Unusual Medial-End Clavicle Fracture Combined with Double Disruption of the Superior Shoulder Suspensory Complex (SSSC) : A Case Report in Triathlon Athlete

Most published floating clavicle report a dislocation or fracture of one or both ends of the clavicle

A Keplerian Disk around the Herbig Ae star HD169142

We present Submillimeter Array observations of the Herbig Ae star HD169142 in 1.3 millimeter continuum emission and 12CO J=2-1 line emission at 1.5 arcsecond resolution that reveal a circumstellar disk. The continuum emission is centered on the star position and resolved, and provides a mass estimate of about 0.02 solar masses for the disk. The CO images show patterns in position and velocity that are well matched by a disk in Keplerian rotation with low inclination to the line-of-sight. We use radiative transfer calculations based on a flared, passive disk model to constrain the disk parameters by comparison to the spectral line emission. The derived disk radius is 235 AU, and the inclination is 13 degrees. The model also necessitates modest depletion of the CO molecules, similar to that found in Keplerian disks around T Tauri stars.Comment: 10 pages, 2 figures, accepted by A

Chemotherapy in patients with early breast cancer: clinical overview and management of long-term side effects

Introduction: Neo/adjuvant therapy for early-stage breast cancer has become increasingly common in the last few decades; as a consequence, the number of breast cancer survivors experiencing often debilitating long-term side effects has increased, and thus the need for a comprehensive approach to the variety of symptoms involved. Areas covered and methods: We performed a literature search on the main public scientific databases (PubMed, Embase, Cochrane, and CrossRef) from 2000 to April 2022 to identify prevention and management strategies for the most common long-term side effects, including fatigue, insomnia, peripheral neuropathy, cognitive impairment, estrogen deprivation, cardiotoxicity, and second cancers. Expert opinion: Long-term toxicities may affect a majority of breast cancer survivors, significantly interfering with their quality of life. Although there are guidelines for the management of isolated side effects, such as peripheral neuropathy, we aim to provide a more inclusive clinical-oriented approach, focusing on both prevention and therapeutic strategies

Investigating physicochemical, volatile and sensory parameters playing a positive or a negative role on tomato liking

This study aimed at providing further insights into the positive and negative drivers of tomato liking. For this purpose, 13 tomato cultivars representing different typologies were characterized for physicochemical parameters and aroma volatiles, and were assessed by a trained panel for sensory descriptors, and by Italian consumers for liking. The relationships among the different parameters and their effects on consumer liking were studied by Partial Least Squares (PLS) analysis. Among physicochemical traits and sensory descriptors, seeds, reducing sugars, firmness, thick epicarp, soluble solids, sour taste, total acidity, citrate, herbaceous aroma and brightness were found to be drivers of liking, whereas pulp thickness, humidity, fruit weight, diacetyl-like odor and mealiness showed an opposite influence. For the aroma volatiles, 2-isobutylthiazole played a key role on liking and its positive contribution seemed to be supported by (Z)-3-hexen-1-ol, but suppressed by 6-methyl-5-hepten-2-ol, especially when tomatoes had a poor volatile fraction. These results represent a contribution to the knowledge that could lead to more effective breeding strategies aimed at improving tomato sensory quality. (c) 2012 Elsevier Ltd. All rights reserved

The Dually Acylated NH2-terminal Domain of Gi1α Is Sufficient to Target a Green Fluorescent Protein Reporter to Caveolin-enriched Plasma Membrane Domains: PALMITOYLATION OF CAVEOLIN-1 IS REQUIRED FOR THE RECOGNITION OF DUALLY ACYLATED G-PROTEIN α SUBUNITS IN VIVO

Here we investigate the molecular mechanisms that govern the targeting of G-protein α subunits to the plasma membrane. For this purpose, we used Gi1α as a model dually acylated G-protein. We fused full-length Gi1α or its extreme NH2-terminal domain (residues 1–32 or 1–122) to green fluorescent protein (GFP) and analyzed the subcellular localization of these fusion proteins. We show that the first 32 amino acids of Gi1α are sufficient to target GFP to caveolin-enriched domains of the plasma membrane in vivo, as demonstrated by co-fractionation and co-immunoprecipitation with caveolin-1. Interestingly, when dual acylation of this 32-amino acid domain was blocked by specific point mutations (G2A or C3S), the resulting GFP fusion proteins were localized to the cytoplasm and excluded from caveolin-rich regions. The myristoylated but nonpalmitoylated (C3S) chimera only partially partitioned into caveolin-containing fractions. However, both nonacylated GFP fusions (G2A and C3S) no longer co-immunoprecipitated with caveolin-1. Taken together, these results indicate that lipid modification of the NH2-terminal of Gi1α is essential for targeting to its correct destination and interaction with caveolin-1. Also, a caveolin-1 mutant lacking all three palmitoylation sites (C133S, C143S, and C156S) was unable to co-immunoprecipitate these dually acylated GFP-G-protein fusions. Thus, dual acylation of the NH2-terminal domain of Gi1α and palmitoylation of caveolin-1 are both required to stabilize and perhaps regulate this reciprocal interaction at the plasma membrane in vivo. Our results provide the first demonstration of a functional role for caveolin-1 palmitoylation in its interaction with signaling molecules

FoxO3a as a positive prognostic marker and a therapeutic target in Tamoxifen-resistant breast cancer

Background: Resistance to endocrine treatments is a major clinical challenge in the management of estrogen receptor positive breast cancers. Although multiple mechanisms leading to endocrine resistance have been proposed, the poor outcome of this subgroup of patients demands additional studies. Methods: FoxO3a involvement in the acquisition and reversion of tamoxifen resistance was assessed in vitro in three parental ER+ breast cancer cells, MCF-7, T47D and ZR-75-1, in the deriving Tamoxifen resistant models (TamR) and in Tet-inducible TamR/FoxO3a stable cell lines, by growth curves, PLA, siRNA, RT-PCR, Western blot, Immunofluorescence, Transmission Electron Microscopy, TUNEL, cell cycle, proteomics analyses and animal models. FoxO3a clinical relevance was validated in silico by Kaplan−Meier survival curves. Results: Here, we show that tamoxifen resistant breast cancer cells (TamR) express low FoxO3a levels. The hyperactive growth factors signaling, characterizing these cells, leads to FoxO3a hyper-phosphorylation and subsequent proteasomal degradation. FoxO3a re-expression by using TamR tetracycline inducible cells or by treating TamR with the anticonvulsant lamotrigine (LTG), restored the sensitivity to the antiestrogen and strongly reduced tumor mass in TamR-derived mouse xenografts. Proteomics data unveiled novel potential mediators of FoxO3a anti-proliferative and pro-apoptotic activity, while the Kaplan−Meier analysis showed that FoxO3a is predictive of a positive response to tamoxifen therapy in Luminal A breast cancer patients. Conclusions: Altogether, our data indicate that FoxO3a is a key target to be exploited in endocrine-resistant tumors. In this context, LTG, being able to induce FoxO3a, might represent a valid candidate in combination therapy to prevent resistance to tamoxifen in patients at risk

Prospects For Identifying Dark Matter With CoGeNT

It has previously been shown that the excess of events reported by the CoGeNT collaboration could be generated by elastically scattering dark matter particles with a mass of approximately 5-15 GeV. This mass range is very similar to that required to generate the annual modulation observed by DAMA/LIBRA and the gamma rays from the region surrounding the Galactic Center identified within the data of the Fermi Gamma Ray Space Telescope. To confidently conclude that CoGeNT's excess is the result of dark matter, however, further data will likely be needed. In this paper, we make projections for the first full year of CoGeNT data, and for its planned upgrade. Not only will this body of data more accurately constrain the spectrum of nuclear recoil events, and corresponding dark matter parameter space, but will also make it possible to identify seasonal variations in the rate. In particular, if the CoGeNT excess is the product of dark matter, then one year of CoGeNT data will likely reveal an annual modulation with a significance of 2-3$\sigma$. The planned CoGeNT upgrade will not only detect such an annual modulation with high significance, but will be capable of measuring the energy spectrum of the modulation amplitude. These measurements will be essential to irrefutably confirming a dark matter origin of these events.Comment: 6 pages, 6 figure

CAV1 inhibits metastatic potential in melanomas through suppression of the Integrin/Src/FAK signaling pathway.

Caveolin-1 (CAV1) is the main structural component of Caveolae which are plasma membrane invaginations that participate in vesicular trafficking and signal transduction events. Although, evidence has recently accumulated describing the function of CAV1 in several cancer types, its role in melanoma tumor formation and progression remains poorly explored. Here, by employing B16F10 melanoma cells as an experimental system, we directly explore the function of CAV1 in melanoma tumor growth and metastasis. We first show that CAV1 expression promotes proliferation while it suppresses migration and invasion of B16F10 cells in vitro. When orthotopically implanted in the skin of mice, B16F10 cells expressing CAV1 form tumors that are similar in size to their control counterpart. An experimental metastasis assay demonstrates that CAV1 expression suppresses the ability of B16F10 cells to form lung metastases in C57Bl/6 syngeneic mice. Additionally, CAV1 protein and mRNA levels are found to be significantly reduced in human metastatic melanoma cell lines and human tissue from metastatic lesions. Finally, we demonstrate that following integrin activation, B16F10 cells expressing CAV1 display reduced expression levels and activity of FAK and Src proteins. CAV1 expression also markedly reduces the expression levels of beta3 Integrin in B16F10 melanoma cells. In summary, our findings provide experimental evidence that CAV1 may function as an antimetastatic gene in malignant melanoma

Requirement of transcription factor NFAT in developing atrial myocardium

Nuclear factor of activated T cell (NFAT) is a ubiquitous regulator involved in multiple biological processes. Here, we demonstrate that NFAT is temporally required in the developing atrial myocardium between embryonic day 14 and P0 (birth). Inhibition of NFAT activity by conditional expression of dominant-negative NFAT causes thinning of the atrial myocardium. The thin myocardium exhibits severe sarcomere disorganization and reduced expression of cardiac troponin-I (cTnI) and cardiac troponin-T (cTnT). Promoter analysis indicates that NFAT binds to and regulates transcription of the cTnI and the cTnT genes. Thus, regulation of cytoskeletal protein gene expression by NFAT may be important for the structural architecture of the developing atrial myocardium