Methods: All 1346 renal transplant procedures performed between 1 January 1967 and 31 December 2006 were reviewed. Clinical data, histological reports and outcomes were available from a prospectively www.selleckchem.com/products/icg-001.html recorded database. The study period was divided into four decades to assess the changes in renal transplantation over time.

Results: Significant changes that have occurred include an increase in donor and recipient ages, a greater proportion of recipients with diabetic nephropathy, a longer wait before the first transplant procedure, a fall in the incidence and impact of acute rejection, a smaller

proportion of deaths due to cardiovascular disease, (P 0.001 for all) and a trend to increased deaths from malignancy (P 0.06) over time. In multivariate analysis, death censored graft survival was significantly influenced by the era of transplantation, selleck chemicals donor and recipient ages, living vs. deceased

donor status, and histological evidence of acute rejection, chronic allograft nephropathy, or disease recurrence. Significant factors in recipient survival were the era of transplantation, recipient age, a primary renal diagnosis of diabetic nephropathy or unspecified chronic renal failure, and biopsy proven acute rejection.

Conclusions: There have been major changes in the clinical practice related to renal transplantation over the past four decades; some have been beneficial and others detrimental to survival. Regular review of outcomes is essential to guide renal services development and maximize graft and recipient survival.”
“In synesthesia, certain

stimuli to one sensory modality lead to sensory perception in another unstimulated modality. In addition to other models, a two-stage model is discussed to explain this phenomenon, ifoxetine which combines two previously formulated hypotheses regarding synesthesia: direct cross-activation and hyperbinding. The direct cross-activation model postulates that direct connections between sensory-specific areas are responsible for co-activation and synesthetic perception. The hyperbinding hypothesis suggests that the inducing stimulus and the synesthetic sensation are coupled by a sensory nexus area, which may be located in the parietal cortex. This latter hypothesis is compatible with the disinhibited feedback model, which suggests unusual feedback from multimodal convergence areas as the cause of synesthesia. In this study, the relevance of these models was tested in a group (n = 1 4) of auditory-visual synesthetes by performing a functional connectivity analysis on functional magnetic resonance imaging (fMRI) data. Different simple and complex sounds were used as stimuli, and functionally defined seed areas in the bilateral auditory cortex (AC) and the left inferior parietal cortex (IPC) were used for the connectivity calculations. We found no differences in the connectivity of the AC and the visual areas between synesthetes and controls.

gov, http://controlled-trials.com and the Cochrane review database using a predefined search strategy.

Results: One hundred forty-one patients from 27 articles were included. Interventions ranged from single (n = 104, 74%), staged (n = 26, 18%) to simultaneous procedures (n = 11, 8%). The largest cohort of patients was treated by carotid

endarterectomy R428 order alone (n = 92, 66%). The majority of patients presented with a symptomatic carotid stenosis and an asymptomatic ipsilateral intracranial aneurysm (n = 70, 50%). Five subarachnoid hemorrhages occurred (4% [ 5/140], three within 30 days of the procedure and two thereafter) of which two were fatal. All five occurred in patients who underwent carotid endarterectomy as a single procedure (5%). Two of the five patients

presented with ruptured posterior communicating artery aneurysms.

Conclusions: Published reports of perioperative aneurysm rupture are rare in individuals with tandem carotid stenosis and intracranial aneurysms. This is the first analysis of all published cases. However, it is limited by the small number of studies and the possible underreporting due to publication bias and underdiagnosis where angiography was not performed. Although we www.selleckchem.com/products/azd9291.html report a low incidence of subarachnoid hemorrhage, analysis of registry data with a larger cohort is warranted to confirm these findings. (J Vasc Surg 2012;56:1739-47.)”
“African swine fever virus (ASFV) is a large double-stranded DNA virus responsible for a lethal pig disease, to which no vaccine has ever been obtained. Its Cell Penetrating Peptide genome encodes a number of proteins involved in virus survival and transmission in its hosts, in particular proteins that inhibit signaling pathways in infected

macrophages and, thus, interfere with the host’s innate immune response. A recently identified novel ASFV viral protein (pI329L) was found to inhibit the Toll-like receptor 3 (TLR3) signaling pathway, TLR3 being a crucial “”danger detector.”" pI329L has been predicted to be a transmembrane protein containing extracellular putative leucine-rich repeats similar to TLR3, suggesting that pI329L might act as a TLR3 decoy. To explore this idea, we used comparative modeling and other structure prediction protocols to propose (a) a model for the TLR3-Toll-interleukin-1 receptor homodimer and (b) a structural fold for pI329L, detailed at atomistic level for its cytoplasmic domain. As this later domain shares only remote sequence relationships with the available TLR3 templates, a more complex modeling strategy was employed that combines the iterative implementation of (multi)threading/assembly/refinement (I-TASSER) structural prediction with expertise-guided posterior refinement. The final pI329L model presents a plausible fold, good structural quality, is consistent with the available experimental data, and it corroborates our hypothesis of pI329L being a TLR3 antagonist.

p62 may serve as a proteotoxic stress sensor, promote segregation and degradation of misfolded proteins by autophagy, and mediate the cross talk between the ubiquitin-proteasome system and autophagy. (Trends Cardiovasc Med 2011; 21:224-228) (C) 2011 Elsevier inc. All rights reserved.”
“Pain was reported by 60-90% of patients with depression, and chronic pain states are often linked to depression. Animal models of pain/depression are generally lacking for the identification of centrally active drugs. In the present

study, pain sensitivity was assessed in a mouse model of anxiety/depression on the basis of chronic corticosterone click here (CORT) administration through the drinking water (CORT model). We measured thermal hyperalgesia as shown by a decrease

in the latency to hind paw licking in the hot plate test and cold allodynia reflected by a decrease in the time spent on the plate set at 20 degrees C in the thermal preference plate test. Subsequently, we determined the effect of chronic administration of the selective serotonin reuptake inhibitor fluoxetine (an antidepressant known to reverse anxiety/depressive-like state in CORT-treated Epacadostat supplier mice) on pain relief. Fluoxetine administration reduced both heat hyperalgesia and cold allodynia, thus unveiling a putative link between mood and nociception in the CORT model. This hypothesis is consistent with previous clinical studies reporting the analgesic efficacy of fluoxetine in depressed patients suffering from pain disorders. Together, these results suggest that the CORT model, with pain/anxiety/depressive-like state, is a good candidate for translational research. NeuroReport 23:525-529 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Graft arteriosclerosis (GA), the major cause of late cardiac allograft failure, is characterized by a diffuse, concentric arterial intimal hyperplasia composed of infiltrating host T cells, macrophages, and predominantly graft-derived smooth muscle-like cells that proliferate and elaborate extracellular matrix, resulting in luminal obstruction and allograft ischemia. Interferon-gamma (IFN-gamma),

a proinflammatory cytokine produced by effector T cells, is a critical mediator for smooth muscle-like cell proliferation. We have exploited Carbachol the power of mouse genetics to examine the function of AIP1, a signaling adaptor molecule involved in vascular inflammation, in two newly established IFN-gamma-mediated models of GA. Our data suggest that AIP1 inhibits intimal formation in GA by downregulating IFN-gamma-activated migratory and proliferative signaling pathways in smooth muscle-like cells. (Trends Cardiovasc Med 2011;21:229-233) (C) 2011 Elsevier Inc. All rights reserved.”
“In women, pain symptoms and nociceptive thresholds vary with the reproductive cycle, suggesting the role of estrogen receptors (ERs) in modulating nociception.

“
“The Kv4 potassium channel alpha subunits, Kv4.1, Kv4.2, and Kv4.3, determine some of the fundamental physiological properties of neurons in the CNS. Kv4 subunits are associated with auxiliary beta-subunits, such as the potassium channel interacting proteins (KChIP1 – 4), which are thought to regulate the trafficking and gating of native Kv4 potassium channels. Intriguingly, KChIP1 is thought to show cell type-selective expression in GABA-ergic inhibitory interneurons,

while other beta-subunits (KChIP2-4) are associated with principal glutamatergic neuron’s. However, nothing is known about the expression of Kv4 family alpha- and beta-subunits Idasanutlin cell line in specific interneurons populations in the BLA. Here, we have used immunofiluorescence, co-immunoprecipitation, and Western Blotting to determine the relative expression of KChIP1 in the different interneuron subtypes within the BLA, and its co-localization with one or more of the Kv4 alpha subunits. WE, show that all three alpha-subunits of Kv4 potassium channel are found in rat BLA neurons, and that

the immunoreactivity of KChIP1 closely resembles that of Kv4.3. Indeed, Kv4.3 showed almost complete co-localization with KChIP1 in the soma and dendrites of a distinct subpopulation of BLA neurons. Dual-immunofluorescence Talazoparib in vitro studies revealed this to be in BLA interneurons immunoreactive for parvalbumin, cholecystokin-8, and somatostatin. Finally, co-immunoprecipitation studies showed that KChIP1 was associated with all three Kv4 alpha subunits. Together our results suggest that KChIP1 is selectively expressed in BLA interneurons where it may function to regulate the activity of A-type potassium channels. Hence, KChIP1 might be considered as a cell type-specific regulator of GABAergic inhibitory Liothyronine Sodium circuits in the BLA. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Although most inbred mouse strains are highly susceptible to mouse hepatitis virus (MHV)

infection, the inbred SJL line of mice is highly resistant to its infection. The principal receptor for MHV is murine CEACAM1 (mCEACAM1). Susceptible strains of mice are homozygous for the 1a allele of mCeacam1, while SJL mice are homozygous for the 1b allele. mCEACAM1a (1a) has a 10- to 100-fold-higher receptor activity than does mCEACAM1b (1b). To explore the hypothesis that MHV susceptibility is due to the different MHV receptor activities of 1a and 1b, we established a chimeric C57BL/6 mouse (cB61ba) in which a part of the N-terminal immunoglobulin (Ig)-like domain of the mCeacam1a (1a) gene, which is responsible for MHV receptor function, is replaced by the corresponding region of mCeacam1b (1b). We compared the MHV susceptibility of these chimeric mice to that of SJL and B6 mice.

Average annual rates of pneumonia-related hospitalizations from 1997 through 1999 (before the introduction of PCV7) and from 2007 through 2009 (well after its introduction) were used to estimate annual declines in hospitalizations due Paclitaxel purchase to pneumonia.

RESULTS

The annual rate of hospitalization for pneumonia among children younger than 2 years of age declined by 551.1 per 100,000 children (95% confidence interval [CI], 445.1 to 657.1), which translates to

47,000 fewer hospitalizations annually than expected on the basis of the rates before PCV7 was introduced. The rate for adults 85 years of age or older declined by 1300.8 per 100,000 (95% CI, 984.0 to 1617.6), which translates to 73,000 fewer hospitalizations annually. For the three age groups of 18 to 39 years, 65 to 74 years, and 75 to 84 years, the annual rate of hospitalization for pneumonia declined by 8.4

per 100,000 (95% CI, 0.6 to 16.2), 85.3 per 100,000 (95% CI, 7.0 to 163.6), and 359.8 per 100,000 (95% CI, 199.6 to 520.0), respectively. Overall, we estimated an age-adjusted annual reduction of 54.8 per 100,000 (95% CI, 41.0 to 68.5), or 168,000 fewer hospitalizations for pneumonia annually.

CONCLUSIONS

Declines in hospitalizations for childhood pneumonia were sustained during the decade after the introduction of PCV7. Substantial reductions R788 in hospitalizations for pneumonia Dapagliflozin among adults were also observed. (Funded by the Centers for Disease Control and Prevention.)”
“Over-expression of heme binding proteins in Escherichia coli often results in sub-optimal heme incorporation and the amount of heme-bound protein

produced usually varies with the protein of interest. Complete heme incorporation is important for biochemical characterization, spectroscopy, structural studies, and for the production of homogeneous commercial proteins with high activity. We have determined that recombinant proteins expressed in E. coli often contain less than a full complement of heme because they rather are partially incorporated with free-base porphyrin. Porphyrin-incorporated proteins have similar spectral characteristics as the desired heme-loaded targets, and thus are difficult to detect, even in purified samples. We present a straightforward and inexpensive solution to this problem that involves the co-expression of native ferrochelatase with the protein of interest. The method is shown to be effective for proteins that contain either Cys- or His-ligated hemes. (C) 2010 Elsevier Inc. All rights reserved.”
“Hepatic myofibroblasts (MFB) show increased proliferation, migration and collagen production, which are crucial for hepatic fibrogenesis. Atorvastatin treatment inhibits proliferation, apoptosis and cytokine production of MFB in bile duct-ligated (BDL) rats in vivo. Here, we have further investigated the underlying mechanisms.

Conclusions

Among appropriately selected patients with severe aortic stenosis who were not suitable candidates for surgery, TAVR reduced the rates of death and hospitalization, with a decrease in symptoms and an improvement in valve hemodynamics that were sustained at 2 years of follow-up. The presence of extensive coexisting conditions may attenuate the survival benefit of TAVR. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)”
“The human papillomavirus (HPV) type 16 E1 boolean AND E4 (16E1 boolean AND E4) protein is expressed in the this website middle to upper layers of infected epithelium and has several roles within the virus life cycle. It is apparent that within the epithelium there

are Wortmannin ic50 multiple species of 16E1 boolean AND E4 that differ in length and/or degree of phosphorylation and that some or all of these can associate with the cellular keratin networks, leading to network disruption. We show here that the cellular cysteine protease calpain cleaves the 16E1 boolean AND E4 protein after amino acid 17 to generate species that lack the N terminus. These C-terminal fragments are able to multimerize and form amyloid-like fibers. This can lead to accumulation of 16E1 boolean AND E4 and disruption of the normal dynamics of the keratin networks. The cleavage of E1 boolean AND E4

proteins by calpain may be a common strategy used by alpha-group viruses, since we show that cleavage of type 18 E1 boolean AND E4 in raft culture is also Janus kinase (JAK) dependent on calpain. Interestingly, the cleavage of 16E1 boolean AND E4 by calpain appears to be highly regulated as differentiation of HPV genome-containing cells by methylcellulose

is insufficient to induce cleavage. We hypothesize that this is important since it ensures that the formation of the amyloid fibers is not prematurely triggered in the lower layers and is restricted to the upper layers, where calpain is active and where disruption of the keratin networks may aid virus release.”
“The ability to resist the urge to eat requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from eating the food and the desire to eat the food. Imaging studies show that obese subjects might have impairments in dopaminergic pathways that regulate neuronal systems associated with reward sensitivity, conditioning and control. It is known that the neuropeptides that regulate energy balance (homeostatic processes) through the hypothalamus also modulate the activity of dopamine cells and their projections into regions involved in the rewarding processes underlying food intake. It is postulated that this could also be a mechanism by which overeating and the resultant resistance to homoeostatic signals impairs the function of circuits involved in reward sensitivity, conditioning and cognitive control.

Primary outcomes were 30-day and 5-year survival. Preoperative, intraoperative, and postoperative variables were assessed for their influence on outcomes using univariate and multivariate analysis, as appropriate. One- and 5-year survival were determined by Kaplan-Meier analysis.

Results: Four hundred eight patients (289 men; 70.8%) with a mean age of 72.4 +/- 8.3 years underwent open AAA repair. Sixty-seven patients (16.4%) underwent nonelective repair. The clamp site was infrarenal in 137 patients (33.6%), suprarenal in 97 patients (23.8%), and supraceliac 8-Bromo-cAMP supplier in 174 patients (42.6%). Thirty-day

survival was 95.6%. One- and 5-year survival were 90.0% +/- 1.5% and 65.1% +/- 3.0%, respectively. Seventy-nine patients (19.4%) had decreased renal function postoperatively compared to preoperatively, 71 patients (17.4%) sustained cardiac complications, and 45 patients (11.0%) sustained pulmonary complications. Patients with chronic obstructive learn more pulmonary disease (91.9% vs 97.2%; P = .004) and chronic renal insufficiency (92.0% vs 98.3%; P = .009) had decreased 30-day survival. Patients with chronic obstructive pulmonary disease (55.8% +/- 5.8% vs 67.3%

+/- 3.6%; P = .013), chronic renal insufficiency (51.2% +/- 5.2% vs 72.8% +/- 3.7%; P = .043), and cerebrovascular disease (46.8% +/- 7.4% vs 67.4% +/- 3.4%; P = .003) had decreased 5-year survival. Patients who had decreased postoperative renal function (41.0% +/- 7.4% vs 72.2% +/- 3.4%; P =.004), and patients who sustained pulmonary complications (45.6% +/- 8.8% vs 66.3% +/- 3.3%; P = .042) had worse 5-year survival.

Conclusions: Open AAA repair can be done with low morbidity and mortality in the era of endovascular aneurysm repair. Careful consideration should be given to preoperative optimization and perioperative care in patients with chronic obstructive pulmonary disease, chronic renal insufficiency, and cerebrovascular disease. Postoperative decrease in renal function and pulmonary complication portend

Dipeptidyl peptidase decreased 5-year survival; strategies to ameliorate these factors should be sought. (J Vase Surg 2011;54:1237-43.)”
“Pharmacological control of seizure activity following nerve agent exposure is critical in reducing neuropathology and improving survival in casualties. Three classes of drugs, anticholinergics, benzodiazepines and excitatory amino acid (EM) antagonists, have been shown to be effective at moderating nerve agent-induced seizures. However, little is known about which brain structures are involved in producing the anticonvulsant response. This study evaluated drugs from each class, injected directly into one of three specific brain structures, the perirhinal cortex, the entorhinal cortex, or the mediodorsal thalamus, for their ability to modulate seizures induced by the nerve agent soman. The drugs evaluated were the anticholinergic scopolamine, the benzodiazepine midazolam, and the EM antagonist MK-801.

Results: Lower socioeconomic status was associated of lower risk-adjusted quality of life ( maximum Duke Activity Status Index P = .0002, less than maximum Duke Activity Status Index P = .0007). Older age, female sex, certain comorbidities, higher New

York Heart Association class, lower left ventricular function, and reoperation were also statistically selleck chemical significantly associated with lower preoperative Duke Activity Status Index.

Conclusion: Lower socioeconomic status is associated with lower risk-adjusted quality of life for patients undergoing cardiac surgery. Quality of life affects morbid outcomes, so further characterization of risk factors for poor quality of life offers an opportunity for intervention.”
“Noradrenergic (NA) neurons within the nucleus of the solitary tract (NST) and caudal ventrolateral medulla (VLM) innervate the hypothalamic paraventricular nucleus (PVN) to initiate and modulate hypothalamic-pituitary-adrenal

(HPA) axis responses to interoceptive stress. Systemic endotoxin (i.e. bacterial lipopolysaccharide, LIPS) activates NA neurons within the NST and VLM that project to the PVN and other brain regions that receive interoceptive signals. The present study examined whether NA neurons with axonal inputs to the PVN are necessary for LPS to activate Fos expression within the PVN and other interoceptive-related brain regions, and to increase plasma corticosterone. Male Sprague-Dawley rats received bilateral stereotaxic microinjections of DSAP (saporin toxin conjugated PFKL to an antibody against dopamine-beta-hydroxylase, H 89 DbH)

into the PVN to destroy NA inputs. Control rats were microinjected with vehicle into the PVN or received no PVN injections. Two weeks later, DSAP and control rats were injected i.p. with LIPS (200 mu g/kg BW) or saline vehicle, and perfused with fixative 2.5-3 h later. Brain tissue sections were processed to reveal nuclear Fos protein and cytoplasmic DbH immunolabeling. DSAP lesions depleted NA terminals in the PVN and bed nucleus of the stria terminalis, reduced the number of NA cell bodies in the NST and VLM, attenuated PVN Fos activation after LPS, and attenuated LPS-induced increases in plasma corticosterone. These findings support the view that NA projections from hind-brain to hypothalamus are necessary for a full HPA axis response to systemic immune challenge. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Objective: Antispastic protocols for arterial grafts are important in arterial grafting for coronary artery bypass grafting surgery. We designed a new nicardipine and nitroglycerin cocktail that is composed of a second-generation dihydropyridine calcium antagonist, nicardipine and nitroglycerin (30 mmol/L), and examined its effect in human internal thoracic and radial arteries.

In this study, a behavioral experiment

revealed that spatial visualizers’ performance decreased evidently from short delay to long delay in a high-load condition, but object visualizers performed stably. In addition, an event-related potential experiment found the slow cortical potentials for the spatial visualizer to be more negative in relation to object visualizers in the 1800-3800 ms stage, although Acalabrutinib spatial visualizers performed worse than the object visualizers. Therefore, the processing advantage of object visualizers, which is caused by the higher neural efficiency of object visualizers than spatial visualizers in object tasks, seems to be at the retention stage rather than the encoding stage. NeuroReport 22:860-864 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Alphaviruses AZD4547 are taken up into the endosome of the cell, where acidic conditions activate the spikes for membrane fusion. This involves dissociation of the three E2-E1 heterodimers of the spike and E1 interaction with the target membrane as a homotrimer. The biosynthesis

of the heterodimer as a pH-resistant p62-E1 precursor appeared to solve the problem of premature activation in the late and acidic parts of the biosynthetic transport pathway in the cell. However, p62 cleavage into E2 and E3 by furin occurs before the spike has left the acidic compartments, accentuating the problem. In this work, we used a furin-resistant Semliki Forest virus (SFV) mutant, SFV(SQL), to study the role of E3 in spike activation. The cleavage Decitabine supplier was reconstituted with proteinase K in vitro using free virus or spikes on SFV(SQL)-infected cells. We found that E3 association with the spikes was pH dependent, requiring acidic conditions, and that the bound E3 suppressed spike activation. This was shown in an in vitro spike activation assay monitoring E1 trimer formation with

liposomes and a fusion-from-within assay with infected cells. Furthermore, the wild type, SFV(wt), was found to bind significant amounts of E3, especially if produced in dense cultures, which lowered the pH of the culture medium. This E3 also suppressed spike activation. The results suggest that furin-cleaved E3 continues to protect the spike from premature activation in acidic compartments of the cell and that its release in the neutral extracellular space primes the spike for low-pH activation.”
“Neurophysiological underpinnings of the integration of information during sentence comprehension have been studied since 1980. However, little is known about integrative processes in sentences containing a word that is semantically congruent, but factually incompatible with the context. In this study, we aimed at investigating the differences between the brain regions involved in responses to factually correct and incorrect sentences. Eighteen healthy volunteers underwent functional MRI while listening passively to 40 correct and 40 incorrect sentences.

The element has a reduced ability to interact with the U1 snRNP compared with a mutant that improves the splice site consensus. An evolutionarily conserved secondary structure is present surrounding the element. The structure modulates interaction with both hnRNP A1 and U1. Analysis of splice isoforms produced from a series of reporter constructs demonstrates that the hnRNP A1-binding site and the secondary structure both contribute to exclusion of Mag exon 12.”
“Mobile group II introns encode reverse transcriptases (RTs) that function

in intron mobility (“”retrohoming”") by a process that requires reverse transcription of a highly structured, 2-2.5-kb intron RNA with high processivity and fidelity. Although the latter properties

Selleckchem AZD5582 are potentially useful for applications in cDNA synthesis and next-generation RNA sequencing (RNA-seq), group II intron RTs have been difficult to purify free of the intron RNA, and their utility as research tools has not been investigated systematically. Here, we developed general methods for the high-level expression and purification of group II intron-encoded RTs as fusion proteins with a rigidly linked, noncleavable solubility tag, and we applied them to group II intron RTs from bacterial see more thermophiles. We thus obtained thermostable group II intron RT fusion proteins that have higher processivity, fidelity, and thermostability than retroviral RTs, synthesize cDNAs at temperatures up to 81 degrees C, and have significant advantages for qRT-PCR, Dehydratase capillary electrophoresis for RNA-structure mapping, and next-generation RNA sequencing. Further, we find that group II intron RTs differ from the retroviral enzymes in template switching with minimal base-pairing to the 3′ ends of new RNA templates, making it possible to efficiently and seamlessly link adaptors containing PCR-primer binding sites to cDNA ends without an RNA ligase step.

This novel template-switching activity enables facile and less biased cloning of nonpolyadenylated RNAs, such as miRNAs or protein-bound RNA fragments. Our findings demonstrate novel biochemical activities and inherent advantages of group II intron RTs for research, biotechnological, and diagnostic methods, with potentially wide applications.”
“Splicing of nuclear pre-mRNA occurs via two steps of the transesterification reaction, forming a lariat intermediate and product. The reactions are catalyzed by the spliceosome, a large ribonucleoprotein complex composed of five small nuclear RNAs and numerous protein factors. The spliceosome shares a similar catalytic core structure with that of fungal group II introns, which can self-splice using the same chemical mechanism. Like group II introns, both catalytic steps of pre-mRNA splicing can efficiently reverse on the affinity-purified spliceosome. The spliceosome also catalyzes a hydrolytic spliced-exon reopening reaction as observed in group II introns, indicating a strong link in their evolutionary relationship.