The presented

methods and techniques make it possible to modify the characteristics of oocytes and embryos and thus may become major tools in mammalian gamete and embryo agricultural or biotechnological applications in the future. (c) 2012 Elsevier B.V. All rights reserved.”
“Enhancer of zeste 2 (EZH2), a polycomb histone methyltransferase, is overexpressed in various cancers, including cervical cancer. Gene expression analysis revealed that increased expression of EZH2 is associated with cervical cancer progression, particularly the progression to invasive squamous cell carcinoma. Enhancer of zeste 2 is known to trimethylate lysine 27 on histone H3, leading to gene silencing that contributes selleck to the progression of tumours into a more aggressive form of cancer. However, the specific

molecular mechanisms by which EZH2 contributes to the development of cervical cancer remain largely unknown. Recently, an EZH2 inhibitor was reported to selectively 17DMAG order inhibit trimethylated lysine 27 on histone H3 and to reactivate silenced genes in cancer cells. In this study, we found that GSK343 (a specific inhibitor of EZH2 methyltransferase) induces phenotypic reprogramming of cancer cells from mesenchymal to epithelial cells, reducing proliferation and cell motility and blocking the invasion of cervical cancer cell lines both in vitro and in vivo. Treatment Sapanisertib price with the EZH2 inhibitor led to increased levels of the epithelial marker E-cadherin and decreased levels of mesenchymal markers such as N-cadherin and vimentin. The observed reprogramming is associated with restrained cervical cancer progression and provides

direct evidence in support of EZH2 as a therapeutic target.”
“Objectives To investigate whether bone erosions in patients with rheumatoid arthritis (RA) show evidence of repair.\n\nMethods 127 erosions were identified in metacarpophalangeal joints 2-4 of the right hands of 30 RA patients treated with tumour necrosis factor inhibitors (TNFi) and 21 sex, age and disease activity-matched patients treated with methotrexate. All erosions were assessed for their exact maximal width and depth by high-resolution mu CT imaging at baseline and after 1 year.\n\nResults All erosions detected at baseline could be visualised at follow-up after 1 year. At baseline, the mean width of bone erosions in the TNFi group was 2.0 mm; their mean depth was 2.3 mm, which was not significantly different from the methotrexate-treated group (width 2.4 mm; depth 2.4 mm). Mean depth of erosions significantly decreased after 1 year of treatment with TNFi (-0.1 mm; p=0.016), whereas their width remained unchanged. In contrast, mean depth and width of erosive lesions increased in the methotrexate-treated group. The reduction in the depth of lesions was confined to erosions showing evidence of sclerosis at the base of the lesion.

Next, nLC-ESI-MS-MS analysis of intact urinary phospholipids was performed, resulting in structural identification of 21 PCs and 12 PEs, followed by quantitative analysis using

a multiple standard addition method. This study demonstrated that nLC-ESI-MS-MS can be powerfully utilized for the study of relative changes in the contents and concentration of urinary PCs and PEs from breast cancer patients: total concentration of PCs and PEs of patient sample increased to (144 +/- 9)% and (171 +/- 11)%, respectively, compared to control sample but they decreased significantly following surgery.”
“Rock bream (Oplegnathus GS-9973 solubility dmso fasciatus) tumor necrosis factor-alpha: (rbTNF-alpha) gene was cloned, recombinantly produced, and the effect of the recombinant rbTNF-alpha on the respiratory burst activity of rock bream phagocytes was analyzed. Structurally, genomic DNA of rbTNF-alpha was comprised with four exons and three introns, and deduced amino acid sequence of its cDNA possessed the TNF family signature, a transmembrane domain, a protease cleavage site, and two cysteine residues,

buy AC220 which are the typical characteristics of TNF-alpha gene in mammals and fish. The chemiluminescent (CL) response of rock bream phagocytes was significantly enhanced by pre-incubation with recombinant rbTNF-alpha, when opsonized zymosan was used as a stimulant of the respiratory burst. However, CL enhancing effect of the recombinant rbTNF-alpha was very weak when the respiratory burst activity of phagocytes was triggered with phorbol-12-myristate-13-acetate (PMA) instead of zymosan. These results suggest that rock bream TNF-alpha might have an ability to prime the respiratory burst activity of phagocytes against receptor-mediated phagocytosis inducing stimulants, such as zymosan, but have little ability Protein Tyrosine Kinase inhibitor against stimulants not accompanying receptor-mediated phagocytosis. (C) 2009 Elsevier Ltd. All rights reserved.”
“The aggregation of proteins with expanded polyglutamine (polyQ) tracts is directly relevant to the formation

of neuronal intranuclear inclusions in Huntington’s disease. In vitro studies have uncovered the effects of flanking sequences as modulators of the driving forces and mechanisms of polyQ aggregation in sequence segments associated with HD. Specifically, a seventeen-residue amphipathic stretch (N17) that is directly N-terminal to the polyQ tract in huntingtin decreases the overall solubility, destabilizes nonfibrillar aggregates, and accelerates fibril formation. Published results from atomistic simulations showed that the N17 module reduces the frequency of intermolecular association. Our reanalysis of these simulation results demonstrates that the N17 module also reduces interchain entanglements between polyQ domains.

Genes and Immunity (2009) 10, 566-578; doi:10.1038/gene.2009.43; published online 4 June 2009″
“We examined the effect of dendritic cells engineered to express an HBV S antigen CD40L fusion gene (HBV S-ecdCD40L). The DNA of HBV S gene and the cDNA of the extracellular domain of human CD40 ligand were linked by cloning. Peripheral blood mononuclear cells (PBMC) from healthy adults were incubated and induced into dendritic cells (DC) in presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4(IL-4). The DCs were transfected

the novel construct, and the impact of the CBL0137 expressed clone assessed. We find that, compared with control groups, modification of DCs with HBV S-ecdCD40L fusion gene resulted in the activation of DCs with upregulated expression of immunologically important cell surface molecules (CD80, CD86 and HLA-DR) and proinflammatory cytokines (IL-12). The DCs modified with HBV S-ecdCD40L are able to stimulate enhanced

allogeneic T-cell proliferation in vitro. Thus, the fusion gene HBV S-ecdCD40L can promote DC’s activation and enhance its function and may prove to be the foundation for a new type of hepatitis B vaccine.”
“Objectives To assess the validity of self-reported Papanicolau (Pap) smear history in Norwegian women and to identify characteristics that influence the validity.\n\nMethods Interview data from a sample of 16,574 Norwegian 3-MA concentration women, aged 18-45, in 2004-2005, was compared with information from the population-based cytology register. Crude validity in the self-reports with respect to ever/never having taken a Pap smear was summarized. The validity of the reported interval since lost Pop smear was assessed by a smoothed distribution of the reported interval, stratified by the registered

interval. Characteristics of influence on validity were identified Lazertinib by logistic regression for true positives (sensitivity and positive predictive value), true negatives (specificity and negative predictive value) and for more than one year discrepancy in time since last Pap smear, between reported and registered interval.\n\nResults Overall validity was summarized by: concordance = 0.9, sensitivity = 0.97, positive predictive value = 0.92, specificity = 0.55, negative predictive value = 0.78 and report-to-records ratio = 1.51. The variance in the reported interval increased proportionally with the registered interval, and women tended to underestimate the interval (telescoping). Age and registered number of years since last Pop smear had the strongest influence on ever/never and time interval validity, respectively.\n\nConclusions Estimated screening rates, based on self-reporting without organized screening, are biased. Telescoping leads to increased risk for developing invasive disease, because women will postpone their next Pap smear.

We present eight patients with symptomatic, self-limiting pen-electrode edema post-DBS electrode implantation who presented post-operatively with distinct clinical presentations with imaging that revealed a hypodense area in the white matter surrounding the DBS electrode. Local and systemic tests for infection were negative. The edema resolved over time without surgical intervention. The etiology of the edema remains obscure. The transient nature of the edema and benign course with rapid and full resolution in all

our patients cautions against any hasty decision to explant the electrode, in the absence of any obvious signs of infection. (C) 2011 Elsevier Ltd. All rights reserved.”
“Objective: We analyzed the efficacy of continuous renal Entinostat inhibitor replacement therapy (CRRT) combined with blood transfusion for patients with crush syndrome Torin 2 cell line from an earthquake.\n\nMethods:

Eight patients with crush syndrome were included. CRRT were performed in six of eight patients with crush syndrome, and transfusion was performed in all eight patients. Routine blood tests, urea nitrogen, creatinine, blood coagulation function, electrolyte levels, and serum myoglobin were determined and analyzed.\n\nResults: Two patients regained their health completely, four patients required amputation but recovered well, and two patients died. The total amount of red blood cells transfused RG-7388 in vitro in the eight cases was 521 U (mean volume = 68.25 U). CRRT was performed 164 times in six patients (mean 27.33 times per person). The routine blood test results and coagulation and renal function parameters improved obviously (P < 0.05) in the six surviving patients.\n\nConclusions: Sufficient blood transfusion

and early dialysis treatment effectively improved the conditions of patients with crush syndrome. (C) 2011 Elsevier Ltd. All rights reserved.”
“Background Recruitment to primary care trials, particularly those involving young children, is known to be difficult. There are limited data available to inform researchers about the effectiveness of different trial recruitment strategies and their associated costs. Purpose To describe, evaluate, and investigate the costs of three strategies for recruiting febrile children to a community-based randomised trial of antipyretics. Methods The three recruitment strategies used in the trial were termed as follows: (1) local’, where paediatric research nurses stationed in primary care sites invited parents of children to participate; (2) remote’, where clinicians at primary care sites faxed details of potentially eligible children to the trial office; and (3) community’, where parents, responding to trial publicity, directly contacted the trial office when their child was unwell.

Moreover, firing was slightly but

significantly increased by ENaC delta subunit agonists (icilin and capsazepine). HMA’s profile of effects was distinct from that of the other drugs. Amiloride, benzamil and EIPA significantly decreased firing (P < 0.01 each) at 1 mu m, while 10 mu m HMA was required for highly significant inhibition (P < 0.0001). Conversely, amiloride, benzamil and EIPA rarely blocked firing entirely at 1 mm, whereas 1 mm HMA blocked 12 of 16 preparations. This pharmacology suggests low-affinity ENaCs are the important spindle mechanotransducer. In agreement with this, immunoreactivity to ENaC alpha, beta and gamma subunits was detected both by Western blot and immunocytochemistry. Immunofluorescence intensity ratios for ENaC alpha, beta or gamma relative to the vesicle marker synaptophysin in the LY3023414 solubility dmso same spindle all significantly exceeded controls (P < 0.001). Ratios for the related brain sodium channel 17-AAG purchase ASIC2 (BNaC1 alpha) were also highly significantly greater (P < 0.005). Analysis of confocal images showed strong colocalisation within the terminal of ENaC/ASIC2 subunits and synaptophysin. This study implicates ENaC and ASIC2 in mammalian mechanotransduction. Moreover, within the terminals they colocalise with synaptophysin, a marker for the synaptic-like vesicles which regulate

afferent excitability in these mechanosensitive endings.”
“Asp187 and Gln190 were predicted as conserved and closely located at the Na+ binding site in a topology and homology model structure of Na+/proline symporter (PutP) of Escherichia coli. The replacement of Asp187 with Ala or Leu did not affect proline transport activity; whereas, change to Gln abolished the active transport. The binding affinity for Na+ or proline of these mutants was similar to that of wild-type (WT) PutP. This

result indicates Asp187 to be responsible Compound C mw for active transport of proline without affecting the binding. Replacement of Gln190 with Ala, Asn, Asp, Leu and Glu had no effect on transport or binding, suggesting that it may not have a role in the transport. However, in the negative D187Q mutant, a second mutation, of Gln190 to Glu or Leu, restored 46 or 7% of the transport activity of WT, respectively, while mutation to Ala, Asn or Asp had no effect. Thus, side chain at position 190 has a crucial role in suppressing the functional defect of the D187Q mutant. We conclude that Asp187 is responsible for transport activity instead of coupling-ion binding by constituting the translocation pathway of the ion and Gln190 provides a suppressing mutation site to regain PutP functional activity.”
“Sugarcane is an important crop and a major source of sugar and alcohol. In this study, we performed de novo assembly and transcriptome annotation for six sugarcane genotypes involved in bi-parental crosses.

The toxicity of these ketone toxins have not been fully characterized nor are the pathogenesis and sequelae of poisoning completely understood. The objective of the current study was to characterize and describe the clinical and pathologic changes of rayless

goldenrod toxicity in goats. Fifteen goats were gavaged with rayless goldenrod to obtain benzofuran ketone doses of 0, 10, 20, 40, and 60 mg/kg/day. After 7 treatment days, AC220 chemical structure the goats were euthanized, necropsied, and tissues were processed for microscopic studies. After 5 or 6 days of treatment, the 40-mg/kg and 60-mg/kg goats were reluctant to move, stood with an erect stance, and became exercise intolerant. They had increased resting heart rate, prolonged recovery following exercise, and increased serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatinine kinase activities. All treated animals developed skeletal myopathy with dose-related distribution and severity. The goats dosed with 20 mg/kg and higher also developed myocardial degeneration and necrosis. Although skeletal myonecrosis was patchy and widely distributed, the quadriceps femoris was consistently damaged, even in low-dosed animals. Myocardial lesions were most severe in the papillary muscles of 60-mg/kg dosed animals. This indicates

that goats are highly susceptible to rayless goldenrod poisoning, and that the characteristic lesion of poisoning is Epigenetics inhibitor skeletal and cardiac

myonecrosis.”
“Purple acid phosphatase (PAP; EC 3.1.3.2) enzymes are metallophosphoesterases that hydrolysis phosphate ester bonds in a wide range of substrates. Twenty-nine PAP-encoding loci have been identified in the Arabidopsis genome, many of which have multiple transcript variants expressed in response to diverse environmental conditions. Having analyzed T-DNA insertion 10058-F4 datasheet mutants, we have provided strong pieces of evidence that AtPAP9 locus encodes at least two types of transcripts, designated as AtPAP9-1 and AtPAP9-2. These transcript variants expressed distinctly during the course of growth in medium containing sufficient phosphate or none. Further histochemical analysis by the use of AtPAP9-1 promoter fused to B-glucuronidase reporter gene indicated the expression of this gene is regulated in a tissue-specific manner. AtPAP9-1 was highly expressed in stipule and vascular tissue, particularly in response to fungal infection. Subcellular localization of AtPAP9-1:green fluorescent fusion protein showed that it must be involved in plasma membrane and cell wall adhesion. (C) 2014 Published by Elsevier B.V.”
“Flixweed (Descurainia Sophia L) is a problematic weed in winter wheat fields in China, which causes great loss of wheat yield. A total of 46 flixweed accessions from winter wheat-planting areas were collected and used for the survey of resistance to tribenuron-methyl and Pro197 mutation diversity.

Oral administration of gabapentin (30, 100 mg/kg) produced a dose-dependent inhibition of allodynia caused by paclitaxel and oxaliplatin, but not vincristine. Intrathecal injection of gabapentin (30, 100 mu g/site) significantly inhibited allodynia induced by paclitaxel, but not oxaliplatin and vincristine. Intraplantar injection of gabapentin (30, 100

mu g/site) did not significantly inhibit allodynia induced by paclitaxel and oxaliplatin. Paclitaxel increased the expression of mRNA of voltage-dependent calcium channel alpha(2)delta-1 subunit, an action site of gabapentin, in the dorsal spinal cord, and oxaliplatin increased it in the dorsal root ganglia. Vincristine was without effects learn more on alpha(2)delta-1 subunit mRNA in these regions. These results suggest that the efficacy of gabapentin in the treatment of mechanical allodynia is dependent on chemotherapy

agent used. It may be partly due to the distinct effects of chemotherapy agents on the expression LY333531 datasheet of alpha(2)delta-1 subunit of voltage-dependent calcium channel.”
“Background: Several urinary biomarkers have been assessed as showing a discriminatory ability to differentially diagnose prostate cancer, albeit with manipulation of the prostate. Here we examine the clinical utility of multiple members of the kallikrein family of proteins in non-manipulative urinary biomarker testing.\n\nMethods: Forty urine samples were collected from patients admitted for urological examination. Twenty, with a confirmed benign diagnosis and 20 with prostate cancer. The levels of 14 kallikrein proteins were measured in patient’s urine and normalized for creatinine.\n\nResults: Galardin Ten of the 14 kallikreins tested had detectable levels in urine. However, none showed statistical significance in discriminating patients. Serum PSA was superior to urine

PSA and other urinary kallikreins in separating patients with and without prostate cancer.\n\nConclusions: We were unable to distinguish men with and without prostate cancer using multiple kallikreins as urinary biomarkers. These results highlight the difficulties in diagnosing prostate cancer via urine testing for soluble biomarkers. (C) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.”
“The need for highly effective tick-borne encephalitis (TBE) vaccines has increased globally due to a variety of factors including climate, social, economic and demographic changes, which are thought to have promoted the expansion of the endemic region of TBE viruses. The first TBE vaccine, FSME-IMMUN (R) Inject, was introduced in the 1970s and has been continually improved since then to enhance both its safety and immunogenicity. The current formulation was established in 2001 and is marketed as FSME-IMMUN (R).

Objective: To evaluate 4EGI-1 purchase the antioxidant, analgesic, antidiarrheal, anthelmintic activities, and general toxicity of the ethanol extract of the roots. Materials and Methods: The extract was assessed for free-radical-scavenging activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, total phenolic content (TPC) by the Folin Ciocalteu reagent, antioxidant activity by the ferric reducing power assay, analgesic activity by the acetic acid-induced writhing and hot-plate

tests, antidiarrheal activity by the castor oil-induced diarrhea model in mice, anthelmintic activity on Paramphistomum cervi and Haemonchus contortus, and general toxicity by the brine shrimp lethality assay. Results: The extract showed free-radical-scavenging activity with an IC 50 value of 44.86 g/mL. TPC was 537.89 mg gallic acid equivalent/100 g of dried plant material. It showed concentration-dependent reducing power, and displayed 42.11 and 69.32% writhing inhibition at doses of 250 and 500 mg/kg body weight, respectively. The extract also significantly raised the pain threshold at the above-mentioned

dose levels. In vivo antidiarrheal property was substantiated by Torin 2 significant prolongation of latent period and decrease in total number of stools compared with the control. The LC 50 against brine shrimp nauplii was 36.21 g/mL. The extract exhibited dose-dependent decrease in paralysis and death time of the helminths. Conclusion: The above results demonstrated that the plant possesses notable bioactivities and somewhat supports its use in folk medicine.”
“Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration

of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. see more In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+)lin(-)Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+)lin(-)Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation.

The major cause for discontinuation was loss of response, in 18 cases. Combination treatment,

obesity and infusion reactions were found to be predictors of drug survival.”
“The aryl hydrocarbon receptor (AHR) is regarded as an important homeostatic transcriptional regulator within physiological and pathophysiological processes, including xenobiotic metabolism, endocrine function, immunity, and cancer. Agonist activation of the AHR is considered deleterious based on toxicological evidence selleck chemical obtained with environmental pollutants, which mediate toxic effects through AHR. However, a multitude of plant-derived constituents, e. g., polyphenols that exhibit beneficial properties, have also been described as ligands for the AHR. It is conceivable that some of the positive aspects of such compounds can be attributed to suppression of AHR activity through antagonism. Therefore, we conducted a dioxin response element reporter-based screen to assess the AHR activity associated with a range of flavonoid compounds. Our screen identified two flavonoids (5-methoxyflavone and 7,4′-dimethoxyisoflavone) Cell Cycle inhibitor with previously unidentified AHR agonist potential. In addition, we have identified

and characterized 6,2′,4′-trimethoxyflavone (TMF) as an AHR ligand that possesses the characteristics of an antagonist having the capacity to compete with agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo[a] pyrene, thus effectively inhibiting AHR-mediated transactivation of a heterologous reporter and endogenous targets, e. g., CYP1A1, independent of cell lineage or species. Furthermore, TMF displays superior action by virtue of having no partial agonist activity, in contrast to other documented antagonists, e. g., alpha-napthoflavone,

which are partial weak agonists. TMF also exhibits no species or promoter dependence with regard to AHR antagonism. TMF therefore represents an improved tool allowing for more precise dissection of AHR function in the absence of any conflicting Evofosfamide manufacturer agonist activity.”
“Trehalose uptake at 65 degrees C in Rhodothermus marinus was characterized. The profile of trehalose uptake as a function of concentration showed two distinct types of saturation kinetics, and the analysis of the data was complicated by the activity of a periplasmic trehalase. The kinetic parameters of this enzyme determined in whole cells were as follows: K-m = 156 +/- 11 mu M and V-max = 21.2 +/- 0.4 nmol/min/mg of total protein. Therefore, trehalose could be acted upon by this periplasmic activity, yielding glucose that subsequently entered the cell via the glucose uptake system, which was also characterized. To distinguish the several contributions in this intricate system, a mathematical model was developed that took into account the experimental kinetic parameters for trehalase, trehalose transport, glucose transport, competition data with trehalose, glucose, and palatinose, and measurements of glucose diffusion out of the periplasm.

SMARCA2 mutations caused NCBRS, typically with short stature, sparse hair, a thin vermillion of the Omipalisib solubility dmso upper lip, an everted lower lip and prominent finger joints. A SMARCE1 mutation caused CSS without typical facial coarseness and with significant digital/nail hypoplasia. ARID1A mutations caused the most severe CSS with severe physical complications. ARID1B mutations caused CSS without typical facial coarseness and with mild digital/nail hypoplasia, or caused syndromic ID. Because of the common underlying mechanism and overlapping clinical features, we propose that these conditions be referred to collectively as

“SWI/SNF-related ID syndromes”. (C) 2013 Wiley Periodicals, Inc.”
“Epithelial PRIMA-1MET inhibitor malignancies frequently metastasize to the serous cavities and result in symptomatic effusions. Cytology has high specificity but moderate sensitivity for the diagnosis of a malignant effusion. We developed and validated a simple, rapid, 3-color flow cytometric panel using the adhesion molecule Ber-EP4 to detect epithelial cells in effusions. One hundred ninety-five consecutive benign and malignant effusions received for routine cytologic examination were analyzed Eighty-three fluid specimens were benign and 76 were malignant as judged by follow-up

data. Ber-EP4 positive cells were detected with flow cytometry in 89.3% of malignant effusions. The sensitivity and specificity of flow cytometry was 88.15% and 97.64% compared with 73.68% and 100% on cytologic examination alone for the presence of a malignant effusion. Flow cytometry is a useful adjunct to cytology for the diagnosis of a malignant effusion and is particularly useful if the cytologic diagnosis is atypical/suspicious or if the cytologic preparations are hypocellular or hemorrhagic.”
“The Drosophila

disconnected (disco) gene encodes a C(2)H(2)-type zinc finger transcription factor required for the development of the central and peripheral nervous systems. We report that disco participates in a positive feedback loop with the Dll gene, a master regulator of ventral appendage development. Dll function is not only required for proper disco expression EPZ-6438 mouse in antenna and leg discs, but is also sufficient for ectopic expression of disco in the developing retina and wing imaginal discs. Conversely, disco gene function is required for the maintenance of Dll expression. We show that Dll phenotypes are partially rescued by the up-regulation of disco expression in the Dll domain. Reduction in disco gene function disrupts antenna and leg development, and the phenotypes closely resemble that produced by Dll alleles. These observations demonstrate that disco plays a fundamental role in the Dll-dependent patterning of antenna and leg, perhaps as a regulator of Dll gene expression.”
“The Mre11/Rad50/Nbs1 protein complex plays central enzymatic and signaling roles in the DNA-damage response.