An Obligatory Role of Mind Bomb-1 in Notch Signaling of Mammalian Development

Background. The Notch signaling pathway is an evolutionarily conserved intercellular signaling module essential for cell fate specification that requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), cooperatively regulate the endocytosis of Notch ligands in Drosophila. However, the respective roles of the mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian development are poorly understood. Methodology/Principal Findings. Through extensive use of mammalian genetics, here we show that Neur1 and Neur2 double mutants and Mib2-1- mice were viable and grossly normal. In contrast, conditional inactivation of MW in various tissues revealed the representative Notch phenotypes: defects of arterial specification as deltalike4 mutants, abnormal cerebellum and skin development as jagged1 conditional mutants, and syndactylism as jagged2 mutants. Conclusions/Significance. Our data provide the first evidence that Mib1 is essential for Jagged as well as Deltalike ligand-mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2 are dispensable.open504

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Effect of tube diameter and capillary number on platelet margination and near-wall dynamics

The effect of tube diameter $D$ and capillary number $Ca$ on platelet margination in blood flow at $\approx 37\%$ tube haematocrit is investigated. The system is modelled as three-dimensional suspension of deformable red blood cells and nearly rigid platelets using a combination of the lattice-Boltzmann, immersed boundary and finite element methods. Results show that margination is facilitated by a non-diffusive radial platelet transport. This effect is important near the edge of the cell-free layer, but it is only observed for $Ca > 0.2$, when red blood cells are tank-treading rather than tumbling. It is also shown that platelet trapping in the cell-free layer is reversible for $Ca \leq 0.2$. Only for the smallest investigated tube ($D = 10 \mu\text{m}$) margination is essentially independent of $Ca$. Once platelets have reached the cell-free layer, they tend to slide rather than tumble. The tumbling rate is essentially independent of $Ca$ but increases with $D$. Tumbling is suppressed by the strong confinement due to the relatively small cell-free layer thickness at $\approx 37\%$ tube haematocrit.Comment: 16 pages, 10 figure

Objective and Subjective Factors as Predictors of Post-Traumatic Stress Symptoms in Parents of Children with Cancer – A Longitudinal Study

BACKGROUND: Parents of children with cancer report post-traumatic stress symptoms (PTSS) years after the child's successful treatment is completed. The aim of the present study was to analyze a number of objective and subjective childhood cancer-related factors as predictors of parental PTSS. METHODS: Data were collected from 224 parents during and after their child's cancer treatment. Data sources include self-report questionnaires and medical records. RESULTS: In a multivariate hierarchical model death of the child, parent's perception of child psychological distress and total symptom burden predicted higher levels of PTSS. In addition, immigrants and unemployed parents reported higher levels of PTSS. The following factors did not predict PTSS: parent gender, family income, previous trauma, child's prognosis, treatment intensity, non-fatal relapse, and parent's satisfaction with the child's care. CONCLUSIONS: Although medical complications can be temporarily stressful, a parent's perception of the child's distress is a more powerful predictor of parental PTSS. The vulnerability of unemployed parents and immigrants should be acknowledged. In addition, findings highlight that the death of a child is as traumatic as could be expected

Optical identification of electronic state levels of an asymmetric InAs/InGaAs/GaAs dot-in-well structure

We have studied the electronic state levels of an asymmetric InAs/InGaAs/GaAs dot-in-well structure, i.e., with an In0.15Ga0.85As quantum well (QW) as capping layer above InAs quantum dots (QDs), via temperature-dependent photoluminescence, photo-modulated reflectance, and rapid thermal annealing (RTA) treatments. It is shown that the carrier transfer via wetting layer (WL) is impeded according to the results of temperature dependent peak energy and line width variation of both the ground states (GS) and excited states (ES) of QDs. The quenching of integrated intensity is ascribed to the thermal escape of electron from the dots to the complex In0.15Ga0.85As QW + InAs WL structure. Additionally, as the RTA temperature increases, the peak of PL blue shifts and the full width at half maximum shrinks. Especially, the intensity ratio of GS to ES reaches the maximum when the energy difference approaches the energy of one or two LO phonon(s) of InAs bulk material, which could be explained by phonon-enhanced inter-sublevels carrier relaxation in such asymmetric dot-in-well structure

Decreased brain venous vasculature visibility on susceptibility-weighted imaging venography in patients with multiple sclerosis is related to chronic cerebrospinal venous insufficiency.

BACKGROUND: The potential pathogenesis between the presence and severity of chronic cerebrospinal venous insufficiency (CCSVI) and its relation to clinical and imaging outcomes in brain parenchyma of multiple sclerosis (MS) patients has not yet been elucidated. The aim of the study was to investigate the relationship between CCSVI, and altered brain parenchyma venous vasculature visibility (VVV) on susceptibility-weighted imaging (SWI) in patients with MS and in sex- and age-matched healthy controls (HC). METHODS: 59 MS patients, 41 relapsing-remitting and 18 secondary-progressive, and 33 HC were imaged on a 3T GE scanner using pre- and post-contrast SWI venography. The presence and severity of CCSVI was determined using extra-cranial and trans-cranial Doppler criteria. Apparent total venous volume (ATVV), venous intracranial fraction (VIF) and average distance-from-vein (DFV) were calculated for various vein mean diameter categories: .9 mm. RESULTS: CCSVI criteria were fulfilled in 79.7% of MS patients and 18.2% of HC (p < .0001). Patients with MS showed decreased overall ATVV, ATVV of veins with a diameter < .3 mm, and increased DFV compared to HC (all p < .0001). Subjects diagnosed with CCSVI had significantly increased DFV (p < .0001), decreased overall ATVV and ATVV of veins with a diameter < .3 mm (p < .003) compared to subjects without CCSVI. The severity of CCSVI was significantly related to decreased VVV in MS (p < .0001) on pre- and post-contrast SWI, but not in HC. CONCLUSIONS: MS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012