The power of possibility: causal learning, counterfactual reasoning, and pretend play

We argue for a theoretical link between the development of an extended period of immaturity in human evolution and the emergence of powerful and wide-ranging causal learning mechanisms, specifically the use of causal models and Bayesian learning. We suggest that exploratory childhood learning, childhood play in particular, and causal cognition are closely connected. We report an empirical study demonstrating one such connection--a link between pretend play and counterfactual causal reasoning. Preschool children given new information about a causal system made very similar inferences both when they considered counterfactuals about the system and when they engaged in pretend play about it. Counterfactual cognition and causally coherent pretence were also significantly correlated even when age, general cognitive development and executive function were controlled for. These findings link a distinctive human form of childhood play and an equally distinctive human form of causal inference. We speculate that, during human evolution, computations that were initially reserved for solving particularly important ecological problems came to be used much more widely and extensively during the long period of protected immaturity.     

ERCC1-XPF endonuclease facilitates DNA double-strand break repair

ERCC1-XPF endonuclease is required for nucleotide excision repair (NER) of helix-distorting DNA lesions. However, mutations in ERCC1 or XPF in humans or mice cause a more severe phenotype than absence of NER, prompting a search for novel repair activities of the nuclease. In Saccharomyces cerevisiae, orthologs of ERCC1-XPF (Rad10-Rad1) participate in the repair of double-strand breaks (DSBs). Rad10-Rad1 contributes to two error-prone DSB repair pathways: microhomology-mediated end joining (a Ku86-independent mechanism) and single-strand annealing. To determine if ERCC1-XPF participates in DSB repair in mammals, mutant cells and mice were screened for sensitivity to gamma irradiation. ERCC1-XPF-deficient fibroblasts were hypersensitive to gamma irradiation, and gammaH2AX foci, a marker of DSBs, persisted in irradiated mutant cells, consistent with a defect in DSB repair. Mutant mice were also hypersensitive to irradiation, establishing an essential role for ERCC1-XPF in protecting against DSBs in vivo. Mice defective in both ERCC1-XPF and Ku86 were not viable. However, Ercc1(-/-) Ku86(-/-) fibroblasts were hypersensitive to gamma irradiation compared to single mutants and accumulated significantly greater chromosomal aberrations. Finally, in vitro repair of DSBs with 3' overhangs led to large deletions in the absence of ERCC1-XPF. These data support the conclusion that, as in yeast, ERCC1-XPF facilitates DSB repair via an end-joining mechanism that is Ku86 independent.     

COPI–TRAPPII activates Rab18 and regulates its lipid droplet association

The transport protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1. In mammals, structures and functions of various TRAPP complexes are beginning to be understood. We found that mammalian TRAPPII was a GEF for both Rab18 and Rab1. Inactivation of TRAPPII‐specific subunits by various methods including siRNA depletion and CRISPR–Cas9‐mediated deletion reduced lipolysis and resulted in aberrantly large lipid droplets. Recruitment of Rab18 onto lipid droplet (LD) surface was defective in TRAPPII‐deleted cells, but the localization of Rab1 on Golgi was not affected. COPI regulates LD homeostasis. We found that the previously documented interaction between TRAPPII and COPI was also required for the recruitment of Rab18 to the LD. We hypothesize that the interaction between COPI and TRAPPII helps bring TRAPPII onto LD surface, and TRAPPII, in turn, activates Rab18 and recruits it on the LD surface to facilitate its functions in LD homeostasis.     

Geomorphic predictors of riparian vegetation in small mountain watersheds

Aims Hydrogeomorphic processes operating at watershed, process zone and site scales influence the distribution of riparian vegetation. However, most studies examining the relationships between hydrogeomorphic processes and riparian vegetation are conducted at site scales. We quantified the relative importance of watershed, process zone and site geomorphic characteristics for predicting riparian plant community types and plant species abundances in four small mountain watersheds in central Nevada, USA.Methods We mapped riparian vegetation types and identified process zones (based on dominant geomorphic process and valley fill material) within the watersheds. We sampled sites in each combination of vegetation type and process zone (n = 184 sites) and collected data on watershed scale factors, valley and stream geomorphic characteristics and on plant cover of each geomorphic surface. Plant community types were defined by cluster and indicator species analyses of plant cover data, and related to geomorphic variables using ordination analysis (nonmetric multidimensional scaling). Linear mixed effects models were used to predict abundances of indicator species.Important findings Variables describing position in the watershed (elevation, contributing area) that are related to gradients of temperature, moisture and stream discharge were of primary importance in predicting plant community types. Variables describing local geomorphic setting (valley width, stream gradient, channel sediments, geomorphic surface height) were of secondary importance, but accurately described the geomorphic setting of indicator species. The process zone classification did not include position in the watershed or channel characteristics and only predicted plant community types with unique geomorphic settings. In small mountain watersheds, predicting riparian vegetation distribution requires explicit consideration of scale and geomorphic context within and among watersheds in addition to site variables.     

7 Integrating autonomous data acquisition and forecasting into regional monitoring efforts; a synopsis of the merhab 2002: eastern gulf of mexico sentinel program

Blooms of the red-tide dinoflagellate, Karenia brevis , occur annually in coastal waters of the eastern Gulf of Mexico (GOMx) and impact marine resources, public health, and community economics. Early forecasting of and subsequent mitigation for blooms are objectives of agency, academic, and private partnerships. The 5-year, NOAA-funded MERHAB 2002: Eastern GOMx Sentinel Program will develop and assess the utility of a networked system of autonomous sampling platforms. The goal of the program is to become a strategic, proactive hardware- and information-technology for operational GOMx coastal observatories and as such, facilitate model initializations and state-wide, adaptive field sampling. Monitoring platforms will utilize both existing and newly established buoys, and autonomous, water-column profiling vehicles incorporating physical, chemical, and biological sensors. The biological sensors, including a bio-optical phytoplankton discriminator and a processor containing a molecular-probe array, previously have provided consistent results in laboratory and field trials and show great promise for remote, autonomous discrimination of K. brevis . Generated data will initialize a coupled bio-physical forecast model and validate remote sensing algorithms for K. brevis blooms. Data acquisition and forecasting efforts will be integrated with a geographically-comprehensive, rapid response component that incorporates adaptive, field sampling and a volunteer sampling network. NOAA's National Coastal Data Development Center will manage instrument data streams and disseminate and integrate all data into existing (and future) coastal partnerships with their associated management and communication network.     

Multiple structures of thick filaments in resting cardiac muscle and their influence on cross-bridge interactions.

Based on two criteria, the tightness of packing of myosin rods within the backbone of the filament and the degree of order of the myosin heads, thick filaments isolated from a control group of rat hearts had three different structures. Two of the structures of thick filaments had ordered myosin heads and were distinguishable from each other by the difference in tightness of packing of the myosin rods. Depending on the packing, their structure has been called loose or tight. The third structure had narrow shafts and disordered myosin heads extending at different angles from the backbone. This structure has been called disordered. After phosphorylation of myosin-binding protein C (MyBP-C) with protein kinase A (PKA), almost all thick filaments exhibited the loose structure. Transitions from one structure to another in quiescent muscles were produced by changing the concentration of extracellular Ca. The probability of interaction between isolated thick and thin filaments in control, PKA-treated preparations, and preparations exposed to different Ca concentrations was estimated by electron microscopy. Interactions were more frequent with phosphorylated thick filaments having the loose structure than with either the tight or disordered structure. In view of the presence of MgATP and the absence of Ca, the interaction between the myosin heads and the thin filaments was most likely the weak attachment that precedes the force-generating steps in the cross-bridge cycle. These results suggest that phosphorylation of MyBP-C in cardiac thick filaments increases the probability of cross-bridges forming weak attachments to thin filaments in the absence of activation. This mechanism may modulate the number of cross-bridges generating force during activation.     

Evidence for independent recruitment of zeta-crystallin/quinone reductase (CRYZ) as a crystallin in camelids and hystricomorph rodents

Zeta-crystallin/quinone reductase (CRYZ) is an NADPH oxidoreductase expressed at very high levels in the lenses of two groups of mammals: camelids and some hystricomorph rodents. It is also expressed at very low levels in all other species tested. Comparative analysis of the mechanisms mediating the high expression of this enzyme/crystallin in the lens of the Ilama (Lama guanacoe) and the guinea pig (Cavia porcellus) provided evidence for independent recruitment of this enzyme as a lens crystallin in both species and allowed us to elucidate for the first time the mechanism of lens recruitment of an enzyme- crystallin. The data presented here show that in both species such recruitment most likely occurred through the generation of new lens promoters from nonfunctional intron sequences by the accumulation of point mutations and/or small deletions and insertions. These results further support the idea that recruitment of CRYZ resulted from an adaptive process in which the high expression of CRYZ in the lens provides some selective advantage rather than from a purely neutral evolutionary process.