Intrapulmonary T Cells Are Sufficient for -Induced Pulmonary Hypertension.

Background: Schistosomiasis is a parasitic infection that can cause pulmonary hypertension (PH). Th2 CD4 T cells are necessary for experimental -PH. However, if T cells migrate to the lung to initiate, the localized inflammation that drives vascular remodeling and PH is unknown.

Activation of platelets and the complement system in mice with -induced pulmonary hypertension.

Schistosomiasis-induced pulmonary hypertension (PH) presents a significant global health burden, yet the underlying mechanisms remain poorly understood. Here, we investigate the involvement of platelets and the complement system in the initiation events leading to -induced PH. We demonstrate that exposure leads to thrombocytopenia, platelet accumulation in the lung, and platelet activation.

Classical dendritic cells contribute to hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic and progressive disease with significant morbidity and mortality. It is characterized by remodeled pulmonary vessels associated with perivascular and intravascular accumulation of inflammatory cells. Although there is compelling evidence that bone marrow-derived cells, such as macrophages and T cells, cluster in the vicinity of pulmonary vascular lesions in humans and contribute to PH development in different animal models, the role of dendritic cells in PH is less clear.

Reversal of pulmonary veno-occlusive disease phenotypes by inhibition of the integrated stress response.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension arising from EIF2AK4 gene mutations or mitomycin C (MMC) administration. The lack of effective PVOD therapies is compounded by a limited understanding of the mechanisms driving vascular remodeling in PVOD. Here we show that administration of MMC in rats mediates activation of protein kinase R (PKR) and the integrated stress response (ISR), which leads to the release of the endothelial adhesion molecule vascular endothelial (VE) cadherin (VE-Cad) in complex with RAD51 to the circulation, disruption of endothelial barrier and vascular remodeling.

Taming the 1,5-sigmatropic shift across protonated spirocyclic 4-pyrazoles.

The condensation of 1,3-diketones with hydrazine to access 4-pyrazoles is a well-established synthetic route that travels through a 4-pyrazol-1-ium intermediate. In the route to a 3,5-diphenyl-4-pyrazole containing a cyclobutane spirocycle, density functional theory calculations predict and experiments show that the protonated intermediate undergoes a rapid 1,5-sigmatropic shift to form a tetrahydrocyclopenta[]pyrazole. Replacing the 3,5-diphenyl groups with 2-furanyl groups decreases the calculated rate of the 1,5-sigmatropic shift by 6.

Using the phase III slope of exhaled methane during a single breath DCO test to assess ventilation heterogeneity.

Background: The Phase III slope from a single breath nitrogen washout test provides information about ventilation heterogeneity (VH) in the lungs.

Purpose: To determine if the Phase III slope from the exhaled tracer gas concentration during a standard, single breath DCO test using rapid gas analysis provides similar information about VH.

Basic Procedures: Retrospective analysis of clinical pulmonary function laboratory data including spirometry, lung volumes, and DCO.

Interstitial macrophage phenotypes in -induced pulmonary hypertension.

Background: Schistosomiasis is a common cause of pulmonary hypertension (PH) worldwide. Type 2 inflammation contributes to the development of Schistosoma-induced PH. Specifically, interstitial macrophages (IMs) derived from monocytes play a pivotal role by producing thrombospondin-1 (TSP-1), which in turn activates TGF-β, thereby driving the pathology of PH.

Nearshore fish community changes along the Toronto waterfront in accordance with management and restoration goals: Insights from two decades of monitoring.

Aquatic habitat in the Greater Toronto Area has been subject to anthropogenic stressors. The subsequent aquatic habitat degradation that followed led to the Toronto and Region waterfront being listed as an Area of Concern in 1987. Thus, extensive shoreline and riparian habitat restoration have been implemented as part of the Toronto and Region Remedial Action Plan in conjunction with local stakeholders, ministries, and NGOs in an overall effort to increase fish, bird, and wildlife habitat.

Hypobaric hypoxia modulated structural characteristics of circulating cell-free DNA in high-altitude pulmonary edema.

The utility of cell-free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for using its full potential. The high-altitude (HA; altitude > 2,500 m above sea level) environment characterized by hypobaric hypoxia offers an observational case-control design to study the differential cfDNA profile in patients with high-altitude pulmonary edema (HAPE) (number of subjects, = 112) and healthy HA sojourners ( = 111).

Click Organocatalysis: Acceleration of Azide-Alkyne Cycloadditions with Mutually Orthogonal Click Reactions.

"Click organocatalysis" uses mutually orthogonal click reactions to organocatalyze a click reaction. We report the development of an isobenzofuran organocatalyst that increases the rate and regioselectivity of an azide-alkyne cycloaddition. The organocatalytic cycle consists of (1) a Diels-Alder reaction of an alkyne with a diarylisobenzofuran to form a benzooxanorbornadiene, (2) a 1,3-dipolar cycloaddition with an azide to form a 4,5-dihydro-1,2,3-triazole, and (3) a retro-Diels-Alder reaction that releases the triazole product and regenerates the diarylisobenzofuran organocatalyst.

Hypobaric hypoxia drives selection of altitude-associated adaptative alleles in the Himalayan population.

Genetic variants play a crucial role in shaping the adaptive phenotypes associated with high-altitude populations. Nevertheless, a comprehensive understanding of the specific impacts of different environments associated with increasing altitudes on the natural selection of these genetic variants remains undetermined. Hence, this study aimed to identify genetic markers responsible for high-altitude adaptation with specific reference to different altitudes, majorly focussing on an altitude elevation range of ∼1500 m and a corresponding decrease of ≥5 % in ambient oxygen availability.

Reversal of pulmonary veno-occlusive disease phenotypes by inhibition of the integrated stress response.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension arising from EIF2AK4 gene mutations or mitomycin C (MMC) administration. The lack of effective PVOD therapies is compounded by a limited understanding of the mechanisms driving the vascular remodeling in PVOD. We show that the administration of MMC in rats mediates the activation of protein kinase R (PKR) and the integrated stress response (ISR), which lead to the release of the endothelial adhesion molecule VE-Cadherin in the complex with Rad51 to the circulation, disruption of endothelial barrier, and vascular remodeling.

Is pulmonary arterial hypertension associated with schistosomiasis distinct from pulmonary arterial hypertension associated with portal hypertension?

Pulmonary arterial hypertension associated with schistosomiasis (SchPAH) and pulmonary arterial hypertension associated with portal hypertension (PoPAH) are lung diseases that develop in the presence of liver diseases. However, mechanistic pathways by which the underlying liver conditions and other drivers contribute to the development and progression of pulmonary arterial hypertension (PAH) are unclear for both etiologies. In turn, these unknowns limit certainty of strategies to prevent, diagnose, and reverse the resultant PAH.

Dexamethasone prophylaxis protects from acute high-altitude illness by modifying the peripheral blood mononuclear cell inflammatory transcriptome.

Acute high-altitude (HA) exposure can induce several pathologies. Dexamethasone (DEX) can be taken prophylactically to prevent HA disease, but the mechanism by which it acts in this setting is unclear. We studied the transcriptome of peripheral blood mononuclear cells (PBMCs) from 16 subjects at low altitude (LA, 225 m) and then 3 days after acute travel to HA (3500 m) during the India-Leh-Dexamethasone-Expedition-2020 (INDEX2020).

Computational study of an oxetane 4-pyrazole as a Diels-Alder diene.

We combine the effects of spirocyclization and hyperconjugation to increase the Diels-Alder reactivity of the 4-pyrazole scaffold. A density functional theory (DFT) investigation predicts that 4-pyrazoles containing an oxetane functionality at the saturated center are extremely reactive despite having a relatively high-lying lowest unoccupied molecular orbital (LUMO) energy.