Flotillin-1 palmitoylation is essential for its stability and subsequent tumor promoting capabilities.

Flotillin-1 contributes to invasion and metastasis in triple negative breast cancer (TNBC) and is modified post-translationally through palmitoylation. Palmitoylation, the process of conjugating palmitoyl-CoA to proteins, plays an essential role in protein stability and trafficking. Thus far, there has not been any investigation into the role of flotillin-1 palmitoylation in the context of metastasis in vivo.

Delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment in models of high-risk childhood leukemia.

High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells.

Viral Biomarker Detection and Validation Using MALDI Mass Spectrometry Imaging (MSI).

(1) Background: MALDI imaging is a technique that still largely depends on time of flight (TOF)-based instrument such as the Bruker UltrafleXtreme. While capable of performing targeted MS/MS, these instruments are unable to perform fragmentation while imaging a tissue section necessitating the reliance of MS1 values for peptide level identifications. With this premise in mind, we have developed a hybrid bioinformatic/image-based method for the identification and validation of viral biomarkers.

An IGF-1R-mTORC1-SRPK2 signaling Axis contributes to FASN regulation in breast cancer.

Background: Fatty acid synthase (FASN) expression is associated with a more aggressive breast cancer phenotype and is regulated downstream of receptor tyrosine kinase (RTK) signaling pathways. Recently, post transcriptional regulation of lipogenic transcripts have been demonstrated as being mediated downstream of serine-arginine rich protein kinase 2 (SRPK2), which acts to phosphorylate serine-arginine rich splicing factors (SRSFs), resulting in RNA binding and various RNA regulatory processes. Though post-transcriptional regulation of FASN has been studied previously, the upstream mediators of these pathways have not been elucidated.

Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors.

Purpose: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells.

Methods: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used.

Metal(loid) pollution, not urbanisation nor parasites predicts low body condition in a wetland bioindicator snake.

Urban ecosystems and remnant habitat 'islands' therein, provide important strongholds for many wildlife species including those of conservation significance. However, the persistence of these habitats can be undermined if their structure and function are too severely disrupted. Urban wetlands, specifically, are usually degraded by a monoculture of invasive vegetation, disrupted hydrology, and chronic-contamination from a suite of anthropogenic pollutants.

Chaphamaparvovirus antigen and nucleic acids are not detected in kidney tissues from cats with chronic renal disease or immunocompromised cats.

Chronic kidney disease (CKD) is a common cause of morbidity and mortality in domestic cats, but the cause is still largely elusive. While some viruses have been associated with this disease, none have been definitively implicated as causative. Recently, was recognized as the cause of murine inclusion body nephropathy, a disease reported for over 40 years in laboratory mice.

Obesity-Modified CD4+ T-Cells Promote an Epithelial-Mesenchymal Transition Phenotype in Prostate Cancer Cells.

Obesity is associated with low-grade chronic inflammation, and metabolic dysregulation. Evidence shows that chronic inflammation inhibits protective immunity mediated by CD4+ T cells. Additionally, obesity-induced inflammation affects prostate cancer progression.

Murine and related chapparvoviruses are nephro-tropic and produce novel accessory proteins in infected kidneys.

Mouse kidney parvovirus (MKPV) is a member of the provisional genus Chapparvovirus that causes renal disease in immune-compromised mice, with a disease course reminiscent of polyomavirus-associated nephropathy in immune-suppressed kidney transplant patients. Here we map four major MKPV transcripts, created by alternative splicing, to a common initiator region, and use mass spectrometry to identify "p10" and "p15" as novel chapparvovirus accessory proteins produced in MKPV-infected kidneys. p15 and the splicing-dependent putative accessory protein NS2 are conserved in all near-complete amniote chapparvovirus genomes currently available (from mammals, birds and a reptile).

Intrinsically reversible superglues via shape adaptation inspired by snail epiphragm.

Adhesives are ubiquitous in daily life and industrial applications. They usually fall into one of two classes: strong but irreversible (e.g.

Immune regeneration in irradiated mice is not impaired by the absence of DPP9 enzymatic activity.

The ubiquitous intracellular protease dipeptidyl peptidase 9 (DPP9) has roles in antigen presentation and B cell signaling. To investigate the importance of DPP9 in immune regeneration, primary and secondary chimeric mice were created in irradiated recipients using fetal liver cells and adult bone marrow cells, respectively, using wild-type (WT) and DPP9 gene-knockin (DPP9) enzyme-inactive mice. Immune cell reconstitution was assessed at 6 and 16 weeks post-transplant.

An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis.

The occurrence of a spontaneous nephropathy with intranuclear inclusions in laboratory mice has puzzled pathologists for over 4 decades, because its etiology remains elusive. The condition is more severe in immunodeficient animals, suggesting an infectious cause. Using metagenomics, we identify the causative agent as an atypical virus, termed "mouse kidney parvovirus" (MKPV), belonging to a divergent genus of Parvoviridae.

Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice.

Antibody-mediated immunity is highly protective against disease. The majority of current vaccines confer protection through humoral immunity, but there is high variability in responsiveness across populations. Identifying immune mechanisms that mediate low antibody responsiveness may provide potential strategies to boost vaccine efficacy.

SAMHD1 enhances immunoglobulin hypermutation by promoting transversion mutation.

Activation-induced deaminase (AID) initiates hypermutation of genes in activated B cells by converting C:G into U:G base pairs. G-phase variants of uracil base excision repair (BER) and mismatch repair (MMR) then deploy translesion polymerases including REV1 and Pol η, which exacerbates mutation. dNTP paucity may contribute to hypermutation, because dNTP levels are reduced in G phase to inhibit viral replication.

Preclinical Evaluation of the Short-Term Toxicity of 4-(N)-Docosahexaenoyl 2´, 2´- Difluorodeoxycytidine (DHA-dFdC).

Purpose: This study was designed to test the short-term toxicity of DHA-dFdC in a mouse model and its efficacy in a mouse model of leukemia at or below its repeat-dose maximum tolerated dose (RD-MTD).

Method: A repeat-dose dose-ranging toxicity study was designed to determine the tolerability of DHA-dFdC when administered to DBA/2 mice by intravenous (i.v.

The pro-fibrotic role of dipeptidyl peptidase 4 in carbon tetrachloride-induced experimental liver injury.

Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration.

Mitochondrial Glycerol-3-Phosphate Acyltransferase-Dependent Phospholipid Synthesis Modulates Phospholipid Mass and IL-2 Production in Jurkat T Cells.

Changes in glycerophospholipid metabolism with age and disease can have a profound effect on immune cell activation and effector function. We previously demonstrated that glycerol-3-phosphate acyltransferase-1, the first and rate limiting step in de novo glycerophospholipid synthesis, plays a role in modulating murine T cell function. The resultant phenotype is characterized by decreased IL-2 production, increased propensity toward apoptosis, and altered membrane glycerophospholipid mass similar to that of an aged T cell.

The impact of invasive cane toads on native wildlife in southern Australia.

Commonly, invaders have different impacts in different places. The spread of cane toads (Rhinella marina: Bufonidae) has been devastating for native fauna in tropical Australia, but the toads' impact remains unstudied in temperate-zone Australia. We surveyed habitat characteristics and fauna in campgrounds along the central eastern coast of Australia, in eight sites that have been colonized by cane toads and another eight that have not.

Age-related increase in IL-17 activates pro-inflammatory signaling in prostate cells.

Background: A close relationship between aging, inflammation, and prostate cancer is widely accepted. Aging is accompanied by a progressive increase in pro-inflammatory cytokines, including interleukin 17 (IL-17), a key pro-inflammatory cytokine that becomes dysregulated with age. However, the contribution of IL-17 to age-related prostate tumorigenesis remains unclear.

ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions.

The formation of the vascular network requires a tightly controlled balance of pro-angiogenic and stabilizing signals. Perturbation of this balance can result in dysregulated blood vessel morphogenesis and drive pathologies including cancer. Here, we have identified a novel gene, ARHGAP18, as an endogenous negative regulator of angiogenesis, limiting pro-angiogenic signaling and promoting vascular stability.

NSAID use reduces breast cancer recurrence in overweight and obese women: role of prostaglandin-aromatase interactions.

Obesity is associated with a worse breast cancer prognosis and elevated levels of inflammation, including greater cyclooxygenase-2 (COX-2) expression and activity in adipose-infiltrating macrophages. The product of this enzyme, the proinflammatory eicosanoid prostaglandin E2 (PGE2), stimulates adipose tissue aromatase expression and subsequent estrogen production, which could promote breast cancer progression. This study demonstrates that daily use of a nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 activity, is associated with reduced estrogen receptor α (ERα)-positive breast cancer recurrence in obese and overweight women.