Generation of two isogenic patient-derived human-induced pluripotent stem cell clones with 6q27 deletion.

We generated two human induced pluripotent cell (hiPSC) isogenic clones from an 11-year-old patient with 6q27 deletion syndrome. The heterozygous deletion encompasses approximately 240 kilobases, affecting 6 genes (promoter region of WDR27, coding regions of C6orf120, PHF10, DYNLT2, ERMARD, LINC00242). The patient suffered from epilepsy, psychosocial retardation, and a metabolic disorder.

Loss of Elp1 in cerebellar granule cell progenitors models ataxia phenotype of Familial Dysautonomia.

Familial Dysautonomia (FD) is an autosomal recessive disorder caused by a splice site mutation in the gene ELP1, which disproportionally affects neurons. While classically characterized by deficits in sensory and autonomic neurons, neuronal defects in the central nervous system have also been described. Although ELP1 expression remains high in the normal developing and adult cerebellum, its role in cerebellar development is unknown.

Predictive modeling of resistance to SMO inhibition in a patient-derived orthotopic xenograft model of SHH medulloblastoma.

Background: Inhibition of the sonic hedgehog (SHH) pathway with Smoothened (SMO) inhibitors is a promising treatment strategy in SHH-activated medulloblastoma, especially in adult patients. However, the problem is that tumors frequently acquire resistance to the treatment. To understand the underlying resistance mechanisms and to find ways to overcome the resistance, preclinical models that became resistant to SMO inhibition are needed.

Safety of a Modified Lipoabdominoplasty Technique for Donor-Site Closure in Abdominal-Based Free Flap Breast Reconstruction.

Background: The aesthetic and functional outcomes of the donor site following abdominal-based free flap breast reconstruction have been suboptimal. The objective of this study is to evaluate a modified liposuction-assisted abdominoplasty technique combined with rectus plication (LPARSP) adopted from cosmetic abdominoplasty practice.

Patients And Methods: All abdominal-based free flap breast reconstructions from 01/2017 to 03/2019 were reviewed.

The Use of Semi-Absorbable Mesh and its Impact on Donor-Site Morbidity and Patient-Reported Outcomes in DIEP Flap Breast Reconstruction.

Background: This study aimed to evaluate the impact of semi-absorbable mesh on donor-site morbidity and patient-reported outcomes in deep inferior epigastric perforator (DIEP) flap breast reconstruction.

Methods: We conducted a retrospective cohort study of all patients who had DIEP flap breast reconstruction in our department from July 2007 to March 2019. Patients were invited to a comparative follow-up visit and grouped according to donor-site closure: primary fascial closure (the no-mesh group) and fascial reinforcement with semi-absorbable mesh in a subfascial position (the mesh group).

Influence of closed incision negative-pressure therapy on abdominal donor-site morbidity in microsurgical breast reconstruction.

Introduction: Closed incision negative-pressure therapy (CINPT) has been shown to shorten the time to heal in post-bariatric abdominoplasty and to lower seroma rates in cosmetic abdominoplasty. The objective of this study was to assess the effect of CINPT on donor-site morbidity following abdominal-based free-flap breast reconstruction.

Patients And Methods: We reviewed medical records from 225 women who had undergone 300 microsurgical free-flap breast reconstructions from the abdomen from November 1, 2007 to March 31, 2019.

Functional loss of a noncanonical BCOR-PRC1.1 complex accelerates SHH-driven medulloblastoma formation.

Medulloblastoma is a malignant childhood brain tumor arising from the developing cerebellum. In Sonic Hedgehog (SHH) subgroup medulloblastoma, aberrant activation of SHH signaling causes increased proliferation of granule neuron progenitors (GNPs), and predisposes these cells to tumorigenesis. A second, cooperating genetic hit is often required to push these hyperplastic cells to malignancy and confer mutation-specific characteristics associated with oncogenic signaling.

Age-dependent release of and response to alarm pheromone in a ponerine ant.

Social insect societies are characterized by division of labour and communication within the colony. The most frequent mode of communication is by chemical signals. In general, pheromones elicit specific responses in the receiver, although reactions may vary depending on the receiving individual's physiological or motivational state.

YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis.

YAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas. Nuclear localization of YAP1-MAMLD1 protein is mediated by MAMLD1 and independent of YAP1-Ser127 phosphorylation.

Enhanced early prediction of clinically relevant neonatal hyperbilirubinemia with machine learning.

Background: Machine learning models may enhance the early detection of clinically relevant hyperbilirubinemia based on patient information available in every hospital.

Methods: We conducted a longitudinal study on preterm and term born neonates with serial measurements of total serum bilirubin in the first two weeks of life. An ensemble, that combines a logistic regression with a random forest classifier, was trained to discriminate between the two classes phototherapy treatment vs.

Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme.

Mutations in chromatin modifier genes are frequently associated with neurodevelopmental diseases. We herein demonstrate that the chromodomain helicase DNA-binding protein 7 (Chd7), frequently associated with CHARGE syndrome, is indispensable for normal cerebellar development. Genetic inactivation of Chd7 in cerebellar granule neuron progenitors leads to cerebellar hypoplasia in mice, due to the impairment of granule neuron differentiation, induction of apoptosis and abnormal localization of Purkinje cells, which closely recapitulates known clinical features in the cerebella of CHARGE patients.

Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.

Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs.

Active medulloblastoma enhancers reveal subgroup-specific cellular origins.

Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking.

Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups.

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling.

Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.

Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified.

Dissecting the genomic complexity underlying medulloblastoma.

Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease.

Marsupial cardiac myosins are similar to those of eutherians in subunit composition and in the correlation of their expression with body size.

Cardiac myosins and their subunit compositions were studied in ten species of marsupial mammals. Using native gel electrophoresis, ventricular myosin in macropodoids showed three isoforms, V(1), V(2) and V(3), and western blots using specific anti-alpha- and anti-beta-cardiac myosin heavy chain (MyHC) antibodies showed their MyHC compositions to be alphaalpha, alphabeta and betabeta, respectively. Atrial myosin showed alphaalpha MyHC composition but differed from V(1) in light chain composition.

Myosin isoforms and fibre types in jaw-closing muscles of Australian marsupials.

Myosin heavy chains (MyHCs) and fibre types in the masseter muscle of seven species of Australian marsupials (brushtail and ringtail possums, bettong, bandicoot, dunnart, two species of antechinuses) spanning three orders were studied by native myosin electrophoresis, SDS-PAGE, immunoblotting and immunohistochemistry. We found only two fibre types in the masseter muscles of these animals: (1) masticatory fibres expressing masticatory MyHC, and (2) hybrid alpha/beta fibres that co-express alpha-cardiac and beta-cardiac MyHCs. Masticatory fibres predominate in most species, being appropriate for predation or for chewing tough vegetable matter.

Jaw-closing muscles of kangaroos express alpha-cardiac myosin heavy chain.

The masseter muscle of eutherian grazing mammals typically express beta or slow myosin heavy chain (MyHC). Myosins in the masseter of 4 species of kangaroos and a slow limb muscle of one of them were compared with their cardiac myosin by pyrophosphate and sodium dodecyl sulphate (SDS) gel electrophoresis, immunoblotting and immunohistochemistry. It was found that ventricular muscle contains three isoforms homologous to V1 (alpha-MyHC homodimer), V2 (heterodimer) and V3 (beta-MyHC homodimer) of eutherian cardiac muscle, and that the masseter contained V1, with traces of V2 and V3, in great contrast to eutherian ruminants, which express only V3.

Metabolic diseases and their possible link to risk indicators of periodontitis.

Background: During the last few years, risk assessment has become one of the main topics of periodontal research. Therefore, the aim of this study was to determine whether a predisposition to metabolic disorders such as diabetes mellitus (in the absence of diagnosed diabetic disease) or hyperlipidemia may be risk indicators for periodontitis.

Methods: One hundred patients ranging in age from 40 to 70 years were examined.

[Quantitative determination of the protein content of milk by ultraviolet spectrophotometry. 3. Determination of proteins in preserved milk samples].

It is reported upon the results of the quantitative estimation of protein content from preserved milk by means of ultraviolet spectrophotometry. In addition to the preservation by boric acid, bronopol, copper sulphate, potassium dichromate and ammonium peroxodisulphate storage at temperatures below 0 degrees C and freeze drying were tested. Besides bronopol and copper sulphate especially physical preservation methods proves fit for the protein estimation by measurements of absorbance at 210 nm, 235 and 280 nm or 210 and 220 nm.