Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain.

Transcription factor 4 (TCF4) has been implicated in a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. Mutations or deletions in TCF4 cause Pitt-Hopkins syndrome (PTHS), a rare neurodevelopmental disorder. A detailed understanding of its spatial expression across the developing brain is necessary for comprehending TCF4 biology and, by extension, to develop effective treatments for TCF4-associated disorders.

Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome.

Background: Angelman syndrome (AS), a severe neurodevelopmental disorder resulting from the loss of the maternal gene, is marked by changes in the brain's white matter (WM). The extent of WM abnormalities seems to correlate with the severity of clinical symptoms, but these deficits are still not well characterized or understood. This study provides the first large-scale measurement of WM volume reduction in children with AS.

Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey.

Angelman syndrome (AS) is a neurogenetic disorder caused by mutations or deletions in the maternally-inherited allele, leading to a loss of UBE3A protein expression in neurons. The paternally-inherited allele is epigenetically silenced in neurons during development by a noncoding transcript (). The absence of neuronal UBE3A results in severe neurological symptoms, including speech and language impairments, intellectual disability, and seizures.

Primary Helicobacter pylori resistance to antimicrobials in the Brussels area in 2021.

This manuscript summarizes current primary resistance of Helicobacter pylori to antibiotics in Brussels in 2021. Resistance rates were estimated at 18% for clarithromycin, 24% for levofloxacin, 52% for metronidazole, and 0% for amoxicillin and tetracycline. When compared to 2016, resistance rates remain stable, except an increase of 30% for metronidazole.

Update of primary Helicobacter pylori resistance to antimicrobials in Brussels, Belgium.

This study aimed to follow the trend of primary antimicrobial resistance in Helicobacter pylori isolates obtained from several centers in Brussels. We observed increasing rates of primary resistance to macrolides (10.5% to 18%) to nitro-imidazoles (28% to 40%) and to fluoroquinolones (12.

A novel role for the late-onset Alzheimer's disease (LOAD)-associated protein Bin1 in regulating postsynaptic trafficking and glutamatergic signaling.

Postsynaptic trafficking plays a key role in regulating synapse structure and function. While spiny excitatory synapses can be stable throughout adult life, their morphology and function is impaired in Alzheimer's disease (AD). However, little is known about how AD risk genes impact synaptic function.

Subcellular organization of UBE3A in human cerebral cortex.

Background: Loss of UBE3A causes Angelman syndrome, whereas excess UBE3A activity appears to increase the risk for autism. Despite this powerful association with neurodevelopmental disorders, there is still much to be learned about UBE3A, including its cellular and subcellular organization in the human brain. The issue is important, since UBE3A's localization is integral to its function.

A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk.

Background: Helicobacter pylori are stomach-dwelling bacteria that are present in about 50% of the global population. Infection is asymptomatic in most cases, but it has been associated with gastritis, gastric ulcers and gastric cancer. Epidemiological evidence shows that progression to cancer depends upon the host and pathogen factors, but questions remain about why cancer phenotypes develop in a minority of infected people.

Cadherin-10 Maintains Excitatory/Inhibitory Ratio through Interactions with Synaptic Proteins.

Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded by within the ASD risk locus 5p14.

Decreased Axon Caliber Underlies Loss of Fiber Tract Integrity, Disproportional Reductions in White Matter Volume, and Microcephaly in Angelman Syndrome Model Mice.

Angelman syndrome (AS) is a debilitating neurodevelopmental disorder caused by loss of function of the maternally inherited allele. It is currently unclear how the consequences of this genetic insult unfold to impair neurodevelopment. We reasoned that by elucidating the basis of microcephaly in AS, a highly penetrant syndromic feature with early postnatal onset, we would gain new insights into the mechanisms by which maternal loss derails neurotypical brain growth and function.

Identification of an elaborate complex mediating postsynaptic inhibition.

Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. The composition of the inhibitory postsynapse and the mechanistic basis of its regulation, however, remain poorly understood. We used an in vivo chemico-genetic proximity-labeling approach to discover inhibitory postsynaptic proteins.

Subcellular organization of UBE3A in neurons.

Ubiquitination regulates a broad array of cellular processes, and defective ubiquitination is implicated in several neurological disorders. Loss of the E3 ubiquitin-protein ligase UBE3A causes Angelman syndrome. Despite its clinical importance, the normal role of UBE3A in neurons is still unclear.

GABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG Abnormalities and Enhances Seizure Susceptibility.

Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts.

Knowing a synapse when you see one.

Recent years have seen a rapidly growing recognition of the complexity and diversity of the myriad individual synaptic connections that define brain synaptic networks. It has also become increasingly apparent that the synapses themselves are a major key to understanding the development, function and adaptability of those synaptic networks. In spite of this growing appreciation, the molecular, structural and functional characteristics of individual synapses and the patterning of their diverse characteristics across functional networks have largely eluded quantitative study with available imaging technologies.

Organization of TNIK in dendritic spines.

Tumor necrosis factor receptor-associated factor 2 (TRAF2)- and noncatalytic region of tyrosine kinase (NCK)-interacting kinase (TNIK) has been identified as an interactor in the psychiatric risk factor, Disrupted in Schizophrenia 1 (DISC1). As a step toward deciphering its function in the brain, we performed high-resolution light and electron microscopic immunocytochemistry. We demonstrate here that TNIK is expressed in neurons throughout the adult mouse brain.

Vacuolating cytotoxin genotypes are strong markers of gastric cancer and duodenal ulcer-associated Helicobacter pylori strains: a matched case-control study.

The Helicobacter pylori virulence gene, cagA, and active forms of the vacuolating cytotoxin gene, vacA, are major determinants of pathogenesis. However, previous studies linking these factors to disease risk have often included patients using aspirin/nonsteroidal anti-inflammatory agents (NSAIDs) or acid-suppressing drugs, both of which may confound results. Also, particularly for gastric cancer (GC), controls have often been of quite different ages.

NF-κB activation and severity of gastritis in Helicobacter pylori-infected children and adults.

Background: In contrast to adults, Helicobacter pylori gastritis in children is reported as milder and ulcer disease as uncommon, but unequivocal data are lacking.

Objectives: To compare the frequency of gastro-duodenal ulcers in children and adults as well as the proportion of Helicobacter pylori infection in these patients and to study the effect of chronological age on NF-κB activation and on severity of gastritis.

Design: Patients referred in one pediatric and one adult facility for upper GI endoscopy were included.

Postsynaptic distribution of IRSp53 in spiny excitatory and inhibitory neurons.

The 53 kDa insulin receptor substrate protein (IRSp53) is highly enriched in the brain. Despite evidence that links mutations of IRSp53 with autism and other neuropsychiatric problems, the functional significance of this protein remains unclear. We used light and electron microscopic immunohistochemistry to demonstrate that IRSp53 is expressed throughout the adult rat brain.

Competition between α-actinin and Ca²⁺-calmodulin controls surface retention of the L-type Ca²⁺ channel Ca(V)1.2.

Regulation of neuronal excitability and cardiac excitation-contraction coupling requires the proper localization of L-type Ca²⁺ channels. We show that the actin-binding protein α-actinin binds to the C-terminal surface targeting motif of α11.2, the central pore-forming Ca(V)1.

Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex.

Glycine receptors (GlyRs) are found in most areas of the brain, and their dysfunction can cause severe neurological disorders. While traditionally thought of as inhibitory receptors, presynaptic-acting GlyRs (preGlyRs) can also facilitate glutamate release under certain circumstances, although the underlying molecular mechanisms are unknown. In the current study, we sought to better understand the role of GlyRs in the facilitation of excitatory neurotransmitter release in mouse visual cortex.

Electron tomography of fiber cell cytoplasm and dense cores of multilamellar bodies from human age-related nuclear cataracts.

Human nuclear cataract formation is a multi-factorial disease with contributions to light scattering from many cellular sources that change their scattering properties over decades. The aging process produces aggregation of cytoplasmic crystallin proteins, which alters the protein packing and texture of the cytoplasm. Previous studies of the cytoplasmic texture quantified increases in density fluctuations in protein packing and theoretically predicted the corresponding scattering.

Electron tomographic analysis of synaptic ultrastructure.

Synaptic function depends on interactions among sets of proteins that assemble into complex supramolecular machines. Molecular biology, electrophysiology, and live-cell imaging studies have provided tantalizing glimpses into the inner workings of the synapse, but fundamental questions remain regarding the functional organization of these "nano-machines." Electron tomography reveals the internal structure of synapses in three dimensions with exceptional spatial resolution.

Maternal loss of Ube3a produces an excitatory/inhibitory imbalance through neuron type-specific synaptic defects.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of UBE3A. AS model mice, which carry a maternal Ube3a null mutation (Ube3a(m-/p+)), recapitulate major features of AS in humans, including enhanced seizure susceptibility. Excitatory neurotransmission onto neocortical pyramidal neurons is diminished in Ube3a(m-/p+) mice, seemingly at odds with enhanced seizure susceptibility.

The sodium-driven chloride/bicarbonate exchanger in presynaptic terminals.

The sodium-driven chloride/bicarbonate exchanger (NDCBE), a member of the SLC4 family of bicarbonate transporters, was recently found to modulate excitatory neurotransmission in hippocampus. By using light and electron microscopic immunohistochemistry, we demonstrate here that NDCBE is expressed throughout the adult rat brain, and selectively concentrates in presynaptic terminals, where it is closely associated with synaptic vesicles. NDCBE is in most glutamatergic axon terminals, and is also present in the terminals of parvalbumin-positive γ-aminobutyric acid (GABA)ergic cells.

Practical use of GenoType® HelicoDR, a molecular test for Helicobacter pylori detection and susceptibility testing.

Compared to culture-based method, the sensitivity, specificity, positive, and negative predictive values of the GenoType(®) HelicoDR for detecting Helicobacter pylori resistance were, respectively, 100, 86.2, 89.7%, and 100% to clarithromycin as well as 82.