D- and L-lactate dehydrogenases during invertebrate evolution

Background: The L-lactate and D-lactate dehydrogenases, which are involved in the reduction of pyruvate to L(-)-lactate and D(+)-lactate, belong to evolutionarily unrelated enzyme families. The genes encoding L-LDH have been used as a model for gene duplication due to the multiple paralogs found in eubacteria, archaebacteria, and eukaryotes. Phylogenetic studies have suggested that several gene duplication events led to the main isozymes of this gene family in chordates, but little is known about the evolution of L-Ldh in invertebrates. While most invertebrates preferentially oxidize L-lactic acid, several species of mollusks, a few arthropods and polychaetes were found to have exclusively D-LDH enzymatic activity. Therefore, it has been suggested that L-LDH and DLDH are mutually exclusive. However, recent characterization of putative mammalian D-LDH with significant similarity to yeast proteins showing D-LDH activity suggests that at least mammals have the two naturally occurring forms of LDH specific to L- and D-lactate. This study describes the phylogenetic relationships of invertebrate L-LDH and D-LDH with special emphasis on crustaceans, and discusses gene duplication events during the evolution of L-Ldh. Results: Our phylogenetic analyses of L-LDH in vertebrates are consistent with the general view that the main isozymes (LDH-A, LDH-B and LDH-C) evolved through a series of gene duplications after the vertebrates diverged from tunicates. We report several gene duplication events in the crustacean, Daphnia pulex, and the leech, Helobdella robusta. Several amino acid sequences with strong similarity to putative mammalian D-LDH and to yeast DLD1 with D-LDH activity were found in both vertebrates and invertebrates. Conclusion: The presence of both L-Ldh and D-Ldh genes in several chordates and invertebrates suggests that the two enzymatic forms are not necessarily mutually exclusive. Although, the evolution of L-Ldh has been punctuated by multiple events of gene duplication in both vertebrates and invertebrates, a shared evolutionary history of this gene in the two groups is apparent. Moreover, the high degree of sequence similarity among D-LDH amino acid sequences suggests that they share a common evolutionary history

A Second Large Subglacial Impact Crater in Northwest Greenland?

Following the discovery of the Hiawatha impact crater beneath the northwest margin of the Greenland Ice Sheet, we explored satellite and aerogeophysical data in search of additional such craters. Here we report the discovery of a possible second subglacial impact crater that is 36.5 km wide and 183 km southeast of the Hiawatha impact crater. Although buried by 2 km of ice, the structure's rim induces a conspicuously circular surface expression, it possesses a central uplift and it causes a negative gravity anomaly. The existence of two closely-spaced and similarlysized complex craters raises the possibility that they formed during related impact events. However, the second structure's morphology is shallower, its overlying ice is conformal and older, and such an event can be explained by chance. We conclude that the identified structure is very likely an impact crater, but it is unlikely to be a twin of the Hiawatha impact crater

A Possible Second Large Subglacial Impact Crater in Northwest Greenland

Following the discovery of the Hiawatha impact crater beneath the northwest margin of the Greenland Ice Sheet, we explored satellite and aerogeophysical data in search of additional such craters. Here we report the discovery of a possible second subglacial impact crater that is 36.5 km wide and 183 km southeast of the Hiawatha impact crater. Although buried by 2 km of ice, the structure's rim induces a conspicuously circular surface expression, it possesses a central uplift and it causes a negative gravity anomaly. The existence of two closely-spaced and similarlysized complex craters raises the possibility that they formed during related impact events. However, the second structure's morphology is shallower, its overlying ice is conformal and older, and such an event can be explained by chance. We conclude that the identified structure is very likely an impact crater, but it is unlikely to be a twin of the Hiawatha impact crater

Paramutation-like Epigenetic Conversion by piRNA at the Telomere of Drosophila virilis

First discovered in maize, paramutation is a phenomenon in which one allele can trigger an epigenetic conversion of an alternate allele. This conversion causes a genetically heterozygous individual to transmit alleles that are functionally the same, in apparent violation of Mendelian segregation. Studies over the past several decades have revealed a strong connection between mechanisms of genome defense against transposable elements by small RNA and the phenomenon of paramutation. For example, a system of paramutation in Drosophila melanogaster has been shown to be mediated by piRNAs, whose primary function is to silence transposable elements in the germline. In this paper, we characterize a second system of piRNA-mediated paramutation-like behavior at the telomere of Drosophila virilis. In Drosophila, telomeres are maintained by arrays of retrotransposons that are regulated by piRNAs. As a result, the telomere and sub-telomeric regions of the chromosome have unique regulatory and chromatin properties. Previous studies have shown that maternally deposited piRNAs derived from a sub-telomeric piRNA cluster can silence the sub-telomeric center divider gene of Drosophila virilis in trans. In this paper, we show that this silencing can also be maintained in the absence of the original silencing allele in a subsequent generation. The precise mechanism of this paramutation-like behavior may be explained by either the production of retrotransposon piRNAs that differ across strains or structural differences in the telomere. Altogether, these results show that the capacity for piRNAs to mediate paramutation in trans may depend on the local chromatin environment and proximity to the uniquely structured telomere regulated by piRNAs. This system promises to provide significant insights into the mechanisms of paramutation

Assessing the role of clay and salts on the origin of MARSIS basal bright reflections

Anomalously bright basal reflections detected by MARSIS at Ultimi Scopuli have been interpreted to indicate the presence of water-saturated materials or ponded liquid water at the base of the South Polar Layered Deposits (SPLD). Because conventional models assume basal temperatures (≤200 K) much lower than the melting point of water, this interpretation has been questioned and other explanations for the source of the bright basal reflections have been proposed, involving clay, hydrated salts, and saline ices. Combining previous published data, simulations, and new laboratory measurements, we demonstrate that the dielectric properties of these materials do not generate strong basal reflections at MARSIS frequencies and Martian temperatures. Plausible candidates remain perchlorates and chlorides brines that exhibit a strong dielectric response at much lower temperatures than other materials. This explanation might require that metastability could be maintained for a long period of time on a geological scale

Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W

Congenital chloride diarrhea is an autosomal recessive disease caused by mutations in the intestinal lumenal membrane Cl−/HCO−3 exchanger, SLC26A3. We report here the novel SLC26A3 mutation G393W in a Mexican child, the first such report in a patient from Central America. SLC26A3 G393W expression in Xenopus oocytes exhibits a mild hypomorphic phenotype, with normal surface expression and moderately reduced anion transport function. However, expression of HA-SLC26A3 in HEK-293 cells reveals intracellular retention and greatly decreased steady-state levels of the mutant polypeptide, in contrast to peripheral membrane expression of the wildtype protein. Whereas wildtype HA-SLC26A3 is apically localized in polarized monolayers of filter-grown MDCK cells and Caco2 cells, mutant HA-SLC26A3 G393W exhibits decreased total polypeptide abundance, with reduced or absent surface expression and sparse punctate (or absent) intracellular distribution. The WT protein is similarly localized in LLC-PK1 cells, but the mutant fails to accumulate to detectable levels. We conclude that the chloride-losing diarrhea phenotype associated with homozygous expression of SLC26A3 G393W likely reflects lack of apical surface expression in enterocytes, secondary to combined abnormalities in polypeptide trafficking and stability. Future progress in development of general or target-specific folding chaperonins and correctors may hold promise for pharmacological rescue of this and similar genetic defects in membrane protein targeting

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page