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Coupling of Indo-Pacific climate variability over the last millennium 期刊论文
NATURE, 2020
作者:  Chow, Brian W.;  Nunez, Vicente;  Kaplan, Luke;  Granger, Adam J.;  Bistrong, Karina;  Zucker, Hannah L.;  Kumar, Payal;  Sabatini, Bernardo L.;  Gu, Chenghua
收藏  |  浏览/下载:34/0  |  提交时间:2020/05/13

Coral records indicate that the variability of the Indian Ocean Dipole over the last millennium is strongly coupled to variability in the El Nino/Southern Oscillation and that recent extremes are unusual but not unprecedented.


The Indian Ocean Dipole (IOD) affects climate and rainfall across the world, and most severely in nations surrounding the Indian Ocean(1-4). The frequency and intensity of positive IOD events increased during the twentieth century(5) and may continue to intensify in a warming world(6). However, confidence in predictions of future IOD change is limited by known biases in IOD models(7) and the lack of information on natural IOD variability before anthropogenic climate change. Here we use precisely dated and highly resolved coral records from the eastern equatorial Indian Ocean, where the signature of IOD variability is strong and unambiguous, to produce a semi-continuous reconstruction of IOD variability that covers five centuries of the last millennium. Our reconstruction demonstrates that extreme positive IOD events were rare before 1960. However, the most extreme event on record (1997) is not unprecedented, because at least one event that was approximately 27 to 42 per cent larger occurred naturally during the seventeenth century. We further show that a persistent, tight coupling existed between the variability of the IOD and the El Nino/Southern Oscillation during the last millennium. Indo-Pacific coupling was characterized by weak interannual variability before approximately 1590, which probably altered teleconnection patterns, and by anomalously strong variability during the seventeenth century, which was associated with societal upheaval in tropical Asia. A tendency towards clustering of positive IOD events is evident in our reconstruction, which-together with the identification of extreme IOD variability and persistent tropical Indo-Pacific climate coupling-may have implications for improving seasonal and decadal predictions and managing the climate risks of future IOD variability.


  
Germline Elongator mutations in Sonic Hedgehog medulloblastoma 期刊论文
NATURE, 2020, 580 (7803) : 396-+
作者:  Helmrich, S.;  Arias, A.;  Lochead, G.;  Wintermantel, T. M.;  Buchhold, M.;  Diehl, S.;  Whitlock, S.
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children(1,2), and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma(3). Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHH alpha subtype(4) and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U-34) position(5,6). Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems(7-9). Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.


  
Neural circuitry linking mating and egg laying in Drosophila females 期刊论文
NATURE, 2020
作者:  Simonov, Arkadiy;  De Baerdemaeker, Trees;  Bostrom, Hanna L. B.;  Rios Gomez, Maria Laura;  Gray, Harry J.;  Chernyshov, Dmitry;  Bosak, Alexey;  Buergi, Hans-Beat;  Goodwin, Andrew L.
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

Mating and egg laying are tightly cooordinated events in the reproductive life of all oviparous females. Oviposition is typically rare in virgin females but is initiated after copulation. Here we identify the neural circuitry that links egg laying to mating status in Drosophila melanogaster. Activation of female-specific oviposition descending neurons (oviDNs) is necessary and sufficient for egg laying, and is equally potent in virgin and mated females. After mating, sex peptide-a protein from the male seminal fluid-triggers many behavioural and physiological changes in the female, including the onset of egg laying(1). Sex peptide is detected by sensory neurons in the uterus(2-4), and silences these neurons and their postsynaptic ascending neurons in the abdominal ganglion(5). We show that these abdominal ganglion neurons directly activate the female-specific pC1 neurons. GABAergic (gamma-aminobutyric-acid-releasing) oviposition inhibitory neurons (oviINs) mediate feed-forward inhibition from pC1 neurons to both oviDNs and their major excitatory input, the oviposition excitatory neurons (oviENs). By attenuating the abdominal ganglion inputs to pC1 neurons and oviINs, sex peptide disinhibits oviDNs to enable egg laying after mating. This circuitry thus coordinates the two key events in female reproduction: mating and egg laying.


Neuron-tracing and labelling experiments in Drosophila females reveal the neural circuitry that coordinates mating and egg laying, and the role of sex peptide from male seminal fluid in triggering these neurons.


  
Probabilistic Forecast of Single-Phase Flow in Porous Media With Uncertain Properties 期刊论文
WATER RESOURCES RESEARCH, 2019
作者:  Yang, Hyung Jun;  Boso, Francesca;  Tchelepi, Hamdi A.;  Tartakovsky, Daniel M.
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
uncertainty quantification  groundwater flow  random conductivity  method of distributions  risk assessment  rare events