A family with severe insulin resistance and diabetes due to a mutation in AKT2   总被引：1，自引：0，他引：1  

George S  Rochford JJ  Wolfrum C  Gray SL  Schinner S  Wilson JC  Soos MA  Murgatroyd PR  Williams RM  Acerini CL  Dunger DB  Barford D  Umpleby AM  Wareham NJ  Davies HA  Schafer AJ  Stoffel M  O'Rahilly S  Barroso I 《Science (New York, N.Y.)》2004,304(5675):1325-1328

Inherited defects in signaling pathways downstream of the insulin receptor have long been suggested to contribute to human type 2 diabetes mellitus. Here we describe a mutation in the gene encoding the protein kinase AKT2/PKBbeta in a family that shows autosomal dominant inheritance of severe insulin resistance and diabetes mellitus. Expression of the mutant kinase in cultured cells disrupted insulin signaling to metabolic end points and inhibited the function of coexpressed, wild-type AKT. These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans.  相似文献   

In utero heat stress alters the postnatal innate immune response of pigs     

Jay S Johnson  Jacob M Maskal  Alan W Duttlinger  Kouassi R Kpodo  Betty R McConn  Christopher J Byrd  Brian T Richert  Jeremy N Marchant-Forde  Donald C Lay  Jr  Shelbi D Perry  Matthew C Lucy  Tim J Safranski 《Journal of animal science》2020,98(12)

The effects of in utero heat stress (IUHS) range from decreased growth performance to altered behavior, but the long-term impact of IUHS on postnatal innate immune function in pigs is unknown. Therefore, the study objective was to determine the effects of early gestation IUHS on the immune, metabolic, and stress response of pigs subjected to an 8 hr lipopolysaccharide (LPS) challenge during postnatal life. Twenty-four pregnant gilts were exposed to thermoneutral (TN; n = 12; 17.5 ± 2.1 °C) or heat stress (HS; n = 12; cyclic 26 to 36 °C) conditions from days 6 to 59 of gestation, and then TN conditions (20.9 ± 2.3 °C) from day 60 of gestation to farrowing. At 12 wk of age, 16 IUHS and 16 in utero thermoneutral (IUTN) pigs were selected, balanced by sex and given an intravenous injection of LPS (2 µg/kg BW mixed with sterile saline [SAL] and injected at 2 µL/kg BW) or SAL (2 µL/kg BW). Body temperature was monitored every 30 min, and blood was obtained at 0, 1, 2, 3, 4, 6, and 8 hr following the LPS challenge. Blood samples were analyzed for glucose, insulin, non-esterified fatty acids (NEFA), cortisol, and cytokine concentrations. In addition, white blood cell counts were determined at 0 and 4 hr. Hour 0 data were used as covariates. Body temperature was increased (P < 0.01) in LPS (40.88 ± 0.08 °C) vs. SAL (39.83 ± 0.08 °C) pigs. Eosinophils tended to be decreased overall (P = 0.09; 43.9%) in IUHS vs. IUTN pigs. Glucose concentrations were reduced overall (P = 0.05; 5.9%) in IUHS vs. IUTN pigs. The NEFA concentrations tended to be greater (P = 0.07; 143.4%) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs tended to have greater (127.4%) circulating NEFA concentrations compared with IUTN-SAL and IUHS-SAL pigs. Cortisol was increased (P = 0.04) in IUHS-LPS compared with IUTN-LPS pigs at 3 hr (21.5%) and 4 hr (64.3%). At 1 hr, tumor necrosis factor α was increased (P = 0.01; 115.1%) in IUHS-LPS compared with IUTN-LPS pigs. Overall, interleukin-1β (IL-1β) and interleukin-6 (IL-6) were greater (P < 0.04; 281.3% and 297.8%, respectively) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs had increased IL-1β and IL-6 concentrations compared with IUTN-SAL and IUHS-SAL pigs. In summary, IUHS altered the postnatal cytokine, metabolic, and physiological stress response of pigs during postnatal life, which may have negative implications toward the innate immune response of IUHS pigs to pathogens.  相似文献   

Impact of lactation on pharmacokinetics of meloxicam in goats     

Tae-Won Kim  Irene Sartini  Beata Łebkowska-Wieruszewska  Andrzej Lisowski  Amnart Poapolathep  Mario Giorgi 《Journal of veterinary pharmacology and therapeutics》2020,43(1):13-18

Use of drug in lactating animal should be carefully considered due to its possibility of changes in pharmacokinetics as well as drug penetration in milk. The aim of this study was to assess the effect of lactation on pharmacokinetics of meloxicam after IV and IM administrations in goats. A crossover design (2 × 2) was used for each lactating and nonlactating group of goats with a 3-week washout period. Meloxicam (0.5 mg/kg) was administered into the jugular vein and upper gluteal muscle by IV and IM routes, respectively. The plasma and milk drug concentrations were determined by high-performance liquid chromatography with diode array detector, and the pharmacokinetic analysis was carried out by noncompartmental analysis. The pharmacokinetic parameters of meloxicam in lactating and nonlactating goats were not significantly different. The IM bioavailability of meloxicam was relatively lower in lactating (75.3 ± 18.6%) than nonlactating goats (103.8 ± 34.7%); however, the difference was not statistically significant. Moreover, AUC ratio between milk and plasma, which represent drug milk penetration, for both IV and IM administrations was less than 1 (about 0.3). In conclusion, pharmacokinetic parameters of meloxicam are not significantly altered by lactation for either the IV or IM routes of administration and this drug does not require a different dosage regimen for lactating animals.  相似文献   

Pharmacokinetics of levamisole after intramuscular and oral administrations to Caspian salmon (Salmo trutta caspius)     

Mohaddeseh A. Tabari  Mohammad Reza Youssefi  Seyed Mehdi Hosseinifard  Ali Akbar Moghaddamnia  Sohrab Kazemi  NadAli Yousefi Sadati  Azadeh Jalali Mothahari  Mario Giorgi 《Journal of veterinary pharmacology and therapeutics》2020,43(3):276-281

The pharmacokinetic parameters of levamisole were determined in the Caspian salmon after intramuscular (IM), oral by gavage, and oral by feed administrations. Eighty-one healthy fish in three different groups received levamisole at the dose of 25 mg/fish by each route. Blood samples were collected at time points of 0, 0.5, 1, 2, 4, 6, 12, 14, and 24 hr after administrations. Plasma levamisole concentrations were measured by a validated high-performance liquid chromatography (HPLC) assay and were analyzed using a noncompartmental approach. The mean terminal half-life was 4.56, 3.95, and 2.91 hr for IM, gavage and feed routes, respectively. The peak plasma concentration for IM, gavage, and feed routes of levamisole were 35.53, 4.63, and 8.36 µg/ml, respectively, at the time of 0.25 for IM, and 1 hr for gavage and feed. The relative bioavailability for gavage and feed routes was 54.80 and 69.30. The similar bioavailability for gavage and feed might be indicative of similar efficacy for these routes of administrations. Further studies are warranted to evaluate the absolute oral bioavailability and the effective dose in Caspian salmon.  相似文献   

Calving date and its variability as a potential trait in the breeding objective to account for reproductive seasonality in alpacas     

Alan Cruz  Juan Pablo Gutiérrez  Richard Torres  Nora Formoso-Rafferty  Renzo Morante  Alonso Burgos  Isabel Cervantes 《Reproduction in domestic animals》2020,55(7):814-821

The low fertility and offspring survival indicators in alpacas can be partially due to their particularity seasonal reproduction that reduces the opportunities of the females to become pregnant within a season, with the survival of the offspring concerned by the availability of food and exposure to diseases that depends on the calving date. Optimizing the date of delivery and reducing its variability are shown as eligible criteria that could be used as selection criteria within the genetic improvement programmes in alpacas, the calving date being a much more appropriate trait to measure and optimize fertility unlike of age at first calving and the calving interval, this due to the reproductive seasonality in camelids. For this study, 6,533 birth date records were taken between 2001 and 2018 of Peruvian alpacas, to estimate the genetic parameters. Models assuming heterogeneity in the residuals were fitted besides classical homogeneous models to address, not only the possibility of forwarding or delaying the calving date, but also the trend to have parturitions in similar dates. The heritability and repeatability ranged from 0.07 to 0.20 for a homogeneity model and from 0.08 to 0.23 for a heterogeneity model, and suggest the possibility of advancing or delaying the calving date. It should be taken into account that the gestation length of camelids makes it difficult to adapt many reproductive traits, and trying to centre the calving date could delay it. It was concluded the feasibility to genetically select the calving date, also in the production of camels and dromedaries, which have the same reproductive characteristics as alpacas. This selection can be combined with other traits. The heterogeneity model was shown to provide a better fit.  相似文献   

Disseminated Rhodococcus equi in an Anglo‐Nubian goat     

Gillian A. Y. Haanen  Chee Kin Lim  Aubrey N. Baird  Mario F. Sola  Stephen D. Lenz 《Veterinary radiology & ultrasound》2020,61(3):E22-E25

Disseminated Rhodococcus equi infection was diagnosed in an Anglo‐Nubian goat presenting for non‐weight bearing lameness of the right pelvic limb. Radiographs showed a moth‐eaten osteolytic lesion in the proximal tibia suggestive of an aggressive bone lesion. Two pulmonary nodules were also present on thoracic radiographs. Initial antemortem cytology of the tibial lesion was suggestive of Rhodococcosis and the goat was sent to necropsy. Necropsy and bacterial culture confirmed the diagnosis of disseminated R. equi infection in the right tibia, lungs, and liver.  相似文献   

Prevalence of serum antibodies to Coxiella burnetii in Alaska Native Persons from the Pribilof Islands     

Gilbert J. Kersh  Kelly Fitzpatrick  Karen Pletnikoff  Michael Brubaker  Michael Bruce  Alan Parkinson 《Zoonoses and public health》2020,67(1):89-92

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Ribozyme-catalyzed transcription of an active ribozyme     

Wochner A  Attwater J  Coulson A  Holliger P 《Science (New York, N.Y.)》2011,332(6026):209-212

A critical event in the origin of life is thought to have been the emergence of an RNA molecule capable of replicating a primordial RNA "genome." Here we describe the evolution and engineering of an RNA polymerase ribozyme capable of synthesizing RNAs of up to 95 nucleotides in length. To overcome its sequence dependence, we recombined traits evolved separately in different ribozyme lineages. This yielded a more general polymerase ribozyme that was able to synthesize a wider spectrum of RNA sequences, as we demonstrate by the accurate synthesis of an enzymatically active RNA, a hammerhead endonuclease ribozyme. This recapitulates a central aspect of an RNA-based genetic system: the RNA-catalyzed synthesis of an active ribozyme from an RNA template.  相似文献   

Nuclear safety. Nuclear power plants and their fuel as terrorist targets     

Chapin DM  Cohen KP  Davis WK  Kintner EE  Koch LJ  Landis JW  Levenson M  Mandil IH  Pate ZT  Rockwell T  Schriesheim A  Simpson JW  Squire A  Starr C  Stone HE  Taylor JJ  Todreas NE  Wolfe B  Zebroski EL 《Science (New York, N.Y.)》2002,297(5589):1997-1999

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Optimizing fen peatland water-table depth for romaine lettuce growth to reduce peat wastage under future climate warming     

Magdalena Matysek  Jonathan Leake  Steven Banwart  Irene Johnson  Susan Page  Jorg Kaduk  Alan Smalley  Alexander Cumming  Donatella Zona 《Soil Use and Management》2022,38(1):341-354

Forty percentage of UK peatlands have been drained for agricultural use, which has caused serious peat wastage and associated greenhouse gas emissions (carbon dioxide (CO₂) and methane (CH₄)). In this study, we evaluated potential trade-offs between water-table management practices for minimizing peat wastage and greenhouse gas emissions, while seeking to sustain romaine lettuce production: one of the most economically relevant crop in the East Anglian Fenlands. In a controlled environment experiment, we measured lettuce yield, CO_2, CH₄ fluxes and dissolved organic carbon (DOC) released from an agricultural fen soil at two temperatures (ambient and +2°C) and three water-table levels (−30 cm, −40 cm and −50 cm below the surface). We showed that increasing the water table from the currently used field level of −50 cm to −40 cm and −30 cm reduced CO₂ emissions, did not affect CH₄ fluxes, but significantly reduced yield and increased DOC leaching. Warming of 2°C increased both lettuce yield (fresh leaf biomass) and peat decomposition through the loss of carbon as CO₂ and DOC. However, there was no difference in the dry leaf biomass between the intermediate (−40 cm) and the low (−50 cm) water table, suggesting that romaine lettuce grown at this higher water level should have similar energetic value as the crop cultivated at −50 cm, representing a possible compromise to decrease peat oxidation and maintain agricultural production.  相似文献