Self-assembly of Mutant Huntingtin Exon-1 Fragments into Large Complex Fibrillar Structures Involves Nucleated Branching

Huntingtin (HTT) fragments with extended polyglutamine tracts self-assemble into amyloid-like fibrillar aggregates. Elucidating the fibril formation mechanism is critical for understanding Huntington's disease pathology and for developing novel therapeutic strategies. Here, we performed systematic experimental and theoretical studies to examine the self-assembly of an aggregation-prone N-terminal HTT exon-1 fragment with 49 glutamines (Ex1Q49). Using high-resolution imaging techniques such as electron microscopy and atomic force microscopy, we show that Ex1Q49 fragments in cell-free assays spontaneously convert into large, highly complex bundles of amyloid fibrils with multiple ends and fibril branching points. Furthermore, we present experimental evidence that two nucleation mechanisms control spontaneous Ex1Q49 fibrillogenesis: (1) a relatively slow primary fibril-independent nucleation process, which involves the spontaneous formation of aggregation-competent fibrillary structures, and (2) a fast secondary fibril-dependent nucleation process, which involves nucleated branching and promotes the rapid assembly of highly complex fibril bundles with multiple ends. The proposed aggregation mechanism is supported by studies with the small molecule O4, which perturbs early events in the aggregation cascade and delays Ex1Q49 fibril assembly, comprehensive mathematical and computational modeling studies, and seeding experiments with small, preformed fibrillar Ex1Q49 aggregates that promote the assembly of amyloid fibrils. Together, our results suggest that nucleated branching in vitro plays a critical role in the formation of complex fibrillar HTT exon-1 aggregates with multiple ends.     

Complete chloroplast genome sequence of Elodea canadensis and comparative analyses with other monocot plastid genomes

Elodea canadensis is an aquatic angiosperm native to North America. It has attracted great attention due to its invasive nature when transported to new areas in its non-native range. We have determined the complete nucleotide sequence of the chloroplast (cp) genome of Elodea. Taxonomically Elodea is a basal monocot, and only few monocot cp genomes representing early lineages of monocots have been sequenced so far. The genome is a circular double-stranded DNA molecule 156,700bp in length, and has a typical structure with large (LSC 86,194bp) and small (SSC 17,810bp) single-copy regions separated by a pair of inverted repeats (IRs 26,348bp each). The Elodea cp genome contains 113 unique genes and 16 duplicated genes in the IR regions. A comparative analysis showed that the gene order and organization of the Elodea cp genome is almost identical to that of Amborella trichopoda, a basal angiosperm. The structure of IRs in Elodea is unique among monocot species with the whole cp genome sequenced. In Elodea and another monocot Lemna minor the borders between IRs and LSC are located upstream of rps19 gene and downstream of trnH-GUG gene, while in most monocots, IR has extended to include both trnH and rps19 genes. A phylogenetic analysis conducted using Bayesian method, based on the DNA sequences of 81 chloroplast genes from 17 monocot taxa provided support for the placement of Elodea together with Lemna as a basal monocot and the next diverging lineage of monocots after Acorales. In comparison with other monocots, the Elodea cp genome has gone through only few rearrangements or gene losses. IR of Elodea has a unique structure among the monocot species studied so far as its structure is similar to that of a basal angiosperm Amborella. This result together with phylogenetic analyses supports the placement of Elodea as a basal monocot to the next diverging lineage of monocots after Acorales. So far, only few cp genomes representing early lineages of monocots have been sequenced and, therefore, this study provides valuable information about the course of evolution in divergence of monocot lineages.     

Biogeographical analysis of rodent endemism and distributional congruence in the southern–central Andes (north‐western Argentina)

The recognition of areas of endemism (AEs) is important for conservation biology and biogeographical regionalization. Our objective was to quantitatively identify AEs and distributional congruence patterns of native rodents at the tropical/temperate transition in the central Andes. We analysed 6200 geo‐referenced distributional records of 80 species in north‐western Argentina using NDM/VNDM software. We found 20 AEs defined by 22 endemic species (27% of the total rodent fauna) and 34 patterns of distributional congruence in non‐endemic rodents. Geographical range congruence follows two main patterns running parallel along the Andes. One is related to the humid eastern slopes of the Andes (Argentinean Yungas forest) and the other to the high Andes (Argentinean Puna plateau). Endemism was mainly restricted to the southernmost part of the Yungas forest and adjacent dryer valleys (Monte desert). Species diversity was highest in the northern sector of the Argentinean Yungas forest, where several species reach their southern distributional range. This incongruence among hotspots of diversity and endemism has also been also noted in diversity studies at continental and global scales. Our results provide a starting point for conservation planning in the southernmost Central Andes, which combines the taper of tropical diversity and range‐restricted species endemic to the tropical–temperate transition. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 112 , 163–179.     

You eat what you are: personality‐dependent filial cannibalism in a fish with paternal care

Many animal parents invest heavily to ensure offspring survival, yet some eventually consume some or all of their very own young. This so‐called filial cannibalism is known from a wide range of taxa, but its adaptive benefit remains largely unclear. The extent to which parents cannibalize their broods varies substantially not only between species, but also between individuals, indicating that intrinsic behavioral differences, or animal personalities, might constitute a relevant proximate trigger for filial cannibalism. Using a marine fish with extensive paternal care, the common goby (Pomatoschistus microps), we investigated the influence of animal personality on filial cannibalism by assessing (1) behavioral consistency across a breeding and a nonbreeding context; (2) correlations between different breeding (egg fanning; filial cannibalism) and nonbreeding (activity) behaviors, and, in a separate experiment; (3) whether previously established personality scores affect filial cannibalism levels. We found consistent individual differences in activity across contexts. Partial filial cannibalism was independent of egg fanning but correlated strongly with activity, where active males cannibalized more eggs than less active males. This pattern was strong initially but vanished as the breeding season progressed. The incidence of whole clutch filial cannibalism increased with activity and clutch size. Our findings indicate that filial cannibalism cannot generally be adjusted independently of male personality and is thus phenotypically less plastic than typically assumed. The present work stresses the multidimensional interaction between animal personality, individual plasticity and the environment in shaping filial cannibalism.     

Demand for sucrose in the genetically obese Zucker (fa/fa) rat

Obese Zucker rats (fa/fa) eat more food than lean controls in free-feeding conditions, which strongly influences their phenotypic expression. Few studies, however, characterize their food consumption in environments that are more representative of foraging conditions, e.g., how effort plays a role in food procurement. This study examined the reinforcing efficacy of sucrose in obese Zucker rats by varying the responses required to obtain single sucrose pellets. Male Zucker rats (15 lean, 14 obese) lever-pressed under eight fixed ratio (FR) schedules of sucrose reinforcement, in which the number of lever-presses required to gain access to a single sucrose pellet varied from 1 to 300. Linear and exponential demand equations, which characterize the value of a reinforcer by its sensitivity to price (FR), were fit to the number of food reinforcers and responses made. Free food consumption was also examined. Obese Zuckers, compared to leans, consumed more food under free-feeding conditions. Moreover, they had higher levels of consumption and response output, but only at low FR values. Both groups were equally sensitive to price increases at higher FR values. This suggests that environmental conditions may interact with genes in the expression of food reinforcer efficacy.     

The effects of colony characteristics on life span and foraging behavior of individual wasps (Polybia occidentalis,Hymenoptera: Vespidae)

Summary We studied the effects of intrinsic colony characteristics and an imposed contingency on the life span and behavior of foragers in the swarm-founding social waspPolybia occidentalis. Data were collected on marked, known-age workers introduced into four observation colonies.To test the hypothesis that colony demographic features affect worker life span, we examined the relationships of colony age and size with worker life span using survivorship analysis. Colony age and size had positive relationships with life span; marked workers from two larger, older colonies had longer life spans (¯X = 24.7 days) than those from two smaller, younger colonies (¯X = 20.1 days).We quantified the effects of experimentally imposed nest damage on forager behavior, to determine which of three predicted behavioral responses by foragers to this contingency (increased probability of foraging for building material, increased rate of foraging, or decrease in age of onset of foraging) would be employed. Increasing the colony level of need for materials used in nest construction (wood pulp and water) by damaging the nests of two colonies did not cause an increase in either the proportion of marked workers that gathered nest materials or in foraging rates of marked individuals, when compared with introduced workers in two simultaneously observed control colonies. Instead, nest damage caused a decrease in the age at which marked workers first foraged for pulp and water. The response to an increase in the need for building materials was an acceleration of behavioral development in some workers.     

Hunting activity and aging among the gidra papuans: A biobehavioral analysis

From the individual-based records of hunting practice for 1,633 hr in total and from the hunters' visual acuity and grip strength observed among the Gidra Papuans in lowland Papua New Guinea, this paper aims to analyze the relationship between the hunting activity and aging. The sensorimotor functions determine the range of age in which the individuals act as active or productive hunters: determined to be from the late teen-age years to about 45 years among the present subjects. In this age range, hunting efficiency increases with age. In terms of weight of animals killed per hunting time, the efficiency of the elder married (aged about 35 to 45 years) was almost four times higher than that of the unmarried (16–17 to late 20s). This aging effect is judged to depend on behavioral abilities that increase in accordance with experience and cumulative knowledge. Simultaneously, the comparison of individual hunters' records in 1971–72 and in 1981 reveals that hunting efficiency is associated with the individualities of the hunters.     

A gain-of-function mutation in the GABA receptor produces synaptic and behavioral abnormalities in the mouse

In mammalian species, inhibition in the brain is mediated predominantly by the activation of GABAA receptors. We report here changes in inhibitory synaptic function and behavior in a mouse line harboring a gain-of-function mutation at Serine 270 (S270) in the GABAA receptor alpha1 subunit. In recombinant alpha1beta2gamma2 receptors, replacement of S270 by Histidine (H) results in an increase in sensitivity to gamma-aminobutyric acid (GABA), and slowing of deactivation following transient activation by saturating concentrations of GABA. Heterozygous mice expressing the S270H mutation are hyper-responsive to human contact, exhibit intention tremor, smaller body size and reduced viability. These mice also displayed reduced motor coordination, were hypoactive in the home cage, but paradoxically were hyperactive in a novel open field environment. Heterozygous knockin mice of both sexes were fertile but females failed to care for offspring. This deficit in maternal behavior prevented production of homozygous animals. Recordings from brain slices prepared from these animals revealed a substantial prolongation of miniature inhibitory postsynaptic currents (IPSCs) and a loss of sensitivity to the anesthetic isoflurane, in neurons that express a substantial amount of the alpha1 subunit. The results suggest that the biophysical properties of GABAA receptors are important in determining the time-course of inhibition in vivo, and suggest that the duration of synaptic inhibition is a critical determinant that influences a variety of behaviors in the mouse.     

An experimental study of leaf swallowing in captive chimpanzees: insights into the origin of a self-medicative behavior and the role of social learning

Chimpanzees in the wild swallow the rough hispid leaves of certain plant species as a means of physically expelling intestinal parasites. A plant with such a leaf texture was introduced in 36 trial sessions to a captive group of 11 healthy adult chimpanzees to investigate the possible origin and acquisition of leaf swallowing behavior. One male (housed separately from the group during testing) and one female, both captive born, spontaneously exhibited the behavior on their first trial without prior opportunity to observe others with this plant. Six other chimpanzees on their first trial displayed a phobic response to these leaves and rejected them entirely, while another two chewed and swallowed the leaves in a normal way. Four individuals eventually exhibited the behavior, after having approached and closely observed the leaf swallowing of the first female to exhibit the behavior in the group. Four of the six individuals that initially avoided the leaves never overcame their phobia toward this plant and were not in proximity to a chimpanzee performing leaf swallowing during test sessions. Individuals born to wild chimpanzee mothers were no more likely to perform the behavior than captive-reared group mates. These results suggest that the acquisition of this behavior is based in part on a propensity to fold and swallow rough, hispid leaves, but that the acquisition and spread of leaf swallowing within a group is likely to be socially influenced. This study provides support for the hypothesis that leaf swallowing originated in the wild from opportunistic feeding behavior and was later passed down in the form of a self-medicative behavioral tradition.Electronic Supplementary Material Supplementary material is available in the online version of this article at