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Our understanding on human neurodegenerative disease was previously limited to clinical data and inferences about the underlying pathology based on histopathological examination. Animal models and in vitro experiments have provided evidence for a cell-autonomous and a non-cell autonomous mechanism for the accumulation of neuropathology. Combining modern neuroimaging tools to identify distinct neural networks (Connectomics) with target-specific Positron Emission Tomography (PET) tracers is an emerging and vibrant field of research with the potential to examine the contributions of cell-autonomous and non-cell autonomous mechanisms to the spread of pathology. The evidence provided here suggests that both cell-autonomous and non-cell autonomous processes relate to the observed in vivo characteristics of protein pathology and neurodegeneration across the disease spectrum. We propose a synergistic model of cell- autonomous and non-cell autonomous accounts that integrates the most critical factors (i.e., protein strain, susceptible cell feature and connectome) contributing to the development of neuronal dysfunction and in turn produces the observed clinical phenotypes. We believe that a timely and longitudinal pursuit of such research programs will greatly advance our understanding of the complex mechanisms driving human neurodegenerative diseases.

Although beta-amyloid (Aβ) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aβ deposition measured with 18F-florbetapir may serve as biomarker for progression risk in Aβ-positive cognitively normal (CN) and MCI patients, including clinical follow-up data and cerebrospinal fluid (CSF) biomarkers. Voxel-wise group comparisons between age and sex-matched Aβ-positive groups (i.e., CN-stables [n = 38] vs. CN-to-MCI/AD progressors [n = 38], MCI-stables [n = 104] versus MCI-to-AD progressors [n = 104]) revealed higher Aβ burden in precuneus, subcortical, and parietal regions in CN-to-MCI/AD progressors and cingulate, temporal, and frontal regions in MCI-to-AD progressors. Importantly, these regional patterns predicted progression to advanced stages on the AD spectrum in the short and the long-term beyond global Aβ burden and CSF biomarkers. These results suggest that distinct regional patterns of Aβ burden are a valuable biomarker for risk of disease progression in CN and MCI.

Tau protein aggregations are a hallmark of amyloid-associated Alzheimer disease and some forms of non–amyloid-associated frontotemporal lobar degeneration. In recent years, several tracers for in vivo tau imaging have been under evaluation. This study investigated the ability of 18F-flortaucipir PET not only to assess tau positivity but also to differentiate between amyloid-positive and -negative forms of neurodegeneration on the basis of different 18F-flortaucipir PET signatures. Methods: The 18F-flortaucipir PET data of 35 patients with amyloid-positive neurodegeneration, 19 patients with amyloid-negative neurodegeneration, and 17 healthy controls were included in a data-driven scaled subprofile model (SSM)/principal-component analysis (PCA) identifying spatial covariance patterns. SSM/PCA pattern expression strengths were tested for their ability to predict amyloid status in a receiver-operating-characteristic analysis and validated with a leave-one-out approach. Results: Pattern expression strengths predicted amyloid status with a sensitivity of 0.94 and a specificity of 0.83. A support vector machine classification based on pattern expression strengths in 2 different SSM/PCA components yielded a prediction accuracy of 98%. Anatomically, prediction performance was driven by parietooccipital gray matter in amyloid-positive patients versus predominant white matter binding in amyloid-negative patients. Conclusion: SSM/PCA-derived binding patterns of 18F-flortaucipir differentiate between amyloid-positive and -negative neurodegenerative diseases with high accuracy. 18F-flortaucipir PET alone may convey additional information equivalent to that from amyloid PET. Together with a perfusion-weighted early-phase acquisition (18F-FDG PET–equivalent), a single scan potentially contains comprehensive information on amyloid (A), tau (T), and neurodegeneration (N) status as required by recent biomarker classification algorithms (A/T/N).

Purpose: Tau pathology progression in Alzheimer's disease (AD) is explained through the network degeneration hypothesis and the neuropathological Braak stages; however, the compatibility of these models remains unclear.Methods: We utilized [18F]AV-1451 tau-PET scans of 39 subjects with AD and 39 sex-matched amyloid-negative healthy controls (HC) in the ADNI (Alzheimer's Disease Neuroimaging Initiative) dataset. The peak cluster of tau-tracer uptake was identified in each Braak stage of neuropathological tau deposition and used to create a seed-based functional connectivity network (FCN) using 198 HC subjects, to identify healthy networks unaffected by neurodegeneration.Results: Voxel-wise tau deposition was both significantly higher inside relative to outside FCNs and correlated significantly and positively with levels of healthy functional connectivity. Within many isolated Braak stages and regions, the correlation between tau and intrinsic functional connectivity was significantly stronger than it was across the whole brain. In this way, each peak cluster of tau was related to multiple Braak stages traditionally associated with both earlier and later stages of disease.Conclusion: We show specificity of healthy FCN topography for AD-pathological tau as well as positive voxel-by-voxel correlations between pathological tau and healthy functional connectivity. We propose a model of "up- and downstream" functional tau progression, suggesting that tau pathology evolves along functional connectivity networks not only "downstream" (i.e., along the expected sequence of the established Braak stages) but also in part "upstream" or "retrograde" (i.e., against the expected sequence of the established Braak stages), with pathology in earlier Braak stages intensified by its functional relationship to later disease stages.Keywords: Alzheimer’s disease; Braak stage; Functional connectivity; Network degeneration hypothesis; PET; Tau.

Impulsive-compulsive behaviours like pathological gambling or hypersexuality are a frequent side effect of dopamine replacement therapy in patients with Parkinson's disease. Multiple imaging studies suggest a significant reduction of presynaptic dopamine transporters in the nucleus accumbens to be a predisposing factor, reflecting either a reduction of mesolimbic projections or, alternatively, a lower presynaptic dopamine transporter expression per se. Here, we aimed to test the hypothesis of fewer mesolimbic projections as a risk factor by using dopamine synthesis capacity as a proxy of dopaminergic terminal density. Furthermore, previous studies have demonstrated a reduction of fronto-striatal connectivity to be associated with increased risk of impulsive-compulsive behaviour in Parkinson's disease. Therefore, another aim of this study was to investigate the relationship between severity of impulsive-compulsive behaviour, dopamine synthesis capacity and fronto-striatal connectivity. Eighty participants underwent resting state functional MRI and anatomical T1-weighted images [mean age: 68 ± 9.9 years, 67% male (patients)]. In 59 participants, 18F-DOPA-PET was obtained and voxel-wise Patlak slopes indicating dopamine synthesis capacity were calculated. All participants completed the QUIP-RS questionnaire, a well validated test to quantify severity of impulsive-compulsive behaviour in Parkinson's disease. A voxel-wise correlation analysis between dopamine synthesis capacity and QUIP-RS score was calculated for striatal regions. To investigate the relationship between symptom severity and functional connectivity, voxel-wise correlations were performed. A negative correlation was found between dopamine synthesis capacity and QUIP-RS score in the nucleus accumbens (r = -0.57, P = 0.001), a region functionally connected to the rostral anterior cingulate cortex. The connectivity strength was modulated by QUIP-RS, i.e. patients with more severe impulsive-compulsive behaviours had a weaker functional connectivity between rostral anterior cingulate cortex and the nucleus accumbens. In addition, cortical thickness and severity of impulsive-compulsive behaviour were positively correlated in the subgenual rostral anterior cingulate cortex. We found three factors to be associated with severity of impulsive-compulsive behaviour: (i) decreased dopamine synthesis capacity in the nucleus accumbens; (ii) decreased functional connectivity of the rostral anterior cingulate cortex with the nucleus accumbens; and (iii) increased cortical thickness of the subgenual rostral anterior cingulate cortex. Rather than a downregulation of dopamine transporters, a reduction of mesolimbic dopaminergic projections in conjunction with a dysfunctional rostral anterior cingulate cortex-a region known to play a key role in impulse control-could be the most crucial neurobiological risk factor for the development of impulsive-compulsive behaviours in patients with Parkinson's disease under dopamine replacement therapy.

Cultivation of pepper has become the fastest growing practice in recent years, and specifically, habanero pepper which has surpassed its traditional area of ​​cultivation, and has expanded to other areas, conquering the markets of the rest of the country and the world. In the present study, 3 doses of solarized manure (40, 60 and 80 t ha-¹) and an absolute control were evaluated for the production of habanero pepper (Capsicum chinense Jacq). The results indicated a significant difference between treatments for the plant height at 30 and 90 days after transplantation. However, for the variables: fruit number and fruit weight (kg per experimental unit, kg m-² and kg per plant), the results indicated that there was no significant difference among the treatments evaluated. For the variables: polar diameter of the fruit, a significant difference was observed. However, the treatments did not show a significant effect on the equatorial diameter of the fruit. Key words: Solarized manure, habanero pepper, organic fertilizers.

The organics alternatives in the vegetables production are a strategy to produce free chemical polluted foods that endanger human health. In the present study, the Hermosa indeterminate tomato variety was used and the following treatments were evaluated in a completely randomized design: Compost 2 tons/ha + VAM and BAC + Compost tea 50% (Treatment 1), Compost 4 tons/ha + VAM and BAC + Compost tea 50% (Treatment 2), Compost 6 tons/ha + VAM and BAC + Compost tea 50% (Treatment 3), VAM and BAC + Compost tea 50% (Treatment 4) and Absolute control (Treatment 5). The results indicate that Treatment 3 (Compost 6 ton/ha + VAM and BAC + Compost tea 50%) had the highest plant height at 120 days after planting (414.07 cm). Regarding the number of fruits per plant, fruit weight per experimental unit, fruit weight per m² and fruit weight per plant, no significant differences were identified. The five treatments show no significant difference in polar and equatorial diameter of the fruit weight, fruit density and unit volume. For five treatments evaluated, the pH, Brix and fruit firmness variables do not show significant difference. Key words: Tomato, Lycopersicum, manure.

See Whitwell (doi:10.1093/brain/awy001) for a scientific commentary on this article.A stereotypical anatomical propagation of tau pathology has been described in Alzheimer's disease. According to recent concepts (network degeneration hypothesis), this propagation is thought to be indicative of misfolded tau proteins possibly spreading along functional networks. If true, tau pathology accumulation should correlate in functionally connected brain regions. Therefore, we examined whether independent components could be identified in the distribution pattern of in vivo tau pathology and whether these components correspond with specific functional connectivity networks. Twenty-two 18F-AV-1451 PET scans of patients with amnestic Alzheimer's disease (mean age = 66.00 ± 7.22 years, 14 males/eight females) were spatially normalized, intensity standardized to the cerebellum, and z-transformed using the mean and deviation image of a healthy control sample to assess Alzheimer's disease-related tau pathology. First, to detect distinct tau pathology networks, the deviation maps were subjected to an independent component analysis. Second, to investigate if regions of high tau burden are associated with functional connectivity networks, we extracted the region with the maximum z-value in each of the generated tau pathology networks and used them as seeds in a subsequent resting-state functional MRI analysis, conducted in a group of healthy adults (n = 26) who were part of the 1000 Functional Connectomes Project. Third, to examine if tau pathology co-localizes with functional connectivity networks, we quantified the spatial overlap between the seed-based networks and the corresponding tau pathology network by calculating the Dice similarity coefficient. Additionally, we assessed if the tau-dependent seed-based networks correspond with known functional resting-state networks. Finally, we examined the relevance of the identified components in regard to the neuropathological Braak stages. We identified 10 independently coherent tau pathology networks with the majority showing a symmetrical bi-hemispheric expansion and coinciding with highly functionally connected brain regions such as the precuneus and cingulate cortex. A fair-to-moderate overlap was observed between the tau pathology networks and corresponding seed-based networks (Dice range: 0.13-0.57), which in turn resembled known resting-state networks, particularly the default mode network (Dice range: 0.42-0.56). Moreover, greater tau burden in the tau pathology networks was associated with more advanced Braak stages. Using the data-driven approach of an independent component analysis, we observed a set of independently coherent tau pathology networks in Alzheimer's disease, which were associated with disease progression and coincided with functional networks previously reported to be impaired in Alzheimer's disease. Together, our results provide novel information regarding the impact of tau pathology networks on the mechanistic pathway of Alzheimer's disease.

Tectona grandis (teak) is an economically important tree. It is a valuable tree whose wood is used in both shipping and carpentry industries. In this work we evaluated 11 treatments to assess the percentage of seed germination of T. grandis. The results showed that after 21 days, four treatments had greater germination percent when compared with the control. These treatments were, (i) when the seeds were exposed to sunlight for three days, 78% germination was observed (ii) the seeds were soaked in water for 72 h, 66% germination was observed (iii) the seeds were soaked in water for 12 h and dried for 12 h at a temperature range of between 22 and 45°C, 79% germination was observed, (iv) finally, the seeds were soaked in fast-flowing water for 24 h and exposed to sunlight for 24 h, 80% germination was observed. In this study we found that the best technique to stimulate germination is to soak the seeds for 24 h, and exposed them to sunlight for 24 h. In conclusion, the technique is easy to apply and also we can treat many seeds at the same time. Key words: Tectona grandis, germination, seeds.

1. A race of corn was discovered in which self-fertilization of genotype Cc produces, not 25 per cent white grains, but 10.85 per cent; that is, the normal 3:1 ratio has been distorted in the direction of a deficiency of the recessive class. 2. To account for these results, a working hypothesis is proposed which involves a zygotic lethal factor partially linked with c. If the original genotype C-L1, c-L1 mutated to C-L1, c-l1, self-fertilization would eliminate many of the potential whites through the action of the lethal. The exact ratio resulting would depend upon the frequency of crossing-over between c and l1; the observed results correspond to about 18 per cent crossing-over. 3. This hypothesis has been confirmed by three breeding tests. (a) Individuals of genotype C-L1, c-l1, which give a deficiency of whites upon self-fertilization, give no deficiency in crosses with C-tester (c-l1, c-L1). (b) The low-white race has thrown high-white races (33 per cent white) of composition C-l1, c-L1. (c) Part of ...

1. The use of the corn-pollinator is recommended to amateur investigators. 2. The P(Pr), R, and C factors for aleurone color, variously combined, gave predictable and readily distinguished ratios. 3. In many cases the exact genotype, with reference to the R and C factors, can be distinguished by superficial appearance. 4. The particolored grains of East and Hayes were identified. In these some partial substitute enables the P and R factors to express themselves, even in the absence of C. This substitute is heritable, but its effectiveness is limited by local conditions in different parts of the ear or of the plant as a whole. 5. Mottling (Emerson), which occurs when the R factor comes in with the male parent only, is conditioned by the presence of a heritable factor or factors. This factor occurs in the C tester family, and is dominant in crosses with families which do not show mottling. The R tester family seems to contain a different factor, which produces apparent mottling only in a small percentage of...

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