The main etiology of CS was predominantly vascular. All patients were treated with a silicon sheet to cover the LY2090314 mouse soft tissue defect and gradually reapproximate the skin margins. In 53% of the patients, a delayed final wound closure was achieved after a mean of 11.9 days. This method allows final closure of fasciotomy wounds without scar contractures, marginal necrosis, infection, or significant pain. (J Vasc Surg 2012;55:1826-8.)”
“The discrete functional classes of enteric neurons in the mammalian gastrointestinal tract have been successfully distinguished on the basis of the unique combination of molecules and enzymes in their cell bodies (“”chemical

coding”"). Whether the same chemical coding exists in varicose axons of different functional classes has not been systematically tested. In this study, we quantified the coexistence of markers that define classes of nerve cell bodies in the myenteric plexus of the guinea-pig ileum, in varicose axons of the same neurons. Profound differences between the combinations of immunohistochemical markers in myenteric nerve cell https://www.selleckchem.com/products/ve-821.html bodies and in their varicosities were identified. These discrepancies were particularly notable for classes of neurons that had previously been classified as cholinergic, based on immunoreactivity

for choline acetyltransferase (ChAT) in their cell bodies. To detect cholinergic varicose axons of enteric neurons in this study, we used Histidine ammonia-lyase antiserum against the vesicular acetylcholine transporter (VAChT). ChAT-immunoreactivity has been reported to be consistently co-localized with 5-hydroxytryptamine (5-HT) in interneuronal tell bodies, yet only 29 +/- 5% (n = 4) of 5-HT-immunoreactive varicosities contained vesicular acetylcholine transporter (VAChT). Somatostatin coexists with ChAT-immunoreactivity in a class of descending interneuron but only 21 +/- 1% (n = 4) of somatostatin-immunoreactive varicosities were VAChT-immunoreactive. Comparable discrepancies were also noted for non-cholinergic markers. The results suggest that chemical coding of cell bodies does

not necessarily reflect chemical coding of varicose axon terminals and that the assumption that nerve cell bodies that contain ChAT are functionally cholinergic may be questionable. (C) 2012 Published by Elsevier Ireland Ltd.”
“It is well-known that amphetamine induces increased locomotor activity in rodents. We previously found that intracerebroventricular (i.c.v.) administration of p-hydroxyamphetamine (p-OHA), an amphetamine metabolite, increases synaptic dopamine (DA) levels in the striatum. In the present study, we investigated the effect of p-OHA on locomotor activity in rodents.

In mice, i.c.v. administration of p-OHA significantly increased locomotor activity in a dose-dependent manner. p-Hydroxynorephedrine, another amphetamine metabolite, did not increase locomotor activity.

“
“The polycystic ovary syndrome (PCOS) is possibly the most common endocrine disorder in premenopausal women. The primary defect in PCOS consists of an exaggerated androgen secretion by the ovaries and the adrenal glands of affected women, which is amplified by several mechanisms including abdominal adiposity and insulin resistance. Abdominal adiposity contributes to hyperandrogenism by favoring insulin resistance and compensatory hyperinsulinism, because insulin facilitates ovarian and adrenal androgen synthesis, among other mechanisms. Furthermore, mounting evidence suggest that androgen excess may also contribute to a predominantly

abdominal disposition of body fat in women, suggesting that women with PCOS suffer from a vicious circle whereby androgen excess favoring 10058-F4 concentration the abdominal deposition of fat further facilitates androgen secretion by the ovaries and adrenals. Familial aggregation of PCOS cases suggests an inherited component in PCOS, yet the genetic mechanisms underlying this inheritance remain elusive. The

present manuscript reviews the hypothesis-free approaches – such as genomics and proteomics – that have been used recently to study PCOS, focusing on studies from our group addressing the gene expression profiles and the proteome of visceral adipose tissue of morbidly obese women presenting with or without PCOS.”
“The role of the hyperpolarization-activated current (Ih) mediated by HCN channels in temperature sensing by the hypothalamus was addressed.

Pomalidomide purchase In warm-sensitive neurons Staurosporine supplier (WSNs), exposure to ZD7288, an inhibitor of Ih mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, decreased their action potential amplitudes and frequencies significantly. By contrast, ZD7288 had little or no effect on temperature-insensitive neurons (TINs). Exposure of WSNs to ZD7288 led to a significant increase in the duration of the inter-spike interval and a reduction of Ih irreversibly. These results suggest that ZD7288 have the contrasting effects on the firing patterns of WSNs versus TINs, which implies HCN channels play a central role in temperature sensing by hypothalamic neurons. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“The Ser/Thr-specific phosphatase PHLPP pleckstrin homology (PH) domain leucine-rich repeat protein phosphatasel provides ‘the brakes’ for Akt and protein kinase C (PKC) signaling. The two isoforms of this recently discovered family, PHLPP1 and PHLPP2, control the amplitude and duration of signaling of Akt and PKC by catalyzing the dephosphorylation of the hydrophobic phosphorylation motif, a C-terminal phosphorylation switch that controls these kinases. Aberrant regulation of either kinase accompanies many diseases, notably diabetes and cancer. By specifically dephosphorylating the hydrophobic motif, PHLPP controls the degree of agonist-evoked signaling by Akt and the cellular levels of PKC.

“
“In Part I of this work, we carried out a logical analysis of a simple model describing the interplay between protein p53, its main negative regulator Mdm2 and DNA damage, and briefly discussed the corresponding differential model (Abou-Jaoude et al, 2009). This analysis allowed us to reproduce several qualitative features of the kinetics of the p53 response to damage and provided an interpretation of the short and long characteristic periods of oscillation reported by Geva-Zatorsky et al. (2006) depending on the irradiation dose Starting from this analysis, we focus here on more quantitative aspects of Talazoparib datasheet the dynamics of our network and combine the differential description of our system with stochastic

simulations which take molecular fluctuations into account We find that the amplitude of the p53 and Mdm2 oscillations is highly variable (to a degree that depends, however, on the bifurcation properties of the system) In contrast, peak width and timing remain more regular, consistent with the experimental data Our simulations also show that noise can induce repeated pulses

of p53 and Mdm2 that, at low damage, resemble the slow irregular fluctuations observed experimentally. EPZ004777 in vivo Adding the stochastic dimension in our modeling further allowed us to account for an increase of the fraction of cells oscillating with a high frequency when the irradiation dose increases, as observed by Geva-Zatorsky et al. (2006) (C) 2010 Elsevier Ltd. All rights reserved”
“Electroencephalographic slow-wave activity (EEG SWA) is an electrophysiological signature of slow (0.5 to 4.0 Hz), synchronized, oscillatory neocortical activity. In healthy individuals, EEG SWA is Galactokinase maximally expressed during non-rapid-eye-movement (non-REM) sleep, and intensifies as a function of prior wake duration.

Many of the cellular and network mechanisms generating EEG SWA have been identified, but a number of questions remain unanswered. For example, although EEG SWA is a marker of sleep need, its precise relationship with sleep homeostasis and its roles in the brain are unknown. In this review, the authors discuss their current understanding of the neural mechanisms and possible functions of EEG SWA.”
“Infection elimination may be an important goal of control programs Only in stochastic infection models can true infection elimination be observed as a fadeout. The phenomena of fadeout and variable prevalence are important in understanding the transmission dynamics of infectious diseases and these phenomena are essential to evaluate the effectiveness of control measures To investigate the stochastic dynamics of Mycobacterium avium subsp paratuberculosis (MAP) infection on US dairy herds with test-based culling intervention, we developed a multi-group stochastic compartmental model (a continuous time Markov chain model) with both horizontal and vertical transmission.

Recent research using VESPA responses to modulations of stimulus contrast has provided new insights into both early visual attention mechanisms and the

specificity Acalabrutinib of visual-processing deficits in schizophrenia. To allow a fuller interpretation of these and future findings, it is necessary to further characterize the VESPA in terms of its underlying cortical generators. To that end, we here examine spatio-temporal variations in the components of the VESPA as a function of stimulus location. We found that the first two VESPA components (C1/P1) each have a posterior dorsal midline focus and reverse in polarity across the horizontal meridian, consistent with retinotopic projections to calcarine cortex (V1) for the stimulus locations tested. Furthermore, the focal scalp topography of the VESPA was strikingly constant across the entire C1-P1 time-frame (50-120 ms) for each stimulus location, with negligible global scalp activity visible at the zero-crossing dividing the two. This indicates a common focal source underpinning both components, which

was further supported www.selleckchem.com/products/4-hydroxytamoxifen-4-ht-afimoxifene.html by a significant correlation between C1 and P1 amplitudes across subjects (r = 0.54; p < 0.05). These results, along with factors implicit in the method of derivation of the contrast-VESPA, lead us to conclude that these responses are dominated by activity from striate cortex. We discuss the implications of this finding for previous and future research using the VESPA. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Efficiency and precision in plant breeding can be enhanced by using diagnostic DNA-based markers for the selection of superior cultivars. This technique has been applied to many crops, including potatoes. The first generation of diagnostic DNA-based markers useful in potato breeding were enabled by several developments: genetic linkage maps based on DNA polymorphisms, linkage mapping of qualitative

and quantitative agronomic traits, cloning and Pomalidomide manufacturer functional analysis of genes for pathogen resistance and genes controlling plant metabolism, and association genetics in collections of tetraploid varieties and advanced breeding clones. Although these have led to significant improvements in potato genetics, the prediction of most, if not all, natural variation in agronomic traits by diagnostic markers ultimately requires the identification of the causal genes and their allelic variants. This objective will be facilitated by new genomic tools, such as genomic resequencing and comparative profiling of the proteome, transcriptome, and metabolome in combination with phenotyping genetic materials relevant for variety development.”
“In former mine workers and residents of Libby, Montana, exposure to amphibole-contaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma.

H255Q was the most common GBA mutation among Greek PD patients (4/172). V460L was only found in control individuals (2/132). Overall, GBA mutations were significantly overrepresented in a subgroup of early onset PD patients, compared to controls (P = 0.019, OR = 4.2; 95%CI = 1.28-13.82), suggesting that GBA mutations may modify age of onset for PD. (C) 2009 Published by Elsevier Ireland Ltd.”
“Recent

studies showed that air pollution is a risk factor for hospitalization for arrhythmias. However, there is limited evidence to suggest which subpopulations are at higher risk for arrhythmia development due to increased air pollutant exposure. This study was undertaken NU7441 molecular weight to examine the modifying effect of specific secondary diagnosis (including hypertension, diabetes, and congestive heart failure) on the relationship between frequency of emergency room (ER) visits for arrhythmias and ambient air pollutants concentrations. ER visits for arrhythmias and ambient air pollution data for Taipei were obtained for the period 2000-2006. The relative risk of selleck ER visits was estimated using a case-crossover approach. Data showed an increased risk of ER visits for arrhythmias in relation to increased O3 levels among individuals with a secondary diagnosis of hypertension and congestive heart failure.”
“The amyloid precursor protein (APP) is cleaved enzymatically by non-amyloidogenic

and amyloidogenic pathways. alpha-Secretase cleaves APP Lonafarnib mouse within P-amyloid protein (A beta) sequence, resulting in the release of a secreted fragment of APP (sAPP alpha) and precluding A beta generation. Cryptotanshinone (CTS), an active component of the medicinal herb Salvia miltiorrhiza, has been shown to improve learning and memory in several pharmacological models of Alzheimer’s disease (AD). However. the effects of CTS on the A beta plaque pathology and the APP processing in AD are unclear. Here we reported that CTS strongly attenuated amyloid plaque deposition in the brain of APP/PS1 transgenic mice. In addition, CTS significantly improved spatial

learning and memory in APP/PS1 mice assessed by the Morris water maze testing. To define the exact molecular mechanisms involved in the beneficial effects of CTS, we investigated the effects of the CTS on APP processing in rat cortical neuronal cells overexpressing Swedish mutant human APP695. CTS was found to decrease A beta generation in concentration-dependent (0-10 mu M) manner. Interestingly, the N-terminal APP cleavage product, sAPP alpha was markedly increased by CTS. Further study showed that alpha-secretase activity was increased by CTS. Taken together, our results suggested CTS improved the cognitive ability in AD transgenic mice and promoted APP metabolism toward the non-amyloidogenic products pathway in rat cortical neuronal cells. CTS shows a promising novel way for the therapy of AD.

(C) 2011 Elsevier Ltd. All rights reserved.”
“Recent research has demonstrated that experiential/environmental factors in early life can program the adult stress response in rats, and Pitavastatin purchase this is manifest

as altered hypothalamic-pituitary-adrenocortical activity and behavior in response to a stressor. Very little work has been devoted to investigating whether the environment during adolescence plays a similar rote in modulating ongoing developmental processes and how this might affect adult stress responding. Periadolescent predator odor (PPO) exposure was used here as a naturalistic model of repeated psychological stress. Behavioral and endocrine responses to PPO changed across the exposure period, and behavioral alterations persisted into adulthood. White adolescent rats showed pronounced avoidance responses upon initial PPO exposure, hyperactivity increased across the exposure period, especially in females. Corticosterone

(cort) responses to stressor exposure also changed in females, with higher physiological baseline levels observed at the end of the exposure period. In adulthood, relative to rats who had received a control manipulation during adolescence, PPO-exposed rats were more fearful in a novel open field and displayed altered responses to a predator odor stress test in adulthood. Moreover, lower levels of the D2 dopamine (DA) receptor were measured in prefrontal (infralimbic and dorsopeduncular) cortices of PPO-exposed rats. OSI-027 These Benzatropine findings suggest that the adolescent period may represent a sensitive period during which developmental programming of the stress response occurs. (c) 2007 Elsevier Ltd. All rights reserved.”
“Background India’s 2011 census revealed a growing imbalance between

the numbers of girls and boys aged 0-6 years, which we postulate is due to increased prenatal sex determination with subsequent selective abortion of female fetuses. We aimed to establish the trends in sex ratio by birth order from 1990 to 2005 with three nationally representative surveys and to quantify the totals of selective abortions of girls with census cohort data.

Methods We assessed sex ratios by birth order in 0.25 million births in three rounds of the nationally representative National Family Health Survey covering the period from 1990 to 2005. We estimated totals of selective abortion of girls by assessing the birth cohorts of children aged 0-6 years in the 1991,2001, and 2011 censuses. Our main statistic was the conditional sex ratio of second-order births after a firstborn girl and we used 3-year rolling weighted averages to test for trends, with differences between trends compared by linear regression.

A neuro-radiological examination showed no evidence of anatomical Citarinostat or structural alterations to the brain. We submitted the subject for a comprehensive neuropsychological assessment of the different cognitive processes involved in topographical orientation to evaluate his ability to navigate the spatial environment.

The results confirmed a severe developmental topographical disorder and deficits in a number

of specific cognitive processes directly or indirectly involved in navigation. The results are discussed with reference to the sole previously described case of developmental topographical disorientation (Pt1; Iaria et al., 2009). F.G. differs from the former case due to the following: the greater severity of his disorder, his complete lack of navigational skills, the failure to develop compensatory strategies, and the presence of a specific deficit in processing the spatial

relationships between the parts of a whole.

The present case not only confirms the existence of developmental topographical-skill disorders, but also sheds light on the architecture of topographical processes and their development in human beings. (C) 2010 Elsevier Ltd. All rights reserved.”
“The stalk of influenza neuraminidase (NA) has been a target of cleavage by various proteases, resulting in the release of catalytically active globular heads from virus particles. However, despite successful cases in a DMXAA research buy number of influenza subtypes, this strategy could not be applied to all influenza viruses due to high variation of the NA stalk. In the present study, reverse genetics was employed to construct non-pathogenic recombinant influenza A viruses, termed rgH1N1(LVPR) and rgH1N1(LVPR-GS), that harbor the NA of H5N1 virus engineered to contain a specific thrombin cleavage site at the stalk region. By using thrombin to cleave NA at its stalk, a productive extraction of NA globular heads could be obtained from purified rgH1N1(LVPR). Furthermore, it was found that the NA of rgH1N1(LVPR-GS) could be cleaved by endogenous thrombin

present in embryonated Quisqualic acid chicken eggs, resulting in the release of NA globular heads into allantoic fluids. These data highlight the use of thrombin cleavage as an effective strategy for extraction of active NA heads directly from live viral particles not only of H5N1 but, theoretically, of any subtype of influenza A viruses. (C) 2009 Elsevier B.V. All rights reserved.”
“It is still a matter of debate whether constructive apraxia (CA) should be considered a form of apraxia or, rather, the motor expression of a more pervasive impairment in visuo-spatial processing. Constructive disorders were linked to visuo-spatial disorders and to deficits in appreciating spatial relations among component sub-parts or problems in reproducing three-dimensionality. We screened a large population of brain-damaged patients for CA. Only patients with constructive disorders and no signs of neglect and/or aphasia were selected.

Finally, we use the model to study protein inhibition and to suggest molecular targets for anti-angiogenic therapies. (C)

2010 Elsevier Ltd. All rights reserved.”
“BACKGROUND: Cerebral arteriovenous malformations (AVMs) do not seem to be static congenital vascular malformations, but rather are dynamically changing YAP-TEAD Inhibitor 1 in vitro pathologies. It is well-known from clinical situations that these AVMs can enlarge or shrink. Nuclear factor kappa B (NF-kappa B) is a nuclear transcription factor that regulates a number of physiological processes, such as inflammation, apoptosis, and cellular growth.

OBJECTIVE: To analyze phosphorylation of NF-kappa B and related molecules in cerebral AVM specimens.

METHODS: We examined 19 specimens of cerebral AVMs from 18 patients. Immunohistochemical analysis

was performed using an NF-kappa B p65 (C22B4) rabbit monoclonal antibody, the phosphorylated form of NF-kappa B (PNF-kappa B) p65 (Ser276) rabbit antibody, and an I kappa B alpha mouse monoclonal antibody.

RESULTS: Expression of NF-kappa B was mainly confined to the endothelial lining and the Repotrectinib ic50 infiltrating inflammatory cells in the perivascular regions. PNF-kappa B showed the highest level of expression in both endothelial cells and perivascular infiltrating cells. PNF-kappa B was intensely expressed in the endothelium and perivascular infiltrating cells of 15 specimens (78.9%). NF-kappa B and I kappa B were also expressed in endothelial cells and perivascular

infiltrating inflammatory cells, but at lower levels than PNF-kappa B. Immunohistochemical studies revealed that PNF-kappa B was mainly concentrated in the nuclei of endothelial and infiltrating inflammatory cells. On the contrary, expression of both NF-kappa B and I kappa B was mainly concentrated in the cytoplasm of endothelial and inflammatory cells.

CONCLUSION: We detected TCL activation of NF-kappa B in the endothelium and perivascular infiltrating inflammatory cells within the cerebral AVM nidus, suggesting a role in the pathophysiology of cerebral AVM.”
“We propose a new model describing the production and the establishment of the stable gradient of the Bicoid protein along-the antero-posterior axis of the embryo of Drosophila. In this model, we consider that bicoid mRNA diffuses along the antero-posterior axis of the embryo and the protein is produced in the ribosomes localized near the syncytial nuclei. Bicoid protein stays localized near the syncytial nuclei as observed in experiments. We calibrate the parameters of the mathematical model with experimental data taken during the cleavage stages 11-14 of the developing embryo of Drosophila. We obtain good agreement between the experimental and the model gradients, with relative errors in the range 5-8%. The inferred diffusion coefficient of bicoid mRNA is in the range 4.6 x 10(-12)-1.

63, 95% CI 1.47-1.80, p < 0.0001), local recurrence (HR 1.78, 95% CI 1.45-2.19, p < 0.0001) and receipt of salvage therapy (HR 1.79,95% CI 1.58-2.02, p < 0.0001) but was not a significant predictor of systemic progression (p = 0.95), cancer specific death (p = 0.15) or overall mortality (p = 0.16).

Conclusions: The presence of a positive margin increased the

risk of biochemical recurrence, local recurrence and the need for salvage treatment but was not independently associated with systemic progression, cancer specific death or overall mortality. Ispinesib concentration These results should be considered when evaluating patients for adjuvant therapy.”
“Neurofibromatosis 2 is a familial syndrome characterized by the development of schwannomas, meningiomas and ependymomas. Most

of them are benign however, their location in the nervous system has harmful effects on important cranial and spinal structures. These tumors are developed as the outcome of NF2 gene (22q12) inactivation. The NF2 protein, merlin or schwannomin belongs to the Ezrin, Radixin, Moesin (ERM) family involved in the cytoskeletal network and has a tumor suppressor function. Inactivating mutations occur as “”de novo”" (more frequently) or as inherited, and most of them are frameshift or nonsense. Our aim is to study NF2 gene alterations in Argentine patients JQ1 concentration and relate them to clinical features. 10 families and 29 single patients were analyzed for: 1) at-risk haplotype by STR-segregation analysis and 2) NF2 gene mutations by SSCP/heteroduplex/sequencing. The at-risk haplotype was uncovered in 8 families and mutations were identified in 5 patients. The molecular data are in full agreement with the clinical features supporting previous reports. The obtained results were important for the detection of mutation-carrying relatives and exclusion of other individuals from risk. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: The true prevalence of Carteolol HCl urolithiasis in

asymptomatic adults is unknown. Unenhanced computerized tomography represents the gold standard for detection. We evaluated the prevalence and symptomatic incidence of urolithiasis in a large cohort of asymptomatic adults using noncontrast computerized tomography.

Materials and Methods: Low dose noncontrast computerized tomography was performed in 5,047 consecutive asymptomatic adults (mean age 56.9 years, 2,747 women and 2,300 men) between 2004 and 2008. Presence, size and location of urinary calculi were recorded. Screening prevalence as well as the incidence of symptomatic stone disease during a 10-year interval (1997 to 2007) was compared against previously established clinical risk factors.

Results: The screening prevalence of asymptomatic urolithiasis was 7.8% (395 of 5,047 adults) with an average of 2.1 stones per case (range 1 to 29) and a mean stone size of 3.0 mm (range 1 to 20). During a 10-year period 20.

Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected CH5183284 cell line cells through the rescue of cell surface MHC-I.”
“Background: Emerging evidence suggests that human cytomegalovirus (HCMV) is highly prevalent in tumours of different origin. This virus is implied to have oncogenic and oncomodulatory functions, through its ability

to control host gene expression. Human endogenous retroviruses (HERV) are also frequently active in tumours of different origin, and are supposed to contribute as cofactors to cancer development. Due to the high prevalence of HCMV in several different tumours, and its ability to control host cell gene expression, we sought to define whether HCMV may affect HERV transcription.

Findings: Infection of 3 established cancer cell lines, 2 primary glioblastoma cells, endothelial cells from 3 donors and monocytes from 4 donors with HCMV (strains VR 1814 or TB40/F) induced reverse transcriptase (RT) activity in all cells tested, but the response varied between donors. Both, gammaretrovirus-related class I elements HERV-T, HERV-W, HERV-F and ERV-9, and betaretrovirus-related class II elements HML-2 -4 and HML-7 -8, as well as spuma-virus related class III elements of the HERV-L group were up-regulated in response to HCMV infection in GliNS1 cells. Up-regulation of HERV activity

was more pronounced in cells harbouring active HCMV infection, but was also selleck inhibitor induced by UV-inactivated virus. The effect was only slightly affected by ganciclovir treatment and was not controlled by the IE72 or IE86 HCMV genes.

Conclusions: Within this brief report we show that HCMV infection induces HERV transcriptional activity in different cell types.”
“Background: SAMHD1 is a restriction factor that potently blocks infection

by HIV-1 and other retroviruses. We have previously demonstrated that SAMHD1 oligomerizes in mammalian cells by immunoprecipitation. Here we investigated the contribution of SAMHD1 oligomerization to retroviral restriction.

Results: SDHB Structural analysis of SAMHD1 and homologous HD domain proteins revealed that key hydrophobic residues Y146, Y154, L428 and Y432 stabilize the extensive dimer interface observed in the SAMHD1 crystal structure. Full-length SAMHD1 variants Y146S/Y154S and L428S/Y432S lost their ability to oligomerize tested by immunoprecipitation in mammalian cells. In agreement with these observations, the Y146S/Y154S variant of a bacterial construct expressing the HD domain of human SAMHD1 (residues 109-626) disrupted the dGTP-dependent tetramerization of SAMHD1 in vitro. Tetramerization-defective variants of the full-length SAMHD1 immunoprecipitated from mammalian cells and of the bacterially-expressed HD domain construct lost their dNTPase activity. The nuclease activity of the HD domain construct was not perturbed by the Y146S/Y154S mutations.