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Abstract The CMS detector, including its muon system, has been operating at the CERN LHC in increasingly challenging conditions for about 15 years. The muon detector was designed to provide excellent triggering and track reconstruction for muons produced in proton–proton collisons at an instantaneous luminosity ( $$\mathcal {L}$$ L ) of $$1 \times 10^{34}$$ 1 × 10 34 cm $$^{-2}$$ - 2 s $$^{-1}$$ - 1 . During the Run 2 data-taking period (2015–2018), the LHC achieved an instantaneous luminosity of twice its design value, resulting in larger background rates and making the efficient detection of muons more difficult. While some backgrounds result from natural radioactivity, cosmic rays, and interactions of the circulating protons with residual gas in the beam pipe, the dominant source of background hits in the muon system arises from proton–proton interactions themselves. Charged hadrons leaving the calorimeters produce energy deposits in the muon chambers. In addition, high-energy particles interacting in the hadron calorimeter and forward shielding elements generate thermal neutrons, which leak out of the calorimeter and shielding structures, filling the CMS cavern. We describe the method used to measure the background rates in the various muon subsystems. These rates, in conjunction with simulations, can be used to estimate the expected backgrounds in the High-Luminosity LHC. This machine will run for at least 10 years starting in 2029 reaching an instantaneous luminosity of $$\mathcal {L} = 5 \times \text {10}^\text {34}\,\text {cm}^\text {-2}\,\text {s}^\text {-1}$$ L = 5 × 10 34 cm -2 s -1 and increasing ultimately to $$\mathcal {L} = 7.5 \times \text {10}^\text {34}\,\text {cm}^\text {-2}\,\text {s}^\text {-1}$$ L = 7.5 × 10 34 cm -2 s -1 . These background estimates have been a key ingredient for the planning and design of the muon detector upgrade.

To target populations at greatest risk ofdeveloping cancer, it is vital to understand the patterns ofrisk factors and screening behaviors along with cancer surveillance data. This study provides data on the prevalence of self-reported cancer history, can- cer risk factors, and cancer screening behaviors in Florida and compares them to rates in the rest ofthe U.S. Data were obtained from the National Health Interview Survey (NHIS), an annual, cross-sectional household survey of the U.S. civilian non-institutionalized population. We analyzed pooled data from the 2000 and 2005 Cancer Control Modules. Compared to the rest of the U.S., Floridians reported a lower prevalence of current smoking, risky drinking, and obesity, and a greater pre- valence of Prostate Specific Antigen (PSA) testing. However, Floridians reported a greater prevalence ofcancer history and a lower prevalence of physical activity, concern for sun protection, lifetime colorectal cancer screening, lifetime breast exam, life- time mammography screening, and lifetime and past year Pap test. The data indicate that Florida lags behind the rest of the U.S. in several areas, particularly cancer screening, and falls short ofthe Healthy People 2020 objectives for health behaviors and screening. These results provide information for key stakeholders and public health policy makers to effectively target Flor- ida residents at greatest risk for cancer and those not receiving recommended cancer screenings. This study also represents a model ofvaluable state-level evaluations that can be conducted using NHIS data. These types of analyses can provide a great- er understanding of state-level variations and lead to more effective public health interventions aimed at reducing cancer burden.

Abstract External signs of disease are frequently used as indicators of disease susceptibility. However, immune profiling can be a more effective indicator to understand how host responses to infection may be shaped by host, pathogen and environmental factors. To better inform wildlife health assessment and research directions, we investigated the utility of a novel multivariate immunophenotyping approach examining innate and adaptive immune responses in differing climatic, pathogen co-infection and demographic contexts across two koala (Phascolarctos cinereus) populations in New South Wales: the Liverpool Plains (LP), and Southern Highlands to South-west Sydney (SHSWS). Relative to the comparatively healthy SHSWS, the LP had greater and more variable innate immune gene expression (IL-1β, IL-6), and KoRV transcription. During extreme heat and drought, koalas from the LP displayed upregulation of a stress pathway gene and reduced adaptive immune genes expression, haematocrit and plasma protein, suggesting the possibility of environmental impacts through multiple pathways. In those koalas, KoRV transcription status, Chlamydia pecorum infection loads, and visible urogenital inflammation were not associated with immune variation, suggesting that immune markers were more sensitive indicators of real-time impacts than observed disease outcomes.

Este artigo tem como objetivo discutir o trabalho do professor de língua inglesa (doravante LI) com base no Interacionismo Sociodiscursivo (ISD) e no marxismo, a partir de recortes de duas pesquisas em nível de doutorado do Programa de Estudos da Linguagem da Universidade Estadual de Londrina e vinculados ao grupo de pesquisa Linguagem e Educação (LED). Ele traz uma reflexão sobre o significado das prescrições no trabalho do professor formador e do professor da educação básica na rede pública e a função que elas ocupam neste contexto, a partir da investigação sobre o material/livro didático selecionado/produzido por professores formadores de professores de LI e dos manuais do professor (MP) de coleções didáticas de LI, aprovados nas avaliações do Programa Nacional do Livro Didático (PNLD) dos anos 2011 e 2014. A discussão desenvolvida neste artigo permite constatar que, as prescrições e autoprescrições que fazem parte do dia a dia do professor podem ser fator gerador de desenvolvimento, contudo, as condições cada vez mais precárias do trabalho docente, nos diversos níveis de ensino, resultam na sobrecarga de trabalho, na desvalorização do professor, podendo tornar os esforços na formação e nas políticas públicas, como é o caso do PNLD e da adoção de livro didático, inócuos

Abstract Chlamydiosis is a significant disease affecting Eastern Australian koala (Phascolarctos cinereus) populations, impacting individual animal welfare and fecundity and therefore influencing population dynamics. The aim of this study was to investigate the effect of a synthetic peptide vaccine based on 4 components of the Chlamydia pecorum major outer membrane protein (MOMP), over an 18-month period in a koala population severely impacted by chlamydiosis. Wild koalas were recruited into a vaccination or a placebo treatment group on a random allocation, then followed through a period of 18 months, with recapture at 6 monthly intervals. Vaccination did not alter clinical disease expression or chlamydial shedding from the ocular or urogenital sites. Vaccination did not stimulate a significant plasma anti-MOMP IgG response, when compared to the placebo group. There was no significant effect of vaccination on IFN-γ and IL-17A mRNA expression of peripheral blood lymphocytes when stimulated with rMOMP. We have demonstrated that a synthetic peptide vaccination against chlamydiosis is not an effective management tool in a koala population with a high prevalence of C. pecorum infection and related disease. The lack of antigenic response found in this study suggests that further research utilising a larger, full-length antigen is an avenue worth investigation if we are to consider vaccination as a part of a management strategy in diseased koala populations.

Background and Objectives: The aim of this study was to analyze the association between maternal risk factors, such as age, body mass index (BMI), and cigarette smoking, and perinatal outcomes. Materials and Methods: We conducted a retrospective analysis based on prospectively collected data at Hospital Universitario de Torrejón (Madrid, Spain) between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks’ gestation were invited to participate. The association between preeclampsia, preterm birth, gestational diabetes mellitus (GDM), small-for-gestational-age (SGA) or fetal-growth-restricted (FGR) neonates, and type of delivery and maternal age, BMI, and cigarette smoking was studied. Logistic mixed models were used to analyze the data. Results: A total of 1921 patients were included in the analysis. Women who were ≥40 years old had a significantly higher risk of having GDM (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.08 to 2.36) and SGA neonates (OR 1.54, 95% CI 1.00 to 2.37). Women with a BMI < 18 had an increased rate of giving birth to SGA and FGR neonates (OR 3.28, 95% CI 1.51 to 7.05, and OR 3.73, 95% CI 1.54 to 8.37, respectively), whereas women with a BMI ≥ 35 had a higher risk of GDM (OR 3.10, 95% CI 1.95 to 4.89). Smoking increased the risk of having SGA and FGR neonates (OR 1.83, 95% CI 1.36 to 2.46, and OR 1.91, 95% CI 1.29 to 2.78). Conclusions: Advanced maternal age, low or high BMI, and smoking status are significant risk factors for pregnancy complications. Both clinicians and society should concentrate their efforts on addressing these factors to enhance reproductive health.

Injuries and bone fractures are the most frequent causes of admission at wildlife rescue centers. Wild birds are more susceptible to open fractures due to their anatomical structure, which can lead to osteomyelitis and necrosis. Antibiotic therapy in these cases is indispensable, but the increase of antimicrobial-resistant isolates in wildlife has become a significant concern in recent years. In this context, the likelihood of antibiotic failure and death of animals with infectious issues is high. This study aimed to isolate, identify, and assess the antimicrobial resistance pattern of bacteria in wounds and open fractures in wild birds. To this end, injured birds admitted to a wildlife rescue center were sampled, and bacterial isolation and identification were performed. Then, antimicrobial susceptibility testing was assessed according to the disk diffusion method. In total, 36 isolates were obtained from 26 different birds. The genera detected were Staphylococcus spp. (63.8%), Escherichia (13.9%), Bacillus (11.1%), Streptococcus (8.3%), and Micrococcus (2.8%). Among Staphylococcus isolates, S. lentus and S. aureus were the most frequent species. Antimicrobial resistance was detected in 82.6% of the isolates, among which clindamycin resistance stood out, and 31.6% of resistant isolates were considered multidrug-resistant. Results from this study highlight the escalating scope of antimicrobial resistance in wildlife. This level of resistance poses a dual concern for wildlife: firstly, the risk of therapeutic failure in species of significant environmental value, and, secondly, the circulation of resistant bacteria in ecosystems.

Escherichia coli carrying IncK-blaCMY-2 plasmids mediating resistance to extended-spectrum cephalosporins (ESC) has been frequently described in food-producing animals and in humans. This study aimed to characterize IncK-blaCMY-2-positive ESC-resistant E. coli isolates from poultry production systems in Denmark, Finland, and Germany, as well as from Danish human blood infections, and further compare their plasmids. Whole-genome sequencing (Illumina) of all isolates (n = 46) confirmed the presence of the blaCMY-2 gene. Minimum inhibitory concentration (MIC) testing revealed a resistant phenotype to cefotaxime as well as resistance to ≥3 antibiotic classes. Conjugative transfer of the blaCMY-2 gene confirmed the resistance being on mobile plasmids. Pangenome analysis showed only one-third of the genes being in the core with the remainder being in the large accessory gene pool. Single nucleotide polymorphism (SNP) analysis on sequence type (ST) 429 and 1286 isolates showed between 0–60 and 13–90 SNP differences, respectively, indicating vertical transmission of closely related clones in the poultry production, including among Danish, Finnish, and German ST429 isolates. A comparison of 22 ST429 isolates from this study with 80 ST429 isolates in Enterobase revealed the widespread geographical occurrence of related isolates associated with poultry production. Long-read sequencing of a representative subset of isolates (n = 28) allowed further characterization and comparison of the IncK-blaCMY-2 plasmids with publicly available plasmid sequences. This analysis revealed the presence of highly similar plasmids in ESC-resistant E. coli from Denmark, Finland, and Germany pointing to the existence of common sources. Moreover, the analysis presented evidence of global plasmid transmission and evolution. Lastly, our results indicate that IncK-blaCMY-2 plasmids and their carriers had been circulating in the Danish production chain with an associated risk of spreading to humans, as exemplified by the similarity of the clinical ST429 isolate to poultry isolates. Its persistence may be driven by co-selection since most IncK-blaCMY-2 plasmids harbor resistance factors to drugs used in veterinary medicine.

The academic performance of our students is being presented as a permanent challenge for the academy due to its complex directly associated with the results of learning. So then, it originates the question: do academics' methodological innovation efforts impact academic performance? To answer this question, we present the results taken from these innovations applied to a Commercial Engineering course at Universidad de Antofagasta. Considering an universe of 251 students in a 4-year time horizon (2018-2021). It is proposed a teaching plann with digital resources for leraning and centered in students increasing the interaction with resources and with peers. The goal of the innovation is to improve the average grade point average by at least 5% and the failure rate (will decrease) by at least 15%. The innovation in the subject has increased the percentage of approved and the participation in lessons.

RESUMEN: Introducción: Síndrome de Plaqueta Pegajosa (SPP) se le denomina a la trombofilia hereditaria autosómica dominante que se caracteriza por hiperagregación plaquetaria pudiendo ocasionar eventos trombóticos arteriales o venosos. In vitro se manifiesta como un incremento de la agregación plaquetaria a bajas concentraciones de epinefrina y/o adenosindifosfato (ADP) Objetivo: Describir la presencia del síndrome de plaqueta pegajosa en una paciente con varios eventos trombóticos y alertar sobre la necesidad de establecer consensos para el diagnóstico adecuado de esta entidad. Presentación del caso: Paciente femenina de 67 años de edad con antecedentes familiares de madre y tías maternas fallecidas por Infarto Agudo del Miocardio (IAM), personales de 3 abortos todos durante la semana 10 de embarazo, 1 trombosis venosa profunda y una tromboembolia pulmonar; que acudió al servicio de emergencia por presentar hemiplejía facio-braquio-crural derecha y disartria, diagnosticándose de Enfermedad Cerebrovascular Isquémica. Fue valorada por la especialidad de Hematología indicándose los estudios causales a los eventos trombóticos según los tiempos establecidos, resultando negativos para las principales trombofilias y encontrándose incremento en la agregación con dos diferentes diluciones del ADP, cumpliendo criterios clínicos y analíticos de Síndrome de Plaqueta Pegajosa. Conclusiones: El Síndrome de Plaqueta Pegajosa, es una trombofilia hereditaria poco conocida por muchos médicos y logrando un diagnóstico oportuno, se puede prevenir o minimizar los riesgos inherentes a esta. Palabras clave: Trastornos de las plaquetas, trombofilia, coagulación sanguínea, trombosis, agregación plaquetaria, plaqueta pegajosa. ABSTRACT: Introduction: Sticky Platelet Syndrome (SPP) is called autosomal dominant inherited thrombophilia characterized by platelet hyperaggregation that can cause arterial or venous thrombotic events. In vitro it manifests as increased platelet aggregation at low concentrations of epinephrine and/or adenosine diphosphate (ADP). Objective: To describe the presence of sticky platelet syndrome in a patient with several thrombotic events and to warn about the need to establish consensus for the proper diagnosis of this entity. Case presentation: A 67-year-old female patient with a family history of a mother and maternal aunts who died of Acute Myocardial Infarction (AMI), personal of 3 abortions all during the 10th week of pregnancy, 1 deep vein thrombosis and a pulmonary thromboembolism; she was admitted into the emergency service for presenting right facio-brachio-crural hemiplegia and dysarthria, being diagnosed with Ischemic Cerebrovascular Disease. She was assessed by the specialty of Hematology, indicating the causal studies for thrombotic events according to the established times, being negative for the main thrombophilias and finding an increase in aggregation with two different dilutions of ADP, fulfilling clinical and analytical criteria for Sticky Platelet Syndrome. Conclusions: Sticky Platelet Syndrome is a hereditary thrombophilia unknown by many doctors and achieving a timely diagnosis, the risks inherent to it can be prevented or minimized. Keywords: Platelet disorders, thrombophilia, blood coagulation, thrombosis, platelet aggregation, sticky platelet.

Nowadays, wild animals are threatened by humans, with the number of species and individuals decreasing during recent years. Wildlife rescue centers play a vital role in the conservation of wildlife populations. This study aims to describe a new release technique, the Speaker Method, to rescue and facilitate the reunion of different baby mammals that arrived at a wildlife rescue center with their mothers within their natural habitat, avoiding the need for captivity. This method is based on a recorded baby’s cry played on a speaker to make a “call effect” in the mother. The efficacy of the Speaker Method for babies’ reunion with their mothers was 45.8% in Hoffmann’s two-toed sloths (Choloepus hoffmanni) and 91.9% in brown-throated sloths (Bradypus variegatus). Among the mantled howler monkeys (Alouatta palliata), 50% of the babies could be released using this new technique. The findings suggest that the method could be helpful in the early release of young individuals, highlighting higher release outcomes in these three species compared to traditional nursery care provided by human caretakers, who face inherent difficulties in raising young animals without their mothers.

Our study evaluated the morphological and functional outcomes, and the side effects, of voretigene neparvovec (VN) gene therapy for RPE65-mediated inherited retinal dystrophies (IRDs) in 12 eyes (six patients) at the Oxford Eye Hospital with a mean follow-up duration of 8.2 (range 1–12) months. All patients reported a subjective vision improvement 1 month after gene therapy. Best-corrected visual acuity (BCVA) remained stable (baseline: 1.28 (±0.71) vs. last follow-up: 1.46 (±0.60); p = 0.25). Average white Full-Field Stimulus Testing (FST) showed a trend towards improvement (baseline: −4.41 (±10.62) dB vs. last follow-up: −11.98 (±13.83) dB; p = 0.18). No changes in central retinal thickness or macular volume were observed. The side effects included mild intraocular inflammation (two eyes) and cataracts (four eyes). Retinal atrophy occurred in 10 eyes (eight mild, two severe) but did not impact FST measurements during the follow-up period. Increased intraocular pressure (IOP) was noted in three patients (six eyes); four eyes (two patients) required glaucoma surgery. The overall safety and effectiveness of VN treatment in our cohort align with previous VN clinical trials, except for the higher occurrence of retinal atrophy and increased IOP in our cohort. This suggests that raised IOP and retinal atrophy may be more common than previously reported.

The outermost layer of the heart, the epicardium, is an essential cell population that contributes, through epithelial-to-mesenchymal transition (EMT), to the formation of different cell types and provides paracrine signals to the developing heart. Despite its quiescent state during adulthood, the adult epicardium reactivates and recapitulates many aspects of embryonic cardiogenesis in response to cardiac injury, thereby supporting cardiac tissue remodeling. Thus, the epicardium has been considered a crucial source of cell progenitors that offers an important contribution to cardiac development and injured hearts. Although several studies have provided evidence regarding cell fate determination in the epicardium, to date, it is unclear whether epicardium-derived cells (EPDCs) come from specific, and predetermined, epicardial cell subpopulations or if they are derived from a common progenitor. In recent years, different approaches have been used to study cell heterogeneity within the epicardial layer using different experimental models. However, the data generated are still insufficient with respect to revealing the complexity of this epithelial layer. In this review, we summarize the previous works documenting the cellular composition, molecular signatures, and diversity within the developing and adult epicardium.

The knowledge of the molecular mechanisms that regulate embryonic myogenesis from early myogenic progenitors to myoblasts, as well as the emergence of adult satellite stem cells (SCs) during development, are key concepts to understanding the genesis and regenerative abilities of the skeletal muscle. Several previous pieces of evidence have revealed that the transcription factor Pitx2 might be a player within the molecular pathways controlling somite-derived muscle progenitors’ fate and SC behavior. However, the role exerted by Pitx2 in the progression from myogenic progenitors to myoblasts including SC precursors remains unsolved. Here, we show that Pitx2 inactivation in uncommitted early myogenic precursors diminished cell proliferation and migration leading to muscle hypotrophy and a low number of SCs with decreased myogenic differentiation potential. However, the loss of Pitx2 in committed myogenic precursors gave rise to normal muscles with standard amounts of SCs exhibiting high levels of Pax7 expression. This SC population includes few MYF5+ SC-primed but increased amount of less proliferative miR-106b+cells, and display myogenic differentiation defects failing to undergo proper muscle regeneration. Overall our results demonstrate that Pitx2 is required in uncommitted myogenic progenitors but it is dispensable in committed precursors for proper myogenesis and reveal a role for this transcription factor in the generation of diverse SC subpopulations.

Muscle regeneration is an important homeostatic process of adult skeletal muscle that recapitulates many aspects of embryonic myogenesis. Satellite cells (SCs) are the main muscle stem cells responsible for skeletal muscle regeneration. SCs reside between the myofiber basal lamina and the sarcolemma of the muscle fiber in a quiescent state. However, in response to physiological stimuli or muscle trauma, activated SCs transiently re-enter the cell cycle to proliferate and subsequently exit the cell cycle to differentiate or self-renew. Recent evidence has stated that SCs display functional heterogeneity linked to regenerative capability with an undifferentiated subgroup that is more prone to self-renewal, as well as committed progenitor cells ready for myogenic differentiation. Several lineage tracing studies suggest that such SC heterogeneity could be associated with different embryonic origins. Although it has been established that SCs are derived from the central dermomyotome, how a small subpopulation of the SCs progeny maintain their stem cell identity while most progress through the myogenic program to construct myofibers is not well understood. In this review, we synthesize the works supporting the different developmental origins of SCs as the genesis of their functional heterogeneity.

Learning games are becoming popular among teachers as educational tools. However, despite all the game development quality processes (e.g., beta testing), there is no total assurance about the game design appropriateness to the students' cognitive skills until the games are used in the classroom. Furthermore, games designed specifically for Intellectual Disabled (ID) users are even harder to evaluate because of the communication issues that this type of players have. ID users' feedback about their learning experience is complex to obtain and not always fully reliable. To address this problem, we use an evidence-based approach for evaluating the game design of Downtown, A Subway Adventure, a game created to improve independent living in users with ID. In this paper we exemplify the whole process of applying Game Analytics techniques to gather actual users' gameplay interaction data in real settings for evaluating the design. Following this process, researchers were able to validate different game aspects (e.g., mechanics) and could also identify game flaws that may be difficult to detect using formative evaluation or other observational-based methods. Results showed that the proposed evidence-based approach using Game Analytics information is an effective way to evaluate both the game design and the implementation, especially in situations where other types of evaluations that require users' involvement are limited.

Abstract Background Microalgae biomass is regarded as a potential feedstock for bioenergy purposes through anaerobic digestion (AD). Even though AD is a well-proven technology, the use of new feedstocks requires in-depth studies. A lot of research has been conducted assessing methane yield without paying attention to the anaerobic microbiome and their activities. For such a goal, the present investigation was designed to link methane yield to those two later sludge characteristics. In this sense, different anaerobic sources were tested, namely adapted to microalgae biomass and adapted to sewage sludge. Results Despite the registered differences for the anaerobic microbiome analysis and specific methane activities towards model substrates, sludge adapted to digest sewage sludge did not affect the methane yield of Chlorella sorokiniana and Scenedesmus sp. Opposite to that, sludge samples adapted to digest microalgae exhibited a concomitant increase in methane yield together with increasing digestion temperatures. More specifically, the values attained were 63.4 ± 1.5, 79.2 ± 3.1 and 108.2 ± 1.9 mL CH4 g COD in−1 for psychrophilic, mesophilic and thermophilic digestions, respectively. While psycro- and mesophilic digestion supported similar yields (most probably linked to their anaerobic microbiome resemblance), the values attained for thermophilic digestion evidenced the usefulness of having a highly specific microbiome. The relative abundance of Firmicutes, particularly Clostridia, and Proteobacteria together with an important abundance of hydrogenotrophic methanogens was highlighted in this inoculum. Conclusion Overall, this study showed that working with tailored anaerobic microbiome could help avoiding pretreatments devoted to methane yield enhancement.

Chlamydia pecorum, an obligate intracellular pathogen, causes significant morbidity and mortality in livestock and the koala (Phascolarctos cinereus). A variety of C. pecorum gene-centric molecular studies have revealed important observations about infection dynamics and genetic diversity in both koala and livestock hosts. In contrast to a variety of C. pecorum molecular studies, to date, only four complete and 16 draft genomes have been published. Of those, only five draft genomes are from koalas. Here, using whole-genome sequencing and a comparative genomics approach, we describe the first two complete C. pecorum genomes collected from diseased koalas. A de novo assembly of DBDeUG_2018 and MC/MarsBar_2018 resolved the chromosomes and chlamydial plasmids each as single, circular contigs. Robust phylogenomic analyses indicate biogeographical separation between strains from northern and southern koala populations, and between strains infecting koala and livestock hosts. Comparative genomics between koala strains identified new, unique, and shared loci that accumulate single-nucleotide polymorphisms and separate between northern and southern, and within northern koala strains. Furthermore, we predicted novel type III secretion system effectors. This investigation constitutes a comprehensive genome-wide comparison between C. pecorum from koalas and provides improvements to annotations of a C. pecorum reference genome. These findings lay the foundations for identifying and understanding host specificity and adaptation behind chlamydial infections affecting koalas.

During limb formation in vertebrates with free digits, the interdigital mesoderm is eliminated by a massive degeneration process that involves apoptosis and cell senescence. The degradation process is preceded by intense DNA damage in zones located close to methylated DNA, accompanied by the activation of the DNA repair response. In this study, we show that trimethylated histone 3 (H3K4me3, H3K9me3, and H3K27me3) overlaps with zones positive for 5mC in the nuclei of interdigital cells. This pattern contrasts with the widespread distribution of acetylated histones (H3K9ac and H4ac) and the histone variant H3.3 throughout the nucleoplasm. Consistent with the intense labeling of acetylated histones, the histone deacetylase genes Hdac1, Hdac2, Hdac3, and Hdac8, and at a more reduced level, Hdac10, are expressed in the interdigits. Furthermore, local treatments with the histone deacetylase inhibitor trichostatin A, which promotes an open chromatin state, induces massive cell death and transcriptional changes reminiscent of, but preceding, the physiological process of interdigit remodeling. Together, these findings suggest that the epigenetic profile of the interdigital mesoderm contributes to the sensitivity to DNA damage that precedes apoptosis during tissue regression.