Brazil never had segregation laws defining membership of an ethnoracial group. Thus, the composition of the Brazilian population is mixed, and its ethnoracial classification is complex. Previous ...studies showed conflicting results on the correlation between genome ancestry and ethnoracial classification in Brazilians. We used 370,539 Single Nucleotide Polymorphisms to quantify this correlation in 5,851 community-dwelling individuals in the South (Pelotas), Southeast (Bambui) and Northeast (Salvador) Brazil. European ancestry was predominant in Pelotas and Bambui (median = 85.3% and 83.8%, respectively). African ancestry was highest in Salvador (median = 50.5%). The strength of the association between the phenotype and median proportion of African ancestry varied largely across populations, with pseudo R(2) values of 0.50 in Pelotas, 0.22 in Bambui and 0.13 in Salvador. The continuous proportion of African genomic ancestry showed a significant S-shape positive association with self-reported Blacks in the three sites, and the reverse trend was found for self reported Whites, with most consistent classifications in the extremes of the high and low proportion of African ancestry. In self-classified Mixed individuals, the predicted probability of having African ancestry was bell-shaped. Our results support the view that ethnoracial self-classification is affected by both genome ancestry and non-biological factors.
Hydroxide Ag(OH)L (L =
L,
L,
L,
L), oxide {AgL}
}(μ-O) (L =
L,
L,
L,
L,
L) or chloride Ag
LCl, Ag(
L)
Cl complexes were obtained from reactions of mono- or bicamphorimine derivatives with Ag(OAc) or ...AgCl. The new complexes were characterized by spectroscopic (NMR, FTIR) and elemental analysis. X-ray photoelectron spectroscopy (XPS), ESI mass spectra and conductivity measurements were undertaken to corroborate formulations. The antimicrobial activity of complexes and some ligands were evaluated towards
and
, and strains of the bacterial species
,
,
and
based on the Minimum Inhibitory Concentrations (MIC). Complexes displayed very high activity against the
species studied with the lowest MIC values (3.9 µg/mL) being observed for complexes
and
against
. A significant feature of these redesigned complexes is their ability to sensitize
, a trait that was not found for the previously investigated Ag(NO
)L complexes. The MIC values of the complexes towards bacteria were in the range of those of Ag(NO
)L and well above those of the precursors Ag(OAc) or AgCl. The activity of the complexes towards normal fibroblasts V79 was evaluated by the MTT (3-4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide) assay. Results showed that the complexes have a significant cytotoxicity.
Eleven new complexes of general formula Ag(NO3)(L-Y)2 corresponding to Ag(I) camphorimine complexes Ag(NO3)(OC10H14NY)2 (Y=NMe2 (1); OH (2); C6H5 (3); 4-MeC6H4, (4); 3,5-(CH3)2C6H3 (5); 3-OHC6H4, ...(6); 3-ClC6H4 (7); 4-ClC6H4 (8); 4-FC6H4 (9); 4-CF3C6H4 (10)) and the camphor sulfonylimine complex Ag(NO3)(O2SNC10H14NY)2 (Y=NH2) were synthesized/characterized and their structural properties and antibacterial activity studied to gain insights into the structure-antimicrobial activity relationships. Five of the complexes were selected as representative examples and structures were optimized by Density Functional Theory calculations. The results show that the imine substituents (Y) at the camphor ligands drive the structure of the complexes from distorted octahedral to trigonal prismatic or linear ionic while the effect of the sulfonylimine ring does not appreciably affects the geometry of the complex. The lipophilicity and polarity which are important parameters concerning the biological activity of the complexes are also high dependent of the characteristics of the camphor ligands. The redox properties of the complexes studied by cyclic voltammetry showed that their reduction potentials are essentially independent of their electronic and steric properties. The antibacterial activity of all the complexes, against Gram-positive (S. aureus Newman) and Gram-negative (Escherichia coli ATCC25922, Pseudomonas aeruginosa 477, Burkholderia contaminans IST408) strains was evaluated through calculation of MIC values. Results show that complexes with camphor imine ligands (1−10) that combine high lipophilicity with low dipolar moment (3–5) exhibit enhanced antibacterial activity. The ability to establish hydrogen bonding emerged as an important contribution to the antibacterial activity of the camphor sulphonylimine complex 11 (Y=NH2).
The antibacterial activity of Ag(I) camphor imine complexes can be tuned through choice of the imine substituents at the camphor ligands. Display omitted
•Eleven new silver camphorimine complexes Ag(NO3)(L-Y)2 were synthesized.•Structures of representative complexes were optimized by Density Functional Theory.•All complexes have antibacterial activity towards Gram-positive/Gram-negative bacteria.•The Y substituent drives the geometry/antibacterial activity of complexes.•The complexes perform better towards Gram-negative than Gram-positive bacteria.
Due to their dynamic properties such as irregular sampling rate and high-frequency sampling, Continuous Time Series (CTS) are found in many applications. Since CTS with irregular sampling rate are ...difficult to model with standard Recurrent Neural Networks (RNNs), RNNs have been generalised to have continuous-time hidden dynamics defined by a Neural Ordinary Differential Equation (Neural ODE), leading to the ODE-RNN model. Another approach that provides a better modelling is that of the Latent ODE model, which constructs a continuous-time model where a latent state is defined at all times. The Latent ODE model uses a standard RNN as the encoder and a Neural ODE as the decoder. However, since the RNN encoder leads to difficulties with missing data and ill-defined latent variables, a Latent ODE-RNN model has recently been proposed that uses a ODE-RNN model as the encoder instead.
Both the Latent ODE and Latent ODE-RNN models are difficult to train due to the vanishing and exploding gradients problem. To overcome this problem, the main contribution of this paper is to propose and illustrate a new model based on a new Latent ODE using an ODE-LSTM (Long Short-Term Memory) network as an encoder - the Latent ODE-LSTM model. To limit the growth of the gradients, the Norm Gradient Clipping strategy was embedded on the Latent ODE-LSTM model.
The performance evaluation of the new Latent ODE-LSTM (with and without Norm Gradient Clipping) for modelling CTS with regular and irregular sampling rates is then demonstrated. Numerical experiments show that the new Latent ODE-LSTM performs better than Latent ODE-RNNs and can avoid the vanishing and exploding gradients during training.
Code implementations developed in this work are available at github.com/CeciliaCoelho/LatentODELSTM.
The history of transgenesis is marked by milestones such as the development of cellular transdifferentiation, recombinant DNA, genetic modification of target cells, and finally, the generation of ...simpler genetically modified organisms (e.g. bacteria and mice). The first transgenic fish was developed in 1984, and since then, continuing technological advancements to improve gene transfer have led to more rapid, accurate, and efficient generation of transgenic animals. Among the established methods are microinjection, electroporation, lipofection, viral vectors, and gene targeting. Here, we review the history of animal transgenesis, with an emphasis on fish, in conjunction with major developments in genetic engineering over the past few decades. Importantly, spermatogonial stem cell modification and transplantation are two common techniques capable of revolutionizing the generation of transgenic fish. Furthermore, we discuss recent progress and future biotechnological prospects of fish transgenesis, which has strong applications for the aquaculture industry. Indeed, some transgenic fish are already available in the current market, validating continued efforts to improve economically important species with biotechnological advancements.
•A brief evolution history of transgenic animals and fish are presented•Primary fish gene delivery techniques were highlighted•Methods for site-specific genomic integration, host-independent transposable elements, and viruses were presented•Spermatogonial-stem-cell transplantation and transgenesis were depicted•And the biotechnological potential of transgenic fish were demonstrated
The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and ...with regards to commonly neglected genetic variants, such as Copy Number Variations (CNVs). In the present study, we investigated the contribution of CNVs on asthma risk among Latin Americans. CNVs were inferred from SNP genotyping data. Genome wide burden and association analyses were conducted to evaluate the impact of CNVs on asthma outcome. We found no significant difference in the numbers of CNVs between asthmatics and non-asthmatics. Nevertheless, we found that CNVs are larger in patients then in healthy controls and that CNVs from cases intersect significantly more genes and regulatory elements. We also found that a deletion at 6p22.1 is associated with asthma symptoms in children from Salvador (Brazil) and in young adults from Pelotas (Brazil). To support our results, we conducted an in silico functional analysis and found that this deletion spans several regulatory elements, including two promoter elements active in lung cells. In conclusion, we found robust evidence that CNVs could contribute for asthma susceptibility. These results uncover a new perspective on the influence of genetic factors modulating asthma risk.
The cytotoxic activity of four sets of camphorimine complexes based on the Cu(I), Cu(II), Ag(I), and Au(I) metal sites were assessed against the cisplatin-sensitive A2780 and OVCAR3 ovarian cancer ...cells. The results showed that the gold complexes were ca. one order of magnitude more active than the silver complexes, which in turn were ca. one order of magnitude more active than the copper complexes. An important finding was that the cytotoxic activity of the Ag(I) and Au(I) camphorimine complexes was higher than that of cisplatin. Another relevant aspect was that the camphorimine complexes did not interact significantly with DNA, in contrast with cisplatin. The cytotoxic activity of the camphorimine complexes displayed a direct relationship with the cellular uptake by OVCAR3 cells, as ascertained by PIXE (particle-induced X-ray emission). The levels of ROS (reactive oxygen species) formation exhibited an inverse relationship with the reduction potentials for the complexes with the same metal, as assessed by cyclic voltammetry. In order to gain insight into the toxicity of the complexes, their cytotoxicity toward nontumoral cells (HDF and V79 fibroblasts) was evaluated. The in vivo cytotoxicity of complex 5 using the nematode Caenorhabditis elegans was also assessed. The silver camphorimine complexes displayed the highest selectivity coefficients (activity vs. toxicity).
Objectives
To investigate the association between African and Native American genomic ancestry and long‐term cognitive trajectories in admixed Brazilians.
Design
Population‐based longitudinal study.
...Setting
Bambui‐Epigen (Brazil) cohort study.
Participants
Adults aged 60 and older (N=1,215)
Measurements
Participants were followed from January 1997 to December 2011. Cognitive function was assessed annually using the Mini‐Mental State Examination (MMSE), totaling 12,208 measurements. We used linear mixed‐effects pattern models to assess MMSE score trajectories. Ancestry was assessed using a genome‐wide approach.
Results
After adjustments for covariates, the highest quintile of African ancestry was associated with poorer baseline cognitive performance (β=–0.73, 95% confidence interval (CI)=–1.36 to –0.11) but not with cognitive trajectory. Educational level modified the baseline association between highest African ancestry and cognitive performance in that the association was observed only in those with very low (<4 years) education (β=–1.13, 95% CI=–2.02 to –0.23). No association was found between Native American ancestry and baseline cognitive function or its trajectory.
Conclusion
Genomic African and Native American ancestry levels had no prognostic value for age‐related cognitive decline in this admixed population.
Currently there is a gap between the rate of new antifungal development and the emergence of resistance among Candida clinical strains, particularly threatened by the extreme adhesiveness of C. ...albicans to indwelling medical devices. Two silver camphorimine complexes, Ag(OH){OC10H14N(C6H4)2NC10H14O} (compound P) and {Ag(OC10H14NC6H4CH3-p)}2(μ-O) (compound Q), are herein demonstrated as having high inhibiting activity towards the growth of Candida albicans and Candida glabrata clinical strains resistant to azoles, the frontline antifungals used in clinical practice. Compounds P and Q were also explored as bioactive coatings to prevent colonization by C. albicans and colonize the surface of indwelling medical devices, resulting in persistent infections. Functionalization of stainless steel with polycaprolactone (PCL) matrix embedded with compounds P or Q was reported for the first time to inhibit the colonization of C. albicans by 82% and 75%, respectively. The coating of PCL loaded with Q or P did not cause cytotoxic effects in mammalian cells, demonstrating the biocompatibility of the explored approach. The identification and further exploration of new approaches for surface engineering based on new molecules that can sensitize resistant strains, as herein demonstrated for complexes P and Q, is a significant step forward to improve the successful treatment of candidiasis.
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