The DoGA consortium expression atlas of promoters and genes in 100 canine tissues.

The dog, Canis lupus familiaris, is an important model for studying human diseases. Unlike many model organisms, the dog genome has a comparatively poor functional annotation, which hampers gene discovery for development, morphology, disease, and behavior. To fill this gap, we established a comprehensive tissue biobank for both the dog and wolf samples.

Primary cilia promote the differentiation of human neurons through the WNT signaling pathway.

Background: Primary cilia emanate from most human cell types, including neurons. Cilia are important for communicating with the cell's immediate environment: signal reception and transduction to/from the ciliated cell. Deregulation of ciliary signaling can lead to ciliopathies and certain neurodevelopmental disorders.

Intellectual disability syndrome associated with a homozygous founder variant in in Ashkenazi Jews.

Background: Neurodevelopmental disorders (NDDs) impact both the development and functioning of the brain and exhibit clinical and genetic variability. RAP and RAB proteins, belonging to the RAS superfamily, are identified as established contributors to NDDs. However, the involvement of SGSM (small G protein signalling modulator), another member of the RAS family, in NDDs has not been previously documented.

Optimized single-cell RNA sequencing protocol to study early genome activation in mammalian preimplantation development.

Here, we present a modification of single-cell tagged reverse transcription protocol to study gene expression on a single-cell level or with limited RNA input. We describe different enzymes for reverse transcription and cDNA amplification, modified lysis buffer, and additional clean-up steps before cDNA amplification. We also detail an optimized single-cell RNA sequencing method for handpicked single cells, or tens to hundreds of cells, as input material to study mammalian preimplantation development.

Carrier screening for Krabbe disease in an isolated inbred community.

Infantile Krabbe disease (OMIM 245200) is a severe, fatal autosomal recessive neurodegenerative disorder that is relatively frequent in two Muslims villages within Jerusalem. After the characterization of the founder mutation, a population carrier screening for Krabbe disease became a component of the Israeli program for the detection and the prevention of birth defects. Between 2010 and 2018, 3366 individuals were tested and among them 247 carriers for Krabbe disease were identified (7.

Viral infection-related gene upregulation in monocytes in children with signs of β-cell autoimmunity.

Objective: The pathogenesis of type 1 diabetes (T1D) is associated with genetic predisposition and immunological changes during presymptomatic disease. Differences in immune cell subset numbers and phenotypes between T1D patients and healthy controls have been described; however, the role and function of these changes in the pathogenesis is still unclear. Here we aimed to analyze the transcriptomic landscapes of peripheral blood mononuclear cells (PBMCs) during presymptomatic disease.

is a multifunctional factor priming human embryonic genome activation.

Double homeobox 4 () is expressed at the early pre-implantation stage in human embryos. Here we show that induced human expression substantially alters the chromatin accessibility of non-coding DNA and activates thousands of newly identified transcribed enhancer-like regions, preferentially located within ERVL-MaLR repeat elements. CRISPR activation of transcribed enhancers by C-terminal DUX4 motifs results in the increased expression of target embryonic genome activation (EGA) genes and .

Generation of RNA sequencing libraries for transcriptome analysis of globin-rich tissues of the domestic dog.

We have developed a protocol for barcoded cDNA libraries of 48 samples to study gene expression across tissues in the domestic dog, by modifying the Single-Cell Tagged Reverse Transcription (STRT) protocol (Islam et al., 2012, 2014). The cDNA reads represent mRNA 5' ends, enabling the study of transcription start sites (TSS).

Infantile SOD1 deficiency syndrome caused by a homozygous SOD1 variant with absence of enzyme activity.

Pathogenic variants in SOD1, encoding superoxide dismutase 1, are responsible for about 20% of all familial amyotrophic lateral sclerosis cases, through a gain-of-function mechanism. Recently, two reports showed that a specific homozygous SOD1 loss-of-function variant is associated with an infantile progressive motor-neurological syndrome. Exome sequencing followed by molecular studies, including cDNA analysis, SOD1 protein levels and enzymatic activity, and plasma neurofilament light chain levels, were undertaken in an infant with severe global developmental delay, axial hypotonia and limb spasticity.

Cystatin B-deficiency triggers ectopic histone H3 tail cleavage during neurogenesis.

Cystatin B (CSTB) acts as an inhibitor of cysteine proteases of the cathepsin family and loss-of-function mutations result in human brain diseases with a genotype-phenotype correlation. In the most severe case, CSTB-deficiency disrupts brain development, and yet the molecular basis of this mechanism is missing. Here, we establish CSTB as a regulator of chromatin structure during neural stem cell renewal and differentiation.

Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypes.

Background: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

Methods: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes.

Differentiation of ciliated human midbrain-derived LUHMES neurons.

Many human cell types are ciliated, including neural progenitors and differentiated neurons. Ciliopathies are characterized by defective cilia and comprise various disease states, including brain phenotypes, where the underlying biological pathways are largely unknown. Our understanding of neuronal cilia is rudimentary, and an easy-to-maintain, ciliated human neuronal cell model is absent.

PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.

Neuroendocrine tumors (NETs) are often diagnosed from the metastases of an unknown primary tumor. Specific immunohistochemical (IHC) markers indicating the location of a primary tumor are needed. The proprotein convertase subtilisin/kexin type 2 (PCSK2) is found in normal neural and neuroendocrine cells, and known to express in NETs.

Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia.

Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses.

Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth.

Treatment of young patients with pilonidal sinus disease with the original (unmodified) Limberg flap standardized for the first time.

Background: Pilonidal sinus disease (PSD) is commonly seen in young adults but may also affect adolescents. Our goal was to present results from operated patients, with a focus on the original Limberg flap, which we standardized for the first time.

Methods: This study was a retrospective review of 60 teenage patients who underwent surgery in a single pediatric surgery center over approximately 15 years.

Ingested foreign bodies in children: Do they really pass spontaneously from the gastrointestinal tract? A single-centre experience with 1000 cases.

Background: Foreign body (FB) ingestion is frequently encountered in all departments that treat children. FB may bring about significant anxiety for parents and physicians. The present study aims to determine the appropriate approach for FB ingestion in children.

Boix-Ochoa (Partial Fundoplication) Treats Reflux, Even in Neurologically Impaired Patients. Can it Take the Title of "Gold Standard" from Total Fundoplication?

Background: In 4-5% of cases of gastroesophageal reflux disease (GERD), surgical treatment is required. The aim of the study was to evaluate the success of Boix-Ochoa antireflux surgery, which is considered more physiologic with a higher failure rate (need for reoperation) than Nissen fundoplication, which is believed to be the gold standard operation.

Method: In the 13 years from 2005 to 2018, the medical records of all children who underwent Boix-Ochoa in a single institution by pediatric surgeons were reviewed retrospectively.

Spironolactone inhibits the growth of cancer stem cells by impairing DNA damage response.

The cancer stem cell (CSC) model suggests that a subpopulation of cells within the tumor, the CSCs, is responsible for cancer relapse and metastasis formation. CSCs hold unique characteristics, such as self-renewal, differentiation abilities, and resistance to chemotherapy, raising the need for discovering drugs that target CSCs. Previously we have found that the antihypertensive drug spironolactone impairs DNA damage response in cancer cells.

Management of traumatic bile duct injuries in children.

Purpose: Pediatric experience with biliary tract injuries (BTI) is limited and mostly consists of case presentations. The purpose of this study is to evaluate clinical and radiological findings of possible BTI, treatment strategies, and results.

Methods: The records of nine patients with the diagnosis of BTI between July 2009 and November 2017 were reviewed retrospectively.

Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma.

Single nucleotide polymorphisms (SNPs) close to the gain-of-function substitution, Asn(107)Ile (rs324981, A>T), in Neuropeptide S Receptor 1 (NPSR1) have been associated with asthma. Furthermore, a functional SNP (rs4751440, G>C) in Neuropeptide S (NPS) encodes a Val(6)Leu substitution on the mature peptide that results in reduced bioactivity. We sought to examine the effects of different combinations of these NPS and NPSR1 variants on downstream signaling and genetic risk of asthma.

Poorly understood and often miscategorized congenital umbilical cord hernia: an alternative repair method.

Purpose: Umbilical cord hernia is poorly understood and often miscategorized as "omphalocele minor". Careless clamping of the cord leads to iatrogenic gut injury in the situation of umbilical cord hernia. This study aimed to determine the characteristics and outcomes of umbilical cord hernias.

Spleen Salvaging Treatment Approaches in Non-parasitic Splenic Cysts in Childhood.

The aim of this study was to evaluate our experience with primary non-parasitic splenic cysts (NPSC) which are relatively rare in children and consist almost exclusively of single case reports or small case series in the literature. The medical records of all patients who presented to our clinic with NPSC between 2005 and 2015 were evaluated retrospectively. There were 22 children whose ages ranged from 2 months to 14 years (mean 9.

Intestinal malrotation needs immediate consideration and investigation.

Background: The aim of this study was to evaluate clinical presentation, diagnostic studies, and volvulus rate and to describe the unusual clinical clues of intestinal malrotation.

Methods: A retrospective descriptive review was carried out of all patients diagnosed with intestinal malrotation between 2002 and 2014. Patients were divided into two groups: infants (≤1 year, n = 16; group 1); and children (>1 year, n = 12; group 2).