MTOR maintains endothelial cell integrity to limit lung vascular injury.

The functional and structural integrity of the endothelium is essential for vascular homeostasis. Loss of barrier function in quiescent and migratory capacity in proliferative endothelium causes exuberant vascular permeability, a cardinal feature of many inflammatory diseases including acute lung injury (ALI). However, the signals governing these fundamental endothelial cell (EC) functions are poorly understood.

Spleen Tyrosine Kinase phosphorylates VE-cadherin to cause endothelial barrier disruption in acute lung injury.

Increased endothelial cell (EC) permeability is a cardinal feature of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Tyrosine phosphorylation of VE-cadherin is a key determinant of EC barrier disruption. However, the identity and role of tyrosine kinases in this context are incompletely understood.

The Protective Role of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Protein Sigma-1 Receptor in Regulating Endothelial Inflammation and Permeability Associated with Acute Lung Injury.

Earlier studies from our lab identified endoplasmic reticulum (ER) chaperone BiP/GRP78, an important component of MAM, to be a novel determinant of endothelial cell (EC) dysfunction associated with acute lung injury (ALI). Sigma1R (Sig1R) is another unique ER receptor chaperone that has been identified to associate with BiP/GRP78 at the MAM and is known to be a pluripotent modulator of cellular homeostasis. However, it is unclear if Sig1R also plays a role in regulating the EC inflammation and permeability associated with ALI.

Therapeutic Targeting of NF-κB in Acute Lung Injury: A Double-Edged Sword.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a devastating disease that can be caused by a variety of conditions including pneumonia, sepsis, trauma, and most recently, COVID-19. Although our understanding of the mechanisms of ALI/ARDS pathogenesis and resolution has considerably increased in recent years, the mortality rate remains unacceptably high (~40%), primarily due to the lack of effective therapies for ALI/ARDS. Dysregulated inflammation, as characterized by massive infiltration of polymorphonuclear leukocytes (PMNs) into the airspace and the associated damage of the capillary-alveolar barrier leading to pulmonary edema and hypoxemia, is a major hallmark of ALI/ARDS.

Essential Role of Rho-Associated Kinase in ABO Immune Complex-Mediated Endothelial Barrier Disruption.

ABO immune complexes (ABO-IC) formed by ABO-incompatible antigen-antibody interaction are associated with hemolysis and platelet destruction in patients transfused with ABO-nonidentical blood products. However, the effects of ABO-IC on endothelial cells (EC) are unclear. ABO-IC were formed in vitro from normal donor-derived plasma and serum.

Autophagy protein ATG7 is a critical regulator of endothelial cell inflammation and permeability.

Endothelial cell (EC) inflammation and permeability are critical pathogenic mechanisms in many inflammatory conditions including acute lung injury. In this study, we investigated the role of ATG7, an essential autophagy regulator with no autophagy-unrelated functions, in the mechanism of EC inflammation and permeability. Knockdown of ATG7 using si-RNA significantly attenuated thrombin-induced expression of proinflammatory molecules such as IL-6, MCP-1, ICAM-1 and VCAM-1.

Critical role of autophagy regulator Beclin1 in endothelial cell inflammation and barrier disruption.

Recent studies have implicated autophagy in several inflammatory diseases involving aberrant endothelial cell (EC) responses, such as acute lung injury (ALI). However, the mechanistic basis for a role of autophagy in EC inflammation and permeability remain poorly understood. In this study, we impaired autophagy by silencing the essential Beclin1 autophagy gene in human pulmonary artery EC.

The search for understanding: the role of paradigms.

Background: Kuhn's ( 1962 ) acknowledgement of a paradigm as a way that scientists make sense of their world and its reality gave recognition to the idea of 'paradigm shift'. This shift exposes the transience of paradigm development shaped by societal and scientific evolution. This ongoing evolutionary development provides the researcher with many paradigms to consider regarding how research is undertaken and the search for understanding achieved.

The Adhesion G-Protein-Coupled Receptor, GPR56/ADGRG1, Inhibits Cell-Extracellular Matrix Signaling to Prevent Metastatic Melanoma Growth.

Metastatic growth is considered a rate-limiting step in cancer progression, and upregulation of extracellular matrix (ECM) deposition and cell-ECM signaling are major drivers of this process. Mechanisms to reverse ECM upregulation in cancer could potentially facilitate its prevention and treatment but they are poorly understood. We previously reported that the adhesion G-protein-coupled receptor GPR56/ADGRG1 is downregulated in melanoma metastases.

The impact of childhood sexual abuse on psychological distress among women in New Zealand.

Problems: In order to better understand the long-term impact of child sex abuse, this study examined the association between women's experience of abuse, health symptoms, and psychological distress in adulthood. There is limited information about child abuse outside the United States.

Methods: Nine hundred sixty-one women participated in a structured interview.

Synthesis and structure of analogues for the Ni-Fe site in hydrogenase enzymes.

Dithiolate bridging Ni-Fe complexes [(dppe)Ni(II)(mu-SEt)(2)Fe(II)(CN)(2)(CO)(2)](6) and [(dppe)Ni(II)(mu-pdt)Fe(II)(CN)(2)(CO)(2)] [dppe = 1,2-bis(diphenylphosphino)ethane and pdt = 1,3-propanedithiolate] have been synthesized and structurally characterized as structural analogues of the active site of Ni-Fe hydrogenase enzymes. The synthesis starts from key intermediate fac-[Fe(CN)(2)(CO)(3)I](-). [(dppe)Ni(II)(mu-SEt)(2)Fe(II)(CN)(2)(CO)(2)](6), which features a near-planar diethanethiolate-bridged Ni-Fe rhomb, and the arrangement of 2CN(-) ligands is cis to each other.

Traumatic events and mental health in the community: a New Zealand study.

Background: Adverse mental health effects in response to a variety of distressing events in specific populations are well documented. However, comparatively little research has been conducted within large community samples outside North America.

Aims: To assess the prevalence and psychological impact of specific traumatic events in a New Zealand community sample.

Sleep loss and performance of anaesthesia trainees and specialists.

Fatigue risk associated with work schedules of hospital doctors is coming under increasing scrutiny, with much of the research and regulatory focus on trainees. However, provision of 24 h services involves both trainees and specialists, who have different but interdependent work patterns. This study examined work patterns, sleep (actigraphy, diaries) and performance (psychomotor vigilance task pre- and post-duty) of 28 anaesthesia trainees and 20 specialists across a two-week work cycle in two urban public hospitals.

"...it's all the same no matter how much fruit or vegetables or fresh air we get": traveller women's perceptions of illness causation and health inequalities.

This paper explores the perceptions of illness causation and health inequalities of Travellers, an ethnic minority group who experience considerable social and health disadvantages in Ireland. In order to allow for subjective meanings to emerge, a qualitative methodology with purposive sampling was employed. Participants in the study were invited to respond to a vignette in a focus group setting.

Traumatic events and physical health in a New Zealand community sample.

Traumatic event exposure and physical health were examined in a community-residing sample of 1,500 New Zealand adults. Half (51%) reported past traumatic event exposure, 9% reported recent (past 12 months) trauma exposure, and 40% reported no exposure. After adjusting for gender, ethnic, and age differences, those experiencing crime and accident trauma exhibited significantly deteriorated physical health, as measured by current physical symptoms, chronic medical conditions, and chronic limitations in daily functioning.