Temporal Specification and Bilaterality of Human Neocortical Topographic Gene Expression

SummaryTranscriptional events involved in the development of human cerebral neocortex are poorly understood. Here, we analyzed the temporal dynamics and laterality of gene expression in human and macaque monkey neocortex. We found that interareal differences exhibit a temporal hourglass pattern, dividing the human neocortical development into three major phases. The first phase, corresponding to prenatal development, is characterized by the highest number of differential expressed genes among areas and gradient-like expression patterns, including those that are different between human and macaque. The second, preadolescent phase, is characterized by lesser interareal expression differences and by an increased synchronization of areal transcriptomes. During the third phase, from adolescence onward, differential expression among areas increases again driven predominantly by a subset of areas, without obvious gradient-like patterns. Analyses of left-right gene expression revealed population-level global symmetry throughout the fetal and postnatal time span. Thus, human neocortical topographic gene expression is temporally specified and globally symmetric

Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia

Graphical Abstract Highlights d Derivation of human neocortical and spinal cord neuroepithelial stem (NES) cells d Zika virus (ZIKV) infects NES cells and radial glia, impairing mitosis and survival d ZIKV induces mitochondrial sequestration of centrosomal phospho-TBK1 d Nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death In Brief Onorati et al. establish neuroepithelial stem (NES) cells as a model for studying human neurodevelopment and ZIKV-induced microcephaly. Together with analyses in human brain slices and microcephalic human fetal tissue, they find that ZIKV predominantly infects NES and radial glial cells, reveal a pivotal role for pTBK1, and find that nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death

Skewed X-inactivation is common in the general female population

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Species-Dependent Posttranscriptional Regulation of NOS1 by FMRP in the Developing Cerebral Cortex

SummaryFragile X syndrome (FXS), the leading monogenic cause of intellectual disability and autism, results from loss of function of the RNA-binding protein FMRP. Here, we show that FMRP regulates translation of neuronal nitric oxide synthase 1 (NOS1) in the developing human neocortex. Whereas NOS1 mRNA is widely expressed, NOS1 protein is transiently coexpressed with FMRP during early synaptogenesis in layer- and region-specific pyramidal neurons. These include midfetal layer 5 subcortically projecting neurons arranged into alternating columns in the prospective Broca's area and orofacial motor cortex. Human NOS1 translation is activated by FMRP via interactions with coding region binding motifs absent from mouse Nos1 mRNA, which is expressed in mouse pyramidal neurons, but not efficiently translated. Correspondingly, neocortical NOS1 protein levels are severely reduced in developing human FXS cases, but not FMRP-deficient mice. Thus, alterations in FMRP posttranscriptional regulation of NOS1 in developing neocortical circuits may contribute to cognitive dysfunction in FXS

Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia

The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation and characterization, including single-cell RNA-seq, of neocortical and spinal cord neuroepithelial stem (NES) cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. By analyzing human NES cells, organotypic fetal brain slices, and a ZIKV-infected micrencephalic brain, we show that ZIKV infects both neocortical and spinal NES cells as well as their fetal homolog, radial glial cells (RGCs), causing disrupted mitoses, supernumerary centrosomes, structural disorganization, and cell death. ZIKV infection of NES cells and RGCs causes centrosomal depletion and mitochondrial sequestration of phospho-TBK1 during mitosis. We also found that nucleoside analogs inhibit ZIKV replication in NES cells, protecting them from ZIKV-induced pTBK1 relocalization and cell death. We established a model system of human neural stem cells to reveal cellular and molecular mechanisms underlying neurodevelopmental defects associated with ZIKV infection and its potential treatment

Morphogenic and structural characteristics of guinea grass pastures submitted to three frequencies and two defoliation severities Características morfogênicas e estruturais de pastos de capim-tanzânia submetidos a três frequências e duas severidades de desfolhação

It was evaluated the morphogenic and structural characteristics of guinea grass under rotational at three grazing intervals and two defoliation intensities. Grazing intervals corresponded to the time needed by the forage canopy to reach 90, 95 or 100% of incident light interception during regrowth and they were evaluated combined to two defoliation severities (post-grazing conditions, 25 and 50 cm of height), being allocated to experimental units according to a complete randomized design, with three replicates and 3 × 2 factorial arrangement. The experiment was conducted from July 2003 to May 2004. For evaluation of morphogenetic and structural characteristics, ten tillers per experimental unit were selected. Morphogenetic and structural characteristics were strongly influenced by seasons of the year inasmuch as leaf elongation rate increased 3.5 fold from winter to summer. In addition to year season effect, there was also an effect of defoliation frequencies on tiller population density, which was greater in the defoliation period corresponding to 90% of light interception, especially if evaluated in relation to the interval corresponding to 100% of light interception. Defoliation frequency is determinant in expression of phenotypic plasticit, acting on the control of stem elongation.<br>Foram avaliadas as características morfogênicas e estruturais do capim-tanzânia sob lotação rotativa em três intervalos de pastejo e duas severidades de desfolhação. Os intervalos de pastejo corresponderam aos tempos necessários para que o dossel forrageiro atingisse 90, 95 ou 100% de interceptação da luz incidente, durante a rebrotação e foram avaliados em combinação a duas severidades de desfolhação (condições pós-pastejo, 25 e 50 cm de altura), sendo alocados às unidades experimentais segundo um delineamento de blocos completos casualizados, com três repetições e arranjo fatorial 3 × 2. O experimento foi realizado de julho de 2003 a maio de 2004. Para avaliação das características morfogênicas e estruturais, foram selecionados dez perfilhos por unidade experimental. As características morfogênicas e estruturais foram fortemente influenciadas pelas épocas do ano, uma vez que a taxa de alongamento de folhas aumentou 3,5 vezes do inverno para o verão. Além do efeito da época do ano, também houve efeito das frequências de desfolhação sobre a densidade populacional de perfilhos, que foi maior no intervalo de desfolhação correspondente a 90% da interceptação luminosa, principalmente se avaliado em relação ao intervalo correspondente a 100% da interceptação luminosa. A frequência de desfolhação é determinante na expressão da plasticidade fenotípica, principalmente por influenciar na densidade populacional de perfilhos, atuando no controle do alongamento dos colmos

Desenvolvimento inicial e estado nutricional de clones de eucalipto no nordeste do Pará Initial growth and nutritional status of Eucalyptus clones in northeast of Para State

O objetivo desta pesquisa foi avaliar o desenvolvimento inicial, nutrição e fertilidade do solo em plantio de clones de eucalipto no nordeste do Pará. Os tratamentos constaram de cinco clones (Eucalyptus grandis x E. urophylla - 03 e 09, E. urophylla x E. camaldulensis - 32, E. grandis x E. pellita - 07 e E. camaldulensis - 11), dispostos em delineamento de blocos ao acaso com quatro repetições. Cinco meses após plantio foram avaliadas a altura e sobrevivência das plantas. Aos 18 meses, além dessas variáveis, foram avaliados o diâmetro à altura do peito (DAP), a fertilidade do solo (profundidades 0-10 e 10-20 cm) e os nutrientes foliares. A altura e o DAP das árvores não variaram entre clones nas épocas de avaliação. Houve diferença na porcentagem de sobrevivência apenas aos 18 meses, sendo do clone 07 a menor média apresentada. Na camada de 0-10 cm foram observados os menores valores de K trocável no solo sob os clones 09 e 07, nas parcelas deste último foram observado também a menor CTC. Na camada de 10-20 cm, o menor valor de N no solo esteve sob o clone 32, enquanto que o K e Ca trocáveis foram encontrados em maiores quantidades sob o clone 03. De maneira geral, foram observadas as maiores concentrações de todos os nutrientes, com exceção do N, nas folhas dos clones 11 e 32. Desta forma, os clones apresentaram respostas nutricionais diferentes na área de estudo, assim como o solo sob cada material genético apresentou valores variados de fertilidade. Essas variações, entretanto, pouco foram observadas no desenvolvimento inicial das árvores.<br>The objective of this research was to determine the initial growth, nutrition and soil fertility of Eucalyptus plantation in Moju, northeast city of Para State, Brazil. The treatments used were five clones (Eucalyptus grandis x E. urophylla - 03 e 09, E. urophylla x E. camaldulensis - 32, E. grandis x E. pellita - 07 e E. camaldulensis - 11), organized in a randomized blocks design with four replications. Five months after planting, the height and survival percentage of plants were measured. At 18 months, besides these variables, diameter, soil fertility at the 0-10 and 10-20 cm depth and plant mineral nutrition were evaluated. The height and diameter did not vary among clones at evaluated times. There was difference in survival percentage just at 18 months, when the 07 clone showed the lower average. At the 0-10 cm soil depth, the lowest K exchangeable was observed under the 09 and 07 clones, the clone 07 also presented the lowest soil CEC. In 10-20 cm depth, the lowest value of N was observed in 32 clone, while the K and Ca were observed in highest levels in 03 clone. In general, higher macro and micronutrients leaves contents were found in the 11 and 32 clones, exception N. The clones presented different nutritional responses over the researched area, as well as the soil fertility under each clone presented varied values. Such variations, however, were little observed in the tree initial growth