Integrative Architectural Chemistry and biology from the Era of Precise Construction Idea

The human visual system is organized as a hierarchy of maps that share the topography of the retina. Known retinotopic maps have been identified using simple visual stimuli under strict fixation, conditions different from everyday vision which is active, dynamic, and complex. This means that it remains unknown how much of the brain is truly visually organized. Here I demonstrate widespread stable visual organization beyond the traditional visual system, in default-mode network and hippocampus. Detailed topographic connectivity with primary visual cortex during movie-watching, resting-state, and retinotopic-mapping experiments revealed that visual-spatial representations throughout the brain are warped by cognitive state. Specifically, traditionally visual regions alternate with default-mode network and hippocampus in preferentially representing the center of the visual field. This visual role of default-mode network and hippocampus would allow these regions to interface between abstract memories and concrete sensory impressions. Together, these results indicate that visual-spatial organization is a fundamental coding principle that structures the communication between distant brain regions.The electron-transferring flavoprotein-menaquinone oxidoreductase ABCX (EtfABCX), also known as FixABCX for its role in nitrogen-fixing organisms, is a member of a family of electron-transferring flavoproteins that catalyze electron bifurcation. EtfABCX enables endergonic reduction of ferredoxin (E°' ∼-450 mV) using NADH (E°' -320 mV) as the electron donor by coupling this reaction to the exergonic reduction of menaquinone (E°' -80 mV). Here we report the 2.9 Å structure of EtfABCX, a membrane-associated flavin-based electron bifurcation (FBEB) complex, from a thermophilic bacterium. EtfABCX forms a superdimer with two membrane-associated EtfCs at the dimer interface that contain two bound menaquinones. The structure reveals that, in contrast to previous predictions, the low-potential electrons bifurcated from EtfAB are most likely directly transferred to ferredoxin, while high-potential electrons reduce the quinone via two [4Fe-4S] clusters in EtfX. Surprisingly, EtfX shares remarkable structural similarity with mammalian [4Fe-4S] cluster-containing ETF ubiquinone oxidoreductase (ETF-QO), suggesting an unexpected evolutionary link between bifurcating and nonbifurcating systems. Based on this structure and spectroscopic studies of a closely related EtfABCX, we propose a detailed mechanism of the catalytic cycle and the accompanying structural changes in this membrane-associated FBEB system.The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). Each of these structures have some overlapping and some distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a "time-of-death" approach to identify diurnal rhythms in RNA transcripts in human cortical regions. Here, we identify molecular rhythms across the three striatal subregions collected from postmortem human brain tissue in subjects without psychiatric or neurological disorders. Core circadian clock genes are rhythmic across all three regions and show strong phase concordance across regions. However, the putamen contains a much larger number of significantly rhythmic transcripts than the other two regions. Moreover, there are many differences in pathways that are rhythmic across regions. Strikingly, the top rhythmic transcripts in NAc (but not the other regions) are predominantly small nucleolar RNAs and long noncoding RNAs, suggesting that a completely different mechanism might be used for the regulation of diurnal rhythms in translation and/or RNA processing in the NAc versus the other regions. Further, although the NAc and putamen are generally in phase with regard to timing of expression rhythms, the NAc and caudate, and caudate and putamen, have several clusters of discordant rhythmic transcripts, suggesting a temporal wave of specific cellular processes across the striatum. Taken together, these studies reveal distinct transcriptome rhythms across the human striatum and are an important step in helping to understand the normal function of diurnal rhythms in these regions and how disruption could lead to pathology.The molecular properties of proteins are influenced by various ions present in the same solution. While site-specific strong interactions between multivalent metal ions and proteins are well characterized, the behavior of other ions that are only weakly interacting with proteins remains elusive. In the current study, using NMR spectroscopy, we have investigated anion-protein interactions for three proteins that are similar in size but differ in overall charge. https://www.selleckchem.com/products/tefinostat.html Using a unique NMR-based approach, we quantified anions accumulated around the proteins. The determined numbers of anions that are electrostatically attracted to the charged proteins were notably smaller than the overall charge valences and were consistent with predictions from the Poisson-Boltzmann theory. This NMR-based approach also allowed us to measure ionic diffusion and characterize the anions interacting with the positively charged proteins. Our data show that these anions rapidly diffuse while bound to the proteins. Using the same experimental approach, we observed the release of the anions from the protein surface upon the formation of the Antp homeodomain-DNA complex. Using paramagnetic relaxation enhancement (PRE), we visualized the spatial distribution of anions around the free proteins and the Antp homeodomain-DNA complex. The obtained PRE data revealed the localization of anions in the vicinity of the highly positively charged regions of the free Antp homeodomain and provided further evidence of the release of anions from the protein surface upon the protein-DNA association. This study sheds light on the dynamic behavior of anions that electrostatically interact with proteins.Zachariae Isstrøm (ZI) and Nioghalvfjerdsfjorden (79N) are marine-terminating glaciers in northeast Greenland that hold an ice volume equivalent to a 1.1-m global sea level rise. ZI lost its floating ice shelf, sped up, retreated at 650 m/y, and experienced a 5-gigaton/y mass loss. Glacier 79N has been more stable despite its exposure to the same climate forcing. We analyze the impact of ocean thermal forcing on the glaciers. A three-dimensional inversion of airborne gravity data reveals an 800-m-deep, broad channel that allows subsurface, warm, Atlantic Intermediate Water (AIW) (+1.[Formula see text]C) to reach the front of ZI via two sills at 350-m depth. Subsurface ocean temperature in that channel has warmed by 1.3[Formula see text]C since 1979. Using an ocean model, we calculate a rate of ice removal at the grounding line by the ocean that increased from 108 m/y to 185 m/y in 1979-2019. Observed ice thinning caused a retreat of its flotation line to increase from 105 m/y to 217 m/y, for a combined grounding line retreat of 13 km in 41 y that matches independent observations within 14%.