Activation of the c-Jun N-terminal kinase pathway by a novel protein kinase related to human germinal center kinase

The c-Jun N-terminal kinase (JNK), or stress-activated protein kinase plays a crucial role in cellular responses stimulated by environmental stress and proinflammatory cytokines. However, the mechanisms that lead to the activation of the JNK pathway have not been elucidated. We have isolated a cDNA encoding a novel protein kinase that has significant sequence similarities to human germinal center kinase (GCK) and human hematopoietic progenitor kinase 1. The novel GCK-like kinase (GLK) has a nucleotide sequence that encodes an ORF of 885 amino acids with 11 kinase subdomains. Endogenous GLK could be activated by UV radiation and proinflammatory cytokine tumor necrosis factor α. When transiently expressed in 293 cells, GLK specifically activated the JNK, but not the p42/44MAPK/extracellular signal-regulated kinase or p38 kinase signaling pathways. Interestingly, deletion of amino acids 353–835 in the putative C-terminal regulatory region, or mutation of Lys-35 in the putative ATP-binding domain, markedly reduced the ability of GLK to activate JNK. This result indicates that both kinase activity and the C-terminal region of GLK are required for maximal activation of JNK. Furthermore, GLK-induced JNK activation could be inhibited by a dominant-negative mutant of mitogen-activated protein kinase kinase kinase 1 (MEKK1) or mitogen-activated protein kinase kinase 4/SAPK/ERK kinase 1 (SEK1), suggesting that GLK may function upstream of MEKK1 in the JNK signaling pathway.

O Ministério Público perante os Poderes Judiciário, Executivo e Legislativo : análise de sua posição constitucional

O Ministério Público como órgão integrado ao Poder Judiciário -- O Ministério Público como órgão do Poder Executivo -- O Ministério Público como órgão vinculado ao Parlamento

The 5' coding region of Paramecium surface antigen genes controls mutually exclusive transcription.

Paramecium tetraurelia stock 51 can express at least 11 different types of surface antigens, yet only a single type is expressed on the surface of an individual cell at any one time. The differential expression of stock 51 type A and B surface antigen genes (51A and 51B) is regulated at the level of transcription. Previously, we reported that nucleotide sequences upstream of position -26 (relative to the start of translation) in the 51A and 51B surface antigen genes are necessary for transcriptional activity but are not sufficient to direct differential transcriptional control. In this report we demonstrate that at least some of the critical elements necessary for differential transcription of the 51A and 51B genes lie within the 5' coding region. A hybrid gene that contains 51B upstream sequences (-475 to +1) attached to the ATG start codon of 51A is not cotranscribed with the 51B gene. In contrast, further substitution with 51B sequences (-1647 to +885) allows the chimeric gene to be coexpressed with 51B. A different hybrid gene containing a substitution of 51B sequence from -26 to +885 in the 51A gene is also coexpressed with 51B, revealing that the critical elements within the coding region of 51B do not require 51B upstream sequences for their effect. Coinjection of the 51A gene with the chimeric gene that contains 51B up to +885 showed that the same sequences that allow coexpression with 51B prevent cotranscription with 51A. Together, these results demonstrate that a region downstream of the transcriptional start site between nucleotide positions +1 and +885 (relative to translational start) is necessary to control differential transcriptional activity.

Genetic and comparative analyses reveal an alternative secondary structure in the region of nt 912 of Escherichia coli 16S rRNA.

Mutations at position 912 of Escherichia coli 16S rRNA result in two notable phenotypes. The C-->U transition confers resistance to streptomycin, a translational-error-inducing antibiotic, while a C-->G transversion causes marked retardation of cell growth rate. Starting with the slow-growing G912 mutant, random mutagenesis was used to isolate a second site mutation that restored growth nearly to the wild-type rate. The second site mutation was identified as a G-->C transversion at position 885 in 16S rRNA. Cells containing the G912 mutation had an increased doubling time, abnormal sucrose gradient ribosome/subunit profile, increased sensitivity to spectinomycin, dependence upon streptomycin for growth in the presence of spectinomycin, and slower translation rate, whereas cells with the G912/C885 double mutation were similar to wild type in these assays. Comparative analysis showed there was significant covariation between positions 912 and 885. Thus the second-site suppressor analysis, the functional assays, and the comparative data suggest that the interaction between nt 912 and nt 885 is conserved and necessary for normal ribosome function. Furthermore, the comparative data suggest that the interaction extends to include G885-G886-G887 pairing with C912-U911-C910. An alternative secondary structure element for the central domain of 16S rRNA is proposed.

The Effects of Ultra-Loose Monetary Policies on Inequality. Bruegel Policy Contribution Issue 2015/09, June 2015

Highlights • Low interest rates, asset purchases and other accommodative monetary policy measures tend to increase asset prices and thereby benefit the wealthier segments of society, at least in the short-term, given that asset holdings are mainly concentrated among richest households. • Such policies also support employment, economic activity, incomes and inflation, which can benefit the poor and middle-class, which have incomes more dependent on employment and which tend to spend a large share of their income on debt service. • Monetary policy should focus on its mandate, while fiscal and social policies should address widening inequalities by revising the national social redistribution systems for improved efficiency, intergenerational equity and fair burden sharing between the wealthy and poor.

Opera / L. Annaei Senecae et ad dicendi facultatem, et ad bene viuendum vtilissima, per Des. Erasmum Roterod. & Matthaeum Fortunatum ... emendata ; adiecta sunt Scholia D. Erasmi Roterodami in bonam partem operis ; Beati Rhenani in Ludum de morte Claudij Caesaris ; Rodolphi Agricolae in Declamationes aliquot commentarioli ; Fernandi Pinciani castigationes in vniuersum opus ; index rerum & verborum locuples

Sign.: a8, a-z6, A-Z6, 2A-2M6, 2N4, 2A-2G6, 2H8, 2I-2K6, 2L4

Eolian and silica deposition of ODP sites in the central North Pacific

Sediments recovered at Ocean Drilling Program Sites 885/886 (central North Pacific Ocean at 44°41'N, 168°14'W and 44°41'N, 168°16'W, respectively) record eolian deposition during the Cenozoic and late Mesozoic. We constructed a record of eolian MAR, which is a proxy for aridity/humidity of the climate in the continental source area. Eolian fluxes are low during the Late Cretaceous through Eocene, reflecting humid conditions in the source area. During the Oligocene, more arid climates prevailed at the source area, as indicated by increased eolian accumulation. The "Diatom Dump", an interval of enhanced silica deposition mainly apparent in the northwest Pacific, is reflected in the record at Sites 885/886 by two- to fivefold higher opal fluxes compared with younger and older sediments. Increased eolian deposition starting at 3.5 Ma and culminating at 2-2.6 Ma are coincident with the onset of Northern Hemisphere glaciation. Sites 885/886 lie 10° north of sites examined previously for the history of eolian deposition in the central North Pacific and therefore allow enhanced understanding of the latitudinal variation of the wind system.