Embryonic Mutant Huntingtin Aggregate Formation in Mouse Models of Huntington’s Disease

The role of aggregate formation in the pathophysiology of Huntington’s disease (HD) remains uncertain. However, the temporal appearance of aggregates tends to correlate with the onset of symptoms and the numbers of neuropil aggregates correlate with the progression of clinical disease. Using highly sensitive immunohistochemical methods we have detected the appearance of diffuse aggregates during embryonic development in the R6/2 and YAC128 mouse models of HD. These are initially seen in developing axonal tracts and appear to spread throughout the cerebrum in the early neonate

Reconstructions of deltaic environments from Holocene palynological records in the Volga delta, northern Caspian Sea

This article was made available through open access by the Brunel Open Access Publishing Fund.New palynological and ostracod data are presented from the Holocene Volga delta, obtained from short cores and surface samples collected in the Damchik region, near Astrakhan, Russian Federation in the northern Caspian Sea. Four phases of delta deposition are recognized and constrained by accelerated mass spectrometry (AMS) radiocarbon ages. Palynological records show that erosive channels, dunes (Baer hills) and inter-dune lakes were present during the period 11,500–8900 cal. BP at the time of the Mangyshlak Caspian lowstand. The period 8900–3770 cal. BP was characterized regionally by extensive steppe vegetation, with forest present at times with warmer, more humid climates, and with halophytic and xerophytic vegetation present at times of drought. The period 3770–2080 cal. BP was a time of active delta deposition, with forest or woodland close to the delta, indicating relatively warm and humid climates and variable Caspian Sea levels. From 2080 cal. BP to the present-day, aquatic pollen is frequent in highstand intervals and herbaceous pollen and fungal hyphae frequent in lowstand intervals. Soils and incised valley sediments are associated with the regional Derbent regression and may be time-equivalent with the ‘Medieval Warm Period’. Fungal spores are an indicator of erosional or aeolian processes, whereas fungal hyphae are associated with soil formation. Freshwater algae, ostracods and dinocysts indicate mainly freshwater conditions during the Holocene with minor brackish influences. Dinocysts present include Spiniferites cruciformis, Caspidinium rugosum, Impagidinium caspienense and Pterocysta cruciformis, the latter a new record for the Caspian Sea. The Holocene Volga delta is a partial analogue for the much larger oil and gas bearing Mio-Pliocene palaeo-Volga delta.Funding for the data collection and field work was provided from the following sources: 1 – IGCP-UNESCO 2003–2008 (Project 481 CASPAGE, Dating Caspian Sea Level Change); 2 – NWO, Netherlands Science Foundation and RFFI, Russian Science Foundation 2005–2008 (Programme: ‘VHR Seismic Stratigraphy and Paleoecology of the Holocene Volga Delta’); and 3 – BP Exploration (Caspian Sea) Sea Ltd. (Azeri-Chirag-Gunashli) 2005–2008 (‘Unravelling the Small-Scale Stratigraphy and Sediment Dynamics of the Modern Volga Delta Using VHR Marine Geophysics’). The palynological work was funded jointly by BP Exploration (Caspian Sea) Ltd., Delft University of Technology and KrA Stratigraphic Ltd. Ostracod analyses were funded by StrataData Ltd. and funding for two additional radiocarbon dates provided by Deltares

Nonperturbative study of the four gluon vertex

In this paper we study the nonperturbative structure of the SU(3) four-gluon vertex in the Landau gauge, concentrating on contributions quadratic in the metric. We employ an approximation scheme where 'one-loop' diagrams are computed using fully dressed gluon and ghost propagators, and tree-level vertices. When a suitable kinematical configuration depending on a single momentum scale p is chosen, only two structures emerge: the tree-level four-gluon vertex, and a tensor orthogonal to it. A detailed numerical analysis reveals that the form factor associated with this latter tensor displays a change of sign (zero-crossing) in the deep infrared, and finally diverges logarithmically. The origin of this characteristic behavior is proven to be entirely due to the masslessness of the ghost propagators forming the corresponding ghost-loop diagram, in close analogy to a similar effect established for the three-gluon vertex. However, in the case at hand, and under the approximations employed, this particular divergence does not affect the form factor proportional to the tree-level tensor, which remains finite in the entire range of momenta, and deviates moderately from its naive tree-level value. It turns out that the kinematic configuration chosen is ideal for carrying out lattice simulations, because it eliminates from the connected Green's function all one-particle reducible contributions, projecting out the genuine one-particle irreducible vertex. Motivated by this possibility, we discuss in detail how a hypothetical lattice measurement of this quantity would compare to the results presented here, and the potential interference from an additional tensorial structure, allowed by Bose symmetry, but not encountered within our scheme

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Oral dosing of rodents using a palatable tablet

Rationale: Delivering orally bioavailable drugs to rodents is an important component to investigating that route of administration in novel treatments for humans. However, the traditional method of oral gavage requires training, is stressful, and can induce oesophageal damage in rodents. Objectives: To demonstrate a novel administrative technique – palatable gelatine tablets – as a stress-free route of oral delivery. Methods: 24 male Lister hooded rats were sacrificed for brain tissue analysis at varying time-points after jelly administration of 30 mg/kg of the wake-promoting drug modafinil. A second group of 22 female rats were tested on locomotor activity after 30 mg/kg modafinil, or after vehicle jellies, with the locomotor data compared to the brain tissue concentrations at the corresponding times. Results: Modafinil was present in the brain tissue at all time-points, reducing in concentration over time. The pattern of brain tissue modafinil concentration is comparable to previously reported results following oral gavage. Modafinil-treated rats were more active than control rats, with greater activity during the later time-periods – similar to that previously reported following intraperitoneal injection of 40 mg/kg modafinil. Conclusions: Palatable jelly tablets are an effective route of administration of thermally-stable orally-bioavailable compounds, eliminating the stress/discomfort and health risk of oral gavage and presenting as an alternative to previously reported palatable routes of administration where high protein and fat levels may adversely affect appetite for food reward, and uptake rate in the gastrointestinal tract.Publisher PDFPeer reviewe

Flammable biomes dominated by eucalypts originated at the Cretaceous-Palaeogene boundary

Fire is a major modifier of communities, but the evolutionary origins of its prevalent role in shaping current biomes are uncertain. Australia is among the most fire-prone continents, with most of the landmass occupied by the fire-dependent sclerophyll and savanna biomes. In contrast to biomes with similar climates in other continents, Australia has a tree flora dominated by a single genus, Eucalyptus, and related Myrtaceae. A unique mechanism in Myrtaceae for enduring and recovering from fire damage likely resulted in this dominance. Here, we find a conserved phylogenetic relationship between post-fire resprouting (epicormic) anatomy and biome evolution, dating from 60 to 62 Ma, in the earliest Palaeogene. Thus, fire-dependent communities likely existed 50 million years earlier than previously thought. We predict that epicormic resprouting could make eucalypt forests and woodlands an excellent long-term carbon bank for reducing atmospheric CO2 compared with biomes with similar fire regimes in other continents

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

Contains fulltext : 70104tjan-heijnen.pdf (publisher's version ) (Open Access)BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. RESULTS: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 - 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. CONCLUSION: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker

The Temporal Signature of Memories: Identification of a General Mechanism for Dynamic Memory Replay in Humans

Reinstatement of dynamic memories requires the replay of neural patterns that unfold over time in a similar manner as during perception. However, little is known about the mechanisms that guide such a temporally structured replay in humans, because previous studies used either unsuitable methods or paradigms to address this question. Here, we overcome these limitations by developing a new analysis method to detect the replay of temporal patterns in a paradigm that requires participants to mentally replay short sound or video clips. We show that memory reinstatement is accompanied by a decrease of low-frequency (8 Hz) power, which carries a temporal phase signature of the replayed stimulus. These replay effects were evident in the visual as well as in the auditory domain and were localized to sensory-specific regions. These results suggest low-frequency phase to be a domain-general mechanism that orchestrates dynamic memory replay in humans

The outcome of trachomatous trichiasis surgery in Ethiopia: risk factors for recurrence.

BACKGROUND: Over 1.2 million people are blind from trachomatous trichiasis (TT). Lid rotation surgery is the mainstay of treatment, but recurrence rates can be high. We investigated the outcomes (recurrence rates and other complications) of posterior lamellar tarsal rotation (PLTR) surgery, one of the two most widely practised TT procedures in endemic settings. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a two-year follow-up study of 1300 participants who had PLTR surgery, conducted by one of five TT nurse surgeons. None had previously undergone TT surgery. All participants received a detailed trachoma eye examination at baseline and 6, 12, 18 and 24 months post-operatively. The study investigated the recurrence rates, other complications and factors associated with recurrence. Recurrence occurred in 207/635 (32.6%) and 108/641 (16.9%) of participants with pre-operative major (>5 trichiatic lashes) and minor (5 lashes (major recurrence). Recurrence was greatest in the first six months after surgery: 172 cases (55%) occurring in this period. Recurrence was associated with major TT pre-operatively (OR 2.39, 95% CI 1.83-3.11), pre-operative entropic lashes compared to misdirected/metaplastic lashes (OR 1.99, 95% CI 1.23-3.20), age over 40 years (OR 1.59, 95% CI 1.14-2.20) and specific surgeons (surgeon recurrence risk range: 18%-53%). Granuloma occurred in 69 (5.7%) and notching in 156 (13.0%). CONCLUSIONS/SIGNIFICANCE: Risk of recurrence is high despite high volume, highly trained surgeons. However, the vast majority are minor recurrences, which may not have significant corneal or visual consequences. Inter-surgeon variation in recurrence is concerning; surgical technique, training and immediate post-operative lid position require further investigation

Impact of chronic stress protocols in learning and memory in rodents: systematic review and meta-analysis

The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals' strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests' performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments.This work was funded by the European Commission (FP7) "SwitchBox" (Contract HEALTH-F2-2010-259772) project and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), and by Fundacao Calouste Gulbenkian (Portugal) (Contract grant number: P-139977; project "Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)"). PSM is supported by an FCT fellowship grant, from the PhD-iHES program, with the reference PDE/BDE/113601/2015.info:eu-repo/semantics/publishedVersio