Oxidative stress protein Oxr1 promotes V-ATPase holoenzyme disassembly in catalytic activity-independent manner.

The vacuolar ATPase (V-ATPase) is a rotary motor proton pump that is regulated by an assembly equilibrium between active holoenzyme and autoinhibited V1 -ATPase and Vo proton channel subcomplexes. Here, we report cryo-EM structures of yeast V-ATPase assembled in vitro from lipid nanodisc reconstituted Vo and mutant V1 . Our analysis identified holoenzymes in three active rotary states, indicating that binding of V1 to Vo provides sufficient free energy to overcome Vo autoinhibition. Moreover, the structures suggest that the unequal spacing of Vo 's proton-carrying glutamic acid residues serves to alleviate the symmetry mismatch between V1 and Vo motors, a notion that is supported by mutagenesis experiments. We also uncover a structure of free V1 bound to Oxr1, a conserved but poorly characterized factor involved in the oxidative stress response. Biochemical experiments show that Oxr1 inhibits V1 -ATPase and causes disassembly of the holoenzyme, suggesting that Oxr1 plays a direct role in V-ATPase regulation.

Structural insights into ClpP protease side exit pore-opening by a pH drop coupled with substrate hydrolysis.

The ClpP serine peptidase is a tetradecameric degradation molecular machine involved in many physiological processes. It becomes a competent ATP-dependent protease when coupled with Clp-ATPases. Small chemical compounds, acyldepsipeptides (ADEPs), are known to cause the dysregulation and activation of ClpP without ATPases and have potential as novel antibiotics. Previously, structural studies of ClpP from various species revealed its structural details, conformational changes, and activation mechanism. Although product release through side exit pores has been proposed, the detailed driving force for product release remains elusive. Herein, we report crystal structures of ClpP from Bacillus subtilis (BsClpP) in unforeseen ADEP-bound states. Cryo-electron microscopy structures of BsClpP revealed various conformational states under different pH conditions. To understand the conformational change required for product release, we investigated the relationship between substrate hydrolysis and the pH-lowering process. The production of hydrolyzed peptides from acidic and basic substrates by proteinase K and BsClpP lowered the pH values. Our data, together with those of previous findings, provide insight into the molecular mechanism of product release by the ClpP self-compartmentalizing protease.

Reversible modification of mitochondrial ADP/ATP translocases by paired Legionella effector proteins.

Adenosine diphosphate (ADP) ribosylation is a reversible posttranslational modification involved in the regulation of numerous cellular processes. Prototype ADP ribosyltransferases (ARTs) from many pathogenic bacteria are known to function as toxins, while other bacterial ARTs have just recently emerged. Recent studies have shown that bacteria also possess enzymes that function as poly-ADP ribose (ADPr) glycohydrolases (PARGs), which reverse poly-ADP ribosylation. However, how bacteria manipulate host target proteins by coordinated reactions of ARTs and ADPr hydrolases (ARHs) remains elusive. The intracellular bacterial pathogen Legionella pneumophila, the causative agent of Legionnaires' disease, transports a large array of effector proteins via the Dot/Icm type IV secretion system to host cells. The effector proteins, which mostly function as enzymes, modulate host cellular processes for the bacteria's benefit. In this study, we identified a pair of L. pneumophila effector proteins, Lpg0080 and Lpg0081, which function as an ART and an ARH, respectively. The two proteins were shown to coordinately modulate mitochondrial ADP/adenosine triphosphate (ATP) translocases (ANTs) by their enzymatic activities to conjugate ADPr to, and remove it from, a key arginine residue. The crystal structures of Lpg0081 and the Lpg0081:ADPr complex indicated that Lpg0081 is a macroD-type ARH with a noncanonical macrodomain, whose folding topology is strikingly distinct from that of the canonical macrodomain that is ubiquitously found in eukaryotic PARGs and ARHs. Our results illustrate that L. pneumophila has acquired an effector pair that coordinately manipulate mitochondrial activity via reversible chemical modification of ANTs.

Histone demethylase AMX-1 is necessary for proper sensitivity to interstrand crosslink DNA damage.

Histone methylation is dynamically regulated to shape the epigenome and adjust central nuclear processes including transcription, cell cycle control and DNA repair. Lysine-specific histone demethylase 2 (LSD2) has been implicated in multiple types of human cancers. However, its functions remain poorly understood. This study investigated the histone demethylase LSD2 homolog AMX-1 in C. elegans and uncovered a potential link between H3K4me2 modulation and DNA interstrand crosslink (ICL) repair. AMX-1 is a histone demethylase and mainly localizes to embryonic cells, the mitotic gut and sheath cells. Lack of AMX-1 expression resulted in embryonic lethality, a decreased brood size and disorganized premeiotic tip germline nuclei. Expression of AMX-1 and of the histone H3K4 demethylase SPR-5 is reciprocally up-regulated upon lack of each other and the mutants show increased H3K4me2 levels in the germline, indicating that AMX-1 and SPR-5 regulate H3K4me2 demethylation. Loss of AMX-1 function activates the CHK-1 kinase acting downstream of ATR and leads to the accumulation of RAD-51 foci and increased DNA damage-dependent apoptosis in the germline. AMX-1 is required for the proper expression of mismatch repair component MutL/MLH-1 and sensitivity against ICLs. Interestingly, formation of ICLs lead to ubiquitination-dependent subcellular relocalization of AMX-1. Taken together, our data suggest that AMX-1 functions in ICL repair in the germline.

N-terminal acetylation promotes synaptonemal complex assembly in C. elegans.

N-terminal acetylation of the first two amino acids on proteins is a prevalent cotranslational modification. Despite its abundance, the biological processes associated with this modification are not well understood. Here, we mapped the pattern of protein N-terminal acetylation in Caenorhabditis elegans, uncovering a conserved set of rules for this protein modification and identifying substrates for the N-terminal acetyltransferase B (NatB) complex. We observed an enrichment for global protein N-terminal acetylation and also specifically for NatB substrates in the nucleus, supporting the importance of this modification for regulating biological functions within this cellular compartment. Peptide profiling analysis provides evidence of cross-talk between N-terminal acetylation and internal modifications in a NAT substrate-specific manner. In vivo studies indicate that N-terminal acetylation is critical for meiosis, as it regulates the assembly of the synaptonemal complex (SC), a proteinaceous structure ubiquitously present during meiosis from yeast to humans. Specifically, N-terminal acetylation of NatB substrate SYP-1, an SC structural component, is critical for SC assembly. These findings provide novel insights into the biological functions of N-terminal acetylation and its essential role during meiosis.

Targeting BRPF3 moderately reverses olaparib resistance in high grade serous ovarian carcinoma.

PARP inhibitors (PARPi) kill cancer cells by stalling DNA replication and preventing DNA repair, resulting in a critical accumulation of DNA damage. Resistance to PARPi is a growing clinical problem in the treatment of high grade serous ovarian carcinoma (HGSOC). Acetylation of histone H3 lysine 14 (H3K14ac) and associated histone acetyltransferases (HATs) and epigenetic readers have known functions in DNA repair and replication. Our objectives are to examine their expression and activities in the context of PARPi-resistant HGSOC, and to determine if targeting H3K14ac or associated proteins has therapeutic potential. Using mass spectrometry profiling of histone modifications, we observed increased H3K14ac enrichment in PARPi-resistant HGSOC cells relative to isogenic PARPi-sensitive lines. By reverse-transcriptase quantitative PCR and RNA-seq, we also observed altered expression of numerous HATs in PARPi-resistant HGSOC cells and a PARPi-resistant PDX model. Knockdown of HATs only modestly altered PARPi response, although knockdown and inhibition of PCAF significantly increased resistance. Pharmacologic inhibition of HBO1 depleted H3K14ac but did not affect PARPi response. However, knockdown and inhibition of BRPF3, a bromodomain and PHD-finger containing protein that is known to interact in a complex with HBO1, did reduce PARPi resistance. This study demonstrates that depletion of H3K14ac does not affect PARPi response in HGSOC. Our data suggest that the bromodomain function of HAT proteins, such as PCAF, or accessory proteins, such as BRPF3, may play a more direct role compared to direct HATs function in PARPi response.

Food security status and breast cancer screening among women in the United States: Evidence from the Health and Retirement Study and Health Care and Nutrition Study.

PURPOSE: To assess the impact of food insecurity on biennial breast cancer screenings (i.e., mammography or breast X-ray) among older women in the United States (US). METHODS: Data from the 2014 and 2016 waves of the Health and Retirement Study and the 2013 Health Care and Nutrition Study were used. The analyses were limited to a nationally representative sample of 2,861 women between 50 and 74 years of age, residing in the US. We employed a propensity score weighting method to balance observed confounders between food-secure and food-insecure women and fit a binary logistic regression to investigate population-level estimates for the association between food security and breast cancer screening. RESULTS: Food insecurity was significantly associated with failure to obtain a mammogram or breast X-ray within the past two years. Food-insecure women had 54% lower odds of reporting breast cancer screening in the past 2 years (adjusted OR = 0.46; 95% CI 0.30-0.70, p-value < 0.001) as compared to food-secure women. Additional factors associated with a higher likelihood of receiving breast cancer screenings included greater educational attainment, higher household income, regular access to health care/advice, not smoking, and not being physically disabled or experiencing depressive symptoms. CONCLUSION: Results demonstrate a socioeconomic gradient existing in regard to the utilization of regular breast cancer screenings among women. Those who tend to have lower education, lower income, and lack of reliable healthcare access are more likely to be food insecure. Thus, more likely to face the financial, logistical, or environmental barriers in obtaining screening services that accompany food insecurity.

Distinguishing nontuberculous mycobacterial lung disease and Mycobacterium tuberculosis lung disease on X-ray images using deep transfer learning.

BACKGROUND: Nontuberculous mycobacterial lung disease (NTM-LD) and Mycobacterium tuberculosis lung disease (MTB-LD) have similar clinical characteristics. Therefore, NTM-LD is sometimes incorrectly diagnosed with MTB-LD and treated incorrectly. To solve these difficulties, we aimed to distinguish the two diseases in chest X-ray images using deep learning technology, which has been used in various fields recently. METHODS: We retrospectively collected chest X-ray images from 3314 patients infected with Mycobacterium tuberculosis (MTB) or nontuberculosis mycobacterium (NTM). After selecting the data according to the diagnostic criteria, various experiments were conducted to create the optimal deep learning model. A performance comparison was performed with the radiologist. Additionally, the model performance was verified using newly collected MTB-LD and NTM-LD patient data. RESULTS: Among the implemented deep learning models, the ensemble model combining EfficientNet B4 and ResNet 50 performed the best in the test data. Also, the ensemble model outperformed the radiologist on all evaluation metrics. In addition, the accuracy of the ensemble model was 0.85 for MTB-LD and 0.78 for NTM-LD on an additional validation dataset consisting of newly collected patients. CONCLUSIONS: In previous studies, it was known that it was difficult to distinguish between MTB-LD and NTM-LD in chest X-ray images, but we have successfully distinguished the two diseases using deep learning methods. This study has the potential to aid clinical decisions if the two diseases need to be differentiated.

Effects of Transcription Elongation Rate and Xrn2 Exonuclease Activity on RNA Polymerase II Termination Suggest Widespread Kinetic Competition.

The torpedo model of transcription termination asserts that the exonuclease Xrn2 attacks the 5'PO4-end exposed by nascent RNA cleavage and chases down the RNA polymerase. We tested this mechanism using a dominant-negative human Xrn2 mutant and found that it delayed termination genome-wide. Xrn2 nuclease inactivation caused strong termination defects downstream of most poly(A) sites and modest delays at some histone and U snRNA genes, suggesting that the torpedo mechanism is not limited to poly(A) site-dependent termination. A central untested feature of the torpedo model is that there is kinetic competition between the exonuclease and the pol II elongation complex. Using pol II rate mutants, we found that slow transcription robustly shifts termination upstream, and fast elongation extends the zone of termination further downstream. These results suggest that kinetic competition between elongating pol II and the Xrn2 exonuclease is integral to termination of transcription on most human genes.

Impact of the Affordable Care Act on participation in the Supplemental Nutrition Assistance Program among low-income older Medicare beneficiaries.

BACKGROUND: The Affordable Care Act (ACA) provisions, especially Medicaid expansion, are believed to have "spillover effects," such as boosting participation in the Supplemental Nutrition Assistance Program (SNAP) among eligible individuals in the United States (US). However, little empirical evidence exists about the impact of the ACA, with its focus on the dual eligible population, on SNAP participation. The current study investigates whether the ACA, under an explicit policy aim of enhancing the interface between Medicare and Medicaid, has improved participation in the SNAP among low-income older Medicare beneficiaries. METHODS: We extracted 2009 through 2018 data from the US Medical Expenditure Panel Survey (MEPS) for low-income (≤ %138 Federal Poverty Level [FPL]) older Medicare beneficiaries (n = 50,466; aged ≥ 65), and low-income (≤ %138 FPL) younger adults (aged 20 to < 65 years, n = 190,443). MEPS respondents of > %138 FPL incomes, younger Medicare and Medicaid beneficiaries, and older adults without Medicare were excluded from this study. Using a quasi-experimental comparative interrupted time-series design, we examined (1) whether ACA's support for the Medicare-Medicaid dual-eligible program, through facilitating the online Medicaid application process, was associated with an increase in SNAP uptake among low-income older Medicare beneficiaries, and (2) in the instance of an association, to assess the magnitude of SNAP uptake that can be explicitly attributed to the policy's implementation. The outcome, SNAP participation, was measured annually from 2009 through 2018. The year 2014 was set as the intervention point when the Medicare-Medicaid Coordination Office started facilitating Medicaid applications online for eligible Medicare beneficiaries. RESULTS: Overall, the change in the probability of SNAP enrollment from the pre- to post-intervention period was 17.4 percentage points higher among low-income older Medicare enrollees, compared to similarly low-income, SNAP-eligible, younger adults (ß = 0.174, P < .001). This boost in SNAP uptake was significant and more apparent among older White (ß = 0.137, P = .049), Asians (ß = 0.408, P = .047), and all non-Hispanic adults (ß = 0.030, P < .001). CONCLUSIONS: The ACA had a positive, measurable effect on SNAP participation among older Medicare beneficiaries. Policymakers should consider additional approaches that link enrollment to multiple programs to increase SNAP participation. Further, there may be a need for additional, targeted efforts to address structural barriers to uptake among African Americans and Hispanics.

SELID: Selective Event Labeling for Intrusion Detection Datasets.

A large volume of security events, generally collected by distributed monitoring sensors, overwhelms human analysts at security operations centers and raises an alert fatigue problem. Machine learning is expected to mitigate this problem by automatically distinguishing between true alerts, or attacks, and falsely reported ones. Machine learning models should first be trained on datasets having correct labels, but the labeling process itself requires considerable human resources. In this paper, we present a new selective sampling scheme for efficient data labeling via unsupervised clustering. The new scheme transforms the byte sequence of an event into a fixed-size vector through content-defined chunking and feature hashing. Then, a clustering algorithm is applied to the vectors, and only a few samples from each cluster are selected for manual labeling. The experimental results demonstrate that the new scheme can select only 2% of the data for labeling without degrading the F1-score of the machine learning model. Two datasets, a private dataset from a real security operations center and a public dataset from the Internet for experimental reproducibility, are used.

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat.

Glucose-rich diets shorten the life spans of various organisms. However, the metabolic processes involved in this phenomenon remain unknown. Here, we show that sterol regulatory element-binding protein (SREBP) and mediator-15 (MDT-15) prevent the life-shortening effects of a glucose-rich diet by regulating fat-converting processes in Caenorhabditis elegans. Up-regulation of the SREBP/MDT-15 transcription factor complex was necessary and sufficient for alleviating the life-shortening effect of a glucose-rich diet. Glucose feeding induced key enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), which are regulated by SREBP and MDT-15. Furthermore, SREBP/MDT-15 reduced the levels of SFAs and moderated glucose toxicity on life span. Our study may help to develop strategies against elevated blood glucose and free fatty acids, which cause glucolipotoxicity in diabetic patients.

Experimental Insights into the Interplay between Histone Modifiers and p53 in Regulating Gene Expression.

Chromatin structure plays a fundamental role in regulating gene expression, with histone modifiers shaping the structure of chromatin by adding or removing chemical changes to histone proteins. The p53 transcription factor controls gene expression, binds target genes, and regulates their activity. While p53 has been extensively studied in cancer research, specifically in relation to fundamental cellular processes, including gene transcription, apoptosis, and cell cycle progression, its association with histone modifiers has received limited attention. This review explores the interplay between histone modifiers and p53 in regulating gene expression. We discuss how histone modifications can influence how p53 binds to target genes and how this interplay can be disrupted in cancer cells. This review provides insights into the complex mechanisms underlying gene regulation and their implications for potential cancer therapy.

Focus-engineered sub-diffraction imaging in infrared-sensitive third-order sum frequency generation microscope.

We experimentally demonstrate sub-diffraction imaging in infrared-sensitive third-order sum frequency generation (TSFG) microscope using focal-field engineering technique. The TSFG interaction studied here makes use of two mid infrared photons and a single 1040 nm pump photon to generate up-converted visible photons. Focal field engineering scheme is implemented using a Toraldo-style single annular phase mask imprinted on the 1040 nm beam using a spatial light modulator. The effect of focal field engineered excitation beam on the non-resonant-TSFG process is studied by imaging isolated silicon sub-micron disks and periodic grating structures. Maximum reduction in the measured TSFG central-lobe size by ∼43% with energy in the central lobe of 35% is observed in the presence of phase mask. Maximum contrast improvement of 30% is observed for periodic grating structures. Furthermore, to validate the infrared sensitivity of the focus engineered TSFG microscope, we demonstrate imaging of amorphous Germanium-based guided-mode resonance structures, and polystyrene latex beads probed near the O-H vibrational region. We also demonstrate the utility of the focus engineered TSFG microscope for high resolution imaging of two-dimensional layered material. Focus-engineered TSFG process is a promising imaging modality that combines infrared selectivity with improved resolution and contrast, making it suitable for nanostructure and surface layer imaging.

Structural basis for recognition of the tumor suppressor protein PTPN14 by the oncoprotein E7 of human papillomavirus.

Human papillomaviruses (HPVs) are causative agents of various diseases associated with cellular hyperproliferation, including cervical cancer, one of the most prevalent tumors in women. E7 is one of the two HPV-encoded oncoproteins and directs recruitment and subsequent degradation of tumor-suppressive proteins such as retinoblastoma protein (pRb) via its LxCxE motif. E7 also triggers tumorigenesis in a pRb-independent pathway through its C-terminal domain, which has yet been largely undetermined, with a lack of structural information in a complex form with a host protein. Herein, we present the crystal structure of the E7 C-terminal domain of HPV18 belonging to the high-risk HPV genotypes bound to the catalytic domain of human nonreceptor-type protein tyrosine phosphatase 14 (PTPN14). They interact directly and potently with each other, with a dissociation constant of 18.2 nM. Ensuing structural analysis revealed the molecular basis of the PTPN14-binding specificity of E7 over other protein tyrosine phosphatases and also led to the identification of PTPN21 as a direct interacting partner of E7. Disruption of HPV18 E7 binding to PTPN14 by structure-based mutagenesis impaired E7's ability to promote keratinocyte proliferation and migration. Likewise, E7 binding-defective PTPN14 was resistant for degradation via proteasome, and it was much more effective than wild-type PTPN14 in attenuating the activity of downstream effectors of Hippo signaling and negatively regulating cell proliferation, migration, and invasion when examined in HPV18-positive HeLa cells. These results therefore demonstrated the significance and therapeutic potential of the intermolecular interaction between HPV E7 and host PTPN14 in HPV-mediated cell transformation and tumorigenesis.

Pre-mRNA splicing is facilitated by an optimal RNA polymerase II elongation rate.

Alternative splicing modulates expression of most human genes. The kinetic model of cotranscriptional splicing suggests that slow elongation expands and that fast elongation compresses the "window of opportunity" for recognition of upstream splice sites, thereby increasing or decreasing inclusion of alternative exons. We tested the model using RNA polymerase II mutants that change average elongation rates genome-wide. Slow and fast elongation affected constitutive and alternative splicing, frequently altering exon inclusion and intron retention in ways not predicted by the model. Cassette exons included by slow and excluded by fast elongation (type I) have weaker splice sites, shorter flanking introns, and distinct sequence motifs relative to "slow-excluded" and "fast-included" exons (type II). Many rate-sensitive exons are misspliced in tumors. Unexpectedly, slow and fast elongation often both increased or both decreased inclusion of a particular exon or retained intron. These results suggest that an optimal rate of transcriptional elongation is required for normal cotranscriptional pre-mRNA splicing.

A Decade of CRISPR-Cas Gnome Editing in C. elegans.

CRISPR-Cas allows us to introduce desired genome editing, including mutations, epitopes, and deletions, with unprecedented efficiency. The development of CRISPR-Cas has progressed to such an extent that it is now applicable in various fields, with the help of model organisms. C. elegans is one of the pioneering animals in which numerous CRISPR-Cas strategies have been rapidly established over the past decade. Ironically, the emergence of numerous methods makes the choice of the correct method difficult. Choosing an appropriate selection or screening approach is the first step in planning a genome modification. This report summarizes the key features and applications of CRISPR-Cas methods using C. elegans, illustrating key strategies. Our overview of significant advances in CRISPR-Cas will help readers understand the current advances in genome editing and navigate various methods of CRISPR-Cas genome editing.

Effectiveness of Using Personal Health Records to Improve Recommended Breast Cancer Screening and Reduce Racial and Geographic Disparities Among Women.

This paper examines the effectiveness of using personal health records (PHRs), which contains detailed health information to improve the use of recommended screening mammography among women at potential risk for breast cancer. It also explores the potential of PHR in reducing disparities in recommended mammography use experienced by minority and underserved women. The primary data used for this study were obtained from the 2015 Health Information National Trends Survey, and they were supplemented by the 2016 Area Health Resource Files. The study sample included women aged 40-75 years with no prior diagnosis of cancer. Because the use of PHRs as a key predictor of breast cancer screening may be endogenously determined, we used the instrumental variable (IV) approach to correct for estimation bias. We found a significant and positive association between the use of PHRs and recommended mammography use among women, with the likelihood of mammography screening increasing with more frequent use of PHRs. Furthermore, the effects of PHR use on mammography screening were found to be greater among Hispanic and Black women and those living in non-metropolitan areas compared with White women and those living in metropolitan areas, respectively. The use of PHRs for health information seeking can empower women at potential risk for breast cancer to participate in recommended screening mammography, particularly among those underserved and racial/ethnic minorities. Policymakers should consider developing policies and programs that can promote PHR use by women, especially medically underserved and minority women.

A sensory-motor neuron type mediates proprioceptive coordination of steering in C. elegans via two TRPC channels.

Animal locomotion is mediated by a sensory system referred to as proprioception. Defects in the proprioceptive coordination of locomotion result in uncontrolled and inefficient movements. However, the molecular mechanisms underlying proprioception are not fully understood. Here, we identify two transient receptor potential cation (TRPC) channels, trp-1 and trp-2, as necessary and sufficient for proprioceptive responses in C. elegans head steering locomotion. Both channels are expressed in the SMDD neurons, which are required and sufficient for head bending, and mediate coordinated head steering by sensing mechanical stretches due to the contraction of head muscle and orchestrating dorsal head muscle contractions. Moreover, the SMDD neurons play dual roles to sense muscle stretch as well as to control muscle contractions. These results demonstrate that distinct locomotion patterns require dynamic and homeostatic modulation of feedback signals between neurons and muscles.

Sequential Changes in Pharyngeal Airway Dimensions After Mandibular Setback Surgery and Its Correlation With Postsurgical Stability in Patients With Mandibular Prognathism.

PURPOSE: This study aimed to evaluate the sequential changes in the pharyngeal airway dimensions after mandibular setback surgery and to verify its correlation with postsurgical mandibular stability in patients with mandibular prognathism. PATIENTS AND METHODS: This retrospective study included 28 patients with mandibular prognathism who underwent surgical orthodontic treatment and isolated mandibular setback surgery. Patients who had cone-beam computed tomography before surgery, immediately after surgery, at short-term follow-up (11.8 ± 5.1 months), and long-term follow-up (43.0 ± 13.1 months) were included. Airway dimensions, including distance, minimum cross-sectional area, and airway volume, were measured to evaluate the changes following mandibular setback surgery. With the measurements of postsurgical mandibular relapse, the relationship between sequential changes in airway dimensions and the mandible was verified using correlation analysis. RESULTS: Airway dimensions decreased immediately after mandibular setback surgery. The decreased airway dimensions recovered during short-term follow-up and maintained to the long-term follow-up. The mandible was set back 7.7 ± 5.1 mm at pogonion immediately after surgery. Postsurgical skeletal relapse was 1.1 mm at pogonion during short-term follow-up. During long-term follow-up, the mandible moved 0.4 mm anteriorly, which was about 50% of the changes during short-term follow-up. Statistically significant correlations were found between the sequential changes in airway dimensions and the postsurgical skeletal relapse. CONCLUSION: The decreased airway dimensions following mandibular setback surgery recovered during short-term follow-up and maintained to the long-term follow-up. Dimensional recovery of the pharyngeal airway was correlated with postsurgical skeletal relapse during the 1-year follow-up period.