The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study.

Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.

Biallelic EPCAM deletions induce tissue-specific DNA repair deficiency and cancer predisposition.

We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss of MSH2. Through the use of patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation of colonic and brain organoids from reprogrammed EPCAM iPSC derived from patient fibroblasts. Differentiation of iPSC to epithelial-colonic organoids exhibited continuous increased EPCAM expression and hypermethylation of the MSH2 promoter.

THOR is a targetable epigenetic biomarker with clinical implications in breast cancer.

Background: Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of death among women worldwide. Early BC is potentially curable, but the mortality rates still observed among BC patients demonstrate the urgent need of novel and more effective diagnostic and therapeutic options. Limitless self-renewal is a hallmark of cancer, governed by telomere maintenance.

Profile of Selected Mineral Elements in Tibiotarsal Bone of the White-Tailed Sea Eagle in Its Natural Habitat.

Mineral bone composition (dry matter, bones ash, P, Ca, Zn, Mn, Mg, and Cu) and Pb levels of tibiotarsi of seven White-Tailed Sea Eagles were assessed. Lead intoxication in different bird species including waterfowl and raptors is being studied worldwide. The bones were analyzed for Pb by mass spectrometry with excitation in inductively coupled plasma (ICP-MS Elan DRC II) and for bone composition by Atomic Emission Spectrometer (Agilent 4100 Microwave Plasma).

Dual role of allele-specific DNA hypermethylation within the TERT promoter in cancer.

Aberrant activation of telomerase in human cancer is achieved by various alterations within the TERT promoter, including cancer-specific DNA hypermethylation of the TERT hypermethylated oncological region (THOR). However, the impact of allele-specific DNA methylation within the TERT promoter on gene transcription remains incompletely understood. Using allele-specific next-generation sequencing, we screened a large cohort of normal and tumor tissues (n = 652) from 10 cancer types and identified that differential allelic methylation (DAM) of THOR is restricted to cancerous tissue and commonly observed in major cancer types.

Mutations in the RAS/MAPK Pathway Drive Replication Repair-Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition.

The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors that harbor many somatic mutations may obscure the interpretation of such targetable genomic events.

A Disorder of Sex Development in a Holstein-Friesian Heifer with a Rare Mosaicism (60,XX/90,XXY): A Genetic, Anatomical, and Histological Study.

In this study, we describe an eighteen-month-old Holstein-Friesian heifer with a deformed vulva, located abdominally. The heifer showed typical signs of estrus. A comprehensive anatomical and histopathological examination revealed a blind-ended vagina and an additional section of urethra, which became a part of the shortened penis.

Congenital Malformations in a Holstein-Fresian Calf with a Unique Mosaic Karyotype: A Case Report.

A Holstein-Fresian calf with multiple congenital malformations was subjected postmortem to anatomical and genetic investigation. The calf was small (20 kg), had shortened limbs and was unable to stand up. It lived only 44 days.

Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma.

Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an opportunity for locoregional therapy, bypassing the blood-brain barrier. We identify three cell-surface targets, EPHA2, HER2 and interleukin 13 receptor α2, expressed on medulloblastomas and ependymomas, but not expressed in the normal developing brain.

DNA methylation of the TERT promoter and its impact on human cancer.

Telomere maintenance is a hallmark of human cancer that enables replicative immortality. Most cancer cells acquire telomere maintenance by telomerase activation through expression of telomerase reverse transcriptase (TERT), a rate-limiting component of the telomerase holoenzyme. Although multiple cancer-specific genetic alterations such as gain of TERT copy number and recurrent TERT promoter mutations (TPM) have been identified, the majority of cancers still express TERT via unknown mechanisms.

Comparative Evaluation of , and L. Essential Oils of Different Origin as Functional Antimicrobials in Foods.

Essential oils can be used as preservatives in foods because of their ability to inhibit bacteria growth in low concentration, which does not influence on foods' organoleptic properties and does not generate the resistance mechanisms in cells. The aim of that work was to compare the effectiveness of commercial oils from black pepper (), rosemary (), lemongrass () and juniper ( L.) with oils obtained in our laboratory.

BRAF V600E mutant oligodendroglioma-like tumors with chromosomal instability in adolescents and young adults.

We performed genome-wide methylation analysis on 136 pediatric low-grade gliomas, identifying a unique cluster consisting of three tumors with oligodendroglioma-like histology, BRAF p.V600E mutations and recurrent whole chromosome gains of 7 and loss of 10. Morphologically, all showed similar features, including a diffusely infiltrative glioma composed of round nuclei with perinuclear halos, a chicken-wire pattern of branching capillaries and microcalcification.

DNA hypermethylation within TERT promoter upregulates TERT expression in cancer.

Replicative immortality is a hallmark of cancer cells governed by telomere maintenance. Approximately 90% of human cancers maintain their telomeres by activating telomerase, driven by the transcriptional upregulation of telomerase reverse transcriptase (TERT). Although TERT promoter mutations (TPMs) are a major cancer-associated genetic mechanism of TERT upregulation, many cancers exhibit TERT upregulation without TPMs.

Combined genetic and epigenetic alterations of the TERT promoter affect clinical and biological behavior of bladder cancer.

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self-renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTp ) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior.

Comparison of pathological lesions in navicular bone (os sesamoideum distale) and analysis of remodelling capacity in warmblood and coldblood horses.

The problem of navicular bone lesions is better understood in warmblood horses. The aim of our research was to compare pathologic lesions of navicular bone of different types of horses divided into age groups. An extra goal was to compare radiographs with anatomical status of navicular bone dissected from the hoof capsule.

The Osteometry of Equine Third Phalanx by the Use of Three-Dimensional Scanning: New Measurement Possibilities.

This study consisted in analyzing the asymmetry between bilateral third phalanges (coffin bones) in cold-blood horses based on the angle range of the plantar margin of the bone. The study employed a scanner projecting a hybrid set of images, consisting of sinusoidal stripes preceded by a Gray code sequence. As it turned out, three-dimensional scanning can be used to effectively determine the angle range for a selected portion of the studied bone.

FANCD2 limits BLM-dependent telomere instability in the alternative lengthening of telomeres pathway.

Fanconi anemia and Bloom syndrome are genomic instability syndromes caused by mutations in proteins that participate in overlapping DNA repair and replication pathways. Here, we show that the monoubiquitinated form of the Fanconi Anemia protein FANCD2 acts in opposition to the BLM DNA helicase to restrain telomere replication and recombination in human cells that utilize the Alternative Lengthening of Telomeres (ALT) pathway. ALT relies on exchanges of telomeric DNA to maintain telomeres, a process that we show FANCD2 suppresses.

The arterial circle of the brain, its branches and connections in selected representatives of the Antilopinae.

The arterial circle of the brain, that is, the circle of Willis, and its branches in ruminants have been chiefly described in farm animals and only in selected wild species. In view of the deficit of information about this vascular region in numerous other species of the Ruminantia, the arteries of the encephalic base were analyzed in five antelope species representing different genera of the Bovidae, Antilopinae. Specimens of the following species were examined: springbuck (Antidorcas marsupialis), blackbuck (Antilope cervicapra), dik-dik (Madoqua kirkii), saiga (Saiga tatarica), and oribi (Ourebia ourebi).

Visualization and quantitative analysis of extrachromosomal telomere-repeat DNA in individual human cells by Halo-FISH.

Current methods for characterizing extrachromosomal nuclear DNA in mammalian cells do not permit single-cell analysis, are often semi-quantitative and frequently biased toward the detection of circular species. To overcome these limitations, we developed Halo-FISH to visualize and quantitatively analyze extrachromosomal DNA in single cells. We demonstrate Halo-FISH by using it to analyze extrachromosomal telomere-repeat (ECTR) in human cells that use the Alternative Lengthening of Telomeres (ALT) pathway(s) to maintain telomere lengths.

Kinematic Modeling of Normal Voluntary Mandibular Opening and Closing Velocity-Initial Study.

Purpose: Determination and quantification of voluntary mandibular velocity movement has not been a thoroughly studied parameter of masticatory movement. This study attempted to objectively define kinematics of mandibular movement based on numerical (digital) analysis of the relations and interactions of velocity diagram records in healthy female individuals.

Materials And Methods: Using a computerized mandibular scanner (K7 Evaluation Software), 72 diagrams of voluntary mandibular velocity movements (36 for opening, 36 for closing) for women with clinically normal motor and functional activities of the masticatory system were recorded.

Age- and sex-related differences of morphometric, densitometric and geometric parameters of tibiotarsal bone in Ross broiler chickens.

For the first time computed tomography has been used to analyze densitometric and geometric parameters in proximal metaphyses and the mid-diaphyses of tibiotarsal bones in broiler chickens in posthatching development as influenced by age and sex. The research was conducted on 60 tibial bones of 2-, 4- and 6-week-old broiler chickens (Ross 308) (10 males and 10 females in each age group). Statistical analysis has been conducted with the use of one-way ANOVA and Fisher's exact test.