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The New World Screwworm, Cochliomyia hominivorax (Calliphoridae), is the most important myiasis-causing species in America. Screwworm myiasis is a zoonosis that can cause severe lesions in livestock, domesticated and wild animals, and occasionally in people. Beyond the sanitary problems associated with this species, these infestations negatively impact economic sectors, such as the cattle industry. Here, we present a chromosome-scale assembly of C. hominivorax's genome, organized in 6 chromosome-length and 515 unplaced scaffolds spanning 534 Mb. There was a clear correspondence between the D. melanogaster linkage groups A-E and the chromosomal-scale scaffolds. Chromosome quotient (CQ) analysis identified a single scaffold from the X chromosome that contains most of the orthologs of genes that are on the D. melanogaster fourth chromosome (linkage group F or dot chromosome). CQ analysis also identified potential X and Y unplaced scaffolds and genes. Y-linkage for selected regions was confirmed by PCR with male and female DNA. Some of the long chromosome-scale scaffolds include Y-linked sequences, suggesting misassembly of these regions. These resources will provide a basis for future studies aiming at understanding the biology and evolution of this devastating obligate parasite.

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BACKGROUND: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). METHODS: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. RESULTS: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. CONCLUSIONS: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.

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Hi-C enables the characterization of the 0conformation of the genome in the three-dimensional nuclear space. This technique has revolutionized our ability to detect interactions between linearly distant genomic sites on a genome-wide scale. Here, we detail a protocol to carry out in situ Hi-C in plants and describe a straightforward bioinformatics pipeline for the analysis of such data, in particular for comparing samples from different organs or conditions.

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The possibility of analyzing chromatin topology in developing plant embryos is hampered by inaccessibility of the embryo sac, deeply embedded in the maternal seed tissue, following double fertilization. Here we describe a protocol to isolate, purify, and prepare developing Boechera stricta embryos for chromosome conformation capture-based methods as in situ Hi-C experiments. Early globular embryos can be isolated by air-pressure microaspiration, and subsequently washed to eliminate residual cells from the endosperm and maternal seed coat, allowing for pure sampling of selected stages of embryogenesis. This protocol allows for the possibility of comparing genome topology during plant embryonic differentiation since early until late embryo development stages.

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The environmental impact arising from poly(ethylene terephthalate) (PET) waste is notable worldwide. Enzymatic PET hydrolysis can provide chemicals that serve as intermediates for value-added product synthesis and savings in the resources. In the present work, some reaction parameters were evaluated on the hydrolysis of post-consumer PET (PC-PET) using a cutinase from Humicola insolens (HiC). The increase in PC-PET specific area leads to an 8.5-fold increase of the initial enzymatic hydrolysis rate (from 0.2 to 1.7 mmol L-1 h-1), showing that this parameter plays a crucial role in PET hydrolysis reaction. The effect of HiC concentration was investigated, and the enzymatic PC-PET hydrolysis kinetic parameters were estimated based on three different mathematical models describing heterogeneous biocatalysis. The model that best fits the experimental data (R2 = 0.981) indicated 1.68 mgprotein mL-1 as a maximum value of the enzyme concentration to optimize the reaction rate. The HiC thermal stability was evaluated, considering that it is a key parameter for its efficient use in PET degradation. The enzyme half-life was shown to be 110 h at 70 ºC and pH 7.0, which outperforms most of the known enzymes displaying PET hydrolysis activity. The results evidence that HiC is a very promising biocatalyst for efficient PET depolymerization.

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BACKGROUND: Wealth mobility, as both relative (positional) and absolute (material) wealth acquisition, may counteract negative consequences of early life adversities on adult health. METHODS: We use longitudinal data (1967-2018) from the INCAP birth cohort, Guatemala (n = 1386). Using wealth as a measure of socio-economic position, we assess the association of life course relative mobility using latent class analysis and absolute material gains using conditional wealth measures. We estimate associations of wealth mobility with indicators of human capital, specifically height, weight status (BMI in kg/m2), psychological distress (WHO SRQ-20 score) and fluid intelligence (Ravens Progressive Matrices score; RPM) in middle adulthood. RESULTS: We identified four latent classes of relative mobility - Stable Low (n = 498), Stable High (n = 223), Downwardly Mobile (n = 201) and Upwardly Mobile (n = 464). Attained schooling (years) was positively associated with membership in Upwardly Mobile (odds ratio; 1.50, 95%CI: 1.31, 1.71) vs Stable Low, and inversely with membership in Downwardly Mobile (0.65, 95%CI: 0.54, 0.79) vs Stable High. Being Upwardly Mobile (vs Stable Low) was positively associated with height (1.88 cm, 95%CI: 1.04, 2.72), relative weight (1.32 kg/m2, 95%CI: 0.57, 2.07), lower psychological distress (-0.82 units, 95%CI: 1.34, -0.29) and fluid intelligence (0.94 units, 95%CI: 0.28, 1.59). Being Downwardly Mobile (vs Stable High) was associated with lower fluid intelligence (-2.69 units, 95%CI: 3.69, -1.68), and higher psychological distress (1.15 units, 95%CI: 0.34, 1.95). Absolute wealth gains (z-scores) from early to middle adulthood were positively associated with relative weight (0.62 kg/m2, 95%CI: 0.28, 0.96), lower psychological distress (-0.37 units, 95%CI: 0.60, -0.14) and fluid intelligence (0.50 units, 95%CI: 0.21, 0.79). CONCLUSIONS: Higher attained schooling provided a pathway for upward relative mobility and higher absolute wealth gains as well as protection against downward relative mobility. Upward mobility was associated with lower psychological distress and higher fluid intelligence but also higher weight status.

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BACKGROUND: Pediatric cancer cure rates differ among high-income countries (HIC) and upper middle-income countries (UMIC). We have compared individual capacities of two major referral pediatric centers from a HIC and an UMIC caring for children with central nervous system (CNS) cancer. METHODS: A quantitative needs assessment questionnaire and key informant interviews, distributed in March of 2017, were used to evaluate the treatment of children with CNS cancer at Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC) children's cancer center in São Paulo, Brazil and Nationwide Children's Hospital (NCH) in Columbus, Ohio, United States of America (USA). RESULTS: Both hospitals had 24-hour pediatric oncology, nursing and intensivist coverage. Supportive care available at both institutions included social workers, psychologists, child life specialists, and physical/occupational/speech therapists. Differences included two part-time neuroradiologists and one pathologist specializing in neuropathology at IOP/GRAACC/UNIFESP, whereas eight full-time neuroradiologists and two neuropathologists at NCH/OSU. There were four pediatric neurosurgeons on staff at each hospital; however, there were only 2 operative days per week at IOP/GRAACC/UNIFESP, compared with 7 days at NCH/OSU. Additionally, time to initiation of radiation therapy at IOP/GRAACC/UNIFESP extended 2-4 weeks compared with less than 1 week at NCH/OSU. CONCLUSIONS: Center-specific differences in resources exist in highly specialized hospitals caring for children with CNS cancer in HIC and UMIC. This quantitative needs assessment may facilitate the development of targeted strategies for effective interventions to improve on the management of children with CNS cancers.

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Germline and somatic genomes are in general the same in a multicellular organism. However, programmed DNA elimination leads to a reduced somatic genome compared to germline cells. Previous work on the parasitic nematode Ascaris demonstrated that programmed DNA elimination encompasses high-fidelity chromosomal breaks and loss of specific genome sequences including a major tandem repeat of 120 bp and ~1,000 germline-expressed genes. However, the precise chromosomal locations of these repeats, breaks regions, and eliminated genes remained unknown. We used PacBio long-read sequencing and chromosome conformation capture (Hi-C) to obtain fully assembled chromosomes of Ascaris germline and somatic genomes, enabling a complete chromosomal view of DNA elimination. We found that all 24 germline chromosomes undergo comprehensive chromosome end remodeling with DNA breaks in their subtelomeric regions and loss of distal sequences including the telomeres at both chromosome ends. All new Ascaris somatic chromosome ends are recapped by de novo telomere healing. We provide an ultrastructural analysis of Ascaris DNA elimination and show that eliminated DNA is incorporated into double membrane-bound structures, similar to micronuclei, during telophase of a DNA elimination mitosis. These micronuclei undergo dynamic changes including loss of active histone marks and localize to the cytoplasm following daughter nuclei formation and cytokinesis where they form autophagosomes. Comparative analysis of nematode chromosomes suggests that chromosome fusions occurred, forming Ascaris sex chromosomes that become independent chromosomes following DNA elimination breaks in somatic cells. These studies provide the first chromosomal view and define novel features and functions of metazoan programmed DNA elimination.

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Introducción El Trastorno Bipolar es una enfermedad que causa discapacidad física y cognitiva, afectando tanto a hombres como mujeres, con edad de inicio temprano y con un alto componente hereditario. Objetivo Estimar el comportamiento del Trastorno Bi­polar, variables sociodemográficas, antecedentes y su relación con los genes CACNA1­C (12p13.3) y DAOA (13q34) entre personas de 18 años y más en áreas específicas de la Región de Azuero de Panamá. Metodología La muestra calculada fue de 267 perso­nas de 18 años y más (IC 95%) utilizando un muestreo aleatorio, de distribución propor­cional según sexo. Se utilizaron las variables: "trastorno bipolar" medido a través del cuestionario de trastornos del estado de ánimo (Mood Disorder Questionnaire, MDQ por sus siglas en inglés); "genes asociados a la bipolaridad" (genes CACNA1­C (12p13.3) y DAOA (13q34)); y un cuestionario de datos sociodemográficos y antecedentes persona­les ­ familiares. El análisis genético se realizó con PCR (tiempo real). Se utilizaron por­centajes como medida de frecuencia relativa y se consideró significancia estadística para un valor de p ≤ 0.05. Resultados La prevalencia de bipolaridad en la muestra es­tudiada fue 3.7% (IC 95% 3.5 ­ 4.1), siendo mayor en mujeres, 6.0% (IC 95% 5.9 ­ 6.3). El 74.2% (IC 95% 73.9 ­ 74.4) de los participantes tenía presente el polimorfismo del gen CACNA1­C (12p13.3), y 19.1% (IC 95% 18.9 ­ 19.4) el del gen DAOA (13q34). Para todas las variables de estudio, la presencia del gen CACNA1­C (12p13.3) fue mayor que la del gen DAOA (13q34). De los 10 casos con MDQ+, 3 presentaron el gen CAC­NA1­C. Conclusión Esta es la primera investigación sobre bipolaridad, genes y otros factores asociados en Panamá. El gen CACNA1­C fue más prevalente que el DAOA y se asoció más al MDQ +.

Introduction Bipolar disorder is a disease that causes physical and cognitive disability, affecting both men and women, with an early onset age and a high hereditary compo­nent. Objective To estimate Bipolar Disorder demeanor, sociodemographic variables, antecedents and its relationship with CACNA1­C (12p13.3) and DAOA (13q34) genes among people aged 18 years and over in specific areas of the Azuero Region of Pana­ma. Methodology The calculated sample was 267 people aged 18 and over (95% CI) using random sampling, proportional distribution according to sex. The variables were used: "bipolar disorder" measured through the Mood Disorder Questionnaire (MDQ); "genes associated with bipolarity" (CACNA1­C (12p13.3) and DAOA (13q34) genes); and a sociodemographic data questionnaire and personal ­ family background. The ge­netic analysis was performed with PCR (real time). Percentages were used as a re of relative frequency and statistical significance was considered for a value of p ≤ 0.05. Results The prevalence of bipolarity in the studied sample was 3.7% (CI 95% 3.5 ­ 4.1), being higher in women, 6.0% (CI 95% 5.9 ­ 6.3). 74.2% (CI 95% 73.9 ­ 74.4) of the participants were aware of the polymorphism of the CACNA1­C gene (12p13.3), and 19.1% (CI 95% 18.9 ­ 19.4) of the DAOA gene (13q34). For all study variables, the pre­sence of the CACNA1­C gene (12p13.3) was greater than that of the DAOA gene (13q34). Of the 10 cases with MDQ +, 3 presented the CACNA1­C gene. ConclusionThis is the first research on bipolarity, genes and other associated factors in Panama. The CACNA1­C gene was more prevalent than DAOA and was more associated with MDQ +.

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Polyurethanes (PU) are the sixth most produced plastics with around 18-million tons in 2016, but since they are not recyclable, they are burned or landfilled, generating damage to human health and ecosystems. To elucidate the mechanisms that landfill microbial communities perform to attack recalcitrant PU plastics, we studied the degradative activity of a mixed microbial culture, selected from a municipal landfill by its capability to grow in a water PU dispersion (WPUD) as the only carbon source, as a model for the BP8 landfill microbial community. The WPUD contains a polyether-polyurethane-acrylate (PE-PU-A) copolymer and xenobiotic additives (N-methylpyrrolidone, isopropanol and glycol ethers). To identify the changes that the BP8 microbial community culture generates to the WPUD additives and copolymer, we performed chemical and physical analyses of the biodegradation process during 25 days of cultivation. These analyses included Nuclear magnetic resonance, Fourier transform infrared spectroscopy, Thermogravimetry, Differential scanning calorimetry, Gel permeation chromatography, and Gas chromatography coupled to mass spectrometry techniques. Moreover, for revealing the BP8 community structure and its genetically encoded potential biodegradative capability we also performed a proximity ligation-based metagenomic analysis. The additives present in the WPUD were consumed early whereas the copolymer was cleaved throughout the 25-days of incubation. The analysis of the biodegradation process and the identified biodegradation products showed that BP8 cleaves esters, C-C, and the recalcitrant aromatic urethanes and ether groups by hydrolytic and oxidative mechanisms, both in the soft and the hard segments of the copolymer. The proximity ligation-based metagenomic analysis allowed the reconstruction of five genomes, three of them from novel species. In the metagenome, genes encoding known enzymes, and putative enzymes and metabolic pathways accounting for the biodegradative activity of the BP8 community over the additives and PE-PU-A copolymer were identified. This is the first study revealing the genetically encoded potential biodegradative capability of a microbial community selected from a landfill, that thrives within a WPUD system and shows potential for bioremediation of polyurethane- and xenobiotic additives-contamitated sites.

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Given Haiti's longstanding socioeconomic burden and recent environmental and epidemiological catastrophes, the capacity for neurosurgery within Haiti has been limited, and outcomes for patients with neurosurgical conditions have remained poor. With few formally trained neurosurgeons (4) in a country of 10.5 million inhabitants, there is a significant need for the development of formal structured neurosurgical training. To mitigate the lack of neurosurgical care within Haiti, the authors established the first neurosurgical residency program within the country by creating an integrated model that uniquely fortifies existing Haitian neurosurgery with government sponsorship (Haitian Ministry of Health and National Medical School) and continual foreign support. By incorporating web-based learning modules, online assessments, teleconferences, and visiting professorships, the residency aims to train neurosurgeons over the course of 3-5 years to meet the healthcare needs of the nation. Although in its infancy, this model aims to facilitate neurosurgical capacity building by ultimately creating a self-sustaining residency program.

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After linear sequences of genomes and epigenomic landscape data, the 3D organization of chromatin in the nucleus is the next level to be explored. Different organisms present a general hierarchical organization, with chromosome territories at the top. Chromatin interaction maps, obtained by chromosome conformation capture (3C)-based methodologies, for eight plant species reveal commonalities, but also differences, among them and with animals. The smallest structures, found in high-resolution maps of the Arabidopsis genome, are single genes. Epigenetic marks (histone modification and DNA methylation), transcriptional activity, and chromatin interaction appear to be correlated, and whether structure is the cause or consequence of the function of interacting regions is being actively investigated.

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