FUNCTIONAL NEUROIMAGING OF VENTRAL AND DORSAL STREAM PATHWAYS IN THE MACAQUE AUDITORY SYSTEM

One fundamental goal of the brain is to predict sensory events in the environment in order to spatially direct actions. In vision, the ability to identify and locate objects depends on two cortical pathways: a ventral “what” stream supporting object recognition and a dorsal “where” stream supporting object localization. While this hierarchical model received strong support in vision, in audition the analogues functional roles have remained rather elusive, particularly for the dorsal “where” stream. Thus, the objective of this thesis was to explore the functional roles of auditory ventral and dorsal stream pathways in the macaque brain. We first explored the representational structure of natural sounds in early regions of the ventral pathway utilizing single-unit electrophysiology. We then used functional magnetic resonance imaging (fMRI) to map the representation of natural sounds along the ventral pathway including regions outside auditory cortex. Finally, using high-field fMRI we examined the functional representation of acoustic space in auditory cortical regions. Overall, our work confirms the role of the ventral stream in decoding sound identity and extends the evidence suggesting that vocalizations carry information that is represented outside auditory cortex. Moreover, our work in the dorsal stream also confirms the role of a posterior dorsal cortical region specialized in processing spatial information and reconciles competitive theories of spatial coding in auditory cortex. However, our space work also indicates a fundamental difference in the representation format for acoustic space in auditory cortex as compared to visual cortex. Taken together, our work confirms the functional roles of the ventral and dorsal streams and suggests incorporating subcortical level processes in the cortical model for a more integrated framework of acoustic processing in the primate brain

Global agricultural intensification during climate change: a role for genomics

Agriculture is now facing the ‘perfect storm’ of climate change, increasing costs of fertilizer and rising food demands from a larger and wealthier human population. These factors point to a global food deficit unless the efficiency and resilience of crop production is increased. The intensification of agriculture has focused on improving production under optimized conditions, with significant agronomic inputs. Furthermore, the intensive cultivation of a limited number of crops has drastically narrowed the number of plant species humans rely on. A new agricultural paradigm is required, reducing dependence on high inputs and increasing crop diversity, yield stability and environmental resilience. Genomics offers unprecedented opportunities to increase crop yield, quality and stability of production through advanced breeding strategies, enhancing the resilience of major crops to climate variability, and increasing the productivity and range of minor crops to diversify the food supply. Here we review the state of the art of genomic-assisted breeding for the most important staples that feed the world, and how to use and adapt such genomic tools to accelerate development of both major and minor crops with desired traits that enhance adaptation to, or mitigate the effects of climate chang

Traits that define yield and genetic gain in East African highland banana breeding

East African highland bananas (Musa spp. AAA group) are an important staple in the Great Lakes region of East Africa. Their production has declined due to pests and diseases. Breeding for host plant resistance is a sustainable option for addressing this challenge. Understanding the relationships between growth parameters and bunch weight (i.e., yield) is crucial to guide breeding efforts for this crop. We investigated cause-effect relationships, through path analysis, in bunch weight of East African highland banana derived hybrids, their parents and grandparents. These family structures were planted in a 7 × 8 rectangular lattice design, replicated twice. Genetic gains for bunch weight (kg plant−1) and yield potential (t ha−1 year−1) were estimated. Significant increases of bunch weight and yield potential were noted from the landrace triploid germplasm, their derived primary tetraploid hybrids and secondary triploid bred-germplasm. Path analysis revealed that fruit length, circumference and number, number of hands and plant cycle number had a direct positive effect on the bunch weight. Days to fruit filling, days to maturity and index of non-spotted leaves had indirect effects on bunch weight. The average genetic gains for bunch weight and yield potential were 1.4% and 1.3% per year, respectively. This is the first report about genetic gains in banana breeding. Our findings may be useful for assessing progress and directing future breeding efforts in banana breeding

Dynamic reconfiguration of macaque brain networks during natural vision

Natural vision engages a wide range of higher-level regions that integrate visual information over the large-scale brain network. How interareal connectivity reconfigures during the processing of ongoing natural visual scenes and how these dynamic functional changes relate to the underlaying anatomical links between regions is not well understood. Here, we hypothesized that macaque visual brain regions are poly-functional sharing the capacity to change their configuration state depending on the nature of visual input. To address this hypothesis, we reconstructed networks from in-vivo diffusion-weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) data obtained in four alert macaque monkeys viewing naturalistic movie scenes. At first, we characterized network properties and found greater interhemispheric density and greater inter-subject variability in free-viewing networks as compared to structural networks. From the structural connectivity, we then captured modules on which we identified hubs during free-viewing that formed a widespread visuo-saccadic network across frontal (FEF, 46v), parietal (LIP, Tpt), and occipitotemporal modules (MT, V4, TEm), and that excluded primary visual cortex. Inter-subject variability of well-connected hubs reflected subject-specific configurations that largely recruited occipito-parietal and frontal modules. Across the cerebral hemispheres, free-viewing networks showed higher correlations among long-distance brain regions as compared to structural networks. From these findings, we hypothesized that long-distance interareal connectivity could reconfigure depending on the ongoing changes in visual scenes. Testing this hypothesis by applying temporally resolved functional connectivity we observed that many structurally defined areas (such as areas V4, MT/MST and LIP) were poly-functional as they were recruited as hub members of multiple network states that changed during the presentation of scenes containing objects, motion, faces, and actions. We suggest that functional flexibility in macaque macroscale brain networks is required for the efficient interareal communication during active natural vision. To further promote the use of naturalistic free-viewing paradigms and increase the development of macaque neuroimaging resources, we share our datasets in the PRIME-DE consortium

Heterobeltiosis in banana and genetic gains through crossbreeding

Heterosis, or hybrid vigour, is the superiority of the hybrid for a certain trait over the mean of its two parents. Heterobeltiosis is a form of heterosis where the hybrid is superior to its best parent. Banana breeding is a tedious, time-consuming process, taking up to two decades to develop a hybrid. Understanding heterosis in banana breeding will contribute to selecting right breeding materials for further crossing, thus increasing banana breeding efficiency. Here we document heterobeltiosis by using the recently bred NARITA ‘Matooke’ hybrids and their ancestors. NARITA hybrids, their parents (4x and 2x), grandparents (3x and 2x), and local 3x ‘Matooke’ cultivar checks were planted in a rectangular lattice design with two replications. Yield and other agronomic data were collected at flowering and harvest. The NARITAs were compared with their 3x ‘Matooke’ grandmothers. Heterobeltiosis on bunch weight was calculated with the data of 3 cycles. All the NARITAs showed heterobeltiosis for bunch weight. NARITA 17 had the highest grandparent heterobeltiosis (ca. 250%). Genetic gains due to crossbreeding were determined for fruit yield considering three generations: matooke cultigen (C0), primary tetraploid hybrids (C1) and secondary tetraploid hybrids (C2). The average genetic gain (from C0 to C2) rates for bunch weight (kg) and yield potential (t ha−1 year−1) were 1.4% and 1.3% per year, respectively

Crossbreeding East African Highland Bananas: Lessons Learnt Relevant to the Botany of the Crop After 21 Years of Genetic Enhancement

East African highland bananas (EAHB) were regarded as sterile. Their screening forfemale fertility with “Calcutta 4” as male parent revealed that 37 EAHB were fertile. Thiswas the foundation for the establishment of the EAHB crossbreeding programs by theInternational Institute of Tropical Agriculture (IITA) and the National Agricultural ResearchOrganization (NARO) in Uganda in the mid-1990s. The aim of this study was to assessthe progress and efficiency of the EAHB breeding program at IITA, Sendusu in Uganda.Data on pollinations, seeds generated and germinated, plus hybrids selected between1995 and 2015 were analyzed. Pollination success and seed germination percentagesfor different cross combinations were calculated. The month of pollination did notresult in significantly different (P= 0.501) pollination success.Musa acuminatasubsp.malaccensisaccession 250 had the highest pollination success (66.8%), followed by thecultivar “Rose” (66.6%) among the diploid males. Twenty-five EAHB out of 41 studiedfor female fertility produced up to 305 seeds per pollinated bunch, and were thereforedeemed fertile. The percentage of seed germination varied among crosses: 26% for2x×4x, 23% for 2x×2x, 11% for 3x×2x,and 7% for 4x×2x. Twenty-seven NARITAhybrids (mostly secondary triploids ensuing from the 4x×2x) were selected for furtherevaluation in the East African region. One so far –“NARITA 7”– was officially released tofarmers in Uganda. Although pollination of EAHB can be conducted throughout the year,the seed set and germination is low. Thus, further research on pollination conditions andoptimization of embryo culture protocols should be done to boost seed set and embryogermination, respectively. More research in floral biology and seed germination as wellas other breeding strategies are required to increase the efficiency of the EAHB breedingprogram

Multi-ancestry genome-wide association study of asthma exacerbations

Altres ajuts: European Regional Development Fund "ERDF A way of making Europe"; Allergopharma-EAACI award 2021; SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020; Sandler Family Foundation; American Asthma Foundation; RWJF Amos Medical Faculty Development Program; National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, R01HL141845); National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844); National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, R56MD013312); National Institute of General Medical Sciences (NIGMS) (RL5GM118984); Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030); National Human Genome Research Institute (NHGRI) (U01HG009080); GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences; Slovenian Research Agency (P3-0067); SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (C3330-16-500106); NHS Research Scotland; Wellcome Trust Biomedical Resource (099177/Z/12/Z); Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII (AC15/00015); UK Medical Research Council and Wellcome (102215/2/13/2); University of Bristol; Swedish Heart-Lung Foundation, Swedish Research Council; Region Stockholm (ALF project and database maintenance); NHS Chair of Pharmacogenetics via the UK Department of Health; Innovative Medicines Initiative (IMI) (115010); European Federation of Pharmaceutical Industries and Associations (EFPIA); Spanish National Cancer Research Centre; Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17); Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); U.S. National Institutes of Health (HL07966); European Social Fund "ESF Investing in your future"; Ministerio de Ciencia, Innovación y Universidades; Universidad de La Laguna (ULL); European Academy of Allergy and Clinical Immunology (EAACI); European Respiratory Society (ERS) (LTRF202101-00861); Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012); Singapore Ministry of Education Academic Research Fund; Singapore Immunology Network (SIgN); National Medical Research Council (NMRC Singapore); Biomedical Research Council (BMRC Singapore); Agency for Science Technology and Research (A*STAR Singapore, N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, H17/01/a0/008); Sime Darby Technology Centre; First Resources Ltd; Genting Plantation; Olam International; U.S. National Institutes of Health (HL138098).Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR) = 0.82, p = 9.05 × 10 and replication: OR = 0.89, p = 5.35 × 10) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR = 0.85, p = 3.10 × 10 and replication: OR = 0.89, p = 1.30 × 10). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense

Mapping child growth failure across low- and middle-income countries

Child growth failure (CGF), manifested as stunting, wasting, and underweight, is associated with high 5 mortality and increased risks of cognitive, physical, and metabolic impairments. Children in low- and middle-income countries (LMICs) face the highest levels of CGF globally. Here we illustrate national and subnational variation of under-5 CGF indicators across LMICs, providing 2000–2017 annual estimates mapped at a high spatial resolution and aggregated to policy-relevant administrative units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the World Health 10 Organization’s ambitious Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and rates of progress exist across regions, countries, and within countries; our maps identify areas where high prevalence persists even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where subnational disparities exist and the highest-need populations reside, these geospatial estimates can support policy-makers in planning locally 15 tailored interventions and efficient directing of resources to accelerate progress in reducing CGF and its health implications

Mapping disparities in education across low- and middle-income countries

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations. Educational attainment is an important social determinant of maternal, newborn, and child health(1-3). As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting(4-6). The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness(7,8); however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health(9-11). Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but-to our knowledge-no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries(12-14). By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.Peer reviewe

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030