Evaluation of the effectiveness of prazosin in conservative treatment of benign prostatic hypertrophy]

Prazosin--a selective blocker of alpha 1-adrenergic receptors--was administered to 30 patients with benign prostatic hypertrophy. Twenty four patients (80%) reported an improvement in voiding and observed more potent urinary stream after the treatment. Average and maximum flow rates increased in 18 patients (60%). Therapy had to be discontinued in 2 patients because of the adverse reactions (hypotension and syncope in one and exacerbation of the coronary disease symptoms in another patient).     

Beetle horns are regulated by the Hox gene,Sex combs reduced,in a species‐ and sex‐specific manner

Discovering the mechanisms that underlie the origin of novel features represents a major frontier in developmental and evolutionary biology. Here we begin to characterize the role of the Hox gene Sex combs reduced (Scr) during the development and evolution of a morphologically novel trait: beetle horns. Beetle horns develop as epidermal outgrowths from the prothorax and/or head, and size and location vary dramatically across species and between sexes. Using both comparative gene expression and larval RNA interference in two species of the horned beetle genus Onthophagus, we show that Scr functions in patterning adult labial mouthpart identity and suppressing wing development in the prothorax. At the same time, however, our results illustrate that Scr has acquired, within its ancestral domain of expression, additional new functions including the regulation of prepupal growth and pupal remodeling of pronotal horn primordia. Furthermore, comparative analyses of our results across both Onthophagus species, which differ in location of horn development (thoracic horns vs. thoracic and head horns) as well as patterns of sexual dimorphism (traditional vs. reversed sexual dimorphism), reveal surprising differences in exactly when, where, and to what degree Scr regulates horn formation in different sexes. These observations suggest that the interactions between Scr and its targets in the regulation of horn development can diversify quickly over remarkably short phylogenetic distances. More generally, our results suggest that the Hox complex can play an integral role in the development and evolution of novel complex traits while maintaining traditional patterning responsibilities.     

Is MLC phosphorylation essential for the recovery from ROCK inhibition in glioma C6 cells?

Inhibition of Rho-associated protein kinase (ROCK) activity in glioma C6 cells induces changes in actin cytoskeleton organization and cell morphology similar to those observed in other types of cells with inhibited RhoA/ROCK signaling pathway. We show that phosphorylation of myosin light chains (MLC) induced by P2Y? receptor stimulation in cells with blocked ROCK correlates in time with actin cytoskeleton reorganization, F-actin redistribution and stress fibers assembly followed by recovery of normal cell morphology. Presented results indicate that myosin light-chain kinase (MLCK) is responsible for the observed phosphorylation of MLC. We also found that the changes induced by P2Y? stimulation in actin cytoskeleton dynamics and morphology of cells with inhibited ROCK, but not in the level of phosphorylated MLC, depend on the presence of calcium in the cell environment.     

Differential Expression of Ecdysone Receptor Leads to Variation in Phenotypic Plasticity across Serial Homologs

Bodies are often made of repeated units, or serial homologs, that develop using the same core gene regulatory network. Local inputs and modifications to this network allow serial homologs to evolve different morphologies, but currently we do not understand which modifications allow these repeated traits to evolve different levels of phenotypic plasticity. Here we describe variation in phenotypic plasticity across serial homologous eyespots of the butterfly Bicyclus anynana, hypothesized to be under selection for similar or different functions in the wet and dry seasonal forms. Specifically, we document the presence of eyespot size and scale brightness plasticity in hindwing eyespots hypothesized to vary in function across seasons, and reduced size plasticity and absence of brightness plasticity in forewing eyespots hypothesized to have the same function across seasons. By exploring the molecular and physiological causes of this variation in plasticity across fore and hindwing serial homologs we discover that: 1) temperature experienced during the wandering stages of larval development alters titers of an ecdysteroid hormone, 20-hydroxyecdysone (20E), in the hemolymph of wet and dry seasonal forms at that stage; 2) the 20E receptor (EcR) is differentially expressed in the forewing and hindwing eyespot centers of both seasonal forms during this critical developmental stage; and 3) manipulations of EcR signaling disproportionately affected hindwing eyespots relative to forewing eyespots. We propose that differential EcR expression across forewing and hindwing eyespots at a critical stage of development explains the variation in levels of phenotypic plasticity across these serial homologues. This finding provides a novel signaling pathway, 20E, and a novel molecular candidate, EcR, for the regulation of levels of phenotypic plasticity across body parts or serial homologs.     

Role of PII proteins in nitrogen fixation control of Herbaspirillum seropedicae strain SmR1

Background  

The PII protein family comprises homotrimeric proteins which act as transducers of the cellular nitrogen and carbon status in prokaryotes and plants. In Herbaspirillum seropedicae, two PII-like proteins (GlnB and GlnK), encoded by the genes glnB and glnK, were identified. The glnB gene is monocistronic and its expression is constitutive, while glnK is located in the nlmAglnKamtB operon and is expressed under nitrogen-limiting conditions.     

Simultaneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces apoptosis of cutaneous T-cell lymphoma (CTCL) cells

Background

mTOR kinase forms the mTORC1 complex by associating with raptor and other proteins and affects a number of key cell functions. mTORC1 activates p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1). In turn, p70S6K1 phosphorylates a S6 protein of the 40S ribosomal subunit (S6rp) and 4E-BP1, with the latter negatively regulating eukaryotic initiation factor 4E (eIF-4E). MNK1 and MNK2 kinases phosphorylate and augment activity of eIF4E. Rapamycin and its analogs are highly specific, potent, and relatively non-toxic inhibitors of mTORC1. Although mTORC1 activation is present in many types of malignancies, rapamycin-type inhibitors shows relatively limited clinical efficacy as single agents. Initially usually indolent, CTCL displays a tendency to progress to the aggressive forms with limited response to therapy and poor prognosis. Our previous study (M. Marzec et al. 2008) has demonstrated that CTCL cells display mTORC1 activation and short-term treatment of CTCL-derived cells with rapamycin suppressed their proliferation and had little effect on the cell survival.

Methods

Cells derived from CTCL were treated with mTORC1 inhibitor rapamycin and MNK inhibitor and evaluated for inhibition of the mTORC1 signaling pathway and cell growth and survival.

Results

Whereas the treatment with rapamycin persistently inhibited mTORC1 signaling, it suppressed only partially the cell growth. MNK kinase mediated the eIF4E phosphorylation and inhibition or depletion of MNK markedly suppressed proliferation of the CTCL cells when combined with the rapamycin-mediated inhibition of mTORC1. While MNK inhibition alone mildly suppressed the CTCL cell growth, the combined MNK and mTORC1 inhibition totally abrogated the growth. Similarly, MNK inhibitor alone displayed a minimal pro-apoptotic effect; in combination with rapamycin it triggered profound cell apoptosis.

Conclusions

These findings indicate that the combined inhibition of mTORC1 and MNK may prove beneficial in the treatment of CTCL and other malignancies.