0 ± 12.8 h,

39.3 ± 13.9 h, 1631 ± 467 IU h dL−1, 0.046 ± 0.01 dL kg−1 min−1 and 1.75 ± 0.52 mL kg−1 respectively. These values were not significantly different to those observed in AlphaNine®, although BeneFIX® displayed higher than expected IVR values and lower than expected clearance values. In conclusion, AlphaNine® showed a comparable half-life, but an IVR significantly higher than that of BeneFIX®. This dissimilarity may have implications on dosing requirements for on-demand treatment regimes affecting CX-5461 manufacturer optimal resource allocation. “
“Summary.  Acquired haemophilia (AH) is an autoimmune syndrome characterized by acute bleeding in patients with negative family and personal history, and factor VIII depletion. Its incidence is 1.6 × 106 population per year. AH is associated with autoimmune diseases, solid tumours, lymphoprolipherative diseases, pregnancy; 50% of the cases idiopathic. Spontaneous or after minor trauma severe bleeding associated with a prolonged activated partial thromboplastin time, not corrected by incubation with normal plasma, with a normal selleck chemicals llc prothrombin

time are the diagnostic hallmarks. The goals of management are the control of bleeding and the suppression of inhibitor. First-line haemostatic treatment includes recombinant factor VIIa and activated prothrombin complex concentrate. Prednisone ± cyclophosphamide and other immunosuppressive agents are the standard intervention for inhibitor eradication. Acquired haemophilia is a rare bleeding disorder caused by autoantibodies to factor VIII (FVIII) in a majority of cases. Antibodies to other clotting factors (factor V and IX) are exceedingly rare. Bleeding is acute, may be mild, but when severe, carries a high risk of death. The incidence according to the UK registry (2007) is 1.6 × 106 population per year [1]. The median age varies in the reported series between 55 and 78 years with no difference between genders, except in the younger age because of the cases related to pregnancy.

Fifty per cent of medchemexpress cases are idiopathic. Frequent associations are autoimmune diseases, solid tumours and lymphoprolipherative diseases (Table 1) [2]. The diagnosis of acquired haemophilia should be suspected in patients with negative family and personal history who experience either sudden spontaneous bleeding or after trivial trauma (intramuscular injection, positioning of a venous catheter) or surgery. Any site can be involved. Bleeding is defined minor or major, according to the specific site, extension and intensity. Minor bleeding, usually spontaneous, involves mainly the skin (ecchymoses); mucoses and muscles can also be affected (melaena, haematuria, methrorrhagia, epistaxis, gengivorrhagia). Major bleeding occurs in a majority of patients (65.5%) and is either spontaneous or secondary to trauma or surgery [2].

Subjective ratings of emotional valence and arousal were assessed during the regulation task and again after 1 week. Memory for the pictures was assessed with

free recall. Results indicated that pictures accompanied by instructions to increase emotion were better recalled than pictures reappraised to decrease emotion. Modulation of emotional arousal elicited by stimuli persisted over a week, but this effect was observed only for men. These findings suggest that cognitive reappraisal can have long-lasting effects on emotional reactions to stimuli. However, the sex differences observed for the effects of reappraisal on emotional reactions highlight the importance of considering individual differences in the effects of regulation. “
“Visual Hallucinations are considered to affect about 20%–40% of patients with Parkinson’s disease. They are generally seen as a side effect of this long-term illness H 89 nmr and can severely affect the daily quality of life of patients. The aim of this study was to determine the coping patterns or strategies used by patients and establish whether the phenomenology and behaviours used by patients enabled control of the phenomenon. Demographic and clinical variables were recorded, including motor measures, cognitive status,

and depressive symptoms. Patient with hallucinations Ivacaftor cost were at a more advance stage of the disease and displayed more depressive symptoms than their non-hallucinating counterparts. Most patients used more than one constructive coping strategy, the most common were simple behavioural strategies based around motor action or cognitive approaches resulting in visual modification. In addition, humour was a common technique used by the patients to deal with the phenomenon. Emotional responses varied between patients, but it was found that the actual 上海皓元 content of the hallucination was not directly associated with whether

it caused trouble to the patient, but perceived stress was strongly correlated with the subjective disturbing nature of visual hallucinations (VHs). This study gives insight into the role of cognitive-behavioural approaches when dealing with VHs and opens up avenues for future studies in helping patient to deal with hallucinations. “
“The recent Journal corrigendum (45:1416) is clarified here relative to the discrepancy between Theriot (2008) and Kaczmarska and Medlin (2009) about the delivery of a data set. The Journal of Phycology has determined from its records of correspondence that NEXUS files were provided by Kaczmarska and Medlin to the Journal, as requested, and sent by the Journal to Theriot. Thus, a data set was transferred as stated in Kaczmarska and Medlin (2009); however, the sequence file did not include an alignment.

Subjective ratings of emotional valence and arousal were assessed during the regulation task and again after 1 week. Memory for the pictures was assessed with

free recall. Results indicated that pictures accompanied by instructions to increase emotion were better recalled than pictures reappraised to decrease emotion. Modulation of emotional arousal elicited by stimuli persisted over a week, but this effect was observed only for men. These findings suggest that cognitive reappraisal can have long-lasting effects on emotional reactions to stimuli. However, the sex differences observed for the effects of reappraisal on emotional reactions highlight the importance of considering individual differences in the effects of regulation. “
“Visual Hallucinations are considered to affect about 20%–40% of patients with Parkinson’s disease. They are generally seen as a side effect of this long-term illness Small molecule library molecular weight and can severely affect the daily quality of life of patients. The aim of this study was to determine the coping patterns or strategies used by patients and establish whether the phenomenology and behaviours used by patients enabled control of the phenomenon. Demographic and clinical variables were recorded, including motor measures, cognitive status,

and depressive symptoms. Patient with hallucinations Daporinad supplier were at a more advance stage of the disease and displayed more depressive symptoms than their non-hallucinating counterparts. Most patients used more than one constructive coping strategy, the most common were simple behavioural strategies based around motor action or cognitive approaches resulting in visual modification. In addition, humour was a common technique used by the patients to deal with the phenomenon. Emotional responses varied between patients, but it was found that the actual 上海皓元医药股份有限公司 content of the hallucination was not directly associated with whether

it caused trouble to the patient, but perceived stress was strongly correlated with the subjective disturbing nature of visual hallucinations (VHs). This study gives insight into the role of cognitive-behavioural approaches when dealing with VHs and opens up avenues for future studies in helping patient to deal with hallucinations. “
“The recent Journal corrigendum (45:1416) is clarified here relative to the discrepancy between Theriot (2008) and Kaczmarska and Medlin (2009) about the delivery of a data set. The Journal of Phycology has determined from its records of correspondence that NEXUS files were provided by Kaczmarska and Medlin to the Journal, as requested, and sent by the Journal to Theriot. Thus, a data set was transferred as stated in Kaczmarska and Medlin (2009); however, the sequence file did not include an alignment.

Potential subjects were excluded for a platelet count <50,000/mm3, absolute neutrophil count <1,000/mm3, hematocrit level <33%, alpha-fetoprotein level >200 ng/mL, Child-Turcotte-Pugh (CTP) score ≥7, or a history of decompensated liver disease or hepatocellular carcinoma (HCC). Patients with other

causes of liver disease, uncontrolled comorbid medical (including malignancies, autoimmune disorders, and immunocompromised states) or psychiatric illnesses, or contraindications to interferon were excluded, as were pregnant or breast-feeding women. Potential participants in the HALT-C Trial were treated in a lead-in phase with peginterferon alfa-2a OSI-906 (180 μg/week subcutaneously) and ribavirin (1,000-1,200 mg/day);13 those who failed to clear hepatitis C virus

(HCV) RNA by week 20, categorized as nonresponders,11, Selleck ICG-001 12 were randomized to 3.5 years of 90 μg/week of peginterferon alfa-2a or to an untreated control group. Subjects with undetectable HCV RNA at treatment week 20 were categorized as responders and received combination treatment for 48 weeks. Responders with detectable HCV RNA after week 20 (breakthrough or relapsers) were also eligible for randomization. In addition, patients failing to achieve a sustained virologic response following 上海皓元 peginterferon and ribavirin treatment administered outside the HALT-C Trial were also eligible for randomization. Of 1,730 screened subjects, 1,050 were randomized.12 Study subjects were seen in one of 10 clinical centers at 3-month intervals through month 48 and every 6 months thereafter until October 2009. Protocol-defined clinical outcomes included a CTP score of ≥7 on two consecutive study visits 3 months apart (6 months apart in the postrandomization phase), variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial

peritonitis, definite HCC, or death either related or unrelated to liver disease. For this analysis we also included liver transplantation and presumed HCC as clinical outcomes. In addition to individual clinical outcomes, we defined three groups of clinical outcome. “Any clinical outcome” was the definition used in the original HALT-C Trial protocol and included death from any cause, presumed or definite HCC, variceal hemorrhage, ascites, spontaneous bacterial peritonitis or hepatic encephalopathy. “Decompensated liver disease” was defined as variceal hemorrhage, ascites, spontaneous bacterial peritonitis, or hepatic encephalopathy. “HCC/Decompensation” was defined as presumed or definite HCC, as defined,14 or decompensated liver disease.

Potential subjects were excluded for a platelet count <50,000/mm3, absolute neutrophil count <1,000/mm3, hematocrit level <33%, alpha-fetoprotein level >200 ng/mL, Child-Turcotte-Pugh (CTP) score ≥7, or a history of decompensated liver disease or hepatocellular carcinoma (HCC). Patients with other

causes of liver disease, uncontrolled comorbid medical (including malignancies, autoimmune disorders, and immunocompromised states) or psychiatric illnesses, or contraindications to interferon were excluded, as were pregnant or breast-feeding women. Potential participants in the HALT-C Trial were treated in a lead-in phase with peginterferon alfa-2a AZD2014 cost (180 μg/week subcutaneously) and ribavirin (1,000-1,200 mg/day);13 those who failed to clear hepatitis C virus

(HCV) RNA by week 20, categorized as nonresponders,11, this website 12 were randomized to 3.5 years of 90 μg/week of peginterferon alfa-2a or to an untreated control group. Subjects with undetectable HCV RNA at treatment week 20 were categorized as responders and received combination treatment for 48 weeks. Responders with detectable HCV RNA after week 20 (breakthrough or relapsers) were also eligible for randomization. In addition, patients failing to achieve a sustained virologic response following 上海皓元 peginterferon and ribavirin treatment administered outside the HALT-C Trial were also eligible for randomization. Of 1,730 screened subjects, 1,050 were randomized.12 Study subjects were seen in one of 10 clinical centers at 3-month intervals through month 48 and every 6 months thereafter until October 2009. Protocol-defined clinical outcomes included a CTP score of ≥7 on two consecutive study visits 3 months apart (6 months apart in the postrandomization phase), variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial

peritonitis, definite HCC, or death either related or unrelated to liver disease. For this analysis we also included liver transplantation and presumed HCC as clinical outcomes. In addition to individual clinical outcomes, we defined three groups of clinical outcome. “Any clinical outcome” was the definition used in the original HALT-C Trial protocol and included death from any cause, presumed or definite HCC, variceal hemorrhage, ascites, spontaneous bacterial peritonitis or hepatic encephalopathy. “Decompensated liver disease” was defined as variceal hemorrhage, ascites, spontaneous bacterial peritonitis, or hepatic encephalopathy. “HCC/Decompensation” was defined as presumed or definite HCC, as defined,14 or decompensated liver disease.

14, 15 Hh pathway activation has also been observed MK0683 manufacturer in some HCC cell lines, although significant heterogeneity exists within actual tumors.16 A vigorous debate exists as to whether liver epithelial cells, such as cholangiocytes and hepatocytes, undergo epithelial-to-mesenchymal transitions (EMT) in injured livers,

but some evidence supports this concept and suggests Hh-mediated regulation.17-21 In viral hepatitis patients, recent data suggests EMT may occur in response to infection.22 HCV infection of hepatoma cell lines in vitro alters cell polarity to expose gap junction complex proteins key to viral entry.23 To our knowledge, such studies have not addressed the effects of altered cell polarity on HCV replication, or mechanisms by which viral infection might promote EMT. We hypothesized that Huh7.5 cells are highly Selleckchem Ixazomib permissive for HCV because they possess a “transitional” phenotype skewed toward mesenchymal characteristics due to increased Hh pathway activity. We subsequently asked whether Hh pathway activation may create an environment conducive to viral replication and whether Hh pathway inhibition would inhibit HCV replication. EMT, epithelial-to-mesenchymal transition; Hh, Hedgehog; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; Ihh, Indian hedgehog; LDH, lactate dehydrogenase;

qRT-PCR, quantitative reverse-transcription polymerase chain reaction; Shh, Sonic hedgehog. Huh7 cells, Huh7.5 cells (a gift from C. Rice, Rockefeller University), LH86 cells (a gift 上海皓元医药股份有限公司 from C. Liu, University of Florida), and HepG2 cells were used for these studies. Primary human hepatic stellate cells were isolated and cultured as described17 and primary human hepatocytes were commercially prepared (a gift from R. Witek, Invitrogen, Durham, NC). JFH1 cDNA (kindly provided by T. Wakita, National Institute of Infectious Diseases, Tokyo, Japan) was used to generate cell culture HCV, and HCV Con1 replicon

(a gift from C. Rice, Rockefeller University) to study HCV replication. Primer sequences for quantitative reverse-transcription polymerase chain reaction (qRT-PCR) reactions are listed in Supporting Table 1. Purchased reagents were: Interferon-α A/D (Sigma-Aldrich, St. Louis, MO), cyclopamine and tomatidine (Toronto Research Chemicals, Toronto, Canada), recombinant N-terminal mouse Shh (StemCell Technologies, Vancouver, Canada), SAG (Enzo Life Sciences, Plymouth Meeting, PA), GDC-0449 (Selleck Chemicals, Houston, TX), and mouse immunoglobulin G (IgG)1 isotype control antibody (R&D Systems, Minneapolis, MN). Antibodies to Shh and Gli1 (Santa Cruz Biotechnology, Santa Cruz, CA), α-SMA (Dako, Carpinteria, CA), and α-tubulin (Sigma-Aldrich) were used for immunoblotting and α-HCV Core (C7-50, Abcam) was used for immunofluorescence/immunoblotting.

This causes neonatal hepatitis, cirrhosis, and hepatocellular carcinoma. We have developed a conformation-specific monoclonal antibody (2C1) that recognizes the pathological polymers formed by α1-antitrypsin. This antibody was used to characterize the Z variant and a novel shutter domain mutant (His334Asp; α1-antitrypsin King’s) identified in a 6-week-old boy who presented with prolonged jaundice. His334Asp α1-antitrypsin rapidly forms polymers that accumulate within the endoplasmic reticulum and show delayed secretion when compared to the wild-type M α1-antitrypsin. The 2C1 antibody recognizes polymers formed by

Z and His334Asp α1-antitrypsin despite the mutations directing their effects C59 wnt chemical structure on different Fulvestrant cell line parts of the protein. This antibody also recognized polymers formed by the Siiyama (Ser53Phe) and Brescia (Gly225Arg) mutants, which also mediate their effects on the shutter region of α1-antitrypsin. Conclusion: Z and shutter domain mutants of α1-antitrypsin form polymers with a shared epitope and so are likely to have a similar structure. HEPATOLOGY 2010 The serpinopathies are conformational diseases characterized by the polymerization and intracellular retention

of members of the serine protease inhibitor or serpin superfamily of proteins.1 The best known is α1-antitrypsin deficiency, with the most common severe deficiency allele being the Z mutation (Glu342Lys). This mutation results in the retention of ordered polymers of α1-antitrypsin as periodic acid Schiff positive inclusion bodies within the endoplasmic reticulum (ER) of hepatocytes.2 These inclusions predispose the individual homozygous for the Z variant of the α1-antitrypsin protease inhibitor (PI*Z) to neonatal hepatitis, cirrhosis, and rarely, hepatocellular carcinoma.3 Deficiency of circulating α1-antitrypsin results in early onset panlobular emphysema.4 The Z mutation of α1-antitrypsin

lies between the head of strand 5A and the base of the mobile reactive center loop5 (Fig. 1). Other mutations that cause α1-antitrypsin deficiency cluster around the shutter region of the protein (Fig. 1). In the classical model of serpin polymerization, these mutations are believed to open β-sheet A, giving rise to 上海皓元医药股份有限公司 a polymerogenic intermediate that has been termed M*.6, 7 The patent β-sheet A then accepts the reactive loop of a second α1-antitrypsin molecule to form a dimer, which can extend into chains of reactive center loop-β-sheet A polymers.2, 6, 8-12 The recent crystal structure of a dimer of another serpin, antithrombin, demonstrated a linkage between a β-hairpin of the reactive loop and strand 5A of one molecule and β-sheet A of another. This dimer was used as the basis of a novel model for the polymer in which helix I is unravelled and the proteins are linked by a β-hairpin containing the reactive center loop and strand 5A.

5 Hz; MatLab, MathWorks, Natick, MA). Spectral analysis was performed for the P3-P4 derivation and the EEG classified based on the mean dominant frequency (MDF) and the relative power of the delta and theta bands.28 Where obvious on visual inspection of the power spectrum, the frequency of the dominant peak was also obtained. Between 17:00 and 19:00 hours, subjects were placed in a quiet, dark, and shielded

hospital click here room and given the opportunity to nap. The EEG was recorded as described above. In addition, the mastoids, submental electromyogram and ocular movements were also recorded. Sleep stages were scored visually for 20-second epochs (C3-A2 derivation) according to standard criteria12 www.selleckchem.com/products/kpt-330.html (Rembrandt Analysis Manager, v. 8; Embla Systems, Broomfield, CO) by one of the authors (A.B.), who had no information on either the subject or the experimental condition. Blocks of consolidated non-REM sleep (sleep stages 2-4, without intervening epochs of wake or stage 1 sleep) of equal length in the two experimental conditions (minimal length: 8 minutes) were selected for subsequent spectral analysis. Power spectra were computed by Fast Fourier Transform (2-second epochs, Hanning window, frequency resolution 0.5 Hz). Artifacts were identified by visual inspection or whenever delta power exceeded a subject-specific threshold. The AAC was

administered at 07:00 hours on study days 4 or 8. It consisted of a flavored, 54 g amino acid mixture, mimicking the composition of the hemoglobin contained in 400 mL of blood.4 The mixture was dispersed in 50-100 mL of water and ingested over a period of 10-15 minutes. Capillary ammonia concentrations were measured prior to and at 上海皓元医药股份有限公司 hourly intervals for 8 hours after the AAC using the Ammonia Checker (Menarini Diagnostics, Firenze, Italy). Subjective

sleepiness was also monitored on an hourly basis using the Karolinska Sleepiness Scale (KSS)29 on both study days 4 and 8. The study protocol was approved by the Hospital of Padua Ethics Committee. All participants provided written, informed consent. The study was conducted according to the Declaration of Helsinki (Hong Kong Amendment) and Good Clinical Practice (European) guidelines. Data are presented as mean (SD) unless otherwise specified. The distribution of variables was assessed by the Shapiro-Wilks’ test and between group comparisons performed using Student’s t or Mann-Whitney U tests, as appropriate. Comparisons between pre- and post-AAC variables were performed by repeated measures analysis of variance (ANOVA) using the variable healthy volunteers versus patients as a “group” factor. Log-transformed average sleep EEG power spectra were analyzed with linear mixed model ANOVA. The factors group (patients versus healthy volunteers) and condition (AAC versus baseline), as well as their interaction, were tested.

5 Hz; MatLab, MathWorks, Natick, MA). Spectral analysis was performed for the P3-P4 derivation and the EEG classified based on the mean dominant frequency (MDF) and the relative power of the delta and theta bands.28 Where obvious on visual inspection of the power spectrum, the frequency of the dominant peak was also obtained. Between 17:00 and 19:00 hours, subjects were placed in a quiet, dark, and shielded

hospital IDH inhibitor clinical trial room and given the opportunity to nap. The EEG was recorded as described above. In addition, the mastoids, submental electromyogram and ocular movements were also recorded. Sleep stages were scored visually for 20-second epochs (C3-A2 derivation) according to standard criteria12 BTK inhibitor (Rembrandt Analysis Manager, v. 8; Embla Systems, Broomfield, CO) by one of the authors (A.B.), who had no information on either the subject or the experimental condition. Blocks of consolidated non-REM sleep (sleep stages 2-4, without intervening epochs of wake or stage 1 sleep) of equal length in the two experimental conditions (minimal length: 8 minutes) were selected for subsequent spectral analysis. Power spectra were computed by Fast Fourier Transform (2-second epochs, Hanning window, frequency resolution 0.5 Hz). Artifacts were identified by visual inspection or whenever delta power exceeded a subject-specific threshold. The AAC was

administered at 07:00 hours on study days 4 or 8. It consisted of a flavored, 54 g amino acid mixture, mimicking the composition of the hemoglobin contained in 400 mL of blood.4 The mixture was dispersed in 50-100 mL of water and ingested over a period of 10-15 minutes. Capillary ammonia concentrations were measured prior to and at MCE hourly intervals for 8 hours after the AAC using the Ammonia Checker (Menarini Diagnostics, Firenze, Italy). Subjective

sleepiness was also monitored on an hourly basis using the Karolinska Sleepiness Scale (KSS)29 on both study days 4 and 8. The study protocol was approved by the Hospital of Padua Ethics Committee. All participants provided written, informed consent. The study was conducted according to the Declaration of Helsinki (Hong Kong Amendment) and Good Clinical Practice (European) guidelines. Data are presented as mean (SD) unless otherwise specified. The distribution of variables was assessed by the Shapiro-Wilks’ test and between group comparisons performed using Student’s t or Mann-Whitney U tests, as appropriate. Comparisons between pre- and post-AAC variables were performed by repeated measures analysis of variance (ANOVA) using the variable healthy volunteers versus patients as a “group” factor. Log-transformed average sleep EEG power spectra were analyzed with linear mixed model ANOVA. The factors group (patients versus healthy volunteers) and condition (AAC versus baseline), as well as their interaction, were tested.

2E). These changes were frequent at 50 weeks but were Selleckchem Adriamycin rare in younger mice. To determine whether altered expression of mitochondria-shaping proteins could account for the morphological changes, the expressions of optic atrophy 1 (Opa1), mitofusins (Mfn1 and 2), and the cytosolic dynamin-related protein 1 (Drp1) and its receptor on the outer mitochondrial membrane, Fis1, were compared. The expression of fusion protein Opa1 was 1.5-fold higher in Hint2−/− mice than in Hint2+/+ mice, whereas Mfn1 and Mfn2 were not different. Fis1 and Drp1 were slightly lower in Hint2−/− mice

(Supporting Fig. 2A,B). To determine whether the accumulation of lipids was related to defective mitochondrial β-oxidation of fatty acids, the activities of CPT1 and CPT2 and of medium- or short-chain hydroxyacyl-CoA dehydrogenase (Hadhsc), which catalyzes the NAD+-dependent dehydrogenation of 3-hydroxyacyl-CoA in the mitochondrial matrix, were measured. The activity of Hadhsc was decreased by 68% in Hint2−/− mice compared with Hint2+/+ mice (Fig. 3A) without a change in expression of the enzyme (Fig. 3B). The activity of CPT did not change (Supporting Fig. 7A). In plasma, free fatty acid concentrations were not different, triglyceride concentrations were

lower in Hint2−/− mice only at 30 weeks, and total cholesterol was slightly higher in Hint2−/− mice (Table 1). Because the Hadhsc enzyme can bind to glutamate dehydrogenase (GDH) in the mitochondrial matrix, which is a potential point of regulation for both enzymes, Lenvatinib mw the activity of 上海皓元 GDH was also measured. GDH activity was decreased by 60% in Hint2−/− livers, with no change in GDH expression (Fig. 3C,D). To determine whether the protein-protein interaction of Hadhsc and GDH was disturbed by the absence of Hint2, the co-immunoprecipitation of GDH and Hadhsc was tested. Co-immunoprecipitation

was successful in Hint2+/+ and Hint2−/− mitochondria (Fig. 3E,F). Because the nonfasting interprandial insulin concentrations were two-fold higher in Hint2−/− than in Hint2+/+ mice (Table 1), a glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed and insulin signaling was examined. The GTT yielded higher glucose values in Hint2−/− than in Hint2+/+ mice (area under the curve, 1,378 ± 312 versus 1,021 ± 281 mmol/L × 120 minutes, respectively; P = 0.09) (Fig. 4A). However, random interprandial blood glucose (Table 1) and fasting blood glucose were not different in Hint2−/− versus Hint2+/+ mice (Fig. 4A,C). The phosphorylation of the threonine-serine kinase, Akt, and the expression of downstream targets were measured in liver homogenates, muscle, and white adipose tissue (WAT) of fasted mice after insulin stimulation (Fig. 4B). Insulin induced phosphorylation of Akt at Ser473 and Thr308 in all tissues (Fig. 4B, Supporting Fig. 3A).