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The appropriate selection of renovation plaster properties is essential for ensuring the durability and effectiveness of conservation works. This study focused on the design and characterization of cement-based renovation mortars modified with synthetic zeolites with different Si/Al ratios. It was assumed that high-silica zeolites would provide more favorable mechanical and hygric performance than low-silica types. Owing to their porous structure and pozzolanic reactivity, zeolites proved to be effective additives, enhancing both the microstructure and functionality of the mortars. The modified mixtures exhibited increased total porosity, higher capillary absorption, and improved moisture transport compared with the reference mortar based on CEM I 52.5R. Dynamic vapor sorption tests confirmed that the zeolite-containing mortars achieved Moisture Buffer Values (MBV) above 2.0 g/m2, which corresponds to the “excellent” moisture buffering class. Electrical resistivity measurements further demonstrated the relationship between denser microstructure and enhanced durability. At the frequency of 10 kHz, the electrical resistivity of the reference mortar reached 43,858 Ω·m, while mortars with 15% ZSM-5 and 15% Na-A achieved 62,110 Ω·m and 21,737 Ω·m. These results show that the addition of high-silica zeolite promotes the formation of a denser and more insulating matrix, highlighting the potential of this method for non-destructive quality assessment. The best overall performance was observed in mortars containing the high-silica zeolite ZSM-5. A 35% replacement of cement with ZSM-5 increased compressive strength by 10.5% compared with the reference mortar R (4.3 MPa). Frost resistance tests showed minimal mass loss (0.03% at 15% and 1.79% at 35% replacement), and ZSM-5 mortars also maintained integrity under salt crystallization. These improvements were attributed to the reaction of reactive SiO2 and Al2O3 from the zeolites with Ca(OH)2, leading to the formation of additional C-S-H. A higher Si/Al ratio promoted a denser, fibrous C-S-H morphology, as confirmed by SEM, which explains the improved strength and durability of mortars modified with ZSM-5.

Polymer-based capacitive humidity sensors emerged around 40 years ago; nevertheless, they currently constitute large part of sensors’ market within a range of medium (climatic and industrial) humidity 20−80%RH due to their linearity, stability and cost-effectiveness. However, for low humidity values (0−20%RH) that type of sensor exhibits increasingly nonlinear characteristics with decreasing of humidity values. This paper presents the results of some experimental trials of CMOS polymer-based capacitive humidity sensors, as well as of modelling the behaviour of that type of sensor. A logarithmic functional relationship between the relative humidity and the change of sensor output value at low humidity is suggested.

In experimental chambers for simulating the atmospheric near-surface conditions of Mars, or in situ measurements on Mars, the measurement of the humidity in carbon dioxide gas at low temperature and under low pressure is needed. For this purpose, polymer-based capacitive humidity sensors are used; however, these sensors are designed for measuring the humidity in the air on the Earth. The manufacturers provide only the generic calibration equation for standard environmental conditions in air, and temperature corrections of humidity signal. Because of the lack of freely available information regarding the behavior of the sensors in CO2, the range of reliable results is limited. For these reasons, capacitive humidity sensors (Sensirion SHT75) were tested at the German Aerospace Center (DLR) in its Martian Simulation Facility (MSF). The sensors were investigated in cells with a continuously humidified carbon dioxide flow, for temperatures between −70 °C and 10 °C, and pressures between 10 hPa and 1000 hPa. For 28 temperature–pressure combinations, the sensor calibration equations were calculated together with temperature–dependent formulas for the coefficients of the equations. The characteristic curves obtained from the tests in CO2 and in air were compared for selected temperature–pressure combinations. The results document a strong cross-sensitivity of the sensors to CO2 and, compared with air, a strong pressure sensitivity as well. The reason could be an interaction of the molecules of CO2 with the adsorption sites on the thin polymeric sensing layer. In these circumstances, an individual calibration for each pressure with respect to temperature is required. The performed experiments have shown that this kind of sensor can be a suitable, lightweight, and relatively inexpensive choice for applications in harsh environments such as on Mars.

Precise deposition of CpG methylation is critical for mammalian development and tissue homeostasis and is often dysregulated in human diseases. The localization of de novo DNA methyltransferase DNMT3A is facilitated by its PWWP domain recognizing histone H3 lysine 36 (H3K36) methylation 1 , 2 and is normally depleted at CpG islands (CGIs) 3 . However, methylation of CGIs regulated by Polycomb repressive complexes (PRCs) has also been observed 4 – 8 . Here, we report that DNMT3A PWWP domain mutations identified in paragangliomas 9 and microcephalic dwarfism 10 promote aberrant localization of DNMT3A to CGIs in a PRC1-dependent manner. DNMT3A PWWP mutants accumulate at regions containing PRC1-mediated formation of monoubiquitylated histone H2A lysine 119 (H2AK119ub), irrespective of the amounts of PRC2-catalyzed formation of trimethylated histone H3 lysine 27 (H3K27me3). DNMT3A interacts with H2AK119ub-modified nucleosomes through a putative amino-terminal ubiquitin-dependent recruitment region, providing an alternative form of DNMT3A genomic targeting that is augmented by the loss of PWWP reader function. Ablation of PRC1 abrogates localization of DNMT3A PWWP mutants to CGIs and prevents aberrant DNA hypermethylation. Our study implies that a balance between DNMT3A recruitment by distinct reader domains guides de novo CpG methylation and may underlie the abnormal DNA methylation landscapes observed in select human cancer subtypes and developmental disorders. DNMT3A PWWP domain mutations promote localization of DNMT3A to CpG islands in a PRC1-dependent manner. DNMT3A interacts with H2AK119ub-modified nucleosomes.

Background Alternative splicing is known to increase the complexity of mammalian transcriptomes since nearly all mammalian genes express multiple pre-mRNA isoforms. However, our knowledge of the extent and function of alternative splicing in early embryonic development is based mainly on a few isolated examples. High throughput technologies now allow us to study genome-wide alternative splicing during mouse development. Results A genome-wide analysis of alternative isoform expression in embryonic day 8.5, 9.5 and 11.5 mouse embryos and placenta was carried out using a splicing-sensitive exon microarray. We show that alternative splicing and isoform expression is frequent across developmental stages and tissues, and is comparable in frequency to the variation in whole-transcript expression. The genes that are alternatively spliced across our samples are disproportionately involved in important developmental processes. Finally, we find that a number of RNA binding proteins, including putative splicing factors, are differentially expressed and spliced across our samples suggesting that such proteins may be involved in regulating tissue and temporal variation in isoform expression. Using an example of a well characterized splicing factor, Fox2 , we demonstrate that changes in Fox2 expression levels can be used to predict changes in inclusion levels of alternative exons that are flanked by Fox2 binding sites. Conclusions We propose that alternative splicing is an important developmental regulatory mechanism. We further propose that gene expression should routinely be monitored at both the whole transcript and the isoform level in developmental studies

Background Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually due to dominant mutations in COL1A1 or COL1A2. Rare recessive forms of OI, caused by mutations in genes involved in various aspects of bone formation, have been described as well. Objective To identify the cause of OI in eight children with severe bone fragility and a clinical diagnosis of OI type IV who had had negative results on COL1A1/COL1A2 Sanger sequencing. Methods Whole exome sequencing was performed in genomic DNA samples from all eight individuals. Results WNT1 mutations were found in four children from three families. WNT1 was the only gene where mutations were found in all of these four patients. Two siblings from a consanguineous family had a homozygous missense mutation affecting a highly conserved cysteine residue in WNT1 (c.428G>T (p.Cys143Phe)). One girl had a homozygous frameshift deletion (c.287_300del(p.Gln96Profs)). A girl from a third family was compound heterozygous for a frameshift insertion and a missense mutation affecting a conserved amino acid (c.946_949insAACA (p.Ser317Lysfs); c.1063G>T (p.Val355Phe)). All of these children had short stature, low bone density, and severe vertebral compression fractures in addition to multiple long bone fractures in the first years of life. The Wnt signalling pathway is one of the key regulators of osteoblast activity. Conclusions Recessive inactivating mutations in WNT1 are a new cause of OI type IV.

This paper presents a method for implementing the configuration structure of an integrated computational core of a pulsed nuclear quadrupole resonance (NQR) sensor based on a field-programmable gate array (FPGA), which comprises the following modules: a three-channel direct digital synthesizer (DDS), a pulse sequence shaper and a software-defined radio. Experimental studies carried out using the in-circuit analyzer SignalTap Logic Analyzer have confirmed the reliability of the correct and stable operation of the functional modules of the configuration structure at all stages of signal transformations, starting from the formation of the envelope of the excitation pulses and ending with the obtainment of low-frequency quadrature signals at the outlet of the compensating filters. The time and frequency dependences of the amplitude of the output signals generated using the DDS based on a 48 bit phase accumulator are investigated. This development can be used when creating pulsed coherent NQR sensors in the frequency range of 1 MHz–50 MHz.

H3K36 methylation is a key epigenetic mark with critical roles in development and disease. Here, we systematically dissect its functions using CRISPR-engineered mouse mesenchymal stem cells lacking combinations of the five H3K36 methyltransferases, culminating in quintuple knockout cells devoid of H3K36me2/3. We show that H3K36me2 influences enhancer activity, supports the expression of their target genes, and safeguards active genes from encroachment of the repressive marks, H3K27me2/3. In addition, we find that the loss of H3K36me triggers redistribution of large heterochromatic H3K9me3 domains into euchromatin, in part mediated by SUV39H1, leading to global epigenomic remodelling, constitutive heterochromatin erosion, and a collapse of 3D genome organization. Parallel analyses in human HNSCC cells overexpressing the H3K36M oncohistone reveal conserved disruptions to the epigenome and chromatin architecture. Together, these results establish H3K36 methylation as a pivotal regulator of chromatin state and genomic structure. The authors show that H3K36 methylation preserves enhancer activity and chromatin structure. Its loss redistributes repressive marks, disrupts 3D genome organization, and destabilizes the epigenome.

Nada Jabado, Jacek Majewski and colleagues identify mutations in multiple histone H3 genes causing recurrent p.Lys36Met alterations in head and neck squamous cell carcinomas. They show that tumors with these p.Lys36Met alterations correspond to a specific DNA methylation cluster along with tumors harboring previously described mutations in NSD1 . Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs) are deadly and common cancers. Recent genomic studies implicate multiple genetic pathways, including cell signaling, cell cycle and immune evasion, in their development. Here we analyze public data sets and uncover a previously unappreciated role of epigenome deregulation in the genesis of 13% of HPV-negative HNSCCs. Specifically, we identify novel recurrent mutations encoding p.Lys36Met (K36M) alterations in multiple H3 histone genes. histones. We further validate the presence of these alterations in multiple independent HNSCC data sets and show that, along with previously described NSD1 mutations, they correspond to a specific DNA methylation cluster. The K36M substitution and NSD1 defects converge on altering methylation of histone H3 at K36 (H3K36), subsequently blocking cellular differentiation and promoting oncogenesis. Our data further indicate limited redundancy for NSD family members in HPV-negative HNSCCs and suggest a potential role for impaired H3K36 methylation in their development. Further investigation of drugs targeting chromatin regulators is warranted in HPV-negative HNSCCs driven by aberrant H3K36 methylation.

Recurrent hydatidiform moles (RHM) are aberrant human pregnancies characterized by absence of, or abnormal, embryonic development, hydropic degeneration of chorionic villi, and hyperproliferation of the trophoblast. Biallelic mutations in two maternal-effect genes, NLRP7 and KHDC3L, underlie the causation of RHM in 60% of patients. We performed exome sequencing on a patient with six pregnancy losses, two miscarriages and four HM, and found no variants that affect the functions of the known genes. We found biallelic missense variants that affect conserved amino acids in PADI6 and segregate with the disease phenotype in the family. PADI6 is another maternal-effect gene and a member of the subcortical maternal complex that has been shown to have recessive variants that affect the gene function in four unrelated women with infertility who also experienced early embryonic arrest during preimplantation development after IVF. We demonstrated that PADI6 co-localizes with NLRP7 in human oocytes and preimplantation embryos and reviewed the morphology and genotypes of four products of conception from our patient. Our data expand the involvement of PADI6 to other forms of reproductive loss and highlight the commonality between infertility, miscarriages, and molar pregnancies, in some cases.