Miracle-dz/UniFAR-FTUs huggingface dataset:
Insight Into Mosquito GnRH-Related Neuropeptide Receptor Specificity Revealed Through Analysis of Naturally Occurring and Synthetic Analogs of This Neuropeptide Family

Adipokinetic hormone (AKH), corzazonin (CRZ) and the AKH/CRZ-related peptide (ACP) are peptides considered homologous to the vertebrate gonadotropin-releasing hormone (GnRH). All three Aedes aegypti GnRH-related neuropeptide receptors have been characterized and functionally deorphanized, which individually exhibit high specificity for their native ligands, which prompted us to investigate the contribution of ligand structures in conferring receptor specificity. In the current study, we designed a series of analogs based on the native ACP sequence in A. aegypti and screened them against the ACP receptor using a heterologous system to identify critical residues required for receptor activation. Specifically, analogs lacking the carboxy-terminal amidation, replacing aromatic residues, as well as truncated analogs were either completely inactive or had very low activities even at high concentration. The next most critical residues were the polar threonine in position 3 and the blocked amino-terminal pyroglutamate, with activity of the latter partially recovered using an alternatively blocked analog. ACP analogs with alanine substitutions at position 2 (valine), 5 (serine), 6 (arginine) and 7 (aspartic acid) positions were less detrimental as were replacements of charged residues. Interestingly, replacing asparagine with an alanine at position 9, creating a C-terminal WAA-amide, resulted in a 5-fold more active analog which may be useful as a lead superagonist compound. Similarly, we utilized this high-throughput approach against an A. aegypti AKH receptor (AKHR-IA) testing a number of mostly naturally-occurring AKH analogs from other insects to determine how substitutions of specific amino acids in the AKH ligand influences receptor activation. AKH analogs having single substitutions compared to the endogenous A. aegypti AKH revealed position 7 (serine) was well tolerated whereas changes to position 6 (proline) had pronounced effects, with receptor activity compromised nearly ten-fold. Substitution of position 3 (threonine) or analogs with combinations of substitutions were quite detrimental with a significant decrease in AKHR-IA activation. Interestingly, analogs with an asparagine residue at position seven displayed improved receptor activation compared to the native mosquito AKH. Collectively, these results advance our understanding of how two GnRH-related systems in A. aegypti sharing the most recent evolutionary origin sustain independence of function and signalling despite their relatively high degree of ligand and receptor homology.
Mollusks associated with the Avicennia schaueriana (Magnoliophyta: Acanthaceae) roots of a hypersaline estuary in northeastern Brazil

Abstract Aim Avicennia schaeuriana is one of the six species that composes the mangrove forests of Brazil and form mangrove fringes along waterways. The mangrove-roots of the A. schaeuriana act as one of the microhabitats used by the invertebrate biodiversity of the estuarine ecosystem. The present note aimed to inventory the malacofauna associated with roots of Avicennia schaueriana of the hypersaline and inverse estuary, highlighting variations in abundance and diversity along a salinity gradient and different seasonal periods. Methods Three sampling stations were delineated along the course of the estuary. At each station 3 transects of 10 meters were placed, and for each of them 3 sample points were selected, and at each point 3 samples of roots of A. schaueriana were obtained. A total of 108 samples were stored in plastic bags containing 4% formaldehyde and subsequently passed through a screening process, with identification of the associated specimens with the lowest possible taxonomic level. Results A total of 171 specimens was recorded, belonging to 10 species, 7 families, and 9 genera of the Bivalvia and Gastropoda classes. The abundance of the specimens differed between the seasonal periods analyzed. Conclusions The highest species richness and abundance of organisms in the rainy period allows inferences about the importance of the estuarine water cycle in regulating the biodiversity of these environments. Thus, the importance of the maintenance and protection of the mangrove forests composed of A. schaueriana, as well as the need for more in-depth studies becomes evident.
Immunogenetics of Parkinson's disease: Translational studies from rodents to humans

Parkinson's disease (PD) is a complex neurodegenerative disease, characterized by a progressive lossof dopaminergic neurons (DN) in the substantia nigra (SN) that innervate the striatum (ST) and pathologicalaccumulation of alpha-synuclein (αsyn) protein in aggregates called Lewy bodies (LB) and Lewy neurites(LN). As a complex disease, PD presents a genetically heterogeneous origin. Mutations in single genesaccount for 5-10% of all the cases. The remaining 90-95% of the cases present a complex andmultifactorial etiology, where there is an interplay between genetic and environmental factors that cansynergize to initiate the selective degeneration of DN in the SN and the development of PD pathology. Inthis thesis, we aimed to contribute to the understating of the genetic architecture of PD, and its implicationsin the DN loss and inflammatory aspects of the disease. We first explored differences in dopaminergicsusceptibility in two mouse strains that have a partial loss of Engrailed 1 (en1), a gene important fordopaminergic neuronal development and survival. Using linkage analysis, we identified 23 loci determiningdopaminergic susceptibility. The next part of the thesis was focus on immune mechanisms in PD, for thatwe used a congenic rat strain to study whether allelic variants of Mhc2ta, could affect α-syn-inducedpathology and dopaminergic neurodegeneration. Our results identified Mhc2ta as a facilitator andaggravator of PD-like αsyn pathology. The last part of this thesis, was focused on determining thefrequency of known pathogenic variants causing PD, in a Swedish multi-center sample collection. Out of7 studied pathogenic variants, we identified the LRRK2 p.G2019S mutation and SNCA duplication to bepresent at a low frequency among Swedish patients, supporting the notion of the very complex geneticarchitecture of PD, and suggesting other factors underlying PD risk in this population. Overall, the resultsgathered in this thesis have given insight into the complex genetics underlying disease risk and identifyingMHC2TA as a potential modulator of the immune response in PD.
Epilepsy and neurobehavioral abnormalities in mice with a KCNB1 pathogenic variant that alters conducting and non-conducting functions of KV2.1

Developmental and epileptic encephalopathies (DEE) are a group of severe epilepsies that usually present with intractable seizures, developmental delay and are at a higher risk for premature mortality. Numerous genes have been identified as a monogenic cause of DEE, including KCNB1. The voltage-gated potassium channel KV2.1, encoded by KCNB1, is primarily responsible for delayed rectifier potassium currents that are important regulators of excitability in electrically excitable cells, including neurons and cardiomyocytes. The de novo pathogenic variant KCNB1-p.G379R was identified in an infant with epileptic spasms, atonic, focal and tonic-clonic seizures that were refractory to treatment with standard antiepileptic drugs. Previous work demonstrated deficits in potassium conductance, but did not assess non-conducting functions. To determine if the G379R variant affected clustering at endoplasmic reticulum-plasma membrane junctions KV2.1-G379R was expressed in HEK293T cells. KV2.1-G379R expression did not induce formation of endoplasmic reticulum-plasma membrane junctions, and co-expression of KV2.1-G379R with KV2.1-WT lowered induction of these structures relative to KV2.1-WT alone, suggesting a dominant negative effect. To model this variant in vivo, we introduced Kcnb1G379R into mice using CRISPR/Cas9 genome editing. We characterized neurological and neurobehavioral phenotypes of Kcnb1G379R/+ (Kcnb1R/+) and Kcnb1G379R/G379R (Kcnb1R/R) mice, and screened for cardiac abnormalities. Immunohistochemistry studies on brains from Kcnb1+/+ (WT), Kcnb1R/+ and Kcnb1R/R mice revealed genotype-dependent differences in the levels and subcellular localization of KV2.1, with reduced plasma membrane expression of the KV2.1-G379R protein, consistent with in vitro data. Kcnb1R/+ and Kcnb1R/R mice displayed profound hyperactivity, repetitive behaviors, impulsivity and reduced anxiety. In addition, both Kcnb1R/+ and Kcnb1R/R mice exhibited abnormal interictal EEG abnormalities, including isolated spike and slow waves. Spontaneous seizure events were observed in Kcnb1R/R mice during exposure to novel environments and/or handling, while both Kcnb1R/+ and Kcnb1R/R mutants were more susceptible to induced seizures. Kcnb1R/+ and Kcnb1R/R mice exhibited prolonged rate-corrected QT interval on surface ECG recording. Overall, the Kcnb1G379R mice recapitulate many features observed in individuals with DEE due to pathogenic variants in KCNB1. This new mouse model of KCNB1 associated DEE will be valuable for improving the understanding of the underlying pathophysiology and will provide a valuable tool for the development of therapies to treat this pharmacoresistant DEE.
Revisional Cochlear Implant Surgeries in Adults

Introduction: Cochlear implant (CI) surgery allows hearing reestablishment among individuals with severe to profound hearing loss. However, only few patients will need a surgical reassessment. Objectives: To verify the incidence of surgical reassessment among adult patients; to verify the reasons that led the second surgery to be performed; to verify the efficacy—and audiological outcomes—of revisional surgery. Method: A longitudinal retrospective cohort study was carried out with the review of medical records, of adult patients, with bilateral severe to profound sensorineural hearing loss who underwent to revisional surgery, from 2004 to 2016 at a CI Center, in Brazil. Results: One hundred fifty-eight CI surgeries were performed among 137 adult patients. Fourteen revisional surgeries were performed among 10 patients: five surgeries were due by displacement of the internal unit; one because of having excessive subcutaneous tissue; one due to non-progression of the electrodes during the initial surgery, one late tympanic membrane perforation, one late facial palsy and, one due to a suture dehiscence in the surgical incision with exposure of the internal unit. Conclusions: The incidence of surgical reassessment among adult CI patients was 8.9%. All implanted patients that underwent a new surgical approach maintained an improved auditory threshold after revisional CI surgery.
Bradykinin sequesters B2 bradykinin receptors and the receptor-coupled Ga SUBUNITS Gaq and Gai in caveolae

Caveolae are small flask-like invaginations on the plasma membrane that contain both G-proteins aim G-protein coupled receptors. Consequently, these structures have been implicated to serve a role in transmembrane signaling. Bradykinin (BK) is a potent vasoactive peptide that acts through B2 BK receptors to stimulate both Gaq and Gai. DDT1 MF2 smooth muscle cells were used to show that eaveolae contain both Gaq, Gai and B2 receptors. Ga subunits and caveolin, a marker protein for eaveolae, were monitored by iminunoblotting, while B2 receptors were monitored as receptor radioligand complexes which were formed prior to cell disruption and caveolae enrichment. At 4°C, both agonist and antagonist receptor complexes were detected in eaveolae, and both types of complexes were acid-sensitive. Elevation of the temperature to 37°C resulted in a recruitment of agonist receptor complexes to caveotae and an increased acid-resistance of these complexes. Furthermore, these con ditions also promoted the recruitment of Gaq and Gci subunits. In contrast, antagonist receptor complexes were not recruited and remained acid-sensitive, and antagonists did not recruit Ga subunits. These results show that agonists for some G-protein-coupled receptors sequester their receptors and receptorcoupled Ga subunits in caveolae. (Less)
Learning with reward prediction errors in a model of the Drosophila mushroom body

Effective decision making in a changing environment demands that accurate predictions are learned about decision outcomes. In Drosophila, such learning is or-chestrated in part by the mushroom body (MB), where dopamine neurons (DANs) signal reinforcing stimuli to modulate plasticity presynaptic to MB output neurons (MBONs). Here, we extend previous MB models, in which DANs signal absolute rewards, proposing instead that DANs signal reward prediction errors (RPEs) by utilising feedback reward predictions from MBONs. We formulate plasticity rules that minimise RPEs, and use simulations to verify that MBONs learn accurate reward predictions. We postulate as yet unobserved connectivity, which not only overcomes limitations in the experimentally constrained model, but also explains additional experimental observations that connect MB physiology to learning. The original, experimentally constrained model and the augmented model capture a broad range of established fly behaviours, and together make five predictions that can be tested using established experimental methods.
Effect of homeopathic medicines on growth, survival and gastrointestinal microbiota of juvenile scallop Argopecten ventricosus

Objective. To study the effect of homeopathic medicines on growth, survival and gastrointestinal (GIT) microbiota of Catarina scallop Argopecten ventricosus. Materials and methods. Five homeopathic treatments (T1) ViP-ViA 1D, (T2) ViP-ViA 7C, (T3) AcF-MsS 1D, (T4) PhA-SiT 7C, (T5) ViT 31C and three controls: (C1) diluted ethanol 1:99, (C2) diluted/succussed ethanol 1C and (C3) distilled water were evaluated (21 days) in triplicate. Microbiota was analysed by sequencing the V3-V5 region of the 16S rRNA genes. Results. The best growth in shell-length corresponded to T1 (117 µm d-1) and T2 (108 µm d-1) and the highest survival (P ≤ 0.05) to T3 and T5, stating T3 as the best HOM-treatment. A clear separation was found in rarefaction curves of HOM-treated against un-treated control scallops. Significant differences (P ≤ 0.05) were found for Phyla (Proteobacteria> Actinobacteria> Firmicutes> Bacterloidetes>Chloroflexi and for Genera: Symbiobacterium> Microbacterium> Methylobacillus> Bacillus> Paenibacillus> Burkholderia> Nostoc> Methylobacterium> Leucobacter). The genus Symbiobacterium was dominant in the HOM-treatment T5 (Vidatox®), finding significant differences (P ≤ 0.05) with respect to all treatments. At species level, Microbacterium maritypicum (Actinobacteria) showed a greater relative abundance (P ≤ 0.05) in T1 and T3 and Symbiobacterium toebii (Firmicutes) was also significantly higher (P ≤ 0.05) in abundance in T5 and T2, both against initial T0. Conclusions. This study showed for the first time, the composition of the GIT microbiota in Catarina scallop A. ventricosus and focused on the potential applicability of homeopathic medicines to improve overall performance and modulate the GIT microbiota of the species.
An integrated study of the biodiversity within the Pseudechiniscus suillus–facettalis group (Heterotardigrada: Echiniscidae)

Pseudechiniscus is the second most species-rich genus in Heterotardigrada and in the family Echiniscidae. However, previous studies have pointed out polyphyly and heterogeneity in this taxon. The recent erection of the genus Acanthechiniscus was another step in making Pseudechiniscus monophyletic, but species identification is still problematic. The present investigation aims at clarifying biodiversity and taxonomy of Pseudechiniscus taxa, with a special focus on species pertaining to the so-called ‘suillus–facettalis group’, by using an integrated approach of morphological and molecular investigations. The analysis of sequences from specimens sampled in Europe and Asia confirms the monophyly of the genus Pseudechiniscus. Inside the genus, two main evolutionary lineages are recognizable: the P. novaezeelandiae lineage and the P. suillus–facettalis group lineage. Inside the P. suillus–facettalis group, COI molecular data points out a very high variability between sampled localities, but in some cases also among specimens sampled in the same locality (up to 33.3% p-distance). The integrated approach to the study of Pseudechiniscus allows confirmation of its monophyly and highlights the relationships in the taxon, pointing to its global distribution.
Genetic diversity in Hemileia vastatrix based on RAPD markers

Random amplified polymorphic DNA (RAPD) was used to assess the genetic structure of Hemileia vastatrix populations. Forty-five rust isolates with different virulence spectra and from different hosts and geographical regions were analyzed. Out of 45 bands, generated with three RAPD primers, 35 (78%) were polymorphic and scored as molecular markers. Cluster analysis exhibits unstructured variability of this pathogen with regard to physiological race, geographical origin or host. The genotypic diversity (H′) inferred from Shannon’s index was higher than gene diversity (Ht), suggesting that diversity is distributed among clonal lineages. Estimates of gene diversity in Africa and Asia populations were higher in total (Ht) as compared to within population diversity (Hs). Genetic differentiation was considerable among coffee rust isolates from Africa (Gst = 0.865) and Asia (Gst = 0.768) but not among isolates from South America (Gst = 0.266). We concluded that genetic diversity in H. vastatrix was moderately low and that the genetic differentiation among populations shows that asexual reproduction is likely to play an important role in the population biology of this fungus. This should be taken into account for the development of breeding programs.
Dopaminergic modulation of the exploration/exploitation trade-off in human decision-making

A central issue in reinforcement learning and decision-making is whether to exploit knowledge of reward values, or to explore novel options. Although it is widely hypothesized that dopamine neurotransmission plays a key role in regulating this balance, causal evidence for a role of dopamine in human exploration is still lacking. Here, we use a combination of computational modeling, pharmacological intervention and functional magnetic resonance imaging (fMRI) to test for a causal effect of dopamine transmission on the exploration-exploitation trade-off in humans. 31 healthy male subjects performed a restless four-armed bandit task in a within-subjects design under three drug conditions: 150mg of the dopamine precursor L-dopa, 2mg of the D2 receptor antagonist haloperidol, and placebo. In all conditions, choice behavior was best explained by an extension of an established Bayesian learning model accounting for perseveration, uncertainty-based exploration and random exploration. Uncertainty-based exploration was attenuated under L-dopa compared to placebo and haloperidol. There was no evidence for a modulation of prediction error signaling or categorical effects of exploration/exploitation under L-dopa, whereas model-based fMRI revealed that L-dopa attenuated neural representations of overall uncertainty in insula and dorsal anterior cingulate cortex. Our results highlight the computational role of these regions in exploration and suggest that dopamine modulates exploration by modulating how this circuit tracks accumulating uncertainty during decision-making.
The physical and mechanical properties of potato (Solanum tuberosum L.) tubers as related to the automatic separation from clods and stones

In the current research, some of the mechanical and physical properties of two industrial varieties of potato tubers that have a prominent role in the mechanised separation process from clods and stones were investigated. These properties include the physical dimension, mass, volume, sphericity, surface area, density, projected areas and Young’s modulus. In addition, the static coefficient of friction and rolling resistance for tubers on five surface materials were determined. The tuber’s size positively affected the physical and mechanical properties of the tubers. The frictional properties of the tubers were affected by the tuber size, the surface type, and the interaction between them. The results showed that most of the apparent properties for the Sante variety were greater than those of the Marfona variety. The static coefficient of friction for the tubers on a wood surface was the maximum and was the minimum value on a galvanized sheet, but for the tuber’s rolling resistance, the results were inversed. The results proposed that the automatic separation of the potato tubers from the impurities using the properties of the crop is possible.
Breaking Bud Dormancy for Flame Seedless Grapevine by Using Some Economic Sources.

This study was carried out for two successive seasons (2013&2014) in a private vineyard located at Aga – Dakahlia Governrate to evaluate the efficiency of some new alternatives on dormancy breaking of Flame Seedless grapevines. The chosen vines were 5 years old, grown in a clay loam soil, spaced at 2x2.5m , irrigated by flood irrigation system . The vines were pruned during the second week of January for the two seasons of the study to obtain bud load of 72 buds/vine (6 canes x 12 buds/cane)and sprayed on the third week of January by phosphoric acid 2%, sulphoric acid 2%, potassium nitrate 5%, potassium hydroxid 1%, zinc sulfate3%, urea10%, H2O2 1%, dormex 4% and mineral oil7%. The result show that all treatments hastened the beginning of bud burst and significantly shortened the duration of bud burst rather than the control treatment. Dormex at 4% was most effective as it gave about 95% bud burst.
Botryosphaeria corticola, sp. nov. on Quercus species, with notes and description of Botryosphaeria stevensii and its anamorph, Diplodia mutila

Botr yosphaeria stevensii frequently has been associated with dieback and canker diseases of oak, mainly in the western Mediterranean area but more rarely in other regions. The species concept of B. stevensii has been unclear, and it is possible that some collections were identified incorrectly. A collection of fungal strains isolated from diseased oak trees and initially identified as B. stevensii was characterized on the basis of morphology and ITS nucleotide sequences. Morphology was compared with the type specimens of Physalospora mutila (= B. stevensii) and its anamorph, Diplodia mutila. It was concluded that the isolates from oak differed from B. stevensii in having larger ascospores and conidia as well as different spore shapes and represented an as yet undescribed species, which is described here as B. corticola. Moreover, ITS sequence data separated B. corticola from all other known species of Botryosphaeria. Amended descriptions of B. stevensii and its anamorph are provided to differentiate B. stevensii from B. corticola and to clarify some of the earlier taxonomic uncertainties.