The diagnostic spectrum of ATP1A3-related disorders: 3 new patients.

Background: ATP1A3-related disorders are rare but increasingly recognized syndromes with overlapping phenotypes.

Clinical Observations: A male child and his mother with c.2452G>A (p.

Infarction of the Splenium of the Corpus Callosum in the Age of COVID-19: A Snapshot in Time.

Background And Purpose: Ischemic infarction of the corpus callosum is rare and infarction isolated to the corpus callosum alone rarer still, accounting for much <1% of ischemic stroke in most stroke registries. About half of callosal infarctions affect the splenium.

Methods: During a 2-week period, at the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City, 4 patients at Montefiore Medical Center in the Bronx were found to have ischemic lesions of the splenium of the corpus callosum, 2 with infarction isolated to the corpus callosum.

Structural Insights into the Mechanism of Mitoribosomal Large Subunit Biogenesis.

In contrast to the bacterial translation machinery, mitoribosomes and mitochondrial translation factors are highly divergent in terms of composition and architecture. There is increasing evidence that the biogenesis of mitoribosomes is an intricate pathway, involving many assembly factors. To better understand this process, we investigated native assembly intermediates of the mitoribosomal large subunit from the human parasite Trypanosoma brucei using cryo-electron microscopy.

Mitoribosomal small subunit biogenesis in trypanosomes involves an extensive assembly machinery.

Mitochondrial ribosomes (mitoribosomes) are large ribonucleoprotein complexes that synthesize proteins encoded by the mitochondrial genome. An extensive cellular machinery responsible for ribosome assembly has been described only for eukaryotic cytosolic ribosomes. Here we report that the assembly of the small mitoribosomal subunit in involves a large number of factors and proceeds through the formation of assembly intermediates, which we analyzed by using cryo-electron microscopy.

Nerve entrapments related to muscle herniation.

Background: Muscle herniation is a muscle protrusion through a fascial defect. It is a rarely reported cause of nerve entrapment.

Methods: We present a case of superficial fibular (peroneal) neuropathy associated with a fibularis (peroneus) brevis muscle herniation and a review of the literature on nerve entrapments secondary to muscle herniation unrelated to compartment syndrome.

Evolutionary shift toward protein-based architecture in trypanosomal mitochondrial ribosomes.

Ribosomal RNA (rRNA) plays key functional and architectural roles in ribosomes. Using electron microscopy, we determined the atomic structure of a highly divergent ribosome found in mitochondria of , a unicellular parasite that causes sleeping sickness in humans. The trypanosomal mitoribosome features the smallest rRNAs and contains more proteins than all known ribosomes.

Dissecting ribosomal particles throughout the kingdoms of life using advanced hybrid mass spectrometry methods.

Biomolecular mass spectrometry has matured strongly over the past decades and has now reached a stage where it can provide deep insights into the structure and composition of large cellular assemblies. Here, we describe a three-tiered hybrid mass spectrometry approach that enables the dissection of macromolecular complexes in order to complement structural studies. To demonstrate the capabilities of the approach, we investigate ribosomes, large ribonucleoprotein particles consisting of a multitude of protein and RNA subunits.

High-resolution structures of mitochondrial ribosomes and their functional implications.

Mitochondrial ribosomes (mitoribosomes) almost exclusively synthesize essential components of the oxidative phosphorylation machinery. Dysfunction of mitochondrial protein biosynthesis leads to human diseases and plays an important role in the altered metabolism of cancer cells. Recent developments in cryo-electron microscopy enabled the structural characterization of complete yeast and mammalian mitoribosomes at near-atomic resolution.

Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates.

The mitochondrial ribosome, which translates all mitochondrial DNA (mtDNA)-encoded proteins, should be tightly regulated pre- and post-transcriptionally. Recently, we found RNA-DNA differences (RDDs) at human mitochondrial 16S (large) rRNA position 947 that were indicative of post-transcriptional modification. Here, we show that these 16S rRNA RDDs result from a 1-methyladenosine (m1A) modification introduced by TRMT61B, thus being the first vertebrate methyltransferase that modifies both tRNA and rRNAs.

Ribosome. The complete structure of the 55S mammalian mitochondrial ribosome.

Mammalian mitochondrial ribosomes (mitoribosomes) synthesize mitochondrially encoded membrane proteins that are critical for mitochondrial function. Here we present the complete atomic structure of the porcine 55S mitoribosome at 3.8 angstrom resolution by cryo-electron microscopy and chemical cross-linking/mass spectrometry.

The complete structure of the large subunit of the mammalian mitochondrial ribosome.

Mitochondrial ribosomes (mitoribosomes) are extensively modified ribosomes of bacterial descent specialized for the synthesis and insertion of membrane proteins that are critical for energy conversion and ATP production inside mitochondria. Mammalian mitoribosomes, which comprise 39S and 28S subunits, have diverged markedly from the bacterial ribosomes from which they are derived, rendering them unique compared to bacterial, eukaryotic cytosolic and fungal mitochondrial ribosomes. We have previously determined at 4.

Architecture of the large subunit of the mammalian mitochondrial ribosome.

Mitochondrial ribosomes synthesize a number of highly hydrophobic proteins encoded on the genome of mitochondria, the organelles in eukaryotic cells that are responsible for energy conversion by oxidative phosphorylation. The ribosomes in mammalian mitochondria have undergone massive structural changes throughout their evolution, including ribosomal RNA shortening and acquisition of mitochondria-specific ribosomal proteins. Here we present the three-dimensional structure of the 39S large subunit of the porcine mitochondrial ribosome determined by cryo-electron microscopy at 4.

Optic neuritis and palatal dysarthria as presenting features of post-infectious GQ1b antibody syndrome.

A 31-year-old man had optic neuritis 2 weeks after a diarrheal illness, followed by several deficits including palatal dysarthria, diplopia, ataxia, sensory dysfunction, and mild dysautonomia. Brain MRI and CSF were normal. Nerve conduction studies were initially normal and subsequently showed mild reduction in sensory amplitudes.

Blood gammadelta T cells, Campylobacter jejuni, and GM1 titers in Guillain-Barré syndrome.

The gammadelta T cells participate in microbial defense, are prevalent in intestinal epithelia, and are activated in autoimmune diseases. We studied whether peripheral blood gammadelta cells and gammadelta subsets are increased in Guillain-Barré syndrome (GBS) and whether elevations are associated with Campylobacter jejuni infection or GM1 elevations. In 20 GBS patients, we performed serial flow cytometry studies of blood gammadelta, Vdelta1, and Vdelta2 cells (+/- CD8+), C jejuni, and ganglioside titers.

Peripheral neuropathy in young-old and old-old patients.

Diabetes is said to account for most cases of neuropathy in the elderly. We reviewed records of 223 young-old (65-79 years) and 77 old-old (>or=80 years) patients referred for evaluation of neuropathic symptoms over a 9-year period. We prospectively validated our findings in 102 consecutive elderly (77 young-old) patients receiving intensive evaluation for neuropathy.

Median mixed and sensory nerve conduction studies in carpal tunnel syndrome.

Objective: To assess the sensitivities and specificities of velocity differences between median mixed nerve conduction across the wrist (Medmxpw) and (I) median mixed nerve conduction in the forearm (Medmxf) and (II) palm to D2 sensory conduction (MedpD2).

Design And Methods: We prospectively studied 67 limbs of patients with clinically definite carpal tunnel syndrome (CTS). Medmxf and Medmxpw were performed by stimulating the median nerve at the elbow and palm respectively and recording at the proximal wrist crease.

Abnormal nerve conduction studies in mice expressing a mutant form of the POU transcription factor SCIP.

We have previously described transgenic mice that harbor a dominant-negative antagonist of the POU protein SCIP (termed deltaSCIP). Native SCIP is expressed in promyelinating Schwann cells, where it represses expression of the myelin structural genes. The deltaSCIP mice display morphologic and behavioral abnormalities, including decreased axonal diameter, increased myelin thickness, developmentally early myelination, and clinical features of neuropathy.

A transgenic mouse model for human hereditary neuropathy with liability to pressure palsies.

Mutations in the gene encoding peripheral myelin protein 22 (PMP22) account for several inherited peripheral neuropathies in humans. We now show that transgenic mice expressing antisense PMP22 RNA exhibit modestly reduced levels of PMP22 together with a phenotype that is reminiscent of hereditary neuropathy with liability to pressure palsies (HNPP), a human disease caused by a 1.5-Mb deletion of a chromosome 17 region that contains the PMP22 gene.