Frondoside A Suppressive Effects on Lung Cancer Survival,Tumor Growth,Angiogenesis, Invasion,and Metastasis

A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 µM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1–0.5 µM) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer.     

Life cycles of the Hymenolepis, Aploparaksis birulai Linstow, 1905 and Aploparaksis brachyphallos (Krabbe, 1869)]

Larvae of A. birulai from Lumbriculus variegatus and A. brachyphallos from Stylodrilus sp. from the Chauna lowland (Chukotka) are described. The species belonging of the larvae was proved experimentally. It was shown that Cysticercus sp. Hrabe, 1958 is a larvacyst of A. birulai. For larvacysts of A. birulai type the name of "floricerk" was suggested and for those of A. brachyphallos type--the name "tailed diplocyst". It is noted that A. uelcal Spassky et Jurpalova, 1968 is a synonym of A. brachyphallos (Krabbe, 1869) nec A. brachyphallos sensu Davies, 1938.     

XVIIITH International Congress of Psychology,Moscow, USSR,August 4-11, 1966. Information and Program

The XVIIIth International Congress of Psychology has been organized by the Society of Psychologists of the USSR, under the auspices of the International Union of Scientific Psychology and the Soviet Steering Committee, under the chairmanship of P. N. Fedosseyev. The Steering Committee was established by the USSR Ministry of Higher Education, the USSR Academy of Sciences, and the RSFSR Ministry of Education. The President of the Congress is A. N. Leont'yev. The Organizing Committee of the Congress is chaired by A. A. Smirnov; and the Program Committee is chaired by A. R. Luriya, with the assistance of P. Fraisse (Paris), acting on behalf of the International Union of Scientific Psychology.     

Yeast diadenosine 5',5'-P1,P4-tetraphosphate alpha,beta-phosphorylase behaves as a dinucleoside tetraphosphate synthetase

The diadenosine 5',5'-P1,P4-tetraphosphate alpha,beta-phosphorylase (Ap4A phosphorylase), recently observed in yeast [Guaranowski, A., & Blanquet, S. (1985) J. Biol. Chem. 260, 3542-3547], is shown to be capable of catalyzing the synthesis of Ap4A from ATP + ADP, i.e., the reverse reaction of the phosphorolysis of Ap4A. The synthesis of Ap4A markedly depends on the presence of a divalent cation (Ca2+, Mn2+, or Mg2+). In vitro, the equilibrium constant K = ([Ap4A][Pi])/[(ATP][ADP]) is very sensitive to pH. Ap4A synthesis is favored at low pH, in agreement with the consumption of one to two protons when ATP + ADP are converted into Ap4A and phosphate. Optimal activity is found at pH 5.9. At pH 7.0 and in the presence of Ca2+, the Vm for Ap4A synthesis is 7.4 s-1 (37 degrees C). Ap4A phosphorylase is, therefore, a valuable candidate for the production of Ap4A in vivo. Ap4A phosphorylase is also capable of producing various Np4N' molecules from NTP and N'DP. The NTP site is specific for purine ribonucleotides (N = A, G), whereas the N'DP site has a broader specificity (N' = A, C, G, U, dA). This finding suggests that the Gp4N' nucleotides, as well as the Ap4N' ones, could occur in yeast cells.     

Activation, regulation, and inhibition of DYRK1A

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a protein kinase with diverse functions in neuronal development and adult brain physiology. Higher than normal levels of DYRK1A are associated with the pathology of neurodegenerative diseases and have been implicated in some neurobiological alterations of Down syndrome, such as mental retardation. It is therefore important to understand the molecular mechanisms that control the activity of DYRK1A. Here we review the current knowledge about the initial self-activation of DYRK1A by tyrosine autophosphorylation and propose that this mechanism presents an ancestral feature of the CMGC group of kinases. However, tyrosine phosphorylation does not appear to regulate the enzymatic activity of DYRK1A. Control of DYRK1A may take place on the level of gene expression, interaction with regulatory proteins and regulated nuclear translocation. Finally, we compare the properties of small molecule inhibitors that target DYRK1A and evaluate their potential application and limitations. The β-carboline alkaloid harmine is currently the most selective and potent inhibitor of DYRK1A and has proven very useful in cellular assays.     

Safe, convenient, portable pipettor

A dafe, convenient, portable pipetting device that will accommodate any size pipette is described. A vacuum bulb eliminates the need for external vacuum. Necessary components, fabrication procedures, and operating techniques are given.     

Interactions of desensitized actomyosin with tropomyosin, troponin A, troponin B, and polyanions

Troponin B is an inhibitor of the Mg⁺⁺-activated ATPase activity of actomyosin. The inhibitory effect, which is observed, however, depends upon whether tropomyosin is also present. In the absence of tropomyosin the inhibition by troponin B is markedly reduced by increasing the ionic strength from 0.03 to 0.07, but is not affected by calcium up to a concentration of 10^-4 M. Troponin A relieves the inhibition in both the absence and presence of calcium, an effect which is also shown by many polyanions and is illustrated by using RNA. Tropomyosin enhances the inhibitory effect of troponin B and renders it more resistant to increasing ionic strength but it does not make the inhibition calcium-sensitive. However, when troponin A or low concentrations of polyanions are added to troponin B and tropomyosin, the actomyosin ATPase activity becomes calcium-sensitive; i.e., in the presence of tropomyosin, troponin A or polyanions do not relieve the inhibitory action of troponin B in the absence of calcium but only in its presence. In marked contrast to this is the effect of troponin A in the absence of tropomyosin where it neutralizes the effect of troponin B under all conditions. Thus troponin A and the polyanions both confer calcium regulation on the troponin B-tropomyosin system. The similar effects exhibited by troponin A and the polyanions suggest that the addition of net negative charge to troponin B is an important factor in the conferral of calcium sensitivity. It is also clear that tropomyosin is an essential component of the regulatory mechanism.     

Systematics, phylogeny and biogeography of Anterastes (Orthoptera, Tettigoniidae, Tettigoniinae): evolution within a refugium

Çıplak, B. (2004). Systematics, phylogeny and biogeography of Anterastes (Orthoptera, Tettigoniidae, Tettigoniinae): evolution within a refugium. — Zoologica Scripta , 33 , 19–44.
The genus Anterastes , distributed in southeastern Europe and the western part of Anatolia, is revised based on previous materials and numerous specimens collected from new localities. A key to all species is presented. Two new species, A. antitauricus sp. n. and A. ucari sp. n. are described. Anterastes akdaghensis Ramme is placed in synonymy with A. babadaghi Uvarov. Cladistic analysis confirmed the monophyly of Anterastes . The relationships among the species of Anterastes are: A. uludaghensis  + (( A. serbicus  +  A. burri  +  A. antitauricus sp. n.) + ( A. anatolicus  +  A. tolunayi  + ( A. niger  + ( A. babadaghi  +  A. turcicus  +  A. ucari sp. n.)))). The biogeography of the genus shows a correlation with its phylogeny. It is assumed that the genus arose from an ancestral stock in northwestern Anatolia in the Pliocene and the later range of this ancestral population expanded and contracted under the effects of the ice ages (glacial and interglacial periods, respectively). It is postulated that speciation within the genus, suggested by phylogenetic analysis, might have occurred when the range of ancestral populations expanded during glacial periods and contracted in subsequent warm periods. The present species may be the product of relict populations remaining in refugia at higher altitudes with alpine or subalpine vegetation in southern Anatolia.     

Biosynthesis, transport, and modification of lipid A.

Lipopolysaccharide (LPS) is the major surface molecule of Gram-negative bacteria and consists of three distinct structural domains: O-antigen, core, and lipid A. The lipid A (endotoxin) domain of LPS is a unique, glucosamine-based phospholipid that serves as the hydrophobic anchor of LPS and is the bioactive component of the molecule that is associated with Gram-negative septic shock. The structural genes encoding the enzymes required for the biosynthesis of Escherchia coli lipid A have been identified and characterized. Lipid A is often viewed as a constitutively synthesized structural molecule. However, determination of the exact chemical structures of lipid A from diverse Gram-negative bacteria shows that the molecule can be further modified in response to environmental stimuli. These modifications have been implicated in virulence of pathogenic Gram-negative bacteria and represent one of the molecular mechanisms of microbial surface remodeling used by bacteria to help evade the innate immune response. The intent of this review is to discuss the enzymatic machinery involved in the biosynthesis of lipid A, transport of the molecule, and finally, those enzymes involved in the modification of its structure in response to environmental stimuli.     

The genus Aerotegmina (Orthoptera, Tettigoniidae, Hexacentrinae): chromosomes, morphological relations, phylogeographical patterns and description of a new species

The genus Aerotegmina Hemp is common on East African mountains. Two species are known and a third, A. taitensis n. sp., is described in this paper. A. kilimandjarica Hemp is widespread while A. shengenae Hemp is endemic to the South Pare Mountains and A. taitensis n. sp. is known only from the Taita Hills. Morphologically, and from their song, A. shengenae and A. taitensis n. sp. are closely related. In chromosome number A. kilimandjarica (2n?=?33) differs clearly from A. shengenae (2n?=?27). Data presented on other flightless Orthoptera suggest that the South Pare Mountains and the Taita Hills, both belonging to the geologically old mountain chain of the Eastern Arc, show a faunistic similarity not shared by any other mountain range in the area. The mechanisms that led to this phylogeographic pattern in flightless Orthoptera in the Eastern Arc Mountains of northern Tanzania and southern Kenya and the inland volcanoes are discussed. A key to the three Aerotegmina species is presented, as well as bioacoustical data of all species compared to the phaneropterine species Euryastes jagoi.     

Cloning, characterization, and tissue distribution of mouse phosphodiesterase 7A1

We have cloned a cDNA representing mouse phosphodiesterases (PDE) 7A1. The open reading frame encodes a protein of 482 amino acids with a predicted molecular mass of 55417. Like human PDE7A variants, mouse PDE7A1 and A2 are 5' splice variants from a common gene. The distinct N-terminal sequence of mouse PDE7A1 is highly homologous to the corresponding sequence of human PDE7A1 with a similarity of 98% but not to that of mouse PDE7A2 (with a similarity of 12%), and is more hydrophilic than that of mouse PDE7A2. Mouse PDE7A1 expressed in SF9 cells has been compared with human PDE7A1 under identical conditions. Mouse PDE7A1 has a Km for cAMP of 0.2 microM, an optimal pH of 7.5, an IC(50) value of 14 microM for 3-isobutyl-1-methylxanthine (IBMX), and is dependent on Mg(2+) for activity. All these characteristics are very similar to those of human PDE7A1. In mice, PDE7A1 is expressed in tissues of the immune system (lymph node, thymus, spleen, and blood leukocyte), testis, brain, kidney and lung but not in skeletal muscle, heart, embryo, or liver, while PDE7A2 is expressed in skeletal muscle, heart, embryo, and kidney, but not in the other tissues. This tissue distribution profile is very similar to that in humans, and hence suggests that PDE7A1 and 7A2 might play a similar role in different species.     

An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication

Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus. NS5b is an RNA-dependent RNA polymerase that polymerizes the newly synthesized RNA. HCV likely uses host proteins for its replication, similar to other RNA viruses. To identify the cellular factors involved in HCV replication, we searched for cellular proteins that interact with the NS5b protein. HnRNP A1 and septin 6 proteins were identified by coimmunoprecipitation and yeast two-hybrid screening, respectively. Interestingly, septin 6 protein also interacts with hnRNP A1. Moreover, hnRNP A1 interacts with the 5'-nontranslated region (5' NTR) and the 3' NTR of HCV RNA containing the cis-acting elements required for replication. Knockdown of hnRNP A1 and overexpression of C-terminally truncated hnRNP A1 reduced HCV replication. In addition, knockdown of septin 6 and overexpression of N-terminally truncated septin 6 inhibited HCV replication. These results indicate that the host proteins hnRNP A1 and septin 6 play important roles in the replication of HCV through RNA-protein and protein-protein interactions.     

Relationship between cellular diadenosine 5',5'-P1,P4-tetraphosphate level, cell density, cell growth stimulation and toxic stresses

In order to elucidate the postulated role of diadenosine 5',5'-P1,P4-tetraphosphate (Ap4A) in cell growth regulation, the Ap4A cellular content was measured in cells submitted to various treatments affecting the cell growth. Ap4A level was found to increase ten times when cells reached confluence, whereas no significant variation of the ATP pool was observed. Cell growth arrest after serum depletion did not cause any variation in the Ap4A pool. A limited increase in the Ap4A pool was observed when growth of arrested cells was reinitiated but this variation reflected only the increase of cell density. No significant variation in the Ap4A intracellular level was observed after submitting two eukaryotic cell lines to various stresses (cytotoxic drugs, ethanol and heat-shock treatments). These results suggest that, in eukaryotic cells, Ap4A is not involved in cell growth stimulation but rather is associated with cell contact growth inhibition. They also suggest that Ap4A is not an 'alarmone', contrary to what has been proposed for bacteria.     

Time-accurate,parallel, multi-zone,multi-block solver to study the human cardio-vascular system

A parallel, time-accurate flow solver is devised to study the human cardio-vascular system. The solver is capable of dealing with moving boundaries and moving grids. It is designed to handle complex, three-dimensional vascular systems. The computational domain is divided into multiple block subdomains. At each cross section the plane is divided into twelve sub-zones to allow flexibility for handling complex geometries and, if needed, appropriate parallel data partitioning. The unsteady, three-dimensional, incompressible Navier-Stokes equations are solved numerically. A second-order in time and third-order upwind finite volume method for solving time-accurate incompressible flows based on pseudo-compressibility and dual time-stepping technique is used. For parallel execution, the flow domain is partitioned. Communication between the subdomains of the flow on Riken's VPP/700E supercomputer is implemented using MPI message-passing library. A series of numerical simulations of biologically relevant flows is used to validate this code.     

A new Ansonia from the Isthmus of Kra, Thailand (Amphibia, Anura, Bufonidae)

A new species of torrent-dwelling bufonid frog of the genus Ansonia is described from the Isthmus of Kra, Thailand. Ansonia kraensis is morphologically similar to Malaysian A. malayana, but differs from it in ventral coloration and larval morphology. Occurrence of A. kraensis in this region suggests a heterogeneous nature of the anuran fauna between northern and southern regions of the Malay Peninsula.     

Safe, convenient, portable pipettor.

A dafe, convenient, portable pipetting device that will accommodate any size pipette is described. A vacuum bulb eliminates the need for external vacuum. Necessary components, fabrication procedures, and operating techniques are given.     

Revisione delle specie: Actinomyces albus,A. chromogenus,A. odorifer,A. thermophylus,A. viridis,A. viridochromogenes,A. hominis,A. innominatus

Riassunto Lo studio comprende una revisione critico-sperimentale della specie Actinomyces albus, della quale vengono considerati come sinonimi circa 30 nomi speeifici, fra i quale A. chromogenus, A. odorifer, A. thermophylus p.p.; della specie é data una diagnosi ed una particolareggiata descrizione.Sono inoltre studiate le specie A. viridis, (= A. viridochromogenus) e A. innominatus, n. nomen. Quest'ultima é preceduta da una breve discussione sulla specie A. homini.

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Summary Twenty-six strains of Actinomyces albus are studied redescribed from morphological, cultural and biochemical standpoints. Many biological activities of A. chromogenus, A. odorifer and A. thermophilus are in common with other species of the same genus, so that they may be considered for sub-specific, (not specific) differentiation. A discussion on A. farcinicus, A. albidoflavus and A. aureus has been originated from mislabeling as A. albus; the group including the two last named species (flavus group) must be revised. A few strains classified A. farcinicus are in no doubt true A. albus, but this real specific entity remains to be revised from Nocard's strain. A. viridis, for the first time described by Lombardo-Pellegrino, has been redescribed three times as a new species under the same binomial, and the fourth as A. viridochromogenes. A. hominis Bostroem is an uncorrect determination for the species originally described by Waksmann and Curtiss, and it is renamed A. innominatus, the binomial A. (Streptothrix) hominis Auct. being a nomen ambiguum. In conclusion, 30 bionmial are appended in sinonimy to A. albus, including Cladothrix dichotoma Macé (1888) non Cohn, G. invulnerabilis Acosta et G. Rossi, C. odorifera Rullm. Actinomyces chromogenus Gasp., A. thermophilus Auct., p.p., A. (Streptothrix) Sanninii (Cif.) Westerd., A. Almquisti Duché, A. Gougeroti Duché, and so on.

     

A novel human nucleolar protein, Nop132, binds to the G proteins, RRAG A/C/D

RRAG A (Rag A)/Gtr1p is a member of the Ras-like small G protein family that genetically interacts with RCC1, a guanine nucleotide exchange factor for RanGTPase. RRAG A/Gtr1p forms a heterodimer with other G proteins, RRAG C and RRAG D/Gtr2p, in a nucleotide-independent manner. To further elucidate the function of RRAG A/Gtr1p, we isolated a protein that interacts with RRAG A. This protein is a novel nucleolar protein, Nop132. Nop132 is associated with the GTP form, but not the GDP form, of RRAG A, suggesting that RRAG A might regulate Nop132 function. Nop132 is also associated with RRAG C and RRAG D. The Nop132 amino acid sequence is similar to the Saccharomyces cerevisiae nucleolar Nop8p, which is associated with Gtr1p, Gtr2p, and Nip7p. Nop132 also interacts with human Nip7 and is colocalized with RRAG A, RRAG C, and Nip7. RNA interference knockdown of Nop132 inhibited cell growth of HeLa cells.     

Class A scavenger receptors, macrophages, and atherosclerosis

The scope of this review is to discuss the new advances in our understanding of the role of scavenger receptor class A in the initiation and modulation of the atherosclerotic process. Through the approaches of gene manipulation in the mouse model, a substantial body of literature has accumulated that depicts scavenger receptor class A as a central player in atherogenesis. In studies of scavenger receptor class A overexpression in macrophages through bone marrow transplantation using transgenic donor material, recipient mice with hyperlipidemia caused either by apolipoprotein E or LDL receptor deficiency did not show convincing changes in the degree of atherosclerosis development compared with controls. Conversely, the deletion of the scavenger receptor class A gene in the mouse has shown, in a consistent and significant fashion, that this receptor serves a pro-atherogenic function under hyperlipidemic conditions, as both apolipoprotein E and LDL receptor-deficient mice had reduced atherosclerosis in the absence of scavenger receptor class A. In addition, we have recently shown that C57BL/6 mice are protected from diet-induced atherosclerosis when they lack scavenger receptor class A, and that the macrophage is the cell type responsible for the effect of scavenger receptor class A deficiency in reducing lesion formation in C57BL/6 and LDL receptor null mice. Together, these results demonstrate that macrophage scavenger receptor class A contributes significantly to atherosclerotic lesion formation, and suggest that the uptake of oxidized or modified lipoproteins by vessel wall macrophages is a central process in atherogenesis.