5-26 5 mL) filled with 18F-FDG in a dynamic thorax phantom

5-26.5 mL) filled with 18F-FDG in a dynamic thorax phantom check details and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise

ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the

respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on the 4D scan protocols can be used Selleck Nutlin3 to improve the accuracy of determining the gross tumor volume for tumors in the lung and abdomen.”
“The effects of dietary manipulation of folate and methionine on plasma homocysteine (Hey) and high-density lipoprotein cholesterol (HDL-C) levels in wild-type and apolipoprotein-E-deficient mice were determined.

A low-folate diet with or without folate and/or methionine supplementation in drinking water was administered for 7 weeks. Fasted Hey rose to 23 mu M on a low-folate/high-methionine diet, but high folate ameliorated the effect of high methionine on fasted plasma Hey to similar to 10 mu M. Determination of nonfasted plasma Hey levels at 6-h intervals revealed a large diurnal variation in Hey consistent with a nocturnal lifestyle. The daily average of nonfasted Hey levels was higher than fasted values for high-methionine diets but lower than fasted values for low-methionine diets. An acute methionine load by gavage of fasted mice increased plasma Hey 2.5 h later, but mice that PF-6463922 mouse had been on high-methionine diets had a lower fold induction. Mice fed high-methionine diets weighed less than mice fed low-methionine diets. Based on these results, two solid-food diets were developed: one containing 2% added methionine and the other containing 2% added glycine. The methionine diet led to fasted plasma Hey levels of >60 mu M, higher than those with methionine supplementation in drinking water. Mice on methionine diets had >20% decreased body weights and decreased HDL-C levels. An HDL turnover study demonstrated that the HDL-C production rate was significantly reduced in mice fed the methionine diet. (C) 2008 Elsevier Inc. All rights reserved.

CONCLUSIONS Taken together, our results reveal that O-GlcNAcy

\n\nCONCLUSIONS Taken together, our results reveal that O-GlcNAcylation represents an important novel regulation of ChREBP activity in the liver under both physiological and pathophysiological conditions. Diabetes 60:1399-1413, 2011″
“We utilized a commercially available materials printer to investigate synthetic multicellular AG-881 molecular weight cell-to-cell

communication because inkjet printing technology makes it easy to print spatiotemporal patterns of soluble biomolecules and live cells. Since cells are genetically programmed to communicate with one another via synthetic biology, cell signaling molecules secreted by one cell microcolony can induce two neighboring cell microcolonies to respond by expressing or stopping the expression of fluorescent protein genes. In this work, we not only characterize the printing parameters such as the initial seeding numbers, spacing distances, microcolony sizes, printing timings, and printed patterns of cells but also demonstrate that the use of the proposed printing technology can provide a useful

means for many synthetic biologists to simplify and speed up the investigation of cell-to-cell communication between synthetic bacterial cells. (C) 2010 Elsevier Ltd. All rights reserved.”
“Stress during pregnancy and the postpartum can influence the well-being of both the mother and her offspring. Prolonged elevated levels of glucocorticoids are associated with depression find more and we developed an animal model of postpartum depression/stress based on high levels of corticosterone (CORT) during the postpartum. Gestational stress is a risk factor for postpartum depression and prenatal and/or postnatal high levels of CORT may have differential effects on

the mother. Thus the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on maternal care, depressive-like behavior and hippocampal cell proliferation in the dam. Only the high dose of CORT administered during the postpartum Selleckchem SU5402 increased depressive-like behavior in the dam. Furthermore the high dose of CORT altered maternal care (reduced time spent on the nest and nursing) regardless of whether administration of CORT was during gestation or postpartum. Gestational and/or postpartum treatment with high CORT and postpartum low CORT reduced cell proliferation in the dentate gyrus of postpartum dams compared to oil-treated controls. Thus prolonged treatment with high levels of CORT postpartum reduced maternal care, hippocampal cell proliferation and induced depressive-like behavior in the dam and therefore might be considered an animal model of postpartum depression. More research is needed to understand the effects of stress hormones during different phases of reproduction and how they affect the brain and behavior of the mother and her offspring. (C) 2010 Elsevier Inc. All rights reserved.

This adds additional evidence that trends in the diagnosis and tr

This adds additional evidence that trends in the diagnosis and treatment for ADHD see more in children move in the exact opposite direction from those who are at highest risk for meeting criteria, for experiencing impairment, for and

downstream socioeconomic sequelae. Contributing factors, such as marginal diagnoses (such as when parent and teacher symptom reports diverge), inadequate insurance coverage, limited time, and lack of familiarity and comfort with diagnostic and prescribing guidelines, may leave the door open to misdiagnosis and treatment. In some cases, this may take the form of over-diagnosis and over-treatment, in the form of false-positive diagnoses with ADHD, and treatments for it, or may alternatively take the form of false-negative diagnoses. If the social and epidemiological data are any indication, it is furthermore likely that such false-positive or false-negative outcomes may break along socioeconomic lines. Increased use of formal screening tools, increased

curricular time for mental health in primary care residencies, www.selleckchem.com/products/cftrinh-172.html support for physicians in the field in the form of referral options and remote consultation and support, may all serve to improve quality of care for individual patients, and may also serve to regularize treatment across socioeconomic and sociodemographic lines, hence reducing disparities. Further research is needed to study the root causes and dynamics that create such disparities, but the steps outlined above may help in the near term. (Int’l. J. Psychiatry in Medicine 2010;40:383-389)”
“Intestinal samples from 156 small Indian mongooses (Herpestes auropunctatus) collected island-wide in Grenada from

April 2011 to March GSK2126458 in vivo 2013 were examined for the presence of Salmonella enterica spp. Nineteen (12%) mongooses were culture-positive for S. enterica spp. of which five serotypes were identified. Salmonella javiana and S. Montevideo were the most commonly isolated serotypes. The other serotypes isolated were S. Rubislaw, S. Panama and S. Arechavaleta. All isolates were susceptible to amoxicillin-clavulanic acid, ampicillin, cefotaxime, ceftazidime, ciprofloxacin, enrofloxacin, gentamicin, nalidixic acid, imipenem and trimethoprim-sulfamethoxazole. One isolate (S. Montevideo) showed resistance to tetracycline and intermediate resistance to streptomycin. The five isolated Salmonella serotypes are potential human pathogens suggesting that the mongoose may play a role in the epidemiology of human salmonellosis in Grenada. (C) 2014 Elsevier Ltd. All rights reserved.”
“HIV-1 infection cannot be cured due to reservoirs formed early after infection.

Prospectively, it provides a promising tool for improving antenat

Prospectively, it provides a promising tool for improving antenatal detection, and highlights the need for appropriate buy GW786034 protocols and pathways, training and

resources to implement effective strategies for prevention.”
“L-Arginine metabolism is important in the maintenance of airway tone. Shift of metabolism from the nitric oxide synthase to arginase pathways contributes to the increased airway responsiveness in asthma. We tested the hypothesis that systemic levels of L-arginine metabolites are biomarkers reflective of airway dysfunction. We used a mouse model of acute allergic airway inflammation to OVA that manifests with significant airway hyperresponsiveness to methacholine. To determine tissue arginase activity in vivo, the isotopic enrichment of an infused L-arginine stable isotope and its product amino acid L-ornithine were measured in lung and airway homogenates using liquid chromatography-tandem mass spectrometry. Tissue and plasma concentrations Antiinfection Compound Library supplier of other L-arginine metabolites, including L-citrulline and symmetric and asymmetric dimethylarginine, were measured and correlated with lung arginase activity and methacholine responsiveness of the airways. The effectiveness of intratracheal instillation of an arginase inhibitor (boronoethylcysteine) on pulmonary arginase activity and circulating concentrations

of L-arginine metabolites was also studied. We demonstrate that 1) plasma indexes of L-arginine bioavailability and impairment of nitric oxide synthase function correlate with airway responsiveness to methacholine;

2) plasma levels of L-ornithine predict in vivo pulmonary arginase activity and airway function; and 3) acute arginase inhibition reduces in vivo pulmonary arginase activity to control levels and normalizes plasma L-ornithine, but not L-arginine, bioavailability in this model. We conclude that plasma L-ornithine may be useful as a systemic biomarker to predict responses to therapeutic interventions targeting airway arginase in asthma.”
“Background: The serine/threonine kinase LKB1 regulates cell growth and polarity in metazoans, and loss of LKB1 function is implicated in the development Vorinostat clinical trial of some epithelial cancers. Despite its fundamental role, the mechanism by which LKB1 regulates polarity establishment and/or maintenance is unclear. In the present study, we use the nematode C. elegans to investigate the role of the LKB1 ortholog PAR-4 in actomyosin contractility, a cellular process essential for polarity establishment and cell division in the early embryo. Results: Using high-resolution time-lapse imaging of GFP-tagged nonmuscle myosin II (NMY-2), we found that par-4 mutations reduce actomyosin contractility during polarity establishment, leading to the mispositioning of anterior PAR proteins and to defects in contractile ring ingression during cytokinesis.

“Interaction of cationic phenosafranin (PSF), anionic 8-an

“Interaction of cationic phenosafranin (PSF), anionic 8-anilino-1-naphthalene sulfonate (ANS) and nonionic nile red (NR) have been studied with the zwitterionic phospholipid, egg yolk L-alpha-phosphatidylcholine (EYPC). The study reveals discernible binding interactions of the three fluorescent probes with IPI145 the EYPC lipid vesicle. Once the binding of the probes with the lipid is established, the effect of cyclic oligosaccharide, beta-cyclodextrin (beta-CD), on these lipid bound probes has been investigated. Different fluorometric techniques

suggest that addition of beta-CD to the probe-lipid complexes leads to the release of the probes from the lipid medium through the formation of probe-beta-CD inclusion complexes. A competitive binding of the probes between beta-cyclodextrin and the lipid is ascribed to be responsible for the effect. This provides an easy avenue selleck chemicals llc for the removal of the probe molecules from the lipid environment. Extension of this work with drug molecules in cell membranes is expected to give rise to a strategy for the removal of adsorbed drugs from the cell membranes by the use of non-toxic beta-cyclodextrin. (C)

2015 Elsevier B.V. All rights reserved.”
“Yamak A, Temsah R, Maharsy W, Caron S, Paradis P, Aries A, Nemer M. Cyclin D-2 rescues size and function of GATA4 haplo-insufficient hearts. Am J Physiol Heart Circ Physiol 303: H1057-H1066, 2012. First published August 24, 2012; doi:10.1152/ajpheart.00250.2012.-Transcription factor GATA4 is a key regulator of cardiomyocyte growth, and differentiation

and 50% reduction in GATA4 levels results in hypoplastic hearts. Search for GATA4 targets/effectors revealed cyclin D-2 (CD2), a member of the D-type cyclins (D-1, D-2, and D-3) that play a vital role in cell growth and differentiation as a direct transcriptional target and a mediator of GATA4 growth in postnatal cardiomyocytes. GATA4 associates with the CD2 promoter in cardiomyocytes and is sufficient to induce endogenous CD2 transcription and to dose-dependently activate the CD2 promoter in heterologous cells. Autophagy Compound Library Cardiomyocyte-specific overexpression of CD2 results in enhanced postnatal cardiac growth because of increased cardiomyocyte proliferation. When these transgenic mice are crossed with Gata4 heterozygote mice, they rescue the hypoplastic cardiac phenotype of Gata4(+/-) mice and enhance cardiomyocyte survival and heart function. The data uncover a role for CD2 in the postnatal heart as an effector of GATA4 in myocyte growth and survival. The finding that postnatal upregulation of a cell-cycle gene in GATA4 haplo-insufficient hearts may be protective opens new avenues for maintaining or restoring cardiac function in GATA4-dependent cardiac disease.

The choriocapillaris was imaged with better resolution of microva

The choriocapillaris was imaged with better resolution of microvascular detail using PV-OCT. Areas of geographic atrophy and choroidal neovascularization imaged by FA were depicted by PV-OCT. Regions of capillary nonperfusion from diabetic retinopathy Doramapimod manufacturer were shown by both

imaging techniques; there was not complete correspondence between microaneurysms shown on FA and PV-OCT images. Conclusions: Phase-variance OCT yields high-resolution imaging of the retinal and choroidal microvasculature that compares favorably with FA. (C) 2014 by the American Academy of Ophthalmology.”
“Methylene blue (M), as a dye in sentinel lymph node mapping (SLNM), has been introduced as an alternative to lymphazurin (L) after the recent shortage of L. M has been evaluated in breast cancer in multiple studies with favorable results. Our study compares L with M in the SLNM of gastrointestinal (GI) tumors.\n\nBetween Jan 2005 and Aug 2008, 122 consecutive patients with GI tumors were enrolled. All patients (pts) underwent SLNM with either L or M by subserosal injection of 2-5 mL of

dye. Efficacy and rates of adverse reactions were compared between the two dyes. Patients were prospectively monitored for adverse reactions including anaphylaxis, development of blue hives, and tissue necrosis.\n\nOf 122 pts, 60 (49.2%) underwent SLNM using L and 62 (50.8%) underwent SLNM using M. Colon cancer (CrCa) was the most common site in both groups. The success rate of L and M in SLNM was 96.6% and 96.7%, respectively, selleck products with similar numbers of total number of lymph nodes per pt, SLNs per pt (< 3), nodal AZD1390 molecular weight positivity, skip metastasis,

and accuracy. The only adverse reaction in the L group was oxygen desaturation > 5% in 5% (3/60) of pts, compared with none in the M group. Cost per vial of L was $210 vs $7 for M.\n\nThe success rate, nodal positivity, average SLNs per patient, and overall accuracy were similar between L and M. Absence of anaphylaxis and lower cost make M more desirable than L in SLNM of GI tumors.”
“Aim: To investigate mononucleotide markers: BAT-25, BAT-26, NR-21, NR-22 and NR-24 in patients with colorectal cancer (CRC), and the status of HSP110T(17), KRAS, BRAF and the MLH1 promoter mutations in microsatellite unstable CRC. Methods: Genetic assessments were performed on samples obtained following resection of CRC in 200 patients. Results: Allelic variations of HSP110T(17) were found in all 18 patients with microsatellite instabilities (MSIs) in at least three markers (high-frequency MSI). By contrast, mutations of HSP110T(17) were absent in all 20 patients with no MSI frequency. Eight out of 182 patients with low (instability in one marker) or no frequency MSI had allelic shifts due to polymorphisms of BAT-25 (1.5%), NR-21 (1.75%) and NR-24 (1.5%). BRAF mutations were associated with >5 bp shortening of HSP110T(17).

The results indicate that CCK/gastrin may increase lung cancer pr

The results indicate that CCK/gastrin may increase lung cancer proliferation in an EGFR-dependent manner.”
“We study the stability of lipid bilayers with artificial domains. In investigating different domain structures, we identify scenarios of stable and unstable arrangements of patches of mixed phospholipids. These are then characterized using Karhunen-Loeve Expansion (KLE), a special form of Principal Components Analysis (PCA). The simulation data are interrogated using KLE to reveal spatiotemporal patterns that explain relevant motions in the

bilayer system. By projecting the high-dimensional dataset onto a small number of key modes, KLE reveals specific 4SC-202 research buy dynamic signatures that can help distinguish and characterize various domain instability mechanisms.

We find that typically very few modes are responsible for describing a find more mechanism of instability to a reasonable extent and can clearly distinguish between stable and unstable arrangements. Different instability modes are characterized as they exhibit unique features Re global deformation or local mixing modes. (C) 2008 Elsevier B.V. All rights reserved.”
“The superfamily of transforming growth factor-beta (TGF-beta) cytokines has been shown to have profound effects on cellular proliferation, differentiation, and growth. Recently, there have been major advances in our understanding of the signaling pathway(s) conveying TGF-beta signals to the nucleus to ultimately control gene ACY-738 manufacturer expression. One tissue that is potently influenced by TGF-beta superfamily signaling is skeletal muscle. Skeletal muscle ontogeny and postnatal physiology have proven to be exquisitely sensitive to the TGF-beta superfamily cytokine milieu in various animal systems from mice to humans. Recently, major strides have been made in understanding the role of TGF-beta and its closely related family member,

myostatin, in these processes. In this overview, we will review recent advances in our understanding of the TGF-beta and myostatin signaling pathways and, in particular, focus on the implications of this signaling pathway for skeletal muscle development, physiology, and pathology.”
“Microsatellite instability (MSI) is one of the leading mechanisms for the carcinogenesis of gastric cancer. Its prognostic value is controversial.\n\nBetween May 1988 and Oct 2003, a total of 214 gastric cancer patients undergoing curative surgery were enrolled, and their MSI statuses were classified as MSI-H (high) or MSI-L/S (low/stable). The clinicopathologic characteristics of MSI-H and MSI-L/S gastric cancers were compared.\n\nThe MSI-H tumors accounted for 11.7 % (n = 25) of the 214 total gastric cancers. Although not statistically significant, the MSI-H gastric cancers were more frequently located in the lower third of the stomach (64 % vs. 49.2 %) and were more often the intestinal type (72 % vs. 61.4 %) compared to the MSI-L/S gastric cancers.

Artesunate was used as a comparator Adverse events were monitore

Artesunate was used as a comparator. Adverse events were monitored and laboratory parameters Oil study Days 0, 2, 5, and 7 post drug administrations were analyzed. Results: Eighteen volunteers completed both rounds of the Study. Both drugs were well tolerated. All adverse events were mild. Significant decrease in hemoglobin compared JQ-EZ-05 cell line to baseline was detected for both drugs 7 days after administration (DHA: 0.48 g/dl, p = 0.007; artesunate 0.38 g/dl, p = 0.001). Transient bone marrow suppression was evidenced by reduction of reticulocytes with a lowest number on study Day 5 (artesunate 75% reduction in reticulocyte

count; DHA 47%, p <0.001 for both drugs compared to baseline). Conclusion: The present study confirmed our previous finding oil significant decrease in hemoglobin. Artesunate appeared to have more negative effects on the numbers of reticulocytes and white blood cells than DHA. Systemic laboratory and toxicity profiles presented in this study may be used as a framework for future clinical studies of artemisinin and its derivatives.”
“The proteins from the posterior silk gland of silkworm hybrids and their parents reared under high temperatures were studied by Selleckchem JPH203 using comparative proteomic and phosphoproteomic

analysis. A total of 82.07, 6.17 and 11.76 % protein spots showed additivity, overdominance and underdominance patterns, respectively. Fifteen differentially expressed protein spots were identified by peptide mass fingerprinting. Among these, four spots, including sHSPs and prohibitin protein that were directly relevant to heat response, were identified. Eleven protein spots were found to play an important role in silk synthesis, and nine protein spots expressed phosphorylation states. According to Gene ontology and KEGG pathway analysis, these nine spots played an important role in stress-induced signal transduction. Expression of most

silk synthesis-related proteins was reduced, whereas stress-responsive proteins increased with heat exposure time in learn more three breeds. Furthermore, most proteins showed under- or overdominance in the hybrids compared to the parents. The results suggested that high temperature could alter the expression of proteins related to silk synthesis and heat response in silkworm. Moreover, differentially expressed proteins occurring in the hybrid and its parents may be the main explanation of the observed heterosis.”
“Midfacial fractures rank first concerning maxillofacial traumatology. Collisions of two heads or head to object are the main causes for these fractures. An investigation based on a transient simulation using the finite element method was performed. A biomechanical head model was created and tested. A transient collision of two heads was simulated. The results were compared to a typical real patient case.

Photoluminescence experiments indicate that energy transfer proce

Photoluminescence experiments indicate that energy transfer processes can be tuned in these donor-acceptor

systems by varying the length and nature of the linker group. In preliminary device testing, ambipolar charge transport behavior is observed in organic field effect transistors, while single active component organic photovoltaic devices consisting of these materials achieved a maximum external quantum efficiency of 30%.”
“This work investigates multi-walled carbon nanotube frequencies via continuum mechanics-based spline collocation simulations using nanobeam-bending models. This modeling approach is suitable for the development of multi-walled carbon nanotube applications. The spline collocation procedure converts partial differential equations of vibration problems of multi-walled carbon nanotubes into a discrete eigenvalue problem. buy PFTα The effects

of surrounding elastic medium stiffness and the van der Waals forces on the dynamic behavior of multi-walled carbon nanotubes are investigated. Copyright (C) 2010 John Wiley & Sons, Ltd.”
“Background: The increase of the proportion of elderly people has implications for health care services. Advances in oral health care and treatment have resulted in a reduced number of edentulous individuals. An increasing number of dentate elderly people have tooth wear, periodontal disease, oral implants, and sophisticated restorations and prostheses. Hence, they are in need of both preventive and Z-IETD-FMK chemical structure curative oral health care continuously. Weakened oral PKC inhibitor health due to neglect of self care and professional care and due to reduced oral health care utilization is already present when elderly people are still community-dwelling. At the moment of (residential) care home admittance, many elderly people are in need of oral health care urgently. The key factor in realizing and maintaining good oral health is daily oral hygiene care. For proper daily oral hygiene care, many residents are dependent on nurses and nurse aides. In 2007, the Dutch guideline “Oral health care

in (residential) care homes for elderly people” was developed. Previous implementation research studies have revealed that implementation of a guideline is very complicated. The overall aim of this study is to compare a supervised versus a non-supervised implementation of the guideline in The Netherlands and Flanders (Belgium).\n\nMethods/Design: The study is a cluster randomized intervention trial with an institution as unit of randomization. A random sample of 12 (residential) care homes accommodating somatic as well as psycho-geriatric residents in The Netherlands as well as in Flanders (Belgium) are randomly allocated to an intervention or control group. Representative samples of 30 residents in each of the 24 (residential) care homes are monitored during a 6-months period. The intervention consists of supervised implementation of the guideline and a daily oral health care protocol.

The objective is to describe the epidemiology and outcomes of DNR

The objective is to describe the epidemiology and outcomes of DNR orders in trauma patients. Methods: We included all adults with trauma to a community Level I Trauma Center over 6 years (2008-2013). We used chi-square, Wilcoxon rank-sum, and multivariate stepwise logistic regression tests to characterize DNR (established in-house vs. pre-existing), describe predictors of establishing an in-house DNR, timing of an in-house DNR (early [within 1 day] vs late), and outcomes (death, ICU stay, major

complications). Dinaciclib Results: Included were 10,053 patients with trauma, of which 1523 had a DNR order in place (15%); 715 (7%) had a pre-existing DNR and 808 (8%) had a DNR established in-house. Increases were observed over time in both the proportions of patients with DNRs established in-house (p = 0.008) and age bigger than = 65 (p smaller than 0.001). Over 90% of patients with an in-house DNR were bigger than = 65 years. The following covariates were independently associated with establishing a DNR in-house: age bigger than = 65, severe neurologic deficit (GCS 3-8), fall mechanism of injury, ED tachycardia, female gender, and comorbidities (p smaller than 0.05 for all). Age

bigger than = 65, female gender, non-surgical service admission and transfers-in were associated with a DNR established early (p smaller than 0.05 for all). As expected, mortality was greater in patients with DNR than those without (22% vs. 1%), as was the development STA-9090 cost https://www.selleckchem.com/products/AZD1480.html of a major complication (8% vs. 5%), while ICU admission was similar (19% vs. 17%). Poor outcomes were greatest in patients with DNR orders executed later in the hospital stay. Conclusions: Our analysis of a broad cohort of patients with traumatic injury establishes the relationship between DNR and patient characteristics and outcomes. At 15%, DNR orders are prevalent in our general trauma population, particularly in patients bigger than = 65 years, and are placed early after arrival. Established prognostic factors, including age and physiologic severity, were determinants for in-house DNR orders.

These data may improve physician predictions of outcomes with DNR and help inform patient preferences, particularly in an environment with increasing use of DNR and increasing age of patients with trauma.”
“The mammalian nucleotide excision repair (Ner) pathway removes dangerous bulky adducts from genomic DNA. Failure to eliminate these lesions can lead to oncogenesis, developmental abnormalities and accelerated ageing. TFIIH is a central Ner factor that opens the damaged DNA through the action of its two helicases (XPB and XPD) prior to incision. Here we review our recently published data that suggest specific and distinct roles for these two helicases in Ner. we also discuss the regulation of XPB and XPD enzymatic activities within TFIIH and repair complexes, and show that mutations impeding enzyme-regulator interaction contribute to genetic disorders.