On the basis of their primary structure, the lysine-rich histones are a unified family of proteins. Each has an amino acid chain which falls into three distinct domains. Only the central domain ...(approximately 80 residues) is in a folded conformation. It is protected from trypsin digestion in chromatin and corresponds to the segment of highest sequence conservation. Without the flanking domains it is able to close two full turns of DNA in the nucleosome and can thus locate the H1 molecule.
The primary purpose of this study was to assess the effect of participation in a cognitively oriented, pretreatment intervention on the control orientation of substance-using behavior of 48 ...adolescents admitted to drug-free outpatient treatment. Subjects were randomly assigned to one of two treatment conditions and to one of two counselors. A comparison of changes in control orientation between groups was made after implementation of the intervention with the treated group and after both groups had participated in six counseling sessions. A 2-way multivariate analysis of covariance showed type of treatment was significant. Follow-up analyses indicated the treated group were significantly more internal than the control group at both posttest occasions. A one-tailed chi-squared test indicated no significant association in substance use for the groups.
Fusarium virguliforme causes soybean sudden death syndrome (SDS) in the United States. The disease was first observed in Arkansas in 1971, and since has been reported in most soybean-producing ...states, with a general movement from the southern to the northern states. In addition to F. virguliforme, three other species, Fusarium brasiliense, Fusarium crassistipitatum, and Fusarium tucumaniae, have been reported to cause SDS in South America. Yield losses caused by F. virguliforme range from slight to 100%. Severely infected plants often have increased flower and pod abortion, reduced seed size, increased defoliation, and prematurely senescence. Foliar symptoms observed in the field are most noticeable from mid to late reproductive growth stages. To manage SDS, research on crop rotations, soil types, tillage practices, seed treatments, and the development and utilization of host resistance has been investigated. This review focuses on what is known about F. virguliforme, the management of SDS in the United States, and how genetic engineering along with other traditional management options may be needed as integrated approaches to manage SDS.
•Fusarium virguliforme causes soybean sudden death syndrome in the United States.•Severely infected plants have compromised growth and yields.•Management strategies including host resistance were reviewed.•Integrated approaches including genetic engineering were examined.
We report the direct measurement of the 7Be solar neutrino signal rate performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The interaction rate of the 0.862 MeV 7Be ...neutrinos is 49+/-3stat+/-4syst counts/(day.100 ton). The hypothesis of no oscillation for 7Be solar neutrinos is inconsistent with our measurement at the 4sigma C.L. Our result is the first direct measurement of the survival probability for solar nu(e) in the transition region between matter-enhanced and vacuum-driven oscillations. The measurement improves the experimental determination of the flux of 7Be, pp, and CNO solar nu(e), and the limit on the effective neutrino magnetic moment using solar neutrinos.
Abstract
Wide-field surveys for transiting planets are well suited to searching diverse stellar populations, enabling a better understanding of the link between the properties of planets and their ...parent stars. We report the discovery of HAT-P-69 b (TOI 625.01) and HAT-P-70 b (TOI 624.01), two new hot Jupiters around A stars from the Hungarian-made Automated Telescope Network (HATNet) survey that have also been observed by the
Transiting Exoplanet Survey Satellite
. HAT-P-69 b has a mass of
M
Jup
and a radius of
R
Jup
and resides in a prograde 4.79 day orbit. HAT-P-70 b has a radius of
R
Jup
and a mass constraint of
M
Jup
and resides in a retrograde 2.74 day orbit. We use the confirmation of these planets around relatively massive stars as an opportunity to explore the occurrence rate of hot Jupiters as a function of stellar mass. We define a sample of 47,126 main-sequence stars brighter than
T
mag
= 10 that yields 31 giant planet candidates, including 18 confirmed planets, 3 candidates, and 10 false positives. We find a net hot Jupiter occurrence rate of 0.41 ± 0.10% within this sample, consistent with the rate measured by
Kepler
for FGK stars. When divided into stellar mass bins, we find the occurrence rate to be 0.71 ± 0.31% for G stars, 0.43 ± 0.15% for F stars, and 0.26 ± 0.11% for A stars. Thus, at this point, we cannot discern any statistically significant trend in the occurrence of hot Jupiters with stellar mass.
High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, and have also been observed in cancer patients who progress on anti-PD-1 immunotherapy. ...Although regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known about CD73 expression in other immune cell populations. We found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73-positive NK cells correlated with larger tumor size in breast cancer patients. In addition, the expression of multiple alternative immune checkpoint receptors including LAG-3, VISTA, PD-1, and PD-L1 was significantly higher in CD73-positive NK cells than in CD73-negative NK cells. Mechanistically, NK cells transport CD73 in intracellular vesicles to the cell surface and the extracellular space via actin polymerization-dependent exocytosis upon engagement of 4-1BBL on tumor cells. These CD73-positive NK cells undergo transcriptional reprogramming and upregulate IL-10 production via STAT3 transcriptional activity, suppressing CD4-positive T cell proliferation and IFN-γ production. Taken together, our results support the notion that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory properties within the tumor microenvironment.
Cancer metastasis can occur at the early stage of tumor development when a primary tumor is at the microscopic size. In particular, the interaction of malignant cells with other cell types including ...cancer-associated fibroblasts (CAF) in promoting metastasis at the early stage of tumor development remains largely unknown. Here, we investigated the role of CAFs in facilitating the initial events of cancer metastasis when primary tumors were at microscopic sizes.
Multicolor-coded cancer cells and CAFs were coimplanted into the transparent zebrafish body and metastasis at a single-cell level was monitored in living animals. Healthy fibroblasts, tumor factor-educated fibroblasts, and CAFs isolated from various tumors were tested for their ability to facilitate metastasis.
We showed that CAFs promoted cancer cell metastasis at the very early stage during primary tumor development. When a primary tumor was at the microscopic size consisting of a few hundred cells, CAFs were able to hijack cancer cells for dissemination from the primary site. Surprisingly, a majority of metastatic cancer cells remained in tight association with CAFs in the circulation. Furthermore, stimulation of non-metastasis-promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to acquisition of their metastatic capacity.
Cancer metastasis occurs at the very early stage of tumor formation consisting of only a few hundred cells. CAFs are the key cellular determinant for metastasis. Our findings provide novel mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs for cancer therapy should be aimed at the early stage during cancer development.
.
ABSTRACT
We present the discovery and characterization of two transiting planets observed by TESS in the light curves of the young and bright (V = 9.67) star HD73583 (TOI-560). We perform an ...intensive spectroscopic and photometric space- and ground-based follow-up in order to confirm and characterize the system. We found that HD73583 is a young (∼500 Myr) active star with a rotational period of 12.08 ± 0.11 d, and a mass and radius of 0.73 ± 0.02 M⊙ and 0.65 ± 0.02 R⊙, respectively. HD 73583 b (Pb = $6.3980420 _{ - 0.0000062 } ^ { + 0.0000067 }$ d) has a mass and radius of $10.2 _{ - 3.1 } ^ { + 3.4 }$ M⊕ and 2.79 ± 0.10 R⊕, respectively, which gives a density of $2.58 _{ - 0.81 } ^ { + 0.95 }$ ${\rm g\, cm^{-3}}$. HD 73583 c (Pc = $18.87974 _{ - 0.00074 } ^ { + 0.00086 }$ d) has a mass and radius of $9.7 _{ - 1.7 } ^ { + 1.8 }$ M⊕ and $2.39 _{ - 0.09 } ^ { + 0.10 }$ R⊕, respectively, which translates to a density of $3.88 _{ - 0.80 } ^ { + 0.91 }$ ${\rm g\, cm^{-3}}$. Both planets are consistent with worlds made of a solid core surrounded by a volatile envelope. Because of their youth and host star brightness, they both are excellent candidates to perform transmission spectroscopy studies. We expect ongoing atmospheric mass-loss for both planets caused by stellar irradiation. We estimate that the detection of evaporating signatures on H and He would be challenging, but doable with present and future instruments.
Overcoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated ...with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-RAS-V12-induced senescence. Mechanistically, a PAK4 - RELB - C/EBPβ axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Ser151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPβ. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition.
The clinical course of myasthenia gravis (MG) is variable, and spontaneous remission is still uncommon. Knowledge of the prognostic factors may help understand the course of MG and thus optimize its ...management. A systematic review search was conducted in MEDLINE and EMBASE for English language studies from 1985 through 2009. We identified additional studies by reviewing bibliographies of retrieved articles and hand search main journal of neurology. Studies evaluating variables associated with or predictive of remission in adult patients with MG were included. Because of methodological heterogeneity, we refrained from statistical pooling, instead, a best evidence synthesis was used for summarizing the results. From 1810 potentially relevant studies, 13 cohort studies met the inclusion criteria. The included studies were heterogeneous considerably in sample size, disease duration, follow‐up years, definition of remission, and analysis. Study quality was limited by retrospective design in most studies and lack of multivariate analysis. Time of diagnosis from onset (<1 year) showed strong evidence of predicting a better remission. In studies using completely stable remission outcomes, there was strong evidence that age at onset (<40 years) was of prognostic importance. Furthermore, gender showed no association with remission. Time of diagnosis from onset and age at onset were found to be predictors of remission. Gender does not seem to predict the course of MG. Our findings should be interpreted with caution because of the clinical and methodological heterogeneity of included studies.