A Brief Historical Perspective on Pulmonary Embolism.

Pulmonary embolism is a major cause of mortality worldwide. In this historical perspective, we aim to provide an overview of the rich medical history surrounding pulmonary embolism. We highlight Virchow's first steps toward understanding the pathophysiology in the 1800s.

One hundred cases of primary spontaneous pneumomediastinum: leukocytosis is common, pleural effusions and age over 40 are rare.

Background: Primary spontaneous pneumomediastinum (PSPM) is a benign condition, but it can be difficult to discriminate from Boerhaave syndrome. The diagnostic difficulty is attributable to a shared constellation of history, signs, and symptoms combined with a poor understanding of the basic vital signs, labs, and diagnostic findings characterizing PSPM. These challenges likely contribute to high resource utilization for diagnosis and management of a benign process.

Development of a novel miR-3648-related gene signature as a prognostic biomarker in esophageal adenocarcinoma.

Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature.

A narrative review of primary spontaneous pneumomediastinum: a poorly understood and resource-intensive problem.

Primary spontaneous pneumomediastinum (PSPM) is a benign self-limited condition that can be difficult to discriminate from esophageal perforation. This may trigger costly work-up, transfers and hospital admissions. To better understand this diagnostic dilemma and current management, we undertook the most comprehensive and up to date review of PSPM.

Cavitary lung lesions and pneumothorax in a healthy patient with active coronavirus-19 (COVID-19) viral pneumonia.

Severe respiratory sequelae drive morbidity-associated with coronavirus 2019 (COVID-19) disease. We report a case of COVID-19 pneumonia complicated by cavitary lesions and pneumothorax in a young healthy male. Pneumothorax management with catheter thoracostomy and rapid resolution of the cavitary lesions are described.

Mitosis-meiosis and sperm-oocyte fate decisions are separable regulatory events.

Germ cell fate decisions are poorly understood, despite their central role in reproduction. One fundamental question has been whether germ cells are regulated to enter the meiotic cell cycle (i.e.

Phosphorylation state of a Tob/BTG protein, FOG-3, regulates initiation and maintenance of the Caenorhabditis elegans sperm fate program.

FOG-3, the single Caenorhabditis elegans Tob/BTG protein, directs germ cells to adopt the sperm fate at the expense of oogenesis. Importantly, FOG-3 activity must be maintained for the continued production of sperm that is typical of the male sex. Vertebrate Tob proteins have antiproliferative activity and ERK phosphorylation of Tob proteins has been proposed to abrogate "antiproliferative" activity.

Chemical reprogramming of Caenorhabditis elegans germ cell fate.

Small molecules can control cell fate in vivo and may allow directed induction of desired cell types, providing an attractive alternative to transplant-based approaches in regenerative medicine. We have chemically induced functional oocytes in Caenorhabditis elegans adults that otherwise produced only sperm. These findings suggest that chemical approaches to therapeutic cell reprogramming may be feasible and provide a powerful platform for analyzing molecular mechanisms of in vivo cell reprogramming.

COMMD1 forms oligomeric complexes targeted to the endocytic membranes via specific interactions with phosphatidylinositol 4,5-bisphosphate.

Copper metabolism Murr1 domain 1 (COMMD1) is a 21-kDa protein involved in copper export from the liver, NF-kappaB signaling, HIV infection, and sodium transport. The precise function of COMMD and the mechanism through which COMMD1 performs its multiple roles are not understood. Recombinant COMMD1 is a soluble protein, yet in cells COMMD1 is largely seen as targeted to cellular membranes.

Solution structure of the N-domain of Wilson disease protein: distinct nucleotide-binding environment and effects of disease mutations.

Wilson disease protein (ATP7B) is a copper-transporting P(1B)-type ATPase that regulates copper homeostasis and biosynthesis of copper-containing enzymes in human tissues. Inactivation of ATP7B or related ATP7A leads to severe neurodegenerative disorders, whereas their overexpression contributes to cancer cell resistance to chemotherapeutics. Copper-transporting ATPases differ from other P-type ATPases in their topology and the sequence of their nucleotide-binding domain (N-domain).

Consequences of copper accumulation in the livers of the Atp7b-/- (Wilson disease gene) knockout mice.

Wilson disease is a severe genetic disorder associated with intracellular copper overload. The affected gene, ATP7B, has been identified, but the molecular events leading to Wilson disease remain poorly understood. Here, we demonstrate that genetically engineered Atp7b-/- mice represent a valuable model for dissecting the disease mechanisms.

The distinct functional properties of the nucleotide-binding domain of ATP7B, the human copper-transporting ATPase: analysis of the Wilson disease mutations E1064A, H1069Q, R1151H, and C1104F.

Copper transport by the P(1)-ATPase ATP7B, or Wilson disease protein (WNDP),1 is essential for human metabolism. Perturbation of WNDP function causes intracellular copper accumulation and severe pathology, known as Wilson disease (WD). Several WD mutations are clustered within the WNDP nucleotide-binding domain (N-domain), where they are predicted to disrupt ATP binding.

The N-terminal metal-binding site 2 of the Wilson's Disease Protein plays a key role in the transfer of copper from Atox1.

The Wilson's disease protein (WNDP) is a copper-transporting ATPase regulating distribution of copper in the liver. Mutations in WNDP lead to a severe metabolic disorder, Wilson's disease. The function of WNDP depends on Atox1, a cytosolic metallochaperone that delivers copper to WNDP.