Orbital characterization of GJ1108A system, and comparison of dynamical mass with model-derived mass for resolved binaries

We report an orbital characterization of GJ1108Aab that is a low-mass binary system in pre-main-sequence phase. Via the combination of astrometry using adaptive optics and radial velocity measurements, an eccentric orbital solution of $e$=0.63 is obtained, which might be induced by the Kozai-Lidov mechanism with a widely separated GJ1108B system. Combined with several observed properties, we confirm the system is indeed young. Columba is the most probable moving group, to which the GJ1108A system belongs, although its membership to the group has not been established. If the age of Columba is assumed for GJ1108A, the dynamical masses of both GJ1108Aa and GJ1108Ab ($M_{\rm dynamical,GJ1108Aa}=0.72\pm0.04 M_{\odot}$ and $M_{\rm dynamical,GJ1108Ab}=0.30\pm0.03 M_{\odot}$) are more massive than what an evolutionary model predicts based on the age and luminosities. We consider the discrepancy in mass comparison can attribute to an age uncertainty; the system is likely older than stars in Columba, and effects that are not implemented in classical models such as accretion history and magnetic activity are not preferred to explain the mass discrepancy. We also discuss the performance of the evolutionary model by compiling similar low-mass objects in evolutionary state based on the literature. Consequently, it is suggested that the current model on average reproduces the mass of resolved low-mass binaries without any significant offsets.Comment: Accepted in Ap

A Large Double-ring Disk Around the Taurus M Dwarf J04124068+2438157

Planet formation imprints signatures on the physical structures of disks. In this paper, we present high-resolution (∼50 mas, 8 au) Atacama Large Millimeter/submillimeter Array observations of 1.3 mm dust continuum and CO line emission toward the disk around the M3.5 star 2MASS J04124068+2438157. The dust disk consists of only two narrow rings at radial distances of 0.″47 and 0.″78 (∼70 and 116 au), with Gaussian σ widths of 5.6 and 8.5 au, respectively. The width of the outer ring is smaller than the estimated pressure scale height by ∼25%, suggesting dust trapping in a radial pressure bump. The dust disk size, set by the location of the outermost ring, is significantly larger (by 3σ) than other disks with similar millimeter luminosity, which can be explained by an early formation of local pressure bump to stop radial drift of millimeter dust grains. After considering the disk’s physical structure and accretion properties, we prefer planet-disk interaction over dead zone or photoevaporation models to explain the observed dust disk morphology. We carry out high-contrast imaging at the L ′ band using Keck/NIRC2 to search for potential young planets, but do not identify any source above 5σ. Within the dust gap between the two rings, we reach a contrast level of ∼7 mag, constraining the possible planet below ∼2-4 M Jup. Analyses of the gap/ring properties suggest that an approximately Saturn-mass planet at ∼90 au is likely responsible for the formation of the outer ring, which can potentially be revealed with JWST

Direct images and spectroscopy of a giant protoplanet driving spiral arms in MWC 758

Understanding the driving forces behind spiral arms in protoplanetary disks remains a challenge due to the faintness of young giant planets. MWC 758 hosts such a protoplanetary disk with a two-armed spiral pattern that is suggested to be driven by an external giant planet. We present new thermal infrared observations that are uniquely sensitive to redder (i.e., colder or more attenuated) planets than past observations at shorter wavelengths. We detect a giant protoplanet, MWC 758c, at a projected separation of ~100 au from the star. The spectrum of MWC 758c is distinct from the rest of the disk and consistent with emission from a planetary atmosphere with Teff = 500 +/- 100 K for a low level of extinction (AV<30), or a hotter object with a higher level of extinction. Both scenarios are commensurate with the predicted properties of the companion responsible for driving the spiral arms. MWC 758c provides evidence that spiral arms in protoplanetary disks can be caused by cold giant planets or by those whose optical emission is highly attenuated. MWC 758c stands out both as one of the youngest giant planets known, and also as one of the coldest and/or most attenuated. Furthermore, MWC 758c is among the first planets to be observed within a system hosting a protoplanetary disk.Comment: Published in Nature Astronom

TIG3 Tumor Suppressor-Dependent Organelle Redistribution and Apoptosis in Skin Cancer Cells

TIG3 is a tumor suppressor protein that limits keratinocyte survival during normal differentiation. It is also important in cancer, as TIG3 level is reduced in tumors and in skin cancer cell lines, suggesting that loss of expression may be required for cancer cell survival. An important goal is identifying how TIG3 limits cell survival. In the present study we show that TIG3 expression in epidermal squamous cell carcinoma SCC-13 cells reduces cell proliferation and promotes morphological and biochemical apoptosis. To identify the mechanism that drives these changes, we demonstrate that TIG3 localizes near the centrosome and that pericentrosomal accumulation of TIG3 alters microtubule and microfilament organization and organelle distribution. Organelle accumulation at the centrosome is a hallmark of apoptosis and we demonstrate that TIG3 promotes pericentrosomal organelle accumulation. These changes are associated with reduced cyclin D1, cyclin E and cyclin A, and increased p21 level. In addition, Bax level is increased and Bcl-XL level is reduced, and cleavage of procaspase 3, procaspase 9 and PARP is enhanced. We propose that pericentrosomal localization of TIG3 is a key event that results in microtubule and microfilament redistribution and pericentrosomal organelle clustering and that leads to cancer cell apoptosis

Total gastrectomy with simultaneous pancreaticosplenectomy or splenectomy in patients with advanced gastric carcinoma

A splenectomy or distal pancreaticosplenectomy is often performed simultaneously with total gastrectomy in the treatment of gastric carcinoma to facilitate dissection of the lymph nodes around the splenic artery and splenic hilus. However, the negative impact of splenectomy and pancreaticosplenectomy has also been reported. A retrospective analysis was performed to evaluate the outcomes of distal pancreaticosplenectomy and total gastrectomy, splenectomy and total gastrectomy, and gastrectomy alone in the patients with advanced gastric carcinoma without distant metastasis. Prognostic factors were examined. No significant differences existed in 5-year survival in the patients who underwent gastrectomy with splenectomy, gastrectomy with distal pancreaticosplenectomy, or gastrectomy alone. Neither splenectomy, nor distal pancreaticosplenectomy were prognostic factors. However, distal pancreaticosplenectomy was an independent predictor of pancreatic fistula. In conclusion, the addition of distal pancreaticosplenectomy or splenectomy to total gastrectomy for gastric cancer increases the risk of severe complications, but does not improve survival. © 1999 Cancer Research Campaig

Adoption and decision factors regarding selective treatment of clinical mastitis on Canadian dairy farms

As clinical mastitis (CM) treatments are responsible for a large portion of antimicrobial use on dairy farms, many selective CM treatment protocols have been developed and evaluated against a blanket treatment approach of CM cases. Selective treatment protocols use outcomes of diagnostic tests to exclude CM cases from antimicrobial treatment when they are unlikely to benefit. To tailor interventions to increase uptake of selective treatment strategies, a comprehension of current on-farm treatment practices and factors affecting treatment decisions is vital. Two questionnaires were conducted among 142 farms across 5 provinces participating in the Canadian Dairy Network for Antimicrobial Stewardship and Resistance in this cross-sectional study. Self-reported adoption of selective CM treatments by dairy farmers was 64%, with median of 82% of cows treated in those herds using selective treatment. Using logistic regression models, the odds to implement a selective CM treatment protocol increased with a decreasing average cow somatic cell count. No other associations were identified between use of a selective CM treatment protocol and farm characteristics (herd size, CM incidence, province, milking system, and housing system). Three subsets of farmers making cow-level CM treatment decisions were identified using a cluster analysis approach: those who based decisions almost exclusively on severity of clinical signs, those who used various udder health indicators, and farmers who also incorporated more general cow information such as production, age, and genetics. When somatic cell count was considered, the median threshold used for treating was >300,000 cells/mL at the last Dairy Herd Improvement test. Various thresholds were present among those considering CM case history. Veterinary laboratories were most frequently used for bacteriological testing. Test results were used to start, change, and stop treatments. Regardless of protocol, reasons for antimicrobial treatment withheld included cow being on a cull list, having a chronic intramammary infection, or being at end of lactation (i.e., close to dry off). If clinical signs persisted after treatment, farmers indicated that they would ask veterinarians for advice, stop treatment, or continue with the same or different antibiotics. Results of this study can be used to design interventions targeting judicious mastitis-related antimicrobial use, and aid discussions between veterinarians and dairy producers regarding CM-related antimicrobial use

Pluronic® block-copolymers in medicine: from chemical and biological versatility to rationalisation and clinical advances

YesThis mini-review highlights the latest advances in the chemistry and biology of Pluronic® triblock copolymers. We focus on their applications in medicine, as drug delivery carriers, biological response modifiers, and pharmaceutical ingredients. Examples of drug delivery systems and formulations currently in clinical use, clinical trials or preclinical development are highlighted. We also discuss the role that Pluronic® copolymers may play in the innovative design of new nanomedicines in the near future.We thank the Leverhulme Trust (Early Career Fellowship no. ECF-2013-414 to NPEB), the University of Warwick (Grant no. RDF 2013-14 to NPEB) and EPSRC (EP/G004897/1 to APB) for support

Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes

We prepared small unilamellar liposomes derivatised with single chain antibody fragments specific for the ED-B domain of B-fibronectin. This extracellular matrix associated protein is expressed around newly forming blood vessels in the vicinity of many types of tumours. The single chain antibody fragments were functionalised by introduction of C-terminal cysteines and linked to liposomes via maleimide groups located at the terminal ends of poly(ethylene glycol) modified phospholipids. The properties of these anti-ED-B single chain antibody fragments-liposomes were analysed in vitro on ED-B fibronectin expressing Caco-2 cells and in vivo by studying their biodistribution and their therapeutic potential in mice bearing subcutanous F9 teratocarcinoma tumours. Radioactively labelled (114mIndium) single chain antibody fragments-liposomes accumulated in the tumours at 2–3-fold higher concentrations during the first 2 h after i.v. injection compared to unmodified liposomes. After 6–24 h both liposome types were found in similar amounts (8–10% injected dose g−1) in the tumours. Animals treated i.v. with single chain antibody fragments-liposomes containing the new cytotoxic agent 2′-deoxy-5-fluorouridylyl-N4-octadecyl-1-β-D-arabinofuranosylcytosine (30 mg kg-1 per dose, five times every 24 h) showed a reduction of tumour growth by 62–90% determined on days 5 and 8, respectively, compared to animals receiving control liposomes. Histological analysis revealed a marked reduction of F9 tumour cells and excessive deposition of fibronectin in the extracellular matrix after treatment with single chain antibody fragments-2-dioxy-5-fluorouridylyl-N4-octadecyl-1-β-D-arabinofuranosylcytosine-liposomes. Single chain antibody fragments-liposomes targeted to ED-B fibronectin positive tumours therefore represent a promising and versatile novel drug delivery system for the treatment of tumours

Influence of the Stability of a Fused Protein and Its Distance to the Amyloidogenic Segment on Fibril Formation

Conversion of native proteins into amyloid fibrils is irreversible and therefore it is difficult to study the interdependence of conformational stability and fibrillation by thermodynamic analyses. Here we approached this problem by fusing amyloidogenic poly-alanine segments derived from the N-terminal domain of the nuclear poly (A) binding protein PABPN1 with a well studied, reversibly unfolding protein, CspB from Bacillus subtilis. Earlier studies had indicated that CspB could maintain its folded structure in fibrils, when it was separated from the amyloidogenic segment by a long linker. When CspB is directly fused with the amyloidogenic segment, it unfolds because its N-terminal chain region becomes integrated into the fibrillar core, as shown by protease mapping experiments. Spacers of either 3 or 16 residues between CspB and the amyloidogenic segment were not sufficient to prevent this loss of CspB structure. Since the low thermodynamic stability of CspB (ΔGD = 12.4 kJ/mol) might be responsible for unfolding and integration of CspB into fibrils, fusions with a CspB mutant with enhanced thermodynamic stability (ΔGD = 26.9 kJ/mol) were studied. This strongly stabilized CspB remained folded and prevented fibril formation in all fusions. Our data show that the conformational stability of a linked, independently structured protein domain can control fibril formation

TRAPPC4-ERK2 Interaction Activates ERK1/2, Modulates Its Nuclear Localization and Regulates Proliferation and Apoptosis of Colorectal Cancer Cells

The trafficking protein particle complex 4 (TRAPPC4) is implicated in vesicle-mediated transport, but its association with disease has rarely been reported. We explored its potential interaction with ERK2, part of the ERK1/2 complex in the Extracellular Signal-regulated Kinase/ Mitogen-activated Protein Kinase (ERK-MAPK) pathway, by a yeast two-hybrid screen and confirmed by co-immunoprecipitation (Co-IP) and glutathione S-transferase (GST) pull-down. Further investigation found that when TRAPPC4 was depleted, activated ERK1/2 specifically decreased in the nucleus, which was accompanied with cell growth suppression and apoptosis in colorectal cancer (CRC) cells. Overexpression of TRAPPC4 promoted cell viability and caused activated ERK1/2 to increase overall, but especially in the nucleus. TRAPPC4 was expressed more highly in the nucleus of CRC cells than in normal colonic epithelium or adenoma which corresponded with nuclear staining of pERK1/2. We demonstrate here that TRAPPC4 may regulate cell proliferation and apoptosis in CRC by interaction with ERK2 and subsequently phosphorylating ERK1/2 as well as modulating the subcellular location of pERK1/2 to activate the relevant signaling pathway