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The collective function of motor proteins is known to be important for the directed transport of many intracellular cargos. However, understanding how multiple motors function as a group remains challenging and requires new methods that enable determination of both the exact number of motors participating in motility and their organization on subcellular cargos. Here we present a biosynthetic method that enables exactly two kinesin-1 molecules to be organized on linear scaffolds that separate the motors by a distance of 50 nm. Tracking the motions of these complexes revealed that while two motors produce longer average run lengths than single kinesins, the system effectively behaves as though a single-motor attachment state dominates motility. It is proposed that negative motor interference derived from asynchronous motor stepping and the communication of forces between motors leads to this behavior by promoting the rapid exchange between different microtubule-bound configurations of the assemblies. [ABSTRACT FROM AUTHOR]

Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field. [ABSTRACT FROM AUTHOR]

Zusammenfassung Aus den Daten von 825 konsekutiven Schlaganfall- und TIA-Patienten wurden retrospektiv 90 Patienten mit Stenosen oder Verschlüssen der A. cerebri media (MCA) im Ultraschallbefund ermittelt.Mittels Survivalanalyse wurde der Einfluss verschiedener Risikofaktoren auf die Rückbildung eines Mediaprozesses untersucht. 90 Patienten wiesen einen Gefäßprozess der MCA auf. Mikroemboliesignale konnten bei 33% nachgewiesen werden, bei 7% wurden rezidivierende sprungartige Flussveränderungen beobachtet. In unserem Patientenkollektiv bildeten sich symptomatische Gefäßprozesse schneller zurück als asymptomatische. Mikroemboliesignale traten ausschließlich bei symptomatischen Gefäßprozessen auf. Sprungartige Flussveränderungen sagten eine schnellere Rückbildung der Stenose voraus.Atherogene Risikofaktoren waren mit langsamer Rückbildung assoziiert. Es gibt zwei Gruppen von Gefäßprozessen der MCA: dynamische, emboligene mit schneller Rückbildung und hohem Ischämierisiko und statische, nicht emboligene mit langsamer Rückbildung und niedrigem Ischämierisiko. Statische Stenosen entsprechen vermutlich arteriosklerotischen Plaques.Dynamische Gefäßprozesse könnten zu einem hohen Prozentsatz durch kardiale oder arterioarterielle Embolien verursacht sein. Summary The data of 825 consecutive patients with ischemic stroke or TIA were retrospectively reviewed for ultrasound findings of stenoses or occlusions of the middle cerebral artery (MCA).Using survival statistics,we studied the influence of various factors on the prognosis of MCA findings.We identified 90 subjects with MCA stenosis or occlusion. Microembolic signals were demonstrated in 33% and spontaneous flow variations in 7%. Symptomatic MCA findings normalized more quickly than asymptomatic findings. Microembolic signals occurred only in symptomatic stenoses.Spontaneous flow variations strongly predicted the disappearance of a stenosis.Atherogenic risk factors were associated with stable ultrasound findings. These data suggest that different types of MCA findings exist: (1) dynamic, emboligenic stenoses or occlusions with early normalization and a high risk for ischemic events and (2) static, nonemboligenic stenoses with rare normalization and a low risk of ischemic events.A high percentage of the former may be of embolic origin, and the latter may be atherosclerotic plaques. [ABSTRACT FROM AUTHOR]

The isotopes 60Fe and 26Al originate from massive stars and their supernovae, reflecting ongoing nucleosynthesis in the Galaxy. We studied the gamma-ray emission from these isotopes at characteristic energies 1173, 1332, and 1809 keV with over 15 yr of SPI data, finding a line flux in 60Fe combined lines of and the Al line flux of above the background and continuum emission for the whole sky. Based on the exponential disk grid maps, we characterize the emission extent of 26Al to find scale parameters and kpc; however, the 60Fe lines are too weak to spatially constrain the emission. Based on a point-source model test across the Galactic plane, the 60Fe emission would not be consistent with a single strong point source in the Galactic center or somewhere else, providing a hint of a diffuse nature. We carried out comparisons of emission morphology maps using different candidate source tracers for both 26Al and 60Fe emissions and suggest that the 60Fe emission is more likely to be concentrated toward the Galactic plane. We determine the 60Fe/26Al γ-ray flux ratio at 18.4% ± 4.2% when using a parameterized spatial morphology model. Across the range of plausible morphologies, it appears possible that 26Al and 60Fe are distributed differently in the Galaxy. Using the best-fitting maps for each of the elements, we constrain flux ratios in the range 0.2–0.4. We discuss the implications for massive star models and their nucleosynthesis. [ABSTRACT FROM AUTHOR]

The hard X-ray detector (HXD) on board Suzaku measured soft γ-rays from the SN Ia SN2014J at 77 ± 2 days after the explosion. Although the confidence level of the signal is about 90% (i.e., 2σ), the 3σ upper limit has been derived at <2.2 × 10−4 ph s−1 cm−2 in the 170–250 keV band as the first independent measurement of soft γ-rays with an instrument other than INTEGRAL. For this analysis, we have examined the reproducibility of the NXB model of HXD/GSO using blank sky data. We find that the residual count rate in the 90–500 keV band is distributed around an average of 0.19% with a standard deviation of 0.42% relative to the NXB rate. The averaged residual signals are consistent with that expected from the cosmic X-ray background. The flux of SN2014J derived from Suzaku measurements taken in one snapshot at t = 77 ± 2 days after the explosion is consistent with the INTEGRAL values averaged over the period between t = 50 and 100 days and also with explosion models of single or double degenerate scenarios. Being sensitive to the total ejecta mass surrounding the radioactive material, the ratio between continuum and line flux in the soft gamma-ray regime might distinguish different progenitor models. The Suzaku data have been examined with this relation at t = 77 ± 2 days, but could not distinguish models between single and double degenerate-progenitors. We disfavor explosion models with larger 56Ni masses than 1 M⊙, from our 1σ error on the 170–250 keV X-ray flux of (1.2 ± 0.7) × 10−4 ph s−1 cm−2. [ABSTRACT FROM AUTHOR]