Structural Insights into the Mechanism of Base Excision by MBD4

DNA glycosylases remove damaged or modified nucleobases by cleaving the N-glycosyl bond and the correct nucleotide is restored through subsequent base excision repair. In addition to excising threatening lesions, DNA glycosylases contribute to epigenetic regulation by mediating DNA demethylation and perform other important functions. However, the catalytic mechanism remains poorly defined for many glycosylases, including MBD4 (methyl-CpG binding domain IV), a member of the helix-hairpin-helix (HhH) superfamily. MBD4 excises thymine from G·T mispairs, suppressing mutations caused by deamination of 5-methylcytosine, and it removes uracil and modified uracils (e.g., 5-hydroxymethyluracil) mispaired with guanine. To investigate the mechanism of MBD4 we solved high-resolution structures of enzyme-DNA complexes at three stages of catalysis. Using a non-cleavable substrate analog, 2′-deoxy-pseudouridine, we determined the first structure of an enzyme-substrate complex for wild-type MBD4, which confirms interactions that mediate lesion recognition and suggests that a catalytic Asp, highly conserved in HhH enzymes, binds the putative nucleophilic water molecule and stabilizes the transition state. Observation that mutating the Asp (to Gly) reduces activity by 2700-fold indicates an important role in catalysis, but probably not one as the nucleophile in a double-displacement reaction, as previously suggested. Consistent with direct-displacement hydrolysis, a structure of the enzyme-product complex indicates a reaction leading to inversion of configuration. A structure with DNA containing 1-azadeoxyribose models a potential oxacarbenium-ion intermediate and suggests the Asp could facilitate migration of the electrophile towards the nucleophilic water. Finally, the structures provide detailed snapshots of the HhH motif, informing how these ubiquitous metal-binding elements mediate DNA binding.     

Coordination polymers of Ln(III): Synthesis, characterization, catalytic and antimicrobial aspects

Coordination polymers of HEAP-ED with La(III), Pr(III), Nd(III), Sm(III), Gd(III), Tb(III) and Dy(III) metal ions have been synthesized and characterized by elemental analyses, electronic spectra, magnetic susceptibilities, FTIR, NMR, scanning electronic microscopy (SEM) and thermogravimetric analyses. Catalytic activity of selected coordination polymers was examined for pharmaceutical important organic synthesis. Antimicrobial activity of isolated Ln(III) coordination polymers against Escherichia coli, Bacillus subtilis, Staphylococcus aureus (bacteria) and Saccharomyces cerevisiae (yeast) were measured. It was observed from the study that the Ln(III) coordination polymers acted as an efficient and effective catalysts and antimicrobial agents.     

Expanded thermal niche for a diving vertebrate: A leatherback turtle diving into near-freezing water

The global distribution of extant reptiles is more limited than that of mammals or birds, with low reptilian species diversity at high latitudes. Central to this limited geographical distribution is the ectothermic nature of reptiles, which means that they generally become torpid at cold temperatures. However, here we report the first detailed telemetry from a leatherback turtle (Dermochelys coriacea) diving in cold water at high latitude. An individual equipped with a satellite tag that relayed temperature-depth profiles dived continuously for many weeks into sub-surface waters as cold as 0.4 °C. Global warming will likely increase the foraging range of leatherback turtles further into temperate and boreal waters.     

A protocol for temporal calibration of general area cladograms

Aim To describe a protocol for incorporating a temporal dimension into historical biogeographical analysis, while maintaining the essential independence of all datasets, involving the generation of general area cladograms. Location Global. Methods General area cladograms (GACs) are a reconstruction of the evolutionary history of a set of areas and unrelated clades within those areas. Nodes on a GAC correspond to speciation events in a group of taxa; general nodes are those at which multiple unrelated clades speciate. We undertake temporal calibration of GACs using molecular clock estimates of splitting events between extant taxa as well as first appearance data from the fossil record. We present two examples based on re‐analysis of previously published data: first, a temporally calibrated GAC generated from secondary Brooks parsimony analysis (BPA) of six extant bird clades from the south‐west of North America using molecular clock estimates of divergence times; and second, an analysis of African Neogene mammals based on a phylogenetic analysis for comparing trees (PACT) analysis. Results A hypothetical example demonstrates how temporal calibration reveals potentially critical information about the timing of both unique and general events, while also illustrating instances of incongruence between dates generated from molecular clock estimates and fossils. For the African Neogene mammal dataset, our analysis reveals that most mammal clades underwent geodispersal associated with the Neogene climatic optimum (c. 16 Ma) and vicariant speciation in central Africa correlated with increased aridity and cooler temperatures around 2.5 Ma. Main conclusions Temporally calibrated GACs are valuable tools for assessing whether coordinated patterns of speciation are associated with large‐scale climatic or tectonic phenomena.     

The Effect of Leaf Age on Gas Exchange and Malate Accumulation in C3-CAM Plant Marrubium Frivaldszkyanum (Lamiaceae)

For the first time the expression of C₃ and CAM in the leaves of different age of Marrubium frivaldszkyanum Boiss, is reported. With increasing leaf age a typical C₃ photosynthesis pattern and high transpiration rate were found. In older leaves a shift to CAM occurred and the 24-h transpiration water loss decreased. A correlation was established between leaf area and accumulation of malate. Water loss at early stages of leaf expansion may be connected with the shift to CAM and the water economy of the whole plant.     

The Amount of BCL6 in B Cells Shortly after Antigen Engagement Determines Their Representation in Subsequent Germinal Centers

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Optimal reproductive phenology under size‐dependent cannibalism

Intra‐cohort cannibalism is an example of a size‐mediated priority effect. If early life stages cannibalize slightly smaller individuals, then parents face a trade‐off between breeding at the best time for larval growth or development and predation risk from offspring born earlier. This game‐theoretic situation among parents may drive adaptive reproductive phenology toward earlier breeding. However, it is not straightforward to quantify how cannibalism affects seasonal egg fitness or to distinguish emergent breeding phenology from alternative adaptive drivers. Here, we devise an age‐structured game‐theoretic mathematical model to find evolutionary stable breeding phenologies. We predict how size‐dependent cannibalism acting on eggs, larvae, or both changes emergent breeding phenology and find that breeding under inter‐cohort cannibalism occurs earlier than the optimal match to environmental conditions. We show that emergent breeding phenology patterns at the level of the population are sensitive to the ontogeny of cannibalism, that is, which life stage is subject to cannibalism. This suggests that the nature of cannibalism among early life stages is a potential driver of the diversity of reproductive phenologies seen across taxa and may be a contributing factor in situations where breeding occurs earlier than expected from environmental conditions.     

Is there modal opponency in the thermal senses?

1. 1.The sensations evoked by pairs of distinct thermal stimuli applied to the back of the hand were studied in 17 volunteer subjects. Four stimulus combinations were used; neutral-cold (NC), neutral-neutral (NN), neutral-warm (NW), and cold-warm (CW).

2. 2.The subjects were first asked to estimate the magnitude of the thermal sensations evoked by the thermal stimuli. On average, the four pairs were reported as increasing magnitude in the following order: NC, CW, NN, and NW, seeming to suggest that the subjects experienced the cold-warm combination as a composite sensation of cold and warmth intermediate between pure cold and pure warmth.

3. 3.When asked only to detect the presence of a cold stimulus, the subjects performed as well for the CW combination as for the CN combination. This second result indicates that the reported composite magnitude of CW does not result from a true opponency of cold and warmth but from a cognitive combination of distinct sensations of cold and warmth.

The fifteenth- and twentieth-century colonization of the Basin of Mexico by the Great-tailed Grackle (Quiscalus mexicanus)

Historical evidence indicates that Great‐tailed Grackles colonized the Basin of Mexico from the Gulf Coast lowlands in the fifteenth century. They were probably assisted by an intentional introduction, but colonization succeeded because of anthropogenic habitat alterations over the previous two centuries. During the Colonial period, grackles withdrew from the Basin, only to recolonize it in recent decades. This withdrawal was also due probably to changes in land use, including drainage of much of the water from the Basin's lakes.