Transport of c-MYC by Kinesin-1 for proteasomal degradation in the cytoplasm

Abstractc-MYC is an oncogenic transcription factor that is degraded by the proteasome pathway. However, the mechanism that regulates delivery of c-MYC to the proteasome for degradation is not well characterized. Here, the results show that the motor protein complex Kinesin-1 transports c-MYC to the cytoplasm for proteasomal degradation. Inhibition of Kinesin-1 function enhanced ubiquitination of c-MYC and induced aggregation of c-MYC in the cytoplasm. Transport studies showed that the c-MYC aggregates moved from the nucleus to the cytoplasm and KIF5B is responsible for the transport in the cytoplasm. Furthermore, inhibition of the proteasomal degradation process also resulted in an accumulation of c-MYC aggregates in the cytoplasm. Moreover, Kinesin-1 was shown to interact with c-MYC and the proteasome subunit S6a. Inhibition of Kinesin-1 function also reduced c-MYC-dependent transformation activities. Taken together, the results strongly suggest that Kinesin-1 transports c-MYC for proteasomal degradation in the cytoplasm and the proper degradation of c-MYC mediated by Kinesin-1 transport is important for transformation activities of c-MYC. In addition, the results indicate that Kinesin-1 transport mechanism is important for degradation of a number of other proteins as well

RR Lyrae variables in Galactic globular clusters - I: The observational scenario

In this paper we revisit observational data concerning RR Lyrae stars in Galactic globular clusters, presenting frequency histograms of fundamentalized periods for the 32 clusters having more than 12 pulsators with well recognized period and pulsation mode. One finds that the range of fundamentalized periods covered by the variables in a given cluster remains fairly constant in varying the cluster metallicity all over the metallicity range spanned by the cluster sample, with the only two exceptions given by M15 and NGC6441. We conclude that the width in temperature of the RR Lyrae instability strip appears largely independent of the cluster metallicity. At the same time, it appears that the fundamentalized periods are not affected by the predicted variation of pulsators luminosity with metal abundance, indicating the occurrence of a correlated variation in the pulsator mass. We discuss mean periods in a selected sample of statistically significant "RR rich" clusters with no less than 10 RRab and 5 RRc variables. One finds a clear evidence for the well known Oosterhoff dichotomy in the mean period of ab-type variables, together with a similarly clear evidence for a constancy of the mean fundamentalized period in passing from Oosterhoff type II to type I clusters. On this basis, the origin of the Oosterhoff dichotomy is discussed, presenting evidence against a strong dependence of the RR Lyrae luminosity on the metal content.Comment: 9 pages, 6 figures. Accepted for publication on A&

Imaging Complex Structure in Shallow Seismic-reflection Data Using Prestack Depth Migration

Prestack depth migration (PSDM) analysis has the potential to significantly improve the accuracy of both shallow seismic reflection images and the measured velocity distributions. In a study designed to image faults in the Alvord Basin, Oregon, at depths from 25–1000 m, PSDM produced a detailed reflection image over the full target depth range. In contrast, poststack time migration produced significant migration artifacts in the upper 100 m that obscured reflection events and limited the structural interpretation in the shallow section. Additionally, an abrupt increase from ~2500 to \u3e3000 m/s in the PSDM velocity model constrained the interpretation of the transition from sedimentary basin fill to basement volcanic rocks. PSDM analysis revealed a complex extensional history with at least two distinct phases of basin growth and a midbasin basement high that forms the division between two major basin compartments

Discovery of a Variable Star Population in NGC 2808

We have applied the image subtraction method to images of the peculiar, bimodal-horizontal branch globular cluster NGC 2808, taken over a total of six nights over a range of five months. As a result, we have found, for the first time, a sizeable population of variable stars in the crowded inner regions of the cluster, thus raising the known RR Lyrae population in the cluster to a total of 18 stars. In addition, an eclipsing binary and two other variables with periods longer than 1 day were also found. Periods, positions and (differential) light curves are provided for all the detected variables. The Oosterhoff classification of NGC 2808, which has recently been associated with a previously unknown dwarf galaxy in Canis Major, is briefly discussed.Comment: 8 pages, 4 figures. A&A, in pres

RR Lyrae stars in Galactic globular clusters. VI. The Period-Amplitude relation

We compare theory and observations for fundamental RR Lyrae in the solar neighborhood and in both Oosterhoff type I (OoI) and type II (OoII) Galactic globular clusters (GGCs). The distribution of cluster RR_ab in the PA_V plane depends not only on the metal abundance, but also on the cluster Horizontal Branch (HB) morphology. On average the observed k_puls parameter, connecting the period to the visual amplitude, increases when moving from metal-poor to metal-rich GGCs. However, this parameter shows marginal changes among OoI clusters with intermediate to red HB types and iron abundances -1.8<= [Fe/H] <=-1.1, whereas its value decreases in OoII clusters with the bluer HB morphology. Moreover, at [Fe/H]=-1.7+-0.1 the OoI clusters present redder HB types and larger values than the OoII clusters. The RR_ab variables in Omega Cen and in the solar neighborhood further support the evidence that the spread in [Fe/H], at fixed k_puls, is of the order of +-0.5 dex. Synthetic HB simulations show that the PA_V plane can provide accurate cluster distance estimates. The RR_ab variables in OoI and in OoII clusters with very blue HB types obey a well-defined M_V(RR)-k_puls relation, while those in OoII clusters with moderately blue HB types present a zero-point that is ~0.05 mag brighter. Regarding field variables, we show that with [Fe/H]=> -1.0 a unique M_V(RR)-k_puls relation can be adopted, independently of the parent HB morphology. Current findings suggest that the PA_V distribution does not seem to be a robust diagnostic for the metal abundance of RR_ab variables. However, the same observables can be used to estimate the absolute magnitude of globular cluster and field RR_ab variables. We show that over the metallicity range -2.4<= [Fe/H] <= 0.0 the M_V(RR)-[Fe/H] relation shows a parabolic behavior.Comment: Paper accepted on A&A, 13 pages, 18 figure

Spherically symmetric solutions of a (4+n)-dimensional Einstein-Yang-Mills model with cosmological constant

We construct solutions of an Einstein-Yang-Mills system including a cosmological constant in 4+n space-time dimensions, where the n-dimensional manifold associated with the extra dimensions is taken to be Ricci flat. Assuming the matter and metric fields to be independent of the n extra coordinates, a spherical symmetric Ansatz for the fields leads to a set of coupled ordinary differential equations. We find that for n > 1 only solutions with either one non-zero Higgs field or with all Higgs fields constant and zero gauge fields exist. We give the analytic solutions available in this model. These are ``embedded'' abelian solutions with a diverging size of the manifold associated with the extra n dimensions. Depending on the choice of parameters, these latter solutions either represent naked singularities or they possess a single horizon. We also present solutions of the effective 4-dimensional Einstein-Yang-Mills-Higgs-dilaton model, where the higher dimensional cosmological constant induces a Liouville-type potential. The solutions are non-abelian solutions with diverging Higgs fields, which exist only up to a maximal value of the cosmological constant.Comment: 13 Tex-pages, 2 eps-figures; discussions changed; some points clarifie

AdS Black Hole Solutions in the Extended New Massive Gravity

We have obtained (warped) AdS black hole solutions in the three dimensional extended new massive gravity. We investigate some properties of black holes and obtain central charges of the two dimensional dual CFT. To obtain the central charges, we use the relation between entropy and temperature according to the AdS/CFT dictionary. For AdS black holes, one can also use the central charge function formalism which leads to the same results.Comment: 24pages, some organization corrected, minor corrections, references added, final published versio

Geophysical Surveys Across the Boise Hydrogeophysical Research Site to Determine Geophysical Parameters of a Shallow, Alluvial Aquifer

At the Boise Hydrogeophysical Research Site (BHRS), we are characterizing the hydrogeophysical parameters of a cobble-and-sand, unconfined aquifer using a wide variety of geophysical methods. Our goal is to develop methods for mapping variations in permeability by combining non-invasive geophysical data with hydrologic measurements. We are using seismic, ground penetrating radar, and electrical methods in a variety of configurations to provide images of and parameter distributions at the BHRS. Issues such as resolution, depth of penetration, and the ability to image the desired parameters will help determine the most effective methods. Supporting data sets from the BHRS include core analyses and geophysical logs from 18 wells at the site. We will use these data to verify our geophysical interpretations. The various geophysical methods and acquisition geometries, combined with the well control, will provide an outstanding data set to characterize the heterogeneity of the subsurface beneath this alluvial aquifer, and find ways to map permeability with geophysical information

Hmga2 deficiency is associated with allometric growth retardation, infertility, and behavioral abnormalities in mice

The high mobility group AT-hook 2 (HMGA2) protein works as an architectural regulator by binding AT-rich DNA sequences to induce conformational changes affecting transcription. Genomic deletions disrupting HMGA2 coding sequences and flanking noncoding sequences cause dwarfism in mice and rabbits. Here, CRISPR/Cas9 was used in mice to generate an Hmga2 null allele that specifically disrupts only the coding sequence. The loss of one or both alleles of Hmga2 resulted in reduced body size of 20% and 60%, respectively, compared to wild-type littermates as well as an allometric reduction in skull length in Hmga2(-/-) mice. Both male and female Hmga2(-/-) mice are infertile, whereas Hmga2(+/-) mice are fertile. Examination of reproductive tissues of Hmga2(-/-) males revealed a significantly reduced size of testis, epididymis, and seminal vesicle compared to controls, and 70% of knock-out males showed externalized penis, but no cryptorchidism was observed. Sperm analyses revealed severe oligospermia in mutant males and slightly decreased sperm viability, increased DNA damage but normal sperm chromatin compaction. Testis histology surprisingly revealed a normal seminiferous epithelium, despite the significant reduction in testis size. In addition, Hmga2(-/-) mice showed a significantly reduced exploratory behavior. In summary, the phenotypic effects in mouse using targeted mutagenesis confirmed that Hmga2 is affecting prenatal and postnatal growth regulation, male reproductive tissue development, and presents the first indication that Hmga2 function is required for normal mouse behavior. No specific effect, despite an allometric reduction, on craniofacial development was noted in contrast to previous reports of an altered craniofacial development in mice and rabbits carrying deletions of both coding and noncoding sequences at the 5 ' part of Hmga2

COVID-19-Associated Cardiovascular Complications

Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications such as myocardial injury, thromboembolic events, arrhythmia, and heart failure. Multiple mechanisms—some overlapping, notably the role of inflammation and IL-6—potentially underlie these complications. The reported cardiac injury may be a result of direct viral invasion of cardiomyocytes with consequent unopposed effects of angiotensin II, increased metabolic demand, immune activation, or microvascular dysfunction. Thromboembolic events have been widely reported in both the venous and arterial systems that have attracted intense interest in the underlying mechanisms. These could potentially be due to endothelial dysfunction secondary to direct viral invasion or inflammation. Additionally, thromboembolic events may also be a consequence of an attempt by the immune system to contain the infection through immunothrombosis and neutrophil extracellular traps. Cardiac arrhythmias have also been reported with a wide range of implicated contributory factors, ranging from direct viral myocardial injury, as well as other factors, including at-risk individuals with underlying inherited arrhythmia syndromes. Heart failure may also occur as a progression from cardiac injury, precipitation secondary to the initiation or withdrawal of certain drugs, or the accumulation of des-Arg9-bradykinin (DABK) with excessive induction of pro-inflammatory G protein coupled receptor B1 (BK1). The presenting cardiovascular symptoms include chest pain, dyspnoea, and palpitations. There is currently intense interest in vaccine-induced thrombosis and in the treatment of Long COVID since many patients who have survived COVID-19 describe persisting health problems. This review will summarise the proposed physiological mechanisms of COVID-19-associated cardiovascular complications