DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart morphology and function

DiGeorge syndrome (DGS) is the most common microdeletion syndrome, and is characterized by congenital cardiac, craniofacial and immune system abnormalities. The cardiac defects in DGS patients include conotruncal and ventricular septal defects. Although the etiology of DGS is critically regulated by TBX1 gene, the molecular pathways underpinning TBX1's role in heart development are not fully understood. In this study, we characterized heart defects and downstream signaling in the zebrafish tbx1^(−/−) mutant, which has craniofacial and immune defects similar to DGS patients. We show that tbx1^(−/−) mutants have defective heart looping, morphology and function. Defective heart looping is accompanied by failure of cardiomyocytes to differentiate normally and failure to change shape from isotropic to anisotropic morphology in the outer curvatures of the heart. This is the first demonstration of tbx1's role in regulating heart looping, cardiomyocyte shape and differentiation, and may explain how Tbx1 regulates conotruncal development in humans. Next we elucidated tbx1's molecular signaling pathway guided by the cardiac phenotype of tbx1^(−/−) mutants. We show for the first time that wnt11r (wnt11 related), a member of the non-canonical Wnt pathway, and its downstream effector gene alcama (activated leukocyte cell adhesion molecule a) regulate heart looping and differentiation similarly to tbx1. Expression of both wnt11r and alcama are downregulated in tbx1^(−/−) mutants. In addition, both wnt11r^(−/−) mutants and alcama morphants have heart looping and differentiation defects similar to tbx1^(−/−) mutants. Strikingly, heart looping and differentiation in tbx1^(−/−) mutants can be partially rescued by ectopic expression of wnt11r or alcama, supporting a model whereby heart looping and differentiation are regulated by tbx1 in a linear pathway through wnt11r and alcama. This is the first study linking tbx1 and non-canonical Wnt signaling and extends our understanding of DGS and heart development

Going in circles is the way forward: the role of recurrence in visual inference

Biological visual systems exhibit abundant recurrent connectivity. State-of-the-art neural network models for visual recognition, by contrast, rely heavily or exclusively on feedforward computation. Any finite-time recurrent neural network (RNN) can be unrolled along time to yield an equivalent feedforward neural network (FNN). This important insight suggests that computational neuroscientists may not need to engage recurrent computation, and that computer-vision engineers may be limiting themselves to a special case of FNN if they build recurrent models. Here we argue, to the contrary, that FNNs are a special case of RNNs and that computational neuroscientists and engineers should engage recurrence to understand how brains and machines can (1) achieve greater and more flexible computational depth, (2) compress complex computations into limited hardware, (3) integrate priors and priorities into visual inference through expectation and attention, (4) exploit sequential dependencies in their data for better inference and prediction, and (5) leverage the power of iterative computation

ANALISIS KELAYAKAN FINANSIAL SAYURAN ORGANIK DI EKOPASTORAL KELURAHAN PAGAL KECAMATAN CIBAL KABUPATEN MANGGARAI

  The research was conducted on organic vegetable business in Pagal Ekopastoral, Cibal Sub-district.  The research aims to determine the income and financial feasibility of organic vegetables with break event point and revenue cost ratio. Data collection with interviews using questionnaires. Data tabulated and analyzed with the method of break event point (BEP) and revenue Cost Ratio (R/C). These two types of analysis are divided into two forms, namely by vegetable type and overall. Based on calculations using bep method of production and price, types of vegetables caisim, pakcoy, chicory, cauliflower and broccoli worth trying or developed next where BEP production of 153.5 kg means the point of return of organic vegetables is occurring at the time of production of 153.5 kg, while BEP organic vegetable prices achieved at a minimum price of Rp. 3,070 / kg, meaning the point of return of organic vegetables at a minimum price of Rp.3,070 /kg. The calculation of R/C Ratio of all types of vegetables obtained a value of 3.25. Meaning that each cost expenditure of Rp. 1, then farmers will get a receipt of Rp.3.25. Based on this value shows that the revenue is greater than the cost of production so it can be said that the organic vegetable business in Ekopastoral is in a profitable position and worth running

Import of ADP/ATP carrier into mitochondria

We have identified the yeast homologue of Neurospora crassa MOM72, the mitochondrial import receptor for the ADP/ATP carrier (AAC), by functional studies and by cDNA sequencing. Mitochondria of a yeast mutant in which the gene for MOM72 was disrupted were impaired in specific binding and import of AAC. Unexpectedly, we found a residual, yet significant import of AAC into mitochondria lacking MOM72 that occurred via the receptor MOM19. We conclude that both MOM72 and MOM19 can direct AAC into mitochondria, albeit with different efficiency. Moreover, the precursor of MOM72 apparently does not require a positively charged sequence at the extreme amino terminus for targeting to mitochondria

Pretreatment With Fragments of Substance-P or With Cholecystokinin Differentially Affects Recovery From Sub-Total Nigrostriatal 6-Hydroxydopamine Lesion

The neuropeptide substance P is known to have mnemogenic and reinforcing actions and can exert neurotrophic and regenerative effects in vitro as well as in vivo. Furthermore, our previous work in the rat showed that either pre- or post-lesion treatment with substance P can promote functional recovery in cases of partial nigrostriatal dopamine lesions. Other work has provided evidence that the effects of substance P might be differentially encoded by its C- and N-terminal fragments. The C-terminal fragment was found to be reinforcing, whereas the mnemogenic as well as neurotrophic properties have been ascribed to the N-terminal sequences. Given these relations, we asked here whether pre-lesion treatment with either a C- or an N-terminal fragment of substance P might differentially affect the behavioral and neurochemical outcome of nigrostriatal dopamine lesions. Therefore, either substance P1−7 or substance P5−11 (37 nmol/kg each) was administered intraperitoneally daily for eight consecutive days before unilateral 6-hydroxy-dopamine lesions of the substantia nigra. Control rats received prelesion treatment with vehicle. Furthermore, we investigated the effects of pre-treatment with Boc-cholecystokinin-4 (0.91 nmol/kg), as we had found an increase in dopamine metabolism in animals that were pre-treated with cholecystokinin-8 in a former study. In accordance with our previous work, drug treatment effects were observed when excluding animals with most severe dopamine lesions: In animals with partial lesions (residual neostriatal dopamine levels of more than 10%), lesion-dependent asymmetries in turning behavior were observed in animals that were pre-treated with vehicle-, substance P1−7 , or Boc-cholecysto-kinin–4,. whereas turning after pre-treatment with substance P5−11 was not significantly asymmetrical. Furthermore, the ipsi- and contra-lateral neostriatal dopamine levels did not differ significantly in this group. Moreover, pre treatment with substance P5−11 affected dopamine metabolism in the neostriatum and in the venral striatum, as indicated by increased ratios of dihydroxyphenyllic acid to dopamine. The data provide the first evidence that the promotive effects of substance-P treatment in the unilateral dopamine lesion model might be mediated by its C-terminal and might depend on actions on residual dopamine mechanisms

PERSEPSI PETANI TERHADAP PERAN PENYULUH PERTANIAN DALAM MENINGKATKAN PRODUKTIVITAS USAHATANI HORTIKULTURA SAYUR SAWI DI DESA TIWATOBI KECAMATAN ILE MANDIRI KABUPATEN FLORES TIMUR

This research had been conducted in Lewokeleng Village, Ile Boleng District, Flores Timur Regency, from February to March 2018. This study aims to know; 1) characteristics of horticultural crops, 2) Perception of farmers on the role of agricultural extension workers as educators, informators, companions, consultants, and mentors in increasing the productivity of vegetable horticultural farming, 3) Perception of farmers to the role of agricultural counselor in increasing the productivity of vegetables farming, and 4) Constraints were faced by farmers in improving productivity of vegetable farming. Data collection method used in this research was survey method. The location of the study was determined intentionally. Respondents were determined as many as 55 farmers, selected by simple random sampling from 122 families of vegetables farmers. The types of the collected data are primary and secondary data. To know the first and second purposes, data was analyzed descriptively and quantitatively, then to know the third purpose, data was analyzed descriptively using likert scale, and to know the fourth purpose, data was analyzed descriptively and quantitatively. The results of research are; 1) The average of productive land which is used by farmers in Lewokeleng Village, Ile Boleng District, East Flores Regency is ​​0.50-1.0 ha. The majority of land which the respondents were working on is self-owned land. The management of vegetable farming, includes land preparation, seeding, planting, maintenance, harvesting and post harvest, and marketing. agriculture in research area is classified as developing agriculture. 2) The role of agricultural counselor in overcoming problems had faced by farmers, most farmers have felt the service of agricultural counselor, the role of the agricultural counselor are 40,36% as educator, 38,55% as informer, 40,48% as companion, 40,00% as consultant, and 40,55% as mentor. The frequency of agricultural counselor activities was low. 3) The perception of farmers on the role of agricultural counselor in increasing the productivity of horticultural crop farming in the village of Lewokeleng included "less good" category with maximum achievement percentage on 37,95% of the range of 36-51%. 4) All respondents faced the same problems which was lack of local government involvement, agricultural counselor involvement, assistance that is inconsistent with the needs of farmers, limited capital, lack of manpower and time, skills and experience of farmers, and markets