Exserohilum israeli, a new species isolated from soil from Timna Park (Israel), and its physiological properties

Fungi isolated from soil in Timna Park (Israel) were found to belong to a new species of Exserohilum for which the name Exserohilum israeli sp. nov. is proposed. The main physiological properties of members of this species are discussed and the influence of temperature and copper concentrations on the growth and morphology of the fungus were investigated.     

A condition for successful escape of a mutant after primary HIV infection

Cytotoxic T lymphocytes (CTLs) vigorously restrict primary human immunodeficiency virus (HIV) infection. However, the frequently erroneous process of viral replication favors the creation of mutants not recognizable by primary CTLs. Variants that tolerate the mutations may have selective advantage and may increase in abundance, until the immune system reacts against them. Therefore, such variants represent a way of propagating the viremia. With the aid of a simple mathematical model, here we estimate the intensity of CTL cross-reactivity against different strains of HIV in a typical progressor. We show that below a critical intensity of cross-reactivity, the concentration of a mutant created at primary peak grows and causes a secondary peak in viremia. Above this critical intensity, such a mutant strain is prevented from reaching a detectable level. We speculate about how this result may contribute to the design of an anti-HIV vaccine.     

Litter in a first–order stream of a temperate deciduous forest (Margaraça Forest, central Portugal)

To evaluate the importance and fate of organic matter inputs in forested streams, we determined the litterfall inputs and the benthic coarse particulate organic matter (CPOM) in one headwater stream flowing through a mixed deciduous forest, during one year. Both vertical traps and the stream bottom were sampled monthly. The material collected was sorted into four main categories: leaves, fruits and flowers, twigs and debris. Litter production was 715 g m−2 y−1 and seasonal, with 73% of the annual total during October–December (autumn). Leaves comprised the largest litter component. Benthic organic matter was 1880 g m−2 y−1, and was also seasonal. Highest accumulation was attained in spring, and twigs and branches comprised the major component. This revised version was published online in July 2006 with corrections to the Cover Date.     

Solution structure of the recombinant human oncoprotein p13 MTCP1

The human oncoprotein p13 ^MTCP1 is coded by the MTCP1 gene, a gene involved in chromosomal translocations associated with T-cell prolymphocytic leukemia, a rare form of human leukemia with a mature T-cell phenotype. The primary sequence of p13 ^MTCP1 is highly and only homologous to that of p14 ^TCL1 , a product coded by the gene TCL1 which is also involved in T-cell prolymphocytic leukemia. These two proteins probably represent the first members of a new family of oncogenic proteins. We present the three-dimensional solution structure of the recombinant p13 ^MTCP1 determined by homonuclear proton two-dimensional NMR methods at 600 MHz. After proton resonance assignments, a total of 1253 distance restraints and 64 dihedral restraints were collected. The solution structure of p13 ^MTCP1 is presented as a set of 20 DYANA structures. The rmsd values with respect to the mean structure for the backbone and all heavy atoms for the conformer family are 1.07 ± 0.19 and 1.71 ± 0.17 Å, when the structured core of the protein (residues 11–103) is considered. The solution structure of p13 ^MTCP1 consists of an orthogonal -barrel, composed of eight antiparallel -strands which present an original arrangement. The two -pleated loops which emerge from this barrel might constitute the interaction surface with a potential molecular partner.     

New insights into the kinetic resistance to anticancer agents

Kinetic resistance plays a major role in the failure of chemotherapy towards many solid tumors. Kinetic resistance to cytotoxic drugs can be reproduced in vitro by growing the cells as multicellular spheroids (Multicellular Resistance) or as hyperconfluent cultures (Confluence-Dependent Resistance). Recent findings on the cell cycle regulation have permitted a better understanding why cancer cells which arrest in long quiescent phases are poorly sensitive to cell-cycle specific anticancer drugs. Two cyclin-dependent kinase inhibitors (CDKI) seem particularly involved in the cell cycle arrest at the G1 to S transition checkpoint: the p53-dependent p21^cip1 protein which is activated by DNA damage and the p27^kip1 which is a mediator of the contact inhibition signal. Cell quiescence could alter drug-induced apoptosis which is partly dependent on an active progression in the cell cycle and which is facilitated by overexpression of oncogenes such as c-Myc or cyclins. Investigations are yet necessary to determine the influence of the cell cycle on the balance between antagonizing (bcl-2, bcl-X_L...) or stimulating (Bax, Bcl-X_S, Fas...) factors in chemotherapy-induced apoptosis. Quiescent cells could also be protected from toxic agents by an enhanced expression of stress proteins, such as HSP27 which is induced by confluence. New strategies are required to circumvent kinetic resistance of solid tumors: adequate choice of anticancer agents whose activity is not altered by quiescence (radiation, cisplatin), recruitment from G1 to S/G2 phases by cell pretreatment with alkylating drugs or attenuation of CDKI activity by specific inhibitors. This revised version was published online in August 2006 with corrections to the Cover Date.