Methods: The parent project recruited healthy women for a ran

\n\nMethods: The parent project recruited healthy women for a randomized, double-blind, clinical trial designed to examine the effect of soy isoflavones on bone. At baseline (n=122), we measured three antioxidant enzymes, iron

status indices (serum ferritin among others), oxidative stress indices (oxidized low-density lipoprotein [oxLDL], urinary isoprostanes [PGF(2 alpha)], protein carbonyls, DNA damage), and waist, hip, and thigh fat mass using dual-energy x-ray absorptiometry (DXA). We calculated insulin resistance using the homeostasis model assessment (HOMA). Multiple regression analysis was used to determine the CVD risk factors that contributed to oxidative stress and centralized fat mass (waist+hip=thigh AndGynFM ratio).\n\nResults: Almost 14% (p<0.0005) of the variability in oxLDL was accounted for by AndGynFM ratio (6.1%, p<0.0005), age Danusertib (4.0%, p=0.012), and serum iron (2.8%, p=0.053). Similarly, 16% (p<0.0001) of the variability in PGF2a was accounted for by the AndGynFM ratio (4.8%, p=0.011), HOMA (3.9%, p=0.021), and serum iron (2.7%, p=0.054). We accounted for 33% (p <= 0.0001) of the variability in AndGynFM ratio by high-density lipoprotein cholesterol

(HDL-C) Selleckchem LY2090314 (4.3%, p=0.008), ferritin (4.9%, p=0.005), HOMA (4.5%, p=0.006), oxLDL (2.6%, p=0.04), and PGF(2 alpha) (3.0%, p=0.025).\n\nConclusions: Our study suggests that reducing centralized fat mass and maintaining a favorable lipid profile, antioxidant status, and iron status all may be important in protecting postmenopausal women from atherosclerotic CVD.”
“AIM: To investigate

the frequency of idiopathic phacodonesis (IP) in senile cataract subjects and the short-term clinical outcomes following cataract surgery.\n\nMETHODS: This institutional case-control study learn more included 1301 consecutive low-income cataract subjects from June to November 2009. Anterior segment were carefully evaluated with dilated pupil under slit-lamp. IP were screened and graded by a criteria set by the authors. Risk factors, surgical outcomes, and operative complications were analyzed.\n\nRESULTS:A total of 42 subjects (3.2%) with IP were diagnosed and classified as grade 1 (36 subjects), grade 2 (5 subjects) and grade 3 (1 subject). Harder lenses and intumescent cataracts were observed in the IP group than the control group (P <0.05). Logistics regression test also indicated the main risk factor was the hardness of the lens. The incidence of zonular dialysis during surgery was 23.8% (10 eyes), which was significantly higher than the controls (0.7%, ( P<0.001). Visual outcomes of the two groups were not statistically or clinically significant.\n\nCONCLUSION: Hard nucleus and intumescent cataract are related to IP in senile cataract subjects in Qinghai, China. With more care being taken, grade 1 and some of the grade 2 IP subjects achieved similar surgical outcomes as compared to controls.

Multilevel selection significantly reduced mortality (6 6% K vs

Multilevel selection significantly reduced mortality (6.6% K vs. 8.5% R) and increased weight (1.30 g/MG K vs. 0.13 g/MG R) resulting in response an order of magnitude greater with Kin than Random. Thus, multilevel selection was effective in reducing detrimental social interactions,

which contributed to improved weight gain. The observed rates of response did not differ significantly from expected, demonstrating that current theory is adequate to explain multilevel selection response. Based on estimated genetic parameters, group selection would always be superior to any other combination of multilevel selection. Further, near optimal results could be attained using multilevel selection if 20% of the weight was on the group component regardless

of group composition. Thus, in nature the conditions Savolitinib in vitro for multilevel selection to be effective NVP-BKM120 in bringing about social change maybe common. In terms of a sustainability of breeding programs, multilevel selection is easy to implement and is expected to give near optimal responses with reduced rates of inbreeding as compared to group selection, the only requirement is that animals be housed in kin groups.”
“Chiral ligand-exchange enantioseparation of aliphatic and aromatic amino acids was successfully performed using a new open-tubular zwitterionic column with tentacle-type polymer stationary phase. The polymeric stationary phase was prepared using 3-chloro-2-hydroxypropyl methacrylate (HPMA-Cl), a new reactive monomer. The preparation procedure of the open-tubular column included silanization, in situ graft polymerization with HPMA-Cl, and L-histidine (L-His) modification. L-His was used as a chiral ligand-exchange selector and copper(II) as a central ion. Successful enantioseparation of six pairs of amino acid enantiomers was achieved with a buffer of 5 mM CuSO4, 20 mM (NH4)(2)SO4 at pH 3.0. (C) 2013 Elsevier Inc. All rights reserved.”
“The cDNAs of six manganese-dependent peroxidases (MnPs) were isolated from white-rot

fungus Polyporus brumalis. The MnP proteins shared similar properties with each other in terms of size (approximately 360-365 amino acids) and primary structure, showing 62-96 % amino acid sequence identity. RT-PCR analysis indicated that these six genes were find more predominantly expressed in shallow stationary culture (SSC) in a liquid medium. Gene expression was induced by treatment with dibutyl phthalate (DBP) and wood chips. Expression of pbmnp4 was strongly induced by both treatments, whereas that of pbmnp5 was induced only by DBP, while pbmnp6 was induced by wood chips only. Then, we overexpressed pbmnp4 in P. brumalis under the control of the GPD promoter. Overexpression of pbmnp4 effectively increased MnP activity; the transformant that had the highest MnP activity also demonstrated the most effective decolorization of Remazol Brilliant Blue R dye.

The prognostic value of LAMP3 in breast cancer was investigated

The prognostic value of LAMP3 in breast cancer was investigated. METHODS: Expression levels of LAMP3 in breast cancer cell lines and patient tissues were determined by real-time polymerase chain reaction and in a tissue microarray by immunohistochemistry. lmmunofluorescent staining was used to evaluate the distribution of LAMP3 in tumor xenografts relative to pimonidazole. Kaplan-Meier analysis as

well as multivariate Cox regression survival analyses were performed. RESULTS: LAMP3 was variably expressed in breast cancer cell lines and induced in an oxygen AS1842856 concentration-dependent manner. LAMP3 protein expression colocalized with hypoxic areas in breast cancer xenografts. LAMP3 mRNA was higher in breast tumors from patients with node-positive (P = .019) and/or steroid hormone receptor-negative tumors (P < .001). Breast cancer patients with high LAMP3 mRNA levels had more locoregional recurrences (P = .032 log-rank). This was limited to patients treated with lumpectomy and radiotherapy as primary treatment (n = 53, P = .009). No association with metastasis-free buy Volasertib survival was found. In multivariate Cox regression analysis, LAMP3 remained as a statistically independent prognostic factor for locoregional recurrence (hazard

ratio, 2.76; 95% confidence interval, 1.01-7.5; P = .048) after correction for menopausal status, histologic grade, tumor size, nodal status, therapy, and steroid hormone receptor status. LAMP3 protein in breast cancer tissue proved also to be of prognostic relevance. CONCLUSIONS: Evidence was provided for an association of LAMP3 with tumor cell hypoxia in breast cancer xenografts. In HKI-272 chemical structure the current breast cancer cohorts, LAMP3 had independent prognostic value. Cancer 2011;117:3670-81. (C) 2011 American Cancer Society.”
“Metastasis is the major cause of death for cancer patients with solid tumours, due mainly to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of metastasis

is therefore essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies. Metastasis is an inefficient process, such that very few cells that leave a tumour successfully form macrometastases in distant sites. This suggests that only a small subset of cells can successfully navigate the metastatic cascade and eventually re-initiate tumour growth to form life-threatening metastases. Recently, there has been growing support for the cancer stem cell (CSC) hypothesis which stipulates that primary tumours are initiated and maintained by a small subpopulation of cancer cells that possess “stem-like” characteristics.


“Background: Human protein kinase CK2 represents a novel t


“Background: Human protein kinase CK2 represents a novel therapeutic target for neoplastic diseases. Inhibitors are in need to explore the druggability and the therapeutic options of this enzyme. A bottleneck in the search for new inhibitors is the availability of the target for testing. Therefore an assay was developed to provide easy access to CK2 for discovery of novel inhibitors. Results: Autodisplay was used to present human CK2 on the surface of Escherichia coli. Heterotetrameric CK2 consists of two subunits, alpha and beta, which were displayed individually

on the surface. Co-display of CK2 alpha and CK2 beta on the cell buy Stattic surface led to the formation of functional holoenzyme, as demonstrated by NaCl dependency of enzymatic activity, which differs from that of the catalytic subunit CK2 alpha without beta. In addition interaction of CK2 alpha and CK2 LY2606368 inhibitor beta at the cell surface was confirmed by co-immunoprecipitation assays. Surface displayed CK2 holoenzyme enabled an easy IC50 value determination. The IC50 values for the known CK2 inhibitors TBB and Silmitasertib were determined to be 50 and 3.3 nM, respectively. Conclusion: Surface-displayed CK2 alpha and CK2 beta assembled on the cell surface of E. coli to an active tetrameric holoenzyme. The whole-cell CK2 autodisplay assay as developed is suitable for

inhibition studies. Furthermore, it can be used to determine quantitative CK2 inhibition data such as IC50 values.

In summary, www.selleckchem.com/products/OSI-906.html this is the first report on the functional surface display of a heterotetrameric enzyme on E. coli.”
“Background: Each year, over 75,000 pregnant women in the United States undergo anesthesia care. The authors set out to assess the effects of the anesthetic sevoflurane on neurotoxicity in pregnant mice and on learning and memory in fetal and offspring mice.\n\nMethods: Pregnant mice (gestational day 14) and mouse primary neurons were treated with 2.5% sevoflurane for 2 h and 4.1% sevoflurane for 6 h, respectively. Brain tissues of both fetal and offspring mice (P31) and the primary neurons were harvested and subjected to Western blot and immunohistochemistry to assess interleukin-6, the synaptic markers postsynaptic density-95 and synaptophysin, and caspase-3 levels. Separately, learning and memory function in the offspring mice was determined in the Morris water maze.\n\nResults: Sevoflurane anesthesia in pregnant mice induced caspase-3 activation, increased interleukin-6 levels (256 +/- 50.98% [ mean +/- SD] vs. 100 +/- 54.12%, P = 0.026), and reduced postsynaptic density-95 (61 +/- 13.53% vs. 100 +/- 10.08%, P = 0.036) and synaptophysin levels in fetal and offspring mice. The sevoflurane anesthesia impaired learning and memory in offspring mice at P31.

Two observers independently assessed the angles, and distances fr

Two observers independently assessed the angles, and distances from sigmoid sinus to bony external meatus. Mastoid size was assessed by two independent techniques: area of pneumatization on Law lateral radiographs; distance from EGFR inhibitor sigmoid to bony external meatus.\n\nResults: Auditory tube angles did not correlate with mastoid size. Variations in auditory tube angles and distances from sigmoid sinus to bony meatus were found in adjacent CT slices.\n\nConclusions: These data do not support the idea that the eustachian bony lumen and external auditory canal meet more nearly straight in ears with evidence of childhood otitis

media.”
“Introduction: One third of the world population is affected by latent tuberculosis, with 9.4 million new cases; medical students have 2 to 50 times the probability of acquiring the infection. Objectives: Establish the baseline prevalence of positive tuberculin skin test (TST) at the beginning of medical studies and determine

the incidence and variables associated with TST conversion in medical students. Materials and Methods: Secondary analysis of a historical cohort (2007-2010) of medical students in a private Peruvian university. The TST conversion was evaluated. A binomial regression analysis was applied for each associated variable. Results: 707 medical students were included, of whom 219 (31%) were male. The basal prevalence of reactive TST was 14.4%. Significant associations were found check details with the year of university entry of 2007-08 (p = 0.007) and a history of tuberculosis (p = 0.02). With a total of 822 person-years, the incidence of conversion was 2.92 cases per 100 person-years (CI95%: 1.96-4.36). The TST conversion was associated with the year of university entry (RR = 2,55; IC95%: 1,06-6,30) and a body mass index >= 25

kg/m(2) (RR = 0,16; IC95%: 0,01-0,97). No association was detected with gender, tobacco or alcohol use. Conclusions: There is evidence of Nepicastat in vitro a high basal prevalence of latent tuberculosis infection in medical students. The incidence rate is within expected values and high in comparison with the general population. People with BMI >= 25 kg/m(2) have protection against a latent infection. In medical students, more attention should be paid to biosecurity.”
“For visual signaling to be effective, animal signals must be detected and discriminated by receivers, often against complex visual backgrounds with varying light levels. Accordingly, in many species, conspicuous visual displays and ornaments have evolved as a means to enhance background contrast and thereby increase the detection and discrimination of male courtship signals by females. Using video playbacks, we tested the hypothesis that visual courtship displays and leg decorations of male Schizocosa ocreata wolf spiders are more conspicuous against complex leaf-litter backgrounds.

All 4 patients with genotype 2 or 3 reached SVR, as compared with

All 4 patients with genotype 2 or 3 reached SVR, as compared with 33% of patients with genotype 1 or 4 (P=0.03). A 48-week course of pegylated IFN-alpha(2a)/ribavirin therapy is effective in patients with recurrent HCV infection after LT.”
“The biliary click here tract is a very rare site for the occurrence of extrapulmonary small cell carcinoma. A 68-year-old Japanese female was being followed up for autoimmune hepatitis, and was referred to our hospital because segmental intrahepatic bile duct dilation was found on routine imaging studies, suggesting intrahepatic cholangiocarcinoma. She underwent

left lobectomy of the liver and concomitant resection of the caudate lobe. Microscopic examination of the explanted liver showed a primary composite tumor comprising small cell and mucinous carcinomas that originated in the intrahepatic bile duct. Further immunohistochemical studies, including cytokeratin-19 and chromogranin-A staining, showed the

two cellular components of the tumor to have similar characteristics. The amphicrine properties indicated that the tumor had a monoclonal origin but with biphenotypic differentiation, which was responsible for the histogenesis of this tumor.”
“Mixed matrix blends containing polyimide (PI) and polyhedral oligomeric silsesquioxanes (POSS) are studied with atomistic molecular dynamics simulation. To examine the effect of functional mTOR target group, two types of DOSS are considered, either octahydrido silsesquioxane (OHS) or octaaminophenyl silsesquioxane (OAPs). The glass transition temperature of the model PI-OAFS blends increases with the incorporation of GAPS, an observation consistent with recent experiments on these systems. Selleckchem SB273005 A decrease in glass transition temperature is shown for the model PI-OHS blends. Radial

distribution functions for both blends are presented to show how packing between the inorganic (POSS) and organic (PI) species in the mixed matrix varies as a function of POSS loading and POSS functionalization. In addition, we report the mobility of the PI chains and POSS molecules in the material by calculating the mean square displacement. These results provide molecular insight about thermal property enhancements afforded by POSS-based additives. (c) 2009 Elsevier Ltd. All rights reserved.”
“Emergent operation after renal transplantation (RT) has traditionally been associated with substantial morbidity and mortality. We reviewed 2340 adult patients who underwent RT at our tertiary care center and identified 55 patients who required acute care surgical consultation within 1 year of transplantation. Of these, 43 were treated operatively and 12 nonoperatively. Primary diagnoses were intestinal problems in 29 patients (53%), including diverticulitis, ischemia, perforation, obstruction, and bleeding; cholecystitis in 10 (18%); fluid collections in six (11%), appendicitis and hernias in two each (4%); gastritis in one (2%); and no diagnosis in five (9%).

The single-port approach was abandoned in four (3 7%) patients wi

The single-port approach was abandoned in four (3.7%) patients with severe pelvic adhesion-an additional port was opened for extensive adhesiolysis. None of the patients with a voluminous uterus needed an additional port. There were no major intraoperative or postoperative complications. Conclusion: The single-port approach using straight, conventional laparoscopic instruments was feasible and safe in the majority of the patients undergoing hysterectomy, Staurosporine mw and was found to be accessible even in cases with a large uterus. The patients benefitted from this approach and had less abdominal wounds.

However, patients with a voluminous uterus tended to have more intraoperative blood loss, and in some cases

with severe adhesions, additional port(s) were required selleck for surgical effectiveness. Copyright (C) 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.”
“Purpose: To investigate the distribution profile of hen egg lysozyme (HEL) through poly-2-hydroxyethyl methacrylate (pHEMA)-based lens materials and silicone hydrogel (SH) lens materials using confocal laser scanning microscopy (CLSM). Methods: Five silicone SH materials (balafilcon A, lotrafilcon A, lotrafilcon B, galyfilcon A, senofilcon A) and four pHEMA-based materials (alphafilcon A, etafilcon A, omafilcon A, vifilcon A) were incubated in 1.9 mg/ml protein solution for 24 hours. The protein solution consisted of HEL, which was conjugated with either fluorescein isothiocyanate (FITC) or lucifer yellow VS dilithium salt (LY). CLSM (Zeiss LSM 510 META) identified the location of the fluorescently labeled protein by using 1 mu m depth scans through the lens. In a second experiment, lenses were incubated with 2% (125)I labeled HEL to determine the amount of deposited

protein on each lens. Both techniques were combined to describe the individual HEL profiles. Results: After the incubation in fluorescently labeled HEL, all pHEMA-based materials and the SH material balafilcon A accumulated protein throughout the entire lens material, while, for the SH lenses lotrafilcon A and lotrafilcon B, HEL Selleck AZD8931 was primarily detected on the lens surface alone. Differences in protein uptake pattern due solely to the two conjugated dyes were most apparent for the SH materials galyfilcon A and senofilcon A; HEL was detected throughout these lenses when conjugated with LY but accumulated primarily on the surface when conjugated with FITC. Conclusion: CLSM in combination with a radiolabel technique can describe both the location and degree of protein deposition on different contact lens materials.”
“The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5 mg/L.


“Reactive oxygen


“Reactive oxygen Small molecule library clinical trial species and their detrimental effects on the brain after transient ischemia/reperfusion (I/R) have been implicated in the pathogenesis of ischemic reperfusion

injury. Thioredoxin-1 (Trx-1) is an endogenous antioxidant protein that has neuroprotective effects. We hypothesized that Trx-1 plays a crucial role in regulating cerebral I/R injury. To be able to test this, 190 Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (tMCAO) with Trx-1 siRNA (small interference RNA) injected 24 h prior to ischemia. At 24 h after tMCAO, we measured neurological deficits, infarct volume, and brain water content, and found that neurological dysfunction, brain infarct size, and brain edema were worse in the Trx-1 siRNA group than in the control group. Oxidative stress was evaluated by measuring superoxide dismutase activity and malondialdehyde level. The levels of Trx-1 and its cofactor, peroxiredoxin (Prdx), were significantly decreased after Trx-1 down-regulated. However, there is no significant difference in the Prdx mRNA level after administration of Trx-1 siRNA. In contrast, Prdx-SO3 protein levels were significantly increased in the Trx-1 siRNA group. We also investigated the

specific role of nuclear factor erythroid 2-related factor 2 (Nrf2) in Trx-1 induction by knocking down Nrf2. Nrf2 siRNA injection decreased Trx-1 Cyclopamine in vivo mRNA and protein expression. Our results suggest that the exacerbation of brain damage was associated with enhanced cerebral peroxidation in brain tissues. Moreover, selleck chemical these results revealed that Trx-1, which is more likely regulated by Nrf2, exerts a neuroprotective role probably through maintaining the reduction activity of Prdx1-4. (C) 2014 Published by Elsevier Ltd. on behalf of IBRO.”
“The central importance of chorismate enzymes in bacteria, fungi, parasites, and plants combined with their absence in mammals makes them attractive

targets for antimicrobials and herbicides. Two of these enzymes, anthranilate synthase (AS) and aminodeoxychorismate synthase (ADCS), are structurally and mechanistically similar. The first catalytic step, amination at C2, is common between them, but AS additionally catalyzes pyruvate elimination, aromatizing the aminated intermediate to anthranilate. Despite prior attempts, the conversion of a pyruvate elimination-deficient enzyme into an elimination-proficient one has not been reported. Janus, a bioinformatics method for predicting mutations required to functionally interconvert homologous enzymes, was employed to predict mutations to convert ADCS into AS. A genetic selection on a library of Janus-predicted mutations was performed. Complementation of an AS-deficient strain of Escherichia coli grown on minimal medium led to several ADCS mutants that allow growth in 6 days compared to 2 days for wild-type AS.

In previous work, pull-off tests were performed on epoxy from cle

In previous work, pull-off tests were performed on epoxy from clear silicone coatings with a thickness gradient on glass substrates. The presence of a thickness gradient introduced a third type of release behavior-fingering. Also present was a mixed mode of release involving void formation or fingering with

peeling. For the MX69 in vivo shear tests described in this study, release of the epoxy from the silicone initiated at the point of load application then proceeded around the circumference of the stud regardless of the direction of the applied force. The final release from the coating started predominately from the thin section of the coating and proceeded to the thick section, again for both loading directions. (C) 2011 Elsevier B.V. All rights reserved.”
“Severe traumatic brain injury (TBI) in adults is associated with abnormalities in arousal and emotional responsivity, which are observed physiologically, behaviourally and via self-report measures. While an accurate measure of physiological arousal is debated, Barry et al. (2005, 2007, 2008) have consistently shown an inverse relationship between skin conductance level (SCL), and mean alpha power (alpha) during an eyes-closed resting condition (EC),

accompanied by an increase in SCL and corresponding decrease in alpha during eyes-open (EO). Thus, alpha may provide a novel index of autonomic arousal. This study Pevonedistat ic50 aimed to elucidate the neural and autonomic correlates of arousal disturbances in TBI.\n\nParticipants were 17 adults with TBI (13 males; mean age 46.50) and 22 matched controls (14 males; mean age 41.25). Mean alpha and SCL were recorded across two 2 minute conditions (EC and EO). Paralleling previous research (e.g., Barry et al., 2007), a significant decrease in alpha was

found from EC to EO for the sample overall, but this was significantly reduced in TBI participants. Further, TBI participants showed diminished regional differences compared to controls. Lower SCLs across EC-EO were also found in TBI participants compared to controls’. Contrasting expectations, an increase in SCL from EC to EC) was not found. This study showed that examining simple alpha changes provides insight into TBI-related arousal disturbances. CCI-779 price Importantly, our findings accord with the nature of TBI, which involves global and region-specific damage. (C) 2013 Elsevier B.V. All rights reserved.”
“Objective: Uterine serous papillary carcinoma (USPC) is an aggressive variant of endometrial cancer characterized by an innate resistance to chemotherapy and poor prognosis. In this study, we evaluated the expression of alpha V-integrins in primary USPC cell lines and the in vitro ability of intetumumab (CNTO 95), a fully human monoclonal antibody against alpha V-integrins, to inhibit USPC cell adhesion and migration.

Furthermore,

inhibiting proteasome activity tends to incr

Furthermore,

inhibiting proteasome activity tends to increase the expression of genes induced during the Environmental Stress Response more than those in the rest of the genome. Our combined results suggest that proteasome-mediated proteolysis of potentially toxic transcription factors tightly modulates the stress response in yeast.”
“The purpose of the current study is to examine the moderating influence of the catechol 0 methyltransferase gene (COMT) on the maternal prenatal smoking/offspring externalizing disorder relationship. The sample consisted of 430 young adults born between 1981 and 1984 at the Mater Misericordiae Mother’s Hospital in Brisbane, Australia, as well as their mothers and peers. Mothers reported their prenatal smoking status during pregnancy, and genetic data was obtained from the youth at a later follow-up in adulthood. The outcome measures in this study were mother and teacher PLX4032 research buy reports of youth attention problems and aggression at age 15, and youth, mother and peer reports of youth attention problems and aggression at age 20 (combined to create latent factors of attention problems and aggression at each age). The COMTVal108/158Met polymorphism (rs4680) significantly interacted with maternal cigarette ERK inhibition smoking during pregnancy to predict youth aggressive behavior

at ages 15 and 20. This gene-environment interaction was not significant for youth attention problems. (C) 2011 Elsevier B.V. All rights reserved.”
“In the auditory midbrain, synaptic mechanisms responsible for the precise temporal coding of inputs in the brainstem are PXD101 mouse absent. Instead, in the inferior colliculus (IC), the diverse temporal firing patterns must be coded by other synaptic mechanisms, about which little is known. Here, we demonstrate the temporal characteristics of sound-evoked excitatory and inhibitory postsynaptic currents (seEPSCs and seIPSCs, respectively) in vivo in response to long-duration tones. The seEPSCs and seIPSCs

differ in the variability of their temporal properties. The seEPSCs have either early or late current peaks, and the early-peaked currents may be either transient or sustained varieties. The seIPSCs have only early-peaked sustained responses but often have offset responses. When measured in a single neuron, the seIPSC peaks usually follow early, transient seEPSCs, but the seIPSCs precede latest-peaking seEPSCs. A model of the firing produced by the integration of asymmetric seEPSCs and seIPSCs showed that the temporal pattern of the early-peaked sustained neurons was easily modified by changing the parameters of the seIPSC. These results suggest that the considerable variability in the peak time and duration of the seEPSCs shapes the overall time course of firing and often precedes or follows the less variable seIPSC.