Furthermore, utilizing SHP099 FCS, we established a method for high-throughput screening of protein aggregation and optimal

solution conditions for structural biological experiments.”
“Bacteria are constantly challenged by foreign genetic elements such as bacteriophages and plasmids. Several defense systems provide immunity against such attackers, including restriction modification (R M) systems and clustered, regularly interspaced short palindromic repeats (CRISPRs). These systems target attacking DNA and thus antagonize natural transformation, which relies on uptake of exogenous DNA to promote acquisition of new genetic traits. It is unclear how this antagonization occurs, because transforming DNA is single stranded, and thus resistant to these immune systems. Here, we propose a simple model whereby these systems

limit transformation by attack of transformed chromosomes once double Verubecestat purchase strandedness is restored by chromosomal replication.”
“As novel genes emerge in the evolution of species, pre-existing genes expand their expression patterns to diversify their functions and the expression patterns of gene duplicates diverge to pursue functional specialization. All these processes require genes to be expressed, however, the level and specificity of gene expression at the early stages of these processes are unclear. In this study, I propose that transcriptional noise is a mechanism to test genes for new functions, and I hypothesize the ‘in-service’ mechanism of gene evolution. In contrast to other hypotheses that suggest that there are specialized sites for gene evolution, such as tumors (Kozlov, 2010) or the testis (Kaessmann, 2010) this hypothesis proposes that emerging genes are expressed nonspecifically in many normal tissues, due to transcriptional noise. New genes are continuously ‘tested’ in various cells and under various conditions, thereby allowing the genes to evolve functions at the sites of their future check details work. The hypothesis of ‘in-service’ gene evolution also proposes that pre-existing genes

are continuously tested under extrinsic conditions, due to transcriptional noise; this testing facilitates the emergence of alternative promoters and the diversification of the genes’ expression patterns and functions. (C) 2011 Elsevier Ltd. All rights reserved.”
“Congenital muscular dystrophies (CMDs) with associated brain abnormalities are a group of disorders characterized by muscular dystrophy and brain and eye abnormalities that are frequently caused by mutations in known or putative glycotransferases involved in protein O-mannosyl glycosylation. Previous work identified alpha-dystroglycan as the major substrate for O-mannosylation and its altered glycosylation the major cause of these disorders.

7% (Middle East) to 58.4% (Asia). When combined by vesicoureteral reflux status children

and renal units with refluxing ureters exhibited an increased risk of renal scarring (odds ratios 2.8 and 3.7, respectively).

Conclusions: Although scarring was different across some regions, only scarring in Asian studies comparing patients displayed a statistically significant difference. A regional effect explained the heterogeneity observed in the overall estimate for patients and partly for renal units. The greatest risk of renal scarring may be imparted by the presence of vesicoureteral reflux.”
“Prenatal morphine treatment and emotional stress both have selleckchem been shown to increase sensitivity to reward-related behaviors. It has been postulated that this increased sensitivity to rewarding stimuli may be the result of an enhanced release of endogenous opioids. In the present study, in vivo autoradiography was employed to investigate the endogenous opioid release in specific brain areas in rats. Pregnant animals were exposed to morphine or saline from day 8 of gestation till birth. Development

of pups was monitored and play behavior was tested on postnatal day 21. Adult rats were exposed to repeated emotional stress or control treatment for five consecutive days and tested in a small open field PU-H71 concentration 5 days later. [(3)H]-Diprenorphine was injected following this test to investigate endogenous opioid release.

Prenatal morphine treatment increased play behavior and endogenous opioid release in a number of cortical and subcortical brain areas after being subjected to an open field challenge later in life. Emotional stress exposure increased locomotor activity in the open field irrespective of the type of prenatal treatment and increased endogenous opioid release in some specific brain areas. It is suggested that the increased release of endogenous opioids in the substantia nigra, the piriform cortex and the septum observed after both types of treatments

is related to the increased sensitivity to reward. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: We report the effectiveness of an antegrade continence enema stopper device Birinapant clinical trial in preventing stomal stenosis in catheterizable channels.

Materials and Methods: All cases in which a channel was created for clean intermittent catheterization during a 5-year period beginning in May 2002 were included in the analysis. For the first 31 months the catheterizable channels were used for clean intermittent catheterization but were not kept patent between catheterizations (group 1, 19 patients). For the next 29 months we began to use an antegrade continence enema stopper in the stoma between catheterizations for a period of 3 to 6 months postoperatively (group 2, 14 patients).

Results: A total of 33 catheterizable channels were studied.

Materials and Methods: To determine the absolute lymphocyte count we retrospectively analyzed the preoperative blood count of 430 patients with a mean age of 60 years treated with primary surgical resection at our cancer center. Absolute lymphocyte count values as a continuous variable and at a level below 1,300 cells per mu l, which was our lowest reference value, were correlated with nuclear grade, pathological stage and TNM stage. We used the Kaplan-Meier method to estimate overall survival, stratified by absolute lymphocyte count status.

Results: As a continuous variable, see more low absolute lymphocyte count was associated with higher grade (p = 0.009), and higher pT stage (p = 0.034)

and TNM stage (p<0.0001). Lymphopenia below 1,300 cells per, mu l. was associated with high grade (p = 0.0043), pT stage (p = 0.051) and TNM stage (p<0.0001). At a median followup of 33.5 months lymphopenia was associated with inferior selleck inhibitor overall survival in a univariate model (p<0.0001),

and on multivariate analysis independent of pT, N and M stages, patient age, grade, smoking history and comorbidities (p = 0.0102). Lymphopenia was also associated with inferior overall survival in a subset of young patients (age 60 years or less) with no distant metastasis (p = 0.014).

Conclusions: In 430 patients with clear cell renal cell carcinoma lymphopenia was associated with lower overall survival independent of pT and TNM stages, nuclear grade, age, tobacco smoking and comorbidity index.”
“Individuals almost with high-functioning autism often display deficits in social interactions and high-level cognitive functions. Such deficits may be influenced by poor ability to process feedback and rewards. The feedback-related negativity (FRN) is an event-related potential (ERP) that is more negative following losses than gains. We examined FRN amplitude in 25 individuals with Autism Spectrum Disorder (ASD) and 25 age- and IQ-matched typically developing control participants

who completed a guessing task with monetary loss/gain feedback. Both groups demonstrated a robust FRN that was more negative to loss trials than gain trials; however, groups did not differ in FRN amplitude as a function of gain or loss trials. N1 and P300 amplitudes did not differentiate groups. FRN amplitude was positively correlated with age in individuals with ASD, but not measures of intelligence, anxiety, behavioral inhibition, or autism severity. Given previous findings of reduced-amplitude error-related negativity (ERN) in ASD, we propose that individuals with ASD may process external, concrete, feedback similar to typically developing individuals, but have difficulty with internal, more abstract, regulation of performance. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Based on the pattern of spontaneous activity, neurons were classified as silent, tonic or bursting. The PD-1/PD-L1 Inhibitor 3 occurrence of distinctive firing modes was not related to topographic allocation. The patterns of spontaneous firing and evoked discharge were highly sensitive to alterations in membrane potential and merged upon de- and hyperpolarizing current injection and synaptic stimulation. Besides projection neurons, recordings revealed the existence of a subpopulation of cells possessing morphological and physiological properties of neocortical

neurogliaform cells. They were considered to be interneurons. Our data suggest that neurons within the different LHb subnuclei Buparlisib datasheet behave electrophysiologically more similar than expected, considering their morphological heterogeneity.

We conclude that the formation of functional neuronal entities within the LHb may be achieved through defined synaptic inputs to particular neurons, rather than by individual neuronal morphologies and intrinsic membrane properties. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Growing colonies of bacteria on the surface of thin agar plates exhibit fractal patterns as a result of nonlinear response to environmental conditions, such as nutrients, solidity of the agar medium and temperature. Here, we examine the effect of glucose on pattern formation by growing colonies of Bacillus thuringiensis isolate KPWP1. We also present Selleckchem VE-822 the theoretical modeling of the colony growth of KPWP1 and the associated spatio-temporal patterns. Our experimental results are in excellent agreement with simulations based on a reaction-diffusion model that describes diffusion-limited aggregation and branching, in which individual cells move actively in the periphery, but become immotile in the inner regions of the growing colony. We obtain

the Hausdorff fractal dimension of the colony patterns: D-H.Expt=1.1969 and D-H. (R.D).=1.1965, for experiment and reaction-diffusion model, respectively. Results of our experiments and modeling clearly show how glucose at higher concentration can prove to be inhibitory for motility of growing colonies of B. thuringiensis cells on semisolid support and be responsible for changes in the growth pattern. (C) 2010 Elsevier Ltd. All rights reserved.”
“Activation of the dopaminergic (DA) neurons of the ventral tegmental area (VTA) by ethanol has been implicated in its rewarding and reinforcing effects. We previously demonstrated that ethanol enhances GABA release onto VTA-DA neurons via activation of 5-HT(2C) receptors and subsequent release of calcium from intracellular stores. Here we demonstrate that excitation of VTA-DA neurons by ethanol is limited by an ethanol-enhancement in GABA release.

Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is

registered, number ISRCTN28163533.

Findings All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis learn more were significantly more common in patients allocated to GCS than selleck chemicals in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio

4.18, 95% CI 2.40-7.27).

Interpretation These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results.”
“OBJECTIVE: The current series represents a preclinical safety validation study for direct parenchymal microinjection of cellular grafts into the ventral horn of the porcine cervical spinal cord.

METHODS: Twenty-four 30- to 40-kg female Yorkshire farm pigs immunosuppressed with cyclosporine underwent a cervical laminectomy and ventral horn human neural progenitor cell injection. Cell transplantation in groups 1 to 3 (n = 6 pigs each) was undertaken with the intent of assessing the safety of varied injection volumes: 10, 25, and 50 mu L injected at 1, 2.5, and 5 mu L/min, respectively. Groups 4 and 5

(n = 3 pigs each) received prolonged immunosuppressant pretreatment in an attempt to demonstrate graft viability. buy 3-deazaneplanocin A The latter was undertaken in an alternate species (mini-pig versus Yorkshire pig).

RESULTS: Neurological morbidity was observed in 1 animal and was attributable to the presence of a resolving epidural hematoma noted at necropsy. Although instances of ventral horn targeting were achieved in all injection groups with a coordinate-based approach, opportunities exist for improvement in accuracy and precision. A relationship between injection volume and graft site cross-sectional area suggested limited reflux. Only animals from group 5 achieved graft survival at a survival end point (t = 1 week).

CONCLUSION: This series demonstrated the functional safety of targeted ventral horn microinjection despite evidence for graft site immune rejection. Improvements in graft delivery may be augmented with an adapter to improve control of the cannula entry angle, intraoperative imaging, or larger graft volumes.

These rhythms are synchronized to the diurnal day/night cycle by environmental cues such as light and temperature. Output pathways check details link the clock to particular biological processes, ensuring that they peak in activity at the appropriate times of day or night. Recently, significant progress was

made in defining the mechanisms by which output pathways are activated at specific times. Here these issues are emphasized by describing how the clock regulates growth and development throughout the life cycle of Arabidopsis thaliana, including seed germination, seedling growth, stress responses and the transition to flowering. This wide impact of the clock on growth and development appears to provide an advantage by enhancing growth and seed production in different environments.”
“Purpose: Recent comparisons of the impact of the surgical approach on pediatric pyeloplasty outcomes have generally incorporated a form of internal ureteral drainage. We hypothesized that the surgical approach does not affect outcomes in children who undergo unstented pyeloplasty and stenting offers no long-term benefit in those with pediatric pyeloplasty.

Materials and Methods: After receiving institutional review board approval we examined the records of all children who underwent initial pyeloplasty from December

2001 find more to December 2009. We compared unstented and stented pyeloplasties, and each surgical approach in the unstented group.

Results: During the study period 367 pyeloplasties were performed, including 231 unstented and 136 stented procedures. When comparing unstented many to stented pyeloplasties, there was no difference in the complication or failure rate. Of unstented pyeloplasties 71, 67 and 93 were done using a transperitoneal laparoscopic approach, a flank approach and dorsal lumbotomy, respectively. There were 5 failures, of which 2 were laparoscopic,

2 used a flank approach and 1 used dorsal lumbotomy (p = 0.51). A total of 31 patients, including 10 treated with a laparoscopic approach, 3 with a flank approach and 18 with dorsal lumbotomy (p = 0.02), required second procedures, of which 24 were temporary drainage for a urine leak. Univariate analysis of factors associated with secondary procedures in the unstented pyeloplasty group showed that only surgical approach was significant (p = 0.05).

Conclusions: In pediatric pyeloplasty there is no significant difference in outcome between stented and unstented repairs. In unstented repairs complications may vary by surgical approach. Regardless of the approach unstented pyeloplasty is safe and effective in the pediatric population.”
“The vagus nerves supply the major cholinergic tone to airway smooth muscles physiologically and play critical roles in the genesis of airway hyperreactivity under some pathological conditions.

Resveratrol supplementation did not improve mitochondrial content, the subcellular localization of cytochrome c protein content, or PGC1 https://www.selleckchem.com/products/SB-431542.html protein content. Resveratrol increased manganese superoxide dismutase (MnSOD), reduced hydrogen peroxide, and lipid peroxidation levels in muscle samples, but

it was unable to significantly reduce protein carbonyl levels. The data suggest that resveratrol has a protective effect against aging-induced oxidative stress in skeletal muscle, likely through the upregulation of MnSOD activity, but sarcopenia was not attenuated by resveratrol.”
“There is converging evidence for genetic, biochemical, and neuropsychological factors to increase the risk for anxiety and anxiety disorders. The pathogenesis of anxiety disorders is assumed to be influenced by a complex interaction of these individual risk factors on several levels,

affecting intermediate phenotypes of anxiety such as the startle reflex. Thus, in the present double-blind, placebo-controlled study we attempted to paradigmatically investigate a multi-level pathogenetic model of Obeticholic anxiety by testing the effect of 300 mg caffeine citrate as an antagonist at the adenosine A2A receptor vs placebo on the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) startle reflex in 110 healthy individuals (male = 56, female = 54) stratified for the adenosine A2A receptor (ADORA2A) 1976T>C MEK162 ic50 polymorphism (rs5751876). In addition to the expected main effect of picture category (highest

startle amplitude for unpleasant, lowest for pleasant pictures) groups across all ADORA2A 1976T>C genotype and intervention (caffeine vs placebo) groups, an interaction effect of genotype, intervention, and picture category was discerned: In ADORA2A 1976TT risk genotype carriers, highest startle magnitudes were observed after caffeine administration in response to unpleasant pictures, with this effect arising particularly from the female subgroup. Our data point to a complex, multi-level, and potentially gender-specific pathogenetic model of anxiety, with genetic and biochemical factors interactively increasing the risk of maladaptive emotional processing and thereby possibly also anxiety disorders. The present findings may eventually aid in improving primary and secondary prevention by sharpening the risk profiles of anxiety-prone individuals. Neuropsychopharmacology (2012) 37, 759-769; doi: 10.1038/npp.2011.253; published online 19 October 2011″
“HIV infection, once established, is never cleared. Rare individuals do, however, control viral replication to low levels. These successful immune responses are primarily linked to certain class I MHC alleles (MHC-I). Because of this association, many AIDS vaccines in development are designed to generate virus-specific CD8+ T cells.

All four types of responses involve the genetic machineries that underlie a number of complex human diseases such as cancer and neurodegenerative diseases, including Alzheimer’s and Parkinson’s. We highlight the types of stress response experiments required to detect the genes and pathways underlying human disease and suggest that studying stress biology in worms can be translated to understanding human disease and provide potential targets for drug discovery.”
“Background: In endothelial dysfunction, vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression (collectively termed cell adhesion

molecules; CAMs) EPZ-6438 chemical structure increase at sites of atherosclerosis and are stimulated by proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). Methods: We evaluated the effect of alpha-tocopherol (AT; 10-150 mu M) and BAY 11-7082 (BAY; 0.1 or 1 mu m) on CAMs mRNA expression as well as their protein in soluble release form (sCAMs) in human aortic

endothelial cells (HAECs) activated by TNF-alpha (1 or 10 ng/ml). Also, we determined the extent of lymphocyte adhesion to activated HAECs. Results: BAY reduced VCAM-1, E-selectin and ICAM-1 mRNA expression by 30, 30 and AMN-107 clinical trial 10%, respectively. Furthermore, protein reduction of sVCAM-1 by 70%, sE-selectin by 51% and sICAM-1 by 25% compared to HAECs stimulated by TNF-alpha was observed (p < 0.05). AT (50, 75 and 150 mu M) decreased VCAM-1 mRNA expression by 30% and sVCAM-1 protein by 33% compared to HAECs stimulated by TNF-alpha (p < 0.05). TNF-alpha-activated HAEC adhesion to human Jurkat T lymphocytes was higher compared

to nonactivated HAECs (p < 0.05). BAY (2 and 5 mu m) reduced this lymphocyte adhesion (p < 0.05). https://www.selleck.cn/products/GDC-0449.html Conclusion: BAY reduces all the CAMs studied as well as cell adhesion, while AT selectively inhibits VCAM-1; both induce endothelial dysfunction improvement. Copyright (C) 2012 S. Karger AG, Basel”
“BACKGROUND: The evidence of or against the presence of a “”July phenomenon”" in resident teaching hospitals has been inconsistent. Moreover, there are limited data on the “”July phenomenon”" in the field of neurosurgery.

OBJECTIVE: To determine whether a “”July phenomenon”" exists for neurosurgical mortality or complications.

METHODS: A search of the National Inpatient Sample database from 1998 to 2008 was performed for all admissions for International Classification of Diseases, 9th Revision codes corresponding to nontraumatic hemorrhage, central nervous system (CNS) trauma, CNS tumor, and hydrocephalus. Generalized linear mixed-model analysis was performed, adjusted for patient demographics and hospital characteristics, for the outcomes of mortality and complications for the month of July compared with all other months in teaching hospitals.

5 g, 2 g, 2 g plus HIF inhibitor U0126 (10(-5)M), 17-[2-(dimethylamino)ethyl] amino-17-desmethoxygeldanamycin (17-DMAG, 10(-5)M), or echinomycin (10(-6)M), or 2 g plus dimethyloxallyl glycine (DMOG; 10(-4)M), a prolyl-hydroxylase inhibitor that stabilizes HIF. The fold-change in PHE and KCl contraction was compared with the control contraction at 0.5-g tension for 1 hour. Vein tissue homogenates were analyzed for HIF-1 alpha, HIF-2 alpha, MMF-2, and MMP-9 messenger RNA (mRNA) and protein amount using real-time reverse transcription

polymerase chain reaction and Western blots.

Results: Compared with control IVC contraction at 0.5-g tension for 1 hour, the PHE and KCl contraction after prolonged 0.5-g tension was 2.0 +/- 0.35 and 1.1 +/- 0.06, respectively. Vein contraction to PHE and KCl after PRN1371 prolonged 2-g tension was significantly reduced (0.87 +/- 0.13 and 0.72 +/- 0.05, respectively). PHE-induced contraction was restored in IVC exposed to prolonged 2-g tension plus the HIF inhibitor SBI-0206965 chemical structure U0126 (1.38 +/- 0.15) or echinomycin (1.99 +/- 0.40). U0126 and echinomycin also restored KCl-induced contraction in NC exposed to prolonged 2-g tension (1.14 +/- 0.05 and 1.11 +/- 0.15, respectively). Treatment with DMOG further reduced PHE- and KCl-induced contraction in veins subjected to prolonged 2-g tension (0.47 +/- 0.06 and 0.57 +/- 0.01, respectively). HIF-1 alpha and HIF-2 alpha

inRNA were overexpressed in NC exposed to prolonged 2-g tension, and the overexpression was reversed by U0126. The overexpression of HIF-1 alpha and HIF-2 alpha in stretched NC was associated with increased MMP-2 and MMP-9 mRNA. The protein amount of HIf-1 alpha,

HIF-2 alpha, MMP-2, and MMP-9 was also increased in NC exposed to prolonged 2-g wall tension.

Conclusions:Prolonged increases in vein wall tension are associated with Selleck Fosbretabulin overexpression of HIF-1 alpha and HIF-2 alpha, increased MMP-2 and MMP-9 expression, and reduced venous contraction in rat IVC. Together with our report that MMP-2 and MMP-9 inhibit NC contraction, the data suggest that increased vein wall tension induces HIF overexpression and causes an increase in MMP expression and reduction of venous contraction, leading to progressive venous dilation and varicose vein formation. (J Vase Surg 2011;53:764-73.)”
“Midkine (MK), a neurotrophic factor with important roles in survival and differentiation of dopaminergic neurons, is upregulated in different brain areas after administration of different drugs of abuse suggesting MK could modulate drugs of abuse-induced pharmacological or neuroadaptative effects. To test this hypothesis, we have studied the effects of amphetamine administration in MK genetically deficient (MK-/-) and wild-type (MK+/+) mice. In conditioning studies, we found that amphetamine induces conditioned place preference (CPP) similarly in both MK-/- and MK+/+ mice.

Moreover, the unique genome carries a nonbleaching protein A (NblA) gene (open reading frame [ORF] 022L), which is present in all phycobilisome-containing organisms and mediates phycobilisome

degradation. Western blot detection confirmed that 022L was expressed after PaV-LD infection in the host filamentous cyanobacterium. In addition, its appearance was companied by Buparlisib concentration a significant decline of phycocyanobilin content and a color change of the cyanobacterial cells from blue-green to yellow-green. The biological function of PaV-LD nblA was further confirmed by expression in a model cyanobacterium via an integration platform, by spectroscopic analysis and electron microscopy observation. The data indicate that PaV-LD is an exceptional cyanophage of filamentous cyanobacteria, and this novel cyanophage will also provide us with a new vision of the cyanophage-host interactions.”
“The mitochondrial inhibitor 1-methyl-4-phenylpyridinium (MPP+) is the toxicologically relevant metabolite of 1-methyl-4-phenyltetrahydropyridine (MPTP), which causes relatively selective degeneration of dopaminergic neurons in the substantia nigra. Dopaminergic LUHMES PS-341 mw cells were used

to investigate whether ATP-depletion can be uncoupled from cell death as a downstream event in these fully post-mitotic human neurons. Biochemical assays indicated that in the homogeneously differentiated cell cultures, MPP+ was taken up by the dopamine transporter (DAT). MPP+ then triggered oxidative stress and caspase activation, as well as ATP-depletion followed by cell death. Enhanced survival of the neurons in the presence of agents interfering with mitochondrial pathology, such as the fission inhibitor Mdivi-1 or a Bax channel click here blocker suggested a pivotal role of mitochondria in this model. However, these compounds did not prevent cellular ATP-depletion. To further investigate whether cells could be rescued despite respiratory chain inhibition by MPP+, we have chosen a diverse set of

pharmacological inhibitors well-known to interfere with MPP+ toxicity. The antioxidant ascorbate, the iron chelator desferoxamine, the stress kinase inhibitor CEP1347, and different caspase inhibitors reduced cell death, but allowed ATP-depletion in protected cells. None of these compounds interfered with MPP+ accumulation in the cells. These findings suggest that ATP-depletion, as the initial mitochondrial effect of MPP+, requires further downstream processes to result in neuronal death. These processes may form self-enhancing signaling loops, that aggravate an initial energetic impairment and eventually determine cell fate. (C) 2011 Elsevier Inc. All rights reserved.”
“Increased conversion of glucose to lactate is a key feature of many cancer cells that promotes rapid growth. Pyruvate kinase M2 (PKM2) expression is increased and facilitates lactate production in cancer cells.