Neuropsychological evaluation of children and adolescents with fetal alcohol spectrum disorders in the Brazilian population.

Fetal Alcohol Spectrum Disorder (FASD) is a collective name for lifelong physical and neurodevelopmental problems caused by the gestational consumption of alcohol affecting fetal development. In Brazil, the lack of awareness among healthcare professionals, and the scarcity of suitable diagnostic tools and trained clinicians, can contribute to the underestimation of FASD prevalence and severity. The present review aims to map and analyze studies conducted in Brazil on children and adolescents with FASD or a history of prenatal alcohol exposure (PAE). Additionally, it intends to report the psychometric properties of the neurodevelopmental assessment tools applied in the selected articles. Searches were carried out in the databases Scielo, LILACS, PePSIC, EMBASE, PsycINFO, Web of Science, selecting original clinical studies that have investigated the neurodevelopment of this population. From a total of 175 studies, ten articles fit the inclusion criteria in which 18 instruments were identified. The most reported deficits were related to language, general intelligence quotient (IQ), adaptive behavior, attention, and visual perception. Our results point to the need for more clinical research on FASD in Brazil, as well as for the standardization and validation of neurodevelopmental assessment tools for the accurate diagnosis of FASD in Brazil.

Pangenome analyses reveal impact of transposable elements and ploidy on the evolution of potato species.

Potato (Solanum sp., family Solanaceae) is the most important noncereal food crop globally. It has over 100 wild relatives in the Solanum section Petota, which features species with both sexual and asexual reproduction and varying ploidy levels. A pangenome of Solanum section Petota composed of 296 accessions was constructed including diploids and polyploids compared via presence/absence variation (PAV). The Petota core (genes shared by at least 97% of the accessions) and shell genomes (shared by 3 to 97%) are enriched in basic molecular and cellular functions, while the cloud genome (genes present in less than 3% of the member accessions) showed enrichment in transposable elements (TEs). Comparison of PAV in domesticated vs. wild accessions was made, and a phylogenetic tree was constructed based on PAVs, grouping accessions into different clades, similar to previous phylogenies produced using DNA markers. A cladewise pangenome approach identified abiotic stress response among the core genes in clade 1+2 and clade 3, and flowering/tuberization among the core genes in clade 4. The TE content differed between the clades, with clade 1+2, which is composed of species from North and Central America with reproductive isolation from species in other clades, having much lower TE content compared to other clades. In contrast, accessions with in vitro propagation history were identified and found to have high levels of TEs. Results indicate a role for TEs in adaptation to new environments, both natural and artificial, for Solanum section Petota.

Development of a Quick-Install Rapid Phenotyping System.

In recent years, there has been a growing need for accessible High-Throughput Plant Phenotyping (HTPP) platforms that can take measurements of plant traits in open fields. This paper presents a phenotyping system designed to address this issue by combining ultrasonic and multispectral sensing of the crop canopy with other diverse measurements under varying environmental conditions. The system demonstrates a throughput increase by a factor of 50 when compared to a manual setup, allowing for efficient mapping of crop status across a field with crops grown in rows of any spacing. Tests presented in this paper illustrate the type of experimentation that can be performed with the platform, emphasizing the output from each sensor. The system integration, versatility, and ergonomics are the most significant contributions. The presented system can be used for studying plant responses to different treatments and/or stresses under diverse farming practices in virtually any field environment. It was shown that crop height and several vegetation indices, most of them common indicators of plant physiological status, can be easily paired with corresponding environmental conditions to facilitate data analysis at the fine spatial scale.

Combined exposure to alcohol and cannabis during development: Mechanisms and outcomes.

Exposure to substances of abuse during pregnancy can have long-lasting effects on offspring. Alcohol is one of the most widely used substances of abuse that leads to the most severe consequences. Recent studies in the United States, Canada, and the United Kingdom showed that between 1% and 7% of all children exhibit signs and symptoms of fetal alcohol spectrum disorder (FASD). Despite preventive campaigns, the rate of children with FASD has not decreased during recent decades. Alcohol consumption often accompanies exposure to such drugs as tobacco, cocaine, opioids, and cannabis. These interactions can be synergistic and exacerbate the deleterious consequences of developmental alcohol exposure. The present review focuses on interactions between alcohol and cannabis exposure and the potential consequences of these interactions.

Genome sequencing of adapted diploid potato clones.

Cultivated potato is a vegetatively propagated crop, and most varieties are autotetraploid with high levels of heterozygosity. Reducing the ploidy and breeding potato at the diploid level can increase efficiency for genetic improvement including greater ease of introgression of diploid wild relatives and more efficient use of genomics and markers in selection. More recently, selfing of diploids for generation of inbred lines for F1 hybrid breeding has had a lot of attention in potato. The current study provides genomics resources for nine legacy non-inbred adapted diploid potato clones developed at Agriculture and Agri-Food Canada. De novo genome sequence assembly using 10× Genomics and Illumina sequencing technologies show the genome sizes ranged from 712 to 948 Mbp. Structural variation was identified by comparison to two references, the potato DMv6.1 genome and the phased RHv3 genome, and a k-mer based analysis of sequence reads showed the genome heterozygosity range of 1 to 9.04% between clones. A genome-wide approach was taken to scan 5 Mb bins to visualize patterns of heterozygous deleterious alleles. These were found dispersed throughout the genome including regions overlapping segregation distortions. Novel variants of the StCDF1 gene conferring earliness of tuberization were found among these clones, which all produce tubers under long days. The genomes will be useful tools for genome design for potato breeding.

Genome Sequencing of up to 6,000-Year-Old Citrullus Seeds Reveals Use of a Bitter-Fleshed Species Prior to Watermelon Domestication.

Iconographic evidence from Egypt suggests that watermelon pulp was consumed there as a dessert by 4,360 BP. Earlier archaeobotanical evidence comes from seeds from Neolithic settlements in Libya, but whether these were watermelons with sweet pulp or other forms is unknown. We generated genome sequences from 6,000- and 3,300-year-old seeds from Libya and Sudan, and from worldwide herbarium collections made between 1824 and 2019, and analyzed these data together with resequenced genomes from important germplasm collections for a total of 131 accessions. Phylogenomic and population-genomic analyses reveal that (1) much of the nuclear genome of both ancient seeds is traceable to West African seed-use "egusi-type" watermelon (Citrullus mucosospermus) rather than domesticated pulp-use watermelon (Citrullus lanatus ssp. vulgaris); (2) the 6,000-year-old watermelon likely had bitter pulp and greenish-white flesh as today found in C. mucosospermus, given alleles in the bitterness regulators ClBT and in the red color marker LYCB; and (3) both ancient genomes showed admixture from C. mucosospermus, C. lanatus ssp. cordophanus, C. lanatus ssp. vulgaris, and even South African Citrullus amarus, and evident introgression between the Libyan seed (UMB-6) and populations of C. lanatus. An unexpected new insight is that Citrullus appears to have initially been collected or cultivated for its seeds, not its flesh, consistent with seed damage patterns induced by human teeth in the oldest Libyan material.

The plastome of Arctic Oxytropis arctobia (Fabaceae) is significantly different from that of O. splendens and other related species.

Anatomical and physiological specializations for plant adaptation to harsh climates result from molecular mechanisms that can be encoded in the nucleus or organelle. In this study, the complete plastomes of an arctic species, Oxytropis arctobia Bunge (Fabaceae), and a closely related temperate species, O. splendens Douglas ex Hook., were assembled, annotated, and analyzed to identify differences that might help explain their adaptation to different environments. This is consistent with the previously sequenced O. bicolor DC. and O. glabra plastomes, O. arctobia and O. splendens plastomes both have the common features of the inverted repeat-lacking clade (IRLC), as well as atpF intron loss, which is unique to the genus. However, significant differences were observed between the plastomes of O. arctobia and O. splendens and other closely related species (Oxytropis spp. and Astragalus spp.), including a 3 kb inversion, two large insertions (>1 kb), significant modifications of the accD gene, and an overall larger size.

Phased, chromosome-scale genome assemblies of tetraploid potato reveal a complex genome, transcriptome, and predicted proteome landscape underpinning genetic diversity.

Cultivated potato is a clonally propagated autotetraploid species with a highly heterogeneous genome. Phased assemblies of six cultivars including two chromosome-scale phased genome assemblies revealed extensive allelic diversity, including altered coding and transcript sequences, preferential allele expression, and structural variation that collectively result in a highly complex transcriptome and predicted proteome, which are distributed across the homologous chromosomes. Wild species contribute to the extensive allelic diversity in tetraploid cultivars, demonstrating ancestral introgressions predating modern breeding efforts. As a clonally propagated autotetraploid that undergoes limited meiosis, dysfunctional and deleterious alleles are not purged in tetraploid potato. Nearly a quarter of the loci bore mutations are predicted to have a high negative impact on protein function, complicating breeder's efforts to reduce genetic load. The StCDF1 locus controls maturity, and analysis of six tetraploid genomes revealed that 12 allelic variants of StCDF1 are correlated with maturity in a dosage-dependent manner. Knowledge of the complexity of the tetraploid potato genome with its rampant structural variation and embedded deleterious and dysfunctional alleles will be key not only to implementing precision breeding of tetraploid cultivars but also to the construction of homozygous, diploid potato germplasm containing favorable alleles to capitalize on heterosis in F1 hybrids.

The complete mitogenome assemblies of 10 diploid potato clones reveal recombination and overlapping variants.

The potato mitogenome is complex and to understand various biological functions and nuclear-cytoplasmic interactions, it is important to characterize its gene content and structure. In this study, the complete mitogenome sequences of nine diploid potato clones along with a diploid Solanum okadae clone were characterized. Each mitogenome was assembled and annotated from Pacific Biosciences (PacBio) long reads and 10X genomics short reads. The results show that each mitogenome consists of multiple circular molecules with similar structure and gene organization, though two groups (clones 07506-01, DW84-1457, 08675-21 and H412-1 in one group, and clones W5281-2, 12625-02, 12120-03 and 11379-03 in another group) could be distinguished, and two mitogenomes (clone 10908-06 and OKA15) were not consistent with those or with each other. Significant differences in the repeat structure of the 10 mitogenomes were found, as was recombination events leading to multiple sub-genomic circles. Comparison between individual molecules revealed a translocation of ∼774 bp region located between a short repeat of 40 bp in molecule 3 of each mitogenome, and an insertion of the same in molecule 2 of the 10908-06 mitogenome. Finally, phylogenetic analyses revealed a close relationship between the mitogenomes of these clones and previously published potato mitogenomes.

A chromosome-level genome of a Kordofan melon illuminates the origin of domesticated watermelons.

Wild relatives or progenitors of crops are important resources for breeding and for understanding domestication. Identifying them, however, is difficult because of extinction, hybridization, and the challenge of distinguishing them from feral forms. Here, we use collection-based systematics, iconography, and resequenced accessions of Citrullus lanatus and other species of Citrullus to search for the potential progenitor of the domesticated watermelon. A Sudanese form with nonbitter whitish pulp, known as the Kordofan melon (C. lanatus subsp. cordophanus), appears to be the closest relative of domesticated watermelons and a possible progenitor, consistent with newly interpreted Egyptian tomb paintings that suggest that the watermelon may have been consumed in the Nile Valley as a dessert by 4360 BP. To gain insights into the genetic changes that occurred from the progenitor to the domesticated watermelon, we assembled and annotated the genome of a Kordofan melon at the chromosome level, using a combination of Pacific Biosciences and Illumina sequencing as well as Hi-C mapping technologies. The genetic signature of bitterness loss is present in the Kordofan melon genome, but the red fruit flesh color only became fixed in the domesticated watermelon. We detected 15,824 genome structural variants (SVs) between the Kordofan melon and a typical modern cultivar, "97103," and mapping the SVs in over 400 Citrullus accessions revealed shifts in allelic frequencies, suggesting that fruit sweetness has gradually increased over the course of watermelon domestication. That a likely progenitor of the watermelon still exists in Sudan has implications for targeted modern breeding efforts.

Complete mitogenome assemblies from a panel of 13 diverse potato taxa.

Mitochondrial DNA is maternally inherited and is shown to affect nuclear-cytoplasmic interactions in potato. Analyzing the mitogenome helps understand the evolutionary relationships and improve breeding programs in potato. We report complete mitogenome sequences from a panel of 13 potato accessions of various taxa. Each mitogenome has three independent circular molecules, except one of the S. bukasovii sample BUK2, which has a single circular molecule. Each mitogenome code for 37 non-redundant protein-coding genes, three rRNAs, 20 tRNAs, and 19 hypothetical open reading frames. Phylogenetic analysis reveals congruency between plastome and mitogenome phylogeny.

The complete plastome sequences of nine diploid potato clones.

Potato (Solanum tuberosum L.) is the world's fourth most important food crop and essential for global food security. The potato chloroplast genomes, the plastomes, are highly conserved and are largely studied for their maternal lineages. In this study, we assembled the complete circular plastome sequences of nine diploid potato clones, with sizes ranging between 155,296 bp and 155,564 bp. Annotation of these plastomes reveals that they each have 141 genes in a similar order. The computational chloroplast DNA typing reveals three plastid DNA types among the nine plastomes and they are grouped according to these types in the phylogeny.

Complete plastome assemblies from a panel of 13 diverse potato taxa.

The chloroplasts are a crucial part of photosynthesizing plant cells and are extensively utilized in phylogenetic studies mainly due to their maternal inheritance. Characterization and analysis of complete plastome sequences is necessary to understand their diversity and evolutionary relationships. Here, a panel of thirteen plastomes from various potato taxa are presented. Though they are highly similar with respect to gene order and content, there is also a great extent of SNPs and InDels between them, with one of the Solanum bukasovii plastomes (BUK2) having the highest number of SNPs and InDels. Five different potato plastome types (C, S, A, W, W2) are present in the panel. Interestingly, the S. tuberosum subsp. tuberosum (TBR) accession has a W-type plastome, which is not commonly found in this species. The S-type plastome has a conserved 48 bp deletion not found in other types, which is responsible for the divergence of the S-type from the C-type plastome. Finally, a phylogenetic analysis shows that these plastomes cluster according to their types. Congruence between the nuclear genome and the plastome phylogeny of these accessions was seen, however with considerable differences, supporting the hypothesis of introgression and hybridization between potato species.

Genome assembly of six polyploid potato genomes.

Genome assembly of polyploid plant genomes is a laborious task as they contain more than two copies of the genome, are often highly heterozygous with a high level of repetitive DNA. Next Generation genome sequencing data representing one Chilean and five Peruvian polyploid potato (Solanum spp.) landrace genomes was used to construct genome assemblies comprising five taxa. Third Generation sequencing data (Linked and Long-read data) was used to improve the assembly for one of the genomes. Native landraces are valuable genetic resources for traits such as disease and pest resistance, environmental tolerance and other qualities of interest such as nutrition and fiber for breeding programs. The need for conservation and enhanced understanding of genetic diversity of cultivated potato from South America is also crucial to North American and European cultivars. Here, we report draft genomes from six polyploid potato landraces representing five taxa, illustrating how Third Generation Sequencing can aid in assembling polyploid genomes.

Structural genome analysis in cultivated potato taxa.

KEY MESSAGE: Twelve potato accessions were selected to represent two principal views on potato taxonomy. The genomes were sequenced and analyzed for structural variation (copy number variation) against three published potato genomes. The common potato (Solanum tuberosum L.) is an important staple crop with a highly heterozygous and complex tetraploid genome. The other taxa of cultivated potato contain varying ploidy levels (2X-5X), and structural variations are common in the genomes of these species, likely contributing to the diversification or agronomic traits during domestication. Increased understanding of the genomes and genomic variation will aid in the exploration of novel agronomic traits. Thus, sequencing data from twelve potato landraces, representing the four ploidy levels, were used to identify structural genomic variation compared to the two currently available reference genomes, a double monoploid potato genome and a diploid inbred clone of S. chacoense. The results of a copy number variation analysis showed that in the majority of the genomes, while the number of deletions is greater than the number of duplications, the number of duplicated genes is greater than the number of deleted ones. Specific regions in the twelve potato genomes have a high density of CNV events. Further, the auxin-induced SAUR genes (involved in abiotic stress), disease resistance genes and the 2-oxoglutarate/Fe(II)-dependent oxygenase superfamily proteins, among others, had increased copy numbers in these sequenced genomes relative to the references.

Current Strategies of Polyploid Plant Genome Sequence Assembly.

Polyploidy or duplication of an entire genome occurs in the majority of angiosperms. The understanding of polyploid genomes is important for the improvement of those crops, which humans rely on for sustenance and basic nutrition. As climate change continues to pose a potential threat to agricultural production, there will increasingly be a demand for plant cultivars that can resist biotic and abiotic stresses and also provide needed and improved nutrition. In the past decade, Next Generation Sequencing (NGS) has fundamentally changed the genomics landscape by providing tools for the exploration of polyploid genomes. Here, we review the challenges of the assembly of polyploid plant genomes, and also present recent advances in genomic resources and functional tools in molecular genetics and breeding. As genomes of diploid and less heterozygous progenitor species are increasingly available, we discuss the lack of complexity of these currently available reference genomes as they relate to polyploid crops. Finally, we review recent approaches of haplotyping by phasing and the impact of third generation technologies on polyploid plant genome assembly.

A Face-Aging App for Smoking Cessation in a Waiting Room Setting: Pilot Study in an HIV Outpatient Clinic.

BACKGROUND: There is strong evidence for the effectiveness of addressing tobacco use in health care settings. However, few smokers receive cessation advice when visiting a hospital. Implementing smoking cessation technology in outpatient waiting rooms could be an effective strategy for change, with the potential to expose almost all patients visiting a health care provider without preluding physician action needed. OBJECTIVE: The objective of this study was to develop an intervention for smoking cessation that would make use of the time patients spend in a waiting room by passively exposing them to a face-aging, public morphing, tablet-based app, to pilot the intervention in a waiting room of an HIV outpatient clinic, and to measure the perceptions of this intervention among smoking and nonsmoking HIV patients. METHODS: We developed a kiosk version of our 3-dimensional face-aging app Smokerface, which shows the user how their face would look with or without cigarette smoking 1 to 15 years in the future. We placed a tablet with the app running on a table in the middle of the waiting room of our HIV outpatient clinic, connected to a large monitor attached to the opposite wall. A researcher noted all the patients who were using the waiting room. If a patient did not initiate app use within 30 seconds of waiting time, the researcher encouraged him or her to do so. Those using the app were asked to complete a questionnaire. RESULTS: During a 19-day period, 464 patients visited the waiting room, of whom 187 (40.3%) tried the app and 179 (38.6%) completed the questionnaire. Of those who completed the questionnaire, 139 of 176 (79.0%) were men and 84 of 179 (46.9%) were smokers. Of the smokers, 55 of 81 (68%) said the intervention motivated them to quit (men: 45, 68%; women: 10, 67%); 41 (51%) said that it motivated them to discuss quitting with their doctor (men: 32, 49%; women: 9, 60%); and 72 (91%) perceived the intervention as fun (men: 57, 90%; women: 15, 94%). Of the nonsmokers, 92 (98%) said that it motivated them never to take up smoking (men: 72, 99%; women: 20, 95%). Among all patients, 102 (22.0%) watched another patient try the app without trying it themselves; thus, a total of 289 (62.3%) of the 464 patients were exposed to the intervention (average waiting time 21 minutes). CONCLUSIONS: A face-aging app implemented in a waiting room provides a novel opportunity to motivate patients visiting a health care provider to quit smoking, to address quitting at their subsequent appointment and thereby encourage physician-delivered smoking cessation, or not to take up smoking.

Targeted Tumor Therapy Remixed-An Update on the Use of Small-Molecule Drugs in Combination Therapies.

Over the last decade, the treatment of tumor patients has been revolutionized by the highly successful introduction of novel targeted therapies, in particular small-molecule kinase inhibitors and monoclonal antibodies, as well as by immunotherapies. Depending on the mutational status, BRAF and MEK inhibitor combinations or immune checkpoint inhibitors are current first-line treatments for metastatic melanoma. However, despite great improvements of survival rates limitations due to tumor heterogeneity, primary and acquired therapy resistance, immune evasion, and economical considerations will need to be overcome. Accordingly, ongoing clinical trials explore the individualized use of small-molecule drugs in new targeted therapy combinations based on patient parameters and tumor biopsies. With focus on melanoma therapy this review aims at providing a comprehensive overview of such novel alternative and combinational therapy strategies currently emerging from basic research. The molecular principles and drug classes that may hold promise for improved tumor therapy combination regimens including kinase inhibition, induction of apoptosis, DNA-damage response inhibition, epigenetic reprogramming, telomerase inhibition, redox modulation, metabolic reprogramming, proteasome inhibition, cancer stem cell transdifferentiation, immune cell signaling modulation, and others, are explained in brief. In addition, relevant targeted therapy combinations in current clinical trials and individualized treatment strategies are highlighted.

Molecular evidence of asymptomatic and multispecies malaria infections in a small community on the north coast of Madang Province, Papua New Guinea

@#Asymptomatic malaria is prevalent in highly endemic areas of Papua New Guinea and is a challenge for malaria prevention and control strategies. We used nested polymerase chain reaction (PCR) to determine the prevalence of asymptomatic malaria and parasite species distribution in a small community on the north coast of Madang, Papua New Guinea. A population household study was conducted in October, 2015. A pretested questionnaire was used to collect demographic data. Giemsa-stained thin and thick blood films were examined for detection, identification and quantification of malaria parasites. Due to wide discrepancies in malaria microscopy results, only molecular analysis data are presented here. The prevalence of asymptomatic malaria was 62.5% (40/64) with mixed multispecies infections accounting for 20% (13/64). The prevalence of malaria parasite carriers observed here in the small community is higher than previously reported for the same region. Asymptomatic malaria remains a challenge for malaria elimination and PCR testing should be considered in areas where malaria transmission is low.