370 research outputs found
Fork pausing allows centromere DNA loop formation and kinetochore assembly
De novo kinetochore assembly, but not template-directed assembly, is dependent on COMA, the kinetochore complex engaged in cohesin recruitment. The slowing of replication fork progression by treatment with phleomycin (PHL), hydroxyurea, or deletion of the replication fork protection protein Csm3 can activate de novo kinetochore assembly in COMA mutants. Centromere DNA looping at the site of de novo kinetochore assembly can be detected shortly after exposure to PHL. Using simulations to explore the thermodynamics of DNA loops, we propose that loop formation is disfavored during bidirectional replication fork migration. One function of replication fork stalling upon encounters with DNA damage or other blockades may be to allow time for thermal fluctuations of the DNA chain to explore numerous configurations. Biasing thermodynamics provides a mechanism to facilitate macromolecular assembly, DNA repair, and other nucleic acid transactions at the replication fork. These loop configurations are essential for sister centromere separation and kinetochore assembly in the absence of the COMA complex
Thermodynamics of Electrolytes on Anisotropic Lattices
The phase behavior of ionic fluids on simple cubic and tetragonal
(anisotropic) lattices has been studied by grand canonical Monte Carlo
simulations. Systems with both the true lattice Coulombic potential and
continuous-space electrostatic interactions have been investigated. At
all degrees of anisotropy, only coexistence between a disordered low-density
phase and an ordered high-density phase with the structure similar to ionic
crystal was found, in contrast to recent theoretical predictions. Tricritical
parameters were determined to be monotonously increasing functions of
anisotropy parameters which is consistent with theoretical calculations based
on the Debye-H\"uckel approach. At large anisotropies a two-dimensional-like
behavior is observed, from which we estimated the dimensionless tricritical
temperature and density for the two-dimensional square lattice electrolyte to
be and .Comment: submitted to PR
Еволюція рослинного світу в природному і культигенному середовищі
У ході засідань Міжнародної наукової конференції “Еволюція рослинного світу в природному і культигенному середовищі”, присвяченої 200-річчю від Дня народження Чарльза Дарвіна, обговорено актуальні питання еволюційної теорії, ботаніки, фізіології рослин, інтродукції, генетики й селекції, екології, збереження і примноження глобального та локального біорізноманіття, лісових культур і фітомеліорації та інших біологічних наук.В ходе заседаний Международной научной конференции “Эволюция растительного мира в естественной и культигенной среде”, посвященной 200-летию со дня рождения Чарльза Дарвина, обсуждены актуальные вопросы эволюционной теории, ботаники, физиологии растений, интродукции, генетики и селекции, экологии, сохранения и приумножения глобального и локального биоразнообразия, лесных культур и фитомелиорации и других биологических наук.During meetings of the International scientific conference “Evolution of the natural and cultivated plants” to devoted a 200-year from the day of birth of Charles Darwin topical problems of the evolutional theory are discussed, including botany, physiology of plants, introduction of plants, genetics and breeding of plants, ecology, preventing the loss of global and loca biodiversity, arboriculture, forest-growing and other biological sciences
Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates
AbstractTwo major infectious forms of vaccinia virus (VACV) have been described: the intracellular mature virion (IMV), and the extracellular enveloped virion (EEV). Due to their stability in the environment, IMVs play a predominant role in host-to-host transmission, whereas EEVs play an important role in dissemination within the host. In a previous report, we demonstrated that mice vaccinated with VACV L1R (IMV immunogen) and A33R (EEV immunogen) were protected from a lethal poxvirus challenge. Vaccination with a combination of both genes conferred greater protection than either gene alone, suggesting that an immune response against both IMV and EEV is advantageous. Here, we report that in mice individually administered DNA vaccines with two different VACV immunogens, A27L (IMV immunogen) or B5R (EEV immunogen), failed to significantly protect; however, vaccination with a combination of both genes conferred a high level of protection. Mice were completely protected when vaccinated with a combination of four VACV genes (A27L + A33R + L1R + B5R). Rhesus macaques vaccinated with this four-gene-combination developed appropriate antibody responses to each protein. Antibody responses elicited by this vaccine cross-reacted with monkeypox virus orthologous proteins. These data indicate that a gene-based vaccine comprised of the VACV A27L + A33R + L1R + B5R genes may be a useful candidate to protect against other orthopoxviruses, including those that cause monkeypox and smallpox
Identification, classification and expression pattern analysis of sugarcane cysteine proteinases
Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis
To describe first dose and steady state antiretroviral drug exposure in the female genital tract
Deconstructing classical water models at interfaces and in bulk
Using concepts from perturbation and local molecular field theories of
liquids we divide the potential of the SPC/E water model into short and long
ranged parts. The short ranged parts define a minimal reference network model
that captures very well the structure of the local hydrogen bond network in
bulk water while ignoring effects of the remaining long ranged interactions.
This deconstruction can provide insight into the different roles that the local
hydrogen bond network, dispersion forces, and long ranged dipolar interactions
play in determining a variety of properties of SPC/E and related classical
models of water. Here we focus on the anomalous behavior of the internal
pressure and the temperature dependence of the density of bulk water. We
further utilize these short ranged models along with local molecular field
theory to quantify the influence of these interactions on the structure of
hydrophobic interfaces and the crossover from small to large scale hydration
behavior. The implications of our findings for theories of hydrophobicity and
possible refinements of classical water models are also discussed
Modulation of intercellular communication by differential regulation and heteromeric mixing of co-expressed connexins
Integrated genomic characterization of pancreatic ductal adenocarcinoma
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine
- …