Intracellular Electric Field and pH Optimize Protein Localization and Movement

Mammalian cell function requires timely and accurate transmission of information from the cell membrane (CM) to the nucleus (N). These pathways have been intensively investigated and many critical components and interactions have been identified. However, the physical forces that control movement of these proteins have received scant attention. Thus, transduction pathways are typically presented schematically with little regard to spatial constraints that might affect the underlying dynamics necessary for protein-protein interactions and molecular movement from the CM to the N. We propose messenger protein localization and movements are highly regulated and governed by Coulomb interactions between: 1. A recently discovered, radially directed E-field from the NM into the CM and 2. Net protein charge determined by its isoelectric point, phosphorylation state, and the cytosolic pH. These interactions, which are widely applied in elecrophoresis, provide a previously unknown mechanism for localization of messenger proteins within the cytoplasm as well as rapid shuttling between the CM and N. Here we show these dynamics optimize the speed, accuracy and efficiency of transduction pathways even allowing measurement of the location and timing of ligand binding at the CM –previously unknown components of intracellular information flow that are, nevertheless, likely necessary for detecting spatial gradients and temporal fluctuations in ligand concentrations within the environment. The model has been applied to the RAF-MEK-ERK pathway and scaffolding protein KSR1 using computer simulations and in-vitro experiments. The computer simulations predicted distinct distributions of phosphorylated and unphosphorylated components of this transduction pathway which were experimentally confirmed in normal breast epithelial cells (HMEC)

Clinical and surgical data of affected members of a classic CFEOM 1 family

BACKGROUND: Congenital fibiosis of the extraocular muscles (CFEOM1) refers to a group of congenital eye movement disorders that are characterized by non-progressive restrictive ophthalmoplegia. We present clinical and surgical data on affected members of a classic CFEOM1 family. METHODS: Ten members of a fifteen-member, three-generation Italian family affected by classic CFEOM participated in this study. Each affected family member underwent ophthalmologic (corrected visual acuity, pupillary function, anterior segment and fundus examination), orthoptic (cover test, cover-uncover test, prism alternate cover test), and preoperative examinations. Eight of the ten affected members had surgery and underwent postoperative examinations. Surgical procedures are listed. RESULTS: All affected members were born with varying degrees of bilateral ptosis and ophthalmoplegia with both eyes fixed in a hypotropic position (classic CFEOM). The affected members clinical data prior to surgery, surgery procedures and postoperative outcomes are presented. On 14 operated eyes to correct ptosis there was an improvement in 12 eyes. In addition, the head position improved in all patients. CONCLUSIONS: Surgery is effective at improving ptosis in the majority of patients with classic CFEOM. However, the surgical approach should be individualized to each patient, as inherited CFEOM exhibits variable expressivity and the clinical features may differ markedly between affected individuals, even within the same family

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Ultrasonic reflection coefficient and surface roughness index of OA articular cartilage: relation to pathological assessment

<p>Abstract</p> <p>Background</p> <p>Early diagnosis of Osteoarthritis (OA) is essential for preventing further cartilage destruction and decreasing severe complications. The aims of this study are to explore the relationship between OA pathological grades and quantitative acoustic parameters and to provide more objective criteria for ultrasonic microscopic evaluation of the OA cartilage.</p> <p>Methods</p> <p>Articular cartilage samples were prepared from rabbit knees and scanned using ultrasound biomicroscopy (UBM). Three quantitative parameters, including the roughness index of the cartilage surface (URI), the reflection coefficients from the cartilage surface (R) and from the cartilage-bone interface (R_bone) were extracted. The osteoarthritis grades of these cartilage samples were qualitatively assessed by histology according to the grading standards of International Osteoarthritis Institute (OARSI). The relationship between these quantitative parameters and the osteoarthritis grades was explored.</p> <p>Results</p> <p>The results showed that URI increased with the OA grade. URI of the normal cartilage samples was significantly lower than the one of the OA cartilage samples. There was no significant difference in URI between the grade 1 cartilage samples and the grade 2 cartilage samples. The reflection coefficient of the cartilage surface reduced significantly with the development of OA (p < 0.05), while the reflection coefficient of the cartilage-bone interface increased with the increase of grade.</p> <p>Conclusion</p> <p>High frequency ultrasound measurements can reflect the changes in the surface roughness index and the ultrasound reflection coefficients of the cartilage samples with different OA grades. This study may provide useful information for the quantitative ultrasonic diagnosis of early OA.</p

Evidence for an excess of B -> D(*) Tau Nu decays

Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg

Search for the decay modes D^0 → e^+e^-, D^0 → μ^+μ^-, and D^0 → e^±μ∓

We present searches for the rare decay modes D^0→e^+e^-, D^0→μ^+μ^-, and D^0→e^±μ^∓ in continuum e^+e^-→cc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468  fb^(-1). These decays are highly Glashow–Iliopoulos–Maiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0→μ^+μ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman–Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0→e^+e^-)<1.7×10^(-7), B(D^0→μ^+μ^-) within [0.6,8.1]×10^(-7), and B(D^0→e^±μ^∓)<3.3×10^(-7)

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