Thermal Phases of Earth-Like Planets: Estimating Thermal Inertia from Eccentricity, Obliquity, and Diurnal Forcing

In order to understand the climate on terrestrial planets orbiting nearby Sun-like stars, one would like to know their thermal inertia. We use a global climate model to simulate the thermal phase variations of Earth-analogs and test whether these data could distinguish between planets with different heat storage and heat transport characteristics. In particular, we consider a temperate climate with polar ice caps (like modern Earth), and a snowball state where the oceans are globally covered in ice. We first quantitatively study the periodic radiative forcing from, and climatic response to, rotation, obliquity, and eccentricity. Orbital eccentricity and seasonal changes in albedo cause variations in the global-mean absorbed flux. The responses of the two climates to these global seasons indicate that the temperate planet has 3 times the bulk heat capacity of the snowball planet due to the presence of liquid water oceans. The temperate obliquity seasons are weaker than one would expect based on thermal inertia alone; this is due to cross-equatorial oceanic and atmospheric energy transport. Thermal inertia and cross-equatorial heat transport have qualitatively different effects on obliquity seasons, insofar as heat transport tends to reduce seasonal amplitude without inducing a phase lag. For an Earth-like planet, however, this effect is masked by the mixing of signals from low thermal inertia regions (sea ice and land) with that from high thermal inertia regions (oceans), which also produces a damped response with small phase lag. We then simulate thermal lightcurves as they would appear to a high-contrast imaging mission (TPF-I/Darwin) and consider the inverse problem of estimating thermal inertia based solely on time-resolved photometry. [Abridged]Comment: 14 pages, 12 figures, ApJ accepte

Comparison of glucose monitoring between Freestyle Libre Pro and iPro2 in patients with diabetes mellitus

Aims/Introduction: Flash and continuous glucose monitoring systems are becomingprevalent in clinical practice. We directly compared a flash glucose monitoring system(FreeStyle Libre Pro [FSL-Pro]) with a continuous glucose monitoring system (iPro2) inpatients with diabetes mellitus.Materials and Methods: Glucose concentrations were simultaneously measured usingthe FSL-Pro, iPro2 and self-monitoring blood glucose in 10 patients with diabetes mellitus,and agreement among them was assessed.Results: Parkes error grid analysis showed that the 92.9 and 7.1% of glucose valuesmeasured using the FSL-Pro fell into areas A and B, respectively, and that 96.3, 2.8 and0.9% of those determined using iPro2 fell into areas A, B and C, respectively. The medianabsolute relative differences compared with self-monitoring blood glucose were 8.1%(3.9–12.7%) and 5.0% (2.6–9.1%) for the FSL-Pro and iPro2, respectively. Analysis of 5,555paired values showed a close correlation between FSL-Pro and iPro2 glucose values(q = 0.96, P < 0.01). Notably, 65.3% of all glucose values were lower for the FSL-Pro thanthe iPro2. Median glucose values also decreased by 3.3% for the FSL-Pro compared withthe iPro2 (177.0 [133.0–228.0] vs 183.0 [145.0–230.0] mg/dL, P < 0.01). The difference inglucose values between the two systems was more pronounced in hypoglycemia. Themedian absolute relative difference between FSL-Pro and iPro2 during hypoglycemia wasmuch larger than that during euglycemia and hyperglycemia.Conclusions: Both the FSL-Pro and iPro2 systems are clinically acceptable, but glucosevalues tended to be lower when measured using the FSL-Pro than the iPro2. Agreementwas not close between these systems during hypoglycemia

Identification of the ultrahigh-risk subgroup in neuroblastoma cases through DNA methylation analysis and its treatment exploiting cancer metabolism

神経芽腫の新たな診断法と治療戦略を創出 --がん細胞の生存戦略「がん代謝」を逆用する--. 京都大学プレスリリース. 2022-11-02.Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed the DNA methylation and expression datasets of neuroblastomas, extracted a candidate gene characterizing the aggressive features, and conducted functional studies. Based on the DNA methylation data, we identified a subgroup of neuroblastoma cases with 11q loss of heterozygosity with extremely poor prognosis. PHGDH, a serine metabolism-related gene, was extracted as a candidate with strong expression and characteristic methylation in this subgroup as well as in cases with MYCN amplification. PHGDH inhibition suppressed neuroblastoma cell proliferation in vitro and in vivo, indicating that the inhibition of serine metabolism by PHGDH inhibitors is a therapeutic alternative for neuroblastoma. Inhibiting the arginine metabolism, which is closely related to serine metabolism using arginine deiminase, had a combination effect both in vitro and in vivo, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. Expression and metabolome analyses of post-dose cells confirmed the synergistic effects of treatments targeting serine and arginine indicated that xCT inhibitors that inhibit cystine uptake could be candidates for further combinatorial treatment. Our results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma

Christopher Simpson The Division-Viol, or, The Art of PLAYING Extempore upon a GROUND. EDITIO SECVNDA Dedication & Recommendation

本訳稿はChristopher Simpson (1605頃－1669) 著 The Division-Viol, or, The Art of PLAYING Ex tempore upon a GROUND. DIVIDED INTO THREE PARTS. EDITIO SECVNDA, London, 1665 の著者による献辞および楽譜出版権所有者による推薦文の全訳である

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene

Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

遺伝性乳癌の遺伝学的・臨床学的特徴を解明 --BRCA1/2 変異乳癌は両アレルの不活化の有無により異なった特徴を持つ--. 京都大学プレスリリース. 2020-10-26.The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants

From ICU Syndromes to ICU Subphenotypes:Consensus Report and Recommendations for Developing Precision Medicine in the ICU

Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach is required and that integrated biologic and physiologic data identify reproducible subpopulations that may respond differently to treatment. This article reviews the current state of the field and considers how to successfully transition to a precision medicine approach. To impact clinical care, identification of subpopulations must do more than differentiate prognosis. It must differentiate response to treatment, ideally by defining subgroups with distinct functional or pathobiological mechanisms (endotypes). There are now multiple examples of reproducible subpopulations of sepsis, acute respiratory distress syndrome, and acute kidney or brain injury described using clinical, physiological, and/or biological data. Many of these subpopulations have demonstrated the potential to define differential treatment response, largely in retrospective studies, and that the same treatment-responsive subpopulations may cross multiple clinical syndromes (treatable traits). To bring about a change in clinical practice, a precision medicine approach must be evaluated in prospective clinical studies requiring novel adaptive trial designs. Several such studies are underway, but there are multiple challenges to be tackled. Such subpopulations must be readily identifiable and be applicable to all critically ill populations around the world. Subdividing clinical syndromes into subpopulations will require large patient numbers. Global collaboration of investigators, clinicians, industry, and patients over many years will therefore be required to transition to a precision medicine approach and ultimately realize treatment advances seen in other medical fields.</p

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology