A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells.

FLT1/VEGFR1 negatively regulates VEGF-A signaling and is required for proper vessel morphogenesis during vascular development and vessel homeostasis. Although a soluble isoform, sFLT1, is often mis-regulated in disease and aging, how sFLT1 is trafficked and secreted from endothelial cells is not well understood. Here we define requirements for constitutive sFLT1 trafficking and secretion in endothelial cells from the Golgi to the plasma membrane, and we show that sFLT1 secretion requires clathrin at or near the Golgi.

A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells.

FLT1/VEGFR1 negatively regulates VEGF-A signaling and is required for proper vessel morphogenesis during vascular development and vessel homeostasis. Although a soluble isoform, sFLT1, is often mis-regulated in disease and aging, how sFLT1 is trafficked and secreted from endothelial cells is not well understood. Here we define requirements for constitutive sFLT1 trafficking and secretion in endothelial cells from the Golgi to the plasma membrane, and we show that sFLT1 secretion requires clathrin at or near the Golgi.

Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies.

The identification of targetable vulnerabilities in the context of therapeutic resistance is a key challenge in cancer treatment. We detected pervasive aberrant splicing as a characteristic feature of chronic lymphocytic leukemia (CLL), irrespective of splicing factor mutation status, which was associated with sensitivity to the spliceosome modulator, E7107. Splicing modulation affected CLL survival pathways, including members of the B cell lymphoma-2 (BCL2) family of proteins, remodeling antiapoptotic dependencies of human and murine CLL cells.

Identification of Novel Protein Expression Changes Following Cisplatin Treatment and Application to Combination Therapy.

Determining the effect of chemotherapeutic treatment on changes in protein expression can provide important targets for overcoming resistance. Due to challenges in simultaneously measuring large numbers of proteins, a paucity of data exists on global changes. To overcome these challenges, we utilized microwestern arrays that allowed us to measure the abundance and modification state of hundreds of cell signaling and transcription factor proteins in cells following drug exposure.

Persistent babesiosis in a Rhesus macaque (Macaca mulatta) infected with a simian-human immunodeficiency virus.

Background: A rhesus macaque developed chronic anemia, lymphocytic leukocytopenia, fever, and anorexia while immunodeficient following inoculation with a simian-human immunodeficiency virus.

Methods: A complete blood count, peripheral blood smear, polymerase chain reaction and gene sequence were performed.

Results: Blood smears demonstrated persistent intraerythrocytic piroplasms with rare Maltese cross forms.

Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques.

Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes.

Microbial quality and bacteria pathogens in private wells used for drinking water in northeastern Ohio.

In agricultural intensive areas, drinking contaminated water from private wells is considered an important cause of acute gastroenteric illnesses (AGI), particularly among high-risk populations. In the summer of 2009, the microbial water quality of 180 randomly selected private wells in two northeastern Ohio counties, a region with a high concentration of dairy farms, was assessed. Forty-five percent (82/180) of water samples were contaminated with total coliforms.

Truncated DNMT3B isoform DNMT3B7 suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma.

Epigenetic changes in pediatric neuroblastoma may contribute to the aggressive pathophysiology of this disease, but little is known about the basis for such changes. In this study, we examined a role for the DNA methyltransferase DNMT3B, in particular, the truncated isoform DNMT3B7, which is generated frequently in cancer. To investigate if aberrant DNMT3B transcripts alter DNA methylation, gene expression, and phenotypic character in neuroblastoma, we measured DNMT3B expression in primary tumors.

Hematologic abnormalities associated with simian immunodeficieny virus (SIV) infection mimic those in HIV infection.

Background: Studies of hematologic abnormalities in HIV-infected patients are confounded by a multitude of factors. A retrospective data analysis of simian immunodeficieny virus (SIV)-infected rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds.

Methods: Hematologic data from RM inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS.

Acute and chronic T cell dynamics in the livers of simian immunodeficiency virus-infected macaques.

The mucosal immune system, particularly the gastrointestinal tract, is critically involved in the pathogenesis of human immunodeficiency virus (HIV) infection. Since the liver drains most of the substances coming from the intestinal tract, it may also play a role in the pathogenesis of HIV infection. Here we examined the percentages and absolute numbers of T cell subsets in the liver in normal and simian immunodeficiency virus (SIV)-infected macaques.

Possible role of glial cells in the onset and progression of Lyme neuroborreliosis.

Background: Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis.

Modification of a common BAL technique to enhance sample diagnostic value.

Bronchoalveolar lavage (BAL) by means of bronchoscopy is a diagnostic tool frequently used for clinical and research purposes in nonhuman primates. Although many institutions use this procedure, the technique is not standardized. One technical aspect that can vary is the method by which fluid is recovered.

Cytologic diagnosis of generalized cutaneous sporotrichosis in a hunting hound.

A 1-year-old male Foxhound/Walker Hound mix was presented to the small animal internal medicine service at Louisiana State University School of Veterinary Medicine with a 6-week history of progressive, multifocal, ulcerative and draining, well-circumscribed lesions in a generalized distribution. Prior to referral, a presumptive diagnosis was made of sterile pyogranulomatous disease; immunosuppressive therapy was instituted but resulted in clinical deterioration. At presentation, the dog had marked neutropenia (1100 neutrophils/microL), and a mild toxic left shift (400 bands/microL).

Congenital Pelger-Huët anomaly in a horse.

A 1.5-year-old male Arabian horse was referred to the Louisiana State University Veterinary Teaching Hospital and Clinic for an open deep laceration involving two thirds of the right trunk. The initial CBC results included an inflammatory leukogram, characterized by a marked degenerative left shift consisting of only immature band neutrophils (7500/microL, reference interval 0-100/microL) with toxic changes and no segmented neutrophils (0/microL, reference interval 2700-6700/microL).