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Sex estimation is one of the most important components in assessing the biological profile of an individual. In an archaeological context, the pelvis, which is the most dimorphic part of the skeleton, is often poorly preserved, which can cause an inability to use morphological sex estimation methods. Therefore, alternative methods are required in such cases. Because the utility of the metric methods based on the femur measurement has been confirmed, and the bone is usually available for examination due to its good preservation, developing methods using the landmarks of the femur could have important implications in sex estimation. This study aimed to derive a discriminant function equation for a Polish archaeological population based on measurements of the proximal end of the femur. The study sample included individuals from a medieval cemetery in Milicz (n = 62) and an early modern necropolis at Czysty Square in Wrocław, Poland (n = 162). The analysis included seven measurements collected from the right and left proximal femora. To estimate the reproducibility of the measurements, intra-and interobserver errors and reliability coefficients were calculated. Subsequently, univariate and stepwise discriminant analyses were performed, and the sex sectioning points and equations were proposed. No differences were observed between measurements of the right and left femora. The results indicated a high utility and reproducibility of the FHD measurement (regardless whether left or right femur was measured). The discriminant equations for sex estimation reached an accuracy of 83.0–92.3%, which implies the utility of the function on Polish historical populations when the other methods for sex estimation cannot be used. [ABSTRACT FROM AUTHOR]

Uncovering the cis -regulatory code that governs when and how much each gene is transcribed in a given genome and cellular state remains a central goal of biology. Here, we discuss major layers of regulation that influence how transcriptional outputs are encoded by DNA sequence and cellular context. We first discuss how transcription factors bind specific DNA sequences in a dosage-dependent and cooperative manner and then proceed to the cofactors that facilitate transcription factor function and mediate the activity of modular cis -regulatory elements such as enhancers, silencers, and promoters. We then consider the complex and poorly understood interplay of these diverse elements within regulatory landscapes and its relationships with chromatin states and nuclear organization. We propose that a mechanistically informed, quantitative model of transcriptional regulation that integrates these multiple regulatory layers will be the key to ultimately cracking the cis -regulatory code. The cis -regulatory code dictates how DNA sequence controls quantitative transcription levels of each gene depending on cellular context. Kim and Wysocka review progress and challenges in understanding the layers of this code, from transcription factor binding to cofactor recruitment and ultimately cis -regulatory element specificity and function within complex regulatory landscapes. [ABSTRACT FROM AUTHOR]

Eukaryotic gene regulation is mediated by cis-regulatory elements, which are embedded within the vast non-coding genomic space and recognized by the transcription factors in a sequence- and context-dependent manner. A large proportion of eukaryotic genomes, including at least half of the human genome, are composed of transposable elements (TEs), which in their ancestral form carried their own cis-regulatory sequences able to exploit the host trans environment to promote TE transcription and facilitate transposition. Although not all present-day TE copies have retained this regulatory function, the preexisting regulatory potential of TEs can provide a rich source of cis-regulatory innovation for the host. Here, we review recent evidence documenting diverse contributions of TE sequences to gene regulation by functioning as enhancers, promoters, silencers and boundary elements. We discuss how TE-derived enhancer sequences can rapidly facilitate changes in existing gene regulatory networks and mediate species- and cell-type-specific regulatory innovations, and we postulate a unique contribution of TEs to species-specific gene expression divergence in pluripotency and early embryogenesis. With advances in genome-wide technologies and analyses, systematic investigation of TEs' cis-regulatory potential is now possible and our understanding of the biological impact of genomic TEs is increasing. [ABSTRACT FROM AUTHOR]

Abstract Various bee products were found to be efficient corrosion inhibitors of aluminium in different environments. In particular, bee pollen was found to be highly effective in alkaline electrolytes, yet its highly complex composition and possible synergistic interactions hinder determination of the compounds acting as active corrosion inhibitors. The main purpose of the following work is to investigate the effect of solvents used for pollen extraction process on the corrosion inhibition of AA5754 alloy in alkaline environment. Both infrared and mass spectroscopies as well as chromatographic analysis were used to determine differences in the composition of each obtained extract. The inhibition efficiency (IE %) of each extract was determined by using the potentiodynamic polarization and impedance studies. The highest IE % , exceeding 90% at 10 gL-1, was recorded for the water/ethanol extract. Most importantly, it has been found that the dichloromethane extract containing less polar compounds enhanced the corrosion rate at low bee pollen concentrations, and offered lower inhibition efficiency at the concentrations above 10 gL-1. The adsorption isotherms were drawn based on dynamic impedance spectroscopy in galvanostatic mode (g-DEIS), while the measurements carried out at elevated temperatures allowed the construction of Arrhenius plots and, consequently, the confirmation of the physical mechanism of adsorption. Graphical abstract Image 1089025 [ABSTRACT FROM AUTHOR]

At the end of 2019, a new classification of breast malignancies was published by the World Health Organization (WHO). Popular name of the classification is the "blue book" and it derives from the colour of its cover. New classification was made available after 7 years from the previous one. In 2019 the WHO introduced new disease entities: mucinous cystadenocarcinoma and tall cell carcinoma of reverse polarity. The most recent classification also contains classification of the microscopic evaluation of ductal carcinoma in situ (DCIS) and of the evaluation of the parameters necessary to define the tumour grade of breast cancer as well as predictive or prognostic parameters. All of above mentioned changes are presented and commented on in the article. [ABSTRACT FROM AUTHOR]

This paper presents congenital anomalies characteristic of Klippel–Feil syndrome, type II, diagnosed in the skeleton of a young to middle‐aged woman uncovered in a cemetery adjacent to the Church of St. Jacob the Apostle in Wągrowiec (Poland), from a grave within an archaeological layer dated to the 14th–17th centuries. A rare type of fusion was identified between the sixth and seventh cervical vertebrae only, co‐occurring with a well‐developed right cervical rib fused to the shaft of the first thoracic rib and articulated via synovial joints with the seventh cervical vertebra. The fusion of the cervical vertebrae involved their bodies, right laminae, and parts of the right articular processes. The interpretation of the presence of Klippel–Feil syndrome is additionally supported by the absence of any evidence of trauma in the cervical region of the spine or of pathological changes in the skeleton indicative of diffuse idiopathic skeletal hyperostosis or ankylosing spondylitis. The formation of Schmorl's nodes and degenerative changes in apophyseal joint surfaces diagnosed in the cervical vertebrae were probably secondary in relation to the observed congenital anomalies. Additionally, examinations revealed ossified insertions of the ligamentum flavum and degenerative changes of the vertebrae in the lower region of the spine as well as incomplete posterior bridge of the atlas, torus mandibularis, and humerus septal aperture. [ABSTRACT FROM AUTHOR]

Abstract The efficiency of AA5754 aluminium alloy corrosion inhibition achieved with maleic, malic, succinic, tartaric, citric, tricarballylic acids and serine in alkaline environment (pH 11) was examined. Selected corrosion inhibitors are characterized by different numbers and distribution of carbonyl and hydroxyl groups within their molecules. We have proposed and verified a novel approach for determining the adsorption isotherms based on the impedance measurements in galvanostatic mode (g-DEIS), allowing to distinguish subtle changes in the adsorption dynamics. It was shown that g-DEIS precisely determines the inhibitor concentration required for the full coverage of aluminium surface with the adsorbed inhibitor monolayer. Our approach was then cross-verified with the ellipsometry, cyclic polarization and classic EIS measurements, while the SEM and XPS analyses served to determine changes in the surface topography and chemistry. We have demonstrated that the investigated compounds significantly decelerate the corrosion rate of AA5754 at low inhibitor concentrations. Inhibition efficiency exceeds 99% at 6.9 mM for tricarballylic, 8.1 mM for citric and 12.0 mM for tartaric acid. The inhibition efficiency was primarily dependent on the high number of carbonyl groups in the molecule, while the inhibition provided by monocarboxylic amino acid (serine) was negligible, reaching 60% at 20 mM. The plotted isotherms fitted the Langmuir adsorption model, with similar values of Gibbs free energy for each studied inhibitor. The adsorption of carboxylic acids onto the surface of aluminium occurred via ligand exchange mechanism. On the basis of electrochemical and XPS studies, we claim that the role played by hydroxyl groups is secondary, while their presence slightly worsens the corrosion resistance of aluminium. Graphical abstract Image [ABSTRACT FROM AUTHOR]

A novel approach is proposed for constructing the adsorption isotherm in corrosion studies, based on a well-known interaction between citric acid and aluminium in alkaline electrolytes. Our approach utilizes the instantaneous impedance measurements via Dynamic Electrochemical Impedance Spectroscopy in galvanostatic mode (g-DEIS). Unlike other common tools, g-DEIS delivers exact information about the concentration required for full surface coverage with adsorbed inhibitor. A significantly larger data set enables observation of multi-stage mechanism of adsorption and complex interaction between citric acid and the metal surface. The obtained impedance results displayed a high convergence with other electrochemical, XPS and SEM studies carried out for verification purposes. It was shown that citric acid exhibits critical concentration with respect to the inhibition efficiency. Chemistry of the adsorbed layer was altered and secondary increase in the corrosion rate was observed in the excess of citric acid, a feature typical for surfactants. Furthermore, authors compared different aluminium alloys with respect to their corrosion resistance mediated by citric acid. The conclusion was reached that regardless of corrosion resistance, the kinetics and mechanism of passive layer formation in Al alloys depends only slightly on alloying additives. AA7020 alloy was an exception because of a specific interaction between zinc and citric acid. [ABSTRACT FROM AUTHOR]

The aim of this article is to present briefly new pathological entities which are recently increasingly commonly used in pathology reports, as well as to discuss their clinical consequences. The new WHO classification of breast diseases includes, inter alia, invasive carcinoma of no special type: this is not a specific entity, but rather a group of malignancies without specific features. The lobular hyperplasia group includes a classical variant and a pleomorphic variant of lobular carcinoma in situ, as well as atypical lobular hyperplasia. The ductal hyperplasia group, according to the current revision of the WHO classification of breast diseases, encompasses: typical (i.e. non-atypical) ductal hyperplasia, columnar cell change, columnar cell hyperplasia, atypical ductal hyperplasia. The mesenchymal breast hyperplasia group includes pseudoangiomatous stromal hyperplasia. We briefly discuss the above mentioned entities together with their respective clinical and therapeutic consequences. [ABSTRACT FROM AUTHOR]

The article presents a case of a 36-year-old female with a rare subtype of breast cancer characterized by choriocarcinomatous differentiation. After interrupting therapy, the patient experienced rapid progression but showed improvement with cisplatin plus etoposide treatment. The rarity of this subtype and the lack of defined chemotherapy regimens make the prognosis uncertain in advanced cases.

The paper presents the electrochemical behaviour of aluminium alloy AA1050 in aqueous alkaline media in the pH range 14–8.5. Electrochemical study was applied in order to obtain comprehensive information on the mechanism and kinetics of the process of anodic dissolution of aluminium, supplemented by monitoring of surface topography using an electron microscope. The corrosion rate of AA1050 increases with increasing concentration of hydroxyl ions OH − . Cathodic reaction occurs in the form of two competing processes, oxygen depolarization and hydrogen evolution. During anodic polarization process up to + 8 V vs Ag | Ag 2 O, activation control of the electrochemical process is converted to diffusion control upon reaching the potential approx. 0 V. Instantaneous impedance spectra in Nyquist projection had at least two time constants: high–frequency loop of capacitive character associated with charge transfer process during anodic dissolution and negative low-frequency capacitance loop. Dynamic processes occurring during anodic dissolution of aluminium alloy can be concluded on the base of instantaneous change of electric parameters. Dynamic Electrochemical Impedance Spectroscopy (DEIS) enables continuous impedance monitoring of non–stationary processes, such as anodic dissolution of aluminium in aqueous alkaline environments. [ABSTRACT FROM AUTHOR]

The most common method of determination of cavitation erosion resistance as well as the magnitude of erosion-corrosion synergistic interaction is based on the weight loss measurements. Nondestructive characterization of installations elements is in most cases impossible to perform. Also, such a measurement does not include local types of failure or alteration of operating conditions. There is an urge to elaborate a method for monitoring of cavitation erosion-corrosion damage. The authors used dynamic impedance technique to study change of electric parameters of various engineering alloys under synergistic interaction of cavitation erosion and corrosion in 3% NaCl solution. Monitoring of electric parameters offers a very good resemblance to failure level identified with weight loss function and microscopic analysis. It was possible to distinguish different stages of material degradation by means of instantaneous impedance measurements. Instantaneous value of charge transfer resistance provides information about synergistic influence of mechanical erosion on corrosion. [ABSTRACT FROM AUTHOR]

Emergence of form and function during embryogenesis arises in large part through cell-type- and cell-state-specific variation in gene expression patterns, mediated by specialized cis-regulatory elements called enhancers. Recent large-scale epigenomic mapping revealed unexpected complexity and dynamics of enhancer utilization patterns, with 400,000 putative human enhancers annotated by the ENCODE project alone. These large-scale efforts were largely enabled through the understanding that enhancers share certain stereotypical chromatin features. However, an important question still lingers: what is the functional significance of enhancer chromatin modification? Here we give an overview of enhancer-associated modifications of histones and DNA and discuss enzymatic activities involved in their dynamic deposition and removal. We describe potential downstream effectors of these marks and propose models for exploring functions of chromatin modification in regulating enhancer activity during development. [ABSTRACT FROM AUTHOR]

Transcriptional enhancers are the primary determinants of tissue-specific gene expression. Although the majority of our current knowledge of enhancer elements comes from detailed analyses of individual loci, recent progress in epigenomics has led to the development of methods for comprehensive and conservation-independent annotation of cell type-specific enhancers. Here, we discuss the advantages and limitations of different genomic approaches to enhancer mapping and summarize observations that have been afforded by the genome-wide views of enhancer landscapes, with a focus on development. We propose that enhancers serve as information integration hubs, at which instructions encoded by the genome are read in the context of a specific cellular state, signaling milieu and chromatin environment, allowing for exquisitely precise spatiotemporal control of gene expression during embryogenesis. [ABSTRACT FROM AUTHOR]

PHD fingers and bromodomains are found in close proximity to each other in many chromatin-associated proteins and can functionally synergize. Recently, it has been demonstrated that the PHD finger of the KAP1 co-repressor functions as an E3 SUMO ligase for the adjacent bromodomain. This PHD-mediated SUMOylation stabilizes the association of the bromodomain with the chromatin modifiers SETDB1 and the nucleosome remodeling and deacetylation (NuRD) complex, thereby promoting establishment of the silent gene expression state. [Copyright &y& Elsevier]

Methylation of lysine 27 on histone H3 (H3K27me) by the Polycomb complex (PRC2) proteins is associated with gene silencing in many developmental processes. A cluster of recent papers () identify the JmjC-domain proteins UTX and JMJD3 as H3K27-specific demethylases that remove this methyl mark, enabling the activation of genes involved in animal body patterning and the inflammatory response. [Copyright &y& Elsevier]

Abstract: Post-translational modifications of histones have been correlated with virtually all chromatin-templated processes, including gene expression regulation, DNA replication, mitosis and meiosis, and DNA repair. In order to better understand the mechanistic basis by which histone modifications participate in the control of cellular processes, it is essential to identify and characterize downstream effector proteins, or “readers”, that are responsible for recognizing different marks and translating them into specific biological outcomes. Ideally, identification of potential histone-binding effectors should occur in an unbiased fashion. Although in the recent years much progress has been made in identifying readers of histone modifications, in particular methylation, recognition of the majority of known histone marks is still poorly understood. Here I describe a simple and unbiased biochemical pull-down assay that allows for the identification of novel histone effector proteins and utilizes biotinylated histone peptides modified at various residues. I provide detailed protocols and suggestions for troubleshooting. [Copyright &y& Elsevier]

This paper provides data concerning the biochemical characteristics of acid phosphatase (AcP) from Russian sturgeon (Acipenser gueldenstaedti) spermatozoa. The extraction was performed in 0.85% NaCl with 0.1% Triton X-100, which stabilized the enzyme. AcP was partially purified by gel filtration. We found two different forms of AcP, i.e. fraction I and fraction II, with molecular weights of 39 kDa and 19 kDa respectively, determined during gel filtration and confirmed electrophoretically. The activity of AcP was different and related to the substrates p-nitrophenylphosphate (pNPP) or β-glycerophosphate (β-GP). It was about 20-fold higher with pNPP as a substrate. Ammonium molybdate was an inhibitor of the 1st and 2nd fraction of AcP, but L-tartaric acid was an inhibitor of fraction II only. [ABSTRACT FROM AUTHOR]

Lysine methylation of histones is recognized as an important component of an epigenetic indexing system demarcating transcriptionally active and inactive chromatin domains. Trimethylation of histone H3 lysine 4 (H3K4me3) marks transcription start sites of virtually all active genes. Recently, we reported that the WD40-repeat protein WDR5 is important for global levels of H3K4me3 and control of HOX gene expression. Here we show that a plant homeodomain (PHD) finger of nucleosome remodelling factor (NURF), an ISWI-containing ATP-dependent chromatin-remodelling complex, mediates a direct preferential association with H3K4me3 tails. Depletion of H3K4me3 causes partial release of the NURF subunit, BPTF (bromodomain and PHD finger transcription factor), from chromatin and defective recruitment of the associated ATPase, SNF2L (also known as ISWI and SMARCA1), to the HOXC8 promoter. Loss of BPTF in Xenopus embryos mimics WDR5 loss-of-function phenotypes, and compromises spatial control of Hox gene expression. These results strongly suggest that WDR5 and NURF function in a common biological pathway in vivo, and that NURF-mediated ATP-dependent chromatin remodelling is directly coupled to H3K4 trimethylation to maintain Hox gene expression patterns during development. We also identify a previously unknown function for the PHD finger as a highly specialized methyl-lysine-binding domain. [ABSTRACT FROM AUTHOR]

Histone modifications mediate changes in gene expression by altering the underlying chromatin structure or by serving as a binding platform to recruit other proteins. One such modification, histone methylation, was thought to be irreversible until last year when Shi and coworkers broke new ground with their discovery of a lysine-specific histone demethylase (LSD1). They showed that LSD1, a nuclear amine oxidase homolog, is a bona fide histone H3 lysine 4 demethylase (). Now, a new study from published in a recent issue of Molecular Cell, together with two studies recently published by and in Nature, reveal that LSD1’s specificity and activity is in fact regulated by associated protein cofactors. [Copyright &y& Elsevier]

Histone H3 lysine 4 (K4) methylation has been linked to the transcriptional activation in a variety of eukaryotic species. Here we show that a common component of MLL1, MLL2, and hSet1 H3 K4 methyltransferase complexes, the WD40-repeat protein WDR5, directly associates with histone H3 di- and trimethylated at K4 and with H3-K4-dimethylated nucleosomes. WDR5 is required for binding of the methyl- transferase complex to the K4-dimethylated H3 tail as well as for global H3 K4 trimethylation and HOX gene activation in human cells. WDR5 is essential for vertebrate development, in that WDR5-depleted X. laevis tadpoles exhibit a variety of developmental defects and abnormal spatial Hox gene expression. Our re suits are the first demonstration that a WD40-repeat protein acts as a module for recognition of a specific histone modification and suggest a mechanism for reading and writing an epigenetic mark for gene activation. [ABSTRACT FROM AUTHOR]

Methylation of arginine (Arg) and lysine residues in histones has been correlated with epigenetic forms of gene regulation. Although histone methyltransferases are known, enzymes that demethylate histones have not been identified. Here, we demonstrate that human peptidylarginine deiminase 4 (PAD4) regulates histone Arg methylation by converting methyl-Arg to citrulline and releasing methylamine. PAD4 targets multiple sites in histones H3 and H4, including those sites methylated by coactivators CARM1 (H3 Arg[sup 17]) and PRMT1 (H4 Arg[sup 3]). A decrease of histone Arg methylation, with a concomitant increase of citrullination, requires PAD4 activity in human HL-60 granulocytes. Moreover, PAD4 activity is linked with the transcriptional regulation of estrogen-responsive genes in MCF-7 cells. These data suggest that PAD4 mediates gene expression by regulating Arg methylation and citrullination in histones. [ABSTRACT FROM AUTHOR]

When herpes simplex virus (HSV) infects human cells, it is able to enter two modes of infection: lytic and latent. A key activator of lytic infection is a virion protein called VP16, which, upon infection of a permissive cell, forms a transcriptional regulatory complex with two cellular proteins – the POU-domain transcription factor Oct-1 and the cell-proliferation factor HCF-1 – to activate transcription of the first set of expressed viral genes. This regulatory complex, called the VP16-induced complex, reveals mechanisms of combinatorial control of transcription. The activities of Oct-1 and HCF-1 – two important regulators of cellular gene expression and proliferation – illuminate strategies by which HSV might coexist with its host. [Copyright &y& Elsevier]

Presents a study that examined the role of the separate regions of an abundant and chromatin-associated protein HCF-1 in cell proliferation associated with the Sin3 histone deacetylase (HDAC) and uncharacterized human trithorax-related Set1 and Ash 2 histone methyltransfase (HMT). Identity of the HCF-1[subN]-interacting proteins; Details of the binding of the HCF-1[subN] subunit with human homologs of the yeast Set1 and Ash2 HMT complex; Discussion on the cosedimentation of HCF-1, Sin3A and Ash2 in high-molecular-weight complexes; Information on the use of cell lines and immunoblot analysis in the study.

Studies the developmental and cell-cycle regulation of Caenorhabditis elegans protein HCF. Development regulation of CeHCF phosphorylation in Caenorhabditis elegans; CeHCF phosphorylation on multiple serine residues in Caenorhabditis elegans; Confirmation of phosphorylation sites by site-directed mutagenesis.

The memory of somatic cell gene expression is reset in the germline in a process that is accompanied by dramatic changes in chromatin modifications. In this issue, show that the histone demethylase Lsd1/Spr-5 may participate in this resetting process in the worm, thereby preventing a decline in germ cell epigenetic stability and viability over ensuing generations. [Copyright &y& Elsevier]

Abstract: Allele frequencies of 15 short tandem repeat loci included in the AmpFlSTR Identifiler kit (Applied Biosystems) were obtained from a sample set of unrelated individuals living in Belarus (n =176). For all loci, no deviation from Hardy–Weinberg equilibrium was found. Results were compared with data available for the Belarusian minority residing in northeastern Poland and for other Slavic populations. Statistically significant differences were observed between Belarusians and all compared populations. The values of heterozygosity, polymorphic information content (PIC), power of discrimination (PD), power of exclusion (PE), paternity index (PI) and matching probability (pM) were calculated. [Copyright &y& Elsevier]

The Site of National Remembrance in Łambinowice, Poland is a complex of former prisoner of war (PoW) and resettlement camps that operated near the village from the time of the Prussian-French War (1870–1871) through the First and Second World Wars, including the interwar period, until the liquidation of the labor camp established by the Polish communist authorities in 1945–1946. Since June 2022, The Central Museum of Prisoners of War has been carrying out a project, a key part of which is the integration of various archaeological research methods for mapping the material remains of the camps that have been preserved until the present day in the local, mostly forested, landscape. Among the most important research problems was the issue of unknown and unmarked PoW burial sites and mass graves. The applied research methodology allowed, among other things, the locating of 60 structures, which can currently be interpreted as the quarters of Italian PoWs interned in Stalag VIII B (344) Lamsdorf at the end of the Second World War. The excavations ended with the identification by name of the first two Italian soldiers. [ABSTRACT FROM AUTHOR]

Introduction: Sialolithiasis remains a clinical problem with unclear etiopathogenesis, lack of prevention methods, and only surgical treatment. Materials and methods: An ultrastructure examination of submandibular sialoliths obtained from patients with chronic sialolithiasis was conducted using a scanning electron microscope and X‐ray photoelectron spectroscopy. Results: Based on the results, we divided sialoliths into three types: calcified (CAL), organic/lipid (LIP), and mixed (MIX). The core structure of the CAL and MIX is very similar. The core of the LIP has a prevalence of organic components. The intermediate layers' structure of the CAL is different from LIP and MIX. In LIP and MIX, the organic component begins to increase in intermediate layers rapidly. The structure of the superficial layers for all types of sialoliths is similar. Conclusions: We introduced a new classification of the submandibular salivary gland stones. Based on the results, it can be said that sialoliths type CAL and LIP have their separate path of origin and development, while MIX is formed as CAL stone, and the further pathway of their growth passes as LIP stones. Organic components were much more than inorganic in all layers of salivary gland stones, which highly prevents their dissolution in the patient's salivary gland duct. [ABSTRACT FROM AUTHOR]

This article presents the general historical context of the mass shootings in the fall of 1939 in the pre-war Gdańsk Pomerania, Poland, and introduces the very term "Pomeranian Crime of 1939." The executions in the Szpęgawski Forest, where between 2,413 and 7,000 people lost their lives, illustrate of the process itself. The results of archaeological research carried out at the site of the mass killings in the Szpęgawski Forest in 2023 is used as a case study. Archaeological research is shedding new light on the crime and its cover-up through analyses of the material evidence. [ABSTRACT FROM AUTHOR]

The paper presents recommendations concerning the surveillance of patients after the treatment of squamous-cell carcinoma (SCC), basal-cell carcinoma (BCC) and Merkel-cell carcinoma (MCC) based on the current European and American recommendations. This overview discusses the methodology and detailed recommendations concerning the post-treatment surveillance, with special attention to the clinical examination, dermatoscopy, imaging diagnostics and patient education. The recommendations emphasise the significance of early monitoring for recurrences, and early detection of new skin cancers, adapted to individual risk factors in a patient and the characteristics of primary cancer. Also the significance of patient education, with regards to the protection against sun radiation and the role of skin self-examination are stressed. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) identified thousands of genetic variants linked to phenotypic traits and disease risk. However, mechanistic understanding of how GWAS variants influence complex morphological traits and can, in certain cases, simultaneously confer normal-range phenotypic variation and disease predisposition, is still largely lacking. Here, we focus on rs6740960, a single nucleotide polymorphism (SNP) at the 2p21 locus, which in GWAS studies has been associated both with normal-range variation in jaw shape and with an increased risk of non-syndromic orofacial clefting. Using in vitro derived embryonic cell types relevant for human facial morphogenesis, we show that this SNP resides in an enhancer that regulates chondrocytic expression of PKDCC - a gene encoding a tyrosine kinase involved in chondrogenesis and skeletal development. In agreement, we demonstrate that the rs6740960 SNP is sufficient to confer chondrocyte-specific differences in PKDCC expression. By deploying dense landmark morphometric analysis of skull elements in mice, we show that changes in Pkdcc dosage are associated with quantitative changes in the maxilla, mandible, and palatine bone shape that are concordant with the facial phenotypes and disease predisposition seen in humans. We further demonstrate that the frequency of the rs6740960 variant strongly deviated among different human populations, and that the activity of its cognate enhancer diverged in hominids. Our study provides a mechanistic explanation of how a common SNP can mediate normal-range and disease-associated morphological variation, with implications for the evolution of human facial features. [ABSTRACT FROM AUTHOR]

A class of cis -regulatory elements, called enhancers, play a central role in orchestrating spatiotemporally precise gene-expression programs during development. Consequently, divergence in enhancer sequence and activity is thought to be an important mediator of inter- and intra-species phenotypic variation. Here, we give an overview of emerging principles of enhancer function, current models of enhancer architecture, genomic substrates from which enhancers emerge during evolution, and the influence of three-dimensional genome organization on long-range gene regulation. We discuss intricate relationships between distinct elements within complex regulatory landscapes and consider their potential impact on specificity and robustness of transcriptional regulation. [ABSTRACT FROM AUTHOR]

Although critical for tuning the timing and level of transcription, enhancer communication with distal promoters is not well understood. Here, we bypass the need for sequence-specific transcription factors (TFs) and recruit activators directly using a chimeric array of gRNA oligos to target dCas9 fused to the activator VP64-p65-Rta (CARGO-VPR). We show that this approach achieves effective activator recruitment to arbitrary genomic sites, even those inaccessible when targeted with a single guide. We utilize CARGO-VPR across the Prdm8-Fgf5 locus in mouse embryonic stem cells (mESCs), where neither gene is expressed. Although activator recruitment to any tested region results in the transcriptional induction of at least one gene, the expression level strongly depends on the genomic distance between the promoter and activator recruitment site. However, the expression-distance relationship for each gene scales distinctly in a manner not attributable to differences in 3D contact frequency, promoter DNA sequence, or the presence of repressive chromatin marks at the locus. [Display omitted] • dCas9 targeting with single gRNAs often fails to result in detectable dCas9 binding • CARGO-VPR achieves effective activator recruitment to arbitrary genomic sites • Expression decays with genomic distance between the promoter and activator binding site • Distance-transcription relationship scales in a gene-specific manner Jensen et al. show that targeting dCas9-VPR using a multiplexed array of RNA guides results in effective activator recruitment to promoter-distal, previously inaccessible genomic sites, allowing for long-range transcriptional activation. The transcriptional response decays with genomic distance between the promoter and activator recruitment site, but the scaling of this relationship is gene specific. [ABSTRACT FROM AUTHOR]

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare (< 1%) primary liver cancer which contains elements of hepatocellular cancer (HCC) and bile duct cancer (CC). On account of the difficulties in reaching preoperative diagnosis, it is frequently diagnosed only after resection is performed. A surgical resection of the liver is the treatment of choice, whilst a liver transplant is a rarely implemented option. The prognosis of cHCC-CC tumours is better than in CC but worse than in HCC. This paper presents the case report of a 62-year-old man undergoing a left hemihepatectomy for a cHCC-CC liver tumour. [ABSTRACT FROM AUTHOR]

Mentalizing is the key socio-cognitive ability. Its heterogeneous structure may result from a variety of forms of mental state inference, which may be based on lower-level processing of cues encoded in the observable behavior of others, or rather involve higher-level computations aimed at understanding another person's perspective. Here we aimed to investigate the representational content of the brain regions engaged in mentalizing. To this end, 61 healthy adults took part in an fMRI study. We explored ROI activity patterns associated with five well-recognized ToM tasks that induce either decoding of mental states from motion kinematics or belief-reasoning. By using multivariate representational similarity analysis, we examined whether these examples of lower- and higher-level forms of social inference induced common or distinct patterns of brain activity. Distinct patterns of brain activity related to decoding of mental states from motion kinematics and belief-reasoning were found in lTPJp and the left IFG, but not the rTPJp. This may indicate that rTPJp supports a general mechanism for the representation of mental states. The divergent patterns of activation in lTPJp and frontal areas likely reflect differences in the degree of involvement of cognitive functions which support the basic mentalizing processes engaged by the two task groups. [ABSTRACT FROM AUTHOR]

Variations in the form of the human face, which plays a role in our individual identities and societal interactions, have fascinated scientists and artists alike. Here, we review our current understanding of the genetics underlying variation in craniofacial morphology and disease-associated dysmorphology, synthesizing decades of progress on Mendelian syndromes in addition to more recent results from genome-wide association studies of human facial shape and disease risk. We also discuss the various approaches used to phenotype and quantify facial shape, which are of particular importance due to the complex, multipartite nature of the craniofacial form. We close by discussing how experimental studies have contributed and will further contribute to our understanding of human genetic variation and then proposing future directions and applications for the field. [ABSTRACT FROM AUTHOR]

CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p5325,26,53,54), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p5325,26,53,54 mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p5325,26,53,54/− embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome. [ABSTRACT FROM AUTHOR]

Developmental gene expression programmes are coordinated by the specialized distal cis-regulatory elements called enhancers, which integrate lineage-and signalling-dependent inputs to guide morphogenesis. In previous work, we characterized the genome-wide repertoire of active enhancers in human neural crest cells (hNCC), an embryonic cell population with critical roles in craniofacial development. We showed that in hNCC, co-occupancy of a master regulator TFAP2A with nuclear receptors NR2F1 and NR2F2 correlates with the presence of permissive enhancer chromatin states. Here, we take advantage of pre-existing human genetic variation to further explore potential cooperation between TFAP2A and NR2F1/F2. We demonstrate that isolated single nucleotide polymorphisms affecting NR2F1/F2-binding sites within hNCC enhancers can alter TFAP2A occupancy and overall chromatin features at the same enhancer allele. We propose that a similar strategy can be used to elucidate other cooperative relationships between transcription factors involved in developmental transitions. Using the neural crest and its major contribution to human craniofacial phenotypes as a paradigm, we discuss how genetic variation might modulate the molecular properties and activity of enhancers, and ultimately impact human phenotypic diversity. [ABSTRACT FROM AUTHOR]

Summary: E2F transcriptional regulators control human-cell proliferation by repressing and activating the transcription of genes required for cell-cycle progression, particularly the S phase. E2F proteins repress transcription in association with retinoblastoma pocket proteins, but less is known about how they activate transcription. Here, we show that the human G1 phase regulator HCF-1 associates with both activator (E2F1 and E2F3a) and repressor (E2F4) E2F proteins, properties that are conserved in insect cells. Human HCF-1-E2F interactions are versatile: their associations and binding to E2F-responsive promoters are cell-cycle selective, and HCF-1 displays coactivator properties when bound to the E2F1 activator and corepressor properties when bound to the E2F4 repressor. During the G1-to-S phase transition, HCF-1 recruits the mixed-lineage leukemia (MLL) and Set-1 histone H3 lysine 4 methyltransferases to E2F-responsive promoters and induces histone methylation and transcriptional activation. These results suggest that HCF-1 induces cell-cycle-specific transcriptional activation by E2F proteins to promote cell proliferation. [Copyright &y& Elsevier]

Cells employ elaborate mechanisms to introduce structural and chemical variation into chromatin. Here, we focus on one such element of variation: methylation of lysine 4 in histone H3 (H3K4). We assess a growing body of literature, including treatment of how the mark is established, the patterns of methylation, and the functional consequences of this epigenetic signature. We discuss structural aspects of the H3K4 methyl recognition by the downstream effectors and propose a distinction between sequence-specific recruitment mechanisms and stabilization on chromatin through methyl-lysine recognition. Finally, we hypothesize how the unique properties of the polyvalent chromatin fiber and associated effectors may amplify small differences in methyl-lysine recognition, simultaneously allowing for a dynamic chromatin architecture. [Copyright &y& Elsevier]

MLL (for mixed-lineage leukemia) is a proto-oncogene that is mutated in a variety of human leukemias. Its product, a homolog of Drosophila melanogaster trithorax, displays intrinsic histone methyltransferase activity and functions genetically to maintain embryonic Hox gene expression. Here we report the biochemical purification of MLL and demonstrate that it associates with a cohort of proteins shared with the yeast and human SET1 histone methyltransferase complexes, including a homolog of Ash2, another Trx-G group protein. Two other members of the novel MLL complex identified here are host cell factor 1 (HCF-1), a transcriptional coregulator, and the related HCF-2, both of which specifically interact with a conserved binding motif in the MLLN (p300) subunit of MLL and provide a potential mechanism for regulating its antagonistic transcriptional properties. Menin, a product of the MEN1 tumor suppressor gene, is also a component of the 1-MDa MLL complex. Abrogation of menin expression phenocopies loss of MLL and reveals a critical role for menin in the maintenance of Hox gene expression. Oncogenic mutant forms of MLL retain an ability to interact with menin but not other identified complex components. These studies link the menin tumor suppressor protein with the MLL histone methyltransferase machinery, with implications for Hox gene expression in development and leukemia pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Some studies suggest that Human Papilloma Virus (HPV) infection is important factor in carcinogenesis of breast tumors. This study' objective was to analyze HPV prevalence in breast cancers of patients from south-central Poland. Materials and methods: The study was performed based on archival paraffin embebbed and formalin fixed blocks in the group of 383 patients with breast cancer. HPV prevalence and its genotype were assessed, respectively by: nested PCR (with two groups of primers: PGMY09/PGMY11 and GP5+/GP6+), quantitative PCR (qPCR). Tumors were classified as HPV positive in case of at least one positive result in nested PCR and positive results in genotyping procedure. For all HPV positive tissues P16 immunostaining was applied in order to confirm active viral infection. Results: In the group of 383 breast cancers, HPV positivity was found in 17 samples (4.4%) in nested PCR. All these samples were subjected to HPV genotyping. This analysis revealed presence of HPV type 16 into two tumors (0.5%). In these two cancers, P16 overexpression was reported. Conclusion: In breast tumors of patients from south-central Poland in Poland, HPV positivity is demonstrated in very low percentage of cases. [ABSTRACT FROM AUTHOR]

Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies focusing on other ancestral groups. Consequently, the degree to which facial traits share a common genetic basis across diverse sets of humans remains largely unknown. We therefore investigated the genetic basis of facial morphology in an East African cohort. We applied an open-ended data-driven phenotyping approach to a sample of 2,595 3D facial images collected on Tanzanian children. This approach segments the face into hierarchically arranged, multivariate features that capture the shape variation after adjusting for age, sex, height, weight, facial size and population stratification. Genome scans of these multivariate shape phenotypes revealed significant (p < 2.5 × 10−8) signals at 20 loci, which were enriched for active chromatin elements in human cranial neural crest cells and embryonic craniofacial tissue, consistent with an early developmental origin of the facial variation. Two of these associations were in highly conserved regions showing craniofacial-specific enhancer activity during embryological development (5q31.1 and 12q21.31). Six of the 20 loci surpassed a stricter threshold accounting for multiple phenotypes with study-wide significance (p < 6.25 × 10−10). Cross-population comparisons indicated 10 association signals were shared with Europeans (seven sharing the same associated SNP), and facilitated fine-mapping of causal variants at previously reported loci. Taken together, these results may point to both shared and population-specific components to the genetic architecture of facial variation. Author summary: Genetic factors play an important role in shaping human facial features. Over the last decade, studies have identified numerous genes associated with various facial traits. The vast majority of these studies have focused on European or Asian populations, while African populations have been underrepresented. Increasing the diversity of these analyses can reveal novel associations and cross-population analyses can help deepen our understanding of known genetic associations. We therefore performed a genome scan of 3D facial features in African children from Tanzania and then compared our results to Europeans. We found 20 regions of the genome associated with facial shape in Tanzanian children, 10 of which were also present in Europeans, indicating evidence for a partly shared genetic basis for human facial shape across populations. In addition, about half of the genetic associations observed in Tanzanians were not present in Europeans, and some of the shared signals differed between populations in the specific genetic variants associated or specific facial traits affected. These results shed light on the shared and population-specific genetic contributors to normal-range facial variation. [ABSTRACT FROM AUTHOR]

The analysis of contemporary genomic data typically operates on one-dimensional phenotypic measurements (e.g. standing height). Here we report on a data-driven, family-informed strategy to facial phenotyping that searches for biologically relevant traits and reduces multivariate 3D facial shape variability into amendable univariate measurements, while preserving its structurally complex nature. We performed a biometric identification of siblings in a sample of 424 children, defining 1,048 sib-shared facial traits. Subsequent quantification and analyses in an independent European cohort (n = 8,246) demonstrated significant heritability for a subset of traits (0.17–0.53) and highlighted 218 genome-wide significant loci (38 also study-wide) associated with facial variation shared by siblings. These loci showed preferential enrichment for active chromatin marks in cranial neural crest cells and embryonic craniofacial tissues and several regions harbor putative craniofacial genes, thereby enhancing our knowledge on the genetic architecture of normal-range facial variation. Author summary: The human face is a highly variable trait composed of distinct features, each influenced by genetic and environmental factors. The strong genetic component is primarily evidenced by the facial similarity between identical twins and the clear facial resemblances within families. Over the past decade, a powerful methodological toolbox of computational and statistical genetics has been developed to study the genetic architecture of complex traits. However, these methods typically require one-dimensional phenotypic measurements (e.g. width of the nose or spacing between the eyes) that fail to accurately describe 3D facial shape. In this paper, we learn from 3D facial data itself, a series of relevant traits that are guided by the facial similarity observed between sibling pairs. Importantly, while preserving the structural convolution of the face, these traits also fit the requirements as input to the well-established statistical tools. In doing so, we have identified many genetic loci that are associated with a wide range of facial features. Some of these regions contained genes related to embryonic facial development, and craniofacial malformations. An improved understanding of the genetic basis of facial shape can have several important applications, for example in developmental biology, medical genetics and forensic sciences. [ABSTRACT FROM AUTHOR]

• Multisine impedance spectroscopy enables multi-frequency readout of DNA hybridization. • Electrochemical analysis of DEFB1 gene allows for recognition of human DNA. • DEFB1 gene was detected using charge transfer and frequency dispersion of capacitance effects. • Multisine detection reveals high discrepancy for identification of human DNA versus animal originated. • Boron-doped diamond served as surface of specifically-anchored oligonucleotide sequences. Albert is a dog (Canis familiaris), but he does not realize this. Albert loves human food (and beer), watching movies on the internet, sleeping in bed, and more. But he should not do all these things. To convince him that, we have desinged a test procedure. The DEFB1 gene is unique to human species. Detecting its presence from saliva and in short periods may offer an advantage in the field of forensic medicine, and influence Albert's bad habits. This study reveals novel utilization of the multisine impedance spectroscopy carried out during potentiodynamic polarization (pDEIS) of the electrode. We have utilized pDEIS to detect DEFB1 gene in collected saliva samples. The detection process was conducted at the boron-doped diamond surfaces functionalized with DEFB1-complimentary oligonucleotide sequence, anchored at the electrode surface. Next, a short-term electrode incubation in presence of target DNA sample allows for achieving DNA hybridization when exposed to human DNA material. The dsDNA orientation vs electrode surface is affected by polarization, and tracked by changes in the electrode kinetics preceded by subtle capacitance dispersion effects. The optimized measurement conditions range between +0.5 and +0.9 V vs Ag|AgCl due to nonspecific DNA adsorption, affecting heterogeneous charge transfer. The DNA hybridization is not achieved in the case of non-complimentary ssDNA originated from any other species subjected to this test. The discussed differences obtained during electrode incubation are supported by the XPS analyses. [ABSTRACT FROM AUTHOR]

The aim of work was the epidemiological analysis of the occurrence of sialolithiasis of the submandibular gland in adults and the evaluation of the ultrastructure of salivary stones. The study sample consisted of 44 sialoliths. Analysis of the structure and chemical composition of sialoliths was performed using a Scanning Electron Microscope and Raman Spectroscopy. Comparing our results with the literature we can say that the epidemiology of sialolithiasis has not changed significantly over the past 50 years. A wide variety of sialoliths structure was observed. In 75% (33) cases a layered structure of salivary stones was observed, while in 25% (11) – homogeneous structure. The various distribution of organic and inorganic components was observed among all the analyzed sialoliths. Raman spectroscopy allows for preliminary analysis of the sialoliths structure with only a qualitative assessment of their composition, which significantly reduces the research value of this method. The presence of organic and inorganic compounds in the core and inner layers of the salivary glands stones confirms 2 basic theories of the formation of sialoliths: inflammation and deposition of the inorganic component as a result of disruption of saliva flow in the salivary glands. [ABSTRACT FROM AUTHOR]

Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although in vitro studies suggest that it may be common, examples of such cooperativity remain scarce in cellular contexts. Here, we demonstrate how "Coordinator," a long DNA motif composed of common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines the regulatory regions of embryonic face and limb mesenchyme. Coordinator guides cooperative and selective binding between the bHLH family mesenchymal regulator TWIST1 and a collective of HD factors associated with regional identities in the face and limb. TWIST1 is required for HD binding and open chromatin at Coordinator sites, whereas HD factors stabilize TWIST1 occupancy at Coordinator and titrate it away from HD-independent sites. This cooperativity results in the shared regulation of genes involved in cell-type and positional identities and ultimately shapes facial morphology and evolution. [Display omitted] • Mutually dependent binding of TWIST1 and homeodomain TFs in embryonic mesenchyme • TF co-binding drives enhancer accessibility and shared transcriptional regulation • Weak TF-TF contacts guided by DNA mediate the selectivity of cooperating partners • TWIST1, partners, and bound targets enriched for face-shape-associated SNPs Epigenomic, biochemical, structural, and human phenotypic analyses of transcription factors that regulate a composite DNA motif in the embryonic face and limb mesenchyme reveal how DNA-guided cooperative binding gives rise to specificity among members of large TF families. This cooperativity promotes the integration of cellular and positional identity programs and contributes to the evolution and individual variation of human facial shape. [ABSTRACT FROM AUTHOR]