Reevaluating the splice-altering variant in TECTA as a cause of nonsyndromic hearing loss DFNA8/12 by functional analysis of RNA.

PURPOSE: The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing (PGT)for them. METHODS: Clinical examination, pedigree analysis and exome sequencing were carried out on the family. Minigene-based splicing analysis, in vivo RNA analysis and protein structure prediction by molecular modeling were conducted on the candidate variant. PGT for the causative variation and chromosome aneuploidis based on SNP analysis has been used for avoidance of hearing loss in this family. RESULTS: All the affected individuals presented with moderate down-sloping hearing loss and whole-exome sequencing identified a novel splice-site variant c.5383+6T>A in the tested subjects within the TECTA locus. Genotyping of all the 32 family members confirmed segregation of this variant and the hearing loss phenotype in the extended family. Functional analysis of RNA and molecular modeling indicates that c.5383+6T>A is a pathogenic splice-site variant and should be considered as genetic cause of the hearing loss. Furthermore, a successful singleton pregnancy with no variation in TECTA c.5383+6 was established and a healthy male child was born by PGT. CONCLUSION: We have identified a novel variant c.5383+6T>A in TECTA ZA-ZP inter-domain, which could be attributable to the early-onset autosomal dominant hearing loss. The implications of our study are valuable in elucidating the disrupted RNA splicing and uncovering the genetic cause of hearing loss with TECTA pathogenic variants, as well as providing reproductive approaches to healthy offspring.

Binder-Responsive DNA Strand Displacement Enables High-Throughput and High-Fidelity Discovering of Small Molecular DNA Binders.

High-throughput screening (HTS) is pivotal in the discovery of small molecules that bind to DNA, yet there are limited sensing mechanisms available for designing HTS assays for DNA binders. Herein, we introduce a binder-responsive toehold-mediated DNA strand displacement (BR-TMSD) technique featuring programmable reaction kinetics in response to DNA-binder interactions. When two DNA binders are used, BR-TMSD is initiated through a rapid binder displacement, followed by the DNA strand displacement. The orthogonal displacement reactions of BR-TMSD enables a high-fidelity, dual-channel HTS assay, returning 19 new DNA binders from a library of 1,170 compounds.

Electronic and elastic properties of metastable Zr3N4: a joint experimental and theoretical study.

The electronic structures and elastic properties of metastable Zr3N4 phases have been investigated using the first-principles calculations with the Heyd-Scuseria-Ernzerhof (HSE06) hybrid functional, in comparison with those of the stable ZrN phase. All three metastable Zr3N4 phases (including orthorhombic, spinel and Th3P4-type phases) are found to be semiconducting with bandgaps of 1.72-1.94 eV. In particular, the computationally indirect bandgap of 1.72 eV of orthorhombic Zr3N4 is consistent with the experimental value of 1.8 eV. The detailed analyses of the electronic structures reveal that the change of electrical conductivity from metallic ZrN to semiconducting Zr3N4 is mainly due to the electron transfer from Zr to N atoms, which weakens the Zr-Zr interactions and reduces the proportion of metallic bonding. In addition, the elastic properties of Zr3N4 and ZrN phases have been calculated. The theoretical hardness values of ZrN and orthorhombic Zr3N4 are 18.06 and 6.98 GPa, respectively, agreeing well with the experimental values of 19.26 and 7.90 GPa. This work may further promote the understanding of the promising Zr-N material system.

The Effect of Hearing Loss and Working Memory Capacity on Context Use and Reliance on Context in Older Adults.

OBJECTIVES: Older adults often complain of difficulty in communicating in noisy environments. Contextual information is considered an important cue for identifying everyday speech. To date, it has not been clear exactly how context use (CU) and reliance on context in older adults are affected by hearing status and cognitive function. The present study examined the effects of semantic context on the performance of speech recognition, recall, perceived listening effort (LE), and noise tolerance, and further explored the impacts of hearing loss and working memory capacity on CU and reliance on context among older adults. DESIGN: Fifty older adults with normal hearing and 56 older adults with mild-to-moderate hearing loss between the ages of 60 and 95 years participated in this study. A median split of the backward digit span further classified the participants into high working memory (HWM) and low working memory (LWM) capacity groups. Each participant performed high- and low-context Repeat and Recall tests, including a sentence repeat and delayed recall task, subjective assessments of LE, and tolerable time under seven signal to noise ratios (SNRs). CU was calculated as the difference between high- and low-context sentences for each outcome measure. The proportion of context use (PCU) in high-context performance was taken as the reliance on context to explain the degree to which participants relied on context when they repeated and recalled high-context sentences. RESULTS: Semantic context helps improve the performance of speech recognition and delayed recall, reduces perceived LE, and prolongs noise tolerance in older adults with and without hearing loss. In addition, the adverse effects of hearing loss on the performance of repeat tasks were more pronounced in low context than in high context, whereas the effects on recall tasks and noise tolerance time were more significant in high context than in low context. Compared with other tasks, the CU and PCU in repeat tasks were more affected by listening status and working memory capacity. In the repeat phase, hearing loss increased older adults' reliance on the context of a relatively challenging listening environment, as shown by the fact that when the SNR was 0 and -5 dB, the PCU (repeat) of the hearing loss group was significantly greater than that of the normal-hearing group, whereas there was no significant difference between the two hearing groups under the remaining SNRs. In addition, older adults with LWM had significantly greater CU and PCU in repeat tasks than those with HWM, especially at SNRs with moderate task demands. CONCLUSIONS: Taken together, semantic context not only improved speech perception intelligibility but also released cognitive resources for memory encoding in older adults. Mild-to-moderate hearing loss and LWM capacity in older adults significantly increased the use and reliance on semantic context, which was also modulated by the level of SNR.

Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers.

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children (n = 67; mean age 2.77 year ± 1.31 SD; 28 females) with prelingual deafness provide a unique opportunity to study this stage. Using functional near-infrared spectroscopy, it was revealed that the brain of CI children was irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition.

Comparative analysis of vestibular endolymphatic hydrops grading methods and hearing loss in Ménière's disease: a retrospective MRI study using 3D-real inversion recovery sequence.

PURPOSE: To compare the correlation between different grading methods of vestibular endolymphatic hydrops (EH) and the severity of hearing loss in Ménière's disease (MD), and evaluate the diagnostic value of these methods in diagnosing MD. METHODS: This retrospective study included 30 patients diagnosed with MD from June 2021 to August 2023. All patients underwent inner ear MR gadolinium-enhanced imaging using three-dimensional (3D)-real inversion recovery sequences and pure-tone audiometry. The EH levels were independently evaluated according to the classification methods outlined by Nakashima et al. (Acta Otolaryngol Suppl 5-8, 2009. https://doi.org/10.1080/00016480902729827 ) (M1), Fang et al. (J Laryngol Otol 126:454-459, 2012. https://doi.org/10.1017/S0022215112000060 ) (M2), Barath et al. (Am J Neuroradiol 35:1387-1392, 2014. https://doi.org/10.3174/ajnr.A3856 ), (M3), Liu et al. (Front Surg 9:874971, 2022. https://doi.org/10.3389/fsurg.2022.874971 ), (M4), and Bernaerts et al. (Neuroradiology 61:421-429, 2019. https://doi.org/10.1007/s00234-019-02155-7 ) (M5), with a subsequent comparison of interobserver agreement. After achieving a consensus, an analysis was performed to explore the correlations between vestibular EH grading using different methods, the average hearing thresholds at low-mid, high-, and full frequencies and clinical stages. The diagnostic capabilities of these methods for MD were then compared. RESULTS: The interobserver consistency of M2-M5 was superior to that of M1. The EH grading based on M4 showed a significant correlation with the average hearing thresholds at low-mid, high-, and full frequencies and clinical stages. M1, M2, M3, and M5 correlated with some parameters. A receiver operating characteristic curve analysis indicated that M5 significantly outperformed M1, M2, M3, and M4 in terms of diagnostic efficiency for MD. CONCLUSION: M4 showed the strongest correlation with the degree of hearing loss in patients with MD, whereas M5 showed the highest diagnostic performance.

A Wide-Band Low-Profile Antenna for a High-Integration Phased Array System.

In this paper, a wide-band, low-profile antenna is presented for a high-integration phased array system. The proposed antenna, implemented using a tightly coupled array, operates over roughly the X-K frequency band and is performant at 8 GHz-18.5 GHz. The antenna can scan to ±60 degrees in both the E- and H-planes. Compared to previous tightly coupled antennas with smaller element spacing, the antenna in this paper reaches 9.4 mm, which corresponds to 0.58 λ of high frequency, suitable for engineering application conditions in production. The antenna can be soldered to BGA T/R chips in this space. Additionally, to facilitate flexible assembly for large arrays, the antenna is manufactured modularly using four elements and its parasitic radiation is analyzed. Then, a method for repressing parasitic radiation is presented. Finally, the antenna is fabricated and measured in a microwave chamber, exhibiting an excellent pattern and scanning radiation. The measured performance agrees with the full-wave finite array simulations.

[Construction and acceptability of different complementary foods texture in infants and young children aged 6 to 23 months].

OBJECTIVE: To construct the complementary food texture in infants and young children aged 6 to 23 months, and observe the acceptability of complementary food of different months old infants. METHODS: Based on the domestic and foreign guidelines, consensus and literatures on complementary feeding, and combined with the characteristics of children's growth and development in China. The complementary food texture index of 6-23 months old infants and young children was constructed. One province was selected in the south and north respectively, one city and one rural area was selected as the observation point in each province. The stratified random sampling principle was adopted in each observation point, 240 infants and young children were selected for the acceptability study. According to the food type, 12 common foods were selected to make the complementary food toolkit. The parents were instructed to make complementary food at home according to the corresponding month age, observe and record the acceptability of single/mixed complementary food feeding. RESULTS: The complementary food texture index of 6 months, 7-8 months, 9-11 months, 12-17 months, 18-23 months was constructed. Caregivers could make complementary food at the corresponding month age according to the established complementary food texture index. The acceptability of single complementary food for infants and young children aged 6-23 months was 98.3%, 98.7%, 99.8%, 96.9% and 97.5%, respectively. The acceptability of mixed complementary food for children aged 7-23 months was 98.3%, 99.6%, 93.8% and 97.5%, respectively. CONCLUSION: The complementary food texture index of different month age can be made at home, and the acceptability of different texture is good.

In Situ Vaccination with An Injectable Nucleic Acid Hydrogel for Synergistic Cancer Immunotherapy.

Recently, therapeutic cancer vaccines have emerged as promising candidates for cancer immunotherapy. Nevertheless, their efficacies are frequently impeded by challenges including inadequate antigen encapsulation, insufficient immune activation, and immunosuppressive tumor microenvironment. Herein, we report a three-in-one hydrogel assembled by nucleic acids (NAs) that can serve as a vaccine to in situ trigger strong immune response against cancer. Through site-specifically grafting the chemodrug, 7-ethyl-10-hydroxycamptothecin (also known as SN38), onto three component phosphorothioate (PS) DNA strands, a Y-shaped motif (Y-motif) with sticky ends is self-assembled, at one terminus of which an unmethylated cytosine-phosphate-guanine (CpG) segment is introduced as an immune agonist. Thereafter, programmed cell death ligand-1 (PD-L1) siRNA that performs as immune checkpoint inhibitor is designed as a crosslinker to assemble with the CpG- and SN38-containing Y-motif, resulting in the formation of final NA hydrogel vaccine. With three functional agents inside, the hydrogel can remarkably induce the immunogenic cell death to enhance the antigen presentation, promoting the dendritic cell maturation and effector T lymphocyte infiltration, as well as relieving the immunosuppressive tumor environment. When inoculated twice at tumor sites, the vaccine demonstrates a substantial antitumor effect in melanoma mouse model, proving its potential as a general platform for synergistic cancer immunotherapy.

A review of the signaling pathways of aerobic and anaerobic exercise on atherosclerosis.

Atherosclerosis (AS), a chronic inflammatory vascular disease with lipid metabolism abnormalities, is one of the major pathological bases of coronary heart disease. As people's lifestyles and diets change, the incidence of AS increases yearly. Physical activity and exercise training have recently been identified as effective strategies for lowering cardiovascular disease (CVD) risk. However, the best exercise mode to ameliorate the risk factors related to AS is not clear. The effect of exercise on AS is affected by the type of exercise, intensity, and duration. In particular, aerobic and anaerobic exercise are the two most widely discussed types of exercise. During exercise, the cardiovascular system undergoes physiological changes via various signaling pathways. The review aims to summarize signaling pathways related to AS in two different exercise types and provide new ideas for the prevention and treatment of AS in clinical practice.

Monte-Carlo based vertical underwater optical communication performance analysis with chlorophyll depth profiles.

Although underwater wireless optical communication (UWOC) has the advantages of high speed, low latency, and high confidentiality, the transmission of light in water will be affected by the absorption and scattering of particles, which will lead to the aggravation of channel path loss as well as channel pulse spreading, finally causing false codes. Therefore, how to analyze the channel impulse response (CIR) effectively is a key task in channel modeling. In this paper, we consider a two-way underwater vertical line-of-sight (LOS) communication system model, based on the inherent optical property (IOP) model of chlorophyll, using the Kopelevich phase function containing water depth information, the CIR curves under different water types and transceiver configurations are plotted using the Monte-Carlo Simulation (MCS). The obtained simulation results are fitted with the double gamma function (DGF) model and the Gaussian model, respectively. The Gaussian model exhibits better properties than the DGF model in each water condition. Based on the closed-form expression of the CIR obtained from the Gaussian model, we solve for the bit error rate (BER) and 3-dB bandwidth of the system under different settings. The conclusions obtained can be used for the design and optimization of underwater vertical channels.

Differential auditory cortical development in left and right cochlear implanted children.

Unilateral aural stimulation has been shown to cause massive cortical reorganization in brain with congenital deafness, particularly during the sensitive period of brain development. However, it is unclear which side of stimulation provides most advantages for auditory development. The left hemisphere dominance of speech and linguistic processing in normal hearing adult brain has led to the assumption of functional and developmental advantages of right over left implantation, but existing evidence is controversial. To test this assumption and provide evidence for clinical choice, we examined 34 prelingually deaf children with unilateral cochlear implants using near-infrared spectroscopy. While controlling for age of implantation, residual hearing, and dominant hand, cortical processing of speech showed neither developmental progress nor influence of implantation side weeks to months after implant activation. In sharp contrast, for nonspeech (music signal vs. noise) processing, left implantation showed functional advantages over right implantation that were not yet discernable using clinical, questionnaire-based outcome measures. These findings support the notion that the right hemisphere develops earlier and is better preserved from adverse environmental influences than its left counterpart. This study thus provides, to our knowledge, the first evidence for differential influences of left and right auditory peripheral stimulation on early cortical development of the human brain.

Delayed progressive sensorineural hearing loss due to a novel compound heterozygous PTPRQ mutation in a Chinese patient.

BACKGROUND: The Protein tyrosine phosphatase receptor Q (PTPRQ) gene encodes a member of the type III receptor-like protein tyrosine phosphatase family found in the stereocilium. Mutations in PTPRQ are mostly associated with deafness, autosomal recessive type 84 (DFNB 84), which usually results in progressive familial hearing loss. METHODS: A 25-year-old woman and her sister, both with postlingual-delayed progressive sensorineural hearing loss, were examined. They were from a nonconsanguineous marriage and had no family history of hearing loss. New compound heterozygous PTPRQ gene mutations, nonsense (c.90C > A, p.Y30X) and splice (c.5426 + 1G > A) mutations in two PTPRQ alleles, were identified in the two sisters and were presumably autosomal recessive. The c.90C > A (p.Y30X) mutation was mapped to exon 2 of PTPRQ (NM_001145026). RESULTS: The c.90C > A mutation leads to a premature stop codon and a truncated protein. The c.5426 + 1G > A mutation leads to a truncated protein lacking the extracellular domain. Hence, both mutations were predicted to be pathogenic, leading to a deficiency of the extracellular, transmembrane, and phosphatase domains because of nonsense-mediated mRNA degradation. CONCLUSIONS: This study increases the spectrum of PTPRQ gene mutations that might be involved in delayed progressive autosomal recessive non-syndromic hearing loss.

[Construction of malnutrition visualization system].

OBJECTIVE: To establish a set of visualization systems suitable for displaying the transition of malnutrition status in different population across time and space in China. METHODS: Based on the data characteristics of the four monitoring systems, including the China Nutrition and Health Surveillance, the China Health and Nutrition Survey, the Project of Children Nutrition Improvement in Poor Rural Regions, and the Nutrition Improvement Program for Rural Compulsory Education Students, to be merged and the requirements of this project, the client/server architecture(C/S architecture) application mode was adopted, the Visual Studio 2019 development tool set, Python 3.7-10 and C # 8.0 language programming were used for data integration, and a complete set of data preprocessing, data conversion and data integration calculation processes were established. RESULTS: The malnutrition visualization system provided a visualization display system for the nutritional status of different populations under the multi database fusion index system based on the integrated malnutrition database. The system was able to not only modify, delete and update data, but query, display and analyze malnutrition conditions including growth retardation, low weight, emaciation, micronutrient deficiency, overweight, and obesity. CONCLUSION: Malnutrition visualization system dynamically presented the time series and spatial distribution of malnutrition among Chinese residents, and explored the regional characteristics and major challenges of nutrition problems in different periods.

[Conditional optimization and methodological evaluation of liquid protein microarray in detecting cystatin C].

OBJECTIVE: To optimize the detection conditions and evaluate of cystatin C(CysC) by liquid protein microarray. METHODS: CysC was detected by double antibody sandwich method using liquid protein microarray. On the basis of determining the optimal concentration combination of captured antibody and detected antibody, the detection conditions were optimized by determining the biological detection limit and lower detection limit, drawing the S-shaped curve and judging the linear range, and establishing the standard curve and regression equation. Methodsologically evaluate the accuracy, precision, reportable range and analytical specificity of the detection method. RESULTS: The optimal concentration combinations of CycC trapping-detection antibodies were 26.6 µg/mL-1∶800. The lower limits of detection and biologic limits of detection of the CysC were 0.037 and 0.237 ng/mL, respectively. Regression equation were as followes: y=-3.315x~2+283.04x+160.89, R~2=0.9921. The relative bias of CysC which was detected on the liquid protein microarry was 5.81%. The dilution recovery and recovery were 70.35%-84.91%(n=3)and 79.94%-122.41%(n=3)respectively. The correlation coefficient of method ology comparison experiment was r=0.616, P<0.05, and there was no significant difference between the two method(t=0.948, P=0.358); The within-run precision range from 3.54% to 4.03%(n=10); The between-run precision range from 12.07% to 15.05%(D=5, n=3); The reportable range was 0.26-3784.04 ng/mL. The analysis of interference test result showed that the both concentrations of hemoglobin(160.00, 71.11 g/L) had interference to the result of CysC detected on the chip. CONCLUSION: This study completed the optimization of conditions and methodological evaluation of liquid protein microarray in detecting CysC.

DNA2 mutation causing multisystemic disorder with impaired mitochondrial DNA maintenance.

PURPOSE: To describe a novel DNA2 variant contributing to defects in mtDNA maintenance and mtDNA depletion syndrome (MDS), and the clinical and histological findings associated with this variation. METHODS: Herein, we describe the case of a patient who presented with hearing loss and myopathy, given the family history of similar findings in the father, was evaluated by sequencing of the deafness gene panel, mitochondrial genome, and the exome. Furthermore, tissue staining, mtDNA copy number detection, mtDNA sequencing, and long-range polymerase chain reaction tests were also conducted on the muscle biopsy specimen. In vitro experiments, including analyses of the mtDNA copy number; levels of ATP, ATPase, and reactive oxygen species (ROS); and the membrane potential, were performed. RESULTS: The DNA2 heterozygous truncating variant c. 2368C > T (p.Q790X) was identified and verified as the cause of an mtDNA copy number decrement in both functional experiments and muscle tissue analyses. These changes were accompanied by reductions in ATP, ATPase, and ROS levels. CONCLUSION: The DNA2 variant was a likely cause of MDS in this patient. These findings expand the mutational spectrum of MDS and improve our understanding of the functions of DNA2 by revealing its novel role in mtDNA maintenance.

Voice Emotion Recognition by Mandarin-Speaking Children with Cochlear Implants.

OBJECTIVES: Emotional expressions are very important in social interactions. Children with cochlear implants can have voice emotion recognition deficits due to device limitations. Mandarin-speaking children with cochlear implants may face greater challenges than those speaking nontonal languages; the pitch information is not well preserved in cochlear implants, and such children could benefit from child-directed speech, which carries more exaggerated distinctive acoustic cues for different emotions. This study investigated voice emotion recognition, using both adult-directed and child-directed materials, in Mandarin-speaking children with cochlear implants compared with normal hearing peers. The authors hypothesized that both the children with cochlear implants and those with normal hearing would perform better with child-directed materials than with adult-directed materials. DESIGN: Thirty children (7.17-17 years of age) with cochlear implants and 27 children with normal hearing (6.92-17.08 years of age) were recruited in this study. Participants completed a nonverbal reasoning test, speech recognition tests, and a voice emotion recognition task. Children with cochlear implants over the age of 10 years also completed the Chinese version of the Nijmegen Cochlear Implant Questionnaire to evaluate the health-related quality of life. The voice emotion recognition task was a five-alternative, forced-choice paradigm, which contains sentences spoken with five emotions (happy, angry, sad, scared, and neutral) in a child-directed or adult-directed manner. RESULTS: Acoustic analyses showed substantial variations across emotions in all materials, mainly on measures of mean fundamental frequency and fundamental frequency range. Mandarin-speaking children with cochlear implants displayed a significantly poorer performance than normal hearing peers in voice emotion perception tasks, regardless of whether the performance is measured in accuracy scores, Hu value, or reaction time. Children with cochlear implants and children with normal hearing were mainly affected by the mean fundamental frequency in speech emotion recognition tasks. Chronological age had a significant effect on speech emotion recognition in children with normal hearing; however, there was no significant correlation between chronological age and accuracy scores in speech emotion recognition in children with implants. Significant effects of specific emotion and test materials (better performance with child-directed materials) in both groups of children were observed. Among the children with cochlear implants, age at implantation, percentage scores of nonverbal intelligence quotient test, and sentence recognition threshold in quiet could predict recognition performance in both accuracy scores and Hu values. Time wearing cochlear implant could predict reaction time in emotion perception tasks among children with cochlear implants. No correlation was observed between the accuracy score in voice emotion perception and the self-reported scores of health-related quality of life; however, the latter were significantly correlated with speech recognition skills among Mandarin-speaking children with cochlear implants. CONCLUSIONS: Mandarin-speaking children with cochlear implants could have significant deficits in voice emotion recognition tasks compared with their normally hearing peers and can benefit from the exaggerated prosody of child-directed speech. The effects of age at cochlear implantation, speech and language development, and cognition could play an important role in voice emotion perception by Mandarin-speaking children with cochlear implants.

The NIN-like protein 5 (ZmNLP5) transcription factor is involved in modulating the nitrogen response in maize.

Maize exhibits marked growth and yield response to supplemental nitrogen (N). Here, we report the functional characterization of a maize NIN-like protein ZmNLP5 as a central hub in a molecular network associated with N metabolism. Predominantly expressed and accumulated in roots and vascular tissues, ZmNLP5 was shown to rapidly respond to nitrate treatment. Under limited N supply, compared with that of wild-type (WT) seedlings, the zmnlp5 mutant seedlings accumulated less nitrate and nitrite in the root tissues and ammonium in the shoot tissues. The zmnlp5 mutant plants accumulated less nitrogen than the WT plants in the ear leaves and seed kernels. Furthermore, the mutants carrying the transgenic ZmNLP5 cDNA fragment significantly increased the nitrate content in the root tissues compared with that of the zmnlp5 mutants. In the zmnlp5 mutant plants, loss of the ZmNLP5 function led to changes in expression for a significant number of genes involved in N signalling and metabolism. We further show that ZmNLP5 directly regulates the expression of nitrite reductase 1.1 (ZmNIR1.1) by binding to the nitrate-responsive cis-element at the 5' UTR of the gene. Interestingly, a natural loss-of-function allele of ZmNLP5 in Mo17 conferred less N accumulation in the ear leaves and seed kernels resembling that of the zmnlp5 mutant plants. Our findings show that ZmNLP5 is involved in mediating the plant response to N in maize.

[Clinical practice guidelines for hereditary non-syndromic deafness].

Genetic factors are a common cause for non-syndromic hearing loss (NSHL). Along with the development and maturity of molecular techniques, genetic diagnosis and counseling is increasingly affecting the clinical practice of NSHL. Newborn hearing screening has facilitated early detection of affected children, whilst genetic screening has enabled identification of the cause of NSHL, and genetic diagnosis and consultation can promote early intervention of deafness. So far 110 pathogenic genes of NSHL have been discovered, though there are still many challenges lying in its clinical identification. The development of genetic counseling and prenatal diagnosis has put forward greater requirements for genetic testing and data interpretation. This guideline has summarized the incidence, mutational spectrum, inheritance mode, pathogenesis, clinical manifestation, genotype - phenotype correlation, genetic testing, treatment and intervention, as well as risk assessment for NSHL, with an aim to provide a reference for genetic consultants, clinical otologists and professionals engaged in genetic testing.

Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese family.

We report on the genetic analysis of a Chinese family in which four male patients presented with postlingual progressive hearing loss, associated with distal muscle wasting and unsteady ataxic gait. Using whole exome sequencing, we identified a new pathogenic variant (c.1463C>T, p.Pro488Leu) in the AIFM1 gene, which encodes the apoptosis-inducing factor mitochondrion-associated 1 precursor. AIFM1 is involved in the mitochondrial respiratory chain and cellular caspase-independent apoptosis pathway and has been reported to cause multiple phenotypes including hearing loss. The p.Pro488Leu missense variant segregated with symptoms in the pedigree. It was not found in the dbSNP database, databases of genomes and SNPs in the Chinese population, in 74 patients with sporadic hearing loss, or in 108 normal individuals.We also verified that this AIFM1variant enhanced cell apoptosis rates compared in 293T cells transfected with wild-type AIFM1. Different variations of AIFM1 give rise to different phenotypes in patients, and this is the second reported family with a variant in the C-terminal domain of AIFM1 showing the phenotype of hearing loss and peripheral neuropathy.