Transposon-taming piRNAs in the germline: Where do they come from?

Mutations in the piRNA pathway protein components lead to transposon activation and fertility defects. In contrast, Gebert et al., (2021) saw no defects in transposon silencing or fertility when they deleted three large germline piRNA clusters in D. melanogaster.

piRNA-mediated gene regulation and adaptation to sex-specific transposon expression in D. melanogaster male germline.

Small noncoding piRNAs act as sequence-specific guides to repress complementary targets in Metazoa. Prior studies in Drosophila ovaries have demonstrated the function of the piRNA pathway in transposon silencing and therefore genome defense. However, the ability of the piRNA program to respond to different transposon landscapes and the role of piRNAs in regulating host gene expression remain poorly understood. Here, we comprehensively analyzed piRNA expression and defined the repertoire of their targets in Drosophila melanogaster testes. Comparison of piRNA programs between sexes revealed sexual dimorphism in piRNA programs that parallel sex-specific transposon expression. Using a novel bioinformatic pipeline, we identified new piRNA clusters and established complex satellites as dual-strand piRNA clusters. While sharing most piRNA clusters, the two sexes employ them differentially to combat the sex-specific transposon landscape. We found two piRNA clusters that produce piRNAs antisense to four host genes in testis, including CG12717/pirate, a SUMO protease gene. piRNAs encoded on the Y chromosome silence pirate, but not its paralog, to exert sex- and paralog-specific gene regulation. Interestingly, pirate is targeted by endogenous siRNAs in a sibling species, Drosophila mauritiana, suggesting distinct but related silencing strategies invented in recent evolution to regulate a conserved protein-coding gene.

RDC complex executes a dynamic piRNA program during Drosophila spermatogenesis to safeguard male fertility.

piRNAs are small non-coding RNAs that guide the silencing of transposons and other targets in animal gonads. In Drosophila female germline, many piRNA source loci dubbed "piRNA clusters" lack hallmarks of active genes and exploit an alternative path for transcription, which relies on the Rhino-Deadlock-Cutoff (RDC) complex. RDC was thought to be absent in testis, so it remains to date unknown how piRNA cluster transcription is regulated in the male germline. We found that components of RDC complex are expressed in male germ cells during early spermatogenesis, from germline stem cells (GSCs) to early spermatocytes. RDC is essential for expression of dual-strand piRNA clusters and transposon silencing in testis; however, it is dispensable for expression of Y-linked Suppressor of Stellate piRNAs and therefore Stellate silencing. Despite intact Stellate repression, males lacking RDC exhibited compromised fertility accompanied by germline DNA damage and GSC loss. Thus, piRNA-guided repression is essential for normal spermatogenesis beyond Stellate silencing. While RDC associates with multiple piRNA clusters in GSCs and early spermatogonia, its localization changes in later stages as RDC concentrates on a single X-linked locus, AT-chX. Dynamic RDC localization is paralleled by changes in piRNA cluster expression, indicating that RDC executes a fluid piRNA program during different stages of spermatogenesis. These results disprove the common belief that RDC is dispensable for piRNA biogenesis in testis and uncover the unexpected, sexually dimorphic and dynamic behavior of a core piRNA pathway machinery.

Role of early hearing aid experience in speech recognition in patients with bilateral congenital microtia following Bonebridge implantation: a retrospective cohort study.

PURPOSE: To identify audiological and demographic variables that predict speech recognition abilities in patients with bilateral microtia who underwent Bonebridge (BB) implantation. METHODS: Fifty patients with bilateral microtia and bilateral conductive hearing loss (CHL) who underwent BB implantation were included. Demographic data, preoperative hearing aid use experience, and audiological outcomes (including pure-tone hearing threshold, sound field hearing threshold [SFHT], and speech recognition ability) for each participant were obtained. The Chinese-Mandarin Speech Test Materials were used to test speech recognition ability. The word recognition score (WRS) of disyllabic words at 65 dB SPL signals was measured before and after BB implantation in quiet and noisy conditions. RESULTS: The mean preoperative WRS under quiet and noisy conditions was 10.44 ± 12.73% and 5.90 ± 8.76%, which was significantly improved to 86.38 ± 9.03% and 80.70 ± 11.34%, respectively, following BB fitting. Multiple linear regression analysis revealed that lower preoperative SFHT suggested higher preoperative WRS under both quiet and noisy conditions. Higher age at implantation predicted higher preoperative WRS under quiet conditions. Furthermore, patients with more preoperative hearing aid experience and lower postoperative SFHT were more likely to have higher postoperative WRS under both quiet and noisy testing conditions. CONCLUSIONS: This study represents the first attempt to identify predictors of preoperative and postoperative speech recognition abilities in patients with bilateral microtia with BB implantation. These findings emphasize that early hearing intervention before implantation surgery, combined with appropriate postoperative fitting, contributes to optimal benefits in terms of postoperative speech recognition ability.

A new active bone-conduction implant: surgical experiences and audiological outcomes in patients with bilateral congenital microtia.

PURPOSE: First-generation bone bridges (BBs) have demonstrated favorable safety and audiological benefits in patients with conductive hearing loss. However, studies on the effects of second-generation BBs are limited, especially among children. In this study, we aimed to explore the surgical and audiological effects of second-generation BBs in patients with bilateral congenital microtia. METHODS: This single-center prospective study included nine Mandarin-speaking patients with bilateral microtia. All the patients underwent BCI Generation 602 (BCI602; MED-EL, Innsbruck, Austria) implant surgery between September 2021 and June 2023. Audiological and sound localization tests were performed under unaided and BB-aided conditions. RESULTS: The transmastoid and retrosigmoid sinus approaches were implemented in three and six patients, respectively. No patient underwent preoperative planning, lifts were unnecessary, and no sigmoid sinus or dural compression occurred. The mean function gain at 0.5-4.0 kHz was 28.06 ± 4.55-dB HL. The word recognition scores improved significantly in quiet under the BB aided condition. Signal-to-noise ratio reduction by 10.56 ± 2.30 dB improved the speech reception threshold in noise. Patients fitted with a unilateral BB demonstrated inferior sound source localization after the initial activation. CONCLUSIONS: Second-generation BBs are safe and effective for patients with bilateral congenital microtia and may be suitable for children with mastoid hypoplasia without preoperative three-dimensional reconstruction.

A Study on the Nonsurgical Correction Treatment Age Window and Long-Term Follow-Up of Infants With Congenital Ear Anomalies in China.

OBJECTIVES: To evaluate the efficacy of ear molding across various initial ages and analyze challenges encountered by infants beyond the optimal treatment age window. METHODS: A retrospective review of 331 infants (527 ears) treated with EarWell was conducted over 5 years from January 2017 to March 2022 at a single center. The treatment duration of the ear molding, success rate, recurrence rate, and complication rate were analyzed among the 3 age groups. Concentrate on evaluating treatment outcomes for infants with an initial age exceeding 42 days. RESULTS: The mean age at initial treatment was 25±28 days. In addition, it includes a child with cryptotia who is 3.5 years old (1278 d). The mean duration of treatment was 7±5 weeks. In the long-term follow-up, the overall treatment success rate was 92%, with 467 ears (88.6%) showing improvement without recurrence, 30 ears (5.7%) experiencing varying degrees of recurrence, and 30 ears (5.7%) showing no improvement or complete recurrence. A total of 20 infants (3%) developed mild skin complications during treatment. CONCLUSIONS: Ear molding is a safe and effective option for the treatment of congenital ear anomalies, with a low recurrence rate during long-term follow-up. For infants with congenital auricular anomalies aged over 42 days, ear molding remains a viable option. Treatment success may be influenced by the age at treatment, the subtype of anomalies, and relies on the assessment of a specialized otologist, expert procedural techniques, as well as thorough understanding and cooperation from parents.

Optimal Choice for Improving the Hearing in Children with Unilateral Microtia and Atresia: Softband or Adhesive Adapter?

INTRODUCTION: A nonsurgical bone conduction hearing aid (BCHA) is a well-established treatment for children with congenital unilateral microtia and atresia (UMA). To date, limited studies have evaluated the audiological characteristics of the different wearing modes in the same nonsurgical BCHA. METHODS: Eighteen patients with UMA aged 5-24 years were included. Warble tones at frequencies of 0.5, 1, 2, and 4 kHz were presented to determine functional hearing gain (FHG) of hearing thresholds (in dB HL) in the sound field. The speech perception abilities were assessed by the speech discrimination score (SDS, in %) of monosyllables, disyllables, and sentences in quiet and noise using the Chinese Mandarin speech test materials. Hearing outcomes were evaluated with the ADHEAR™ worn on a softband and with an adhesive adapter. A correlational analysis was conducted to analyze the correlations between variables (e.g., age, height, weight, body mass index [BMI], bone conduction pure-tone threshold, and air conduction pure-tone threshold) and the differences in the two wearing modes. RESULTS: The mean FHG (standard deviation, SD) at 0.5-4 kHz was 20.63 (3.94) dB HL with the adhesive adapter and 26.39 (3.15) dB HL with the softband. When aided with the BCHA, significant improvements in SDS were revealed in all Mandarin speech test material lists either in quiet or noise for both wearing modes. Compared with the adapter mode, the softband provided higher aided SDS values. Correctional analyses revealed that higher BMI values were positively associated with larger delta outcomes between the two coupling methods of the softband and adhesive adapter in patients with UMA. Furthermore, a larger delta average FHG of 0.5-4 kHz was consistently associated with larger delta monosyllabic SDS in quiet, disyllabic SDS in quiet, and disyllabic SDS in noise. DISCUSSION: To the best of our knowledge, this is the first study to compare the hearing benefits of coupling methods using novel adhesive adapters and conventional softbands with the same audio processor (ADHEAR™). Under uniform internal settings, softband integration provided more hearing benefits than adhesive adapter integration, and the differences were more obvious in patients with higher BMI values. Besides, a brief measurement of FHG can be utilized to predict individualized speech perception levels.

Audiological and subjective benefit with a new adhesive bone conduction hearing aid in children with congenital unilateral microtia and atresia.

PURPOSE: This study aimed to evaluate the audiological benefits and subjective satisfaction in using a new adhesive bone conduction hearing aid in children with congenital unilateral microtia and atresia. METHODS: We evaluated the effectiveness of the hearing aid using the sound field hearing threshold, speech recognition ability under quiet and noise, and subjective questionnaires in 13 children (5-15 years old). RESULTS: The mean sound field hearing threshold significantly improved with a gain of 25.4 ± 4.9 dB HL. Mean word recognition scores were ameliorated in quiet and noise by 1.9 ± 2.5% and 7.3 ± 5.3%, respectively. Speech recognition ability results in noise varied; when the speech signal and noise were presented from the front, the mean speech recognition ability improved by 2.5 ± 1.6 dB signal-to-noise ratios (SNR). When noise was presented towards the normal hearing side, speech understanding was improved by 2.9 ± 1.6 dB SNR. When the speech signal was presented from the atretic side with noise from the normal hearing side, an improvement of 5.7 ± 3.4 dB SNR (p < 0.001) was noted. However, when noise was presented towards the newly aided atretic ear, no statistical significance was found. The questionnaire results indicated that the hearing device provided benefits in speech recognition ability in different complex situations, with high satisfaction rates. CONCLUSION: The adhesive bone conduction hearing aid investigated here offers a concealed and aesthetic method to improve hearing in children with congenital unilateral microtia and atresia during their early years, with high subjective satisfaction.

Constructing Morphologically Tunable Copper Oxide-Based Nanomaterials on Cu Wire with/without the Deposition of Manganese Oxide as Bifunctional Materials for Glucose Sensing and Supercapacitors.

Morphologically tunable copper oxide-based nanomaterials on Cu wire have been synthesized through a one-step alkali-assisted surface oxidation process for non-enzymatic glucose sensing. Subsequently, copper oxide-based nanomaterials on Cu wire as a supporting matrix to deposit manganese oxide for the construction of heterostructured Mn-Cu bimetallic oxide architectures through spontaneous redox reaction in the KMnO4 solution for supercapacitors. Field emission scanning electron microscopy (FESEM), field emission transmission electron microscopy (FETEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) confirmed that morphological and phase transformation from Cu(OH)2 to CuO occurred in copper oxide-based nanomaterials on Cu wire with different degrees of growth reaction. In non-enzymatic glucose sensing, morphologically tunable copper oxide-based nanomaterials owned the high tunability of electrocatalytically active sites and intrinsic catalytic activity to meet efficient glucose electrooxidation for obtaining promoted non-enzymatic glucose sensing performances (sensitivity of 2331 µA mM-1 cm-2 and the limit of detection of 0.02 mM). In the supercapacitor, heterostructured Mn-Cu bimetallic oxide-based nanomaterials delivered abundant redox-active sites and continuous conductive network to optimize the synergistic effect of Mn and Cu redox species for boosting the pseudo-capacitance performance (areal capacitance value of 79.4 mF cm-2 at 0.2 mA cm-2 current density and capacitance retention of 74.9% after 1000 cycles). It concluded that morphologically tunable copper oxide-based nanomaterials on Cu wire with/without deposition of manganese oxide could be good candidates for the future design of synergistic multifunctional materials in electrochemical techniques.

Sound-localisation performance in patients with congenital unilateral microtia and atresia fitted with an active middle ear implant.

OBJECTIVE: This study assessed the safety and sound-localisation ability of the Vibrant Soundbridge (VSB) (Med-EL, Innsbruck, Austria) in patients with unilateral microtia and atresia (MA). METHODS: This was a single-centre retrospective research study. Twelve subjects with unilateral conductive hearing loss (UCHL) caused by ipsilateral MA were recruited, each of whom underwent VSB implantation and auricular reconstruction. The bone-conduction (BC) threshold was measured postoperatively, and the accuracy of sound localisation was evaluated at least 6 months after surgery. Horizontal sound-localisation performance was investigated with the VSB activated and inactivated, at varying sound stimuli levels (65, 70 and 75 dB SPL). Localisation benefit was analysed via the mean absolute error (MAE). RESULTS: There was no statistical difference in mean BC threshold of impaired ears measured preoperatively and postoperatively. When compared with VSB-inactivated condition, the MAE increased significantly in unilateral MA patients in the VSB-activated condition. Besides, sound-localisation performance worsened remarkably when sound was presented at 70 dB SPL and 75 dB SPL. Regarding the side of signal location, the average MAE with the VSB device was much higher than that without the VSB when sound was from the normal-hearing ear. However, no significant difference was observed when sound was located from the impaired ear. CONCLUSION: This study demonstrates that in patients with unilateral MA, the VSB device does not affect inner-ear function. Sound-localisation ability is not improved, but deteriorated at follow-up. Our results suggest that the VSB-aided localisation abilities may be related to the thresholds between the ears, plasticity of auditory system and duration of use of VSB.

Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection.

Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti-DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host-cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease.

Audiological effectiveness of Bonebridge implantation for bilateral congenital malformation of the external and middle ear.

PURPOSE: To evaluate the audiological effectiveness of Bonebridge implantation in patients with bilateral congenital malformation of the external and middle ear. METHODS: Twenty-eight cases [17 boys and 11 girls; median age, 12 years (range 8-36 years)] had unilateral Bonebridge implantation. Audiological tests were performed preoperatively and postoperatively, and included the pure-tone audiometry test, speech discrimination score (SDS), and evaluation of the unaided and aided hearing thresholds in sound fields. For the group of patients aged > 12 years, Mandarin Speech Test Materials were used to determine the SDS. For the other cases, the Mandarin Lexical Neighborhood Test was used. The daily life efficacy was assessed using the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire postoperatively. The t and t' tests were used in the statistical analyses. RESULTS: The hearing threshold with the Bonebridge improved by 25-35 dB HL, compared to that of the unaided condition. The SDS of patients aged > 12 years improved by about 50%; the SDS also improved by 10-20% in the three patients aged < 12 years. According to the APHAB, the mean Bonebridge scores of ease of communication, background noise, and reverberation decreased by 60.3 ± 15.7, 50.2 ± 11.1, and 59.4 ± 7.8, respectively, compared to the preoperative scores, and the Bonebridge score of aversiveness was higher (69.8 ± 10.8) than the unaided score. CONCLUSIONS: The audiological effectiveness of the Bonebridge was significant and noticeable in bilateral congenital malformation of the external and middle ear. The Bonebridge can be an alternative and effective solution for those patients to improve hearing.

Profiling of translatomes of in vivo-grown pollen tubes reveals genes with roles in micropylar guidance during pollination in Arabidopsis.

Transcriptome profiling has been used to identify genes expressed in pollen tubes elongating in vitro; however, little is known of the transcriptome of in vivo-grown pollen tubes due to the difficulty of collecting pollen that is elongating within the solid maternal gynoecium. Using a pollen-specific promoter (ProLAT52) to generate epitope-tagged polysomal-RNA complexes that could be affinity purified, we obtained mRNAs undergoing translation (the translatome) of in vivo-grown pollen tubes from self-pollinated gynoecia of Arabidopsis thaliana. Translatomes of pollen grains as well as in vivo- and in vitro-cultured pollen tubes were assayed by microarray analyses, revealing over 500 transcripts specifically enriched in in vivo-elongating pollen tubes. Functional analyses of several in vivo mutants (iv) of these pollination-enhanced transcripts revealed partial pollination/fertilization and seed formation defects in siliques (iv2, iv4, and iv6). Cytological observation confirmed the involvement of these genes in specialized processes including micropylar guidance (IV6 and IV4), pollen tube burst (IV2), and repulsion of multiple pollen tubes in embryo sac (IV2). In summary, the selective immunopurification of transcripts engaged with polysomes in pollen tubes within self-fertilized florets has identified a cohort of pollination-enriched transcripts that facilitated the identification of genes important in in vivo pollen tube biology.

Escalation of genome defense capacity enables control of an expanding meiotic driver.

From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity1,2. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, which controls selfish elements in the metazoan germline, diverse target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases via enzymatic cleavage1,3. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via the innovation of new specificity factors4,5. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to the evolution of specificity factors, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the defense capacity of the piRNA pathway to control a recently expanded selfish gene in Drosophila melanogaster. Through an in vivo RNAi screen for repressors of Stellate-a recently evolved and expanded selfish meiotic driver6-8-we discovered a novel defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to drastically elevate Aub and AGO3 expression in the D. melanogaster lineage, thereby escalating the silencing capacity of the piRNA pathway to control expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life9-12, we envision that augmenting the defense capacity to quantitatively match selfish genes is likely a repeatedly employed defense strategy in evolution.

[Clinical features of congenitally enlarged bony portion of Eustachian tube].

Objective:To investigate the clinical features of patients with congenitally enlarged bony portions of the Eustachian tube（ET）. Methods:The medical history, physical examination, hearing test, temporal bone high resolution computed tomography（HRCT） of six patients（nine ears） with congenitally enlarged bony portion of the ET were retrospectively analyzed. Results:Four patients were men and two were women. The minimum, maximum, and average ages were 5, 21, and（14.7±6.4） years, respectively. Three malformations were bilateral and three were left-sided. Three ears had conductive hearing loss（average bone and air conduction thresholds were 13.7 dB and 71.3 dB）, three had mixed hearing loss（average bone and air conduction thresholds were 27.7 dB and 83.7 dB）, and one had extremely severe sensorineural hearing loss. The average maximum length and width of the enlarged bony ET on temporal bone HRCT were（22.61±2.94） mm and（6.50±2.33） mm, respectively. The enlargement was combined with an external auditory canal malformation in six ears, narrow tympanic cavity in six, tympanic antrum malformation in five, ossicular chain malformation in seven, cochlear malformation in six, helicotrema malformation in three, vestibule widening in two, semicircular canal malformation in three, vestibular window malformation in six, facial nerve abnormality in five, internal auditory meatus malformation in two, low middle cranial fossa in eight, and severe internal carotid artery malformation in one. Conclusion:Bony ET enlargement is a rare congenital middle ear malformation which could combined with other ear malformations. Patients can have no ET dysfunction but different patterns of hearing loss. The defect is usually found unintentionally during imaging, and the HRCT of temporal bone is significant.

Rice LGD1 containing RNA binding activity affects growth and development through alternative promoters.

Tiller initiation and panicle development are important agronomical traits for grain production in Oryza sativa L. (rice), but their regulatory mechanisms are not yet fully understood. In this study, T-DNA mutant and RNAi transgenic approaches were used to functionally characterize a unique rice gene, LAGGING GROWTH AND DEVELOPMENT 1 (LGD1). The lgd1 mutant showed slow growth, reduced tiller number and plant height, altered panicle architecture and reduced grain yield. The fewer unelongated internodes and cells in lgd1 led to respective reductions in tiller number and to semi-dwarfism. Several independent LGD1-RNAi lines exhibited defective phenotypes similar to those observed in lgd1. Interestingly, LGD1 encodes multiple transcripts with different transcription start sites (TSSs), which were validated by RNA ligase-mediated rapid amplification of 5' and 3' cDNA ends (RLM-RACE). Additionally, GUS assays and a luciferase promoter assay confirmed the promoter activities of LGD1.1 and LGD1.5. LGD1 encoding a von Willebrand factor type A (vWA) domain containing protein is a single gene in rice that is seemingly specific to grasses. GFP-tagged LGD1 isoforms were predominantly detected in the nucleus, and weakly in the cytoplasm. In vitro northwestern analysis showed the RNA-binding activity of the recombinant C-terminal LGD1 protein. Our results demonstrated that LGD1 pleiotropically regulated rice vegetative growth and development through both the distinct spatiotemporal expression patterns of its multiple transcripts and RNA binding activity. Hence, the study of LGD1 will strengthen our understanding of the molecular basis of the multiple transcripts, and their corresponding polypeptides with RNA binding activity, that regulate pleiotropic effects in rice.

Genetic control of a sex-specific piRNA program.

Sexually dimorphic traits in morphologies are widely studied,1,2,3,4 but those in essential molecular pathways remain largely unexplored. Previous work showed substantial sex differences in Drosophila gonadal piRNAs,5 which guide PIWI proteins to silence selfish genetic elements, thereby safeguarding fertility.6,7,8 However, the genetic control mechanisms of piRNA sexual dimorphism remain unknown. Here, we showed that most sex differences in the piRNA program originate from the germ line rather than the gonadal somatic cells. Building on this, we dissected the contribution of sex chromosomes and cellular sexual identity toward the sex-specific germline piRNA program. We found that the presence of the Y chromosome is sufficient to recapitulate some aspects of the male piRNA program in a female cellular environment. Meanwhile, sexual identity controls the sexually divergent piRNA production from X-linked and autosomal loci, revealing a crucial input from sex determination into piRNA biogenesis. Sexual identity regulates piRNA biogenesis through Sxl, and this effect is mediated, in part, through chromatin proteins Phf7 and Kipferl. Together, our work delineated the genetic control of a sex-specific piRNA program, where sex chromosomes and sexual identity collectively sculpt an essential molecular trait.

Clinical manifestations and treatment strategies for congenital aural atresia with temporomandibular joint retroposition: a retrospective study of 30 patients.

BACKGROUND: Patients with congenital aural atresia (CAA) can present with concomitant temporomandibular joint (TMJ) retroposition, implying that even with a high Jahrsdoerfer score, canaloplasty and tympanoplasty cannot be performed. Therefore, this study aimed to summarize the clinical manifestations and share our diagnostic and treatment experience of this rare entity, which has not been described previously. METHODS: Thirty patients (30 ears) with CAA and TMJ retroposition without maxillofacial dysplasia were included. Diagnosis was based on patient history, physical examination, pure-tone average test results, and temporal bone high-resolution computed tomography (HRCT) findings. Their Jahrsdoerfer scores and interventions were also recorded. RESULTS: Twenty-four and six patients among the 30 patients (males, n = 15) had CAA and TMJ retroposition on the right and left sides, respectively. Seventeen ears had a normal auricle; most had an enlarged cavum conchae and a large tragus. Twelve ears had an accessory auricle, and two had a preauricular fistula. All external auditory canals had complete atresia, including four with a shallow concavity and four with a small orifice in the cavum conchae. Temporal bone HRCT revealed poor or undeveloped tympanic temporal bone in the diseased ears, atresia in the external auditory canals, and partial/complete occupation of the mandibular condyle with or without soft tissue. The average Jahrsdoerfer score was 8.17. Thirteen patients opted for different surgeries, three wore a bone-conduction hearing aid, and fourteen chose no intervention. CONCLUSIONS: CAA with TMJ retroposition was often unilateral, typically on the right side. Most patients had normal auricles, with an enlarged cavum conchae and a large tragus ("mirror ear"). Even with a high Jahrsdoerfer score, traditional hearing reconstruction surgery could not be performed. Patients can undergo Vibrant Soundbridge or Bonebridge implantation or wear bone-conduction hearing aids to improve hearing levels, or refuse intervention because of mild hearing loss. The TMJ location can be used as a Jahrsdoerfer Grading System supplement for preoperative evaluation.