bluuebunny/crossref_metadata_2025_split huggingface dataset:
The distribution of distances to the edge of species coexistence
Authors: Desallais Mario , Loreau Michel , Arnoldi Jean-François 
Published: January 2024

AbstractIn Lotka-Volterra community models, given a set of biotic interactions, recent approaches have analysed the probability of finding a set of species intrinsic growth rates (representing intraspecific demographic features) that will allow coexistence. Several metrics have been used to quantify the fragility of coexistence in the face of variations in those intrinsic growth rates (representing environmental perturbations), thus probing a notion of ‘distance’ to the edge of coexistence of the community. Here, for any set of interacting species, we derive an analytical expression for the whole distribution of distances to the edge of their coexistence. Remarkably, this distribution is entirely driven by (at most) two characteristic distances that can be directly computed from the matrix of species interactions. We illustrate on data from experimental plant communities that our results offer new ways to study the contextual role of species in maintaining coexistence, and allow us to quantify the extent to which intraspecific features and biotic interactions combine favorably (making coexistence more robust than expected), or unfavourably (making coexistence less robust than expected). Our work synthesizes different study of coexistence and proposes new, easily calculable metrics to enrich research on community persistence in the face of environmental disturbances.
Investments in photoreceptors compete with investments in optics to determine eye design
Authors: Heras Francisco J H , Laughlin Simon B 
Published: January 2024

AbstractBecause an animal invests in an eye’s optics and photoreceptor array to meet behavioural needs at minimum cost, optics and photoreceptors compete for resources to maximise eye performance. This competition has not previously been investigated. Its outcome depends on the relative costs and benefits of investing space, materials and energy in optics and photoreceptors. We introduce a measure of cost, specific volume in µm3sr−1, which relates to performance via optical, physiological and geometrical constraints. We model apposition compound eyes and simple (camera type) eyes to calculate the performance surface across the morphospace of eyes of given type and total cost. This surface identifies the allocation of resources that maximises efficiency and shows how efficiency reduces as eye morphology departs from optimum. Using published data, we calculate specific volumes to estimate the investments in optics and photoreceptors that insects make, and compare these with our models. We find that efficient allocation can explain three robust trends: fast flying diurnal insects allocate>50% of eye volume to photoreceptor arrays, their photoreceptors’ photosensitive waveguides (rhabdomeres, rhabdoms) are much longer than simple eyes’, and length increases systematically with spatial resolution. We conclude that photoreceptor costs often equal or exceed optical costs, therefore competition between optics and photoreceptors for resources is a major factor in eye design, and matching investments in optics and photoreceptors to maximise efficiency is a design principle. Our methodology can be developed to view the adaptive radiation of eyes through a cost:benefit lens.
SIRT1 mediates the antagonism of Wnt/β-catenin pathway by vitamin D in colon carcinoma cells
Authors: García-Martínez José Manuel , Chocarro-Calvo Ana , Martínez-Useros Javier , Regueira-Acebedo Nerea , Fernández-Aceñero María Jesús , Muñoz Alberto , Larriba María Jesús , García-Jiménez Custodia 
Published: January 2024

ABSTRACTCancer initiation and progression result from both genetic alterations and epigenetic reprograming caused by environmental or endogenous factors which can lead to aberrant cell signalling. Most colorectal cancers (CRC) are linked to the abnormal activation of the Wnt/ β-catenin pathway, whose key feature is the accumulation of acetylated β-catenin protein within the nucleus of colon epithelial cells. Nuclear β- catenin acts as a transcriptional co-activator that alters the expression of many target genes involved in cell proliferation and invasion. The most active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol) can antagonize the over-activated Wnt/ β-catenin pathway via binding to its high affinity receptor VDR. Here, we show that the activation of the SIRT1 deacetylase by 1,25(OH)2D3-bound VDR promotes deacetylation and nuclear exclusion of β-catenin and, consequently, the downregulation of its pro-tumorigenic target genes and the inhibition of human colon carcinoma cell proliferation. Notably, orthogonal SIRT1 activation systematically drives nuclear exclusion of β-catenin, highlighting the key role of SIRT1 in CRC. Since nuclear localization of β-catenin is a critical driver of CRC initiation and progression that requires its acetylation, our results provide a mechanistic basis for the epidemiological evidence linking vitamin D deficiency and increased CRC risk and mortality.
Drivers of Bird Communities in an Urban Neighborhood Vary by Scale
Authors: Darracq Andrea , Bliznick Clay , Yeager Ray , Turner Jay , Prathiba Pradeep , Pease Jacob , Whiteman Howard , Smith Ted , Bhatnagar Aruni 
Published: January 2024

AbstractGiven the accelerated pace of global biodiversity loss and rapid urbanization, it is becoming increasingly urgent to identify ways to minimize the costs and maximize the benefits of urban environments for wild flora and fauna. For instance, it has been estimated that 48% of all bird species are experiencing population declines. One of the main drivers of these declines is habitat loss and degradation associated with urbanization. Increased urbanization necessitates a better understanding of how to conserve birds in urban areas. Although relationships between urbanization and bird communities have been explored extensively, few studies have been conducted in residential neighborhoods, and the influence of urban environmental conditions, particularly air pollution, on bird communities remains unclear. In this study, we examined relationships between bird community metrics and environmental measures related to vegetation and air pollution within a residential neighborhood at multiple spatial scales. We found that bird species richness and the average number of native species were positively related to greenness (as measured by the normalized difference vegetation index; NDVI) within 50 m, and negatively associated with ambient levels of NO2at 200 m. Similarly, we found the Hill-Shannon diversity index was positively associated with canopy cover, but negatively associated with NO2at 200 m. The average number of invasive bird species, however, was negatively correlated with canopy cover at 50 m. The average number of native birds was negatively related to ultrafine particle (<100 nm in diameter) concentration. Unlike native bird abundances, invasive bird abundances were not sensitive to NO2or ultrafine particles. Thus, our research suggests that reductions in air pollution, in combination with greening efforts that increase NDVI and canopy cover via the restoration of vegetation within urban neighborhoods, are likely to increase bird diversity and the abundances of native birds while reducing the abundance of invasive birds.
Phenotype-specific melanoma uptake of fatty acid from human adipocytes activates AXL and CAV1-dependent β-catenin nuclear accumulation
Authors: Chocarro-Calvo Ana , Jociles-Ortega Miguel , García-Martinez José Manuel , Louphrasitthiphol Pakavarin , Garcia Yurena Vivas , Ramírez-Sánchez Ana , Chauhan Jagat , Fiuza M Carmen , Duran Manuel , García-Jiménez Custodia , Goding Colin R. 
Published: January 2024

AbstractPhenotypic diversity of cancer cells within tumors generated through bi-directional interactions with the tumor microenvironment has emerged as a major driver of disease progression and therapy resistance. Nutrient availability plays a critical role in determining phenotype, but whether specific nutrients elicit different responses on distinct phenotypes is poorly understood. Here we show, using melanoma as a model, that only MITFLowundifferentiated cells, but not MITFHighcells, are competent to drive lipolysis in human adipocytes. In contrast to MITFHighmelanomas, adipocyte-derived free fatty acids are taken up by undifferentiated MITFLowcells via a fatty acid transporter (FATP)-independent mechanism. Importantly, oleic acid (OA), a monounsaturated long chain fatty acid abundant in adipose tissue and lymph, reprograms MITFLowundifferentiated melanoma cells to a highly invasive state by ligand-independent activation of AXL, a receptor tyrosine kinase associated with therapy resistance in a wide range of cancers. AXL activation by OA then drives SRC-dependent formation and nuclear translocation of a β-catenin-CAV1 complex. The results highlight how a specific nutritional input drives phenotype-specific activation of a pro-metastasis program with implications for FATP-targeted therapies.
crossNN: an explainable framework for cross-platform DNA methylation-based classification of cancer
Authors: Yuan Dongsheng , Jugas Robin , Pokorna Petra , Sterba Jaroslav , Slaby Ondrej , Schmid Simone , Siewert Christin , Osberg Brendan , Capper David , Zeiner Pia , Weber Katharina , Harter Patrick , Jabareen Nabil , Mackowiak Sebastian , Ishaque Naveed , Eils Roland , Lukassen Sören , Euskirchen Philipp 
Published: January 2024

AbstractDNA methylation-based classification of brain tumors has emerged as a powerful and indispensable diagnostic technique. Initial implementations have used methylation microarrays for data generation, but different sequencing approaches are increasingly used. Most current classifiers, however, rely on a fixed methylation feature space, rendering them incompatible with other platforms, especially different flavors of DNA sequencing. Here, we describe crossNN, a neural network-based machine learning framework which can accurately classify tumor entities using DNA methylation profiles obtained from different platforms and with different epigenome coverage and sequencing depth. It outperforms other deep- and shallow machine learning models with respect to precision as well as simplicity and computational requirements while still being fully explainable. Validation in a large cohort of >1,900 tumors profiled using different microarray and sequencing platforms, including low-pass nanopore and targeted bisulfite sequencing, demonstrates the robustness and scalability of the model.
Dual-domain joint learning reconstruction method (JLRM) combined with physical process for spectral computed tomography
Authors: Ma Genwei , Zhao Xing 
Published: January 2024

AbstractSpectral computed tomography (SCT) is an powerful imaging modality with broad applications and advantages such as contrast enhancement, artifact reduction, and material differentiation. The positive process or data collected process of SCT is a nonlinear physical process existing scatter and noise, which make it is an extremely ill-posed inverse problem in mathematics. In this paper, we propose a dual-domain iterative network combining a joint learning reconstruction method (JLRM) with a physical process. Specifically, a physical module network is constructed according to the SCT physical process to accurately describe this forward process, which makes the nonlinear use of the traditional mathematical iterative algorithm effective and stable. Additionally, we build a residualto-residual strategy with an attention mechanism to overcome the slow speed of the traditional mathematical iterative algorithm. We have verified the feasibility of the method through our winning submission to the AAPM DL-spectral CT challenge, and demonstrated that high-accuracy also basis material decomposition results can be achieved with noisy data.
Estimated genetics prevalence of early-onset Parkinson’s disease caused byPRKNmutations
Authors: Diogo Dorothée , Wong Emily H.M. , DeBoever Christopher , Qu Wei , Lee Jonghun , Crawford Stephen , Hioki Takeshi , Padmanabhan Jaya , Prilutsky Daria , Proetzel Gabriele 
Published: January 2024

AbstractBackgroundEstimating the prevalence of rare diseases is challenging due to very limited natural history studies, lack of studies in diverse populations, and frequent under or misdiagnosis. We leveraged human genetics to estimate the genetic prevalence (eGP) of familial Parkinson’s disease (PD) caused by biallelic pathogenic variants in theParkin(PRKN) gene (PRKN-PD).MethodsWe curated the reportedPRKN-PD pathogenic variants and obtained the heterozygous carrier frequencies of these variants from gnomAD and the Japanese Multi-omics reference panel (jMorp). We used the carrier frequencies to estimate the eGP ofPRKN-PD in eight genetic ancestries.ResultsNon-Japanese East Asians presented the highest eGP ofPRKN-PD (24 per 100,000 individuals, 95% CI=4-165 per 100,000 individuals), followed by Non-Finnish Europeans (22 in 100,000 individuals, 95% CI = 11-64 per 100,000 individuals). Based on the proportions of races and ethnicities, we estimated the eGP in the USA and the world-wide eGP to be 18 per 100,000 individuals (95% CI=7-68 per 100,000 individuals). and 13 per 100,000 individuals (95% CI=3-70 per 100,000 individuals), respectively. These estimates were significantly reduced when excluding structural variants (world-wide eGP=2 per 100,000 individuals, 95% CI=1-5 per 100,000 individuals).ConclusionsThis is the first study estimating thePRKN-PD genetic prevalence. Our results suggest that the prevalence of the disease may be higher than previously reported, highlighting potential underdiagnosis. We also demonstrate the importance of carefully considering the known genetic epidemiology of each disease, and its limitations, when using the approach applied in this study to estimate the disease genetic prevalence.
The Concept of Stroma AReactive Invasion Front Areas (SARIFA) as a New Prognostic Biomarker for Lipid-driven Cancers Holds True in Pancreatic Ductal Adenocarcinoma
Authors: Grochowski Przemyslaw , Grosser Bianca , Sommer Florian , Probst Andreas , Waidhauser Johanna , Schenkirsch Gerhard , Reitsam Nic G. , Märkl Bruno 
Published: January 2024

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) is a ‘difficult-to-treat’ entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion front areas), which are an area at the tumour invasion front lacking desmoplastic stroma reaction upon malignant invasion in the surrounding tissue, leading to direct contact between tumour cells and adipocytes. SARIFA showed its significance in gastric and colorectal carcinoma, revealing lipid metabolism alternations that promote tumour progression.MethodsWe reviewed the SARIFA status of 174 PDAC cases on all available H&E-stained tumour slides from archival Whipple-resection specimens. SARIFA positivity was defined as SARIFA detection in at least 66% of the available slides. To investigate alterations in tumour metabolism and microenvironment, we performed immunohistochemical staining for FABP4, CD36 and CD68. To verify and quantify a supposed delipidation of adipocytes, adipose tissue was digitally morphometrised.ResultsIn total, 54 cases (31%) were classified as SARIFA positive and 120 (69%) as SARIFA negative. Patients with SARIFA-positive PDAC showed a significantly worse overall survival compared with SARIFA-negative cases (median overall survival: 9.9 months vs. 18.0 months, HR: 1.558 (1.081–2.247), 95% CI, p = 0.018), which was independent from other prognostic markers (p = 0.014). At the invasion front of SARIFA-positive PDAC, we observed significantly higher expression of FABP4 (p<0.0001) and higher concentrations of CD68+macrophages (p=0.031) related to a higher risk of tumour progression. CD36 staining showed no significant expression differences. The adipocyte areas at the invasion front were significantly smaller, with mean values of 4021 ± 1058 µm2and 1812 ± 1008 µm2for the SARIFA-positive and -negative cases, respectively. The area differences between the SARIFA-positive invasion front area and the other three parameters were highly significant (p < 0.001)ConclusionsSARIFA is a promising prognostic biomarker for PDAC. Its assessment is characterised by simplicity and low effort. The mechanisms behind SARIFA suggest a tumour-promoting increased lipid metabolism and altered immune background, both showing new therapeutic avenues.
Health services provided at the time of abortion in the US: a scoping review of the qualitative and quantitative evidence
Authors: Mahoney Katherine M , Bravo Licia , McAllister Arden , Bogar Kacie , Hennessey Sean , Schreiber Courtney A. , Abernathy Alice 
Published: January 2024

AbstractObjectivesWhile it is well documented that abortion access is associated with improved health, pregnancy-related, and socioeconomic outcomes, the association between abortion access and other reproductive health outcomes is less well described. Abortion-providing clinics also offer preventative reproductive health services. We conducted a scoping review to ascertain the extent to which preventive reproductive healthcare services (contraception, sexually transmitted infection testing and treatment, cervical cancer screening) are affected by abortion access in the United States.MethodsResearchers screened articles and extracted data from PubMed, Embase, Scopus and CINAHL. We excluded articles that did not link abortion to contraception, sexually transmitted infection testing and treatment and cervical cancer screening; or took place outside the US.Results5,359 papers were screened, 74 were included for full text review. Sixty-five were about contraception, seven on STIs, one on cervical cancer screening, and one on other services. The association between policies that restrict or protect abortion access and preventative health services has not been studied on a national scale. Drivers of variation were: insurance and billing policies; regulatory requirements of abortion-providing facilities, lack of staff training in clinics that did not specialize in abortion care; and limited follow up after abortion.ConclusionsAbortion--providing clinics are a highly utilized access point for reproductive health services. More research is needed to determine the public health impact of constrained abortion access on contraceptive use, STI rates and cervical cancer in regions where many abortion-providing clinics have closed.ImplicationsAttention should be paid to changing trends in contraceptive use, STI rates and cervical cancer as abortion-providing clinics close, this may reduce access to reproductive health services broadly.
Sex-specific effects of Birth Weight on Longitudinal Behavioural Outcomes; a Mendelian Randomisation Approach using Polygenic Scores
Authors: Byg Lars Meinertz , Wang Carol , Attia John , Whitehouse Andrew , Pennell Craig 
Published: January 2024

AbstractIntroIt is unclear if sex differences in behaviour arising from birth weight (BW) are genuine because of the cross-sectional nature and potential confounding in previous studies. We aimed to test if sex differences associated with birth weight phenotype were reproducible using a Mendelian randomisation approach, i.e. polygenic score for birthweight across childhood and adolescence.MethodUtilising data from the Raine study we had 1484 genotyped participants with a total of 6446 child behaviour checklist assessments across childhood and adolescence. We used BW polygenic scores in linear mixed-effects models to predict parentally-assessed attention, aggression and social problems scales; we also derived estimates and significance for a sex-by-genotype interaction. We used a Bonferroni corrected significance threshold and tested robustness of the results with teacher assessments of behaviour as well as a second polygenic score.ResultsWe found a sex-by-genotype interaction with lower BW polygenic scores (BW-PGS) associated with increased aggression in males compared to females. These findings were consistent across various analyses, including teacher assessments. Surprisingly, a lower BW-PGS showed protective effects in females, while lower BW phenotype had detrimental effects in males with evidence of a genotype-phenotype mismatch increasing aggression problems in males only.ConclusionThis study underscores the genuine nature of behavioural sex differences arising from low BW and highlights the sex-dependent and diverging effects of environmental and genetic BW determinants.
Treatment of a genetic liver disease in mice through transient prime editor expression
Authors: Rothgangl Tanja , Ioannidi Eleonora I. , Weber Yanik , Tálas András , Böck Desirée , Matsushita Mai , Villiger Elina Andrea , Schmidheini Lukas , Moon Jennifer , Lin Paulo J.C. , Fan Steven H.Y. , Marquart Kim F. , Schwerdel Cornelia , Rimann Nicole , Faccin Erica , Villiger Lukas , Muramatsu Hiromi , Vadovics Máté , Cremonesi Alessio , Thöny Beat , Kopf Manfred , Häberle Johannes , Pardi Norbert , Tam Ying K. , Schwank Gerald 
Published: January 2024

AbstractPrime editing is a versatile genome editing technology that does not rely on DNA double-strand break formation and homology-directed repair (HDR). This makes it a promising tool for correcting pathogenic mutations in tissues consisting predominantly of postmitotic cells, such as the liver. While recent studies have already demonstrated proof-of-concept forin vivoprime editing, the use of viral delivery vectors resulted in prolonged prime editor (PE) expression, posing challenges for clinical application. Here, we developed anin vivoprime editing approach where we delivered the pegRNA using self-complementary adeno-associated viral (scAAV) vectors and the prime editor using nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs). This methodology led to transient expression of the PE for 48h and 26% editing at theDnmt1locus using AAV doses of 2.5×1013vector genomes (vg)/kg and a single dose of 3mg/kg mRNA-LNP. When targeting the pathogenic mutation in the Pahenu2mouse model of phenylketonuria (PKU), we achieved 4.3% gene correction using an AAV dose of 2.5×1013vg/kg and three doses of 2 mg/kg mRNA-LNP. Editing was specific to the liver and the intended locus, and was sufficient to reduce blood L-phenylalanine (Phe) levels from over 1500 µmol/l to below the therapeutic threshold of 600 µmol/l. Our study demonstrates the feasibility ofin vivogene correction in the liver with transient PE expression, bringing prime editing closer to clinical application.
Evolution of human pair bonds as a consequence of male-biased mating sex ratios?
Authors: Nitschke Matthew C. , Kumar Viney , Milliner Katrina E. , Hawkes Kristen , Kim Peter S. 
Published: January 2024

AbstractCompared to our closest primate relatives, human life history involves greater longevity, which includes a distinctive postmenopausal life stage. The extension of the human lifes-pan (and continued fertility in old males) without lengthening female fertility directly changes the ratio of fertile males to fertile females, called the adult sex ratio (ASR). Additionally, this affects a more fine-grained ratio, the operational sex ratio (OSR), defined as the ratio of males to females currently able to conceive. Here, we construct an ODE model with minimal age structure, in which males compete for paternities using either a multiple-mating or mate-guarding strategy. Our focus is on investigating the differences of strategy choice between populations with chimpanzee-like and human-like life histories. By simulating the system, we determine the dominant strategy and its dependence on various parameter combinations. We introduce a new measure we call the lifetime paternity opportunities (LPO) of a given male strategy. The LPO directly calculates the payoffs of different male strategies and hence enables us to predict when strategies may shift. Our results show that an increase in OSR and ASR correlates well with a change in the dominant strategy from multiple mating to guarding.