9me2, which can be subsequently maintained independently of siRNAs. However, the genome of the clonally propagating duckweedSpirodela polyrhiza(Lemnaceae) has low levels of DNA methylation, very low expression of RdDM components, and near absence of 24-nt siRNAs. Moreover, some genes encoding RdDM factors, DNA methylation maintenance, and RNA silencing mechanisms are missing from the genome. Here, we investigated the distribution of TEs and their epigenetic marks in theSpirodelagenome. While abundant degenerated TEs have largely lost DNA methylation and H3K9me2 is low, they remain marked by the heterochromatin associated H3K9me1 and H3K27me1 modifications. By contrast, we found high levels of DNA methylation and H3K9me2 in the relatively few intact TEs which are source of 24-nt siRNAs like RdDM-controlled TEs in other angiosperms. The data suggest that, potentially as adaptation to vegetative propagation, RdDM extent, silencing components, and targets are different from other angiosperms, preferentially focused on potentially intact TEs. It also provides evidence for heterochromatin maintenance independently of DNA methylation in flowering plants. These discoveries highlight the diversity of silencing mechanisms that exist in plants and the importance of using disparate model species to discover these mechanisms.
Perceived biodiversity: is what we measure also what we see and hear?
Authors: Rozario Kevin , Shaw Taylor , Marselle Melissa , Oh Rachel Rui Ying , Schröger Erich , Giraldo Botero Mateo , Frey Julian , Ștefan Valentin , Müller Sandra , Scherer-Lorenzen Michael , Jaroszewicz Bogdan , Verheyen Kris , Bonn Aletta
Published: April 2024

1. Biodiversity is crucial for human health and well-being. Perceived biodiversity - people’s subjective experience of biodiversity - seems to be particularly relevant for mental well-being.

2. Using photographs and audio recordings of forests that varied in levels of species richness, we conducted two sorting studies to assess how people perceive visual and acoustic diversity and whether their perceptions align with measured tree and bird species richness (‘actual diversity’). Per study, 48 participants were asked to sort the stimuli according to any similarity-based sorting criteria they liked (‘open sorts’) and perceived diversity (‘closed sorts’).

3. The main perceived visual forest characteristics identified by participants in the open visual sorts were vegetation density, light conditions, forest structural attributes and colours. The main perceived acoustic forest characteristics identified in the open acoustic sorts comprised bird song characteristics, physical properties such as volume, references to the time of day or seasonality and evoked emotions.

4. Perceived visual and acoustic diversity were significantly correlated with actual tree and bird species richness, respectively. Notably, the relationship was twice as strong for the acoustic sense. The acoustic sense may thus be crucial to obtain a more thorough understanding of perceived biodiversity.

5. We further computed several visual and acoustic diversity indices from the photos and audio recordings, e.g. colourfulness or acoustic complexity, and assessed their relevance for perceived and actual diversity. While all acoustic diversity indices were significantly associated with perceived acoustic diversity and bird richness, we could not identify a visual diversity index that captured perceived visual diversity and tree richness.

6. Our results suggest that people can perceive species richness. Our identified visual and acoustic forest characteristics may help to better understand perceived diversity and how it differs from actual diversity. We present acoustic diversity indices that quantify aspects of perceived and actual acoustic diversity. These indices may serve as cost-efficient tools to manage and plan greenspaces to promote biodiversity and mental well-being.
Long-term Exposure to Methyl Jasmonate Increases Myrosinases TGG1 and TGG2 in Arabidopsiscoi1andmyc2,3,4Mutants
Authors: Mirzaei Mohamadreza , Poormassalehgoo Andisheh , Endo Kaichiro , Dubas Ewa , Yamada Kenji
Published: April 2024

Myrosinase is an enzyme that activates a group of metabolites, namely glucosinolates, which are involved in the defense against herbivores and pathogens. InArabidopsis thaliana, THIOGLUCOSIDE GLUCOHYDROLASE 1 (TGG1) and TGG2 are two myrosinases that accumulate in specialized myrosin cells of rosette leaves. Here, we show that prolonged exposure to the wounding hormone methyl jasmonate (MeJA) enhancesTGG1andTGG2expression independent of the canonical jasmonic acid (JA) signaling pathway. We found that airborne MeJA treatment for up to 5-days enhanced bothTGG1andTGG2gene expression and their protein levels in Arabidopsis leaves.TGG1andTGG2gene expression did not stop in two JA signaling pathway mutants, namelycoi1-16andmyc2,3,4, after 5-days of MeJA treatment, although other typical JA responses were completely stopped in these two mutants. FAMA is a transcription factor that participates in the specification of myrosin cell development, but it does not appear to be involved inTGG1andTGG2gene expression regulation in the 5-day MeJA treatment, as its expression did not increase. Taken together, our results suggest the existence of an alternative JA signaling pathway that is activated by long-term exposure to MeJA.
Macro-environment strongly interacts with warming in a global analysis of decomposition
Authors: Schwieger Sarah , Dorrepaal Ellen , Petit Bon Matteo , Vandvik Vigdis , le Roux Elizabeth , Strack Maria , Yang Yan , Venn Susanna , van den Hoogen Johan , Valiño Fernando , Thomas Haydn J.D. , te Beest Mariska , Suzuki Satoshi , Petraglia Alessandro , Myers-Smith Isla H. , Munir Tariq Muhammad , Michelsen Anders , Løkken Jørn Olav , Li Qi , Koike Takayoshi , Klanderud Kari , Karr Ellen Haakonsen , Jónsdóttir Ingibjörg Svala , Hollister Robert D. , Hofgaard Annika , Hassan Ibrahim A. , Genxu Wang , Filippova Nina , Crowther Thomas W. , Clark Karin , Christiansen Casper T. , Casanova-Katny Angelica , Carbognani Michele , Bokhorst Stef , Björnsdóttir Katrín , Asplund Johan , Althuizen Inge , Alonso Rocío , Alatalo Juha , Agathokleous Evgenios , Aerts Rien , Sarneel Judith M.
Published: April 2024

Empirical studies worldwide show substantial variability in plant litter decomposition responses to warming, leaving the overall impact of climate change on this process uncertain. We conducted a meta-analysis of 109 experimental warming studies across seven continents, utilizing natural and standardized plant material, to assess the overarching effect of warming on decomposition and identify potential moderating factors.

Warming influences decomposition differently across macro-environmental gradients of moisture and temperature. Negative warming effects on decomposition in warmer, low-moisture areas were counterbalanced by the positive, though not significant, warming effects in colder areas, resulting in an overall non-significant effect. We determine that at least 5.2 degrees of warming is required for a significant increase in decomposition. This is particularly relevant given the past decade’s global warmth in higher latitudes, holding a significant proportion of terrestrial carbon. Low-quality plant litter was more sensitive to warming. Therefore, future vegetation changes toward low-quality, temperature-sensitive plants could increase carbon release and reduce the net supply of stored organic matter in the soil by increasing the decomposition of low-quality litter with warming. Our findings emphasize the connection between warming responses, macro-environment, and litter characteristics, refining predictions of climate change’s consequences on key ecosystem processes and its contextual dependencies.
Lower adaptive immunity in invasive Egyptian geese compared to sympatric native waterfowls
Authors: Messina Simone , Prüter Hanna , Czirják Gábor Árpád , Costantini David
Published: April 2024

Successful invasive species increase their spreading success by trading-off nutritional and metabolic resources allocated to reproduction and range expansion with other costly body functions. One proposed mechanism for the reallocation of resources is a trade-off with the immune function and the regulation of oxidative status. Relying on a panel of blood-based markers of immune function and oxidative status quantified in an invasive species (Egyptian goose) and two native competing species (mallard and mute swan) in Germany, we tested the hypothesis that the invasive species would have (i) lower investment in immune function, (ii) lower levels of oxidative damage, and (iii) no higher antioxidant defences compared to the native species. We found lower levels of adaptive immune markers (lymphocytes and immunoglobulin Y), in the invasive species compared to the two native species. Reactive oxygen metabolites, a marker of oxidative damage, were also lower in Egyptian geese compared to the other species, while levels of antioxidants were generally similar. Mute swans showed the highest levels of heterophils, lysozymes and haemolysis among the three species, possibly due to its larger body mass. Our results point to a reduced investment in adaptive immune function in the invasive species as a possible resources-saving immunological strategy due to the loss of co-evolved parasites in the new colonised habitats, as observed in a previous study. A lower investment in immune function may benefit other energy-demanding activities, such as reproduction, dispersal, and territoriality.

Research highlights

Our results point to a reduced investment in adaptive immune function in invasive Egyptian geese compared to native and sympatric waterfowl species, as a possible resources-saving immunological strategy due to the loss of co-evolved parasites in the new colonised habitats.
Learning Gaussian Graphical Models from Correlated Data
Authors: Song Zeyuan , Gunn Sophia , Monti Stefano , Peloso Gina Marie , Liu Ching-Ti , Lunetta Kathryn , Sebastiani Paola
Published: April 2024

Gaussian Graphical Models (GGM) have been widely used in biomedical research to explore complex relationships between many variables. There are well established procedures to build GGMs from a sample of independent and identical distributed observations. However, many studies include clustered and longitudinal data that result in correlated observations and ignoring this correlation among observations can lead to inflated Type I error. In this paper, we propose a Bootstrap algorithm to infer GGM from correlated data. We use extensive simulations of correlated data from family-based studies to show that the Bootstrap method does not inflate the Type I error while retaining statistical power compared to alternative solutions. We apply our method to learn the GGM that represents complex relations between 47 Polygenic Risk Scores generated using genome-wide genotype data from a family-based study known as the Long Life Family Study. By comparing it to the conventional methods that ignore within-cluster correlation, we show that our method controls the Type I error well in this real example.
Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice
Authors: Chen Yueyi , Xiao Tiange , Kimbrough Adam
Published: April 2024

Background

The rise in overdose deaths from synthetic opioids, especially fentanyl, necessitates the development of preclinical models to study fentanyl use disorder (FUD). While there has been progress with rodent models, additional translationally relevant models are needed to examine excessive fentanyl intake and withdrawal symptoms.

Methods

The study performed intravenous self-administration (IVSA) of fentanyl in male and female C57BL/6J mice for 14 days. Mechanical pain sensitivity during withdrawal was assessed using the von Frey test. Anxiety-like behavior was evaluated via the open field test one-week into abstinence and incubation of craving for fentanyl was assessed four weeks into abstinence.

Results

Both male and female mice demonstrated a significant escalation in fentanyl intake over the 14 days of self-administration, with significant front-loading observed in the final days of self-administration. Increased mechanical pain sensitivity was present from 36- to 48-hour into withdrawal and increased anxiety-like behavior was found 1 week into abstinence. Four weeks into abstinence, mice showed significantly higher active lever pressing than the final self-administration session prior to abstinence.

Conclusions

The study establishes a translationally relevant mouse model of IVSA of fentanyl, effectively encapsulating critical aspects of FUD, including escalation of drug intake, front-loading behavior, withdrawal symptoms, and prolonged craving for drug into abstinence. This model offers a robust basis for further exploration into behavioral and neurobiological mechanisms involved in fentanyl dependence and potential therapeutic strategies.
RUNX1 is Expressed in a Subpopulation of Dermal Fibroblasts and Higher RUNX1 Levels are Associated with the Severity of Systemic Sclerosis
Authors: Parvizi Rezvan , Gong Zhiyun , Jarnagin Helen C. , Toledo Diana M. , Abel Tamar R. , Popovich Dillon , Morrisson Madeline J. , Shenk Sasha , Hinchcliff Monique E. , Garlick Jonathan A. , Pioli Patricia A. , Whitfield Michael L.
Published: April 2024

The activation of Runt-related transcription factor 1 (RUNX1) in fibroblasts has been implicated in wound healing and fibrosis; however, the role of RUNX1 in the fibrotic progression of the autoimmune disease systemic sclerosis (SSc) is not known. Through gene expression analysis, we have demonstrated an association between the severity of dermal fibrosis and the expression levels ofRUNX1in the skin of patients with SSc. Additionally, we identified hypomethylated CpG sites proximal to theRUNX1gene, implicating their potential role in the increased expression ofRUNX1. Analysis of single-cell RNA-seq data from skin biopsies of individuals with SSc revealed thatRUNX1is higher in subpopulations of fibroblasts enriched in SSc, which are believed to contribute to fibrosis. Lastly, modulation ofRUNX1activity using an inhibitor caused a reduction in fibroblast contraction and proliferation rates. Altogether, this study is the first to demonstrate a potential role forRUNX1in the pathogenesis of systemic sclerosis dermal fibrosis.
Human V4 size predicts crowding distance
Authors: Kurzawski Jan W , Qiu Brenda S , Majaj Najib J , Benson Noah C , Pelli Denis , Winawer Jonathan
Published: April 2024

Visual recognition is limited by both object size (acuity) and spacing. The spacing limit, called "crowding", is the failure to recognize an object in the presence of other objects. Here, we take advantage of individual differences in crowding behavior to investigate its biological basis. Crowding distance, the minimum object spacing needed for recognition, varies 2-fold among healthy adults. We test the conjecture that this variation in psychophysical crowding distance is due to variation in cortical map size. To test this, we made paired measurements of brain and behavior in 50 observers. We used psychophysics to measure crowding distance and calculate λ, the number of letters that fit into each observer's visual field without crowding. In the same observers, we used fMRI to measure the surface area A (mm^2) of retinotopic maps V1, V2, V3, and V4. Across observers, λ is proportional to the surface area of V4 but is uncorrelated with the surface area of V1 to V3. The proportional relationship of λ to area of V4 indicates conservation of cortical crowding distance across individuals: letters can be recognized if they are spaced by at least 1.4 mm on the V4 map, irrespective of map size and psychophysical crowding distance. We conclude that the size of V4 predicts the spacing limit of visual perception.
BioEncoder: a metric learning toolkit for comparative organismal biology
Authors: Lürig Moritz D. , Di Martino Emanuela , Porto Arthur
Published: April 2024

In the realm of biological image analysis, deep learning (DL) has been a transformative force. Tasks like finding areas of interest within an image (segmentation) and/or sorting images into groups (classification), can now be automated and achieve unprecedented efficiency and accuracy. However, conventional DL methods are challenged by large-scale biodiversity datasets, which are characterized by unbalanced classes and small phenotypic differences between them. Here we present BioEncoder, a user-friendly toolkit for metric learning, which overcomes the aforementioned challenges by focussing on learning relationships between individual data points rather than on the separability of classes. This approach simplifies training of robust image classification models for biologists, democratizing access to advanced DL techniques. BioEncoder is encapsulated in a Python package, crafted for ease of use and flexibility across diverse datasets. It features taxon-agnostic data loaders, custom augmentation options, and streamlined hyperparameter adjustments through text-based configuration files. The toolkit’s significance lies in its potential to unlock new possibilities in biological image analysis - from phenomics and disease diagnosis to species identification and ecosystem monitoring. BioEncoder focuses on the urgent need for toolkits bridging the gap between complex DL methodologies and practical applications in biological research.
A compact encoding of the genome suitable for machine learning prediction of traits and genetic risk scores
Authors: Fatapour Yasaman , Brody James P.
Published: April 2024

Genotype to phenotype prediction is a central problem in biology and medicine. Machine learning is a natural tool to address this problem. However, a person’s genotype is usually represented by a few million single-nucleotide polymorphisms and most datasets only have a few thousand patients. Thus, this problem typically has many more predictors than the number of samples (patients), making it unsuitable for machine learning.

The objective of this paper is to examine the efficacy of a compact genotype representation, which employs a limited number of predictors, in predicting a person’s phenotype through the application of machine learning.

We characterized a person’s genotype using chromosome-scale length variation, a measure that is computed as the average value of reported log R ratios across a portion of a chromosome. We computed these numbers from data collected by the NIH All of Us program. We used the AutoML function (h2o.ai) in binary classification mode to identify the best models to differentiate between male/female, Black/white, white/Asian, and Black/Asian. We also used the AutoML function in regression mode to predict the height of people based on their age and genotype.

Our results showed that we could effectively classify a person, using only information from chromosomes 1-22, as Male/Female (AUC=0.9988±0.0001), White/Black (AUC=0.970± 0.002), Asian/White (AUC=0.877± 0.002), and Black/Asian (AUC=0.966± 0.002). This approach also effectively predicted height.

In conclusion, we have shown that this compact representation of a person’s genotype, along with machine learning, can effectively predict a person’s phenotype.
Osmosensing in trabecular meshwork cells
Authors: Baumann Jackson M. , Yarishkin Oleg , Lakk Monika , Rudzitis Christopher N. , Tseng Yun Ting , Križaj David
Published: April 2024

Aqueous humor drainage from the anterior eye constitutes a key determinant of intraocular pressure (IOP) under homeostatic and pathological conditions. Swelling of the trabecular meshwork (TM) increases its flow resistance but the mechanisms that sense and transduce osmotic gradients remain poorly understood. We used optical molecular analyses, optical imaging and electrophysiology to investigate TM osmotransduction and its role in calcium and chloride homeostasis. Anisosmotic conditions elicited proportional changes in TM cell volume. Swelling, but not shrinking, evoked increases in intracellular calcium concentration [Ca2+]TM. Hypotonicity-evoked calcium signals were sensitive to HC067047, a selective blocker of TRPV4 channels, whereas the agonist GSK1016790A promoted swelling under isotonic conditions. TRPV4 inhibition partially suppressed hypotonicity-induced volume increases and reduced the magnitude of the swelling-induced membrane current, with a substantial fraction of the swelling-evoked current abrogated by Cl-channel antagonists DIDS and niflumic acid. The volume-sensing transcriptome of primary human TM cells showed expression of TRPV4, TRPM4, AQP1, and TMEMC3B genes. Cl-channel expression was dominated by ANO6 transcripts, auxiliary levels of ANO3, ANO7 and ANO10 and modest expression of LTTRC genes that encode volume-activated anion channels. Thus, TRPV4-mediated cation influx works with Cl-efflux to sense and respond to osmotic stress, potentially contributing to pathological swelling, calcium overload and intracellular signaling that could exacerbate functional disturbances in inflammatory disease and glaucoma.