Mechanistic distinctions between agrin and laminin-1 induced aggregation of acetylcholine receptors

BACKGROUND: One of the earliest steps in synaptogenesis at the neuromuscular junction is the aggregation of nicotinic acetylcholine receptors at the postsynaptic membrane. This study presents quantitative analyses of receptor and α-Dystroglycan aggregation in response to agrin and laminin-1, alone or in combination. RESULTS: Both laminin and agrin increased overall expression of receptors on the plasma membrane. Following a 24 hour exposure, agrin increased the number of receptor aggregates but did not affect the number of α-Dystroglycan aggregates, while the reverse was true of laminin-1. Laminin also increased receptor concentration within aggregates, while agrin had no such effect. Finally, the spatial distribution of aggregates was indistinguishable from random in the case of laminin, while agrin induced aggregates were closer together than predicted by a random model. CONCLUSIONS: Agrin and laminin-1 both increase acetylcholine receptor aggregate size after 24 hours, but several lines of evidence indicate that this is achieved via different mechanisms. Agrin and laminin had different effects on the number and density of receptor and α-Dystroglycan aggregates. Moreover the random distribution of laminin induced (as opposed to agrin induced) receptor aggregates suggests that the former may influence aggregate size by simple mass action effects due to increased receptor expression

Second harmonic generating (SHG) nanoprobes for in vivo imaging

Fluorescence microscopy has profoundly changed cell and molecular biology studies by permitting tagged gene products to be followed as they function and interact. The ability of a fluorescent dye to absorb and emit light of different wavelengths allows it to generate startling contrast that, in the best cases, can permit single molecule detection and tracking. However, in many experimental settings, fluorescent probes fall short of their potential due to dye bleaching, dye signal saturation, and tissue autofluorescence. Here, we demonstrate that second harmonic generating (SHG) nanoprobes can be used for in vivo imaging, circumventing many of the limitations of classical fluorescence probes. Under intense illumination, such as at the focus of a laser-scanning microscope, these SHG nanocrystals convert two photons into one photon of half the wavelength; thus, when imaged by conventional two-photon microscopy, SHG nanoprobes appear to generate a signal with an inverse Stokes shift like a fluorescent dye, but with a narrower emission. Unlike commonly used fluorescent probes, SHG nanoprobes neither bleach nor blink, and the signal they generate does not saturate with increasing illumination intensity. The resulting contrast and detectability of SHG nanoprobes provide unique advantages for molecular imaging of living cells and tissues

MRI findings associated with anterior cruciate ligament tears in National Football League athletes

BACKGROUND: Anterior cruciate ligament (ACL) tears are a high-frequency injury requiring a lengthy recovery in professional American football players. Concomitant pathology associated with ACL tears as identified on magnetic resonance imaging (MRI) is not well understood in these athletes. PURPOSE: To describe the MRI findings of concomitant injuries associated with ACL tears among athletes in the National Football League (NFL). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Of 314 ACL injuries in NFL athletes from 2015 through 2019, 191 complete MRI scans from the time of primary ACL injury were identified and reviewed by 2 fellowship-trained musculoskeletal radiologists. Data were collected on ACL tear type and location, as well as presence and location of bone bruises, meniscal tears, articular cartilage pathology, and concomitant ligament pathology. Mechanism data from video review were linked with imaging data to assess association between injury mechanism (contact vs noncontact) and presence of concomitant pathology. RESULTS: Bone bruises were evident in 94.8% of ACL tears in this cohort, most often in the lateral tibial plateau (81%). Meniscal, additional ligamentous, and/or cartilage injury was present in 89% of these knees. Meniscal tears were present in 70% of knees, lateral (59%) more than medial (41%). Additional ligamentous injury was present in 71% of all MRI scans, more often a grade 1/2 sprain (67%) rather than a grade 3 tear (33%), and most often involving the medial collateral ligament (MCL) (57%) and least often the posterior cruciate ligament (10%). Chondral damage was evident in 49% of all MRI scans, with ≥1 full-thickness defect in 25% of all MRI scans, most often lateral. Most (79%) ACL tears did not involve direct contact to the injured lower extremity. Direct contact injuries (21%) were more likely to have a concomitant MCL tear and/or medial patellofemoral ligament injury and less likely to have a medial meniscal tear. CONCLUSION: ACL tears were rarely isolated injuries in this cohort of professional American football athletes. Bone bruises were almost always present, and additional meniscal, ligamentous, and chondral injuries were also common. MRI findings varied by injury mechanism

Now you see it, now you don't - the circumstellar disk in the GRO J1008--57 system

Multiwavelength observations are reported here of the Be/X-ray binary pulsar system GRO J1008-57. Over ten years worth of data are gathered together to show that the periodic X-ray outbursts are dependant on both the binary motion and the size of the circumstellar disk. In the first instance an accurate orbital solution is determined from pulse periods, and in the second case the strength and shape of the Halpha emission line is shown to be a valuable indicator of disk size and its behaviour. Furthermore, the shape of the emission line permits a direct determination of the disk size which is in good agreement with theoretical estimates. A detailed study of the pulse period variations during outbursts determined the binary period to be 247.8, in good agreement with the period determined from the recurrence of the outbursts.Comment: Accepted for publication in MNRA

When lack of control enhances closeness to others : the case of unemployment and economic threat

When personal control is threatened, people often turn to their own group and show negativity towards others. In three studies, we tested an alternative prediction that the salient lack of personal control (vs. control) experienced in the context of unemployment can lead to connectedness and more positive perception of similar others (e.g., members of groups affected by unemployment or the economic crisis). In two European countries, we found experimental (Study 1: Poland) and correlational (Study 2: Spain) evidence that a lowered sense of control of unemployed people was related to more favorable intergroup evaluations. Furthermore, when lack of control related to unemployment threat was experimentally induced, participants perceived a Greek outgroup more positively, and this effect was mediated by identification with and similarity to this group (Study 3). We discuss the role of the shared experience of collective uncontrollability in promoting positive intergroup relation

Application-Layer Connector Synthesis

International audienceThe heterogeneity characterizing the systems populating the Ubiquitous Computing environment prevents their seamless interoperability. Heterogeneous protocols may be willing to cooperate in order to reach some common goal even though they meet dynamically and do not have a priori knowledge of each other. Despite numerous e orts have been done in the literature, the automated and run-time interoperability is still an open challenge for such environment. We consider interoperability as the ability for two Networked Systems (NSs) to communicate and correctly coordinate to achieve their goal(s). In this chapter we report the main outcomes of our past and recent research on automatically achieving protocol interoperability via connector synthesis. We consider application-layer connectors by referring to two conceptually distinct notions of connector: coordinator and mediator. The former is used when the NSs to be connected are already able to communicate but they need to be speci cally coordinated in order to reach their goal(s). The latter goes a step forward representing a solution for both achieving correct coordination and enabling communication between highly heterogeneous NSs. In the past, most of the works in the literature described e orts to the automatic synthesis of coordinators while, in recent years the focus moved also to the automatic synthesis of mediators. Within the Connect project, by considering our past experience on automatic coordinator synthesis as a baseline, we propose a formal theory of mediators and a related method for automatically eliciting a way for the protocols to interoperate. The solution we propose is the automated synthesis of emerging mediating connectors (i.e., mediators for short)

Clustering-based approaches to SAGE data mining

Serial analysis of gene expression (SAGE) is one of the most powerful tools for global gene expression profiling. It has led to several biological discoveries and biomedical applications, such as the prediction of new gene functions and the identification of biomarkers in human cancer research. Clustering techniques have become fundamental approaches in these applications. This paper reviews relevant clustering techniques specifically designed for this type of data. It places an emphasis on current limitations and opportunities in this area for supporting biologically-meaningful data mining and visualisation

Observations of Accreting Pulsars

We summarize five years of continuous monitoring of accretion-powered pulsars with the Burst and Transient Source Experiment (BATSE) on the Compton Gamma Ray Observatory. Our 20-70 keV observations have determined or refined the orbital parameters of 13 binaries, discovered 5 new transient accreting pulsars, measured the pulsed flux history during outbursts of 12 transients (GRO J1744-28, 4U 0115+634, GRO J1750-27, GS 0834-430, 2S 1417-624, GRO J1948+32, EXO 2030+375, GRO J1008-57, A 0535+26, GRO J2058+42, 4U 1145-619 and A 1118-616), and also measured the accretion torque history of during outbursts of 6 of those transients whose orbital parameters were also known. We have also continuously measured the pulsed flux and spin frequency for eight persistently accreting pulsars (Her X-1, Cen X-3, Vela X-1, OAO 1657-415, GX 301-2, 4U 1626-67, 4U 1538-52, and GX 1+4). Because of their continuity and uniformity over a long baseline, BATSE observations have provided new insights into the long-term behavior of accreting magnetic stars. We have found that all accreting pulsars show stochastic variations in their spin frequencies and luminosities, including those displaying secular spin-up or spin-down on long time scales, blurring the conventional distinction between disk-fed and wind-fed binaries. Pulsed flux and accretion torque are strongly correlated in outbursts of transient accreting pulsars, but uncorrelated, or even anticorrelated, in persistent sources.Comment: LaTeX, psfig, 90 pages, 42 figures. To appear in Dec. 1997 ApJS, Vol 113, #

A Puzzling Paucity of Double Peaked X-ray Pulsars

Accretion powered pulsars exhibit a variety of lightcurves. In this paper we propose to classify the observed lightcurves as single or double pulsed.We analyze the lightcurves of 86 accretion powered pulsars and assign them to these classes. We present three datasets: first in which the classification can be easily done, second for which the classification is more difficult and not certain, and third for which we were unable to classify the pulsar because of lack of published data. We analyze a simple model in which the angles between the magnetic and rotation axis $\beta$, and between the rotation axis and the line of sight $\theta$ are random, and show that it is inconsistent with the data. We also present a model in whichthe angle between the magnetic axis and rotation axis is restricted and compare it with the data. This leads to an upper limit on the angle $\beta < 40^\circ$. We conclude that there must be a mechanism that leads to alignment of the magnetic and spin axis in X-ray pulsars.Comment: submitted to A&

Hard Spectra of X-Ray Pulsars from INTEGRAL Data

We present spectra for 34 accretion-powered X-ray and one millisecond pulsars that were within the field of view of the INTEGRAL observatory over two years (December 2002 - January 2005) of its in-orbit operation and that were detected by its instruments at a statistically significant level (> 8 sigma in the energy range 18--60 keV). There are seven recently discovered objects of this class among the pulsars studied: 2RXP J130159.6-635806, IGR/AX J16320-4751, IGR J16358-4726, AX J163904-4642, IGR J16465-4507, SAX/IGR J18027-2017 and AX J1841.0-0535. We have also obtained hard X-ray (> 20 keV) spectra for the accretion-powered pulsars A 0114+650, RX J0146.9+6121, AX J1820.5-1434, AX J1841.0-0535 and the millisecond pulsar XTE J1807-294 for the first time. We analyze the evolution of spectral parameters as a function of the intensity of the sources and compare these with the results of previous studies.Comment: 33 pages, 2 figures Astronomy Letters, 31, pp. 729 (2005