5,318 research outputs found
Papillary Renal Carcinoma Presenting as a Cancer of Unknown Primary (CUP) and Diagnosed through Gene Expression Profiling
Cancer of unknown primary (CUP) is a clinical syndrome representing many types of cancers and diagnoses are typically made after review of clinical presentation, pathology (including immunohistochemical staining) and imaging studies. Treatment with systemic chemotherapy has been shown to result in fairly reproducible objective response rates. Herein, a case of a patient who was initially diagnosed with a poorly differentiated adenocarcinoma of unknown origin is reported. After mRNA gene expression profiling (commercially available CancerTYPE ID), a specific diagnosis of papillary renal cell carcinoma (RCC) was made and then confirmed with additional immunohistochemical staining. The patient was treated with targeted therapy and an objective radiographic response was seen. A literature review suggests this to be the first patient with papillary RCC, identified by molecular profiling, and benefitting from a targeted agent that otherwise would not have been considered in the setting of CUP. This case underscores the importance of considering the use of newer testing technologies in the interest of offering patients more specific, targeted therapy in order to improve efficacy and spare patients toxicities of less specific, empiric chemotherapeutic regimens
MicroR159 regulation of most conserved targets in Arabidopsis has negligible phenotypic effects
BACKGROUND A current challenge of microRNA (miRNA) research is the identification of biologically relevant miRNA:target gene relationships. In plants, high miRNA:target gene complementarity has enabled accurate target predictions, and slicing of target mRNAs has facilitated target validation through rapid amplification of 5' cDNA ends (5'-RACE) analysis. Together, these approaches have identified more than 20 targets potentially regulated by the deeply conserved miR159 family in Arabidopsis, including eight MYB genes with highly conserved miR159 target sites. However, genetic analysis has revealed the functional specificity of the major family members, miR159a and miR159b is limited to only two targets, MYB33 and MYB65. Here, we examine the functional role of miR159 regulation for the other potential MYB target genes. RESULTS For these target genes, functional analysis failed to identify miR159 regulation that resulted in any major phenotypic impact, either at the morphological or molecular level. This appears to be mainly due to the quiescent nature of the remaining family member, MIR159c. Although its expression overlaps in a temporal and spatial cell-specific manner with a subset of these targets in anthers, the abundance of miR159c is extremely low and concomitantly a mir159c mutant displays no anther defects. Examination of potential miR159c targets with conserved miR159 binding sites found neither their spatial or temporal expression domains appeared miR159 regulated, despite the detection of miR159-guided cleavage products by 5'-RACE. Moreover, expression of a miR159-resistant target (mMYB101) resulted predominantly in plants that are indistinguishable from wild type. Plants that displayed altered morphological phenotypes were found to be ectopically expressing the mMYB101 transgene, and hence were misrepresentative of the in vivo functional role of miR159. CONCLUSIONS This study presents a novel explanation for a paradox common to plant and animal miRNA systems, where among many potential miRNA-target relationships usually only a few appear physiologically relevant. The identification of a quiescent miR159c:target gene regulatory module in anthers provides a likely rationale for the presence of conserved miR159 binding sites in many targets for which miR159 regulation has no obvious functional role. Remnants from the demise of such modules may lead to an overestimation of miRNA regulatory complexity when investigated using bioinformatic, 5'-RACE or transgenic approaches.RSA was funded by an ANU postgraduate scholarship and by a CSIRO Emerging Science Initiative. JL is the recipient of an ANU international student postgraduate scholarship. This research was supported by an Australian Research Council grant DP0773270
Salt-dependent rheology and surface tension of protein condensates using optical traps
An increasing number of proteins with intrinsically disordered domains have
been shown to phase separate in buffer to form liquid-like phases. These
protein condensates serve as simple models for the investigation of the more
complex membrane-less organelles in cells. To understand the function of such
proteins in cells, the material properties of the condensates they form are
important. However, these material properties are not well understood. Here, we
develop a novel method based on optical traps to study the frequency-dependent
rheology and the surface tension of PGL-3 condensates as a function of salt
concentration. We find that PGL-3 droplets are predominantly viscous but also
exhibit elastic properties. As the salt concentration is reduced, their elastic
modulus, viscosity and surface tension increase. Our findings show that salt
concentration has a strong influence on the rheology and dynamics of protein
condensates suggesting an important role of electrostatic interactions for
their material properties.Comment: 5 pages, 3 figures, 1 supplemen
Demographic performance of brownlip abalone : exploration of wild and cultured harvest potential
This research provides the most comprehensive evaluation of Brownlip abalone (Haliotis conicopora) biology and fisheries assessment to date, thereby laying a solid foundation for future management of the Brownlip abalone fishery in Western Australia (WA). For wild populations, it has provided the most reliable estimates of natural and fishing mortality, size composition and the first to model growth throughout all stages of life
Interstellar Carbodiimide (HNCNH) - A New Astronomical Detection from the GBT PRIMOS Survey via Maser Emission Features
In this work, we identify carbodiimide (HNCNH), which is an isomer of the
well-known interstellar species cyanamide (NH2CN), in weak maser emission,
using data from the GBT PRIMOS survey toward Sgr B2(N). All spectral lines
observed are in emission and have energy levels in excess of 170 K, indicating
that the molecule likely resides in relatively hot gas that characterizes the
denser regions of this star forming region. The anticipated abundance of this
molecule from ice mantle experiments is ~10% of the abundance of NH2CN, which
in Sgr B2(N) corresponds to ~2 x 10^13 cm-2. Such an abundance results in
transition intensities well below the detection limit of any current
astronomical facility and, as such, HNCNH could only be detected by those
transitions which are amplified by masing.Comment: Accepted in The Astrophysical Journal Letters, 13 pages, 2 figures,
generated using AAS LaTeX Macros v 5.
Spatial and Temporal Distribution of Imidacloprid Within the Crown of Eastern Hemlock
Systemic imidacloprid is the most widely used insecticide to control the hemlock woolly adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae), an exotic pest of eastern hemlock, Tsuga canadensis (L.) Carriére in the United States. This study was conducted to 1) determine the effect of treatment timing (spring vs. fall) and application method (trunk injection vs. soil injection) on the spatial and temporal distribution of imidacloprid within the crown of A. tsugae-free eastern hemlock using a competitive enzyme-linked immunosorbent assay (ELISA), 2) compare ELISA to gas chromatography-mass spectrometry (GC/MS) for the detection of imidacloprid in xylem fluid, and 3) determine the concentration of imidacloprid in leaf tissue using high performance liquid chromatography with tandem mass spectrometric (LC/MS/MS) detection methods. Xylem fluid concentrations of imidacloprid were found to be significantly higher for spring applications than for fall applications and for trunk injections than soil injections in the first year posttreatment. A total of 69% of samples analyzed by ELISA gave 1.8 times higher concentrations of imidacloprid than those found by GC/MS, leading to evidence of a matrix effect and overestimation of imidacloprid in xylem fluid by ELISA. A comparison of the presence of imidacloprid with xylem fluid and in leaf tissue on the same branch showed significant differences, suggesting that imidacloprid moved intermittently within the crown of eastern hemlock
- …