The three major axes of terrestrial ecosystem function.

The leaf economics spectrum1,2 and the global spectrum of plant forms and functions3 revealed fundamental axes of variation in plant traits, which represent different ecological strategies that are shaped by the evolutionary development of plant species2. Ecosystem functions depend on environmental conditions and the traits of species that comprise the ecological communities4. However, the axes of variation of ecosystem functions are largely unknown, which limits our understanding of how ecosystems respond as a whole to anthropogenic drivers, climate and environmental variability4,5. Here we derive a set of ecosystem functions6 from a dataset of surface gas exchange measurements across major terrestrial biomes. We find that most of the variability within ecosystem functions (71.8%) is captured by three key axes. The first axis reflects maximum ecosystem productivity and is mostly explained by vegetation structure. The second axis reflects ecosystem water-use strategies and is jointly explained by variation in vegetation height and climate. The third axis, which represents ecosystem carbon-use efficiency, features a gradient related to aridity, and is explained primarily by variation in vegetation structure. We show that two state-of-the-art land surface models reproduce the first and most important axis of ecosystem functions. However, the models tend to simulate more strongly correlated functions than those observed, which limits their ability to accurately predict the full range of responses to environmental changes in carbon, water and energy cycling in terrestrial ecosystems7,8.

Regeneration of Nonhuman Primate Hearts With Human Induced Pluripotent Stem Cell-Derived Cardiac Spheroids.

BACKGROUND: The clinical application of human induced pluripotent stem cell-derived cardiomyocytes (CMs) for cardiac repair commenced with the epicardial delivery of engineered cardiac tissue; however, the feasibility of the direct delivery of human induced pluripotent stem cell-derived CMs into the cardiac muscle layer, which has reportedly induced electrical integration, is unclear because of concerns about poor engraftment of CMs and posttransplant arrhythmias. Thus, in this study, we prepared purified human induced pluripotent stem cell-derived cardiac spheroids (hiPSC-CSs) and investigated whether their direct injection could regenerate infarcted nonhuman primate hearts. METHODS: We performed 2 separate experiments to explore the appropriate number of human induced pluripotent stem cell-derived CMs. In the first experiment, 10 cynomolgus monkeys were subjected to myocardial infarction 2 weeks before transplantation and were designated as recipients of hiPSC-CSs containing 2×107 CMs or the vehicle. The animals were euthanized 12 weeks after transplantation for histological analysis, and cardiac function and arrhythmia were monitored during the observational period. In the second study, we repeated the equivalent transplantation study using more CMs (6×107 CMs). RESULTS: Recipients of hiPSC-CSs containing 2×107 CMs showed limited CM grafts and transient increases in fractional shortening compared with those of the vehicle (fractional shortening at 4 weeks after transplantation: 26.2±2.1%; 19.3±1.8%; P<0.05), with a low incidence of posttransplant arrhythmia. Transplantation of increased dose of CMs resulted in significantly greater engraftment and long-term contractile benefits (fractional shortening at 12 weeks after transplantation: 22.5±1.0%; 16.6±1.1%; P<0.01, left ventricular ejection fraction at 12 weeks after transplantation: 49.0±1.4%; 36.3±2.9%; P<0.01). The incidence of posttransplant arrhythmia slightly increased in recipients of hiPSC-CSs containing 6×107 CMs. CONCLUSIONS: We demonstrated that direct injection of hiPSC-CSs restores the contractile functions of injured primate hearts with an acceptable risk of posttransplant arrhythmia. Although the mechanism for the functional benefits is not fully elucidated, these findings provide a strong rationale for conducting clinical trials using the equivalent CM products.

Interaction between Gtr2p and ribosomal Rps31p affects the incorporation of Rps31p into ribosomes of Saccharomyces cerevisiae.

In yeast, ras-like small G proteins, Gtr1p and Gtr2p, form heterodimers that affect cell division, detect amino acids, and regulate the activity of TORC1, a protein complex that integrates various signals, including those related to nutrient availability, growth factors, and stress signals. To explore novel roles of Gtr2p, yeast two-hybrid screening was performed using gtr2S23Np, an active form of Gtr2p, which identified Rps31p and Rpl12p as Gtr2p-interacting proteins. In the present study, we found that Gtr2p, but not Gtr1p, interacts with Rps31p, a 40S ribosomal subunit, and a component of the ubiquitin fusion protein Ubi3p, which is essential for the initiation and elongation of translation. In yeast cells expressing gtr2Q66Lp, an inactive form of Gtr2p, the interaction between Rps31p and gtr2Q66Lp, as well as the level of exogenous expression of Rps31p, was reduced. However, the level of exogenous expression of Rpl12p was unaffected. Introducing a mutation in ubiquitin target lysine residues to arginine (rps31-K5R) restored the level of exogenously expressed Rps31p and rescued the rapamycin and caffeine sensitivity of gtr2Q66L cells. Sucrose density gradient centrifugation of yeast cell lysate expressing Rps31p and gtr2Q66Lp revealed that exogenously expressed Rps31p was poorly incorporated, whereas rps31-K5Rp was efficiently incorporated, into ribosomes. These results suggest that Gtr2p influences incorporation of Rps31p into ribosomes and contributes to drug resistance through its interaction with Rps31p.

Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base.

The central protease of eukaryotes, the 26S proteasome, has a 20S proteolytic core particle (CP) and an attached 19S regulatory particle (RP). The RP is further subdivided into lid and base subcomplexes. Little is known about RP assembly. Here, we show that four conserved assembly factors govern biogenesis of the yeast RP base. Nas2 forms a complex with the Rpt4 and Rpt5 ATPases and enhances 26S proteasome formation in vivo and in vitro. Other RP subcomplexes contain Hsm3, which is related to mammalian proteasome subunit S5b. Hsm3 also contributes to base assembly. Larger Hsm3-containing complexes include two additional proteins, Nas6 and Rpn14, which function as assembly chaperones as well. Specific deletion combinations affecting these four factors cause severe perturbations to RP assembly. Our results demonstrate that proteasomal RP biogenesis requires multiple, functionally overlapping chaperones and suggest a model in which subunits form specific subcomplexes that then assemble into the base.

Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration.

Advances in stem cell biology have facilitated cardiac regeneration, and many animal studies and several initial clinical trials have been conducted using human pluripotent stem cell-derived cardiomyocytes (PSC-CMs). Most preclinical and clinical studies have typically transplanted PSC-CMs via the following two distinct approaches: direct intramyocardial injection or epicardial delivery of engineered heart tissue. Both approaches present common disadvantages, including a mandatory thoracotomy and poor engraftment. Furthermore, a standard transplantation approach has yet to be established. In this study, we tested the feasibility of performing intracoronary administration of PSC-CMs based on a commonly used method of transplanting somatic stem cells. Six male cynomolgus monkeys underwent intracoronary administration of dispersed human PSC-CMs or PSC-CM aggregates, which are called cardiac spheroids, with multiple cell dosages. The recipient animals were sacrificed at 4 weeks post-transplantation for histological analysis. Intracoronary administration of dispersed human PSC-CMs in the cynomolgus monkeys did not lead to coronary embolism or graft survival. Although the transplanted cardiac spheroids became partially engrafted, they also induced scar formation due to cardiac ischemic injury. Cardiac engraftment and scar formation were reasonably consistent with the spheroid size or cell dosage. These findings indicate that intracoronary transplantation of PSC-CMs is an inefficient therapeutic approach.

Carbon uptake in Eurasian boreal forests dominates the high-latitude net ecosystem carbon budget.

Arctic-boreal landscapes are experiencing profound warming, along with changes in ecosystem moisture status and disturbance from fire. This region is of global importance in terms of carbon feedbacks to climate, yet the sign (sink or source) and magnitude of the Arctic-boreal carbon budget within recent years remains highly uncertain. Here, we provide new estimates of recent (2003-2015) vegetation gross primary productivity (GPP), ecosystem respiration (Reco ), net ecosystem CO2 exchange (NEE; Reco - GPP), and terrestrial methane (CH4 ) emissions for the Arctic-boreal zone using a satellite data-driven process-model for northern ecosystems (TCFM-Arctic), calibrated and evaluated using measurements from >60 tower eddy covariance (EC) sites. We used TCFM-Arctic to obtain daily 1-km2 flux estimates and annual carbon budgets for the pan-Arctic-boreal region. Across the domain, the model indicated an overall average NEE sink of -850 Tg CO2 -C year-1 . Eurasian boreal zones, especially those in Siberia, contributed to a majority of the net sink. In contrast, the tundra biome was relatively carbon neutral (ranging from small sink to source). Regional CH4 emissions from tundra and boreal wetlands (not accounting for aquatic CH4 ) were estimated at 35 Tg CH4 -C year-1 . Accounting for additional emissions from open water aquatic bodies and from fire, using available estimates from the literature, reduced the total regional NEE sink by 21% and shifted many far northern tundra landscapes, and some boreal forests, to a net carbon source. This assessment, based on in situ observations and models, improves our understanding of the high-latitude carbon status and also indicates a continued need for integrated site-to-regional assessments to monitor the vulnerability of these ecosystems to climate change.

Involvement of Gtr1p in the oxidative stress response in yeast Saccharomyces cerevisiae.

Yeast Gtr1p is a GTPase that forms a heterodimer with Gtr2p, another GTPase; it is involved in regulating TORC1 activity in nutrient signaling, including amino acid availability and growth control. Gtr1p is a positive regulator of TORC1, a kinase that regulates various cellular functions (e.g., protein synthesis and autophagy) under specific nutrient and environmental conditions, including oxidative stress. In this study, we examined the roles of Gtr1p in oxidative stress responses. We found that yeast cells expressing guanosine diphosphatase (GDP)-bound Gtr1p (Gtr1-S20Lp) were resistant to hydrogen peroxide (H2O2), whereas guanosine triphosphate (GTP)-bound Gtr1p (Gtr1-Q65Lp) was sensitive to H2O2 compared with the wild type. Consistent with these findings, yeast cells lacking Iml1p, a component of the GTPase-activating protein complex for Gtr1p, exhibited the H2O2-sensitive phenotype. In gtr1S20L cells, autophagy was highly induced under oxidative stress. gtr1Q65L cells showed decreased expression of the SNQ2 gene, which encodes a multidrug transporter involved in resistance to oxidative stress, and the overexpression of SNQ2 rescued the oxidative stress sensitivity of gtr1Q65L cells. These results suggest that Gtr1p is involved in oxidative stress responses through mechanisms that include autophagy and SNQ2 expression.

Fundidesulfovibrio magnetotacticus sp. nov., a sulphate-reducing magnetotactic bacterium, isolated from sediments and freshwater of a pond.

A sulphate-reducing magnetotactic bacterium, designated strain FSS-1T, was isolated from sediments and freshwater of Suwa Pond located in Hidaka, Saitama, Japan. Strain FSS-1T was a motile, Gram-negative and curved rod-shaped bacterium that synthesizes bullet-shaped magnetite (Fe3O4) nanoparticles in each cell. Strain FSS-1T was able to grow in the range of pH 6.5-8.0 (optimum, pH 7.0), 22-34 °C (optimum, 28 °C) and with 0-8.0 g l-1 NaCl (optimum, 0-2.0 g l-1 NaCl). Strain FSS-1T grew well in the presence of 50 µM ferric quinate as an iron source. The major fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. The major menaquinone was MK-7 (H2). Strain FSS-1T contained desulfoviridin, cytochrome c 3 and catalase, but did not contain oxidase. Strain FSS-1T used fumarate, lactate, pyruvate, malate, formate/acetate, succinate, tartrate, ethanol, 1-propanol, peptone, soytone and yeast extract as electron donors, while the strain used sulphate, thiosulphate and fumarate as electron acceptors. Fumarate was fermented in the absence of electron acceptors. Analysis of the 16S rRNA gene sequence showed that strain FSS-1T is a member of the genus Fundidesulfovibrio. The gene sequence showed 96.7, 95.0, 92.0, 91.2 and 91.4% similarities to the most closely related members of the genera Fundidesulfovibrio putealis B7-43T, Fundidesulfovibrio butyratiphilus BSYT, Desulfolutivibrio sulfoxidireducens DSM 107105T, Desulfolutivibrio sulfodismutans ThAc01T and Solidesulfovibrio magneticus RS-1T, respectively. The DNA G+C content of strain FSS-1T was 67.5 mol%. The average nucleotide identity value between strain FSS-1T and F. putealis B7-43T was 80.7 %. Therefore, strain FSS-1T represents a novel species within the genus Fundidesulfovibrio, for which the name Fundidesulfovibrio magnetotacticus sp. nov. is proposed (=JCM 32405T=DSM 110007T).

Novel LCAT (Lecithin:Cholesterol Acyltransferase) Activator DS-8190a Prevents the Progression of Plaque Accumulation in Atherosclerosis Models.

OBJECTIVE: Enhancement of LCAT (lecithin:cholesterol acyltransferase) activity has possibility to be beneficial for atherosclerosis. To evaluate this concept, we characterized our novel, orally administered, small-molecule LCAT activator DS-8190a, which was created from high-throughput screening and subsequent derivatization. We also focused on its mechanism of LCAT activation and the therapeutic activity with improvement of HDL (high-density lipoprotein) functionality. Approach and Results: DS-8190a activated human and cynomolgus monkey but not mouse LCAT enzymes in vitro. DS-8190a was orally administered to cynomolgus monkeys and dose dependently increased LCAT activity (2.0-fold in 3 mg/kg group on day 7), resulting in HDL cholesterol elevation without drastic changes of non-HDL cholesterol. Atheroprotective effects were then evaluated using Ldl-r KO×hLcat Tg mice fed a Western diet for 8 weeks. DS-8190a treatment achieved significant reduction of atherosclerotic lesion area (48.3% reduction in 10 mg/kg treatment group). Furthermore, we conducted reverse cholesterol transport study using Ldl-r KO×hLcat Tg mice intraperitoneally injected with J774A.1 cells loaded with [3H]-cholesterol and confirmed significant increases of [3H] count in plasma (1.4-fold) and feces (1.4-fold on day 2 and 1.5-fold on day3) in the DS-8190a-treated group. With regard to the molecular mechanism involved, direct binding of DS-8190a to human LCAT protein was confirmed by 2 different approaches: affinity purification by DS-8190a-immobilized beads and thermal shift assay. In addition, the candidate binding site of DS-8190a in human LCAT protein was identified by photoaffinity labeling. CONCLUSIONS: This study demonstrates the potential of DS-8190a as a novel therapeutic for atherosclerosis. In addition, this compound proves that a small-molecule direct LCAT activator can achieve HDL-C elevation in monkey and reduction of atherosclerotic lesion area with enhanced HDL function in rodent.

A Survey of Near-Miss Dispensing Errors in Hospital Pharmacies in Japan: DEPP-J Study-Multi-Center Prospective Observational Study-

The aim of this study was to determine the proportion of near-miss dispensing errors in hospital pharmacies in Japan. A prospective multi-center observational study was conducted between December 2018 and March 2019. The primary objective was to determine the proportion of near-miss dispensing errors in hospital pharmacy departments. The secondary objective was to determine the predictive factors for near-miss dispensing errors using multiple logistic regression analysis. The study was approved by the ethical committee at The Institute of Medical Sciences, University of Tokyo, Japan. A multi-center prospective observational study was conducted in 20 hospitals comprising 8862 beds. Across the 20 hospitals, we assessed data from 553 pharmacists and 53039 prescriptions. A near-miss dispensing error proportion of 0.87% (n = 461) was observed in the study. We found predictive factors for dispensing errors in day-time shifts: a higher number of drugs in a prescription, higher number of quantified drugs, such as liquid or powder formula, in a prescription, and higher number of topical agents in a prescription; but we did not observe for career experience level for clinical pharmacists. For night-time and weekend shifts, we observed a negative correlation of near-miss dispensing errors with clinical pharmacist experience level. We found an overall incidence of near-miss dispensing errors of 0.87%. Predictive factors for errors in night-time and weekend shifts was inexperienced pharmacists. We recommended that pharmacy managers should consider education or improved work flow to avoid near-miss dispensing errors by younger pharmacists, especially those working night or weekend shifts.

Multilevel simulation of hard-sphere mixtures.

We present a multilevel Monte Carlo simulation method for analyzing multi-scale physical systems via a hierarchy of coarse-grained representations, to obtain numerically exact results, at the most detailed level. We apply the method to a mixture of size-asymmetric hard spheres, in the grand canonical ensemble. A three-level version of the method is compared with a previously studied two-level version. The extra level interpolates between the full mixture and a coarse-grained description where only the large particles are present-this is achieved by restricting the small particles to regions close to the large ones. The three-level method improves the performance of the estimator, at fixed computational cost. We analyze the asymptotic variance of the estimator and discuss the mechanisms for the improved performance.

WDR35 is involved in subcellular localization of acetylated tubulin in 293T cells.

WDR35/IFT121 is an intraflagellar transport protein in primary cilia, which is associated with RagA, an mTORC1-activating protein. To elucidate the functions of the interaction between WDR35 and RagA in primary cilia, as well as mTOR signaling, we identified WDR35-interacting proteins using mass spectrometry. We found that WDR35 associates with CCT complex proteins including TCP1/CCT1, which act as molecular chaperones for α-tubulin folding. Immunostaining showed that acetylated α-tubulin was concentrated in the vicinity of primary cilia in 293T cells. In contrast, acetylated tubulin was dispersed in WDR35 partial knockout cells established from 293T cells. Similarly, scattered subcellular localization of acetylated tubulin was observed in RagA knockout cells. RagA was present in the primary cilia of NIH3T3 cells, and the GDP form of RagA exhibited strong binding to WDR35 and negative regulation of primary cilium formation. These results suggest that WDR35 is involved in the subcellular localization of acetylated tubulin in primary cilia via its interactions with TCP1 and/or RagA family proteins.

Statistical upscaling of ecosystem CO2 fluxes across the terrestrial tundra and boreal domain: Regional patterns and uncertainties.

The regional variability in tundra and boreal carbon dioxide (CO2 ) fluxes can be high, complicating efforts to quantify sink-source patterns across the entire region. Statistical models are increasingly used to predict (i.e., upscale) CO2 fluxes across large spatial domains, but the reliability of different modeling techniques, each with different specifications and assumptions, has not been assessed in detail. Here, we compile eddy covariance and chamber measurements of annual and growing season CO2 fluxes of gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem exchange (NEE) during 1990-2015 from 148 terrestrial high-latitude (i.e., tundra and boreal) sites to analyze the spatial patterns and drivers of CO2 fluxes and test the accuracy and uncertainty of different statistical models. CO2 fluxes were upscaled at relatively high spatial resolution (1 km2 ) across the high-latitude region using five commonly used statistical models and their ensemble, that is, the median of all five models, using climatic, vegetation, and soil predictors. We found the performance of machine learning and ensemble predictions to outperform traditional regression methods. We also found the predictive performance of NEE-focused models to be low, relative to models predicting GPP and ER. Our data compilation and ensemble predictions showed that CO2 sink strength was larger in the boreal biome (observed and predicted average annual NEE -46 and -29 g C m-2  yr-1 , respectively) compared to tundra (average annual NEE +10 and -2 g C m-2  yr-1 ). This pattern was associated with large spatial variability, reflecting local heterogeneity in soil organic carbon stocks, climate, and vegetation productivity. The terrestrial ecosystem CO2 budget, estimated using the annual NEE ensemble prediction, suggests the high-latitude region was on average an annual CO2 sink during 1990-2015, although uncertainty remains high.

Safe and effective transvenous lead extraction for elderly patients utilizing non-laser and laser tools: a single-center experience in Japan.

Transvenous lead extraction (TLE) for cardiac implantable electric device (CIED) infection is becoming increasingly common, but is believed to be particularly risky in elderly patients. This study aimed to clarify the safety and effectiveness of TLE in the elderly, evaluating the use of both non-laser and laser extraction tools. We retrospectively analyzed the characteristics, device type, indications, procedures, and clinical results in younger (YG; age: 15-79 years; n = 48) and elderly groups (EG; age: ≥ 80 years; n = 27) of patients who underwent percutaneous TLE between April 2014 and December 2019 at our hospital. The average age was 68 and 88 years in the YG and EG, respectively. Indications for TLE were infection in 33 (68.8%) patients and other in 15 (30.6%) patients in the YG, and infection in all 27 (100%) EG patients. Bloodstream infection was detected in 9 and 4 patients in the YG and EG, respectively, with methicillin-resistant Staphylococcus epidermidis being the most common causative pathogen. All TLE procedures were performed under general anesthesia in an operating room with cardiovascular surgeon backup. An excimer laser sheath (76 leads), a laser followed by a mechanical sheath (45 leads), Evolution RL® (17 leads), a mechanical sheath (9 leads), and manual traction (one lead) were employed to extract a total of 148 leads (98 and 50 in the YG and EG, respectively). A mechanical sheath or Evolution RL® was more frequently used in the YG. The respective average implantation durations in the YG and EG were 5.3 and 5.0 years, respectively, which were comparable (p = 0.46). Procedural success rates were identical between the YG and EG (99% vs. 100%, respectively). There was only one procedure-related complication in the entire cohort (cardiac tamponade in a YG patient). Taken together, the success rates of TLE were high in the EG, with no complications, with extraction being the indication for infection in all EG patients. Percutaneous TLE was safe and effective in elderly patients using both non-laser and laser techniques.

A case of transient ventricular pre-excitation associated with takotsubo cardiomyopathy.

A 75-year-old woman, who had never exhibited a delta wave before, was diagnosed with sigmoid colon cancer and underwent surgical operation. Takotsubo cardiomyopathy (TC) occurred shortly after the operation. About 2 weeks following the onset of TC, a 12­lead electrocardiogram revealed a delta wave that was present for 50 days, and the patient was diagnosed with transient ventricular pre-excitation. The delta wave disappeared prior to patient's discharge and was never observed thereafter. This transient appearance of a delta wave may be related to a pathological modulation of the autonomic nervous system during the acute phase of TC.

Good response to methotrexate is associated with a decrease in the gene expression of ABCG2, a drug transporter, in patients with rheumatoid arthritis.

OBJECTIVES: Methotrexate (MTX) is used as an anchor drug in the treatment of rheumatoid arthritis (RA), although more than a half of the patients with RA require additional treatments. We designed a prospective study involving two medical centers in Japan to examine the association between the expression of MTX-related genes including a drug transporter ATP-binding cassette sub-family G member 2 (ABCG2) gene and the clinical response to MTX in MTX-naive patients with RA. METHODS: The primary endpoint of this study was good response based on the European League Against Rheumatism (EULAR) response criteria by Disease Activity Score using 28-joint count (DAS28). We evaluated the association between the baseline expression of six genes involved in the intracellular pharmacokinetics of MTX, including ABCG2, as well as their temporal changes, and the clinical response at week 12 from the initiation of MTX. RESULTS: Based on the clinical response at 12 weeks after the initiation of MTX, 24 patients were classified into good responders (n = 9) and non-good responders (n = 15; 10 moderate responders and 5 non-responders) groups. A univariate logistic regression analysis of the baseline gene expression levels to predict the EULAR good response at week 12 showed a significant association with ABCG2 expression alone. Furthermore, the rate of baseline expression of ABCG2 mRNA above the cut-off value determined using a receiver operating characteristic curve was higher in good responders than in non-good responders (p = .012). Moreover, ABCG2 expression decreased in almost all good responders, but not in non-good responders, after MTX treatment for 12 weeks (median -76% vs. +41% from baseline, respectively; p = .011). The ABCG2 expression level did not correlate with DAS28 at baseline or week 12. CONCLUSIONS: Our study revealed that good response to MTX is associated with a decrease in the expression of ABCG2 in patients with RA.

RagA, an mTORC1 activator, interacts with a hedgehog signaling protein, WDR35/IFT121.

Small Ras-like GTPases act as molecular switches for various signal transduction pathways. RagA, RagB/RagC and RagD are small Ras-like GTPases that play regulatory roles in mTORC1. Lack of proper activation of mTORC1 can lead to diseases, such as cancer and diabetes. In this study, we found an interaction between RagA and WDR35. Mutations of WDR35 may cause genetic diseases including Sensenbrenner syndrome. WDR35 seems to be a hedgehog signaling protein with a possible ciliary function and a possible upstream regulator of RagA. RagB is a homologue of RagA and is also associated with WDR35. WDR35 is present in the endoplasmic reticulum, but usually not in lysosomes, where Rag family proteins act as an mTORC1 switch. Over-expression of WDR35 results in decreased phosphorylation of ribosome S6 protein in a RagA-, RagB- and RagC-dependent manner. Thus, WDR35 is associated with RagA, RagB and RagC and might negatively influence mTORC1 activity.

Increased high-latitude photosynthetic carbon gain offset by respiration carbon loss during an anomalous warm winter to spring transition.

Arctic and boreal ecosystems play an important role in the global carbon (C) budget, and whether they act as a future net C sink or source depends on climate and environmental change. Here, we used complementary in situ measurements, model simulations, and satellite observations to investigate the net carbon dioxide (CO2 ) seasonal cycle and its climatic and environmental controls across Alaska and northwestern Canada during the anomalously warm winter to spring conditions of 2015 and 2016 (relative to 2010-2014). In the warm spring, we found that photosynthesis was enhanced more than respiration, leading to greater CO2 uptake. However, photosynthetic enhancement from spring warming was partially offset by greater ecosystem respiration during the preceding anomalously warm winter, resulting in nearly neutral effects on the annual net CO2 balance. Eddy covariance CO2 flux measurements showed that air temperature has a primary influence on net CO2 exchange in winter and spring, while soil moisture has a primary control on net CO2 exchange in the fall. The net CO2 exchange was generally more moisture limited in the boreal region than in the Arctic tundra. Our analysis indicates complex seasonal interactions of underlying C cycle processes in response to changing climate and hydrology that may not manifest in changes in net annual CO2 exchange. Therefore, a better understanding of the seasonal response of C cycle processes may provide important insights for predicting future carbon-climate feedbacks and their consequences on atmospheric CO2 dynamics in the northern high latitudes.

Correction of coarse-graining errors by a two-level method: Application to the Asakura-Oosawa model.

We present a method that exploits self-consistent simulation of coarse-grained and fine-grained models in order to analyze properties of physical systems. The method uses the coarse-grained model to obtain a first estimate of the quantity of interest, before computing a correction by analyzing properties of the fine system. We illustrate the method by applying it to the Asakura-Oosawa model of colloid-polymer mixtures. We show that the liquid-vapor critical point in that system is affected by three-body interactions which are neglected in the corresponding coarse-grained model. We analyze the size of this effect and the nature of the three-body interactions. We also analyze the accuracy of the method as a function of the associated computational effort.

Regeneration of Escherichia coli from Minicells through Lateral Gene Transfer.

Recently, artificial life has been created with artificial materials and methods. Life can be created when genomic DNA molecules are integrated in liposomes containing biochemical reactions for biogenic needs. However, it is not yet known whether the integration of these parts will be able to occur in nature and constitute a living system. I planned to regenerate bacteria from biologically active liposomes by inserting genomic DNA using only natural materials and methods. Minicells of Escherichia coli, containing plasmids and activated SOS proteins, act as protocells. Four new E. coli strains were regenerated from minicells by inserting the genomes by using the system for conjugation between F- and Hfr strains. Cells of the four regenerated strains showed the same genetic markers as the two genome donors. Pulse-field gel electrophoresis of their genomes showed admixing of those of both donors. In addition, the genomes of the four regenerated strains had chimeric genome of the two donors. These results show that synthesis of life can occur in nature without artificial arrangement.IMPORTANCE What is the difference between inanimate objects and organisms? Organisms always have genomic DNA. When organisms lose their genomes, they can neither grow nor reproduce. As the result, organisms turn into inanimate objects without their genomes. In this study, I regenerated microbes from cells that had lost their genomes (cell corpses) by inserting another genome. All steps of regeneration used the natural behavior of microbes. The same regeneration of microbes could happen in nature. These primitive lives have plasticity, which accelerates evolution and provides various kinds of life in the world.