Partial Overlap Research Articles

PATH-36. DO GENE EXPRESSION PROFILES BETTER PREDICT OLIGODENDROGLIOMA SURVIVAL?

Abstract The WHO 2021 classification of oligodendroglioma grade 2 (G2) and grade 3 (G3), is separated by histopathology alone and does not universally reflect survival outcome. DNA methylation-based profiling also fails to separate oligodendroglioma grades. Our aim was to define transcriptome-based molecular subgroups that predict survival of oligodendroglioma (IDH-mutant and 1p/19q-codeleted) patients. Clinical and whole-transcriptome data for oligodendroglioma were obtained from TCGA (n=132), CGGA (n=53), and the Exsegen Genomics Research Biobank (n=16) (CTRI/2021/09/036861); while that of control brain samples (n=9) were obtained from CPTAC. Overall survival (OS) was significantly different in TCGA samples between WHO CNS G2 and G3 oligodendrogliomas (log-rank test, p=0.0001); but, not in CGGA (p=0.1833) or Exsegen (p>0.06) samples. Genes with highly variable expression (Median Absolute Deviation, i.e. MAD>1; 1645 genes) across TCGA oligodendroglioma and CPTAC control brain samples were used to exclude 9 oligodendroglioma samples with Pearson’s correlation>0.75 with control brain samples. Consensus clustering (K-means and spectral) of remaining 124 TCGA oligodendroglioma samples identified three significantly different (SigClust, p<0.05) transcriptomic classes using 1347 highly variable genes (MAD>1) in these samples. Principal component analysis (PCA) on expression of 1347 genes in TCGA samples revealed partial overlap of G2 and G3 tumours; but transcriptomic classes with distinct OS could be identified at both extremes of survival. Gene expression signatures for each transcriptomic class were developed using core TCGA samples from each class. For further validation, gene signatures were used to predict the transcriptomic classes of CGGA and Exsegen samples based on highest cosine similarity between sample gene expression and gene signature of each transcriptomic class. OS was significantly different between the transcriptomic classes in TCGA samples and predicted ones in CGGA samples. Transcriptome profiling separated oligodendrogliomas into distinct classes which can predict survival and potentially augment grading and refine prognostication and treatment options.

Multi-quenching electrochemiluminescence system based on resonance energy transfer from self-enhanced Ce(III, IV)-MOF@Ru to CuO@PDA@AuNPs for ultrasensitive detection of HER2

This study presents an innovative approach based on electrochemiluminescence resonance energy transfer (ECL-RET) through the introduction of a new pattern donor-acceptor couple. The donor of self-enhanced Ce(III, IV)-MOF@Ru is created by immobilizing Ru(bpy)32+ on Ce-based metal-organic frameworks (Ce(III, IV)-MOF). The acceptor of CuO@PDA@AuNPs is the CuO nanospheres polydopamine (PDA) framework grafted with gold nanoparticles (AuNPs). An ultrasensitive detection of human epidermal growth factor receptor-2 (HER2) was achieved through the development of a quenched ECL immunosensor. Ce(III, IV)-MOF, a unique 3D infinite extension framework, was recognized for its excellent nanostructure and remarkable capacity to greatly activate tripropylamine (TPrA) and generate abundant radicals. Fortunately, it was simultaneously utilized as a highly effective coreactant accelerator and encapsulation agent, thereby facilitating the immobilization of Ru(bpy)32+ and the generation of radicals for creating a self-enhanced emitter of Ce(III, IV)-MOF@Ru. Consequently, by effectively reducing the distance of electron transmission and minimizing the loss of energy, Ce(III, IV)-MOF@Ru achieved a significantly high efficiency in ECL. More importantly, CuO@PDA@AuNPs was prepared as a perfect quenching agent. The ultraviolet-visible (UV–vis) spectra of CuO@PDA@AuNPs exhibited partial overlap with ECL spectra of Ce(III, IV)-MOF@Ru, thus efficiently initiating the ECL-RET interaction between the donor and acceptor. With the purpose of demonstrating the superiority of newly obtained self-enhanced nanoemitter and donor-acceptor couple, an ECL immunoassay was proposed for the analysis of HER2 with range of 0.2 fg/mL ∼ 10 ng/mL and the limit of detection of 0.067 fg/mL. Therefore, this method supplies convenient and significant strategy for the clinical analysis.

Proteome profiling of polyomavirus nuclear replication centers using iPOND.

Polyomaviruses (PyVs) cause diverse diseases in a variety of mammalian hosts. During the life cycle, PyVs recruit nuclear host factors to viral genomes to facilitate replication and transcription. While host factors involved in DNA replication, DNA damage sensing and repair, and cell cycle regulation have been observed to bind PyV DNA, the complete set of viral and host proteins comprising the PyV replisome remains incompletely characterized. Here, the iPOND-MS technique (Isolation of Proteins on Nascent DNA coupled with Mass Spectrometry) was used to identify the proteome bound to murine PyV (MuPyV) DNA immediately following synthesis and 2 hours post-synthesis. Several novel MuPyV DNA interactors were identified on newly synthesized viral DNA (vDNA), including MCM complex members, DNA primase, DNA polymerase alpha, DNA ligase, and replication factor C. Though displaying partial overlap, the host and viral proteins bound to MuPyV DNA 2 hours post-synthesis lacked many of the replication proteins found on newly synthesized vDNA. These data help distinguish between the host factors critical for MuPyV DNA replication and those involved in downstream processing.IMPORTANCEPolyomaviruses are the causative agents of serious diseases in humans, including progressive multifocal leukoencephalopathy (PML), BK virus nephropathy, and Merkel cell carcinoma. The exact mechanisms by which the virus replicates, and which host cell proteins are required, are incompletely characterized. Identifying the host proteins necessary for efficient viral replication in the cell may reveal targets for downstream targets that may suppress viral replication in vivo.

Spatial disparities in cancer incidence and mortality, indicating gaps in prevention and/or care

Abstract Background There is a rich literature on the distribution of cancer incidence and mortality in socioeconomically different regions of the world, but none of the studies has compared the spatial distribution of mortality and morbidity to see if they are consistent with each other. Methods All malignant neoplasms and separately by cervical, colorectal, breast, pancreatic, lung and oral cancers were studied in the Hungarian population aged 25-64 years for the period 2007-2018 at the municipality level by sex. In each case, the spatial distribution of morbidity and mortality and their clusters were compared with each other and with the level of deprivation using disease mapping, spatial regression, risk analysis and spatial scan statistics. Results All-cause cancer morbidity and mortality showed a significant association with deprivation. However, the slope of the increase in mortality with increasing deprivation was much steeper than for morbidity in both sexes. The association between deprivation and morbidity was not consistent across all cancers. No significant association was found for male colorectal cancer (RR: 1.003; 95%CI 0.986-1.019), pancreatic cancer (1.014; 95%CI 0.983-1.045) and female colorectal cancer morbidity (RR: 0.977; 95%CI 0.991-1.029), whereas a negative association was found for breast cancer morbidity (RR: 0.977; 95%CI 0.963-0.991). In contrast, a positive association between deprivation and mortality was found for each type of cancer, although with different RRs. However, disease mapping analyses showed only partial overlap between high-risk morbidity and mortality areas, often independent of deprivation. Conclusions Our results highlight not only the diverse relationship between the epidemiological situation and deprivation, but also the disproportionate relationship between cancer morbidity and mortality, thus identifying geographical regions and sub-regions with populations that require special public health attention. Key messages • Comparative spatial analysis of cancer morbidity and mortality at the municipality level is strongly recommended to identify populations in need of targeted cancer prevention and/or care. • The usefulness of comparative spatial analysis of cancer morbidity and mortality is demonstrated in Hungary, one of the countries with the most unfavourable cancer burden in international comparison.

Alternative sulphur metabolism in the fungal pathogen Candida parapsilosis

Candida parapsilosis is an opportunistic fungal pathogen commonly isolated from the environment and associated with nosocomial infection outbreaks worldwide. We describe here the construction of a large collection of gene disruptions, greatly increasing the molecular tools available for probing gene function in C. parapsilosis. We use these to identify transcription factors associated with multiple metabolic pathways, and in particular to dissect the network regulating the assimilation of sulphur. We find that, unlike in other yeasts and filamentous fungi, the transcription factor Met4 is not the main regulator of methionine synthesis. In C. parapsilosis, assimilation of inorganic sulphur (sulphate) and synthesis of cysteine and methionine is regulated by Met28, a paralog of Met4, whereas Met4 regulates expression of a wide array of transporters and enzymes involved in the assimilation of organosulfur compounds. Analysis of transcription factor binding sites suggests that Met4 is recruited by the DNA-binding protein Met32, and Met28 is recruited by Cbf1. Despite having different target genes, Met4 and Met28 have partial functional overlap, possibly because Met4 can contribute to assimilation of inorganic sulphur in the absence of Met28.

PWAS Hub for exploring gene-based associations of common complex diseases.

PWAS (proteome-wide association study) is an innovative genetic association approach that complements widely used methods like GWAS (genome-wide association study). The PWAS approach involves consecutive phases. Initially, machine learning modeling and probabilistic considerations quantify the impact of genetic variants on protein-coding genes' biochemical functions. Secondly, for each individual, aggregating the variants per gene determines a gene-damaging score. Finally, standard statistical tests are activated in the case-control setting to yield statistically significant genes per phenotype. The PWAS Hub offers a user-friendly interface for an in-depth exploration of gene-disease associations from the UK Biobank (UKB). Results from PWAS cover 99 common diseases and conditions, each with over 10,000 diagnosed individuals per phenotype. Users can explore genes associated with these diseases, with separate analyses conducted for males and females. For each phenotype, the analyses account for sex-based genetic effects, inheritance modes (dominant and recessive), and the pleiotropic nature of associated genes. The PWAS Hub showcases its usefulness for asthma by navigating through proteomic-genetic analyses. Inspecting PWAS asthma-listed genes (a total of 27) provide insights into the underlying cellular and molecular mechanisms. Comparison of PWAS-statistically significant genes for common diseases to the Open Targets benchmark shows partial but significant overlap in gene associations for most phenotypes. Graphical tools facilitate comparing genetic effects between PWAS and coding GWAS results, aiding in understanding the sex-specific genetic impact on common diseases. This adaptable platform is attractive to clinicians, researchers, and individuals interested in delving into gene-disease associations and sex-specific genetic effects.

The role of two major nucleoid-associated proteins in Streptomyces, HupA and HupS, in stress survival and gene expression regulation

BackgroundStreptomyces are sporulating soil bacteria with enormous potential for secondary metabolites biosynthesis. Regulatory networks governing Streptomyces coelicolor differentiation and secondary metabolites production are complex and composed of numerous regulatory proteins ranging from specific transcriptional regulators to sigma factors. Nucleoid-associated proteins (NAPs) are also believed to contribute to regulation of gene expression. Upon DNA binding, these proteins impact DNA accessibility. Among NAPs, HU proteins are the most widespread and abundant. Unlike other bacteria, the Streptomyces genomes encode two HU homologs: HupA and HupS, which differ in structure and expression profile. However, it remained unclear whether the functions of both homologs overlap. Additionally, although both proteins have been shown to bind the chromosome, their rolesin transcriptional regulation have not been studied so far.ResultsIn this study, we explore whether HupA and HupS affect S. coelicolor growth under optimal and stressful conditions and how they control global gene expression. By testing both single and double mutants, we address the question of the complementarity of both HU homologs. We show that the lack of both hup genes led to growth and sporulation inhibition, as well as increased spore fragility. We also demonstrate that both HU homologs can be considered global transcriptional regulators, influencing expression of between 2% and 6% genes encoding among others proteins linked to global regulatory networks and secondary metabolite production.ConclusionsWe identify the independent HupA and HupS regulons, as well as genes under the control of both HupA and HupS proteins. Our data indicate a partial overlap between the functions of HupA and HupS during S. coelicolor growth. HupA and HupS play important roles in Streptomyces regulatory network and impact secondary metabolite clusters.

Magnetic connectivity from the Sun to the Earth with MHD models. I. Impact of the magnetic modelling on connectivity validation

The magnetic connectivity between the Sun and the Earth is crucial to our understanding of the solar wind and space weather events. However, establishing this connectivity is challenging because of the lack of direct observations, which explains the need for reliable simulations. The method most often used to make such measurements over the last few years is the two-step ballistic method, but it has many free parameters that can affect the final result. Thus, we want to provide a connectivity method based on self-consistent magnetohydrodynamics (MHD) models. To this end, we combined the COCONUT coronal model with the EUHFORIA heliospheric model to compute the magnetic field lines from the Earth to the Sun. We then developed a way to quantify both the spatial and temporal uncertainty associated with this computation. To validate our method, we selected four cases already studied in the literature and associated with high-speed-stream events coming from unambiguous coronal holes visible on the disk. We always find a partial overlap with the assumed CH of origin. The extent of this overlap is 19<!PCT!> for event 1, 100<!PCT!> for event 2, 45<!PCT!> for event 3, and 100<!PCT!> for event 4. We looked at the polarity at Earth over the full Carrington rotation to better understand these results. We find that, on average, MHD simulations provide a very good polarity estimation, showing 69<!PCT!> agreement with real data for event 1, 36<!PCT!> for event 2, 68<!PCT!> for event 3, and 69<!PCT!> for event 4. For events 1 and 3, we can then explain the mixed results by the spatial and temporal uncertainty. An interesting result is that, for MHD models, minimum-activity cases appear to be more challenging because of the multiple recurrent crossings of the HCS, while maximum-activity cases appear easier because of the latitudinal extent of the HCS. A similar result was also found with Parker Solar Probe data in another study. We demonstrate that it is possible to use MHD models to compute magnetic connectivity and that this approach provides results of equal quality to those from the two-step ballistic method, with additional possibilities for improvements as the models integrate more critical physics.

Seasonal variation in the food composition of the Bolkar Mountain Viper, Montivipera bulgardaghica (Nilson & Andren, 1985), in the Central Taurus Mountains, Anatolia

The Bolkar Mountain Viper, Montivipera bulgardaghica (Nilson & Andren, 1985), is a mountain viper found in the eastern Mediterranean region. In this study, we present data on the seasonal variation in diet composition across two different habitats in the Central Taurus Mountains of Anatolia, Türkiye. The Karboğazı population inhabits a subalpine shrubland, while the Göller Yaylası population resides in forested land. The vipers primarily consumed Lacertidae (47%), followed by Orthoptera (27%), Chilopoda (18%), and Scincidae (8%) in number. In spring, the diet of the Karboğazı population was mainly composed of Lacertidae but shifts toward Orthoptera during summer and autumn. In contrast, the Göller Yaylası population fed on Lacertidae throughout the entire active season. Overall, the Karboğazı population primarily consumed invertebrates, whereas the Göller Yaylası population predominantly fed on lizards. Both populations exhibited partial niche overlap. There was no significant difference in diet composition between sexes, but prey type and quantity varied with the season. Prey diversity increased in summer and decreased in autumn and spring, corresponding with the prey availability in the environment.

Profiling genetically driven alternative splicing across the Indonesian archipelago

One of the regulatory mechanisms influencing the functional capacity of genes is alternative splicing (AS). Previous studies exploring the splicing landscape of human tissues have shown that AS has contributed to human biology, especially in disease progression and the immune response. Nonetheless, this phenomenon remains poorly characterized across human populations, and it is unclear how genetic and environmental variation contribute to AS. Here, we examine a set of 115 Indonesian samples from three traditional island populations spanning the genetic ancestry cline that characterizes Island Southeast Asia. We conduct a global AS analysis between islands to ascertain the degree of functionally significant AS events and their consequences. Using an event-based statistical model, we detected over 1,500 significant differential AS events across all comparisons. Additionally, we identify over 6,000 genetic variants associated with changes in splicing (splicing quantitative trait loci [sQTLs]), some of which are driven by Papuan-like genetic ancestry, and only show partial overlap with other publicly available sQTL datasets derived from other populations. Computational predictions of RNA binding activity reveal that a fraction of these sQTLs directly modulate the binding propensity of proteins involved in the splicing regulation of immune genes. Overall, these results contribute toward elucidating the role of genetic variation in shaping gene regulation in one of the most diverse regions in the world.

Anomaly inflow, dualities, and quantum simulation of Abelian lattice gauge theories induced by measurements

Previous work [] has demonstrated that quantum simulation of Abelian lattice gauge theories (Wegner models including the toric code in a limit) in general dimensions can be achieved by local adaptive measurements on symmetry-protected topological (SPT) states with higher-form generalized global symmetries. The entanglement structure of the resource SPT state reflects the geometric structure of the gauge theory. In this work we explicitly demonstrate the anomaly inflow mechanism between the deconfining phase of the simulated gauge theory on the boundary and the SPT state in the bulk by showing that the anomalous gauge variation of the boundary state obtained by bulk measurement matches that of the bulk theory. Moreover, we construct the resource state and the measurement pattern for the measurement-based quantum simulation of a lattice gauge theory with a matter field (Fradkin-Shenker model), where a simple scheme to protect gauge invariance of the simulated state against errors is proposed. We further consider taking an overlap between the wave function of the resource state for lattice gauge theories and that of a parameterized product state, and we derive precise dualities between partition functions with insertion of defects corresponding to gauging higher-form global symmetries, as well as measurement-induced phases where states induced by a partial overlap possess different (symmetry-protected) topological orders. Measurement-assisted operators to dualize quantum Hamiltonians of lattice gauge theories and their noninvertibility are also presented. Published by the American Physical Society 2024

Healthy nutrition – prevention of chronic non-communicable diseases. Overview of recommendations

The article provides an overview of the National Recommendations on healthy nutrition available in Europe, Asia (China), the USA and the Russian Federation, assesses the compliance of the presented guidelines with the principles of a healthy diet according to the recommendations of the World Health Organization, and analyzes their role in the prevention of the development of non-infectious diseases, including number of diseases of the cardiovascular system. A search of relevant literature for the review was conducted in PubMed (www.pubmed.gov) using English keywords (“national dietary guidelines”, “WHO diet”, “FBDG”, “dietary guidelines”, “cardiovascular factors”), the website of the National Project of the Russian Federation “Healthy Nutrition” (https://здоровое-питание.рф), eLIBRARY.RU (https://elibrary.ru/defaultx.asp) using keywords in Russian (“ESSE-RF”, “risk factors for non-infectious diseases”, “nutrition”). Publications published between 1995 and 2022 were considered. The review included the National Recommendations in force for 2023, as well as the results of cohort and multicenter studies, the purpose of which was to assess the impact of current recommendations on the development of traditional cardiovascular risk factors, associated clinical conditions (myocardial infarction, stroke, etc.), as well as the impact on general mortality. Publications with completely duplicate data and conclusions were excluded, and in case of partial overlap, both sources were indicated. As a result, a list was compiled of articles, newsletters, and links with up-to-date information on the National Guidelines.

Cell Senescence and the Genetics of Melanoma Development.

Cutaneous malignant melanoma is an aggressive skin cancer with an approximate lifetime risk of 1 in 38 in the UK. While exposure to ultraviolet radiation is a key environmental risk factor for melanoma, up to ~10% of patients report a family history of melanoma, and ~1% have a strong family history. The understanding of causal mutations in melanoma has been critical to the development of novel targeted therapies that have contributed to improved outcomes for late-stage patients. Here, we review current knowledge of the genes affected by familial melanoma mutations and their partial overlap with driver genes commonly mutated in sporadic melanoma development. One theme linking a set of susceptibility loci/genes is the regulation of skin pigmentation and suntanning. The largest functional set of susceptibility variants, typically with high penetrance, includes CDKN2A, RB1, and telomerase reverse transcriptase (TERT) mutations, associated with attenuation of cell senescence. We discuss the mechanisms of action of these gene sets in the biology and progression of nevi and melanoma.

A sensitive electrochemiluminescence immunosensor for CEA detection based on the ECL-RET between zinc-based metal–organic frameworks and ZiF-8@PDA

In this study, we developed a new system that using zinc-based metal–organic frameworks NH2-Zn-PTC as the donor and ZiF-8@PDA as the acceptor to achieve highly sensitive detection of carcinoembryonic antigen (CEA), using the fundamentals of electrochemiluminescence resonance energy transfer (ECL-RET). Firstly, the aggregation-induced quenching effect (ACQ) was eliminated by the coordination of PTC in MOF and the ECL signal was improved. Secondly, the ECL signal was further amplified by using Au NPs and amino groups as co-reaction promoters to generate more SO4.−. In addition, the introduction of ZiF-8@PDA as an acceptor and NH2-Zn-PTC as a donor took advantage of the feature of partial overlap of the UV–vis absorption spectrum and ECL emission spectra between the two, thereby effectively initiating the ECL-RET behavior, which improved the detection sensitivity of the sensor. The prepared immunosensor showed good linearity in the concentration range of 10−4 to 80 ng/mL with a detection limit of 18.20 fg/mL. This makes it promising for clinical testing of tumor markers.

My turn or yours? Me-you-distinction in feature-based action planning.

Binding accounts propose that action planning involves temporarily binding codes of the action's unique features, such as its location and duration. Such binding becomes evident when another action (B) is initiated while maintaining the Action Plan A. Action B is usually impaired if it partially overlaps with the planned Action A (as opposed to full or no feature overlap). In Experiment 1, in which participants bimanually operated two keys, we replicated these partial overlap costs. In Experiment 2, two participants sat side by side, each handling one key. We tested whether Action B would be affected by duration overlap with the planned Action A of another person similarly as by duration overlap with a planned Action A of the participant's other hand. Here, we found no partial overlap costs. However, in Experiment 3, proposing a common reward yielded partial overlap costs. This suggests that in joint action planning, another person's action plan can impact own actions through feature binding, but only with sufficient incentives to corepresent the other's actions (i.e., when goal achievement depends on both participants' performance). This furthers the understanding of how we represent other people's yet-to-be-executed action plans alongside our own. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Nine Neuroimaging-AI Endophenotypes Unravel Disease Heterogeneity and Partial Overlap across Four Brain Disorders: A Dimensional Neuroanatomical Representation.

Disease heterogeneity poses a significant challenge for precision diagnostics. Recent work leveraging artificial intelligence has offered promise to dissect this heterogeneity by identifying complex intermediate brain phenotypes, herein called dimensional neuroimaging endophenotypes (DNEs). We advance the argument that these DNEs capture the degree of expression of respective neuroanatomical patterns measured, offering a dimensional neuroanatomical representation for studying disease heterogeneity and similarities of neurologic and neuropsychiatric diseases. We investigate the presence of nine such DNEs derived from independent yet harmonized studies on Alzheimer's disease (AD1-2)1, autism spectrum disorder (ASD1-3)2, late-life depression (LLD1-2)3, and schizophrenia (SCZ1-2)4, in the general population of 39,178 participants in the UK Biobank study. Phenome-wide associations revealed prominent associations between the nine DNEs and phenotypes related to the brain and other human organ systems. This phenotypic landscape aligns with the SNP-phenotype genome-wide associations, revealing 31 genomic loci associated with the nine DNEs (Bonferroni corrected P-value < 5×10-8/9). The DNEs exhibited significant genetic correlations, colocalization, and causal relationships with multiple human organ systems and chronic diseases. A causal effect (odds ratio=1.25 [1.11, 1.40], P-value=8.72×10-4) was established from AD2, characterized by focal medial temporal lobe atrophy, to AD. The nine DNEs, along with their polygenic risk scores, significantly enhanced the predictive accuracy for 14 systemic disease categories, particularly for conditions related to mental health and the central nervous system, as well as mortality outcomes. These findings underscore the potential of the nine DNEs to capture the expression of disease-related brain phenotypes in individuals of the general population and to relate such measures with genetics, lifestyle factors, and chronic diseases. All results are publicly available at https://labs-laboratory.com/medicine/.

Formation and retrieval of cell assemblies in a biologically realistic spiking neural network model of area CA3 in the mouse hippocampus

The hippocampal formation is critical for episodic memory, with area Cornu Ammonis 3 (CA3) a necessary substrate for auto-associative pattern completion. Recent theoretical and experimental evidence suggests that the formation and retrieval of cell assemblies enable these functions. Yet, how cell assemblies are formed and retrieved in a full-scale spiking neural network (SNN) of CA3 that incorporates the observed diversity of neurons and connections within this circuit is not well understood. Here, we demonstrate that a data-driven SNN model quantitatively reflecting the neuron type-specific population sizes, intrinsic electrophysiology, connectivity statistics, synaptic signaling, and long-term plasticity of the mouse CA3 is capable of robust auto-association and pattern completion via cell assemblies. Our results show that a broad range of assembly sizes could successfully and systematically retrieve patterns from heavily incomplete or corrupted cues after a limited number of presentations. Furthermore, performance was robust with respect to partial overlap of assemblies through shared cells, substantially enhancing memory capacity. These novel findings provide computational evidence that the specific biological properties of the CA3 circuit produce an effective neural substrate for associative learning in the mammalian brain.

Chronometric data and stratigraphic evidence support discontinuity between Neanderthals and early Homo sapiens in the Italian Peninsula

The process by which Palaeolithic Europe was transformed from a Neanderthal-dominated region to one occupied exclusively by Homo sapiens has proven challenging to diagnose. A blurred chronology has made it difficult to determine when Neanderthals disappeared and whether modern humans overlapped with them. Italy is a crucial region because here we can identify not only Late Mousterian industries, assumed to be associated with Neanderthals, but also early Upper Palaeolithic industries linked with the appearance of early H. sapiens, such as the Uluzzian and the Aurignacian. Here, we present a chronometric dataset of 105 new determinations (74 radiocarbon and 31 luminescence ages) from four key southern Italian sites: Cavallo, Castelcivita, Cala, and Oscurusciuto. We built Bayesian-based chronometric models incorporating these results alongside the relative stratigraphic sequences at each site. The results suggest; 1) that the disappearance of Neanderthals probably pre-dated the appearance of early modern humans in the region and; 2) that there was a partial overlap in the chronology of the Uluzzian and Protoaurignacian, suggesting that these industries may have been produced by different human groups in Europe.

Population-level changes in perinatal death for pregnancies prior to and during the COVID-19 pandemic: A pregnancy cohort analysis.

Results of population-level studies examining the effect of the COVID-19 pandemic on the risks of perinatal death have varied considerably. To explore trends in the risk of perinatal death among pregnancies beginning prior to and during the pandemic using a pregnancy cohort approach. This secondary analysis included data from singleton pregnancies ≥20 weeks' gestation in Alberta, Canada, beginning between 5 March 2017 and 4 March 2021. Perinatal death (i.e. stillbirth or neonatal death) was the primary outcome considered. The risk of this outcome was calculated for pregnancies with varying gestational overlap with the pandemic (i.e. none, 0-20 weeks, entire pregnancy). Interrupted time series analysis was used to further determine temporal trends in the outcome by time period of interest. There were 190,853 pregnancies during the analysis period. Overall, the risk of perinatal death decreased with increasing levels of pandemic exposure; this outcome was experienced in 1.0% (95% confidence interval [CI] 0.9, 1.0), 0.9% (95% CI 0.8, 1.1) and 0.8% (95% CI 0.7, 0.9) of pregnancies with no overlap, partial overlap and complete pandemic overlap respectively. Pregnancies beginning during the pandemic that had high antepartum risk scores less frequently led to perinatal death compared to those beginning prior; 3.3% (95% CI 2.7, 3.9) versus 5.7% (95% CI 5.0, 6.5) respectively. Interrupted time-series analysis revealed a decreasing temporal trend in perinatal death for pregnancies beginning ≤40 weeks prior to the start of the COVID-19 pandemic (i.e. with pandemic exposure), with no trend for pregnancies beginning >40 weeks pre-pandemic (i.e. no pandemic exposure). We observed a decrease in perinatal death for pregnancies overlapping with the COVID-19 pandemic in Alberta, particularly among those at high risk of these outcomes. Specific pandemic control measures and government response programmes in our setting may have contributed to this finding.

Quantitative Raman Spectroscopy of Urea and Thiourea in the Reaction Mixtures of Allantoin and 4,5‐Dihydroxyimidazolidine‐2‐Tione Formation

ABSTRACTThe present work introduces a new approach to quantitative determine the reagent concentrations (thiourea and urea) using in situ Raman spectroscopy in the reaction mixture exemplified by the reactions of formation of allantoin and 4,5‐dihydroxyimidazolidine‐2‐thione. The approach comprises the use of a commercially available immersion probe (MarqMetrix Process Elite BallProbe with sapphire lens) as a standard for the immersion probe band at 790 cm−1 of optical glass. This leads to a linear dependence of the ratio of the intensity of non‐overlapping analyte bands at 1003 cm−1 of ‐C‐N‐ vibrations in urea to the one of the 790 cm−1 immersion probe band on the concentration of urea in the test solution. The definable method parameters such as precision (repeatability and reproducibility), linearity, limit of detection (LoD), limit of quantitation (LoQ), and accuracy were determined. The quantitative Raman spectroscopy method is linear, precise within the range of determined concentrations from 0.75 to 2.00 M and can be used to calculate the kinetics of allantoin formation. Using thiourea as an example, it is shown that despite the partial overlap of the analyte band at 730 cm−1 of the ‐C=S vibrations of thiourea with the immersion probe band at 790 cm−1, the method to determine thiourea in the reaction of 4,5‐dihydroxyimidazolidine‐2‐thione preparation is also linear and precise in the range of determined concentrations from 0.10 to 1.57 M.