ALBERT

Description: BRCA2 is a multi-faceted protein critical for the proper regulation of homology-directed repair of DNA double-strand breaks. Elucidating the mechanistic features of BRCA2 is crucial for understanding homologous recombination and how patient-derived mutations impact future cancer risk. Eight centrally located BRC repeats in BRCA2 mediate binding and regulation of RAD51 on resected DNA substrates. Herein, we dissect the biochemical and cellular features of the BRC repeats tethered to the DNA binding domain of BRCA2. To understand how the BRC repeats and isolated domains of BRCA2 contribute to RAD51 binding, we analyzed both the biochemical and cellular properties of these proteins. In contrast to the individual BRC repeat units, we find that the BRC5–8 region potentiates RAD51-mediated DNA strand pairing and provides complementation functions exceeding those of BRC repeats 1–4. Furthermore, BRC5–8 can efficiently repair nuclease-induced DNA double-strand breaks and accelerate the assembly of RAD51 repair complexes upon DNA damage. These findings highlight the importance of the BRC5–8 domain in stabilizing the RAD51 filament and promoting homology-directed repair under conditions of cellular DNA damage.

Description: Electrophysiological recordings in animals have indicated that visual cortex γ-band oscillatory activity is predominantly observed in superficial cortical layers, whereas α- and β-band activity is stronger in deep layers. These rhythms, as well as the different cortical layers, have also been closely related to feedforward and feedback streams of information....

Description: The genes of all organisms have been shaped by selective pressures. The relationship between gene sequence and fitness has tremendous implications for understanding both evolutionary processes and functional constraints on the encoded proteins. Here, we have exploited deep sequencing technology to experimentally determine the fitness of all possible individual point mutants under controlled conditions for a nine-amino acid region of Hsp90. Over the past five decades, limited glimpses into the relationship between gene sequence and function have sparked a long debate regarding the distribution, relative proportion, and evolutionary significance of deleterious, neutral, and advantageous mutations. Our systematic experimental measurement of fitness effects of Hsp90 mutants in yeast, evaluated in the light of existing population genetic theory, are remarkably consistent with a nearly neutral model of molecular evolution.

Description: Marine fish populations have high variation in cohort strength, and the production of juveniles (recruitment) may have persistent positive or negative residuals (autocorrelation) after accounting for spawning biomass. Autocorrelated recruitment will occur whenever average recruitment levels change between oceanographic regimes or due to predator release, but may also indicate persistent environmental and biological effects on shorter time-scales. Here, we use estimates of recruitment variability and autocorrelation to simulate the stationary distribution of spawning biomass for 100 real-world stocks when unfished, fished at F MSY , or fished following a harvest control rule where fishing mortality decreases as a function of spawning biomass. Results show that unfished stocks have spawning biomass (SB) below its deterministic equilibrium value (SB 0 ) 58% of the time, and below 0.5SB 0 5% of the time on average across all stocks. Similarly, stocks fished at the level producing deterministic maximum sustainable yield ( F MSY ) are below its deterministic prediction of spawning biomass (SB MSY ) 60% of the time and below 0.5SB MSY 8% of the time. These probabilities are greater for stocks with high recruitment variability, positive autocorrelation, and high natural mortality—traits that are particularly associated with clupeids and scombrids. An elevated probability of stochastic depletion, i.e. biomass below the deterministic equilibrium expectation, implies that management actions required when biomass drops below a threshold may be triggered more frequently than expected. Therefore, we conclude by suggesting that fisheries scientists routinely calculate these probabilities during stock assessments as a decision support tool for fisheries managers.

Description: The Habshan industrial site in the United Arab Emirates produces a regional-scale pollution plume associated with oil- and gas-processing, discharging high loadings of sulfates and chlorides into the atmosphere, which interact with ambient aerosol population. Aerosol particles and trace gas chemistry at this site were studied on two flights in the summer of 2002. Measurements were collected along vertical plume profiles to show changes associated with atmospheric processing of particle and gas components. Close to the outlet stack, particle concentrations were over 10000 cm -3 , dropping to 〈 2000 cm -3 in more dilute plume around 1500 m above the stack. Particles collected close to the stack and within the dilute plume were individually measured for size, morphology, composition, and mixing state using transmission electron microscopy coupled with energy dispersive x-ray spectroscopy. Close to the stack, most coarse particles consisted of mineral dust and NaCl crystals from burning oil brines, while sulfate droplets dominated the fine mode. In more dilute plume, at least 1500 m above the stack, the particle spectrum was more diverse, with a significant increase in internally mixed particle types. Dilute plume samples consisted of coarse NaCl/silicate aggregates or NaCl-rich droplets, often with a sulfate component, while fine-fraction particles were of mixed-cation sulfates, also internally mixed with nanospherical-soot or silicates. Thus, both chloride and sulfate components of the pollution plume reacted rapidly with ambient mineral dust to form coated and aggregate particles, enhancing particle size, hygroscopicity, and reactivity of the coarse mode. The fine-fraction sulfate-bearing particles formed in the plume contribute to regional transport of sulfates, while coarse sulfate-bearing fractions locally reduce the SO 2 loading through sedimentation. The chloride- and sulfate-bearing internally mixed particles formed in the plume markedly change reflectivity and scattering properties of the ambient aerosol population, as well as its hygroscopic and ice nucleation properties.

Description: The Journal of Organic Chemistry DOI: 10.1021/acs.joc.5b02897

Description: Chemoreceptor arrays are supramolecular transmembrane machines of unknown structure that allow bacteria to sense their surroundings and respond by chemotaxis. We have combined X-ray crystallography of purified proteins with electron cryotomography of native arrays inside cells to reveal the arrangement of the component transmembrane receptors, histidine kinases (CheA) and CheW coupling proteins. Trimers of receptor dimers lie at the vertices of a hexagonal lattice in a “two-facing-two” configuration surrounding a ring of alternating CheA regulatory domains (P5) and CheW couplers. Whereas the CheA kinase domains (P4) project downward below the ring, the CheA dimerization domains (P3) link neighboring rings to form an extended, stable array. This highly interconnected protein architecture underlies the remarkable sensitivity and cooperative nature of transmembrane signaling in bacterial chemotaxis.

Description: Defining mechanisms governing translation of molecular binding events into immune activation is central to understanding immune function. In the lectin pathway of complement, the pattern recognition molecules (PRMs) mannan-binding lectin (MBL) and ficolins complexed with the MBL-associated serine proteases (MASP)-1 and MASP-2 cleave C4 and C2 to generate C3 convertase....

Description: Mutations are the source of evolutionary variation. The interactions of multiple mutations can have important effects on fitness and evolutionary trajectories. We have recently described the distribution of fitness effects of all single mutations for a nine-amino-acid region of yeast Hsp90 (Hsp82) implicated in substrate binding. Here, we report and discuss the distribution of intragenic epistatic effects within this region in seven Hsp90 point mutant backgrounds of neutral to slightly deleterious effect, resulting in an analysis of more than 1,000 double mutants. We find negative epistasis between substitutions to be common, and positive epistasis to be rare—resulting in a pattern that indicates a drastic change in the distribution of fitness effects one step away from the wild type. This can be well explained by a concave relationship between phenotype and genotype (i.e., a concave shape of the local fitness landscape), suggesting mutational robustness intrinsic to the local sequence space. Structural analyses indicate that, in this region, epistatic effects are most pronounced when a solvent-inaccessible position is involved in the interaction. In contrast, all 18 observations of positive epistasis involved at least one mutation at a solvent-exposed position. By combining the analysis of evolutionary and biophysical properties of an epistatic landscape, these results contribute to a more detailed understanding of the complexity of protein evolution.

Description: Organic-walled microfossils (acritarchs) provide age constraints for the previously poorly dated Cambrian and Lower Ordovician turbiditic Goldenville and Halifax Groups in the northern Appalachian Meguma terrane of Nova Scotia and address controversies about stratigraphy and provenance. The oldest exposed formation of the ~8-km-thick Goldenville Group contains the trace fossil Oldhamia , which suggests an age of late Early Cambrian, whereas the coticule-bearing uppermost formation yielded an acritarch species consistent with Middle Cambrian (Epoch 3) age. The conformably overlying ~5-km-thick Halifax Group includes basal pyritiferous units that yielded a Late Cambrian (Furongian) assemblage of acritarch species, providing further confirmation that the underlying manganese-bearing formations are of Cambrian Epoch 3 age, and not Ordovician as recently claimed. Overlying nonpyritiferous formations contain the Early Ordovician graptolite Rhabdinopora flabelliformis flabelliformis and acritarchs of similar age. Samples collected up section from the graptolite occurrence yielded acritarch species that are indicative of the later Tremadocian and Floian. The new fossil data confirm a gap in age of ~30 m.y. between the Halifax Group and the overlying Silurian to Lower Devonian Rockville Notch Group. The new ages are consistent with stratigraphic units defined in regional mapping and support recent interpretation of fundamental differences in depositional and tectonic environments between the northwestern and southeastern parts of the Meguma terrane. They also provide new constraints on paleogeography of the terrane by confirming age similarities to stratigraphy in north Wales, with which correlation has been proposed previously based mainly on lithological similarities.