After adjustment for all potential confounding variables except maternal age, the HR for risk of BPAD for each 10-year increase in paternal age was 1.28 [95% confidence interval (Cl) 1.11-1.48], but this

fell to 1.20 (95% CI 0.97-1.48) after adjusting for maternal age. A similar result was found for maternal age and risk of BPAD [HR 1.30 (95% CI 1.08-1.56) before adjustment for paternal age, HR 1.12 Sonidegib nmr (95% Cl 0.86-1.45) after adjustment]. The HR associated with having either parent aged 30 years or over was 1.26 (95% CI 1.01-1.57) and it was 1.45 (95%, CI 1.16-1.81) if both parents were >30 years.

Conclusions. Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages.”
“The time a phenotype takes to achieve a stationary state from an initial

condition depends on multiple factors. In particular, it Tanespimycin order is a function of both its fitness and its mutation rate. We evaluate the average time, referred to as the characteristic time, T-c, that the system takes to reach a final steady state of simple models of populations formed by self-replicative sequences. The dependence of T-c on the mutation rate and on the fitness landscape is also studied. For simple fitness landscapes, e.g. single peak, the characteristic time can be analytically obtained as a function of the system parameters. In this case, T-c for obtaining the quasispecies distribution presents a maximum at a Q-value that depends on the initial conditions and decreases monotonously as the mutation rate tends to zero. For most of the complex landscapes handled in this paper, the characteristic time to achieve the quasispecies distribution picked around the fittest phenotype attains a local minimum for a given mutation rate between 0 and the Q-value at which T-c reaches its local maximum. Thus, in these cases, an optimum value for the mutation rate exists that corresponds to the lowest value of the characteristic

time Cilengitide for quasispecies evolution. (C) 2012 Elsevier Ltd. All rights reserved.”
“Background. Although central nervous system (CNS) involvement in adult myotonic dystrophy type I (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect.

Method. We examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders.

Results.

This view had been based on studies which have assumed cooperation to be discrete rather than continuous

(i.e., individuals can either fully cooperate or else fully defect, but they cannot continuously vary their level of cooperation). In real world cooperation, however, cooperation is often continuous. In this paper, we re-examine the evolution of reciprocity in sizable groups by presenting a model of the n-person prisoner’s dilemma that assumes continuous rather than discrete cooperation. This model shows that continuous reciprocity has a dramatically wider basin of attraction than discrete reciprocity, and that this basin’s size increases with efficiency of cooperation (marginal per capita return). Further, we find that assortative Akt inhibitor interaction interacts synergistically with continuous reciprocity to a much greater extent than it does with discrete reciprocity. These results suggest that previous models may have underestimated reciprocity’s adaptiveness in groups. Acalabrutinib concentration However, we also find that the invasion of continuous reciprocators into a population of unconditional defectors

becomes realistic only within a narrow parameter space in which the efficiency of cooperation is close to its maximum bound. Therefore our model suggests that continuous reciprocity can evolve in large groups more easily than discrete reciprocity only under unusual circumstances. (C) 2010 Elsevier Ltd. All rights reserved.”
“13-Cis-retinoic acid (13-cis-RA) causes depression-related behavior in mice. Hypothalamic dysregulation has been implicated in clinical depression. In fact, apoptosis of hypothalamic neurons may lead AR-13324 nmr to depression after myocardial infarction. Our objective was to determine if 13-cis-RA affects cultured hypothalamic cell number. Treatment of GT1-7 hypothalamic cells with 10 mu M 13-cis-RA for 48 h decreased cell growth to 45.6 +/- 13% of control. To determine if this decrease in cell number was due to 13-cis-RA acting as an oxidant, cells were treated with I 3-cis-RA and ascorbic acid or butylated hydroxyanisole (BHA) for 24 or 48 h. Neither antioxidant alleviated the inhibitory affects

of 13-cis-RA. In addition, 13-cis-RA treatment did not increase superoxide anion production, indicating 13-cis-RA was not acting as an oxidant. To determine if 13-cis-RA was acting via retinoic acid receptors (RARs) to decrease cell number, GT1-7 cells were treated with 13-cis-RA and the RAR pan-antagonist, AGN 193109. Treatment with the RAR-antagonist blocked the ability of 13-cis-RA to decrease cell number, indicating this phenomenon was a RAR-independent mechanism. We hypothesize that the ability of I 3-cis-RA to decrease hypothalamic cell number may contribute to the increased depression-related behaviors observed in mice. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

628) and all secondary efficacy parameters.

Conclusions These data suggest that 20 mg of bifeprunox may be efficacious in improving symptoms in patients with an acute exacerbation of schizophrenia. Bifeprunox appeared to be safe and well tolerated by patients in this 6-week study.”
“Peroxisome-derived Woronin bodies of the Ascomycota IACS-10759 cost phyla, and the endoplasmic reticulum (ER)-derived septal pore cap (SPC) of the Basidiomycota, are both fungal organelles that prevent cytoplasmic bleeding when multicellular hyphal filaments are

wounded. Analysis of Woronin body constituent proteins suggests that these organelles evolved in part through gene duplication and co-opting of non-essential genes for new functions, indicating that new organelles can arise through typical evolutionary mechanisms. Interestingly, clades possessing the Woronin body and SPC also produce the largest and most complex multicellular fungal reproductive structures. Certain Woronin body and SPC mutants have defects in growth and development, suggesting functions beyond cellular wound healing. I argue that studying these specialized systems will help to reveal the basis for fungal diversity and provide PLX4032 nmr general principles for co-evolution of organelles and multicellular complexity.”
“In the central nervous system,

the endocannabinoid anandamide [N-arachidonoylethanolamine (AEA)] is believed to increase food intake through on-demand activation of hypothalamic circuits. The present study examined the effects of hypothalamic paraventricular nucleus (PVN) injections of AEA (25-400 pmol) on food intake and energy substrate oxidation [respiratory quotient (RQ)]. PVN administration of AEA increased eating behavior and RQ, indicating enhanced carbohydrate oxidation. Further, PVN administration of the cannabinoid type 1 receptor inverse agonist AM251 (5-10 mu g) attenuated both the eating and the RQ responses elicited selleck compound by AEA (100 pmol). AM251 administered alone did not

alter food intake or RQ. Overall, these findings are consistent with a role for PVN cannabinoid type 1 receptors in the regulation of eating and energy homeostasis. NeuroReport 23: 425-429 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“MicroRNAs (miRNAs) are small noncoding RNA molecules that function as posttranscriptional regulators of gene expression. Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV), a B-cell-tropic virus associated with KS and B-cell lymphomas, encodes 12 miRNA genes that are highly expressed in these tumor cells. One viral miRNA, miR-K12-11, shares 100% seed sequence homology with hsa-miR-155, an oncogenic human miRNA that functions as a key regulator of hematopoiesis and B-cell differentiation. So far, in vitro studies have shown that both miRNAs can regulate a common set of cellular target genes, suggesting that miR-K12-11 may mimic miR-155 function.

Conclusions: The present study shows that aneurysm sac filling may have a role as an adjuvant procedure to the present EVAR technique. The strength of the proximal fixation of three different stent grafts increases significantly in this in vitro setting. Further in vivo research must be done to see if this could facilitate the treatment of aneurysms with short infrarenal necks. (J Vase Surg 2010;52:152-8.)”
“Objective: Abdominal aortic aneurysm (AAA) development is associated with increased angiogenesis and overexpression of vascular endothelial growth factor (VEGF). Inhibition

of angiogenesis Pifithrin-�� mw results in attenuation of experimental aneurysms. This study investigated the effects of recombinant human (rh)VEGF on experimental aneurysms.

Methods: Apolipoprotein E-deficient

(apoE(-/-)) mice were assigned to one of four groups: (1) normal saline infusion (sham), (2) angiotensin-II (AngII) infusion, (3) AngII infusion plus 100 mu g daily rhVEGF for 14 days (AngII + 14dVEGF), or (4) AngII infusion plus 100 mu g daily rhVEGF for 21 days (AngII + 21dVEGF). Aortic maximum diameter and cross-sectional area were determined by magnetic resonance imaging and microscopy. All mice were sacrificed at day 28.

Results: Aneurysms developed in all mice in the AngII+14dVEGF and AngII+21dVEGF groups by day 21 compared with 40% in the AngII group. Treatment with rhVEGF increased maximum aortic diameter (P <.002) and crosssectional area of aneurysms (P <.005) at day 21. This effect was maintained at day 28 (P <.0005). Decreasing GW3965 molecular weight rhVEGF treatment from 21 to 14 days did not attenuate aneurysm formation. Treatment with rhVEGF upregulated matrix metalloproteinase 2 gene MK 2206 expression within the aortic wall (P <.0009).

Conclusions: Treatment with

rhVEGF intensified the formation of Angll-induced aneurysms. Further studies are needed to investigate if antiangiogenic therapy may be a valid medical therapy against aneurysm expansion or rupture. (J Vase Surg 2010;52:159-66.)”
“Objective: Vascular smooth muscle cells (SMCs) are exposed to fluid shear stress (FSS) after interventional procedures such as balloon-angioplasty. Whereas the effects of hemodynamic forces on endothelial cells are explored in detail, the influence of FSS on smooth muscle cell function is poorly characterized. Here, we investigated the effect of FSS on SMC gene expression and function.

Methods: Laminar FSS of arterial level (14 dynes/cm(2)) was applied to SMC cultures for 24 hours in a parallel-plate flow chamber. The effect of FSS on gene expression was first screened with microarray technology, and results further verified by real time polymerase chain reaction (RT-PCR) and immunoblotting. Tissue factor pathway inhibitor-2 (TFPI-2) and caspase-3 protein expression was studied in the rat carotid artery after balloon-injury, and the effect of TFPI-2 on SMC DNA synthesis and apoptosis was examined in vitro.

Nitrite has previously been shown to protect against reperfusion injury in animal models of focal cerebral and heart ischemia. Nitrite therapy after murine cardiac arrest improved 22 h survival through MCC950 order improvements in myocardial contractility. These improvements accompanied transient mitochondrial inhibition which reduced oxidative injury

to the heart. Based on preliminary evidence that nitrite may also protect against ischemic brain injury, we sought to test this hypothesis in a rat model of asphyxia cardiac arrest with prolonged survival (7 d). Cardiac arrest resulted in hippocampal CA1 delayed neuronal death well characterized in this and other cardiac arrest models. Nitrite therapy did not alter post-arrest hemodynamics but did result in significant (75%) increases in CA1 neuron survival. This was associated with increases in hippocampal nitrite and S-nitrosothiol levels but not cGMP shortly

after therapy. Mitochondrial function 1 h after resuscitation trended towards improvement with nitrite therapy. Based on promising preclinical data, the first ever phase I trial of nitrite infusions in human cardiac arrest survivors has been undertaken. We present preliminary data showing low dose nitrite infusion did not result in hypotension or cause methemoglobinemia. Nitrite thus appears safe and effective for clinical translation as a promising therapy against cardiac arrest mediated

heart and brain injury. (C) 2012 Elsevier Inc. All rights reserved.”
“Control of smallpox by mass vaccination was one of the most effective see more public health measures ever employed Temsirolimus mw for eradicating a devastating infectious disease. However, new methods are needed for monitoring smallpox immunity within current vulnerable populations, and for the development of replacement vaccines for use by immunocompromized or low-responding individuals. As a measure for achieving this goal, we developed a protein microarray of the vaccinia virus proteome by using high-throughput baculovirus expression and purification of individual elements. The array was validated with therapeutic-grade, human hyperimmune sera, and these data were compared to results obtained from individuals vaccinated against smallpox using Dryvax. A high level of reproducibility with a very low background were apparent in repetitive assays that confirmed previously reported antigens and identified new proteins that may be important for neutralizing viral infection. Our results suggest that proteins recognized by antibodies from all vaccinees constituted <10% of the total vaccinia proteome.”
“Our societies generate increasing volumes of organic wastes. Considering that we also need alternatives to oil, an opportunity exists to extract liquid fuels or even industrial solvents from these abundant wastes.

Results: Mean followup was 72 months (range 12 to 84). At 6-year followup in 29 patients mean pad use improved from 5.6 daily at baseline to 0.41 and intrinsic sphincter deficiency improved from 27.2 to 78.6 (p <0.001). As measured on the visual analog scale,

68% of patients considered themselves dry. On the Patient Global Impression Index questionnaire 64% were very much improved, 23% were much improved and 13% were only minimally improved or unchanged. No patients considered themselves worse after the procedure. Complications necessitating device removal developed in 21.1% of patients.

Conclusions: Relative ease of insertion and the ability to tailor this therapy to individual needs makes this an attractive option for the challenging treatment for recurrent stress urinary incontinence due to intrinsic sphincter deficiency.”
“Background: On September 21, 2009, China began administering vaccines, obtained this website from 10 different manufacturers, against 2009 pandemic influenza A (H1N1) virus infection in priority populations. We aimed to assess the safety of this vaccination program.

Methods: We designed a plan for passive surveillance for adverse events after immunization with the influenza A (H1N1) vaccine. Physicians or vaccination providers were required to report the numbers of vaccinees and all adverse events to their local Center for Disease Control and Prevention

(CDC), which then reported the data to the Chinese CDC through the online National Immunization Information System’s National Adverse Event Following Immunization Bleomycin in vitro Surveillance System. Data were collected through March selleck kinase inhibitor 21, 2010, and were verified and analyzed by the Chinese CDC.

Results: A total of 89.6 million doses of vaccine were administered from September 21, 2009, through March 21, 2010, and 8067 vaccinees reported having an adverse event, for a rate of 90.0 per 1 million doses. The age-specific rates of adverse events ranged from 31.4 per 1 million doses among persons 60 years of age or older to 130.6 per 1 million doses among persons 9 years

of age or younger, and the manufacturer-specific rates ranged from 4.6 to 185.4 per 1 million doses. A total of 6552 of the 8067 adverse events (81.2%; rate, 73.1 per 1 million doses) were verified as vaccine reactions; 1083 of the 8067 (13.4%; rate, 12.1 per 1 million doses) were rare and more serious (vs. common, minor events), most of which (1050) were allergic reactions. Eleven cases of the Guillain-Barre syndrome were reported, for a rate of 0.1 per 1 million doses, which is lower than the background rate in China.

Conclusions: No pattern of adverse events that would be of concern was observed after the administration of influenza A (H1N1) vaccine, nor was there evidence of an increased risk of the Guillain-Barre syndrome.

N Engl J Med 2011;364:638-47.

As expected, the reverse mutations, R77K and E81N, introduced in M-THA induce Anlotinib price a phenotype similar to that due to M-MOK These features indicate a novel mechanism for energy depletion during lyssavirus-induced apoptosis.”
“Cognitive deficits in schizophrenia include impairments at automatic,

preattentive stages of sensory information processing. These deficits are evident in the prepulse inhibition- (PPI) and habituation of the auditory startle response paradigm, the paired tone paradigm in the EEG, and the peak recovery function of auditory evoked potentials (AEP). Administration of NMDA receptor antagonists reliably disrupts PPI and habituation of the startle, but not gating of AEPs in rodents. In the peak recovery paradigm, patients with schizophrenia

and primates treated with NMDA receptor antagonists show reduced maximal response at long interstimulus intervals (ISI), but normal responses at short ISIs. Thus reduced NMDA receptor signalling may underlie alterations in these paradigms observed mTOR inhibitor in schizophrenia. We tested the paradigms mentioned in mouse mutants with reduced expression of the NR1 subunit of the NMDA receptor (N = 15) and their wild- type littermates (N = 16). The NR1 mutant mice showed impaired habituation and PPI of the auditory startle response, as well as impaired gating in the paired tone paradigm. Deficits between the two gating measures did not correlate, corroborating previous evidence that these paradigms measure distinct processes. In the peak recovery paradigm, the NR1 mutants showed increased responses of the AEPs P1 and N1 at short ISIs but no difference between

groups were observed at long ISIs. In conclusion, the NR1 hypomorphic mice modelled sensory and sensorimotor gating and startle habituation deficits observed in schizophrenia, but failed to model alterations in the peak recovery function.”
“A flurry of recent reports on the role of activating and inhibitory Selleck Batimastat forms of the killer cell immunoglobulin-like receptors (KIR) in natural killer (NK) cell activity against human immunodeficiency virus type 1 (HIV-1) have yielded widely divergent results. The role of the activating NK receptor encoded by the KIR3DS1 allele and its putative ligands, members of the HLA class I Bw4Ile80 cluster, in early HIV-1 disease is controversial. We selected 60 treatment-naive adults for study from the OPTIONS cohort of individuals with early HIV-1 infection in San Francisco. We performed NK cell functional assays measuring gamma interferon (IFN-gamma) and CD107a expression by NK cells in the unstimulated state and after stimulation by the major histocompatibility complex class I-deficient 721.221 B-lymphoblastoid cell line. In addition, we measured CD38 expression (a T-cell activation marker) on T and NK cells. Persons who have at least one copy of the KIR3DS1 gene had higher IFN-gamma and CD107a expression in the unstimulated state compared to those who do not possess this gene.

POU4F3 is a transcription factor associated with human hearing impairment. Pou4f3 knockout mice (Pou4f3(-/-)) have no cochlear hair cells, resulting in complete deafness. Although the hair cells appear to form properly, they progressively degenerate via apoptosis. In order to rescue the hair cells in the knockout mice, we produced explant cultures from mouse cochleae at an early embryonic stage and treated the cells with z-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), a general caspase inhibitor. Hair cell numbers in the

Y-27632 cell line knockout mice treated with z-VAD-fmk were significantly higher than in the untreated mice. We found that the time window that z-VAD-fmk has a protective effect is between E14.5 (P=0.001) to E16.5 (P=0.03), but not after E18.5. The source of the surviving hair cells is not due to proliferation, as measured by 5-bromo-2-deoxyuridine (BrdU) labeling, or to supporting cell transdifferentiation to hair cells, since there was no change in supporting cell numbers. Instead, the survival appears to be a direct effect of the anti-apoptotic agent on the dying hair cells with an early developmental window. These results help towards providing

a comprehensive understanding of the molecular mechanisms of NCT-501 hair cell death, which might lead to the development of new therapeutic anti-apoptotic agents to alleviate hereditary hearing loss (HL). (c) 2010 IBRO. Published by Elsevier Ltd. All rights Sitaxentan reserved.”
“The hemagglutinin (HA) envelope protein of influenza viruses mediates essential viral functions, including receptor binding and membrane fusion, and is the major viral antigen for antibody neutralization. The 1957 H2N2 subtype

(Asian flu) was one of the three great influenza pandemics of the last century and caused 1 million deaths globally from 1957 to 1968. Three crystal structures of 1957 H2 HAs have been determined at 1.60 to 1.75 angstrom resolutions to investigate the structural basis for their antigenicity and evolution from avian to human binding specificity that contributed to its introduction into the human population. These structures, which represent the highest resolutions yet recorded for a complete ectodomain of a glycosylated viral surface antigen, along with the results of glycan microarray binding analysis, suggest that a hydrophobicity switch at residue 226 and elongation of receptor-binding sites were both critical for avian H2 HA to acquire human receptor specificity. H2 influenza viruses continue to circulate in birds and pigs and, therefore, remain a substantial threat for transmission to humans. The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine.

RESULTS: Of 17 patients with aCVD, 1 (5.9%) developed ICH and none experienced NHND or death during the median 31.4-month follow-up period. Of 11 patients with sCVD, 2 Selleck Torin 2 (18.2%) developed ICH and 3 (27.3%) experienced

new or worsened NHND over the median 9.7-month follow-up period. One of these patients subsequently died. Overall frequency of ICH or NHND was significantly lower in patients with aCVD versus sCVD (P = 0.022). Respective annual event rates were 1.4 versus 19.0%. aCVD patients had significantly higher cumulative event-free survival (P = 0.0016).

CONCLUSION: Cranial dAVFs with aCVD may have a less aggressive clinical course than those with sCVD.”
“Purpose: The complications of lower urinary tract reconstruction have been well documented in children with neurogenic bladders. While most

series include small numbers of nonneurogenic diagnoses, this group is typically underrepresented. Despite a number of fundamental anatomical and functional differences, a direct comparison of surgical complications of lower urinary tract reconstruction in patients with neurogenic vs nonneurogenic bladders has not been learn more performed.

Materials and Methods: We identified patients undergoing lower urinary tract reconstruction incorporating enterocystoplasty from 1996 to 2006. We performed a retrospective review of operative notes and medical records of patients who met inclusion criteria. Patients were divided into a neurogenic group and a nonneurogenic group based on the underlying diagnosis. The 2 groups were compared with respect to demographics, historical data, operative techniques, perioperative morbidity, long-term complications and need for surgical revision.

Results: Of the 127 patients who met inclusion criteria 72 were assigned to the nonneurogenic group and 55 to the neurogenic TNF-alpha inhibitor group. Overall the rates

of significant perioperative morbidity (39%), long-term complications (54%) and need for surgical revision (39%) were substantial. The rates of catheter related complications, rehospitalization for dehydration and spontaneous bladder rupture were higher in the neurogenic group (p <0.05).

Conclusions: Reconstruction of the lower urinary tract in children is associated with a considerable rate of complications and need for surgical revision regardless of whether the bladder is neurogenic or nonneurogenic. Children with neurogenic bladders are more prone to spontaneous rupture, catheter mishaps and early rehospitalization for dehydration.”
“OBJECTIVE: Preference-based quality of life (QOL) instruments integrate all factors contributing to QOL and provide a comprehensive valuation of a health state. QOL values of the general public for cerebral aneurysm health states are not well understood.

Moreover, injection with a selective alpha 4 beta 2 nAchR agonist, RJR2403 oxalate, induced a pronounced parasympathetic response with a smaller sympathetic response. Collectively, these data show that activations of alpha 4 beta 2 nAchRs elicits a parasympathetic cardiovascular response and activation of a7 nAchRs elicits a sympathetic cardiovascular response. These data suggest that specific subtypes of nicotinic receptors at the level of the ganglia may play distinct roles in mediating sympathetic or parasympathetic activation. (C) selleck chemical 2009 Elsevier Ireland Ltd. All rights reserved.”
“Background Cognitive impairment is an important contributor to disability. Limited clinical trial evidence

exists regarding the impact of physical exercise on cognitive function (CF). We report results of a pilot study to provide estimates of the relative impact of physical activity (PA) on 1-year changes in cognitive outcomes and to characterize relationships between changes in mobility disability and changes in cognition in older adults at increased

risk for disability.

Methods. Sedentary persons (102) at increased risk for disability (aged 70-89 years) were randomized to moderate-intensity PA or health education. Participants were administered the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), modified Stroop test. and Modified Mini-Mental State Examination at baseline and 1 year.

Results. Group differences were not significant but improvements in cognitive scores were associated with improvements in physical function. this website Specifically, the DSST significantly correlated with change in the Short Physical Performance Battery score (r=.38, p=.0002), in chair stand score (r=.26 p=.012), in balance score (r =.21 p =.046), and in 400-m gait speed (r=.15, p=.147). Change recall on the RAVLT and in the Stroop test was also positively correlated with changes in chair stand and balance. respectively.

Conclusions. These results provide further support for the benefits of exercise on CF in older adults. An adequately powered clinical trial of PA involving older adults at increased risk for

cognitive disability PI3K inhibitor is needed to expand the indications for prescribing exercise for prevention of decline in brain function.”
“Benign Familial Neonatal Convulsions (BFNC) are a rare epilepsy disorder with an autosomal-dominant inheritance. It is linked to mutations in the potassium channel genes KCNQ2 and KCNQ3. These encode for Kv7.2 and Kv7.3 potassium ion channels, which produce an M-current that regulates the potential firing action in neurons through modulation of the membrane potential. We report on the biophysical and biochemical properties of V589X, T359K and P410fs12X mutant-KCNQ2 ion channels that were detected in three BFNC families. Mutant KCNQ2 cDNAs were co-expressed with WT-KCNQ2 and KCNQ3 cDNAs in HEK293 cells to mimic heterozygous expression of the KCNQ2 mutations in BFNC patients.