Nucleolin RNA levels or protein were not modified during FCV infection; however, as a consequence of the infection, nucleolin was seen to relocalize from

the nucleoli to the nucleoplasm, as well as to the perinuclear area where it colocalizes with the feline calicivirus NS6/7 protein. In addition, antibodies to nucleolin were able to precipitate viral RNA from feline calicivirus-infected cells, indicating a direct or indirect association of nucleolin with the viral RNA during virus replication. Small interfering Liproxstatin-1 in vitro RNA (siRNA)-mediated knockdown of nucleolin resulted in a reduction of the cytopathic effect and virus yield in CrFK cells. Taken together, these results demonstrate that nucleolin is a nucleolar component that interacts with viral RNA and NS6/7 and is required for feline calicivirus replication.”
“Lentiviral vectors are potent gene transfer vehicles frequently applied in research and lately also in clinical applications. Recent improvements have come from combining lentiviral vectors with engineered envelope proteins, which now allow targeting of cell Elacridar in vitro entry to any cell population of interest, as well as the transduction of quiescent cells of the haematopoietic system. We propose

that measles virus envelope glycoproteins are especially well suited for this purpose because they can mediate pH-independent cell entry at the cell surface membrane and can induce

cytoskeleton rearrangements that facilitate the transport of lentiviral core particles to the cell nucleus. Lentiviral vectors pseudotyped with measles virus glycoproteins are expected to improve the safety and efficacy of gene transfer to human cells.”
“In this report, a core-changeable needle enzymatic reactor was developed for highly efficient proteolysis. A piece of enzyme-immobilized fiber core was inserted into the needle of a syringe pump to form a flow-through bioreactor. The novel in-needle bioreactor could be regenerated by changing buy ML323 its fiber core. The feasibility and performance of the unique bioreactor were demonstrated by the tryptic digestion of BSA and lysozyme and the digestion time was significantly reduced to less than 5 s. The digests were identified by MALDI-TOF MS with sequence coverages comparable to those obtained by the conventional in-solution tryptic digestion. The present in-needle bioreactor provides a promising platform for the high-throughput protein identification.”
“Variation in the complement receptor 1 gene (CR1) has been identified in recent genome-wide association studies as a risk factor for Alzheimer’s disease.

In this study, we investigated the basis of this chemoresistance by applying the ‘side population’ (SP) analysis to blood samples from B-CLL patients. We report the existence of few natural SP cells, which harbors phenotypic and cytogenetic hallmarks of B-CLL in most patients with this disease (n = 22). SP cells appeared resistant to conventional B-CLL treatments, such as Fludarabine, Bendamustin or Rituximab. Indeed, treatment with Fludarabine (16/18 cases) or Bendamustin (5/7 cases) resulted in complete elimination

of non-SP, whereas cells displaying the SP phenotype were the only surviving. Although some Buparlisib nmr B-CLL SP cells were innately chemoresistant, chemotherapy by Fludarabine selected not only innate SP cells but also induced some acquired SP cells, which arose from non-SP by drug-driven evolution. This SP selection by chemotherapeutic treatments is further supported by the overall increase of the SP percentage in patients who experienced chemotherapy in the preceding year. Functionally, proliferative PS-341 ic50 stimulation of SP cells was able to partially replenish in vitro the non-SP cell compartment of the B-CLL disease. The chemoresistance of B-CLL relies, in our model, on the cellular heterogeneity of B-CLL SP cells and on their regenerating dynamics. Leukemia (2010) 24, 1885-1892; doi:10.1038/leu.2010.176; published

online 9 September 2010″
“In individuals with ASD, difficulties with language comprehension selleckchem are most evident when higher-level semantic-pragmatic language processing is required, for instance when context has to be used to interpret the meaning of an utterance. Until now, it is unclear at what level of processing; and for what type of context these difficulties in language

comprehension occur. Therefore, in the current fMRI study, we investigated the neural correlates of the integration of contextual information during; auditory language comprehension in 24 adults with ASD and 24 matched control participants. Different levels of context processing were manipulated by using spoken sentences that were correct or contained either a semantic or world knowledge anomaly. Our findings demonstrated significant differences between the groups in inferior frontal cortex that were only present for sentences with a world knowledge anomaly. Relative to the ASD group, the control group showed significantly increased activation in left inferior frontal gyrus (LIFG) for sentences with a world knowledge anomaly compared to correct sentences. This effect possibly indicates reduced integrative capacities of the ASD group. Furthermore, world knowledge anomalies elicited significantly stronger activation in right inferior frontal gyrus (RIFG) in the control group compared to the ASD group. This additional RIFG activation probably reflects revision of the situation model after new, conflicting information.

We identified cross-reactive antibodies from A/Brisbane/59/2007 sera that recognize non-HA epitopes in pdmH1N1 virus. Passive serum transfer showed that cross-reactive sH1N1-induced antibodies conferred protection in naive recipient mice during pdmH1N1 virus challenge. The presence or absence of anti-HA antibodies, therefore, is not the sole indicator of the effectiveness of protective cross-reactive antibody immunity. Measurement of additional antibody repertoires targeting Apoptosis inhibitor the non-HA antigens of influenza virus should be taken into consideration in assessing

protection and immunization strategies. We propose that preexisting cross-protective non-HA antibody immunity Quizartinib molecular weight may have had an overall protective effect during the 2009 pdmH1N1 outbreak, thereby reducing disease severity in human infections.”
“Much research shows that early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal

manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational

memory also depended upon timing of manipulation. Enhanced MK-1775 datasheet performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. (C) 2012 Elsevier Ltd. All rights reserved.”
“The Step Trial showed that the MRKAd5 HIV-1 subtype B Gag/Pol/Nef vaccine did not protect men from HIV infection or reduce setpoint plasma viral RNA (vRNA) levels but, unexpectedly, it did modestly enhance susceptibility to HIV infection in adenovirus types (Ad5)-seropositive, uncircumcised men. As part of the process to understand the results of the Step Trial, we designed a study to determine whether rhesus macaques chronically infected with a host-range mutant Ad5 (Ad5hr) and then immunized with a replication defective Ad5 SIVmac239 Gag/Pol/Nef vaccine were more resistant or susceptible to SIV infection than unimmunized rhesus macaques challenged with a series of escalating dose penile exposures to SIVmac 251.

35 mg per deciliter vs. 4.5 mg per deciliter [0.4 mmol per liter vs. 0.3 mmol per liter], P = 0.008). Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P0.001), and edema was more frequent (12.9% vs. 6.4%, P = 0.007).

CONCLUSIONS

As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance

to type 2 diabetes mellitus by 72% but was associated with significant weight selleck screening library gain and edema.”
“BACKGROUND

Exposure to methylmercury from fish consumption has been linked to a potentially increased risk of cardiovascular disease, but evidence from prior studies is equivocal. Beneficial effects of the ingestion of fish and selenium may also modify such effects.

METHODS

Among subjects from two U. S. cohorts (a total of 51,529 men and 121,700 women) whose

toenail clippings had been stored, we prospectively identified incident cases of cardiovascular disease (coronary heart disease and stroke) in 3427 participants and matched them to risk-set-sampled controls according to age, sex, race, and smoking status. Toenail mercury and selenium concentrations were assessed with the use of neutron-activation analysis. Other demographic characteristics, cardiovascular risk factors, fish consumption, and lifestyle habits were assessed by means of validated questionnaires. GSK1838705A supplier Associations between mercury exposure and incident cardiovascular disease were evaluated with the use of conditional logistic regression.

RESULTS

Median toenail mercury concentrations

were 0.23 mu g per gram (interdecile range, 0.06 to 0.94) in the case participants and 0.25 mu g per gram (interdecile range, 0.07 to 0.97) in the controls. In multivariate analyses, participants with higher mercury exposures did not have a higher risk of cardiovascular disease. For comparisons of the fifth quintile of mercury exposure with the first quintile, the relative risks were as follows: coronary heart disease, 0.85 (95% confidence interval [CI], 0.69 to 1.04; P = 0.10 for trend); stroke, 0.84 (95% CI, 0.62 to 1.14; P = 0.27 for trend); and total cardiovascular disease, 0.85 (95% CI, 0.72 to 1.01; P = 0.06 for trend). selleck compound Findings were similar in analyses of participants with low selenium concentrations or low overall fish consumption and in several additional sensitivity analyses.

CONCLUSIONS

We found no evidence of any clinically relevant adverse effects of mercury exposure on coronary heart disease, stroke, or total cardiovascular disease in U. S. adults at the exposure levels seen in this study.”
“BACKGROUND

Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA B* 1502 allele.

In this study we further characterized VCV resistance in a lab-adapted, VCV-resistant RU570 virus (RU570-VCV(res)). We show that K305R, R315Q, and K319T amino acid changes in the V3 loop, along with P437S in C4, completely reproduced

the resistance phenotype in a chimeric ADA envelope containing the C2-V5 region from RU570 passage control gp120. The K305R amino acid change primarily impacted the degree of resistance, whereas K319T contributed to both resistance and virus infectivity. The P437S mutation in C4 had more influence on the relative degree of virus infectivity, while the R315Q mutation contributed to the virus concentration-dependent phenotypic resistance pattern observed for RU570-VCV(res). RU570-VCV(res) pseudovirus Volasertib chemical structure entry with VCV-bound CCR5 was dramatically reduced by Y10A, D11A, Y14A, and Y15A mutations in the N terminus of CCR5, whereas these mutations had less impact on entry in the absence of VCV. Notably, an additional Q315E/I317F substitution in the crown region of the V3 loop enhanced resistance to VCV, resulting in a stronger dependence on the N terminus

for viral entry. By fitting the envelope mutations to a molecular PF477736 datasheet model of a recently described docked N-terminal CCR5 peptide consisting of residues 2 to 15 in complex with HIV-1 gp120 CD4, potential new interactions in gp120 with the N terminus of CCR5 were uncovered. The cumulative results of this study suggest that as the RU570 VCV-resistant virus adapted to use the drug-bound receptor, it also developed

an increased reliance on the N terminus of CCR5.”
“The present study examined the relationship between P200 and phonological processing in Chinese word recognition. Participants did a semantic judgment task on pairs of words. The critical pairs were all semantically unrelated in one of three conditions: homophonic, rhyme, or phonologically unrelated. Noting the possibility that P200 may be affected by phonological similarity and orthographic similarity and that literature studies may not have assessed such effects separately, the present study used visually dissimilar word pairs sharing no phonetic radicals. Relative to the control pairs, both the homophonic and rhyme pairs learn more elicited a significantly larger P200 with a scalp distribution centering at the centroparietal areas. The results present strong evidence that P200 can be modulated by lexical phonology alone, independent of sub-lexical phonology, or lexical or sub-lexical orthography. P200 effects were comparable in amplitude and topography between the homophonic and the rhyme conditions, suggesting that P200 is sensitive to phonology at both the syllabic and the sub-syllabic levels. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Autophagy is an important component of host innate and adaptive immunity to viruses. It is critical for the degradation of intracellular pathogens and for promoting antigen presentation.

Nitric oxide synthase/nitric oxide (NOS/NO) system in the RVLM modulates cardiovascular activities. Our experiments were designed to test the hypothesis that orexin-A (OXA) is involved in the mechanism of stress-induced hypertension (SIH) by adjusting NOS/NO system in the RVLM. The stress-induced

hypertensive rats (SIHR) model was established by electric foot-shocks and noises. Here we examined the expression of OXA immunoreactive (OXA-IR) 5-Fluoracil purchase cells in the lateral hypothalamus (LH) and the protein level of orexin 1 receptor (OX1R) in the RVLM of SIHR, and we found that the expressions of OXA-IR and OX1R were higher than those of the control group. The double-staining immunohistochemical evidence showed that OX1R immunoreactive (OX1R-IR) cells and neuronal nitric oxide synthase (nNOS) or inducible nitric oxide

synthase ��-Nicotinamide mouse (iNOS) immunoreactive (IR) cells were co-localizated in the RVLM. Microinjection of OXA (10, 50, 100 pmol/100 nl) into the unilateral (right) RVLM of control rats or SIHR produced pressor and tachycardiac effects in a dose-dependent manner. SB-408124 (100 pmol/100 nl, an antagonist of OX1R) or TCS OX2 29 (100 pmol/100 nl, an antagonist of OX2R) partly abolished the cardiovascular effects of exogenously-administrated OXA into the RVLM of control rats and SIHR, and lowered the increased systolic blood pressure (SBP) and heart rate (HR) of SIHR, with no difference in statistical significance between the two antagonists’ effects. Microinjection into the RVLM of both control and SIHR groups

of 7-Ni (0.05 pmol/100 nl, nNOS inhibitor) or Methylene Blue [100 pmol/100 nl, an inhibitor of soluble guanylate cyclase (sGC)] suppressed the OXA-induced increase of SBP and HR, whereas microinjection of AG (1, 10, 100 pmol/100 nl) had no obvious effects on the OXA-induced increase of SBP and HR. Our results indicate that OXA in the RVLM may participate in the central regulation of cardiovascular activities in SIHR, and OX1R and OX2R both have important roles in it. The cardiovascular effects of OXA in the RVLM may be induced by nNOS-derived click here NO, which activated sGC-associated signaling pathway. (c) 2012 Elsevier Ltd. All rights reserved.”
“Acute graft-versus-host disease (GvHD) limits the applicability of allogeneic hematopoietic cell transplantation for the treatment of leukemia. GvHD occurs as a consequence of multiple activating events in antigen-presenting cells (APCs) and T cells (Tcs). Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase involved in multiple signaling events of immune cells. Therefore, we hypothesized that Syk may be a promising target to inhibit GvHD, which involves activation of different immune cell populations. In vivo expansion of luciferase(+) donor Tcs in mice developing GvHD was reduced by treatment with the Syk inhibitor Fostamatinib, which led to increased survival and reduced histologically confirmed GvHD severity.

Storage and emptying symptoms were recorded in 87.6% and 84.6% of group 1 patients, respectively. Opening and maximum flow detrusor pressure significantly correlated with urethral sphincter volume,

and mean and maximum urethral closure pressure and detrusor thickness correlated with urethral sphincter volume. Dysfunctional voiding could be diagnosed by ultrasound when an increase in detrusor thickness and striated sphincter volume were observed. A threshold sphincter volume P5091 price of 1.96 cm(3) had 100% sensitivity and 63.2% specificity, and a threshold detrusor thickness of 4.95 mm had 100% sensitivity and 85.4% specificity for identifying patients with dysfunctional voiding.

Conclusions: We think that perineal ultrasound is useful in the evaluation of dysfunctional voiding in women with recurrent urinary tract infections.”
“Background: Alternatives to surgery are needed for the treatment of vulvar intraepithelial neoplasia. We investigated

the effectiveness of imiquimod 5% cream, a topical immune-response modulator, for the treatment of this condition.

Methods: Fifty-two patients with grade 2 or 3 vulvar intraepithelial neoplasia were randomly assigned to receive either imiquimod or placebo, applied twice weekly for 16 weeks. The primary buy SB431542 outcome was a reduction of more than 25% in lesion size at 20 weeks. Secondary outcomes were histologic regression, clearance of human papillomavirus (HPV) from the lesion, changes in Bcl-w immune cells in the epidermis and dermis of the vulva, relief of symptoms, improvement of quality of life, and durability of response. Reduction in lesion size was classified as complete response

(elimination), strong partial response (76 to 99% reduction), weak partial response (26 to 75% reduction), or no response (lessthan/equal 25% reduction). The follow-up period was 12 months.

Results: Lesion size was reduced by more than 25% at 20 weeks in 21 of the 26 patients (81%) treated with imiquimod and in none of those treated with placebo (P<0.001). Histologic regression was significantly greater in the imiquimod group than in the placebo group (P<0.001). At baseline, 50 patients (96%) tested positive for HPV DNA. HPV cleared from the lesion in 15 patients in the imiquimod group (58%), as compared with 2 in the placebo group (8%) (P<0.001). The number of immune epidermal cells increased significantly and the number of immune dermal cells decreased significantly with imiquimod as compared with placebo. Imiquimod reduced pruritus and pain at 20 weeks (P=0.008 and P=0.004, respectively) and at 12 months (P=0.04 and P=0.02, respectively).

The primary outcomes were in-hospital mortality, stroke, hospital charges, and discharge disposition. Subgroup analyses were performed to evaluate these outcomes by neurologic presentation using chi(2) and multivariable logistic regression.

Results: Of the 404,256 discharges for carotid revascularization,

CAS utilization was 66% higher in 2006 than in 2005 (9.3% vs 14%, P = .0004). Crude mortality, stroke, and median charges remained higher for CAS than for CEA; discharge to home was more common after CEA. Results improved from 2005 to 2007. By logistic regression of the total cohort from 2005 to CH5183284 datasheet 2006, CAS was independently predictive of mortality (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.08-2.00; P < .0001). Independent predictors of stroke included CAS (OR, 1.43; 95% CI, 1.18-1.73; P < .0001) and symptomatic disease (OR, 2.4; 95% CI, 2.06-2.93;P < .0001). Among subgroups based on neurological presentation, regression showed that

CAS significantly increased the odds of stroke in asymptomatic patients (OR, 1.6; 95% CI, 1.2-2.0; P = .0003). Among symptomatic patients, CAS increased the odds of in-hospital death (OR, 3.0; 95% CI, 1.7-5.1, P < .0001) and trended toward significance for stroke CP 690550 (OR, 1.7; 95% CI, 1.0-2.8; P = .0569).

Conclusion: Utilization of CAS has increased from the years 2005 to 2007 with some improvements in the outcome. Despite improvements in outcome, resource utilization remains significantly higher for CAS than CEA. (J Vasc Surg 2011;53:307-15.)”
“Amyloid beta peptide 1-40 (A beta(1-40)) is closely associated

with the progressive neuronal loss and cognitive decline observed in Alzheimer’s disease (AD). This study aimed to establish a proteomic strategy for the profiling of AD tissues for disease-specific changes in protein abundance. Intrahippocampal injection of A beta(1-40) Tryptophan synthase induced spatial memory and learning decline in rats. Proteomic analysis revealed the changes in protein expression in the rat hippocampus treated with A beta(1-40). Four proteins of interest which was in abundance was significantly altered in A beta(1-40)-treated rats were identified by peptide mass fingerprint (PMF). These proteins corresponded to synapsin Ib, protein disulfide-isomerase A3 precursor, tubulin beta chain and ATP synthase beta subunit. Our results provide new insights into the relationship between A beta and the pathogenesis of AD, and suggest potential targets for the therapy of AD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Background: Current data suggest microembolization to the brain may result in long-term cognitive dysfunction despite the absence of immediate clinically obvious cerebrovascular events.

From a genetic screen, we found that the cytochrome P450 oxygenase CYP-13A12 acts in response to the EGL-9-HIF-1 pathway to facilitate the O2-ON response. CYP-13A12 MG-132 supplier promotes oxidation of polyunsaturated fatty acids into eicosanoids, signaling molecules that can

strongly affect inflammatory pain and ischemia-reperfusion injury responses in mammals. We propose that roles of the EGL-9-HIF-1 pathway and cytochrome P450 in controlling responses to reoxygenation after anoxia are evolutionarily conserved.”
“Robust transmission of information despite the presence of variation is a fundamental problem in cellular functions. However, the capability and characteristics of information transmission in signaling pathways remain poorly understood. We

describe robustness and compensation of information transmission of signaling pathways at the cell population level. We calculated the mutual information transmitted through signaling pathways for the growth factor-mediated gene expression. Growth factors appeared to carry only information sufficient for a binary decision. Information transmission was generally more robust than average signal intensity despite pharmacological perturbations, and compensation of learn more information transmission occurred. Information transmission to the biological output of neurite extension appeared robust. Cells may use information entropy as information so that messages can be robustly transmitted despite variation in molecular activities among individual cells.”
“The Y chromosome and the mitochondrial genome have been used to estimate when the common patrilineal and matrilineal ancestors of humans PKC412 cost lived. We sequenced the genomes of 69 males from nine populations, including two in which we find basal branches of the Y-chromosome tree. We identify ancient phylogenetic structure within African haplogroups and resolve a long-standing ambiguity deep within the tree. Applying equivalent methodologies to the Y chromosome and the mitochondrial genome, we estimate the time to the most recent common ancestor (T-MRCA) of the Y chromosome to be 120 to 156 thousand years and the mitochondrial genome

T-MRCA to be 99 to 148 thousand years. Our findings suggest that, contrary to previous claims, male lineages do not coalesce significantly more recently than female lineages.”
“Genetic variation within the male-specific portion of the Y chromosome (MSY) can clarify the origins of contemporary populations, but previous studies were hampered by partial genetic information. Population sequencing of 1204 Sardinian males identified 11,763 MSY single-nucleotide polymorphisms, 6751 of which have not previously been observed. We constructed a MSY phylogenetic tree containing all main haplogroups found in Europe, along with many Sardinian-specific lineage clusters within each haplogroup. The tree was calibrated with archaeological data from the initial expansion of the Sardinian population similar to 7700 years ago.

Blockade of neutrophil reactive oxygen species attenuates G-CSF-mediated MPC and OB apoptosis. These data show that the expansion of BM neutrophils selleck products by G-CSF contributes to the transient degradation of retention mechanisms within the BM niche, facilitating enhanced HSPC egress/mobilization.”
“Quantification of protein and PTM abundance in biological samples

is an important component of proteomic studies Label free methods for quantification using MS are attractive because they are simple to implement and applicable to any experimental system We demonstrate that PTM stoichiometry can be accurately measured using label free quantification and selected reaction monitoring Use of selected reaction monitoring is advantageous with complex biological samples and we show this approach can be used to quantify multiple PTMs independently on a single peptide”
“Oxidative stress is implicated as an important factor in the development of Alzheimer’s disease (AD). In the present study, we have investigated

the effects of edaravone (9 mg/kg, 3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, in a streptozotocin (STZ-3 mg/kg) induced rat model of sporadic AD (sAD). Treatment with edaravone significantly improved STZ-induced cognitive damage as evaluated in Morris water maze and step-down tests and markedly restored changes in malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE) adducts, hydroxyl radical ((OH)-O-center dot), hydrogen peroxide (H2O2), total superoxide dismutase (T-SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and protein carbonyl OTX015 concentration selleck chemicals (PC) levels. In addition, histomorphological observations confirmed the protective effect of edaravone on neuronal degeneration. Moreover, hyperphosphorylation

of tau resulting from intracerebroventricular streptozotocin (ICV-STZ) injection was decreased by the administration of edaravone. These results provide experimental evidence demonstrating preventive effects of edaravone on cognitive dysfunction, oxidative stress and hyperphosphorylation of tau in ICV-STZ rats. Since edaravone has been used for treatment of patients with stroke, it represents a safe and established therapeutic intervention that has the potential for a novel application in the treatment of age-related neurodegenerative disorders associated with cognitive decline, such as AD. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.”
“Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from chimaeric fusion genes or point mutations such as BCR-ABL1 or JAK2 V617F. We report here the cloning and functional characterization of two novel fusion genes BCR-RET and FGFR1OP-RET in chronic myelomonocytic leukemia (CMML) cases generated by two balanced translocations t(10; 22)(q11;q11) and t(6;10)(q27;q11), respectively.