In the present study, locomotor activity in a novel environment

In the present study, locomotor activity in a novel environment

and dopamine turnover was significantly decreased in orexin-deficient mice compared to WT mice, which suggests that psychostimulants may be useful for maintaining wakefulness in orexin deficiency. We also examined the effects of orexin deficiency on psychostimulant-induced hyperlocomotion. The hyperlocomotion induced by methamphetamine and methylphenidate was lower, whereas that induced by MDMA was higher in orexin KO mice compared to WT mice. The sensitivities against psychostimulants MK-4827 in orexin/ataxin-3 mice differed from those in orexin KO mice. These results indicate that the effectiveness of each psychostimulant, which is closely related to its monoaminergic function, was influenced by orexin deficiency itself as well as by the different pathophysiological background in orexin deficiency. (C) 2009 Published by Elsevier Ltd.”
“The logic of cellular decision-making is largely Anlotinib controlled by regulatory circuits defining molecular switches. Such switching elements allow to turn a graded input signal into an all-or-nothing output. Traditional studies have focused on this bistable picture of regulation, but higher-order scenarios involving tristable and tetrastable states are possible too. Are these multiswitches allowed in simple gene regulatory networks? Are they likely to be observed? If

not, why not? In this paper we present the examination of this question by means of a simple but powerful geometric approach. We examine the relation

between multistability, the degree of multimerization of the regulators and the role of autoloops within a deterministic setting, finding that N-stable circuits are possible, although their likelihood to occur rapidly decays with the order of the switch. Our work indicates that, despite two-component circuits are able to implement multistability, they are optimal for Boolean switches. The evolutionary Cell press implications are outlined. (C) 2009 Elsevier Ltd. All rights reserved.”
“Transcranial magnetic stimulation (TMS) is a unique method for non-invasive brain imaging. The fundamental difference between TMS and other available non-invasive brain imaging techniques is that when a physiological response is evoked by stimulation of a cortical area, that specific cortical area is causally related to the response. With other imaging methods, it is only possible to detect and map a brain area that participates in a given task or reaction. TMS has been shown to be clinically accurate and effective in mapping cortical motor areas and applicable to the functional assessment of motor tracts following stroke, for example. Many hundreds of studies have been published indicating that repetitive TMS (rTMS) may also have multiple therapeutic applications.

Inhibition of CaMKK did not affect the glycolytic activation indu

Inhibition of CaMKK did not affect the glycolytic activation induced by another herpes virus, herpes simplex virus type 1 (HSV-1). Furthermore, inhibition of CaMKK had a

much smaller impact on HSV-1 replication than on that of HCMV. These data suggest that the role of CaMKK during the viral life cycle is, in this regard, HCMV specific. Taken together, our results suggest that CaMKK is an important factor for HCMV replication and HCMV-mediated glycolytic activation.”
“BACKGROUND: Epilepsy surgery for magnetic resonance imaging (MRI)-negative patients has a less favorable outcome.

OBJECTIVE: Detection of subclinical abnormal gyration Idasanutlin price (SAG) patterns and their potential contribution to assessment of the topography of the epileptogenic zone

(EZ) is addressed in MRI-negative patients with frontal lobe epilepsy.

METHODS: Between September 1998 and July 2005, 12 MRI-negative frontal lobe epilepsy patients underwent stereoelectroencephalography with postcorticectomy follow-up of longer than 1 year (average, 3.3 years). Original software (BrainVISA/Anatomist, http://brainvisa.info) trained on a database of normal volunteers was used to determine which sulci had morphology out of the normal range (SAG). Topography find more of the EZ, SAG pattern, corticectomy, postoperative seizure control, and histopathology were analyzed.

RESULTS: At last follow-up, 8 of 12 patients (66.7%) Oxygenase were Engel class I (7 IA and 1 IB), 2 class II, and 2 class IV. Small focal cortical dysplasia was histologically diagnosed in 9 of the 12 patients (75%), including 7 of 8 seizure-free patients (87.5%). A SAG pattern was found

to be in the EZ area in 9 patients (75%), in the ipsilateral frontal lobe out of the EZ in 2, and limited to the contralateral hemisphere in 1.

CONCLUSION: SAG patterns appear to be associated with the topography of the EZ in MRI-negative frontal lobe epilepsy and may have a useful role in preoperative assessment. Small focal cortical dysplasia not detected with MRI is often found on histopathological examination, particularly in the depth of the posterior part of the superior frontal sulcus and intermediate frontal sulcus, suggesting a specific developmental critical zone in these locations.”
“Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL) cells are predominantly infected with latent Kaposi’s sarcoma-associated herpesvirus (KSHV), presenting a barrier to the destruction of tumor cells. Latent KSHV can be reactivated to undergo lytic replication. Here we report that in PEL cells, oxidative stress induced by upregulated reactive oxygen species (ROS) can lead to KSHV reactivation or cell death. ROS are upregulated by NF-kappa B inhibition and are required for subsequent KSHV reactivation.

Conversely, discrete genetic anomalies are involved in Down, Rett

Conversely, discrete genetic anomalies are involved in Down, Rett and Fragile X syndromes, tuberous sclerosis and neurofibromatosis, the less familiar Phelan-McDermid, Sotos, Kleefstra, Coffin-Lowry and “”ATRX”" syndromes, and the disorders of imprinting, Angelman and Prader-Willi

syndromes. NDDs have been termed “”synaptopathies”" in reference to structural and functional disturbance of synaptic plasticity, several involve abnormal Ras-Kinase signalling (“”rasopathies”"), and many are characterized by disrupted cerebral connectivity and an imbalance between excitatory and inhibitory transmission. However, at a different level of integration, NDDs are accompanied by aberrant “”epigenetic”" regulation of processes critical for normal and orderly development of the brain. Epigenetics refers to potentially-heritable (by mitosis and/or meiosis) mechanisms Selleckchem Luminespib controlling gene expression without changes in DNA sequence. In certain NDDs, prototypical epigenetic processes of DNA methylation and covalent histone marking are impacted. Conversely, others involve anomalies in chromatin-modelling, mRNA splicing/editing,

mRNA translation, ribosome biogenesis and/or the regulatory actions of small nucleolar RNAs and micro-RNAs. Since epigenetic mechanisms are modifiable, this raises the hope of novel therapy, though questions remain concerning efficacy and safety. LY2835219 purchase The above issues are critically surveyed in this review, which advocates a broad-based epigenetic

framework for understanding and ultimately treating a diverse assemblage of NDDs (“”epigenopathies”") lying at the interface of genetic, developmental and environmental processes.

This article is part of the Special Issue entitled ‘Neurodevelopmental Disorders’. (c) 2012 Elsevier Ltd. All rights reserved.”
“High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and cause anogenital and head and neck squamous cell carcinomas (SCCs). AZD4547 in vitro The E7 gene is considered the predominant viral oncogene and drives proliferation and genome instability. While the implementation of routine screens has greatly reduced the incidence of cervical cancers which are almost exclusively HPV positive, the proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV oncogene expression and genome load are linked to disease progression, but genetic risk factors that regulate oncogene abundance and/or genome amplification remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome characterized at least in part by extreme susceptibility to SCCs. FA results from mutations in one of 15 genes in the FA pathway, whose protein products assemble in the nucleus and play important roles in DNA damage repair.

CONCLUSION: Complete microsurgical occlusion of the residual aneu

CONCLUSION: Complete microsurgical occlusion of the residual aneurysm is possible. However, in large or giant aneurysms direct microsurgery is a challenging high-risk procedure, and we recommend that these patients be referred to a dedicated

neurovascular center to minimize surgical complications. Even in experienced hands, use of different bypass procedures may be the best option for demanding growing lesions, especially those in the posterior Selleckchem Mocetinostat circulation.”
“We systematically reviewed reports about determinants of HIV infection in injecting drug users from 2000 to 2009, classifying findings by type of environmental influence. We then modelled changes in risk environments in regions with severe HIV epidemics associated with injecting drug use. Of 94 studies identified, 25 intentionally examined risk environments. Modelling of HIV epidemics showed substantial heterogeneity in the number of HIV infections that are attributed to injecting drug use and unprotected sex. We estimate that, during 2010-15, HIV prevalence could

be reduced by 41% in Odessa (Ukraine), 43% in Karachi (Pakistan), and 30% in Nairobi (Kenya) through a 60% reduction of the unmet need of programmes for opioid substitution, needle exchange, and antiretroviral therapy. Mitigation of patient transition to injecting drugs from non-injecting forms could avert a 98% increase in learn more HIV infections in Karachi; whereas elimination of laws prohibiting opioid substitution with concomitant scale-up could prevent 14% of HIV infections in Nairobi. Optimisation of effectiveness and coverage of interventions is crucial for regions with rapidly growing epidemics. Delineation of environmental risk factors provides a crucial insight into HIV prevention. Evidence-informed, rights-based, combination interventions protecting IDUs’ access to HIV prevention and treatment could substantially curtail HIV epidemics.”
“BACKGROUND: The International Study of Intracranial Aneurysms found that for patients with no previous history of subarachnoid

hemorrhage, small (< 7 mm) anterior circulation and posterior circulation aneurysms had a 0% and 2.5% risk of subarachnoid hemorrhage MTMR9 over 5 years, respectively.

OBJECTIVE: To determine whether cerebral aneurysms shrink with rupture.

METHODS: The clinical databases of 7 sites were screened for patients with imaging of cerebral aneurysms before and after rupture. Inclusion criteria included documented subarachnoid hemorrhage by imaging or lumbar puncture and intracranial imaging before and after cerebral aneurysm rupture. The patients were evaluated for aneurysm maximal height, maximal width, neck diameter, and other measurement parameters. Only a change of >= 2 mm was considered a true change.

RESULTS: Data on 13 patients who met inclusion criteria were collected. The median age was 60, and 11 of the 13 patients (84.6%) were female. Only 5 patients had posterior circulation aneurysms.

5-HT also promotes an efflux of DA through reversal of the direct

5-HT also promotes an efflux of DA through reversal of the direction of DA transport. By analogy with the mechanism of action described for amphetamine, the consequences of 5-HT entering DA terminals might explain both the excitatory and inhibitory effects of 5-HT on presynaptic DA terminal activity, but the physiological relevance of this mechanism is far from clear. The recent data suggest that the endogenous 5-HT system affects striatal DA release in GSK923295 mouse a state-dependent manner associated with the conditional involvement of various 5-HT receptors such as 5-HT(2A), 5-HT(2C), 5-HT(3), and 5-HT(4) receptors.

Methodological and pharmacological issues have prevented

a comprehensive overview of the influence of 5-HT on striatal DA activity. The distribution of striatal 5-HT receptors

and their restricted influence on DA neuron activity suggest that the endogenous 5-HT system exerts multiple and subtle influences on DA-mediated behaviors.”
“We explored the attenuating effects of NP-9 on beta-amyloid (A beta) aggregation and amyloid-induced toxicity. NP-9 is a recently reported monoamine oxidase B (MAO-B), and acetylcholinesterase (AChE) inhibitor. In the present study, we found that NP-9 inhibited AChE activity in a dose-dependent manner with a maximal inhibition dose of 8 mg/kg, i.p. It inhibited A beta aggregation, observed through thioflavin-T assay (IC50 = 60 mu M) and scanning electron GSKJ4 microscopy (S.E.M.) (no fibril formation). NP-9 has shown marked protection against scopolamine and Levetiracetam A beta(1-42)-induced memory impairments. It also minimized neuronal loss and amyloid plaque deposition in the brains

of A beta(1-42)-induced mice model. Therefore, NP-9 could be a promising lead molecule for AD, with effects against MAO-B, AChE, A beta aggregation, and A beta(1-42) induced toxicity. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Dysfunction of serotonergic systems is thought to play an important role in a number of neurological and psychiatric disorders. Recent studies suggest that there is anatomical and functional diversity among serotonergic systems innervating forebrain systems involved in the control of physiologic and behavioral responses, including the control of emotional states.

Here, we highlight the methods that have been used to investigate the heterogeneity of serotonergic systems and review the evidence for the unique anatomical, hodological, and functional properties of topographically organized subpopulations of serotonergic neurons in the midbrain and pontine raphe complex.

The emerging understanding of the topographically organized synaptic regulation of brainstem serotonergic systems, the topography of the efferent projections of these systems, and their functional properties, should enable identification of novel therapeutic approaches to treatment of neurological and psychiatric conditions that are associated with dysregulation of serotonergic systems.

The patient was operated on urgently The proximal portion of the

The patient was operated on urgently. The proximal portion of the endograft had eroded into the previously placed Dacron elephant trunk limb. The proximal portion of the endograft was removed and was replaced with a Dacron graft. The management of this patient forms the basis of this report. (J Vase Surg 2009;49:491-3.)”
“A 61-year-old woman with neurofibromatosis type I (Recklinghausen’s

disease) was referred for massive swelling of the right forearm, pain, increasing numbness, and impaired movement of the fingers. Angiography demonstrated a 13- x 11-mm aneurysm and a capped rupture BGJ398 solubility dmso of the ulnar artery. Because of the complicated soft-tissue condition, interventional treatment was indicated. Two 360 degrees coils were placed for embolization of the ruptured aneurysm. Arterial involvement in neurofibromatosis is a well known but infrequent occurrence. Stenotic lesions predominate. Aneurysmal defects are less common, and rupture of peripheral arteries is exceptional. CDK inhibitor (J Vasc Surg 2009;49:494-6.)”
“Non-uniform terminology in the world’s venous literature has continued to pose a significant hindrance to the dissemination of knowledge regarding the management of chronic venous disorders. This VEIN-TERM

consensus document was developed by a transatlantic interdisciplinary faculty of experts under the auspices of the American Venous Forum (AVF), NCT-501 mouse the European Venous Forum (EVF), the International Union of Phlebology (IUP), the American College of Phlebology (ACP),

and the International Union of Angiology (IUA). It provides recommendations for fundamental venous terminology, focusing oil terms that were identified as creating interpretive problems, with the intent of promoting the use of a common scientific language in the investigation and management of chronic venous disorders. The VEIN-TERM consensus document is intended to augment previous transatlantic/international interdisciplinary efforts in standardizing venous nomenclature which are referenced in this article. (J Vasc Surg 2009;49:498-501.)”
“Recent evidence has suggested that bone marrow derived progenitor cells may contribute to the development of intimal hyperplasia after arterial injury, a process that classically has been believed to involve extracellular matrix deposition and the migration and proliferation of cells within the arterial wall. The first studies demonstrating the existence of bone marrow derived cells in the neointima employed mouse models of arterial injury in conjunction with whole bone marrow transplant. Later studies have shown specifically that bone marrow derived hematopoietic or mesenchymal stern cells call be recruited to the neointima and differentiate into smooth muscle cells or endothelial cells.

(C)

(C) buy PF299804 Published by Elsevier Ltd.”
“H1N1 influenza causes substantial seasonal illness and was the subtype of the 2009 influenza pandemic. Precise measures of antigenic distance between the vaccine and circulating virus strains help researchers design influenza vaccines with high vaccine effectiveness. We here introduce a sequence-based method to predict vaccine effectiveness in humans. Historical epidemiological data show that this sequence-based method is as predictive of vaccine effectiveness as hemagglutination inhibition assay data from ferret animal

model studies. Interestingly, the expected vaccine effectiveness is greater against H1N1 than H3N2, suggesting a stronger immune response against H1N1 than H3N2. The evolution rate of hemagglutinin in H1N1 is also shown to be greater than that in H3N2, presumably due to greater immune selection pressure.”
“Herpes simplex virus (HSV) and other alphaherpesviruses must move from sites of latency in ganglia to see more peripheral epithelial cells. How HSV navigates in neuronal axons is not well understood.

Two HSV membrane proteins, gE/gI and US9, are key to understanding the processes by which viral glycoproteins, unenveloped capsids, and enveloped virions are transported toward axon tips. Whether gE/gI and US9 function to promote the

loading of viral proteins onto microtubule motors in neuron cell bodies or to tether viral proteins onto microtubule motors within axons is not clear. One impediment to understanding how HSV gE/gI and US9 function in axonal transport relates to observations that gE(-), gI(-), or US9(-) mutants are not absolutely blocked in axonal transport. Mutants are significantly reduced in numbers of capsids and glycoproteins in distal axons, but there are less extensive effects in proximal axons. We constructed find more HSV recombinants lacking both gE and US9 that transported no detectable capsids and glycoproteins to distal axons and failed to spread from axon tips to adjacent cells. Live-cell imaging of a gE(-)/US9(-) double mutant that expressed fluorescent capsids and gB demonstrated >90% diminished capsids and gB in medial axons and no evidence for decreased rates of transport, stalling, or increased retrograde transport. Instead, capsids, gB, and enveloped virions failed to enter proximal axons. We concluded that gE/gI and US9 function in neuron cell bodies, in a cooperative fashion, to promote the loading of HSV capsids and vesicles containing glycoproteins and enveloped virions onto microtubule motors or their transport into proximal axons.

Altered MAPK signaling has been associated with the inflammatory

Altered MAPK signaling has been associated with the inflammatory and autoimmune diseases lupus and arthritis and with some pathogenic viral infections. HIV-1 infection is characterized by chronic GSK1904529A nmr immune inflammation, aberrantly heightened CD8(+) T cell activation levels, and altered T cell function. The relationship between MAPK pathway function, HIV-1-induced activation (CD38 and HLA-DR), and exhaustion (Tim-3) markers in circulating CD8(+) T

cells remains unknown. Phosphorylation of the MAPK effector proteins ERK and p38 was examined by “”phosflow”" flow cytometry in 79 recently HIV-1-infected, antiretroviral-treatment-na ve adults and 21 risk-matched HIV-1-negative controls. We identified a subset of CD8(+) T cells refractory to phorbol 12-myristate 13-acetate plus ionomycin-induced ERK1/2 phosphorylation (referred to as p-ERK1/2-refractory cells) that was greatly expanded in HIV-1-infected adults. The CD8(+) p-ERK1/2-refractory cells were highly activated (CD38+ HLA-DR+) but not exhausted (Tim-3 negative), tended to have low CD8 expression, and were enriched in intermediate and late transitional memory states of differentiation (CD45RA(-) CD28(-) CD27(+/-)). Targeting MAPK pathways to restore ERK1/2 signaling may normalize immune inflammation levels and restore CD8(+) T cell function

during HIV-1 infection.”
“Occlusal disharmony induces chronic stress, which results in learning deficits in association with the morphologic changes in the hippocampus, e.g., neuronal degeneration and increased hypertrophied glial fibrillary acidic Pifithrin-�� cell line protein-positive cells. To investigate the mechanisms underlying impaired hippocampal function resulting from occlusal disharmony, we examined the effects of the bite-raised condition on the septohippocampal cholinergic system by assessing acetylcholine ISRIB release in the hippocampus and choline acetyltransferase immunoreactivity in the medial septal nucleus in aged SAMP8 mice that underwent the bite raising procedure. Aged bite-raised mice showed decreased acetylcholine release in the hippocampus and a reduced number of choline acetyltransferase-immunopositive neurons in the medial

septal nucleus compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice enhances the age-related decline in the septohippocampal cholinergic system, leading to impaired learning. (c) 2012 Elsevier Ireland Ltd. All rights reserved.”
“It has been suggested that discrepant findings regarding low basal cortisol levels and enhanced suppression of cortisol in response to dexamethasone (DEX) administration in post-traumatic stress disorder (PTSD) may reflect individual differences in gender, trauma type, stage of development at trauma occurrence (e.g., childhood vs. adulthood), early pre-traumatic risk factors, or other individual differences. This study examined salivary cortisol levels at 08.00h and 16.00h as well as cortisol response to 0.

This suggests that cognitive impairment results from subtle, sub-

This suggests that cognitive impairment results from subtle, sub-lethal changes In the cortex. Recently,

changes in the structural coherence in mini- or microcolumns without loss of neurons have been linked to loss of function. Here we use a density map method to quantify microcolumnar structure in both banks of the sulcus principalis (prefrontal cortical area 46) of 16 (ventral) and 19 (dorsal) behaviorally tested female rhesus monkeys from 6 to 33 years of age, While total neuronal density does not change with age In either of these banks, there Is a significant age-related reduction in the strength of microcolumns in both regions on the order of 40%. This likely reflects a subtle but definite loss of organization In the structure of the this website cortical microcolumn. The reduction in strength in ventral area 46 correlates with cognitive impairments in learning and memory while the reduction in dorsal area 46 does not. This result is congruent with published data attributing cognitive functions to ventral area 46 that are similar to our particular cognitive battery which does not optimally tap cognitive functions attributed to dorsal area 46. While the exact mechanisms underlying this loss of microcolumnar organization remain to be

determined, It Is plausible that they reflect age-related alterations in dendritic and/or axonal organization which alter connectivity and may contribute to age-related declines In cognitive performance. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“In the enteric nervous system (ENS)

excitatory nicotinic cholinergic transmission is mediated by neuronal nicotinic acetylcholine receptors JQ1 nmr (nAChR) and is critical for the regulation of gastric motility. nAChRs are ligand-gated pentameric ion channels Eltanexor molecular weight found in the CNS and peripheral nervous system. The expression of heteromeric nAChR and receptor subunit mRNAs was investigated in the neonatal rat ENS using receptor autoradiography with the radiolabeled ligand (125)I-epibatidine, and in situ hybridization with subtype specific probes for ligand binding alpha (alpha 2, alpha 3, alpha 4, alpha 5, alpha 6) and structural beta (beta 2, beta 3, beta 4) subunits. The results showed strong nicotine sensitive binding of (125)I-epibatidine around the stomach, and small and large intestines. The binding was partially displaced by A85380, a nicotinic ligand which differentiates between different heteromeric nAChR subtypes, suggesting a mixed receptor population. Radioactive In situ hybridization detected expression of alpha 3, alpha 5, alpha 7, beta 2 and beta 4 mRNA in the myenteric plexus of the stomach, and small and large intestines. In the submucosal plexus of the small and large intestines expression of alpha 3, alpha 5 and beta 4 was found in some ganglia. There was no signal for alpha 4, alpha 6 and beta 3 In the ENS but positive hybridization signal for alpha 2 transcripts was seen in some areas of the small Intestines.

Findings Under-5 deaths have continued to decline, reaching 7 2 m

Findings Under-5 deaths have continued to decline, reaching 7.2 million in 2011 of which 2.2 million were early neonatal, 0.7 million late neonatal, 2.1 million postneonatal, and 2.2 million during childhood (ages 1-4 years). Comparing rates of decline from 1990 to 2000 with 2000 to 2011 shows that 106 countries have accelerated declines in the child mortality rate in the past decade. Maternal mortality has also continued to decline from 409 100 OSI-027 (uncertainty interval 382 900-437 900) in 1990 to 273 500 (256 300-291 700) deaths in 2011. We estimate

that 56 100 maternal deaths in 2011 were HIV-related deaths during pregnancy. Based on recent trends in developing countries, 31 countries will achieve MDG 4, 13 countries MDG 5, and nine countries will achieve both.

Interpretation Even though progress on reducing maternal and child mortality in most countries is accelerating, most developing countries will take many years past 2015 to achieve the targets of the MDGs 4 and 5. Similarly, Panobinostat in vivo although there continues to be progress on maternal mortality the pace is slow, without any overall evidence of acceleration. Immediate concerted action is needed

for a large number of countries to achieve MDG 4 and MDG 5.”
“Contact inhibition of locomotion (CIL) is the process by which cells in vitro change their direction of migration upon contact with another cell. Here, we revisit the concept that CIL plays a central role in the migration of single cells and in collective migration, during both health and disease. Importantly, malignant

cells exhibit a diminished CIL behaviour which allows them to invade healthy tissues. Accumulating evidence indicates that CIL occurs in vivo and that regulation of small Rho GTPases is important in the collapse of cell protrusions upon cell contact, the first step of CIL. Finally, we propose possible cell surface proteins that could be involved in the initial contact that regulates Rho GTPases during CIL.”
“Human Fas ligand is a medically important transmembrane glycoprotein directing the induction of apoptosis. The influence of N-terminal part (Q103-P138) truncation of human Fas ligand extracellular DNA/RNA Synthesis inhibitor domain (hFasLECD) on the expression of N-terminal FLAG-(Gly)(5)-tagged hFasLECD (NFG5-hFasLECD) with partial N-glycosylation-sites deletion in Pichia pastoris was investigated. The N-terminal part truncation significantly improved the secretion level of both singly (N184Q) and doubly (N184Q, N250Q) N-glycosylation-sites deleted NFG5-hFasLECD. The highly purified N-terminal truncated NFG5-hFasLECD with the double N-glycosylation-sites deletion mutation was obtained using single-step cation-exchange chromatography.