Monocytes and macrophages comprise a variety of subsets with diverse functions. It is thought that these cells play a crucial role in homeostasis of peripheral organs, key immunological processes and ...development of various diseases. Among these diseases, fibrosis is a life-threatening disease of unknown aetiology. Its pathogenesis is poorly understood, and there are few effective therapies. The development of fibrosis is associated with activation of monocytes and macrophages. However, the specific subtypes of monocytes and macrophages that are involved in fibrosis have not yet been identified. Here we show that Ceacam1
Msr1
Ly6C
F4/80
Mac1
monocytes, which we term segregated-nucleus-containing atypical monocytes (SatM), share granulocyte characteristics, are regulated by CCAAT/enhancer binding protein β (C/EBPβ), and are critical for fibrosis. Cebpb deficiency results in a complete lack of SatM. Furthermore, the development of bleomycin-induced fibrosis, but not inflammation, was prevented in chimaeric mice with Cebpb
haematopoietic cells. Adoptive transfer of SatM into Cebpb
mice resulted in fibrosis. Notably, SatM are derived from Ly6C
FcεRI
granulocyte/macrophage progenitors, and a newly identified SatM progenitor downstream of Ly6C
FcεRI
granulocyte/macrophage progenitors, but not from macrophage/dendritic-cell progenitors. Our results show that SatM are critical for fibrosis and that C/EBPβ licenses differentiation of SatM from their committed progenitor.
Macrophages consist of at least two subgroups, M1 and M2 (refs 1-3). Whereas M1 macrophages are proinflammatory and have a central role in host defence against bacterial and viral infections, M2 ...macrophages are associated with responses to anti-inflammatory reactions, helminth infection, tissue remodelling, fibrosis and tumour progression. Trib1 is an adaptor protein involved in protein degradation by interacting with COP1 ubiquitin ligase. Genome-wide association studies in humans have implicated TRIB1 in lipid metabolism. Here we show that Trib1 is critical for the differentiation of F4/80(+)MR(+) tissue-resident macrophages--that share characteristics with M2 macrophages (which we term M2-like macrophages)--and eosinophils but not for the differentiation of M1 myeloid cells. Trib1 deficiency results in a severe reduction of M2-like macrophages in various organs, including bone marrow, spleen, lung and adipose tissues. Aberrant expression of C/EBPα in Trib1-deficient bone marrow cells is responsible for the defects in macrophage differentiation. Unexpectedly, mice lacking Trib1 in haematopoietic cells show diminished adipose tissue mass accompanied by evidence of increased lipolysis, even when fed a normal diet. Supplementation of M2-like macrophages rescues the pathophysiology, indicating that a lack of these macrophages is the cause of lipolysis. In response to a high-fat diet, mice lacking Trib1 in haematopoietic cells develop hypertriglyceridaemia and insulin resistance, together with increased proinflammatory cytokine gene induction. Collectively, these results demonstrate that Trib1 is critical for adipose tissue maintenance and suppression of metabolic disorders by controlling the differentiation of tissue-resident M2-like macrophages.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This paper documents the production and validation of retrieved rainfall data obtained from satellite-borne microwave radiometers by the Global Satellite Mapping of Precipitation (GSMaP) Project. ...Using various attributes of precipitation derived from Tropical Rainfall Measuring Mission (TRMM) satellite data, the GSMaP has implemented hydrometeor profiles derived from Precipitation Radar (PR), statistical rain/no-rain classification, and scattering algorithms using polarization-corrected temperatures (PCTs) at 85.5 and 37 GHz. Combined scattering-based surface rainfalls are computed depending on rainfall intensities. PCT85 is not used for stronger rainfalls, because strong depressions of PCT85 are related to tall precipitation-top heights. Therefore, for stronger rainfalls, PCT37 is used, with PCT85 used for weaker rainfalls. With the suspiciously strong rainfalls retrieved from PCT85 deleted, the combined rainfalls correspond well to the PR rain rates over land. The GSMaP algorithm for the TRMM Microwave Imager (TMI) is validated using the TRMM PR, ground radar Kwajalein (KWAJ) radar and COBRA, and Radar Automated Meteorological Data Acquisition System (AMeDAS) precipitation analysis (RA). Monthly surface rainfalls retrieved from six microwave radiometers (GSMaP_MWR) are compared with the gauge-based dataset. Rain rates retrieved from the TMI (GSMaP_TMI) are in better agreement with the PR estimates over land everywhere except over tropical Africa in the boreal summer. Validation results of the KWAJ radar and COBRA show a good linear relationship for instantaneous rainfall rates, while validation around Japan using the RA shows a good relationship in the warm season. Poor results, connected to weak-precipitation cases, are found in the cold season around Japan.
An estimation method for specific attenuation and equivalent radar reflectivity in the melting layer using a dual Ka-band radar system was studied. The system consists of two identically designed ...Ka-radars. When a precipitation system comes between the two radars, the radars observe the system from opposite directions. The radar applies the frequency-modulated continuous-wave type and is designed for the measurement of the scattering characteristics of precipitation particles. The precipitation echoes suffer from rain attenuation. The reduction due to rain attenuation symmetrically appears in both radar echoes. By differentiating averaged measured radar reflectivity with range, the specific attenuation can be estimated. After obtaining the specific attenuation, equivalent radar reflectivity is estimated. In the melting layer, specific attenuation and the equivalent radar reflectivity vary largely along the radio path, and the estimated specific attenuation is very sensitive to the setup configuration of the experiment. The accuracy of the estimated specific attenuation was found to depend on the curvature, that is, the doubly differentiated value of the equivalent radar reflectivity with respect to range and the distance for the differentiation. The measurement system and actual procedure for the data analysis are also described.
This study was conducted with the aim of achieving the simultaneous screening of various additives in polymer materials by utilizing a solvent-free pyrolyzer/thermal desorption gas chromatography ...mass spectrometry (Py/TD-GC-MS) method. As a first step to achieve this goal, simultaneous screening has been examined by selecting major substances representing plasticizers and flame retardants, such as short chain chlorinated paraffins (SCCPs), decabromodiphenyl ether (DecaBDE), hexabromocyclododecane (HBCDD), and di(2-ethylhexyl) phthalate (DEHP). A quantitative MS analysis was performed to check for the peak areas and sensitivities. Since Py/TD-GC-MS is fraught with the risk of thermal degradation of the sample, temperatures during the analytical process were finely tuned for securing reliable results. The instrumental sensitivity was confirmed by the S/N ratio on each component. The detection limits of all components were less than 50 mg/kg, which are sufficiently lower than the regulatory criteria. With regard to reproducibility, a relative standard deviation (RSD) of about 5% was confirmed by employing a spike recovery test on a polystyrene polymer solution containing mixed standard solution (ca. 1000 mg/kg). In conclusion, the results obtained in this study indicate that Py/TD-GC-MS is applicable for the screening of major flame retardants and plasticizers in real samples with sufficient reproducibility at regulatory levels.
A phased array weather radar (PAWR) can complete one volume scan in 30 s, thus enabling us to obtain high spatiotemporal resolution echo intensities and wind fields of storms. Using its rapid ...scanning capability, we investigated the evolution of a convective storm in detail. To describe the evolution of convective storms, we used the following definitions. The precipitation cell is defined as a three-dimensionally contiguous region of 40 dBZ or greater. The precipitation core is defined by a threshold of positive deviation greater than 7 dBZ, which is a difference from the average reflectivity during the mature stage of the cell. An updraft core is defined as an updraft region of 1 m s−1 or stronger at a height of 2 km.An isolated convective storm was observed by two PAWRs on 7 August 2015 in the Kinki District, western Japan. The storm was judged as a single cell, according to the above definition. We identified nine precipitation cores and five updraft cores within 49 min in the mature stage of the cell. A long-lasting updraft core and its branches moved southwestward or southeastward. Around these updraft cores, the precipitation cores were generated successively. The updraft core with the longest duration lasted 73.5 min; in contrast, the lifetimes of the precipitation cores were from 4.5 min to 14.5 min. The precipitation cell was maintained by the successive generations of updraft cores which lifted humid air associated with a low-level southwesterly inflow. The total amounts of water vapor inflow supplied by all the identified updraft cores were proportional to the volumes of the precipitation cell, with a correlation coefficient of 0.75. Thus, the extremely high spatiotemporal resolution of the PAWR observations provides us with new evidence that an isolated convective storm can be formed by multiple precipitation cores and updraft cores.
The chemical synthesis of human interleukin‐2 (IL‐2) , having a core 1 sugar, by a ligation method is reported. Although IL‐2 is a globular glycoprotein, its C‐terminal region, in particular ...(99‐133), is extremely insoluble when synthesized by solid‐phase method. To overcome this problem, the side‐chain carboxylic acid of the Glu residues was protected by a picolyl ester, thus reversing its polarity from negative to positive. This reverse polarity protection significantly increased the isoelectric point of the peptide segment and made it positive under acidic conditions and facilitated the purification. An efficient method to prepare the prolyl peptide thioester required for the synthesis of the (28‐65) segment was also developed. These efforts resulted in the total synthesis of the glycosylated IL‐2 having full biological activity.
Take your Pic: Total synthesis of the glycosylated human interleukin‐2 (IL‐2) has been achieved. The poor solubility of the C‐terminal half during purification and ligation was overcome by using the reverse polarity protection of the carboxylic acid by a picolyl (Pic) ester. Together with a new prolyl thioester synthesis for the (28–65) segment, the desired IL‐2, having full biological activity, was successfully prepared.
This study aimed to clarify whether the influence of undernutrition status and the degree of glycemic disorders affected the prognosis of patients with sepsis. A total of 307 adult patients with ...sepsis were retrospectively enrolled and analyzed. Characteristics, including nutrition status, calculated according to the Controlling Nutritional Status (CONUT) score of survivors and non-survivors, were examined. The independent prognostic factors of these patients with sepsis were extracted using multivariable logistic regression analysis. The CONUT scores in three glycemic categories were compared. Most patients with sepsis (94.8%) in the study had an undernutrition status according to their CONUT scores. High CONUT scores (odds ratio, 1.214;
= 0.002), indicating a poor nutritional status, were associated with high mortality. The CONUT scores in the hypoglycemic group were significantly higher than those in other groups with an undernutrition status (vs. hyperglycemic,
< 0.001; vs. intermediate glycemic,
= 0.006). The undernutrition statuses of patients with sepsis in the study scored using the CONUT were independent predictors of prognostic factors.
Ice crystals in upper-tropospheric outflow layers of typhoons are an important factor in determining typhoon intensity and track through radiative cooling of the secondary circulation. Quantitative ...representation of ice crystal distribution is fundamental for accurate reproduction of typhoon intensity and track in cloud-resolving numerical models. This study used hydrometeor videosondes (HYVISs) released from Okinawa Island (Japan) to conduct microphysical observations of ice crystals in the outflow layer of Typhoon Francisco (2013). During the approach of the typhoon center, seven HYVISs were released between 02:53 JST October 23, 2013 and 13:33 JST October 24, 2013 at distances of between 230 and 550 km from the typhoon center (r = 230 and 550 km). The observation site was located at the downshear left flank, and at least three HYVISs were released within 100 km of active convection in the eyewall from which outflow-layer clouds extended. During the observations, the central pressure of the typhoon increased slightly from 945 to 960 hPa. Ice particles were observed at heights of 7–14 km. The numbers of ice particles tended to decrease with distance from the typhoon center. The maximum number concentrations of ice crystals were 180 and 20 L−1 at r = 230 and 550 km, respectively. Ice particles with diameter of a few tens of micrometers were found dominant. Large particles with diameter > 100 μm were restricted to just outside the eyewall and the inner-core precipitation region. Ice supersaturation layers with thickness > 2 km were present from r = 230 to 360 km, i.e., reasonably close to the typhoon center. In addition, supercooled liquid droplets were observed in areas with relative humidity >95% in two profiles (r = 260 and 290 km). Conversely, there was no ice supersaturation layer in the outermost profile at r = 550 km. Saw-like radar echo patterns were common along the bottom of outflow-layer clouds, below which a considerably drier layer was evident. Saturation ratio minima relative to ice within the dry layer were 0.01–0.34 (for relative humidities of 1%–31%). It was considered that ice particles formed in the upper levels of rainbands near the typhoon center, and that they were sublimated in both the dry layer below the outflow layer and the ice subsaturation area in the outermost region of the typhoon, which resulted in decreased number concentrations of ice particles.
•Upper-tropospheric outflow-layer clouds of Typhoon Francisco (2013) were observed.•Microphysical quantities of ice particles were measured throughout the outflow layer.•Dissipation process of ice particles was clarified.•Supercooled water droplets existed in the outflow-layer clouds of the typhoon.•A saw-like radar echo pattern was found along the bottom of the outflow-layer clouds.
Abstract
Rainfall velocity, raindrop size distribution (DSD), and vertical wind velocity were simultaneously observed with 2.05- and 1.54-
μ
m coherent Doppler lidars during convective and stratiform ...rain events. A retrieval method is based on identifying two separate spectra from the convolution of the aerosol and precipitation Doppler lidar spectra. The vertical wind velocity was retrieved from the aerosol spectrum peak and then the terminal rainfall velocity corrected by the vertical air motion from the precipitation spectrum peak was obtained. The DSD was derived from the precipitation spectrum using the relationship between the raindrop size and the terminal rainfall velocity. A comparison of the 1-min-averaged rainfall velocity from Doppler lidar measurements at a minimum range and that from a collocated ground-based optical disdrometer revealed high correlation coefficients of over 0.89 for both convective and stratiform rain events. The 1-min-averaged DSDs retrieved from the Doppler lidar spectrum using parametric and nonparametric methods are also in good agreement with those measured with the optical disdrometer with a correlation coefficient of over 0.80 for all rain events. To retrieve the DSD, the parametric method assumes a mathematical function for the DSD and the nonparametric method computes the direct deconvolution of the measured Doppler lidar spectrum without assuming a DSD function. It is confirmed that the Doppler lidar can retrieve the rainfall velocity and DSD during relatively heavy rain, whereas the ratio of valid data significantly decreases in light rain events because it is extremely difficult to separate the overlapping rain and aerosol peaks in the Doppler spectrum.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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