Spectral Diagnostic Model for Agricultural Robot System Based on Binary Wavelet Algorithm.

The application of agricultural robots can liberate labor. The improvement of robot sensing systems is the premise of making it work. At present, more research is being conducted on weeding and harvesting systems of field robot, but less research is being conducted on crop disease and insect pest perception, nutritional element diagnosis and precision fertilizer spraying systems. In this study, the effects of the nitrogen application rate on the absorption and accumulation of nitrogen, phosphorus and potassium in sweet maize were determined. Firstly, linear, parabolic, exponential and logarithmic diagnostic models of nitrogen, phosphorus and potassium contents were constructed by spectral characteristic variables. Secondly, the partial least squares regression and neural network nonlinear diagnosis model of nitrogen, phosphorus and potassium contents were constructed by the high-frequency wavelet sensitivity coefficient of binary wavelet decomposition. The results show that the neural network nonlinear diagnosis model of nitrogen, phosphorus and potassium content based on the high-frequency wavelet sensitivity coefficient of binary wavelet decomposition is better. The R2, MRE and NRMSE of nn of nitrogen, phosphorus and potassium were 0.974, 1.65% and 0.0198; 0.969, 9.02% and 0.1041; and 0.821, 2.16% and 0.0301, respectively. The model can provide growth monitoring for sweet corn and a perception model for the nutrient element perception system of an agricultural robot, while making preliminary preparations for the realization of intelligent and accurate field fertilization.

An Exergoeconomic Analysis of a Gas-Type Industrial Drying System of Black Tea.

The performance evaluation and optimization of an energy conversion system design of an energy intensive drying system applied the method of combining exergy and economy is a theme of global concern. In this study, a gas-type industrial drying system of black tea with a capacity of 100 kg/h is used to investigate the exergetic and economic performance through the exergy and exergoeconomic methodology. The result shows that the drying rate of tea varies from the maximum value of 3.48 gwater/gdry matter h to the minimum 0.18 gwater/gdry matter h. The highest exergy destruction rate is found for the drying chamber (74.92 kW), followed by the combustion chamber (20.42 kW) in the initial drying system, and 51.83 kW and 21.15 kW in the redrying system. Similarly, the highest cost of the exergy destruction rate is found for the drying chamber (18.497 USD/h), followed by the combustion chamber (5.041 USD/h) in the initial drying system, and 12.796 USD/h and 5.222 USD/h in the redrying system. Furthermore, we analyzed the unit exergy rate consumed and the unit exergy cost of water removal in different drying sections of the drying system, and determined the optimal ordering of each component. These results mentioned above indicate that, whether from an energy or economic perspective, the component improvements should prioritize the drying chamber. Accordingly, minimizing exergy destruction and the cost of the exergy destruction rate can be considered as a strategy for improving the performance of energy and economy. Overall, the main results provide a more intuitive judgment for system improvement and optimization, and the exergy and exergoeconomic methodology can be commended as a method for agricultural product industrial drying from the perspective of exergoeconomics.

Fabrication and Performance of Graphene Flexible Pressure Sensor with Micro/Nano Structure.

Laser-induced graphene (LIG) has been widely used in flexible sensors due to its excellent mechanical properties and high conductivity. In this paper, a flexible pressure sensor prepared by bionic micro/nanostructure design and LIG mass fraction regulation is reported. First, prepared LIG and conductive carbon paste (CCP) solutions were mixed to obtain a conductive polymer. After the taro leaf structure was etched on the surface of the aluminum alloy plate by Nd:YAG laser processing, the conductive polymer was evenly coated on the template. Pressure sensors were packaged with a stencil transfer printing combined with an Ecoflex flexible substrate. Finally, the effects of different laser flux and the proportion of LIG in the composite on the sensitivity of the sensor are discussed. The results show that when the laser flux is 71.66 J·cm-2 and the mass fraction of LIG is 5%, the sensor has the best response characteristics, with a response time and a recovery time of 86 ms and 101 ms, respectively, with a sensitivity of 1.2 kPa-1 over a pressure range of 0-6 kPa, and stability of 650 cycle tests. The LIG/CCP sensor with a bionic structure demonstrates its potential in wearable devices.

Fingerprint identification of white clover cultivars based on SSR molecular markers.

White clover (Trifolium repens L.) is an important perennial legume forage with high productivity and quality. To strengthen the basic research on the genetic characteristics, fingerprint identification and adaptability of white clover germplasm resources, Simple sequence repeat (SSR) molecular markers were applied to 10 white clover cultivars to assess the genetic diversity and related lines of white clover at the molecular level in order to lay a theoretical foundation for the selection of high-quality seeds and cultivars of white clover. A total of 120 different bands were amplified by 29 pairs of SSR primers with good polymorphism, of which 103 (89.5%) were polymorphic. Meanwhile, the PIC of each primer was 0.181-0.588, with an average of 0.329. Analysis of molecular variance revealed that 57% of the genetic variation occurred within cultivars and 43% occurred among cultivars. The results of cluster analysis and the principal coordinate analysis revealed that the parental relationships of the 10 cultivars, with the 'Purple' cultivar very distantly related to the other 9 cultivars and the closest parental relationship between 'Ladino' and 'Sulky'. The fingerprints constructed by three representative primers (gtrs679, gtrs319, and gtrs678) have a strong identification ability. In summary, the SSR markers had good polymorphism and could be used for DNA fingerprint analysis of white clover cultivars.

Research Progress of Graphene-Based Flexible Humidity Sensor.

Graphene is a new type of carbon material with a flexible, two-dimensional structure. Due to the excellent stability of its lattice structure and its mechanical flexibility, graphene-based materials can be applied in flexible humidity sensors. At present, the application of graphene-based flexible humidity sensors in the fields of medical care and environmental monitoring is attracting widespread attention. In this review, the basic properties of graphene oxide (GO) and reduced graphene oxide (rGO) as moisture-sensitive materials and methods for their preparation were introduced. Moreover, three methods for improving the performance of moisture-sensitive materials were discussed. The working principle of different types of graphene-based humidity sensors were introduced. The progress in the research on graphene-based flexible humidity sensors in four respects: Human respiration, skin moisture, human sweat, and environmental humidity were discussed. Finally, the future research, following the development trends and challenges, to develop the potential of integrated, graphene-based flexible humidity sensors were discussed.

Research Progress on the Early Monitoring of Pine Wilt Disease Using Hyperspectral Techniques.

Pine wilt disease (PWD) caused by pine wood nematode (PWN, Bursaphelenchus xylophilus) originated in North America and has since spread to Asia and Europe. PWN is currently a quarantine object in 52 countries. In recent years, pine wilt disease has caused considerable economic losses to the pine forest production industry in China, as it is difficult to control. Thus, one of the key strategies for controlling pine wilt disease is to identify epidemic points as early as possible. The use of hyperspectral cameras mounted on drones is expected to enable PWD monitoring over large areas of forest, and hyperspectral images can reflect different stages of PWD. The trend of applying hyperspectral techniques to the monitoring of pine wilt disease is analyzed, and the corresponding strategies to address the existing technical problems are proposed, such as data collection of early warning stages, needs of using unmanned aerial vehicles (UAVs), and establishment of models after preprocessing.

Higher serum VGF protein levels discriminate bipolar depression from major depressive disorder.

Misdiagnosis between major depressive disorder (MDD) and bipolar depression (BD) is quite common. Our previous study found significantly lower serum VGF (non-acronymic) in MDD patients. However, it is unclear whether same changes occur in BD patients. Therefore, we aimed to investigate the relationship between serum VGF levels in BD and MDD patients. General information, scores of 17-item Hamilton Depression Rating Scale (HDRS), and fasting blood samples of all participants including 30 MDD patients, 20 BD patients, and 30 healthy controls (HC) were collected. Serum VGF levels were measured by Enzyme-linked immunosorbent assay kits. Pearson correlation analysis was used to analyze correlations between serum VGF levels and clinical information. Receiver operating characteristic (ROC) curve and likelihood ratios (LRs) were used to analyze the differential potential of serum VGF. Serum VGF levels were significantly lower in MDD patients but higher in BD patients compared with HC (both PTukey < 0.01). No correlation was found between serum VGF levels and any data of subjects. The optimal cutoff for serum VGF in discriminating BD patients from MDD patients was ≥1093.85 pg/ml (AUC = 0.990, sensitivity of 95%, specificity of 100% and accuracy of 95%). LRs further confirmed the differential efficiency of serum VGF in distinguishing BD and MDD patients with +LR of infinity and -LR of 0. The results suggest that serum VGF level changed significantly in MDD and BD patients and serum VGF may be an indicator for differentiating BD patients from MDD patients.

The Novel Activity of Carbamazepine as an Activation Modulator Extends from NaV1.7 Mutations to the NaV1.8-S242T Mutant Channel from a Patient with Painful Diabetic Neuropathy.

Neuropathic pain in patients carrying sodium channel gain-of-function mutations is generally refractory to pharmacotherapy. However, we have shown that pretreatment of cells with clinically achievable concentration of carbamazepine (CBZ; 30 µM) depolarizes the voltage dependence of activation in some NaV1.7 mutations such as S241T, a novel CBZ mode of action of this drug. CBZ reduces the excitability of dorsal root ganglion (DRG) neurons expressing NaV1.7-S241T mutant channels, and individuals carrying the S241T mutation respond to treatment with CBZ. Whether the novel activation-modulating activity of CBZ is specific to NaV1.7, and whether this pharmacogenomic approach can be extended to other sodium channel subtypes, are not known. We report here the novel NaV1.8-S242T mutation, which corresponds to the NaV1.7-S241T mutation, in a patient with neuropathic pain and diabetic peripheral neuropathy. Voltage-clamp recordings demonstrated hyperpolarized and accelerated activation of NaV1.8-S242T. Current-clamp recordings showed that NaV1.8-S242T channels render DRG neurons hyperexcitable. Structural modeling shows that despite a substantial difference in the primary amino acid sequence of NaV1.7 and NaV1.8, the S242 (NaV1.8) and S241 (NaV1.7) residues have similar position and orientation in the domain I S4-S5 linker of the channel. Pretreatment with a clinically achievable concentration of CBZ corrected the voltage dependence of activation of NaV1.8-S242T channels and reduced DRG neuron excitability as predicted from our pharmacogenomic model. These findings extend the novel activation modulation mode of action of CBZ to a second sodium channel subtype, NaV1.8.

Nonmuscle myosin II isoforms interact with sodium channel alpha subunits.

Sodium channels play pivotal roles in health and diseases due to their ability to control cellular excitability. The pore-forming α-subunits (sodium channel alpha subunits) of the voltage-sensitive channels (i.e., Nav1.1-1.9) and the nonvoltage-dependent channel (i.e., Nax) share a common structural motif and selectivity for sodium ions. We hypothesized that the actin-based nonmuscle myosin II motor proteins, nonmuscle myosin heavy chain-IIA/myh9, and nonmuscle myosin heavy chain-IIB/myh10 might interact with sodium channel alpha subunits to play an important role in their transport, trafficking, and/or function. Immunochemical and electrophysiological assays were conducted using rodent nervous (brain and dorsal root ganglia) tissues and ND7/23 cells coexpressing Nav subunits and recombinant myosins. Immunoprecipitation of myh9 and myh10 from rodent brain tissues led to the coimmunoprecipitation of Nax, Nav1.2, and Nav1.3 subunits, but not Nav1.1 and Nav1.6 subunits, expressed there. Similarly, immunoprecipitation of myh9 and myh10 from rodent dorsal root ganglia tissues led to the coimmunoprecipitation of Nav1.7 and Nav1.8 subunits, but not Nav1.9 subunits, expressed there. The functional implication of one of these interactions was assessed by coexpressing myh10 along with Nav1.8 subunits in ND7/23 cells. Myh10 overexpression led to three-fold increase ( P < 0.01) in the current density of Nav1.8 channels expressed in ND7/23 cells. Myh10 coexpression also hyperpolarized voltage-dependent activation and steady-state fast inactivation of Nav1.8 channels. In addition, coexpression of myh10 reduced ( P < 0.01) the offset of fast inactivation and the amplitude of the ramp currents of Nav1.8 channels. These results indicate that nonmuscle myosin heavy chain-IIs interact with sodium channel alpha subunits subunits in an isoform-dependent manner and influence their functional properties.

CD24 is a Potential Biomarker for Prognosis in Human Breast Carcinoma.

BACKGROUND/AIMS: CD24 is a highly glycosylated mucin-like antigen on the cell surface, which has recently emerged as a novel oncogene and metastasis promoter. We performed bioinformatics analysis to investigate whether CD24 can serve as a prognostic indicator in breast cancer. METHODS: CD24 expression was assessed using SAGE Genie tools and Oncomine analysis. The PrognoScan database, Kaplan-Meier Plotter, and bc-GenExMiner were used to identify the prognostic roles of CD24 in breast cancer. RESULTS: We found that CD24 was more frequently overexpressed in breast cancer than in normal breast tissue and correlated with worse prognosis. Meanwhile, high CD24 expression was associated with increased risk of HER2, basal-like, triple-negative breast cancer, and higher Scarff-Bloom-Richardson grade. Data mining in multiple big databases confirmed a positive correlation between CD24 mRNA expression and SDC1 mRNA expression in breast cancer tissue. CONCLUSIONS: Our findings suggest that CD24 overexpression is more common in breast cancer than in corresponding normal tissue. In addition, CD24 and SDC1 can serve as prognostic indicators for breast cancer. However, large-scale and comprehensive research is needed to further confirm these results.

Familial gain-of-function Nav1.9 mutation in a painful channelopathy.

OBJECTIVE: Gain-of-function mutations in Nav1.9 have been identified in three families with rare heritable pain disorders, and in patients with painful small-fibre neuropathy. Identification and functional assessment of new Nav1.9 mutations will help to elucidate the phenotypic spectrum of Nav1.9 channelopathies. METHODS: Patients from a large family with early-onset pain symptoms were evaluated by clinical examination and genomic screening for mutations in SCN9A and SCN11A. Electrophysiological recordings and multistate modelling analysis were implemented for functional analyses. RESULTS: A novel Nav1.9 mutation, p.Arg222His, was identified in patients with early-onset pain in distal extremities including joints and gastrointestinal disturbances, but was absent from an asymptomatic blood relative. This mutation alters channel structure by substituting the highly conserved first arginine residue in transmembrane segment 4 (domain 1), the voltage sensor, with histidine. Voltage-clamp recordings demonstrate a hyperpolarising shift and acceleration of activation of the p.Arg222His mutant channel, which make it easier to open the channel. When expressed in dorsal root ganglion neurons, mutant p.Arg222His channels increase excitability via a depolarisation of resting potential and increased evoked firing. CONCLUSIONS: This study expands the spectrum of heritable pain disorders linked to gain-of-function mutations in Nav1.9, strengthening human validation of this channel as a potential therapeutic target for pain.

A SCN10A SNP biases human pain sensitivity.

BACKGROUND: Nav1.8 sodium channels, encoded by SCN10A, are preferentially expressed in nociceptive neurons and play an important role in human pain. Although rare gain-of-function variants in SCN10A have been identified in individuals with painful peripheral neuropathies, whether more common variants in SCN10A can have an effect at the channel level and at the dorsal root ganglion, neuronal level leading to a pain disorder or an altered normal pain threshold has not been determined. RESULTS: Candidate single nucleotide polymorphism association approach together with experimental pain testing in human subjects was used to explore possible common SCN10A missense variants that might affect human pain sensitivity. We demonstrated an association between rs6795970 (G > A; p.Ala1073Val) and higher thresholds for mechanical pain in a discovery cohort (496 subjects) and confirmed it in a larger replication cohort (1005 female subjects). Functional assessments showed that although the minor allele shifts channel activation by -4.3 mV, a proexcitatory attribute, it accelerates inactivation, an antiexcitatory attribute, with the net effect being reduced repetitive firing of dorsal root ganglion neurons, consistent with lower mechanical pain sensitivity. CONCLUSIONS: At the association and mechanistic levels, the SCN10A single nucleotide polymorphism rs6795970 biases human pain sensitivity.

Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.

Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.

Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy.

Sodium channel Nav1.9 is expressed in peripheral nociceptive neurons, as well as visceral afferents, and has been shown to act as a threshold channel. Painful peripheral neuropathy represents a significant public health challenge and may involve gain-of-function variants in sodium channels that are preferentially expressed in peripheral sensory neurons. Although gain-of-function variants of peripheral sodium channels Nav1.7 and Nav1.8 have recently been found in painful small fibre neuropathy, the aetiology of peripheral neuropathy in many cases remains unknown. We evaluated 459 patients who were referred for possible painful peripheral neuropathy, and confirmed the diagnosis of small fibre neuropathy in a cohort of 393 patients (369 patients with pure small fibre neuropathy, and small fibre neuropathy together with large fibre involvement in an additional 24 patients). From this cohort of 393 patients with peripheral neuropathy, we sequenced SCN11A in 345 patients without mutations in SCN9A and SCN10A, and found eight variants in 12 patients. Functional profiling by electrophysiological recordings showed that these Nav1.9 mutations confer gain-of-function attributes to the channel, depolarize resting membrane potential of dorsal root ganglion neurons, enhance spontaneous firing, and increase evoked firing of these neurons. Our data show, for the first time, missense mutations of Nav1.9 in individuals with painful peripheral neuropathy. These genetic and functional observations identify missense mutations of Nav1.9 as a cause of painful peripheral neuropathy.

Gain-of-function Nav1.8 mutations in painful neuropathy.

Painful peripheral neuropathy often occurs without apparent underlying cause. Gain-of-function variants of sodium channel Na(v)1.7 have recently been found in ∼30% of cases of idiopathic painful small-fiber neuropathy. Here, we describe mutations in Na(v)1.8, another sodium channel that is specifically expressed in dorsal root ganglion (DRG) neurons and peripheral nerve axons, in patients with painful neuropathy. Seven Na(v)1.8 mutations were identified in 9 subjects within a series of 104 patients with painful predominantly small-fiber neuropathy. Three mutations met criteria for potential pathogenicity based on predictive algorithms and were assessed by voltage and current clamp. Functional profiling showed that two of these three Na(v)1.8 mutations enhance the channel's response to depolarization and produce hyperexcitability in DRG neurons. These observations suggest that mutations of Na(v)1.8 contribute to painful peripheral neuropathy.

Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H.

The link between sodium channel Nav1.7 and pain has been strengthened by identification of gain-of-function mutations in patients with inherited erythromelalgia (IEM), a genetic model of neuropathic pain in humans. A firm mechanistic link to nociceptor dysfunction has been precluded because assessments of the effect of the mutations on nociceptor function have thus far depended on electrophysiological recordings from dorsal root ganglia (DRG) neurons transfected with wild-type (WT) or mutant Nav1.7 channels, which do not permit accurate calibration of the level of Nav1.7 channel expression. Here, we report an analysis of the function of WT Nav1.7 and IEM L858H mutation within small DRG neurons using dynamic-clamp. We describe the functional relationship between current threshold for action potential generation and the level of WT Nav1.7 conductance in primary nociceptive neurons and demonstrate the basis for hyperexcitability at physiologically relevant levels of L858H channel conductance. We demonstrate that the L858H mutation, when modeled using dynamic-clamp at physiological levels within DRG neurons, produces a dramatically enhanced persistent current, resulting in 27-fold amplification of net sodium influx during subthreshold depolarizations and even greater amplification during interspike intervals, which provide a mechanistic basis for reduced current threshold and enhanced action potential firing probability. These results show, for the first time, a linear correlation between the level of Nav1.7 conductance and current threshold in DRG neurons. Our observations demonstrate changes in sodium influx that provide a mechanistic link between the altered biophysical properties of a mutant Nav1.7 channel and nociceptor hyperexcitability underlying the pain phenotype in IEM.

The G1662S NaV1.8 mutation in small fibre neuropathy: impaired inactivation underlying DRG neuron hyperexcitability.

OBJECTIVE: Painful small fibre neuropathy (SFN) represents a significant public health problem, with no cause apparent in one-half of cases (termed idiopathic, I-SFN). Gain-of-function mutations of sodium channel NaV1.7 have recently been identified in nearly 30% of patients with biopsy-confirmed I-SFN. More recently, gain-of-function mutations of NaV1.8 have been found in patients with I-SFN. These NaV1.8 mutations accelerate recovery from inactivation, enhance the response to slow depolarisations, and enhance activation at the channel level, thereby producing hyperexcitability of small dorsal root ganglion (DRG) neurons, which include nociceptors, at the cellular level. Identification and functional profiling of additional NaV1.8 variants are necessary to determine the spectrum of changes in channel properties that underlie DRG neuron hyperexcitability in these patients. METHODS: Two patients with painful SFN were evaluated by skin biopsy, quantitative sensory testing, nerve conduction studies, screening of genomic DNA for mutations in SCN9A and SCN10A and electrophysiological functional analysis. RESULTS: A novel sodium channel NaV1.8 mutation G1662S was identified in both patients. Voltage-clamp analysis revealed that the NaV1.8/G1662S substitution impairs fast-inactivation, depolarising the midpoint (V1/2) by approximately 7 mV. Expression of G1662S mutant channels within DRG neurons rendered these cells hyperexcitable. CONCLUSIONS: We report for the first time a mutation of NaV1.8 which impairs inactivation, in patients with painful I-SFN. Together with our earlier results, our observations indicate that an array of NaV1.8 mutations, which affect channel function in multiple ways, can contribute to the pathophysiology of painful peripheral neuropathy.

Large field-of-view pine wilt disease tree detection based on improved YOLO v4 model with UAV images.

Introduction: Pine wilt disease spreads rapidly, leading to the death of a large number of pine trees. Exploring the corresponding prevention and control measures for different stages of pine wilt disease is of great significance for its prevention and control. Methods: To address the issue of rapid detection of pine wilt in a large field of view, we used a drone to collect multiple sets of diseased tree samples at different times of the year, which made the model trained by deep learning more generalizable. This research improved the YOLO v4(You Only Look Once version 4) network for detecting pine wilt disease, and the channel attention mechanism module was used to improve the learning ability of the neural network. Results: The ablation experiment found that adding the attention mechanism SENet module combined with the self-designed feature enhancement module based on the feature pyramid had the best improvement effect, and the mAP of the improved model was 79.91%. Discussion: Comparing the improved YOLO v4 model with SSD, Faster RCNN, YOLO v3, and YOLO v5, it was found that the mAP of the improved YOLO v4 model was significantly higher than the other four models, which provided an efficient solution for intelligent diagnosis of pine wood nematode disease. The improved YOLO v4 model enables precise location and identification of pine wilt trees under changing light conditions. Deployment of the model on a UAV enables large-scale detection of pine wilt disease and helps to solve the challenges of rapid detection and prevention of pine wilt disease.

Interaction of voltage-gated sodium channel Nav1.6 (SCN8A) with microtubule-associated protein Map1b.

The mechanism by which voltage-gated sodium channels are trafficked to the surface of neurons is not well understood. Our previous work implicated the cytoplasmic N terminus of the sodium channel Na(v)1.6 in this process. We report that the N terminus plus the first transmembrane segment (residues 1-153) is sufficient to direct a reporter to the cell surface. To identify proteins that interact with the 117-residue N-terminal domain, we carried out a yeast two-hybrid screen of a mouse brain cDNA library. Three clones containing overlapping portions of the light chain of microtubule-associated protein Map1b (Mtap1b) were recovered from the screen. Interaction between endogenous Na(v)1.6 channels and Map1b in mouse brain was confirmed by co-immunoprecipitation. Map1b did not interact with the N terminus of the related channel Na(v)1.1. Alanine-scanning mutagenesis of the Na(v)1.6 N terminus demonstrated that residues 77-80 (VAVP) contribute to interaction with Map1b. Co-expression of Na(v)1.6 with Map1b in neuronal cell line ND7/23 resulted in a 50% increase in current density, demonstrating a functional role for this interaction. Mutation of the Map1b binding site of Na(v)1.6 prevented generation of sodium current in transfected cells. The data indicate that Map1b facilitates trafficking of Na(v)1.6 to the neuronal cell surface.

Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy.

OBJECTIVE: Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I-SFN). We sought to identify a genetic basis for I-SFN by screening patients with biopsy-confirmed idiopathic SFN for mutations in the SCN9A gene, encoding voltage-gated sodium channel Na(V)1.7, which is preferentially expressed in small diameter peripheral axons. METHODS: Patients referred with possible I-SFN, who met the criteria of ≥2 SFN-related symptoms, normal strength, tendon reflexes, vibration sense, and nerve conduction studies, and reduced intraepidermal nerve fiber density (IENFD) plus abnormal quantitative sensory testing (QST) and no underlying etiology for SFN, were assessed clinically and by screening of SCN9A for mutations and functional analyses. RESULTS: Twenty-eight patients who met stringent criteria for I-SFN including abnormal IENFD and QST underwent SCN9A gene analyses. Of these 28 patients with biopsy-confirmed I-SFN, 8 were found to carry novel mutations in SCN9A. Functional analysis revealed multiple gain of function changes in the mutant channels; each of the mutations rendered dorsal root ganglion neurons hyperexcitable. INTERPRETATION: We show for the first time that gain of function mutations in sodium channel Na(V)1.7, which render dorsal root ganglion neurons hyperexcitable, are present in a substantial proportion (28.6%; 8 of 28) of patients meeting strict criteria for I-SFN. These results point to a broader role of Na(V)1.7 mutations in neurological disease than previously considered from studies on rare genetic syndromes, and suggest an etiological basis for I-SFN, whereby expression of gain of function mutant sodium channels in small diameter peripheral axons may cause these fibers to degenerate.