Multiple plasma membrane reporters discern LHFPL5 region that blocks trafficking to the plasma membrane.

The mechano-electrical transduction (MET) channel of the inner ear receptor cells, termed hair cells, is a protein complex that enables our senses of hearing and balance. Hair cell MET requires an elaborate interplay of multiple proteins that form the MET channel. One of the MET complex components is the transmembrane protein LHFPL5, which is required for hair cell MET and hearing.

Targeting TGF-β signaling in the multiple myeloma microenvironment: Steering CARs and T cells in the right direction.

Multiple myeloma (MM) remains a lethal hematologic cancer characterized by the expansion of transformed plasma cells within the permissive bone marrow (BM) milieu. The emergence of relapsed and/or refractory MM (RRMM) is provoked through clonal evolution of malignant plasma cells that harbor genomic, metabolic and proteomic perturbations. For most patients, relapsed disease remains a major cause of overall mortality.

Healthy myeloid-derived suppressor cells express the surface ectoenzyme Vanin-2 (VNN2).

Study of human monocytic Myeloid-Derived Suppressor cells Mo-MDSC (CD14 HLA-DR) has been hampered by the lack of positive cell-surface markers. In order to identify positive markers for Mo-MDSC, we performed microarray analysis comparing Mo-MDSC cells from healthy subjects versus CD14 HLA-DR monocytes. We have identified the surface ectoenzyme Vanin-2(VNN2) protein as a novel biomarker highly-enriched in healthy subjects Mo-MDSC.

Using chimeric antigen receptor T-cell therapy to fight glioblastoma multiforme: past, present and future developments.

Introduction: Glioblastoma multiforme (GBM) constitutes one of the deadliest tumors to afflict humans, although it is still considered an orphan disease. Despite testing multiple new and innovative therapies in ongoing clinical trials, the median survival for this type of malignancy is less than two years after initial diagnosis, regardless of therapy. One class of promising new therapies are chimeric antigen receptor T cells or CAR-T which have been shown to be very effective at treating refractory liquid tumors such as B-cell malignancies.

Breakage of CRISPR/Cas9-Induced Chromosome Bridges in Mitotic Cells.

Chromosomal instability, the most frequent form of plasticity in cancer cells, often proceeds through the formation of chromosome bridges. Despite the importance of these bridges in tumor initiation and progression, debate remains over how and when they are resolved. In this study, we investigated the behavior and properties of chromosome bridges to gain insight into the potential mechanisms underlying bridge-induced genome instability.

A Liquid Biopsy to Assess Brain Tumor Recurrence: Presence of Circulating Mo-MDSC and CD14+ VNN2+ Myeloid Cells as Biomarkers That Distinguish Brain Metastasis From Radiation Necrosis Following Stereotactic Radiosurgery.

Background: Brain metastases (BM) are the most common type of brain tumor malignancy in the US. They are also the most common indication for stereotactic radiosurgery (SRS). However, the incidence of both local recurrence and radiation necrosis (RN) is increasing as treatments improve.

Design and Refinement of a Data Quality Assessment Workflow for a Large Pediatric Research Network.

Background: Clinical data research networks (CDRNs) aggregate electronic health record data from multiple hospitals to enable large-scale research. A critical operation toward building a CDRN is conducting continual evaluations to optimize data quality. The key challenges include determining the assessment coverage on big datasets, handling data variability over time, and facilitating communication with data teams.

Radiation-Induced Malignant Transformation of Preneoplastic and Normal Breast Primary Epithelial Cells.

Radiation is used in multiple procedures as a therapeutic and diagnostic tool. However, ionizing radiation can induce mutations in the DNA of irradiated cells, which can promote tumorigenesis. As malignant transformation is a process that takes many years, there are intermediate stages of cells that have initiated the process but have not yet evolved into cancer.

Modeling and Characterization of Traffic Flows in Urban Environments.

Currently, one of the main challenges faced in large metropolitan areas is traffic congestion. To address this problem, adequate traffic control could produce many benefits, including reduced pollutant emissions and reduced travel times. If it were possible to characterize the state of traffic by predicting future traffic conditions for optimizing the route of automated vehicles, and if these measures could be taken to preventively mitigate the effects of congestion with its related problems, the overall traffic flow could be improved.

Towards Realistic Urban Traffic Experiments Using DFROUTER: Heuristic, Validation and Extensions.

Traffic congestion is an important problem faced by Intelligent Transportation Systems (ITS), requiring models that allow predicting the impact of different solutions on urban traffic flow. Such an approach typically requires the use of simulations, which should be as realistic as possible. However, achieving high degrees of realism can be complex when the actual traffic patterns, defined through an Origin/Destination (O-D) matrix for the vehicles in a city, remain unknown.

The ratio of HLA-DR and VNN2 expression on CD14 myeloid derived suppressor cells can distinguish glioblastoma from radiation necrosis patients.

Glioblastoma (GBM) is the most aggressive and lethal type of brain cancer with a median survival of less than two years even following aggressive treatment (Stupp et al., N Engl J Med 352:987-996, 2005). Among the many challenges in treating patients with this devastating disease is the ability to differentiate Magnetic Resonance Imaging (MRI) images that appear following radiation therapy, often termed "radiation necrosis" from true GBM recurrence.

Does imiquimod pretreatment optimize 308-nm excimer laser (UVB) therapy in psoriasis patients?

Background/purpose: Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques.

Overexpression of AQP3 and AQP10 in the skin exacerbates psoriasiform acanthosis.

We previously observed that aquaporin-3 and aquaporin-10 are upregulated in the epidermis of hand dermatitis patients (Med. Hypotheses, 84, 2015, 498). To address the functional relevance of this upregulation, we overexpressed AQP3/AQP10 in mice using the human K1 promoter.

Expanding the List of Dysregulated Immunosuppressive Cells in Psoriasis.

Traditionally, myeloid-derived suppressor cells (MDSC) have been studied in regard to their increased numbers of circulating cells in cancer patients. Recent research efforts have also increased awareness of MDSC in non-malignant inflammatory diseases, including asthma, inflammatory bowel disease, and arthritis. Psoriasis can now be added to the growing list of inflammatory disorders with an MDSC component.

Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death.

Photodynamic therapy (PDT) is an emerging treatment for malignant and inflammatory dermal disorders. Photoirradiation of the silicon phthalocyanine (Pc) 4 photosensitizer with red light generates singlet oxygen and other reactive oxygen species to induce cell death. We previously reported that Pc 4-PDT elicited cell death in lymphoid-derived (Jurkat) and epithelial-derived (A431) cell lines in vitro, and furthermore that Jurkat cells were more sensitive than A431 cells to treatment.

Development of a Functional Biomarker for Use in Cell-Based Therapy Studies in Seropositive Rheumatoid Arthritis.

Unlabelled: Cell-based therapy has potential therapeutic value in autoimmune diseases such as rheumatoid arthritis (RA). In RA, reduction of disease activity has been associated with improvement in the function of regulatory T cells (Treg) and attenuated responses of proinflammatory effector T cells (Teff). Mesenchymal stem cells (MSCs) and related multipotent adult progenitor cells (MAPC) have strong anti-inflammatory and immunomodulatory properties and may be able to "reset" the immune system to a pre-RA state.

Current knowledge on psoriasis and autoimmune diseases.

Psoriasis is a prevalent, chronic inflammatory disease of the skin, mediated by crosstalk between epidermal keratinocytes, dermal vascular cells, and immunocytes such as antigen presenting cells (APCs) and T cells. Exclusive cellular "responsibility" for the induction and maintenance of psoriatic plaques has not been clearly defined. Increased proliferation of keratinocytes and endothelial cells in conjunction with APC/T cell/monocyte/macrophage inflammation leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin.

Case report of individual with cutaneous immunodeficiency and novel 1p36 duplication.

Introduction: Crusted or Norwegian scabies is an infectious skin dermatopathology usually associated with an underlying immunodeficiency condition. It is caused when the mite Sarcoptes scabiei infects the skin, and the immune system is unable to control its spread, leading to a massive hyperinfestation with a simultaneous inflammatory and hyperkeratotic reaction. This is the first report of a novel 1p36 duplication associated with a recurrent infection of crusted scabies.

Increased, but Functionally Impaired, CD14(+) HLA-DR(-/low) Myeloid-Derived Suppressor Cells in Psoriasis: A Mechanism of Dysregulated T Cells.

The clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14(+) HLA-DR(-/low) monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis.

Breast primary epithelial cells that escape p16-dependent stasis enter a telomere-driven crisis state.

Breast cancer is the most common malignant disease in women, but some basic questions remain in breast cancer biology. To answer these, several cell models were developed. Recently, the use of improved cell-culture conditions has enabled the development of a new primary cell model with certain luminal characteristics.

Psoriasis and cardiovascular risk factors: increased serum myeloperoxidase and corresponding immunocellular overexpression by Cd11b(+) CD68(+) macrophages in skin lesions.

Background: Recent studies report independent associations between psoriasis, cardiovascular (CV) events and risk factors. Blood Myeloperoxidase (MPO) from activated myeloid cells is associated with CV risk mainly through lipid oxidation, induction of endothelial dysfunction and release of IL-12 from macrophages.

Objectives: To elucidate associations between psoriasis and conventional CV risk factors.

Psoriasis patients exhibit impairment of the high potency CCR5(+) T regulatory cell subset.

CCR5 expression on CD4(+)CD25(high)Foxp3(+) regulatory T cells (Tregs) has been reported to be crucial for limiting Th1 inflammation associated with autoimmunity and bacterial infections. We inquired whether abnormalities in chemokine receptors expressed on Tregs might be involved in the psoriatic pathogenesis. Indeed, the proportion of CCR5(+) Treg was 58.

Increased mammogram-induced DNA damage in mammary epithelial cells aged in vitro.

Concerned about the risks of mammography screening in the adult population, we analyzed the ability of human mammary epithelial cells to cope with mammogram-induced DNA damage. Our study shows that an X-ray dose of 20 mGy, which is the standard dose received by the breast surface per two-view mammogram X-ray exploration, induces increased frequencies of DNA double-strand breaks to in vitro aged-but not to young-human mammary epithelial cells. We provide evidence that aged epithelial breast cells are more radiosensitive than younger ones.

The dark side of regulatory T cells in psoriasis.

Psoriasis is a hereditary disease elicited by chronic activation of cutaneous T cells. Delineating the mechanistic interplay of the cell subsets involved is key to developing the next generation of effective treatments. In this issue, Bovenschen et al.