The component polypeptide chains of bovine insulin nucleate or inhibit aggregation of the parent protein in a conformation-dependent manner

Amyloid fibrils are typically rigid, unbrariched structures with diameters of similar to 10 nm and lengths up to several micrometres, and are associated with more than 20 diseases including Alzheimer's disease and type II diabetes. Insulin is a small, predominantly alpha-helical protein consisting of 51 residues in two disulfide-linked polypeptide chains that readily assembles into amyloid fibrils under conditions of low PH and elevated temperature. We demonstrate here that both the A-chain and the B-chain of insulin are capable of forming amyloid fibrils in isolation under similar conditions, with fibrillar morphologies that differ from those composed of intact insulin. Both the A-chain and B-chain fibrils were found to be able to cross-seed the fibrillization of the parent protein, although these reactions were substantially less efficient than self-seeding with fibrils composed of full-length insulin. In both cases, the cross-seeded fibrils were morphologically distinct from the seeding, material, but shared common characteristics with typical insulin fibrils, including a very similar helical repeat. The broader distribution of heights of the cross-seeded fibrils compared to typical insulin fibrils, however, indicates that their underling protofilament hierarchy may be subtly different. In addition, and remarkably in view of this seeding behavior, the soluble forms of the A-chain and B-chain peptides were found to be capable of inhibiting insulin fibril formation. Studies using mass spectrometry suggest that this behavior might be attributable to complex formation between insulin and the A-chain and B-chain peptides. The finding that the same chemical form of a polypeptide chain in different physical states can either stimulate or inhibit the conversion of a protein into amyloid fibrils sheds new light on the mechanisms underlying fibril formation, fibril strain propagation and amyloid disease initiation and progression. (c) 2006 Elsevier Ltd. All rights reserved.

Suboptimal system recovery from communication loss in a multi-robot localization scenario using EKF algorithms

This paper describes a multi-robot localization scenario where, for a period of time, the robot team loses communication with one of the robots due to system error. In this novel approach, extended Kalman filter (EKF) algorithms utilize relative measurements to localize the robots in space. These measurements are used to reliably compensate "dead-com" periods were no information can be exchanged between the members of the robot group.

Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in extreme parasitism

Powdery mildews are phytopathogens whose growth and reproduction are entirely dependent on living plant cells. The molecular basis of this life-style, obligate biotrophy, remains unknown. We present the genome analysis of barley powdery mildew, Blumeria graminis f.sp. hordei (Blumeria), as well as a comparison with the analysis of two powdery mildews pathogenic on dicotyledonous plants. These genomes display massive retrotransposon proliferation, genome-size expansion, and gene losses. The missing genes encode enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, probably reflecting their redundancy in an exclusively biotrophic life-style. Among the 248 candidate effectors of pathogenesis identified in the Blumeria genome, very few (less than 10) define a core set conserved in all three mildews, suggesting thatmost effectors represent species-specific adaptations.

Emotional well-being and adjustment to vision loss in later life: a meta-synthesis of qualitative studies.

Purpose: To review perceived emotional well-being in older people with visual impairment and perceived factors that inhibit/facilitate psychosocial adjustment to vision loss. Method: The databases of MEDLINE, EMBASE, PsycINFO and CINAHL were searched for studies published from January 1980 to December 2010, which recruited older people with irreversible vision loss, and used qualitative methods for both data collection and analysis. Results sections of the papers were synthesised using a thematic-style analysis to identify the emergent and dominant themes. Results: Seventeen qualitative papers were included in the review, and five main themes emerged from the synthesis: 1) the trauma of an ophthalmic diagnosis, 2) impact of vision loss on daily life, 3) negative impact of visual impairment on psychosocial well-being, 4) factors that inhibit social well-being, and 5) factors that facilitate psychological well-being. We found the response shift model useful for explaining our synthesis. Conclusions: Acquired visual impairment can have a significant impact on older people's well-being and make psychosocial adjustment to the condition a major challenge. Acceptance of the condition and a positive attitude facilitate successful psychosocial adjustment to vision loss as well as social support from family, friends and peers who have successfully adjusted to the condition. [Box: see text].

Neural and psychological maturation of decision-making in adolescence and young adulthood

We examined the maturation of decision-making from early adolescence to mid-adulthood using fMRI of a variant of the Iowa gambling task. We have previously shown that performance in this task relies on sensitivity to accumulating negative outcomes in ventromedial PFC and dorsolateral PFC. Here, we further formalize outcome evaluation (as driven by prediction errors [PE], using a reinforcement learning model) and examine its development. Task performance improved significantly during adolescence, stabilizing in adulthood. Performance relied on greater impact of negative compared with positive PEs, the relative impact of which matured from adolescence into adulthood. Adolescents also showed increased exploratory behavior, expressed as a propensity to shift responding between options independently of outcome quality, whereas adults showed no systematic shifting patterns. The correlation between PE representation and improved performance strengthened with age for activation in ventral and dorsal PFC, ventral striatum, and temporal and parietal cortices. There was a medial-lateral distinction in the prefrontal substrates of effective PE utilization between adults and adolescents: Increased utilization of negative PEs, a hallmark of successful performance in the task, was associated with increased activation in ventromedial PFC in adults, but decreased activation in ventrolateral PFC and striatum in adolescents. These results suggest that adults and adolescents engage qualitatively distinct neural and psychological processes during decision-making, the development of which is not exclusively dependent on reward-processing maturation.

Atmospheric impact of Arctic Sea ice loss in a coupled ocean–atmosphere simulation

The atmospheric response to an idealized decline in Arctic sea ice is investigated in a novel fully coupled climate model experiment. In this experiment two ensembles of single-year model integrations are performed starting on 1 April, the approximate start of the ice melt season. By perturbing the initial conditions of sea ice thickness (SIT), declines in both sea ice concentration and SIT, which result in sea ice distributions that are similar to the recent sea ice minima of 2007 and 2012, are induced. In the ice loss regions there are strong (~3 K) local increases in sea surface temperature (SST); additionally, there are remote increases in SST in the central North Pacific and subpolar gyre in the North Atlantic. Over the central Arctic there are increases in surface air temperature (SAT) of ~8 K due to increases in ocean–atmosphere heat fluxes. There are increases in SAT over continental North America that are in good agreement with recent changes as seen by reanalysis data. It is estimated that up to two-thirds of the observed increase in SAT in this region could be related to Arctic sea ice loss. In early summer there is a significant but weak atmospheric circulation response that projects onto the summer North Atlantic Oscillation (NAO). In early summer and early autumn there is an equatorward shift of the eddy-driven jet over the North Atlantic as a result of a reduction in the meridional temperature gradients. In winter there is no projection onto a particular phase of the NAO.

Internalizing symptomatology and academic achievement: bi-directional prospective relations in adolescence

Prior research has documented negative, concurrent relations between internalizing symptomatology and academic achievement among adolescents. The present study provided the first rigorous, longitudinal examination of the bi-directional, prospective relations between adolescent internalizing symptomatology and academic achievement. One hundred and thirty adolescents reported depression and anxiety annually from 6th through 10th grades, and GPA records were obtained annually from schools. Results showed that a) high depression and anxiety at the beginning of a school year predicted lower GPA during that school year, and b) low GPA in any school year predicted higher depression and anxiety at the beginning of the following school year. These findings underscore the tight link between adolescent internalizing symptomatology and academic achievement.

Unilateral Correction of Space Loss in the Mixed Dentition

Distalization of maxillary molars is indicated for correction of Class II dental malocclusion and for space gain in cases of space deficiency. The ideal treatment with an intraoral fixed appliance for molar distalization should fulfill the following requirements: patient compliance; acceptable esthetics; comfort; minimum anterior anchor loss (as evidenced by inclination of incisors); bodily movement of the molars to avoid undesirable effects and unstable outcomes; and minimum time required during sessions for placement and activations. The purpose of this paper was to present an alternative treatment for space recovery in the area of the maxillary right second premolar when there has been significant mesial movement of the permanent maxillary right first molar. We used a modified appliance that allows unilateral molar distalization in cases of unilateral tooth/arch size discrepancy using the opposite side as anchor, thus reducing the mesialization of the anterior teeth. (Pediatr Dent 2008;30:334-41) Received August 17, 2006 / Last Revision October 17, 2007 / Revision Accepted October 17, 2007

High intake of fruits and vegetables predicts weight loss in Brazilian overweight adults

To determine whether changes in dietary intakes predict weight loss, we studied 80 overweight adults who attended a nutritional counseling program during 6 months of follow-up at a primary health care center in Brazil. Habitual diet was assessed using a validated food frequency questionnaire at baseline and after 6 months. The mean age (+/-SD) of the participants was 46.5 +/- 9.5 years, and their mean body mass index was 29 +/- 3 kg/m(2) at baseline. After 6 months, the differences in body weight and fruit/vegetable intake were -1.4 +/- 3 kg and 109 +/- 320 g daily, respectively. Using multiple linear regression models adjusted for age, sex, changes in walking time, and total energy intake, the increased intake of dietary fiber from fruits/vegetables was associated with a greater weight loss (beta 1 [95% confidence interval (CI)] = -0.180 [-0.269, -0.0911) after 6 months of follow-up. Similar results were observed for increased intake of vegetables (beta 1 [95% CI] = -0.00497 [-0.008, -0.0021) and fruits (beta 1 [95% CI] = -0.00290 [-0.005, -0.001]) as predictors of weight loss. The increase of 100 g/d of vegetables and fruits represented a body weight loss of 500 and 300 g after 6 months, respectively (P <.05). Our findings support the relevance of increased intakes of fruits and vegetables that may help avoid weight gain in overweight adults. (C) 2008 Elsevier Inc. All rights reserved.

Cutaneous Resistance to Evaporative Water Loss in Brazilian Rhinella (Anura: Bufonidae) from Contrasting Environments

Influenced by taxonomic position. For example, bufonids are regarded as exhibiting a permeable skin that seems typical for terrestrial anurans. However, this assumption is supported by information on only four bufonid species; therefore, the enormous ecological diversity of the family remains poorly Investigated. To assess whether variation in R(s) within related bufonids correlates with environmental aridity, we measured area-specific rates of EWL of two Brazilian populations of Rhinella granulosa (previously Bufo granulosus), one from the Atlantic Forest and other from the semi-arid Caatinga, and compared both with the forest species R. ornato. Rhinella granulosa from the Atlantic Forest had higher cutaneous resistance than conspecifics from Caatinga and R. ornata. Rhinella ornato presented the lowest cutaneous resistance values. However, Rs were very close to zero In all three populations. We conclude that enhanced Rs is not part of the suite of traits allowing R. granulosa to exploit the Caatinga, and that variation in R(s) within bufonids may relate to traits other than water conservation. Some Information on microhabitat occupation and ventral skin morphology supports the idea that exceptional abilities for detecting and taking up water may be the key factors enhancing the survival of R. granulosa, and possibly other bufonids, in xeric environments.

Intermittent Therapy with 1,25 Vitamin D and Calcitonin Prevents Cyclosporin-Induced Alveolar Bone Loss in Rats

Bone loss associated with cyclosporin A (CsA) therapy can result in serious morbidity to patients. Intermittent administration of 1,25 Vitamin D and calcitonin reduces osteopenia in a murine model of postmenopausal osteoporosis. The purpose of this study was to evaluate the effects of this therapeutic approach on CsA-induced alveolar bone loss in rats. Forty male Wistar rats were allocated to four experimental groups according to the treatment received during 8 weeks: (1) CsA (10 mg/kg/day, s.c.); (2) 1,25 Vitamin D (2 mu g/kg, p.o.; in weeks 1, 3, 5, and 7) plus calcitonin (2 mu g/kg, i.p.; in weeks 2, 4, 6, and 8); (3) CsA concurrently with intermittent 1,25 Vitamin D and calcitonin administration; and (4) the control treatment group (vehicle). At the end of the 8-week treatment period, serum concentrations of bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase (TRAP-5b), osteocalcin, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were measured and an analysis of bone volume, bone surface, number of osteoblasts, and osteoclasts was performed. CsA administration resulted in significant alveolar bone resorption, as assessed by a lower bone volume and an increased number of osteoclasts, and increased serum bone-specific alkaline phosphatase, TRAP-5b, IL-1 beta, IL-6, and TNF-alpha concentrations. The intermittent administration of calcitriol and calcitonin prevented the CsA-induced osteopenic changes and the increased serum concentrations of TRAP-5b and inflammatory cytokines. Intermittent calcitriol/calcitonin therapy prevents CsA-induced alveolar bone loss in rats and normalizes the production of associated inflammatory mediators.