In all three epilepsy models, we found that longer delays and/or higher concentrations of convulsants were necessary to generate spontaneous epileptiform activity in Prnp0/0 mice. These results together indicate an increased seizure threshold in Prnp0/0 mice, suggesting that loss of PrP function cannot explain a predisposition to seizures initiation in CJD. (C) 2011 IBRO. Published by Elsevier learn more Ltd. All rights reserved.”
“Previous research has suggested that older adults’ ability to detect a word as correctly or incorrectly

spelled is intact, relative to younger adults. The purpose of the present experiment was to investigate the stability of misspelling detection processes across older adulthood when misspellings are presented in the context of reading.

Participants included 180 older adults represented equally from three decades: young-old adults in their 60s, middle-old adults in their 70s, and old-old adults in their 80s. They read sentences about health-related topics one word at a time and pressed a key to detect misspellings. A repeated

measures analysis of variance was conducted on misspelling detection accuracy as well as response times for correctly detected misspellings.

There was a consistent age-related find more decline in misspelling detection, where middle-old and old-old adults were less accurate and slower than young-old adults in detecting misspellings.

Requiring misspelling detection during reading increases the working memory demands that are necessary for successful comprehension. In Tanespimycin order resource-demanding contexts, the top-down verification process of confirming a word’s orthographic features becomes more difficult with increasing age.”
“In the early neonatal period activation of GABA(B) receptors attenuates calcium current through N-type calcium channels while enhancing current through L-type calcium channels in rat hippocampal

neurons. The attenuation of N-type calcium current has been previously demonstrated to occur through direct interactions of the beta gamma subunits of G(i/o) G-proteins, but the signal transduction pathway for the enhancement of L-type calcium channels in mammalian neurons remains unknown. In the present study, calcium currents were elicited in acute cultures from postnatal day 6-8 rat hippocampi in the presence of various modulators of protein kinase A (PKA) and protein kinase C (PKC) pathways. Overnight treatment with an inhibitor of G(i/o) (pertussis toxin, 200 ng/ml) abolished the attenuation of calcium current by the GABA(B) agonist, baclofen (10 mu M) with no effect on the enhancement of calcium current. These data indicate that while the attenuation of N-type calcium current is mediated by the G(i/o) subtype of G-protein, the enhancement of L-type calcium current requires activation of a different G-protein.

1 in kinetic resolution of 4-nitrophenyl 2-methylheptanoate. Enzyme variants were expressed in Pichia pastoris by using the episomal vector pBGP1 which allowed efficient secretory expression check details of the lipase. Iterative rounds of CASTing yielded variants with good selectivity toward both the (S)- and the (R)-enantiomer. The best obtained enzyme variants had E-values of 52 (S)

and 27 (R).”
“1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity and behavioral impairment in rodents similar to Parkinson’s disease. The MPTP mouse model is widely used to evaluate new protective agents. EGb 761 is a well-defined mixture of active compounds extracted from Ginkgo biloba leaves according to a standardized procedure. We have shown that EGb 761 attenuates the loss of striatel dopamine levels and prevents the neurodegeneration of the nigrostriatal

pathway induced by MPTP. This finding shows that neuroprotective effects of EGb 761 act, in part, on the dopamine system. Therefore, this study investigates whether EGb 761 exerts dopaminergic neuroprotection through the regulation of dopamine-related gene expression in MPTP-induced Parkinsonism. selleck Male C57BL/6J mice were injected with MPTP (30 mg/kg, i.p.) for 5 days and later with EGb 761 (40 mg/kg, i.p.) daily for 18 days. The expression of selected genes was evaluated in the striatum and midbrain by quantitative PCR. The genes for tyrosine hydroxylase (Th), vesicular monoamine

transporter 2 (Vmat2), dopamine transporter (Dat), dopamine D2 receptor (Da-d2r), and transcription factors (Pitx3 and Nurr1) related to dopamine neurotransmission were selected for the analysis. EGb 761 administration to MPTP-treated mice protected Th (41%), Vmat2 (15%), Dat (102%), Da-d2r (46%), Pitx3 (63%), and Nurr1 (148%) mRNA levels in the midbrain, all of which were up-regulated. However, EGb 761 partially reversed the MPTP effect exclusively for Th (48%) and Nurrl (96%) mRNA in the striatum. Only Th and Nurr1 mRNA and protein levels were regulated”
“Although an important role for mast cells in several this website viral infections has been demonstrated, its role in the invasion of highly pathogenic H5N1 influenza virus is unknown. In the present study, we demonstrate that mast cells were activated significantly by H5N1 virus (A/chicken/Henan/1/2004) infection both in vivo and in vitro. Mast cells could possibly intensify the lung injury that results from H5N1 infection by releasing proinflammatory mediators, including histamine, tryptase, and gamma interferon (IFN-gamma). Lung lesions and apoptosis induced by H5N1 infection were reduced dramatically by treatment with ketotifen, which is a mast cell degranulation inhibitor. A combination of ketotifen and the neuraminidase inhibitor oseltamivir protected 100% of the mice from death postinfection.

Our experiments resulted in the identification of 213 phosphotyrosine sites on 181 genistein-regulated proteins. Many identified phosphoproteins, including nine protein kinases, eight receptors, five protein phosphatases, seven transcriptical regulators and four signal adaptors, were novel inhibitory effectors with no previously known function in the anti-cancer mechanism of genistein. Functional analysis suggested that genistein-regulated protein tyrosine phosphorylation mainly by inhibiting the activity of tyrosine kinase EGFR, PDGFR, insulin receptor, Ab1, Fgr, Itk, Fyn and Src.

Core signaling molecules inhibited by genistein can be functionally categorized into the canonial Receptor-MAPK or Receptor-P13K/AKT learn more cascades. The method used here may be suitable for the identification of inhibitory effectors and tyrosine kinases regulated by anti-cancer drugs.”
“Atypical high-level vision in autism is sometimes attributed to a core deficit in the function of lateral geniculate nucleus magnocells or their retinal drives. While some physiological measures provide indirect, suggestive evidence for such a deficit, support from behavioural measures is lacking and contradictory. We assessed luminance contrast increment thresholds on pulsed- and steady- pedestals in 17 children with autism https://www.selleckchem.com/products/sbe-b-cd.html spectrum conditions (ASC) compared to 17 typically developing children; these two conditions correspond to widely-used

indices of magnocellular and parvocellular function. As a group, children with ASC had C188-9 concentration strikingly elevated thresholds on the steady pedestal-paradigm, yet performed similarly to controls on the pulsed pedestal paradigm, a finding that would typically be interpreted to reflect impaired magnocellular function. The effect size of the impairment was

large and a substantial minority (41.2%) of the ASC group showed significantly impaired performance on an individual basis. This finding is consistent with a selective magnocellular deficit. It directly contradicts previous claims that such deficits are confined to ‘complex’ visual stimuli and likely does not reflect atypical attention, adaptation or high-level vision. The pattern of results is not clearly predicted by notions of imbalance of excitation versus inhibition, atypical lateral connectivity or enhanced perceptual function that account for a range of other findings associated with perception in autism. It may be amenable to explanation in terms of decreased endogenous neural noise, a novel alternative we outline here. (C) 2013 Elsevier Ltd. All rights reserved.”
“The light-dependent regulation of stromal enzymes by thioredoxin (Trx)-catalysed disulphide/dithiol exchange is known as a classical mechanism for control of chloroplast metabolism. Recent proteome studies show that Trx targets are present not only in the stroma but in all chloroplast compartments, from the envelope to the thylakoid lumen.

(C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Tuberculosis is recognized as the world’s leading bacterial cause of death. Yet 95% of infection is believed to exist in an asymptomatic ‘latent’ form that is defined not by the identification of bacteria,

but by the host immune response in the form of reactivity to tuberculosis proteins in the tuberculin skin test. It seems likely that clinically defined latent tuberculosis actually represents a spectrum that runs from elimination of live bacilli to subclinical AG-014699 manufacturer disease: hence, it might be unhelpful to use a single term to describe all these conditions. To support this view, here we focus on recent increased understanding of the heterogeneity in both bacillary physiology and host immune response that 5-Fluoracil purchase potentially illuminates new therapeutic and diagnostic approaches to this condition.”
“It is estimated that 37 million people worldwide suffer from blindness and 124 million people have impaired vision. While the relatively recently developed therapies, antivascular endothelial growth factor inhibitors for the treatment of age-related macular degeneration, and prostaglandin analogues

for the treatment of glaucoma are beneficial for some patients, there are many individuals with sight-threatening diseases for whom no effective pharmacological therapy is available. For many of these diseases, the molecular mechanisms remain to be comprehensively elucidated, thus precluding the design of successful therapies against specific pathological targets. The current review summarises recent attempts to elucidate molecular mechanisms of ocular diseases, including diabetic retinal disease, age-related macular degeneration and inherited blindness using proteomic methodologies. A novel hypothesis can be generated from global protein expression analysis of disease tissue, which can then be addressed with cellular and in vivo functional studies. For example, the identification of extracellular carbonic anhydrase

from the vitreous MDV3100 datasheet of diabetic retinopathy patients using MS based proteomics led to the elucidation of a new pathway involved in intraretinal edema, which could be inhibited by a number of agents targeting different proteins in this pathway in relevant animal models. The potential of protein biomarkers for diagnosis and the identification of novel disease mechanisms are also discussed.”
“Objective: Since the introduction of the cut-and-sew Cox maze procedure for atrial fibrillation, there has been substantial innovation in techniques for ablation. Use of alternative energy sources for ablation simplified the procedure and has resulted in dramatic increase in the number of patients with atrial fibrillation treated by surgical ablation. Despite its increasingly widespread adoption, there is lack of rigorous clinical evidence to establish this procedure as an effective clinical therapy.

Improperly buy ABT-737 folded molecules must exit folding cycles and be degraded. In the endoplasmic reticulum (ER), prolonged substrate cycling is detrimental because it expends chaperone and energy resources and increases toxic reactive oxygen species. In budding yeast, we found that unfolded protein

O-mannosylation terminated failed folding attempts through the Pmt1/Pmt2 complex. O-mannosylation incapacitated target molecule folding and removed them from folding cycles by reducing engagement with the Kar2 chaperone. In an in vitro protein refolding assay, the modification intrinsically and irreversibly disabled the folding potential of the substrate. Thus, protein folding termination can involve a covalent glycosylation event.”
“Treslin/TICRR (TopBP1-interacting, replication stimulating protein/TopBP1-interacting, checkpoint, and replication regulator), the human ortholog of the yeast Sld3 protein, is an essential DNA replication factor that is regulated by cyclin-dependent kinases and the DNA damage checkpoint. We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR GSK461364 ic50 throughout the cell

cycle. We show that MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holoheticase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, we found MTBP is required for DNA replication irrespective of a cell’s p53 status. We propose that MTBP acts with Treslin/TICRR to integrate signals from cell find more cycle and DNA damage response pathways to control the initiation of DNA replication in human cells.”
“Plasmodium falciparum transmission by Anopheles gambiae mosquitoes is remarkably efficient, resulting in a very high prevalence of human malaria infection in sub-Saharan

Africa. A combination of genetic mapping, linkage group selection, and functional genomics was used to identify Pfs47 as a P. falciparum gene that allows the parasite to infect A. gambiae without activating the mosquito immune system. Disruption of Pfs47 greatly reduced parasite survival in the mosquito, and this phenotype could be reverted by genetic complementation of the parasite or by disruption of the mosquito complement-like system. Pfs47 suppresses midgut nitration responses that are critical to activate the complement-like system. We provide direct experimental evidence that immune evasion mediated by Pfs47 is critical for efficient human malaria transmission by A. gambiae.”
“The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamethoxazole and other sulfa drugs interfere with tetrahydrobiopterin biosynthesis through inhibition of sepiapterin reductase.

RESULTS: Between January 1999 and December 2007, 41 patients were identified with fractures of the clivus. We found a 0.21% overall incidence among all head-injured patients presenting to our institution and a 2.3% incidence among those patients with a cranial fracture. Ten of 41 patients (24.4%) died, and neurological

and vascular complications associated with central cranial base fractures were observed in 19 of 41 patients (46%). Furthermore, associated cranial fractures remote from the central cranial base and associated intracranial hemorrhages were observed in 40 of 41 (97.6%) and 33 of 41 (80.5%) patients, respectively. In terms of outcomes, 26 of 41 patients (63.5%) had a Glasgow Coma Scale score of 12 or greater at the time of discharge from the hospital.

CONCLUSION: selleck compound We demonstrate a lower than previously reported mortality rate in patients GSK1904529A concentration with clival fractures. Nevertheless, as a result of location,

fractures of the clivus were frequently associated with a high rate of complications and neurological sequelae.”
“A recombinant antibody fusion protein, V3HCL, which was shown previously to have specific reactivity for potato leafroll virus (PLRV), was labeled with biotin using standard chemical coupling procedures and by an in vivo method. The in vivo method proved superior giving reproducible VMCL-biotin preparations. A fully recombinant ELISA was devised incorporating V3HCL, V3HCL-biotin and streptavidin alkaline phosphatase conjugate. This assay gave comparable results for PLRV detection in potato to an assay based on immunoglobulins. The V3HCL-biotin preparations were stable and retained specific activity for more than 1 year when stored at 4 degrees C or -20 degrees C. The results demonstrate that scFv reagents derived from synthetic phage display platforms can provide effective alternatives to assays incorporating immune reagents. (C) 2009 Elsevier B.V. All rights reserved.”
“OBJECTIVE STAT inhibitor To assess the feasibility of 5-aminolevulinic acid (5-ALA) fluorescence guidance for resection of recurrent malignant brain tumors.

METHODS:

In a Multicenter prospective, single-arm, uncontrolled phase 11 study, 36 patients with recurrent glioma (World Health Organization grade III/IV) received 5-ALA before surgery. After microsurgical resection, biopsies from pathological and nonpathological areas (as identified under conventional white light) were obtained to determine the positive predictive value (PPV) of 5-ALA-induced tissue fluorescence in detecting tumors. Adverse events, neurological examinations, and survival data were documented for a minimal follow-up of 6 months.

RESULTS: The patient-based PPV, defined as the percentage of patients showing positive tumor cell identification in all biopsies taken from areas of weak and strong fluorescence was 97.2% for pathological areas and 79.4% in nonpathological areas. Within areas of strong fluorescence, PPV was higher (91.7%) compared with that of weak fluorescence (82.4%).

Collectively, we demonstrated that MRx102 has potent antileukemic activity both in vitro and in vivo, has the potential to eliminate AML stem/progenitor cells and overcome microenvironmental

protection of leukemic see more cells, and warrants clinical investigation. Leukemia (2012) 26, 443-450; doi:10.1038/leu.2011.246; published online 9 September 2011″
“Introduction: The development of novel bifunctional chelates for attaching copper-64 to biomolecules has been an active area of research for several years. However, many of these Cu-64-chelates have poor in vivo stability or harsh radiolabeling conditions.

Methods: In this study, two triazacyclononane analogs: C-NE3TA (4-carboxymethyl-7-[2-(carboxymethylamino)-3-(4-nitro-phenyl)-propy]-[1,4,7]triazo-nan-1-yl-acetic acid) and N-NE3TA (4-carboxymethyl-7-[2-carboxymethyl-(4-nitro-benzyl)-amino]-ethyl-[1,4,7]triazonan-1-yl-acetic acid)

were evaluated for their labeling efficiency with Cu-64 at room temperature and evaluated in vitro and in vivo. In vitro studies included complexation kinetics with Cu(II) using a spectrophotometric method and rat serum stability, while the in vivo biodistribution was evaluated using SOD GDC-0973 clinical trial mice.

Results: C-NE3TA and N-NE3TA were labeled at >95% efficiency up to similar to 3.4 Ci/mu mol. Both C-NE3TA and N-NE3TA formed complexes with Cu(II) almost immediately, with the Cu(II) complexation by C-NE3TA being faster than the formation of Cu(II)-N-NE3TA. Both Cu-64-N-NE3TA and Cu-64-C-NE3TA were 96.1% and 90.5% intact after 48 h incubation in rat serum, respectively. This is compared to Cu-64 complexes of the control chelators, p-NH2-Bn-DOTA and p-NH2-Bn-NOTA, with 93.9% and 97.9% retention of Cu-64 in the complex, respectively.

OSI-744 ic50 In vivo evaluation of Cu-64-N-NE3TA and Cu-64-C-NE3TA demonstrates good clearance from normal tissues except for the liver, where 59% and 51% of the radioactivity is retained at 24 h compared to 1 h for Cu-64-N-NE3TA and Cu-64-C-NE3TA, respectively. This compares to 78% and 3% retention for Cu-64-p-NH2-Bn-DOTA and Cu-64-p-NH2-Bn-NOTA.

Conclusions: These studies demonstrate that While N-NE3TA and C-NE3TA appear to be superior chelators for Cu-64 than p-NH2-Bn-DOTA, they are not better than p-NH2-Bn-NOTA. Nevertheless, it may still be interesting to evaluate these chelators after conjugation to biomolecules. (C) 2012 Elsevier Inc. All rights reserved.”
“The rates of deamidation of alpha-synuclein and single Asn residues in 13 Asn-sequence mutants have been measured for 5 x 10(-5) M protein in both the absence and presence of 10(-2)M sodium dodecyl sulfate (SDS).

To determine if the pathway uses GABA as its transmitter, we used immunocytochemistry (ICC) to study glutamic acid decarboxlyase(67) (GAD(67)) colocalization with fluoro-gold (FG) in the ventral BST and MPN after applying FG to the RRF. To determine if the pathway is activated with mating, we studied FG-Fos colocalization in the ventral BST of recently mated males. The ventral BST expresses Fos with mating and is the major pathway source. To determine to what

extent other GABAergic cells in the ventral BST are activated with mating, we studied Fos colocalization with GAD(67) mRNA visualized by in situ hybridization (ISH). We also looked for GAD(67) mRNA in RRF cells. Almost all ventral BST and MPNm BMS-777607 solubility dmso cells projecting to the RRF (95-97%) and most ventral BST cells activated with mating (89%), were GABAergic. GABAergic cells were also seen in the RRF. RRF-projecting cells represented 37% of ventral BST cells activated with mating. Their activation may reflect arousal and anticipation of sexual reward. Among ventral BST cells that project to the RRF, 14% were activated with mating, consistent with how much of this pathway is needed for mating. The activated GABAergic cells that do not project to the RRF may release GABA locally and inhibit ejaculation. (C) 2011 IBRO.

Paclitaxel Published by Elsevier Ltd. All rights reserved.”
“Purpose: We assessed the value of [C-11]choline positron emission tomography/computerized find more tomography in patients with prostate cancer in whom biochemical failure developed after radical prostatectomy but who showed no disease evidence on conventional imaging.

Materials and Methods: Considered for this study were 2,124 patients treated with radical prostatectomy who underwent [C-11]choline positron emission tomography/computerized tomography to restage disease between December 2004 and January 2007. Study inclusion criteria were 1)

previous radical prostatectomy and pelvic lymph node dissection, 2) increasing prostate specific antigen beyond 0.2 ng/ml after radical prostatectomy, 3) no lymph node disease at radical prostatectomy, 4) no evidence of metastatic disease on conventional imaging, 5) no androgen deprivation therapy and 6) no adjuvant or salvage radiotherapy. These criteria were satisfied in 109 of the 2,124 patients (5%).

Results: Median prostate specific antigen at imaging was 0.81 ng/ml (range 0.22 to 16.76 ml). Imaging suggested local recurrence in 4 patients (4%) and pelvic lymph node disease in 8 (7%). Scans were positive in 5%, 15% and 28% of patients with prostate specific antigen less than 1, between 1 and 2, and greater than 2 ng/ml, respectively (p <0.05). Prostate specific antigen was the only significant predictor of tomography results (p <0.05).

33%) were identified from 97,218 GB and AB operations performed between 2007 and 2010 in this retrospective registry study. Significant differences were identified in male gender (21.1% vs 31.4%; P < .001), preoperative body mass index (BMI; 44.5 +/- 6.6 vs 45.3 +/- 7; P < .001), and African-American race (10.5% vs 18%; P < .001) between non-CPIVCF and CPIVCF groups. The CPIVCF group had more patients with previous nonbariatric surgery (50% vs 43.6%; P = .02), a history of venous thromboembolism (VTE; 21.4% vs 3.1%; P < .001), impairment of functional

status (7.8% vs 3.1%; P < .001), lower extremity edema (47.2% vs 27.1%; P < .001), obesity hypoventilation syndrome (7.1% vs 2.1%; P < .001), obstructive sleep apnea syndrome (58.1% vs 43.3%; P < .001), and pulmonary hypertension (13% vs 4.1%; BAY 11-7082 manufacturer P < .001). Patients in the CPIVCF group were more likely to receive GB than gastric banding (77% vs 58.1%; P < .001) and an open surgical approach (21.4% vs 4.8%; P < .001). Operative duration was longer in the CPIVCF group (119 +/- 67 Verubecestat in vivo vs 89 +/- 52 minutes; P < .001). The CPIVCF group also had a longer length of hospital stay (3 +/- 2 vs 2 +/- 6 days; P = .048), was associated with higher incidence of deep venous thrombosis (DVT; 0.93% vs 0.12%; P < .001), and had a higher mortality (0.31% vs 0.03%; P = .003) from PE and indeterminate

causes. In multivariate analysis, male gender, African-American race, previous nonbariatric surgery, a high BMI, obesity hypoventilation syndrome, history of VTE, lower extremity edema, and pulmonary hypertension

were preoperative factors associated with PD0325901 research buy CPIVCF.

Conclusions: CPIVCF was associated with specific clinical features, increased health care resource utilization, and a higher mortality in patients undergoing bariatric operations. Although selected patient characteristics influence surgeons to perform CPIVCF, this study was unable to establish an outcome benefit for CPIVCF. (J Vasc Surg 2012;55:1690-5.)”
“Stimulation of the dorsal periaqueductal gray matter (DPAG) produces defensive behaviors which are reminiscent of panic attacks. Recent evidence from our laboratory showed that DPAG-evoked defensive behaviors are markedly attenuated in short-term methimazole-induced hypothyroidism. It is not clear, however, whether these effects were due to an increase in thyrotropin releasing hormone (TRH), a decrease in thyroid hormones or to the overall effects of hypothyroidism. Accordingly, here we examined whether the peripheral injection of TRH has any effect either on the panic-like behaviors induced by electrical stimulation of DPAG or anxiety-like behaviors of rats exposed to the elevated plus-maze (EPM). Rats whose stimulation of DPAG produced flight responses (galloping or jumping) with intensities below 60 LA were injected with 1 mu g/kg TRH (i.p.) and stimulated 10 min after that. The day after, rats were treated with saline and subjected to the same stimulation procedure.

In addition, Th2 cells in chronic regulatory environments become functionally impaired, indicating cell-intrinsic regulation, which compromises protective Th2 memory. We discuss these pathways and consider the potential for reversing unresponsiveness through stimulatory signals or replacement by new responder populations. Future vaccine or therapeutic strategies should aim to minimize extrinsic regulatory effects and simultaneously negate Th2 anergy to drive effector responses into a long-term functionally competent state.”
“Transgenic Arabidopsis conditionally expressing the bacterial avrRpm1 type III effector under the control of a dexamethasone-responsive

EPZ-6438 cell line promoter were used for proteomics studies. This model system permits study of an individual effector without interference from additional bacterial components. Coupling of different prefractionation approaches to high resolution 2-DE facilitated the discovery of low abundance proteins – enabling the identification of proteins that have escaped detection in similar experiments. A total of 34 differentially regulated protein spots were identified. Four of these (a remorin, a protein phosphatase 2C (PP2C), an RNA-binding protein, and a C2-domain-containing protein) are potentially early signaling components in the interaction between AvrRpm1 and the cognate disease resistance gene

product, resistance to Pseudomonas syringae pv. maculicola 1 (RPM1). For the remorin and RNA-binding protein, involvement of PTM and post-transcriptional

regulation are implicated, respectively.”
“Human cytomegalovirus (HCMV) is the leading selleck cause of congenital infection, associated with severe birth defects and intrauterine growth retardation. The mechanism of HCMV transmission via the maternal-fetal interface is largely unknown, and there are no animal models for HCMV. The initial stages of infection are believed to occur in the maternal decidua. GDC-0449 mouse Here we employed a novel decidual organ culture, using both clinically derived and laboratory-derived viral strains, for the ex vivo modeling of HCMV transmission in the maternal-fetal interface. Viral spread in the tissue was demonstrated by the progression of infected-cell foci, with a 1.3- to 2-log increase in HCMV DNA and RNA levels between days 2 and 9 postinfection, the expression of immediate-early and late proteins, the appearance of typical histopathological features of natural infection, and dose-dependent inhibition of infection by ganciclovir and acyclovir. HCMV infected a wide range of cells in the decidua, including invasive cytotrophoblasts, macrophages, and endothelial, decidual, and dendritic cells. Cell-to-cell viral spread was revealed by focal extension of infected-cell clusters, inability to recover infectious extracellular virus, and high relative proportions (88 to 93%) of cell-associated viral DNA.