FRMD4A Upregulation in Human Squamous Cell Carcinoma Promotes Tumor Growth and Metastasis and Is Associated with Poor Prognosis

New therapeutic strategies are needed to improve treatment of head and neck squamous cell carcinoma (HNSCC), an aggressive tumor with poor survival rates. FRMD4A is a human epidermal stem cell marker implicated previously in epithelial polarity that is upregulated in SCC cells. Here, we report that FRMD4A upregulation occurs in primary human HNSCCs where high expression levels correlate with increased risks of relapse. FRMD4A silencing decreased growth and metastasis of human SCC xenografts in skin and tongue, reduced SCC proliferation and intercellular adhesion, and stimulated caspase-3 activity and expression of terminal differentiation markers. Notably, FRMD4A attenuation caused nuclear accumulation of YAP, suggesting a potential role for FRMD4A in Hippo signaling. Treatment with the HSP90 inhibitor 17-DMAG or ligation of CD44 with hyaluronan caused nuclear depletion of FRMD4A, nuclear accumulation of YAP and reduced SCC growth and metastasis. Together, our findings suggest FRMD4A as a novel candidate therapeutic target in HNSCC based on the key role in metastatic growth we have identified

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

The effects of implementing recitation activities on success rates in a college calculus course

Over a period of six years, three different types of recitation sessions were implemented into the large enrollment section of a college calculus course. During the fall semesters, the results on the departmental final examination, the DFW rates, and the one-year retention rates of students as STEM majors were examined by the type of recitation session used with the large enrollment section. The three types of recitation sessions studied were: (1) optional mentoring sessions at the Math Assistance Center conducted by undergraduate students (peer mentors), (2) required mentoring sessions conducted by graduate students, and (3) required VGNA (Verbal, Graphical or Geometric, Numeric, and Algebraic) Concept activities, which were also coupled with mentoring sessions conducted by graduate students. The success of the students in the large enrollment section of the course, which included one of the three different types of recitation sessions, was compared to the success of students in the small enrollment sections of the course (enrollments less than 50 students). The effects of using each type of recitation session on raising departmental final examination scores, lowering DFW rates, and raising one-year retention rates is presented. The results of this study demonstrate methods of raising student success rates in large enrollment (lecture-format) courses

A view through a window: Social relations, material objects and locality

In this article the authors ask what it would mean to think sociologically about the window as a specific material and symbolic object. Drawing on qualitative analysis of a series of comparative interviews with residents in three different streets in a diverse local area of Glasgow, they explore what the use and experience of windows tells us about their respondents’ very different relationships to the places where they live. On the one hand, the window, as a material feature of the home, helps us grasp the lived reality of class inequality and how such inequality shapes people’s day-to-day experience. On the other hand, windows are symbolically charged objects, existing at the border of the domestic and public world. For this reason, they feature in important ways in local debates over the appearance, ownership and conservation of the built environment. The article explores these struggles, and shows what they reveal about the construction of belonging in the neighbourhood, a process which is both classed and racialised at one and the same time.ESR

Correlated Excitonic Signatures in a Nanoscale van der Waals Antiferromagnet

Composite quasi-particles with emergent functionalities in spintronic and quantum information science can be realized in correlated materials due to entangled charge, spin, orbital, and lattice degrees of freedom. Here we show that by reducing the lateral dimension of correlated antiferromagnet NiPS3 flakes to tens of nanometers, we can switch-off the bulk spin-orbit entangled exciton in the near-infrared (1.47 eV) and activate visible-range (1.8 to 2.2 eV) transitions with charge-transfer character. These ultra-sharp lines (<120 ueV at 4.2 K) share the spin-correlated nature of the bulk exciton by displaying a Neel temperature dependent linear polarization. Furthermore, exciton photoluminescence lineshape analysis reveals a polaronic character via coupling with at-least 3 phonon modes and a comb-like Stark effect through discretization of charges in each layer. These findings augment the knowledge on the many-body nature of excitonic quasi-particles in correlated antiferromagnets and also establish the nanoscale platform as promising for maturing integrated magneto-optic devices

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD