ObjectivesTo evaluate the effectiveness and safety of de-

\n\nObjectives\n\nTo evaluate the effectiveness and safety of de-escalation antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic shock caused by any micro-organism.\n\nSearch strategy\n\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 8); MEDLINE via PubMed (from inception to August 2010); 4 EMBASE (from inception to August 2010); LILACS (from inception to August 2010); Current Controlled Trials and bibliographic

references of relevant studies. We also contacted the main authors in the area. We applied no language restriction.\n\nSelection criteria\n\nWe planned to include randomized controlled trials comparing de-escalation (based on Metabolism inhibitor culture results) versus standard therapy for adults with sepsis, severe sepsis or septic shock. The primary outcome was mortality (at 28 days, hospital discharge or the end of the follow-up period). Studies including patients initially treated with an empirical but not adequate antimicrobial therapy were not considered for inclusion.\n\nData collection and analysis\n\nTwo authors planned to independently select

and extract data and evaluate methodological quality of all studies. We planned to use relative risk (risk ratio) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals. We planned to use the random-effects statistical model when AZ 628 order the estimate effects of two or more studies could be combined in a metaanalysis.\n\nMain results\n\nWe retrieved 436 references via the search strategy. No randomized

controlled trials testing de-escalation antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic shock could be included in this review.\n\nAuthors’ conclusions\n\nThere is no adequate, direct evidence as to whether de-escalation of antimicrobial agents is effective and safe for adults with sepsis, severe sepsis or septic shock. Therefore, it is not possible to either recommend or not recommend the de-escalation of antimicrobial agents selleck kinase inhibitor in clinical practice for septic patients. This uncertainty warrants further research via randomized controlled trials or cohort studies.”
“Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing’s disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism.

Systematic electronic searches (Cochrane library, Medline, Embase

Systematic electronic searches (Cochrane library, Medline, Embase, Clinical trial registers) were learn more conducted in May 2009. Included trials reported completed cure of warts and data were extracted from these

trials. We performed random-effects meta-analysis and assessed heterogeneity using the I(2) statistic and conducted a pooled analysis of each treatment. We found 77 relevant studies of which the majority were of low methodological quality. Salicylic acid (SA) was superior to placebo with a risk ratio (RR) for cure of 1.60 [95% confidence interval (CI) 1.15-2.24]. Cryotherapy was not statistically better than placebo, RR 0 89 (95% CI 0.27-2.92), but aggressive cryotherapy was significantly better than gentle cryotherapy with a RR of 2 06 (95% 1.20-3.52). Combined therapy of SA and cryotherapy CH5183284 had a higher cure rate than either SA or cryotherapy alone. The results of the pooled analysis found a cure rate of 23% (5-73%) in placebo trials, 52% (0-87%) in SA trials, 49% (0-69%) in cryotherapy trials, 54% (45-75%) in aggressive cryotherapy trials and 58% (38-78%) in the combined cryotherapy and SA trials. Aside from the use of SA and aggressive cryotherapy there is insufficient evidence from RCTs to support the use of other therapies. Higher quality evidence is needed to evaluate other therapies.”
“Psoriasis vulgaris is considered a chronic inflammatory disease, but its immunopathogenesis has not been well understood. The tumor necrosis factor alpha-induced

protein 3 (TNFAIP3) gene functions in negative-feedback regulation of inflammation, and its single nucleotide polymorphism is associated with psoriasis. However, the relationship MAPK Inhibitor Library manufacturer between the expression level of the TNFAIP3 gene in immune cells and psoriasis is not known so far. In the present study, TNFAIP3 mRNA expression levels in peripheral blood mononuclear cells from 44 patients with psoriasis vulgaris and 30 healthy controls were determined using real-time reverse transcription-PCR analysis. We found that expression of TNFAIP3 mRNA in all patients negatively correlated

with the psoriatic area and severity index (PASI) (r = -0.5126; P = 0.0004) as well as with the percentage of body surface area affected by psoriasis (r = -0.5013; P = 0.0005). Patients were divided into mild and severe groups based on the mean PASI score. Expression of TNFAIP3 mRNA in the mild group was higher than that in the severe group (P = 0.0064). Moreover, compared with that in healthy controls, the expression of TNFAIP3 mRNA in the mild group was significantly upregulated (P = 0.0004), but the expression of TNFAIP3 mRNA in the severe group was not. These results suggest that the expression level of TNFAIP3 plays an important role in the pathology of psoriasis vulgaris and that the loss of upregulation of TNFAIP3 expression may contribute to the severity of psoriasis vulgaris.”
“Two alternative hypotheses explain the degradation of organics in the Viking Labeled Release experiment on Mars.

We provide evidence to support a possible hypothesis which could

We provide evidence to support a possible hypothesis which could explain much of the

conflicting clinical and experimental evidence.”
“Multivariate regression is increasingly used to study the relation between fMRI spatial activation patterns and experimental stimuli or behavioral ratings. With linear models, informative brain locations are identified by mapping the model coefficients. This is a central aspect in neuroimaging, as it provides the sought-after link between the activity of neuronal populations and subject’s perception, cognition or behavior. Here, we show that mapping of informative brain locations using multivariate linear regression (MLR) may lead to incorrect conclusions and interpretations. P005091 MLR algorithms for high dimensional data are designed to deal with targets (stimuli or behavioral ratings, in fMRI) separately, and the predictive map of a model integrates information deriving from both neural activity patterns and experimental design. Not accounting explicitly for the presence of other targets whose associated activity spatially overlaps with the one of interest may lead to predictive maps of troublesome interpretation. We propose a new model that can correctly identify the spatial patterns associated with a target while achieving good generalization. For each target, the training is based

on an augmented dataset, which includes all remaining targets. TH-302 chemical structure The estimation on such datasets produces both maps and interaction coefficients, which are then used to generalize. The proposed formulation is independent of the regression algorithm employed. We validate this model on simulated fMRI data and on a publicly available dataset. Results indicate that our method achieves high spatial sensitivity and good generalization and that it helps disentangle specific neural effects from interaction with predictive maps associated with other targets. Hum Brain Mapp 35:2163-2177, 2014. (c) 2013 Wiley Periodicals, Inc.”
“Objectives: 1) Evaluate the effects

of monopolar cautery on cochlear implant devices. 2) Determine whether 123 voltage fluctuations within the cochlear implant adversely affect the CHIR 99021 cochlear implant devices Study Design: Two Med-El cochlear implants modified to record voltage difference from the apical and proximal electrodes were implanted into an unembalmed, fresh cadaver. Cautery was applied to the ipsilateral pectoralis major muscle and ipsilateral temporalis muscle at bipolar, monopolar coagulation, and monopolar cut settings of 50 W. The intensity in each modality setting was increased by increments of 10 W to a maximum of 100 W. Integrity testing was performed before, during, and after each cautery setting. Voltage fluctuations were measured during cautery, and maximal voltage changes for each setting were noted. After explantation, devices were returned to the manufacturer for in-depth failure analysis to evaluate for any damage to the devices.

This effect was equivalent in size to the effect observed for con

This effect was equivalent in size to the effect observed for controls, demonstrating normal face-sensitivity of the N170 component in DP. Face inversion enhanced N170 amplitudes in the

control group, but not for DPs, suggesting that many DPs do not differentiate between upright and inverted faces in the typical manner. These N170 face inversion effects were present for younger but not older controls, while they were absent for both younger and older DPs. Results suggest that the early face-sensitivity of visual processing is preserved in most individuals with DP, but that the face processing system in many DPs is not selectively tuned to the canonical upright orientation of faces. (C) 2012 Elsevier Ltd. All rights reserved.”
“Background. Castleman disease (CD), or angiofollicular CAL-101 concentration lymph-node hyperplasia, is an atypical lymphoproliferative disorder with heterogeneous clinical manifestations. Renal involvement in CD has been described in only single-case reports, which have included various types of renal diseases.\n\nMethods. Nineteen Epigenetics inhibitor patients with histologically documented CD and renal biopsies available were included. Clinical features and renal histological findings were reviewed, and the available

samples were immunolabelled with anti-vascular endothelial growth factor (VEGF) antibody.\n\nResults. Nineteen CD cases were identified: 89% were multicentric, and 84% were of the plasma-cell or mixed type. Four cases (21%) were associated with human immunodeficiency virus (HIV) infection. Among

HIV-negative patients, two main patterns of renal involvement were found: (i) a small-vessel lesions group (SVL) (60%) with endotheliosis Selleckchem CRT0066101 and glomerular double contours in all patients and with superimposed glomerular/arteriolar thrombi or mesangiolysis in most; and (ii) AA amyloidosis (20%). Renal histology was more heterogeneous among HIV-positive patients. Decreases in glomerular VEGF were observed only in some patients with SVL, whereas VEGF staining was normal in all other histological groups. Interestingly, glomerular VEGF loss associated with SVL was correlated with plasma C-reactive protein levels, a marker of CD activity.\n\123 nConclusions. Small-vessel lesions are the most frequent renal involvement in CD, whereas loss of glomerular VEGF is correlated with CD activity and could have a role in SVL pathophysiology.”
“Compared with unmodified F127, the concentration range exhibiting sol-gel transition increased for the CL4-F127-CL4 (F-CL4); however, it decreased for the CL12-F127-CL12 (F-CL12), even though both F-CL4 and F-CL12 were hydrophobically modified by the oligocaprolactone (OCL). To understand the abnormal behavior of the OCL end capped F127, the difference in basic nanoassemblies among the F127, F-CL4, and F-CL12 were investigated at a low concentration of 0.10 wt % as well as at high concentrations exhibiting sol-gel transitions.

The composite end-point during the four-year observation period w

The composite end-point during the four-year observation period was more frequently reached in hyperglycaemic than in normoglycaemic non-DM patients (78.6% vs 56.9%, respectively; p = 0.04).\n\nConclusions: Acute hyperglycaemia in non-DM patients hospitalised due to ACS was

found to be an 3 unfavourable long-term (four-year) risk factor, and may also be an unfavourable in-hospital risk factor. In contrast, acute hyperglycaemia did not affect cardiovascular outcomes in DM patients.”
“Aim. The aim of the study was to test the association between circulating levels of matrix prometalloproteinase1 (pro-MMP1) and its tissue inhibitors TIMP1 and TIMP2 with prevalent cardiovascular events. Methods. Prevalent cardiovascular events were documented in 500 participants of the Cyprus study (46% men) over the age of 40. Serum levels of pro-MMP1, TIMP1 this website and TIMP2 were measured with ELISA and the association between quartiles of serum levels and presence of cardiovascular disease (CVD) was tested using multivariable CUDC-907 inhibitor binary regression models. Results. Lower serum levels of pro-MMP1 and TIMP1 were strongly associated with presence of CVD at baseline even after adjustment for conventional risk factors (P-for (trend)=0.006 and P=0.001, respectively) and inflammatory factors (P-for (trend)=0.005 and P=0.002, respectively)

with people in the highest quartile of pro-MMP1 having a reduced odds for cardiovascular disease by about 70% compared to the lowest quartile

(ORadjusted=0.26; 95% CI=0.19 to 0.75; P=0.01), whereas people with TIMP1 levels bigger than 1000 ng/mL had a 75% reduced odds for CVD compared to the rest (ORadjusted=0.25; 95% CI=0.11 to 0.60; P-for (trend)=0.002). TIMP2 levels were associated with prevalent cardiovascular disease. Conclusion. A strong selleckchem association between lower levels of circulating pro-MMP1 and TIMP1 and risk of prevalent cardiovascular disease in a general population cohort over 40 years is evident, independent from common cardiovascular and inflammatory risk factors. The role of MMP1 and its tissue inhibitors, should be tested further in prospective studies of cardiovascular disease.”
“Copao (Eulychnia acida Phil., Cactaceae) is an endemic species occurring in arid areas of northern Chile. The fruits are commercialized by peasants within the Elqui and Limari valleys and are appreciated for its acidic and refreshing taste. We now report the total phenolic (TP) and total flavonoid (TF) content, antioxidant activity, phenolic composition and main phenolic distribution in pulp and epicarp of copao fruits from different harvesting places from both valleys. The ascorbic acid content was determined in fresh fruit pulp, epicarp and juice. The phenolic-enriched extract was analyzed for antioxidant effect and composition. Ferulic acid, 9,10-dihydroxy-4,7-megastigmadien-3-one hexoside, isorhamnetin and quercetin glycosides were identified by HPLC-DAD-MS/MS analysis.

The methylene blue sensitized reactions exhibit all of the charac

The methylene blue sensitized reactions exhibit all of the characteristics of a singlet oxygen reaction including isotope effects for the formation of a hydroperoxysuffonium ylide and the ability of I and 2 to quench the BIBF 1120 price time-resolved emission of singlet oxygen at 1270 nm. The product compositions in the N-methylquinolinium tetrafluoroborate and pyrylium-cation-sensitized

reactions are dramatically different and are both different from that anticipated for the participation of singlet oxygen. This argues for different reaction mechanisms for all three sensitizers. However, both the quinolinium and pyrylium-cation-sensitized reactions display all of the characteristics of electron-transfer-initiated photooxygenations. Both sensitizers were quenched at nearly diffusion-limited rates by 1 and 2. Laser flash photolysis of mixtures of either sensitizer and 1 or 2 resulted in direct observation of the reduced sensitizer and the sulfide radical cation. In addition, electron-transfer reactions involving both sensitizers were shown to be exergonic. These results are consistent with the previously proposed outer sphere electron-transfer mechanism for N-methylquinolinium tetrafluoroborate and Tubastatin A were used to argue for a new inner sphere mechanism for the pyrylium cation reactions.”
“This study

sought to determine the frequency and clinical significance of nonhabitual seizures in 101 consecutive buy GDC-0973 patients undergoing presurgical intracranial electroencephalography intracranial (icEEG) recording. We compared clinical data, recording details, and

postsurgical outcome in patients with nonhabitual seizures to those without nonhabitual seizures during icEEG. In patients with nonhabitual seizures we compared icEEG recordings of nonhabitual seizures to recordings of habitual seizures. Nonhabitual seizures were recorded in 10% of patients. Those patients had a significantly higher rate of procedure-related complications compared to patients without nonhabitual seizures. Ultimate seizure outcome did not differ between the groups. Nonhabitual seizures often occurred within the first 3days of icEEG recording and had larger seizure-onset zones compared to the patient’s habitual seizures. Nonhabitual seizures have no effect on outcome of epilepsy surgery but may serve as important markers of procedure-related complications during icEEG.”
“The time over threshold (TOT) method has several advantages over direct pulse height analysis based on analog to digital converters (ADCs). A key advantage is the simplicity of the conversion circuit which leads to a high level of integration and a low power consumption. The TOT technique is well suited to build multi-channel readout systems for pixelated detectors as described in our previous work that also exploits the Pulse Width Modulation (PWM) method.


“P>Transient receptor ion channel 1 (TRPV1) is a nocice


“P>Transient receptor ion channel 1 (TRPV1) is a nociceptor involved in visceral hypersensitivity. Aminoglycosides like neomycin are not only potent antibiotics but in vitro data suggest that neomycin also acts as a TRPV1-antagonist and alleviates somatic pain responses. To what extent neomycin reduces visceral https://www.selleckchem.com/products/ABT-263.html hypersensitivity remains unknown. Therefore, we aimed to investigate whether neomycin can inhibit in vivo TRPV1-dependent hypersensitivity responses in two rat models of visceral pain. In the first model rats were pretreated with intraperitoneal (i.p.) capsazepine, the selective TRPV1 antagonist SB-705498, neomycin or vehicle alone and 30 min later instilled

with intracolonic TRPV1-activating capsaicin. Likewise, rats were pretreated with 10 days oral neomycin and then subjected to intracolonic capsaicin. The visceromotor response (VMR) to distension was measured before and after capsaicin application. In addition, the VMR to distension was measured in adult maternal separated Silmitasertib Metabolism inhibitor rats before and after acute stress. Before the 2nd distension protocol these rats were treated with i.p. neomycin, amoxycillin or vehicle alone. Our results showed that capsaicin administration induced an enhanced VMR to distension that was prevented by i.p. capsazepine, SB-705498 and neomycin. Oral neomycin

treatment changed bacterial faecal content but could not inhibit capsaicin induced visceral hypersensitivity. In maternal separated rats acute stress induced an enhanced response to distension that was reversed by i.p. neomycin, but not amoxycillin. These data indicate that (i.p.) neomycin can inhibit visceral hypersensitivity to distension in a nonbactericidal manner and suggest that TRPV1-modulation may

be involved.”
“Extracorporeal membrane oxygenation (ECMO) is an effective respiratory and circulatory support in patients in refractory cardiogenic shock or cardiac arrest. Peripheral ECMO sometimes requires left heart drainage; however, few reports state that pulmonary arterial (PA) venting Selleckchem ATM inhibitor is required during ECMO support. We present a case of a 14-year-old boy who required PA venting during ECMO support after resuscitation from near-drowning in freshwater. A biventricular assist device with an oxygenator implantation was intended on day 1; however, we were unable to proceed because of increasing of pulmonary vascular resistance from the acute lung injury. Central ECMO with PA venting was then performed. On day 13, central ECMO was converted to biventricular assist device with an oxygenator, which was removed on day 16. This case suggests that PA venting during ECMO support may be necessary in some cases of respiratory and circulatory failure with high pulmonary vascular resistance after near-drowning.

Objectives To investigate whether LL-37 could affect TLR3 signall

Objectives To investigate whether LL-37 could affect TLR3 signalling and antiviral activity in normal human epidermal keratinocytes (NHEKs). Methods We investigated the production of IFN-beta in NHEKs stimulated with a TLR3 ligand, poly (I:C), in the presence of LL-37. To examine the effect of LL-37 and poly (I:C) on antiviral activity, a virus plaque assay using herpes simplex (HS) virus type-1 was carried out. The uptake of poly (I:C) conjugated with fluorescein isothiocyanate (FITC) into the keratinocytes BAY 73-4506 mouse was observed in the presence of LL-37. Immunostaining for TLR3 and LL-37 was performed using skin samples from HS. Results LL-37 and

poly (I:C) synergistically induced the expression of IFN-beta in NHEKs. Furthermore, co-stimulation with LL-37 and poly (I:C) significantly decreased the viral plaque numbers compared with poly (I:C) or LL-37 alone. LL-37 enhanced the uptake of FITC-conjugated poly (I:C) into cells. Immunohistochemical analysis demonstrated that the expression of TLR3 and LL-37 is up-regulated in HS AG-120 in vitro lesions. Conclusions Our findings suggest that LL-37 augments the antiviral activity induced by dsRNA in keratinocytes, which may contribute to the innate immune response to cutaneous

viral infections such as HS.”
“An instrument made by ourselves was used to fabricate biodegradable chitosan-heparin artificial vascular prosthesis with small internal diameter (2 mm) and different crosslinking degree from CDK activation biodegradable chitosan, chitosan derivates and heparin. In vivo and in vitro degradation studies, inflammatory analysis and electron microscope scanning of this artificial vascular prosthesis were performed. It was observed that 50% of the prosthesis decomposed in vivo and was replaced by natural tissues. The degradation process of the chitosan-heparin artificial vascular prosthesis of small diameter could be controlled by changing the crosslinking degree. This kind of artificial vascular prosthesis shows good biocompatibility that can be controllability designed

to achieve desirable in vascular replacement application.”
“Dynamic light scattering (DLS) is a technique capable of determining the hydrodynamic radius of proteins. From this parameter, a molecular weight can be assessed provided that an appropriate calibration curve is available. To this goal, a globin-based calibration curve was used to determine the polymerization state of a recombinant hemoglobin-based oxygen carrier and to assess the equivalent molecular weight of hemoglobins conjugated with polyethylene glycol molecules. The good agreement between DLS values and those obtained from gel filtration chromatography is a consequence of the high similarity in structure, shape, and density within the globin superfamily.

Frailty risk factors for each patient were collected at three dif

Frailty risk factors for each patient were collected at three different times over the period

of a year. In the first study, data from the group of patients were used to determine the frailty state of a new incoming patient. The results were valuable for determining the degree of frailty of a specific patient in relation to other patients in an elderly population. The most representative similarity degrees were between 73.4% and 71.6% considering 61 frailty factors from 64 patient instances. Additionally, from the provided results, a physician could group the elders by their degree of similarity influencing their Nocodazole supplier care and treatment. In the second study, the same mobile tool was used to analyze the frailty syndrome https://www.selleckchem.com/products/GSK690693.html from a nutritional

viewpoint on 10 patients of the initial group during 1 year. Data were acquired at three different times, corresponding to three assessments: initial, spontaneous, and after protein supplementation. The subsequent analysis revealed a general deterioration of the subset of elders from the initial assessment to the spontaneous assessment and also an improvement of biochemical and anthropometric parameters in men and women from the spontaneous assessment to the assessment after the administration of a protein supplement.\n\nConclusions: The problem of creating a general frailty index is still unsolved. However, in recent years, there has been an increase in the amount of research on this subject. Our studies took advantage of mobile device features (accelerometer sensors, wireless communication capabilities, and processing capacities among others) to develop a new method that achieves an objective assessment of frailty based on similarity results for an elderly population, providing an essential support for physicians.”
“Spontaneous pacemakery-aminobutyric AP26113 in vitro acid (GABA) receptor-mediated synaptic activity (PGA) occurs in a subset of tissue samples from pediatric epilepsy surgery patients. In the present study, based on single-cell electrophysiological recordings from 120 cases, we describe the etiologies, cell types, and primary electrophysiological features of PGA. Cells displaying PGA

occurred more frequently in the areas &greatest anatomical abnormality in cases of focal cortical dysplasia (CD), often associated with hemimegalencephaly (HME), and only rarely in nonCD etiologies. PGA was characterized by rhythmic synaptic events (5-10 Hz) and was observed in normal-like, dysmorphic cytomegalic, and immature pyramidal neurons. PGA was action potential-dependent, mediated by GABAA receptors, and unaffected by antagonism of glutamate receptors. We propose that PGA is a unique electrophysiological characteristic associated with CD and HME. It could represent an abnormal signal that may contribute to epileptogenesis in malformed postnatal cortex by facilitating pyramidal neuron synchrony. (C) 2013 Elsevier Inc. All rights reserved.


“This clinical article reports a technique, apicotomy, for


“This clinical article reports a technique, apicotomy, for managing dilacerated or ankylosed canines. The records of 3 patients successfully treated with apicotomy are presented. Orthodontists observe clinically significant incidences

of impacted maxillary learn more canines in their daily practices. Several procedures have been described to bring an ankylosed, impacted tooth into occlusion. Luxation is the most widely used solution, but there are risks involved with that approach, and the success rate is low. Surgical repositioning has also been used, but morbidity is high, and the aggressiveness of the procedure might also contraindicate it. Ankylosis might be related to the anatomic position of the canine’s root apex and its adjacent anatomic structures. Apicotomy is a guided fracture of a canine root apex, followed by its orthodontic traction. It is a conservative surgical alternative for treating impacted canines with dilacerations or apical root ankylosis.”
“Smart biomaterials play a key role when aiming at successful

tissue repair by means of regenerative C59 cost medicine approaches, and are expected to contain chemical as well as mechanical cues that will guide the regenerative process. Recent advances in the understanding of stem cell biology and mechanosensing have shed new light onto the importance of the local microenvironment in determining cell fate. Herein we report the biological properties of a bioactive, biodegradable calcium phosphate glass/polylactic acid composite biomaterial that promotes bone marrow-derived endothelial progenitor cell (EPC) mobilisation, differentiation and angiogenesis through the creation of a controlled bone healing-like

microenvironment. The angiogenic response is triggered by biochemical and mechanical selleck products cues provided by the composite, which activate two synergistic cell signalling pathways: a biochemical one mediated by the calcium-sensing receptor and a mechanosensitive one regulated by non-muscle myosin II contraction. Together, these signals promote a synergistic response by activating EPCs-mediated VEGF and VEGFR-2 synthesis, which in turn promote progenitor cell homing, differentiation and tubulogenesis. These findings highlight the importance of controlling microenvironmental cues for stem/progenitor cell tissue engineering and offer exciting new therapeutical opportunities for biomaterialbased vascularisation approaches and clinical applications.”
“Eukaryotic DNA replication is preceded by the assembly of prereplication complexes (pre-RCs) at or very near origins in G1 phase, which licenses origin firing in S phase. The archaeal DNA replication machinery broadly resembles the eukaryal apparatus, though simpler in form. The eukaryotic replication initiator origin recognition complex (ORC), which serially recruits Cdc6 and other pre-RC proteins, comprises six components, Orc1-6.