Regulation of voltage-gated Ca channels by lipids

Great skepticism has surrounded the question of whether modulation of voltage-gated Ca²⁺ channels (VGCCs) by the polyunsaturated free fatty acid arachidonic acid (AA) has any physiological basis. Here we synthesize findings from studies of both native and recombinant channels where micromolar concentrations of AA consistently inhibit both native and recombinant activity by stabilizing VGCCs in one or more closed states. Structural requirements for these inhibitory actions include a chain length of at least 18 carbons and multiple double bonds located near the fatty acid's carboxy terminus. Acting at a second site, AA increases the rate of VGCC activation kinetics, and in Ca_V2.2 channels, increases current amplitude. We present evidence that phosphatidylinositol 4,5-bisphosphate (PIP₂), a palmitoylated accessory subunit (β_2a) of VGCCs and AA appear to have overlapping sites of action giving rise to complex channel behavior. Their actions converge in a physiologically relevant manner during muscarinic modulation of VGCCs. We speculate that M₁ muscarinic receptors may stimulate multiple lipases to break down the PIP₂ associated with VGCCs and leave PIP₂'s freed fatty acid tails bound to the channels to confer modulation. This unexpectedly simple scheme gives rise to unanticipated predictions and redirects thinking about lipid regulation of VGCCs.     

Plant action: Multiple levels of regulation

This lecture is devoted to the relative contribution of various levels of regulation of the actin cytoskeleton functioning in the cell. Regulation at the levels of gene expression, mRNA and protein synthesis and stability, processes of actin polymerization/depolymerization and actin structures reorganization is briefly considered. Novel information about the pathways of signal transduction to the actin cytoskeleton with the involvement of Arp2/3 complex and RIC proteins is highlighted.     

Morphological diversity of leaves of <Emphasis Type="Italic">Pseudoprotophyllum</Emphasis> (Platanaceae) from the Turonian-Coniacian of the northern coast of the Sea of Okhotsk

Fossil plants of the Chingandzha flora were studied from volcanogenic sediments of the Chingandzha and Rond formations on the northern coast of the Sea of Okhotsk. It was concluded that all platanaceous leaves earlier described in this flora as different taxa belong to one highly variable species, Pseudoprotophyllum cordatum Samyl. emend. Shczepetov et Golovneva.     

Late Glacial and Holocene environmental and climatic changes from a limnological transect through Colombia, northern South America

We present a synthesis of the palaeolimnological and palaeoclimatic reconstructions of four sites in Colombia. The record from Lake El Caimito, the westernmost site on the Pacific Coast, dates from the Late Holocene and shows lacustrine sedimentation frequently interrupted by fluvial pulses. These pulses probably reflect periods of increased precipitation related to La Niña phases. East of El Caimito site is the Patía swamp, situated between the Western and Central Andean Cordilleras. The Patía records the dynamics of forest expansion/reduction and changes in water levels. Although the climatic signal of the Patia core is difficult to reconstruct, there is a clear increase in humidity in the Mid-Holocene. The Fúquene Lake record, on the Eastern Andean Cordillera, records dry and cold conditions during the Late Pleistocene, very humid conditions for the early Mid-Holocene, and dry conditions during the mid-Late Holocene. Las Margaritas site, on the eastern savannas, records dry conditions during the Early Holocene and overall humid conditions for the Mid- and Late Holocene. Climate conditions from the Fuquene and Las Margaritas sites seem to reflect the Holocene movements of the Intertropical Convergence Zone (ITCZ); the latter site being more affected by humidity coming from the Amazon region.     

Phylogeography of the cactophilic species Drosophila gouveai: demographic events and divergence timing in dry vegetation enclaves in eastern Brazil

Aim  The aim of this study was to assess the causal mechanisms underlying populational subdivision in Drosophila gouveai , a cactophilic species associated with xeric vegetation enclaves in eastern Brazil. A secondary aim was to investigate the genetic effects of Pleistocene climatic fluctuations on these environments.
Location  Dry vegetation enclaves within the limits of the Cerrado domain in eastern Brazil.
Methods  We determined the mitochondrial DNA haplotypes of 55 individuals (representing 12 populations) based on sequence data of a 483-bp fragment from the cytochrome c oxidase subunit II (COII) gene. Phylogenetic and coalescent analyses were used to test for the occurrence of demographic events and to infer the time of divergence amongst genetically independent groups.
Results  Our analyses revealed the existence of two divergent subclades (G1 and G2) plus an introgressed clade restricted to the southernmost range of D. gouveai . Subclades G1 and G2 displayed genetic footprints of range expansion and segregated geographical distributions in south-eastern and some central highland regions, east and west of the Paraná River valley. Molecular dating indicated that the main demographic and diversification events occurred in the late to middle Pleistocene.
Main conclusions  The phylogeographical and genetic patterns observed for D. gouveai in this study are consistent with changes in the distribution of dry vegetation in eastern Brazil. All of the estimates obtained by molecular dating indicate that range expansion and isolation pre-dated the Last Glacial Maximum, occurring during the late to middle Pleistocene, and were probably triggered by climatic changes during the Pleistocene. The current patchy geographical distribution and population subdivision in D. gouveai is apparently closely linked to these past events.     

Effects of neurotropin on seizure activity in picrotoxin kindling]

It is shown that both intracerebral and intraperitoneal neurotropin administration resulted in a decrease of seizure susceptibility of preliminary picrotoxin--kindled rats. On the other hand, neurotropin did not change the course of kindling development. Under conditions of acute picrotoxin--induced seizures it was observed that preliminary cycloheximide (protein-synthesis blocker) administration abolished anticonvulsant properties of neurotropin. It is concluded that anticonvulsant effects of neurotropin are realized via modulation of endogenous peptides synthesis and, in particular, cerulein.     

Characterization of newly established colorectal cancer cell lines: correlation between cytogenetic abnormalities and allelic deletions associated with multistep tumorigenesis

We have established a series of 20 colorectal cancer cell lines and performed cytogenetic and RFLP analyses to show that the recurrent genetic abnormalities of chromosomes 1, 5, 17 and 18 associated with multistep tumorigenesis in colorectal cancer, and frequently detected as recurrent abnormalities in primary tumours, are also retained in long-term established cell lines. Earlier studies by us and other investigators showed that allelic losses of chromosomes 1 and 17 in primary colorectal cancers predicted poorer survival for the patients (P = 0.03). We utilized the cell lines to identify specific chromosomal sites or gene(s) on chromosomes 1 and 17 which confer more aggressive phenotype. Cytogenetic deletions of chromosome 1p were detected in 14 out of the 20 (70%) cell lines, whereas allelic deletions for 1p using polymorphic markers were detected in 13 out of 18 (72%) informative cell lines for at least one polymorphic marker. We have performed Northern blotting, immunohistochemical staining (p53 mRNA, protein) and RFLP analysis using several probes including p53 and nm23. RFLP analysis using a total of seven polymorphic markers located on 17p and 17q arms showed allelic losses aroundthe p53 locus in 16 out of the 20 cell lines (80%), four of which were losses of thep53 locus itself. In addition, seven cell lines (out of nine informative cases) also showed losses of thenm23 gene, four with concurrent losses of thep53 locus, while the remaining three were homozygous. In addition, five out of seven cell lines withnm23 deletions were derived from hepatic metastatic tumours, and one cell line was obtained from recurrent tumour. A comparison between allelic deletions of 1p and functional loss ofnm23 gene revealed a close association between these two events in cell lines derived from hepatic metastasis. Following immunohistochemical staining, nine out of the twenty cell lines showed high levels (25–80%) of mutant p53, four showed intermediate levels (>20%), and seven had undetectable levels of the protein. Of these seven, four showed complete absence of mRNA. Of the remaining three cell lines one showed aberrant mRNA due to germline rearrangement of thep53 gene, whereas in two cell lines normal levels of mRNA were present. Nineteen of the 20 cell lines had normal germline configurations for thep53 gene, while one showed a rearrangement. These data suggest that functional loss ofp53 andnm23 genes accomplished by a variety of mechanisms may be associated with poor prognosis and survival. In addition, concurrent deletions of chromosome regions 17p, 17q and 1p were closely associated with high-stage hepatic metastatic disease. These cell lines with well-characterized genetic alterations and known clinical history provide an invaluable source of material for various biological and clinical studies relating to multistep colorectal tumorigenesis.     

Specific Features of the Formation of a Halo during Pathogenesis as a Response of Cereal Epidermal Cells to Penetration of Powdery Mildew Causative Agents

A cytophysiological study was carried out of the functional status of a halo as a response of the host plant to contact with a powdery mildew pathogen. Interactions of the powdery mildew causative agents with barley, wheat, wheat–wheat-grass hybrids, wheat-aegilops lines, and aegilops with different genotypic resistance lead to the expression of haloes during pathogens, which are induced by infection pegs of the primary growth tubes, appressoria, and hyphal lobes. Haloes are visualized using cytochemical reactions to proteins and scanning electron microscopy. The observed differences in the size of haloes and intensity of their staining (uniform or zonal) are related, to a great extent, to individual reactions of the plant cell at the penetration site and, to a lesser extent, to the level of genotypic resistance. An analysis of electron microscopy and cytochemistry studies suggests that the halo as a physiologically active zone is localized at the level of the plant cell plasmalemma. Active taxis of the cell organelles to the site of infection during the formation of a halo suggests that some kind of informational signals to changes in the cell metabolism are spread from the halo zone, which lead to compatible or incompatible interactions.     

Distinguishing Drift and Selection Empirically: “The Great Snail Debate” of the 1950s

Biologists and philosophers have been extremely pessimistic about the possibility of demonstrating random drift in nature, particularly when it comes to distinguishing random drift from natural selection. However, examination of a historical case – Maxime Lamotte’s study of natural populations of the land snail, Cepaea nemoralis in the 1950s – shows that while some pessimism is warranted, it has been overstated. Indeed, by describing a unique signature for drift and showing that this signature obtained in the populations under study, Lamotte was able to make a good case for a significant role for␣drift. It may be difficult to disentangle the causes of drift and selection acting in a population, but it is not (always) impossible.