With the continuous growth of internet usage, Google Trends has emerged as a source of information to investigate how social trends evolve over time. Knowing how the level of interest in conservation ...topics--approximated using Google search volume--varies over time can help support targeted conservation science communication. However, the evolution of search volume over time and the mechanisms that drive peaks in searches are poorly understood. We conducted time series analyses on Google search data from 2004 to 2013 to investigate: (i) whether interests in selected conservation topics have declined and (ii) the effect of news reporting and academic publishing on search volume. Although trends were sensitive to the term used as benchmark, we did not find that public interest towards conservation topics such as climate change, ecosystem services, deforestation, orangutan, invasive species and habitat loss was declining. We found, however, a robust downward trend for endangered species and an upward trend for ecosystem services. The quantity of news articles was related to patterns in Google search volume, whereas the number of research articles was not a good predictor but lagged behind Google search volume, indicating the role of news in the transfer of conservation science to the public.
Adaptive B cell responses are initiated by B cell receptor–antigen engagement. Despite its importance, the early stages of B cell interaction with antigen in vivo remain elusive. Using fluorescent ...particulate antigen in combination with multiphoton microscopy and immune staining, we identified the follicle-subcapsular sinus (SCS) boundary of the lymph node as a site for B cell-antigen acquisition. In this macrophage-rich region, antigen accumulated shortly after administration, where specific follicular B cells were retained for long periods of time. These B cells acquired antigen cumulatively and became the main antigen carriers inside the follicle before polarizing to the B cell-T cell border. These observations not only provide evidence of a B cell role as antigen transporters into the follicle, but also highlight the boundary between the follicle and the SCS as a site for initiation of B cell responses.
Papillary craniopharyngiomas (PCPs) are particularly challenging lesions requiring accurate diagnosis to plan the best therapy. Our aim was to define a narrow duct-like recess identified on MR ...imaging at the base of papillary craniopharyngiomas with a strict third ventricle location.
A duct-like recess at the infundibular portion of craniopharyngiomas was observed on conventional T1WI and T2WI in 3 strict third ventricle papillary craniopharyngiomas in our craniopharyngioma series (
= 125). We systematically investigated this finding on the MR imaging of 2582 craniopharyngiomas and 10 other categories of third ventricle tumors (
= 690) published in the modern era (1986-2020). The diagnostic value and significance of this finding are addressed.
The duct-like recess was recognized in 52 papillary craniopharyngiomas, including 3 of our own cases, as a narrow canal-shaped cavity invaginated at the tumor undersurface, just behind the optic chiasm. This structure largely involves papillary craniopharyngiomas with a strict third ventricle topography (96%), follows the same diagonal trajectory as the pituitary stalk, and finishes at a closed end. The duct-like recess sign identifies the papillary craniopharyngioma type with a specificity of 100% and a sensitivity of 38% in the overall craniopharyngioma population. This finding can also establish the strictly intra-third ventricle location of the lesion with a 90% specificity and 33% sensitivity. These recesses appear as hypointense circular spots on axial/coronal T1WI and T2WI. Their content apparently corresponds to CSF freely flowing within the suprasellar cistern.
The presence of a duct-like recess at the infundibular portion of a third ventricle tumor represents a distinctive hallmark of papillary craniopharyngiomas that can be used as a simple MR imaging sign to reliably diagnose these lesions.
Highlights • Opioid analgesics that are unused after surgery may contribute to drug diversion. • 54% of opioids in this study remained unused 3 weeks after dental surgery. • Little research has ...examined pharmacy programs to promote safe drug disposal. • Patients in our intervention were more willing to dispose of unused opioids.
Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in ...transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis.
Abstract
We present a photometric analysis of globular cluster 47 Tuc (NGC 104) using near-IR imaging data from the GeMS/GSAOI Galactic Globular Cluster Survey (G4CS), which is in operation at ...Gemini-South telescope. Our survey is designed to obtain AO-assisted deep imaging with near diffraction-limited spatial resolution of the central fields of Milky Way globular clusters. The G4CS near-IR photometry was combined with an optical photometry catalog that was obtained from Hubble Space Telescope survey data to produce a high-quality color–magnitude diagram that reaches down to
K
s
≈ 21 Vega mag. We used the software suite BASE-9, which uses an adaptive Metropolis sampling algorithm to perform a Markov chain Monte Carlo Bayesian analysis, and obtained probability distributions and precise estimates for the age, distance, and extinction cluster parameters. Our best estimate for the age of 47 Tuc is
12.42
−
0.05
+
0.05
± 0.08 Gyr and our true distance modulus estimate is (
m
−
M
)
0
= 13.250
−
0.003
+
0.003
± 0.028 mag, which are in tight agreement with previous studies using Gaia DR2 parallax and detached eclipsing binaries.
B cells recognize foreign antigens by virtue of cell surface immunoglobulin receptors and are most effectively activated by membrane-bound ligands. Here, we show that in the early stages of this ...process, B cells exhibit a two-phase response in which they first spread over the antigen-bearing membrane and then contract, thereby collecting bound antigen into a central aggregate. The extent of this response, which is both signaling- and actin-dependent, determines the quantity of antigen accumulated and hence the degree of B cell activation. Brownian dynamic simulations reproduce essential features of the antigen collection process and suggest a possible basis for affinity discrimination. We propose that dynamic spreading is an important step of the immune response.
Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved ...in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival. Either genetic knockdown or pharmacological inhibition of PRMT5 with the inhibitor EPZ015666 significantly inhibited growth of both cell lines and patient MM cells. Furthermore, PRMT5 inhibition abrogated NF-κB signaling. Interestingly, mass spectrometry identified a tripartite motif-containing protein 21 TRIM21 as a new PRMT5-partner, and we delineated a TRIM21-dependent mechanism of NF-κB inhibition. Importantly, oral administration of EPZ015666 significantly decreased MM growth in a humanized murine model of MM. These data both demonstrate the oncogenic role and prognostic relevance of PRMT5 in MM pathogenesis, and provide the rationale for novel therapies targeting PRMT5 to improve patient outcome.
Proteasome inhibition is an effective therapy for multiple myeloma (MM) patients; however, the emergence of drug resistance is common. Novel therapeutic strategies to overcome proteasome inhibitor ...resistance are needed. In this study, we examined whether targeting deubiquitylating (DUB) enzymes upstream of 20S proteasome overcomes proteasome inhibitor resistance. Gene expression analysis, immunohistochemical studies of MM patient bone marrow, reverse transcription-PCR and protein analysis show that Rpn11/POH1, a DUB enzyme upstream of 20S proteasome, is more highly expressed in patient MM cells than in normal plasma cells. Importantly, Rpn11 expression directly correlates with poor patient survival. Loss-of-function studies show that Rpn11-siRNA knockdown decreases MM cell viability. Pharmacological inhibition of Rpn11 with O-phenanthroline (OPA) blocks cellular proteasome function, induces apoptosis in MM cells and overcomes resistance to proteasome inhibitor bortezomib. Mechanistically, Rpn11 inhibition in MM cells activates caspase cascade and endoplasmic stress response signaling. Human MM xenograft model studies demonstrate that OPA treatment reduces progression of tumor growth and prolongs survival in mice. Finally, blockade of Rpn11 increases the cytotoxic activity of anti-MM agents lenalidomide, pomalidomide or dexamethasone. Overall, our preclinical data provide the rationale for targeting DUB enzyme Rpn11 upstream of 20S proteasome to enhance cytotoxicity and overcome proteasome inhibitor resistance in MM.
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