Although the translation of these findings to human is limited by

Although the translation of these findings to human is limited by the small study size and species differences,

these results from animals chronically exposed to up to 150 times the clinical UPA exposure are considered significant and supportive to the chronic administration of UPA for more than 3 months in women of reproductive age. (C) 2013 Elsevier Inc. All rights reserved.”
“Glucose oxidase (beta-D-glucose:oxygen 1-oxidoreductase; EC is used in the food and beverage industry as a preservative and stabilizer and is commonly derived from the fungus Aspergillus niger. Although the safety of glucose oxidase preparations from A. niger is well-established, LY3023414 the use of preparations derived from other fungal species is of interest; however,

an assessment of their safety is warranted. Here, we report on the safety of a glucose oxidase preparation derived from the fungus Penicilliurn chrysogenum (designated as PGO) for commercial use in food processing, as well as an ingredient in food. In a repeated dose 90-day oral toxicity study conducted in rats, PGO was without compound-related adverse effects at doses of up to 15,600 U/kg body weight/day, equivalent to 193 mg total organic solids/kg body weight/day. In addition, PGO was non-genotoxic in a series of genotoxicity tests, including a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and a combined in vivo mammalian erythrocyte micronucleus test and comet assay. The results of these studies support the safe use of PGO in food for human consumption. (C) 2013 Elsevier Inc. All rights reserved.”
“Styrene (S) is lung tumorigenic in mice but not in rats. Methisazone S and its alkene-oxidized metabolite styrene oxide (SO) were not lung toxic in CYP2F2(-/-) [knockout] mice,

indicating S-induced mouse lung tumors are mediated through mouse-specific CYP2F2-generated ring-oxidized metabolite(s) in lung bronchioles. The human relevance of the CYP2F MOA was assessed by insertion of a human CYP2F1, 2A13, 2B6 transgene into CYP2F2(-/-) mice; CYP2F1 expression and activity were confirmed in the transgenic (TG) mice. No evidence of cytotoxicity or increased cell proliferation (BrdU labeling) was seen in TG mice treated with either S or SO (200 mg/kg/day ip for 5 days). In contrast to S and SO, 4HS (105 mg/kg/day ip for 5 days) increased BrdU labeling 5-10-fold in WT mice, <3-fold increase in KO mice and 2-4-fold in TG mice. The limited response of 4HS in KO and TG mice may result from intrinsic toxicity or from further metabolism; regardless of the MOA, these findings indicate that the CYP2F-mediated tumorigenic MOA in WT mice is not operative for S, SO, or for 4HS putatively derived from metabolism of S by CYP2F1 in humans, and thus S-induced mouse lung tumors are unlikely to be relevant to human risk. (C) 2013 Published by Elsevier Inc.

We identified cross-reactive antibodies from A/Brisbane/59/2007 s

We identified cross-reactive antibodies from A/Brisbane/59/2007 sera that recognize non-HA epitopes in pdmH1N1 virus. Passive serum transfer showed that cross-reactive sH1N1-induced antibodies conferred protection in naive recipient mice during pdmH1N1 virus challenge. The presence or absence of anti-HA antibodies, therefore, is not the sole indicator of the effectiveness of protective cross-reactive antibody immunity. Measurement of additional antibody repertoires targeting Cytoskeletal Signaling inhibitor the non-HA antigens of influenza virus should be taken into consideration in assessing

protection and immunization strategies. We propose that preexisting cross-protective non-HA antibody immunity AZD1480 ic50 may have had an overall protective effect during the 2009 pdmH1N1 outbreak, thereby reducing disease severity in human infections.”
“Much research shows that early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal

manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational

memory also depended upon timing of manipulation. Enhanced Immune system performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. (C) 2012 Elsevier Ltd. All rights reserved.”
“The Step Trial showed that the MRKAd5 HIV-1 subtype B Gag/Pol/Nef vaccine did not protect men from HIV infection or reduce setpoint plasma viral RNA (vRNA) levels but, unexpectedly, it did modestly enhance susceptibility to HIV infection in adenovirus types (Ad5)-seropositive, uncircumcised men. As part of the process to understand the results of the Step Trial, we designed a study to determine whether rhesus macaques chronically infected with a host-range mutant Ad5 (Ad5hr) and then immunized with a replication defective Ad5 SIVmac239 Gag/Pol/Nef vaccine were more resistant or susceptible to SIV infection than unimmunized rhesus macaques challenged with a series of escalating dose penile exposures to SIVmac 251.

The primary end point was overall survival Secondary end points

The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals.


Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone

recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy Protein Tyrosine Kinase inhibitor group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P = 0.24).


Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival.

Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials. gov number, NCT00003653.)”
“Extracellular signal-regulated protein kinase (ERK1/2) is a member of the mitogen-activated protein kinase (MAPK) signaling pathway and a key molecular target for ethanol (EtOH) and other drugs of abuse.

The aim of the study was to assess the role of two MAPK pathways, ERK1/2 and c-Jun N-terminal kinase (JNK), on the modulation of EtOH and sucrose self-administration.

C57BL/6J mice were trained to lever press on a fixed-ratio 4 schedule with 9% EtOH/2% sucrose, or 2% sucrose, as the reinforcer. In experiments 1 and 2, mice were injected with the MEK1/2 inhibitor SL 327 (0-100 mg/kg) and the JNK inhibitor AS 6012452 Gemcitabine molecular weight (0-56 mg/kg) prior to self-administration.

In experiment 3, SL 327 (0-100 mg/kg) was administered prior to performance on a progressive ratio (PR) schedule of EtOH reinforcement. In experiment 4, SL 327 and AS 601245 were injected 2 h before a locomotor test.

SL 327 (30 mg/kg) significantly increased EtOH self-administration without affecting locomotion. Higher doses of SL 327 and AS 601245 reduced EtOH-reinforced responding and locomotor activity. Reductions of both ligands on sucrose self-administration were due to decreases in motor activity. SL 327 pretreatment had no effect on PR responding.

ERK1/2 activity is more directly involved in modulating the reinforcing properties of EtOH than JNK activity due to its selective potentiation of EtOH-reinforced responding.

Here, Hsp90 overexpression restored

Here, Hsp90 overexpression restored Selleck Rapamycin IKK1 levels in MC160- expressing cells, suggesting that MC160 competitively interacted with Hsp90. In support of this, further investigation showed

that a mutant MC160 protein comprising only the C-terminal region (C protein) immunoprecipitated with Hsp90. In contrast, Hsp90 IP with a mutant MC160 protein consisting of only the N-terminal tandem death effector domains (DEDs) (N protein) was dramatically decreased. Since cells expressing either the N or C mutant MC160 protein remained similarly resistant to TNF-alpha-induced NF-kappa B activation, the N mutant protein probably utilized a different mechanism for inhibiting NF-kappa B. One likely mechanism for the N protein lies in its association with the DED-containing procaspase-8 protein, a cellular apoptosis precursor protein that regulates NF-kappa B activation. Here, IPs revealed that this association relied on the presence of

the DED-containing N terminus of the MC160 protein but not the C-terminal portion. These interactions appear Ulixertinib in vitro to have relevance with NF-kappa B activation, since the expression of the viral DEDs strongly inhibited procaspase-8-mediated NF-kappa B activation, an event not substantially altered by the C protein. Thus, the MC160 protein utilizes at least two distinct mechanisms for impeding NF-kappa B activation, association with Hsp90 to result in IKK1 protein degradation or interaction with procaspase-8.”
“The purpose of this study is to compare the variability of PCT results obtained by automatic selection of the arterial input function

(AIF), venous output function (VOF) and symmetry axis versus manual selection.

Imaging data from 30 PCT studies obtained as part of standard clinical stroke care at our institution in patients with suspected acute hemispheric ischemic stroke were retrospectively reviewed. Two observers performed the post-processing of 30 CTP datasets. Each observer processed triclocarban the data twice, the first time employing manual selection of AIF, VOF and symmetry axis, and a second time using automated selection of these same parameters, with the user being allowed to adjust them whenever deemed appropriate. The volumes of infarct core and of total perfusion defect were recorded. The cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and blood-brain barrier permeability (BBBP) values in standardized regions of interest were recorded. Interobserver variability was quantified using the Bland and Altman’s approach.

Automated post-processing yielded lower coefficients of variation for the volume of the infarct core and the volume of the total perfusion defect (15.7% and 5.8%, respectively) compared to manual post-processing (31.0% and 12.2%, respectively). Automated post-processing yielded lower coefficients of variation for PCT values (11.3% for CBV, 9.7% for CBF, and 9.5% for MTT) compared to manual post-processing (23.7% for CBV, 32.8% for CBF, and 16.

After LP lesioning, the velocity of post-saccadic pursuits in the

After LP lesioning, the velocity of post-saccadic pursuits in the ipsiversive and down-ward directions decreased by 20-40% in all three monkeys. These deficits lasted for at least I month, and some recovery was observed. In the amplitudes of catch-up saccades, no consistent changes were seen among the three monkeys after LP lesioning. These results suggest an involvement of LP in the primate smooth pursuit eye movement control. (C) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Purpose: Needle biopsy Gleason scores are often upgraded after

pathological examination of the prostate following radical prostatectomy. 3-MA mw It has been suggested that larger prostates would be associated with a greater risk of upgrading since a smaller percentage of the gland is sampled and, thus, the highest grade disease would more likely be missed, assuming an equal number of cores is taken from similar locations. We examined the likelihood of clinically relevant upgrading after radical prostatectomy as a function of transrectal ultrasound volume.

Materials and Methods: We examined the association between transrectal ultrasound volume and upgrading (higher Gleason score category in the radical prostatectomy specimen than

in the biopsy) in 586 men treated with radical prostatectomy between 1995 and 2006 in the SEARCH database who underwent at least a sextant biopsy using multivariate logistic regression. Transrectal ultrasound volume was categorized as 20 or less (in 71), Anacetrapib 21 to 40 (in 334), 41 to 60 (in 123) and greater than 60 cm(3) (in 58). Gleason score was examined as a categorical variable of 2-6, 3 + 4 and 4 + 3 or greater.

Results: Overall 138 cases (24%) were upgraded, 80 (14%) were downgraded, and 368 (62%) had identical biopsy and pathological Gleason sum groups. Larger transrectal ultrasound volume was significantly associated with decreased likelihood of upgrading (p trend < 0.001). For transrectal ultrasound volumes greater than 60, 41 to 60, 21 to 40 and 20 cm(3) or less, the estimated multivariate adjusted probability of upgrading was 12.6%, 27.5%, 36.4% and 45.5%

for Gleason 2-6 tumors, and 6.1%, 8.5%, 18.9% and 20.9% for Gleason 3 + 4 tumors, respectively.

Conclusions: Larger transrectal ultrasound volumes were at decreased risk for clinically significant upgrading after radical prostatectomy. This fact should be kept in mind when deciding on treatment decisions for men with apparently low grade prostate cancer on biopsy.”
“To study the effect of adrenal steroids on neuropeptide Y (NPY) synthesis in the hypothalamic-pituitary system, we examined NPY expression in rats treated with dexamethasone (a synthetic glucocorticoid) by in situ hybridization and immunohistochemistry. Rats were injected daily with dexamethasone (0.2 mg/100 g/day for 10 days, sc) or sesame oil (vehicle control), or non-injected (intact control).

25, 0 5 and 0 75 mg/day groups was -12 3, -12 5 and -11 8, respec

25, 0.5 and 0.75 mg/day groups was -12.3, -12.5 and -11.8, respectively. The proportion Selleck 4SC-202 of IRLS responders at week 2, when all patients were receiving pramipexole at a dose of 0.25 mg/day, was 34.0-37.7%. At 6 weeks, when the patients were on 0.25, 0.5 or 0.75 mg/day, IRLS responders defined as those having a >= 50% reduction in IRLS score accounted for 60.4, 58.5 and 49.1%, respectively. Older age above the median value

(>= 55 years) and low IRLS score at baseline (<21.5 points) were significantly associated with early response to low-dose pramipexole therapy. The type and frequency of adverse events were consistent with the known safety profile for dopamine agonists in RLS. Conclusions: Pramipexole at 0.25-0.75 mg/day is efficacious, safe and well tolerated in Japanese patients with primary RLS. Copyright (C) 2010 S. Karger AG, Basel”
“Background. Neopterin, a GTP metabolite expressed by macrophages, is a marker of immune activation. We hypothesize that levels of this serum marker alter with donor age, reflecting increased chronic immune activation in normal Enzalutamide chemical structure aging. In addition to age, we assessed gender, race, body mass index (BMI), and percentage of body fat (%fat) as potential covariates.

Methods. Serum was obtained from 426 healthy participants whose age ranged from 18 to 87 years. Anthropometric measures included %fat and

BMI. Neopterin concentrations were

measured by competitive ELISA. The paired associations between neopterin and age, BMI, or %fat were analyzed by Spearman’s correlation or by linear regression of log-transformed neopterin, whereas overall associations were modeled by multiple regression of log-transformed neopterin as a function of age, gender, race, BMI, %fat, and interaction terms.

Results. Across all participants, neopterin exhibited a positive association with age, BMI, and %fat. Multiple regression Baricitinib modeling of neopterin in women and men as a function of age, BMI, and race revealed that each covariate contributed significantly to neopterin values and that optimal modeling required an interaction term between race and BMI. The covariate %fat was highly correlated with BMI and could be substituted for BMI to yield similar regression coefficients.

Conclusion. The association of age and gender with neopterin levels and their modification by race, BMI, or %fat reflect the biology underlying chronic immune activation and perhaps gender differences in disease incidence, morbidity, and mortality.”
“Frontal asymmetric activation has been proposed to be the underlying mechanism for depression. Some case studies have reported that the enhancement of a relative right frontal alpha activity by an asymmetry neurofeedback training leads to improvement in depressive symptoms.

In response to this need, increased efforts to develop rapid and

In response to this need, increased efforts to develop rapid and reliable diagnostic techniques have been undertaken; a single-step reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay was developed to detect virus in vector mosquitoes (Aedes aegypti) using the Flock House Virus (FHV) as a model. The robustness of the RT-LAMP reaction was revealed by its ability to detect FHV from an “”all-in-one”" template using whole mosquito bodies within 30 min. Furthermore, RT-LAMP identified successfully a mosquito Nutlin-3a order carrying just a single FHV particle, a level easily overlooked in conventional analysis such as plaque forming assays. These observations

suggest that RT-LAMP is more reliable and useful for routine diagnosis of vector mosquitoes in regions where the prevalence of vector-borne diseases such as West Nile fever or dengue fever are common. (c) 2008 Elsevier B.V. All rights reserved.”
“Color processing

begins with the absorption of light by cone photoreceptors, and progresses through a series of hierarchical stages: Retinal signals carrying color information are transmitted through the lateral geniculate nucleus of the thalamus (LGN) tip to the primary visual cortex (V1). Front V1, the signals are processed by the second Visual area (V2); then by cells located in subcompartments (“”globs”") within the posterior inferior temporal (PIT) cortex, a brain region that encompasses area V4 and brain regions immediately anterior to V4. Color signals are then processed by regions deep within the inferior temporal (IT) cortex including area learn more TE. As a heuristic, one can consider each of these stages to be involved in constructing a distinct aspect of the color percept. The three cone types are the basis for trichromacy; retinal ganglion cells that respond in an opponent fashion to activation of different cone classes are the basis for color opponency (these “”cone-opponent”" cells increase their firing rate above baseline to activation of one cone class and decrease AMP deaminase their firing

rate below baseline to activation of a different cone class); double-opponent neurons in the V1 generate local color contrast and are the building blocks for color constancy; glob cells elaborate the perception of hue; and IT integrates color perception in the context of behavior. Finally, though nothing is known, these signals presumably interface with motor programs and emotional centers of the brain to mediate the widely acknowledged emotional salience of color.”
“Modified Vaccinia Virus Ankara (MVA) is employed widely as an experimental and human vaccine vector for its lack of replication in mammalian cells and high expression of heterologous genes. Recombinant MVA technology can be improved greatly by combining transient host-range selection (based on the restoration in MVA of the deleted vaccinia gene K1L) with the differential expression of fluorescent proteins.

A variety of demographic, lesion-related and procedure-related va

A variety of demographic, lesion-related and procedure-related variables were evaluated for potential impact of technical success and patency. The follow-up protocol included clinical assessment, and color and spectral Doppler evaluation of the stented vessel(s).

Results: The clinical presentation was chronic mesenteric ischemia in 12 patients, acute mesenteric vascular syndromes in 10 patients, foregut ischemia/ischemic pancreatitis in three patients, and prior to endovascular repair of aortic aneurysm in one INCB024360 patient. The treated vessel was SMA in 22 procedures, CA in three, and both SMA and CA in one. Technical success was achieved in 23 of the 27 attempted recanalizations (85%). Three patients

who failed the attempt underwent open bypass, and another one underwent retrograde recanalization and stenting of the SMA. Procedure success was only significantly

related to patient age <70 years or procedure performance after the year 2006. Notably, the presence of a stump, ostial plaque, extensive vascular calcification, recanalization IWR-1 purchase route (intraluminal vs subintimal), occlusion length, and vessel diameter had no significant impact on procedure success. Traditional duplex criteria proved unreliable in predicting restenosis. Life table analysis of freedom from symptom recurrence showed a primary and assisted rates of 58% and 80% at 1 year, and 33% and 60% at 2 years, respectively. Clinical recurrences developed in six patients (four presented with abdominal angina and weight loss, two presented with abdominal catastrophe). There were six access-related complications SPTLC1 and no procedural deaths. Four delayed deaths occurred during follow-up (two cardiac causes, two due to abdominal sepsis).

Conclusions: Endovascular recanalization of mesenteric artery occlusion is both feasible and successful, provided careful planning is used. (J Vasc Surg 2012;55:1674-81.)”
“Many studies have investigated hypothalamus-pituitary-adrenal (HPA) axis responses to psychosocial stress in adults. In children, much less is known about HPA axis reactivity, and a sizable number of studies has

not detected a significant cortisol response. Moreover, there is a tack of studies comparing adults’ and children’s responses to identical stressors. The aim of the present study was to modify an existing laboratory stressor to serve as a potent stressor in children and to allow for direct comparison between children’s and adults’ stress responses. Thirty children, ages 9-12 (14 female), and 31 young adults, ages 18-25 (17 female), were exposed to the modified protocol (TSST-M). A significant increase in salivary cortisol was observed in response to the TSST-M, F(2.5, 125.4) = 19.65, p <.001, eta(2) = .28, and overall, no differences were found between children’s and adults’ responses, F(2.5, 125.4) = .31, n.s.


Conclusions: In more than a third of patients wit


Conclusions: In more than a third of patients with posterior urethral valves renal function reserve is completely depleted at presentation. Decreased or absent renal function reserve may be used as an early indicator of long-term renal deterioration.”
“We investigated the relationship between short-latency and long-latency somatosensory-evoked potentials (SEPs) relating to voluntary movement. In general, the amplitudes of short-latency components in SEPs are attenuated during movement,

find more whereas those of long-latency are enhanced, and this phenomenon is termed ‘gating effects’. This study aimed to examine the relationship of changes in amplitude between short-latency and long-latency SEPs. SEPs were recorded from 11 participants at Fz, Cz, Pz, and C4′ by stimulating the left median nerve. Two tasks were conducted; Control and Movement. In Control, the participant was asked to relax with no specific task. In Movement, the participant was encouraged to continue a rapid drumming motion of all fingers of the left hand at a self-paced rate. The amplitudes of short-latency SEPs, the P25 at C4′ and N30 at Fz, were significantly

smaller in the Movement than Control condition. By contrast, the amplitudes of long-latency SEPs, the N140 at Fz, Cz, and Pz were significantly larger in INCB28060 purchase Movement than Control condition. Moreover, a significant positive correlation was observed in the rate of amplitude change between the frontal N30 and vertex N140, indicating that for the participants with a frontal N30 of smaller amplitude during Movement, the amplitude of the vertex N140 was smaller. We inferred that the neural activities in movement-related cortices affected the Celecoxib sources for the frontal N30 and vertex N140 in the same neuronal network simultaneously. NeuroReport 22:1000-1004 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Studies of the salivary cortisol awakening response (CAR) may be confounded by delays between waking in the morning and obtaining the ‘waking’ salivary

sample. We used wrist actigraphy to provide objective information about waking time, and studied the influence of delays in taking the waking sample on the CAR. Eighty-three men and women (mean age 61.30 years) who were referred to hospital with suspected coronary artery disease were studied. Saliva samples were obtained on waking and 15 and 30 min later. The mean interval between waking defined by actigraphy and reported waking time was 6.12 +/- (S.D.) 14.8 min, with 55.4% having no delay. The waking saliva sample was obtained an average 5.78 +/- 15.0 min after self-reported waking, and 12.24 +/- 20.3 min after objective waking. The waking cortisol value was significantly higher in participants who had a delay between waking and sampling > 15 min (mean 14.46 +/- 6.34 nmol/l) than in those with zero (mean 10.45 +/- 6.41 nmol/l) or 1-15 min delays (mean 11.51 +/- 5.99 nmol/l, p = 0.043).

Here, we review recent studies in the monkey that have contribute

Here, we review recent studies in the monkey that have contributed to our understanding of the neuronal implementation of ECFs, with a focus on task-switching paradigms. These paradigms have revealed that ECFs are distributed Selleckchem Elafibranor across both the parietal and frontal lobes.”
“Women with temporal lobe epilepsy have a higher incidence of reproductive disorders, which have been linked to alterations in the pulsatile release of gonadotropin-releasing hormone (GnRH). These experiments tested the hypothesis that the number

of GnRH neurons is reduced in an animal model of temporal lobe epilepsy. The effects of pilocarpine-induced status epilepticus (SE) and the subsequent spontaneous recurrent eizures on the number of GnRH-positive neurons were studied in adult female mice. Systemic injections of pilocarpine were used to induce SE, and diazepam was administered 90 min after the first seizure. Control mice received all drugs except pilocarpine. The mice were euthanized either 1 week or 3 months after SE (i.e. after spontaneous recurrent seizures were Liproxstatin-1 ic50 observed). Even though the estrous cycle was disrupted after SE, and hippocampal damage was detected in both the CA1 and CA3 regions, pilocarpine-treated mice did not show a significant decrease in total or regional numbers

of GnRH-immunopositive neurons. Therefore, these data do not support the hypothesis that a reduction in the number of GnRH neurons is responsible for the disruption of the estrous cycle after pilocarpine-induced epilepsy, which suggests that other mechanisms contribute to Phosphoglycerate kinase female reproductive disorders associated with chronic epilepsy. (C) 2011 IBRO. Published

by Elsevier Ltd. All rights reserved.”
“The liver is the largest organ in the body, with many complex, essential functions, such as metabolism, deintoxication, and secretion, often regulated via post-translational modifications, especially phosphorylation. Thus, the detection of phosphoproteins and phosphorylation sites is important to comprehensively explore human liver biological function. The human Chang liver cell line is among the first derived from non-malignant tissue, and its phosphoproteome profile has never been globally analyzed. To develop the complete phosphoproteome and probe the roles of protein phosphorylation in normal human liver, we adopted a shotgun strategy based on strong cation exchange chromatograph, titanium dioxide and LC-MS/MS to isolate and identify phosphorylated proteins. Two types of MS approach, Q-TOF and IT, were used and compared to identify phosphosites from complex protein mixtures of these cells. A total of 1035 phosphorylation sites and 686 phosphorylated peptides were identified from 607 phosphoproteins. A search using the public database of PhosphoSite showed that approximately 344 phosphoproteins and 760 phosphorylation sites appeared to be novel.