A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration-Resistant Prostate Cancer.

Purpose: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, herein referred as DNA-PK) is a multifunctional kinase of high cancer relevance. DNA-PK is deregulated in multiple tumor types, including prostate cancer, and is associated with poor outcomes. DNA-PK was previously nominated as a therapeutic target and DNA-PK inhibitors are currently undergoing clinical investigation.

Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer.

The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death.

Functional characterization of the corticular photosynthetic apparatus in grapevine.

A comparative analysis of functional characteristics of the grapevine leaf photosynthetic apparatus (LPA) and corticular photosynthetic apparatus (CPA) in chlorenchyma tissues of first-year lignified vine was performed. Obtained results demonstrate significant differences between the functional properties of the CPA and the LPA. CPA contains an increased proportion (about 2/3) of Q-non-reducing centers of photosystem II (PSII) that is confirmed by elevated O-J phase in fluorescence kinetics, high PSIIβ content, and slower Q reoxidation.

EZH2 Inhibition Sensitizes CARM1-High, Homologous Recombination Proficient Ovarian Cancers to PARP Inhibition.

In response to DNA double-strand breaks, MAD2L2-containing shieldin complex plays a critical role in the choice between homologous recombination (HR) and non-homologous end-joining (NHEJ)-mediated repair. Here we show that EZH2 inhibition upregulates MAD2L2 and sensitizes HR-proficient epithelial ovarian cancer (EOC) to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor in a CARM1-dependent manner. CARM1 promotes MAD2L2 silencing by driving the switch from the SWI/SNF complex to EZH2 through methylating the BAF155 subunit of the SWI/SNF complex on the MAD2L2 promoter.

Structural and molecular strategy of photosynthetic apparatus organisation of wild flora halophytes.

Structural and molecular parameters of photosynthetic apparatus in plants with different strategies for the accumulation of salts were investigated. CO gas exchange rate, content of pigments, mesostructure, chloroplast ultrastructure and the biochemical composition of the membrane structural components in leaves were measured. The objects of the study were euhalophytes (Salicornia perennans, Suaeda salsa, Halocnemum strobilaceum), crynohalophyte (Limonium gmelinii), glycohalophyte (Artemisia santonica).

Suppression of RAC1-driven malignant melanoma by group A PAK inhibitors.

Activating mutations in the RAC1 gene have recently been discovered as driver events in malignant melanoma. Expression of this gene is associated with melanocyte proliferation, and melanoma cells bearing this mutation are insensitive to BRAF inhibitors such as vemurafenib and dabrafenib, and also may evade immune surveillance due to enhanced expression of PD-L1. Activating mutations in RAC1 are of special interest, as small-molecule inhibitors for the RAC effector p21-activated kinase (PAK) are in late-stage clinical development and might impede oncogenic signaling from mutant RAC1.

Mesophyll cell ultrastructure of wheat leaves etiolated by lead and selenium.

The ultrastructure of mesophyll cells was studied in leaves of the Triticum aestivum L. cv. "Trizo" seedlings after two weeks of growth on soil contaminated by Pb and/or Se.

An Essential Role for the Tumor-Suppressor Merlin in Regulating Fatty Acid Synthesis.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas, and meningiomas. Mutational inactivation of the gene encoding the protein Merlin is found in most sporadic and inherited schwannomas, but the molecular mechanisms underlying neoplastic changes in schwannoma cells remain unclear. We report here that Nf2-deficient cells display elevated expression levels of key enzymes involved in lipogenesis and that this upregulation is caused by increased activity of Torc1.

Targeting group I p21-activated kinases to control malignant peripheral nerve sheath tumor growth and metastasis.

Malignant peripheral nerve sheath tumors (MPNSTs) are devastating sarcomas for which no effective medical therapies are available. Over 50% of MPSNTs are associated with mutations in NF1 tumor suppressor gene, resulting in activation of Ras and its effectors, including the Raf/Mek/Erk and PI3K/Akt/mTORC1 signaling cascades, and also the WNT/β-catenin pathway. As Group I p21-activated kinases (Group I Paks, PAK1/2/3) have been shown to modulate Ras-driven oncogenesis, we asked if these enzymes might regulate signaling in MPNSTs.

Targeting PAK1.

p21-Activated kinase 1 (PAK1) has attracted much attention as a potential therapeutic target due to its central role in many oncogenic signaling pathways, its frequent dysregulation in cancers and neurological disorders, and its tractability as a target for small-molecule inhibition. To date, several PAK1-targeting compounds have been developed as preclinical agents, including one that has been evaluated in a clinical trial. A series of ATP-competitive inhibitors, allosteric inhibitors and peptide inhibitors with distinct biochemical and pharmacokinetic properties represent useful laboratory tools for studies on the role of PAK1 in biology and in disease contexts, and could lead to promising therapeutic agents.

Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type 1.

The variable manifestation of phenotypes that occur in patients with neurofibromatosis type 1 (NF1) includes benign and malignant neurocutaneous tumors for which no adequate treatment exists. Cell-based screening of known bioactive compounds library identified the protein phosphatase 2A (PP2A) inhibitor Cantharidin and the L-type calcium channel blocker Nifedipine as potential candidates for NF1 pharmacotherapy. Validation of screening results using human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells showed that Cantharidin effectively impeded MPNST cell growth, while Nifedipine treatment significantly decreased local tumor growth in an MPNST xenograft animal model.

Photochemical activity and the structure of chloroplasts in Arabidopsis thaliana L. mutants deficient in phytochrome A and B.

The reduced content of photoreceptors, such as phytochromes, can decrease the efficiency of photosynthesis and activity of the photosystem II (PSII). For the confirmation of this hypothesis, the effect of deficiency in both phytochromes (Phy) A and B (double mutant, DM) in 7-27-day-old Arabidopsis thaliana plants on the photosynthetic activity was studied in absence and presence of UV-A radiation as a stress factor. The DM with reduced content of apoproteins of PhyA and PhyB and wild type (WT) plants with were grown in white and red light (WL and RL, respectively) of high (130 μmol quanta m s) and low (40 μmol quanta m s) intensity.

Biochemistry and cell ultrastructure changes during senescence of Beta vulgaris L. leaf.

The comparative study of biochemical and ultrastructure features in senescing sugar beet (Beta vulgaris L.) leaves was carried out. One group of plants was grown under normal conditions in washed river sand and poured in turn with nitrate-containing mineral solution or water (N plants).

[LIGHT-DEPENDENT SYNTHESIS OF CELL MEMBRANES IN THE Brc-1 MUTANT OF CHLAMYDOMONAS REINHARDTII].

The structural organization of cells of the Brc-1 mutant of the unicellular green algae Chlamydomonas reinhardtii grown in the light and in the dark has been studied. The Brc-1 mutant contains the brc-1 mutation in the nucleus gene LTS3. In the light, all membrane structures in mutant cells form normally and are well developed.

[Valve-like structures in motor cells of the leaf of Distichlis spicata "Yesen 4A" (Poaceae)].

The salt gland of the leaf of Distichlis directly contacts the cells of interfascicular aquiferous parenchyma (motor cells). The cytoplasmic strand of motor cells produce deep invaginations, which form with the participation of mitochondria. The constriction of the cytoplasmic strand at the site of the localization of mitochondria leads to the fusion of the tonoplast and plasmalemma with mitochondrial membranes and the formation of a thin one-layer plate, a valve.

[Structural-functional organization of the cells of Brc-1 mutant Chlamydomonas reinhardtii, supplying protoporphyrin IX in the dark].

The structural-functional characteristics of the cells of wild type CC-124 and Brc-1 mutant of the unicellular green algae Chlamydomonas reinhardtii while growing in the dark and light were studied. It has been shown that the cells of the wild type in heterotrophic and mixotrophic growth conditions had a well developed structure and high functional activity due to the ability of the cells to synthesize chlorophyll both in the light and in the dark. The cells of Brc-1 mutant lost their ability to synthesize chlorophyll in the dark and the cells' color was orange due to brc-1 mutation in the nuclear gene LTS3 that regulated the activity of Mg-chelatase enzyme.

[Mitochondrial dysfunction in children with hepatic forms of glycogen storage disease].

Aim: The purpose of the study was to assess mitochondrial dysfunction severity in patients with hepatic forms of glycogen storage disease (GSD).

Patients And Methods: We examined 53 children with GSD in the dynamics. Distribution of children by disease types was: 1st group--children with GSD type I, 2nd group--children with GSD type III, 3rd group--children with GSD type VI and IX; comparison group consisted of 34 healthy children.

[POSSIBILITIES FOR THE USE OF THE ANTI-LEUKOTRIENE DRUG MONTELUKAST IN COMBINED THERAPY OF PATIENTS WITH BRONCHIAL ASTHMA AND COLD-INDUCED BRONCHIAL HYPERACTIVITY].

Aim: To study effectiveness of the use of the anti-leukotriene drug montelukast in combination with inhalation glucocorticoid and long-acting beta-agonist in patients with bronchial asthma (BA) and cold-induced bronchial hyperactivity (CBHA) with a view to optimizing control of the disease.

Materials And Methods: We carried out an open comparative prospective study of patients with persistent BA in a cold season under conditions of real clinical practice. The patients were divided into 2 groups.

[Ultrastructural organization and composition of carotenoids in the eyespot in the mutant Chlamydomonas reinhardtii].

Biogenesis of the ultrastructure of the eyespot in the chloroplasts of unicellular green algae Chlamydomonas reinhardtii has been studied. We have found that the development of the structure of the eyespot correlates with the accumulation of carotenoids. Depending on their accumulation, the eyespots form from 1 to 4 lines of lipid-carotenoid globules.

Effects of polyaromatic hydrocarbons on photosystem II activity in pea leaves.

The acute effects of three typical polyaromatic hydrocarbons (PAHs): naphthalene (Naph), phenanthrene (Phen) and fluoranthene (Flu) on photochemical activity of photosystem II (PSII) in detached leaves of 3-week-old pea plants were studied. The leaves were exposed in water with PAHs under white light for 0.5-72 h.

PAK signalling during the development and progression of cancer.

p21-Activated kinases (PAKs) are positioned at the nexus of several oncogenic signalling pathways. Overexpression or mutational activation of PAK isoforms frequently occurs in various human tumours, and recent data suggest that excessive PAK activity drives many of the cellular processes that are the hallmarks of cancer. In this Review, we discuss the mechanisms of PAK activation in cancer, the key substrates that mediate the developmental and oncogenic effects of this family of kinases, and how small-molecule inhibitors of these enzymes might be best developed and deployed for the treatment of cancer.

[Comparative analysis of the exogenous ammonium influence on soybean tissue and Chlamydomonas cells].

In this work we studied the influence of exogenous ammonium on the total protein and chlorophyll contents, on the number of ribosomes and on the expression of ribosomal genes encoding the small subunit 18S rRNA and rpS6 protein in unicellular green alga Chlamydomonas reinhardtii and in callus tissue of Glycine max. Comparative analysis of two sets of data showed that although the lack of ammonium resulted in reduction of the number of ribosomes in alga and plant cells, this effect was not caused by decreasing of the expression level of the ribosomal genes. Possible mechanisms of the ammonium regulatory role in the ribosome biogenesis are discussed.

PKM2 enters the morpheein academy.

In this issue of Molecular Cell, Gao et al. (2012) show that the glycolytic enzyme PKM2, in its dimeric form, possesses protein kinase activity and phosphorylates STAT3 in the nucleus, thereby driving expression of genes that promote transformation.

[The "crystals" in the sugar beet (Beta vulgaris L.) leaves].

Crystal containing cells widely distributed in plant tissues, though the origin of the crystals and their functions are still opened to question. Membrane vesicles in beet leaves are visible in electronic microscope. They originate in cytoplasm and penetrate into vacuole by pinocytosis with participation of tonoplast.

[Secondary autoimmune hemolytic anemia as a result of B19 parvovirus persistence in immunodeficient patients].

Aim: To ascertain informative value of immunological diagnosis of B19 parvovirus in combination with polymerase chain reaction (PCR); to analyse frequency of development of secondary autoimmune hemolytic anemia (AIHA) in immunodeficient patients as a result of virus persistence--persistent infection eliminated only by treatment causing suppression of erythropoiesis.

Material And Methods: B19 parvovirus detection was performed in blood serum of 207 subjects: 144 patients with anemia (Hb < 100 g/1) and 500 blood donors. DNA of parvovirus B19 was detected in the sera by PCR, antibodies to this virus--by enzyme immunoassay (EIA).