Understanding recessive disease risk in multi-ethnic populations with different degrees of consanguinity.

Population medical genetics aims at translating clinically relevant findings from recent studies of large cohorts into healthcare for individuals. Genetic counseling concerning reproductive risks and options is still mainly based on family history, and consanguinity is viewed to increase the risk for recessive diseases regardless of the demographics. However, in an increasingly multi-ethnic society with diverse approaches to partner selection, healthcare professionals should also sharpen their intuition for the influence of different mating schemes in non-equilibrium dynamics. We, therefore, revisited the so-called out-of-Africa model and studied in forward simulations with discrete and not overlapping generations the effect of inbreeding on the average number of recessive lethals in the genome. We were able to reproduce in both frameworks the drop in the incidence of recessive disorders, which is a transient phenomenon during and after the growth phase of a population, and therefore showed their equivalence. With the simulation frameworks, we also provide the means to study and visualize the effect of different kin sizes and mating schemes on these parameters for educational purposes.

Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group.

Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis. Ruxolitinib (RUX) is approved for second-line therapy in high-risk PV pts with hydroxyurea intolerance or resistance. The RuxoBEAT trial (NCT02577926, registered on October 1, 2015, at clinicaltrials.gov) is a multicenter, open-label, two-arm phase-IIb trial with a target population of 380 pts with PV or ET, randomized to receive RUX or best available therapy. This pre-specified futility analysis assesses the early clinical benefit and tolerability of RUX in previously untreated PV pts (6-week cytoreduction was allowed). Twenty-eight patients were randomly assigned to receive RUX. Compared to baseline, after 6 months of treatment, there was a significant reduction of median hematocrit (46 to 41%), the median number of phlebotomies per year (4.0 to 0), and median patient-reported pruritus scores (2 to 1), and a trend for reduced night sweat scores (1.5 to 0). JAK2V617F allele burden, as part of the scientific research program, also significantly decreased. One hundred nine adverse events (AEs) occurred in 24/28 patients (all grade 1 to 3), and no pt permanently discontinued treatment because of AEs. Thus, treatment with ruxolitinib in untreated PV pts is feasible, well-tolerated, and efficient regarding the above-mentioned endpoints.

Age-dependent performance of BRAF mutation testing in Lynch syndrome diagnostics.

BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age-specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS-associated CRCs and unselected MSI CRCs in different age groups as available from published studies, databases and population-based patient cohorts. Sensitivity/specificity analysis of BRAF testing for exclusion of LS and cost calculations were performed. Among 969 MSI CRCs from LS carriers in the literature and German HNPCC Consortium, 15 (1.6%) harbored BRAF mutations. Six of seven LS patients with BRAF-mutant CRC and reported age were <50 years. Among 339 of 756 (44.8%) of BRAF mutations detected in unselected MSI CRC, only 2 of 339 (0.6%) BRAF mutations were detected in patients <50 years. The inclusion of BRAF testing led to high risk of missing LS patients and increased costs at age <50 years. BRAF testing in patients <50 years carries a high risk of missing a hereditary cancer predisposition and is cost-inefficient. We suggest direct referral of MSI CRC patients <50 years to genetic counseling without BRAF testing.

Chloroplast-localized BICAT proteins shape stromal calcium signals and are required for efficient photosynthesis.

The photosynthetic machinery of plants must be regulated to maximize the efficiency of light reactions and CO2 fixation. Changes in free Ca2+ in the stroma of chloroplasts have been observed at the transition between light and darkness, and also in response to stress stimuli. Such Ca2+ dynamics have been proposed to regulate photosynthetic capacity. However, the molecular mechanisms of Ca2+ fluxes in the chloroplasts have been unknown. By employing a Ca2+ reporter-based approach, we identified two chloroplast-localized Ca2+ transporters in Arabidopsis thaliana, BICAT1 and BICAT2, that determine the amplitude of the darkness-induced Ca2+ signal in the chloroplast stroma. BICAT2 mediated Ca2+ uptake across the chloroplast envelope, and its knockout mutation strongly dampened the dark-induced [Ca2+ ]stroma signal. Conversely, this Ca2+ transient was increased in knockout mutants of BICAT1, which transports Ca2+ into the thylakoid lumen. Knockout mutation of BICAT2 caused severe defects in chloroplast morphology, pigmentation and photosynthetic light reactions, rendering bicat2 mutants barely viable under autotrophic growth conditions, while bicat1 mutants were less affected. These results show that BICAT transporters play a role in chloroplast Ca2+ homeostasis. They are also involved in the regulation of photosynthesis and plant productivity. Further work will be required to reveal whether the effect on photosynthesis is a direct result of their role as Ca2+ transporters.

External validation of molecular subtype classifications of colorectal cancer based on microsatellite instability, CIMP, BRAF and KRAS.

BACKGROUND: Competing molecular classification systems have been proposed to complement the TNM staging system for a better prediction of survival in colorectal cancer (CRC). However, validation studies are so far lacking. The aim of this study was to validate and extend previously published molecular classifications of CRC in a large independent cohort of CRC patients. METHODS: CRC patients were recruited into a population-based cohort study (DACHS). Molecular subtypes were categorized based on three previously published classifications. Cox-proportional hazard models, based on the same set of patients and using the same confounders as reported by the original studies, were used to determine overall, cancer-specific, or relapse-free survival for each subtype. Hazard ratios and confidence intervals, as well as Kaplan-Meier plots were compared to those reported by the original studies. RESULTS: We observed similar patterns of worse survival for the microsatellite stable (MSS)/BRAF-mutated and MSS/KRAS-mutated subtypes in our validation analyses, which were included in two of the validated classifications. Of the two MSI subtypes, one defined by additional presence of CIMP-high and BRAF-mutation and the other by tumors negative for CIMP, BRAF and KRAS-mutations, we could not confirm associations with better prognosis as suggested by one of the classifications. For two of the published classifications, we were able to provide results for additional subgroups not included in the original studies (men, other disease stages, other locations). CONCLUSIONS: External validation of three previously proposed classifications confirmed findings of worse survival for CRC patients with MSS subtypes and BRAF or KRAS mutations. Regarding MSI subtypes, other patient characteristics such as stage of the tumor, may influence the potential survival benefit. Further integration of methylation, genetic, and immunological information is needed to develop and validate a comprehensive classification that will have relevance for use in clinical practice.

High-Stakes Collaborative Testing: Why Not?

Phenomenon: Studies of high-stakes collaborative testing remain sparse, especially in medical education. We explored high-stakes collaborative testing in medical education, looking specifically at the experiences of students in established and newly formed teams. APPROACH: Third-year psychiatry students at 5 medical schools across 6 sites participated, with 4 participating as established team sites and 2 as comparison team sites. For the collaborative test, we used the National Board of Medical Examiners Psychiatry subject test, administering it via a 2-stage process. Students at all sites were randomly selected to participate in a focus group, with 8-10 students per site (N = 49). We also examined quantitative data for additional triangulation. FINDINGS: Students described a range of heightened emotions around the collaborative test yet perceived it as valuable regardless if they were in established or newly formed teams. Students described learning about the subject matter, themselves, others, and interpersonal dynamics during collaborative testing. Triangulation of these results via quantitative data supported these themes. Insights: Despite student concerns, high-stakes collaborative tests may be both valuable and feasible. The data suggest that high-stakes tests (tests of learning or summative evaluation) could also become tests for learning or formative evaluation. The paucity of research into this methodology in medical education suggests more research is needed.

Video Modeling of SBIRT for Alcohol Use Disorders Increases Student Empathy in Standardized Patient Encounters.

OBJECTIVES: The purpose of this study was to assess the usefulness of adding video models of brief alcohol assessment and counseling to a standardized patient (SP) curriculum that covers and tests acquisition of this skill. METHODS: The authors conducted a single-center, retrospective cohort study of third- and fourth-year medical students between 2013 and 2015. All students completed a standardized patient (SP) encounter illustrating the diagnosis of alcohol use disorder, followed by an SP exam on the same topic. Beginning in August 2014, the authors supplemented the existing formative SP exercise on problem drinking with one of two 5-min videos demonstrating screening, brief intervention, and referral for treatment (SBIRT). P values and Z tests were performed to evaluate differences between students who did and did not see the video in knowledge and skills related to alcohol use disorders. RESULTS: One hundred ninety-four students were included in this analysis. Compared to controls, subjects did not differ in their ability to uncover and accurately characterize an alcohol problem during a standardized encounter (mean exam score 41.29 vs 40.93, subject vs control, p = 0.539). However, the SPs' rating of students' expressions of empathy were significantly higher for the group who saw the video (81.63 vs 69.79%, p < 0.05). CONCLUSIONS: The findings did not confirm the original hypothesis that the videos would improve students' recognition and knowledge of alcohol-related conditions. However, feedback from the SPs produced the serendipitous finding that the communication skills demonstrated in the videos had a sustained effect in enhancing students' professional behavior.

A New Radio Frequency Plasma Oxygen Primary Ion Source on Nano Secondary Ion Mass Spectrometry for Improved Lateral Resolution and Detection of Electropositive Elements at Single Cell Level.

An important application field of secondary ion mass spectrometry at the nanometer scale (NanoSIMS) is the detection of chemical elements and, in particular, metals at the subcellular level in biological samples. The detection of many trace metals requires an oxygen primary ion source to allow the generation of positive secondary ions with high yield in the NanoSIMS. The duoplasmatron oxygen source is commonly used in this ion microprobe but cannot achieve the same quality of images as the cesium primary ion source used to produce negative secondary ions (C(-), CN(-), S(-), P(-)) due to a larger primary ion beam size. In this paper, a new type of an oxygen ion source using a rf plasma is fitted and characterized on a NanoSIMS50L. The performances of this primary ion source in terms of current density and achievable lateral resolution have been characterized and compared to the conventional duoplasmatron and cesium sources. The new rf plasma oxygen source offered a net improvement in terms of primary beam current density compared to the commonly used duoplasmatron source, which resulted in higher ultimate lateral resolutions down to 37 nm and which provided a 5-45 times higher apparent sensitivity for electropositive elements. Other advantages include a better long-term stability and reduced maintenance. This new rf plasma oxygen primary ion source has been applied to the localization of essential macroelements and trace metals at basal levels in two biological models, cells of Chlamydomonas reinhardtii and Arabidopsis thaliana.

The ADMSEP Milestones Project.

OBJECTIVE: Credentialing bodies mandate that a medical school's curriculum be based upon recognized guidelines. Within the field of psychiatry, the Association of Directors of Medical Student Education in Psychiatry (ADMSEP) has previously published recommended guidelines for the pre-clinical and clerkship curriculum. Ongoing changes within the Liaison Committee on Medical Education's requirements for medical school curricula, and the publication of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, necessitated review of these guidelines. METHODS: ADMSEP convened a task force of psychiatric educators to develop a consensus report outlining new guidelines. The ADMSEP membership reviewed and approved this final document. RESULTS: The guidelines outline six core learning objectives with corresponding competencies. Each of these competencies specifies accompanying milestones to be achieved through the course of medical school. CONCLUSIONS: ADMSEP believes these guidelines will aid educators in crafting a school's psychiatric curriculum. Clearly articulated milestones may foster the further development of validated educational and assessment tools by ADMSEP and other organizations.

Team Emotional Intelligence, Team Interactions, and Gender in Medical Students During a Psychiatry Clerkship.

OBJECTIVE: This study examined the relationship between team emotional intelligence, quality of team interactions, and gender. METHODS: Psychiatry clerkship students participating in Team-Based Learning (TBL, n = 484) or no TBL (control, n = 265) completed the Workgroup Emotional Intelligence Profile (WEIP-S) and the Team Performance Scale (TPS). RESULTS: Significant correlations (p < 0.01) existed between quality of team interactions (i.e., TPS) and team emotional intelligence (i.e., WEIP-S) subscales, but not gender. Control and TBL groups experienced significant increases in WEIP-S subscales pre to post (p < 0.01, η (2) = .08), with the TBL group experiencing significantly higher gains in three of four subscales. Control group scored higher on TPS. CONCLUSIONS: A significant relationship exists between team emotional intelligence and quality of team interactions. Gender was unrelated to TPS or WEIP-S subscales. TBL group experienced higher gains in WEIP-S subscales while the control group experienced slightly higher TPS scores. Results suggest implications for medical educators who use TBL.

Exploring adolescent mental health during the COVID-19 crisis - strengths and difficulties.

Introduction: The SARS-CoV-2 pandemic has significantly impacted children and adolescents, leading to mental health challenges. Knowledge on their resources and difficulties is crucial and there is a need for valid instruments to assess their psychosocial condition especially in this exceptional situation. We assessed psychopathological symptoms using the SDQ during the pandemic, comparing to pre-pandemic data. Our study aims to understand adolescents' strengths and difficulties amidst COVID-19, evaluating the SDQ's utility in crisis settings. Methods: Within the German school-based surveillance study ("B-Fast"), we assessed behavioral strengths and difficulties in 664 adolescents aged 11-17 years during the peak of the German COVID-19 pandemic using the validated Strengths and Difficulties Questionnaire (SDQ) for both external and self-assessed data collection. Data were collected between November 2020 and April 2021. We compared self-assessed SDQ-scores to pre-pandemic data from a comparable sample and examined adolescent classification as "normal" or "borderline/abnormal" based on both external and self-assessed SDQ subscale scores using established cut-off values. Additionally, we conducted sex and rater-based score comparisons. Results: In our study, we observed a significant worsening of "Emotional Symptoms" compared to pre-pandemic levels, while "Conduct Problems" and "Prosocial Behavior" showed improvement. Variations in classification to "normal" and "abnormal" emerged when applying German versus British cut-off values. Females scored higher on "Emotional Symptoms" while males scored higher on "Hyperactivity Symptoms." Correlations between external and self-assessed SDQ ratings ranged from 0.43 (p < 0.001) for "Prosocial Behavior" among girls to 0.62 (p < 0.001) for "Peer Problems" among boys, indicating moderate to high consistency. Discussion/conclusion: Our study contributes to understanding the psychosocial impact of the COVID-19 pandemic on German adolescents. Compared to other symptoms, we observed a particular worsening in "Emotional Symptoms" based on our data. Despite the moderate correlation between parental and self-reported evaluations, there appears to be a certain discrepancy in the perception of adolescent quality of life. Therefore, it seems prudent to assess both the external and self-reported evaluations and amalgamate the results from both parties to obtain a comprehensive problem profile of the individual. These findings underscore the importance of using country-specific cutoff values and reaffirm the utility of the SDQ as a valuable assessment tool, even within the unique circumstances posed by a pandemic.

Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age.

Regeneration of bone defects is often limited due to compromised bone tissue physiology. Previous studies suggest that engineered extracellular matrices enhance the regenerative capacity of mesenchymal stromal cells. In this study, we used human-induced pluripotent stem cells, a scalable source of young mesenchymal progenitors (hiPSC-MPs), to generate extracellular matrix (iECM) and test its effects on the osteogenic capacity of human bone-marrow mesenchymal stromal cells (BMSCs). iECM was deposited as a layer on cell culture dishes and into three-dimensional (3D) silk-based spongy scaffolds. After decellularization, iECM maintained inherent structural proteins including collagens, fibronectin and laminin, and contained minimal residual DNA. Young adult and aged BMSCs cultured on the iECM layer in osteogenic medium exhibited a significant increase in proliferation, osteogenic marker expression, and mineralization as compared to tissue culture plastic. With BMSCs from aged donors, matrix mineralization was only detected when cultured on iECM, but not on tissue culture plastic. When cultured in 3D iECM/silk scaffolds, BMSCs exhibited significantly increased osteogenic gene expression levels and bone matrix deposition. iECM layer showed a similar enhancement of aged BMSC proliferation, osteogenic gene expression, and mineralization compared with extracellular matrix layers derived from young adult or aged BMSCs. However, iECM increased osteogenic differentiation and decreased adipocyte formation compared with single protein substrates including collagen and fibronectin. Together, our data suggest that the microenvironment comprised of iECM can enhance the osteogenic activity of BMSCs, providing a bioactive and scalable biomaterial strategy for enhancing bone regeneration in patients with delayed or failed bone healing.

Comparison of Outcomes After Arthroscopic Superior Capsule Reconstruction Versus Arthroscopic Partial Repair or Arthroscopic Debridement for Irreparable Rotator Cuff Tears.

Background: Arthroscopic superior capsule reconstruction (SCR), arthroscopic partial repair (PR), and arthroscopic debridement (DB) are valid treatment options for irreparable rotator cuff (RC) tears. Purpose/Hypothesis: The purpose of this study was to compare clinical, functional, and radiological outcomes of arthroscopic SCR with arthroscopic PR and arthroscopic DB in patients with irreparable posterosuperior RC tears. It was hypothesized that SCR would lead to superior clinical and functional outcomes compared with PR or DB. Study Design: Cohort study; Level of evidence, 3. Methods: Clinical and functional outcomes of this single-center retrospective study included range of motion, strength, and the age- and sex-adjusted Constant-Murley score. Patient-reported outcome measures (PROMs) involved the quick Disabilities of the Arm, Shoulder and Hand score, the Subjective Shoulder Value, and the visual analog scale for pain. Graft and repaired tendon integrity was evaluated by magnetic resonance imaging (MRI) at 12 months of follow-up. Results: In total, 57 patients treated with SCR (n = 20), PR (n = 17), and DB (n = 20) were included. The mean clinical follow-up was 33.8 ± 17.9 months. Preoperative clinical and functional characteristics were comparable among the 3 groups. The range of motion and clinical and functional scores of all 3 groups significantly improved from pre- to postoperatively. Postoperative PROMs showed no differences among all 3 study groups. SCR revealed significantly higher postoperative strength compared with PR (P = .001) and DB (P = .004). Postoperative MRI revealed a rerupture in 4 patients with SCR (20%). Postoperative MRI showed a rerupture in 9 patients with PR ( 53%). Fatty muscle infiltration of the supraspinatus and infraspinatus significantly progressed within all 3 study groups in postoperative MRI scans. No clinical and functional differences were observed between intact and reruptured PR. Conclusion: Patients who underwent SCR had better postoperative strength recovery than patients who underwent PR or DB.

The use of coupled HSQC spectra to aid in stereochemical assignments of molecules with severe proton spectral overlap.

INTRODUCTION: A simple glycoside with only 13 carbons exhibited extensive overlapping of four of the glycosidic protons, causing extreme difficulty in the determination of the stereochemistry of the pyranose unit. However, acquisition of a high-resolution coupled heteronuclear single-quantum coherence (HSQC) spectrum overcame this problem. This spectrum provides a useful method for determining vicinal proton coupling constants between strongly coupled protons. OBJECTIVE: To show the potential of high-resolution coupled HSQC spectra in overcoming spectral overlap. METHODOLOGY: The sample was obtained by methanol extraction, followed by fractionation and column chromatography of the dried leaves of Montrichardia arborescens (Araceae). NMR spectra were obtained on 1.5 mg of sample dissolved in 120 µL of CD3OD containing 0.1% trimethylsilyl (TMS) as internal standard. A gradient-selected HSQC spectrum was obtained using standard Varian library pulse sequences in phase sensitive mode. The high-resolution coupled HSQC spectrum focused on the saccharide region with a 1025 Hz ¹H spectral window, a 6300 Hz ¹³C spectral window, 1024 data points, a 0.3 Hz relaxation delay, 384 time increments (linear predicted to 4096), and 80 scans per time increment. RESULTS: The use of a high-resolution coupled HSQC spectrum allowed determination of the coupling patterns of the various pyranose protons with sufficient accuracy. This enabled completion of the assignments and identification of the pyranose unit as glucose. CONCLUSION: The study has shown the effectiveness of the use of a high-resolution coupled HSQC spectrum in the assignment of molecules with severe spectral overlap.

Variable-temperature ¹H-NMR studies on two C-glycosylflavones.

Two known C-glycosylflavones, swertisin and embinoidin, were isolated from the leaves of Anthurium aripoense, and characterized by room temperature 1D and 2D NMR experiments. At this temperature, the ¹H- and ¹³C-NMR spectra of these C-glycosylflavones revealed doubling of signals, which suggested the presence of two rotamers in solution. Variable-temperature (VT) ¹H-NMR studies supported this hypothesis. The T-ROESY data, in addition to the theoretical (MM2) calculations utilizing the Chem3D Pro software, confirmed the hypothesis that the two rotamers interchange via rotation about the C-glycosidic bond.

The Evolution of Reverse Total Shoulder Arthroplasty-From the First Steps to Novel Implant Designs and Surgical Techniques.

PURPOSE OF REVIEW: The purpose of this review is to summarize recent literature regarding the latest design modifications and biomechanical evolutions of reverse total shoulder arthroplasty and their impact on postoperative outcomes. RECENT FINDINGS: Over the past decade, worldwide implantation rates of reverse total shoulder arthroplasty have drastically increased for various shoulder pathologies. While Paul Grammont's design principles first published in 1985 for reverse total shoulder arthroplasty remained unchanged, several adjustments were made to address postoperative clinical and biomechanical challenges such as implant glenoid loosening, scapular notching, or limited range of motion in order to maximize functional outcomes and increase the longevity of reverse total shoulder arthroplasty. However, the adequate and stable fixation of prosthetic components can be challenging, especially in massive osteoarthritis with concomitant bone loss. To overcome such issues, surgical navigation and patient-specific instruments may be a viable tool to improve accurate prosthetic component positioning. Nevertheless, larger clinical series on the accuracy and possible complications of this novel technique are still missing.

Cryoablation versus radiofrequency energy for the ablation of atrioventricular nodal reentrant tachycardia (the CYRANO Study): results from a large multicenter prospective randomized trial.

BACKGROUND: Cryoablation has emerged as an alternative to radiofrequency catheter ablation (RFCA) for the treatment of atrioventricular (AV) nodal reentrant tachycardia (AVNRT). The purpose of this prospective randomized study was to test whether cryoablation is as effective as RFCA during both short-term and long-term follow-up with a lower risk of permanent AV block. METHODS AND RESULTS: A total of 509 patients underwent slow pathway cryoablation (n=251) or RFCA (n=258). The primary end point was immediate ablation failure, permanent AV block, and AVNRT recurrence during a 6-month follow-up. Secondary end points included procedural parameters, device functionality, and pain perception. Significantly more patients in the cryoablation group than the RFCA group reached the primary end point (12.6% versus 6.3%; P=0.018). Whereas immediate ablation success (96.8% versus 98.4%) and occurrence of permanent AV block (0% versus 0.4%) did not differ, AVNRT recurrence was significantly more frequent in the cryoablation group (9.4% versus 4.4%; P=0.029). In the cryoablation group, procedure duration was longer (138±54 versus 123±48 minutes; P=0.0012) and more device problems occurred (13 versus 2 patients; P=0.033). Pain perception was lower in the cryoablation group (P<0.001). CONCLUSIONS: Cryoablation for AVNRT is as effective as RFCA over the short term but is associated with a higher recurrence rate at the 6-month follow-up. The risk of permanent AV block does not differ significantly between cryoablation and RFCA. The potential benefits of cryoenergy relative to ablation safety and pain perception are counterbalanced by longer procedure times, more device problems, and a high recurrence rate. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00196222.

Salt tolerance of Arabidopsis thaliana requires maturation of N-glycosylated proteins in the Golgi apparatus.

Protein N-glycosylation in the endoplasmic reticulum (ER) and in the Golgi apparatus is an essential process in eukaryotic cells. Although the N-glycosylation pathway in the ER has been shown to regulate protein quality control, salt tolerance, and cellulose biosynthesis in plants, no biological roles have been linked functionally to N-glycan modifications that occur in the Golgi apparatus. Herein, we provide evidence that mutants defective in N-glycan maturation, such as complex glycan 1 (cgl1), are more salt-sensitive than wild type. Salt stress caused growth inhibition, aberrant root-tip morphology, and callose accumulation in cgl1, which were also observed in an ER oligosaccharyltransferase mutant, staurosporin and temperature sensitive 3a (stt3a). Unlike stt3a, cgl1 did not cause constitutive activation of the unfolded protein response. Instead, aberrant modification of the plasma membrane glycoprotein KORRIGAN 1/RADIALLY SWOLLEN 2 (KOR1/RSW2) that is necessary for cellulose biosynthesis occurred in cgl1 and stt3a. Genetic analyses identified specific interactions among rsw2, stt3a, and cgl1 mutations, indicating that the function of KOR1/RSW2 protein depends on complex N-glycans. Furthermore, cellulose deficient rsw1-1 and rsw2-1 plants were also salt-sensitive. These results establish that plant protein N-glycosylation functions beyond protein folding in the ER and is necessary for sufficient cell-wall formation under salt stress.