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1.
World J Clin Cases ; 12(7): 1346-1355, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38524520

ABSTRACT

BACKGROUND: Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic pulps. The therapeutic management of radicular cysts is controversial. There is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy, but without the use of the guided tissue regeneration (GTR) technique in the same surgical procedure. The present clinical case describes the management of a radicular cyst with microsurgical approach, performance of an apicoectomy of the tooth associated with the entity, application of GTR technique, use of a resorbable membrane of type I bovine collagen, and bovine xenograft. CASE SUMMARY: A 68-year-old patient presented with a radicular cyst from an upper lateral incisor. The microsurgical management used was aimed at enucleating the chemical membrane, performing apicoectomy of the tooth along with careful and precise retrograde filling, and implementing GTR technique using a resorbable collagen membrane and bovine xenograft. The diagnosis of radicular cyst was confirmed using histopathological analysis. The patient underwent follow-up evaluations at 10 and 30 d postoperatively. At 4 months postoperative evaluation, she remained asymptomatic, and radiographs showed significant periapical healing with adequate bone formation. CONCLUSION: These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft, contributes to bone regeneration.

2.
Int J Mol Sci ; 24(23)2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38069207

ABSTRACT

Pyogenic granuloma (PG) is a benign vascular lesion found predominantly in the oral cavity. Characterized by rapid growth and propensity to bleed, PG presents diagnostic challenges due to its similarity and alarming proliferation. This narrative review synthesizes current knowledge on the epidemiology, etiopathogenesis, clinical manifestations, and management of oral PG, with emphasis on recent advances in diagnostic and therapeutic approaches. The epidemiology of the injury is meticulously analyzed, revealing a higher incidence in women and a wide range of ages of onset. It delves into the etiopathogenesis, highlighting the uncertainty surrounding the exact causal factors, although historical attributions suggest an infectious origin. It exhaustively analyzes the clinical and histopathological aspects of oral PG, offering information on its various presentations and the importance of an accurate diagnosis to guide effective treatment. It details treatment strategies, emphasizing the personalized approach based on individual patient characteristics. This comprehensive review consolidates current knowledge on oral PG, highlighting the need for further research to clarify its pathogenesis and optimize treatment protocols.


Subject(s)
Granuloma, Pyogenic , Humans , Female , Granuloma, Pyogenic/diagnosis , Granuloma, Pyogenic/epidemiology , Granuloma, Pyogenic/etiology , Mouth Mucosa/pathology , Mouth/pathology
4.
Microorganisms ; 11(9)2023 Sep 04.
Article in English | MEDLINE | ID: mdl-37764076

ABSTRACT

The prevalence of Listeria monocytogenes in 30 samples of poultry was determined using culture-dependent (isolation on OCLA and confirmation by conventional polymerase chain reaction -PCR-, OCLA&PCR) and culture-independent (real-time polymerase chain reaction, q-PCR) methods. L. monocytogenes was detected in 15 samples (50.0%) by OCLA&PCR and in 20 (66.7%) by q-PCR. The concentrations (log10 cfu/g) of L. monocytogenes (q-PCR) ranged from 2.40 to 5.22 (total cells) and from <2.15 to 3.93 (viable cells). The two methods, q-PCR using a viability marker (v-PCR) and OCLA&PCR (gold standard), were compared for their capacity to detect viable cells of L. monocytogenes, with the potential to cause human disease. The values for sensitivity, specificity and efficiency of the v-PCR were 100%, 66.7% and 83.3%, respectively. The agreement between the two methods (kappa coefficient) was 0.67. The presence of nine virulence genes (hlyA, actA, inlB, inlA, inlC, inlJ, prfA, plcA and iap) was studied in 45 L. monocytogenes isolates (three from each positive sample) using PCR. All the strains harbored between six and nine virulence genes. Fifteen isolates (33.3% of the total) did not show the potential to form biofilm on a polystyrene surface, as determined by a crystal violet assay. The remaining strains were classified as weak (23 isolates, 51.1% of the total), moderate (one isolate, 2.2%) or strong (six isolates, 13.3%) biofilm producers. The strains were tested for susceptibility to a panel of 15 antibiotics. An average of 5.11 ± 1.30 resistances per isolate was observed. When the values for resistance and for reduced susceptibility were taken jointly, this figure rose to 6.91 ± 1.59. There was a prevalence of resistance or reduced susceptibility of more than 50.0% for oxacillin, cefoxitin, cefotaxime, cefepime ciprofloxacin, enrofloxacin and nitrofurantoin. For the remaining antibiotics tested, the corresponding values ranged from 0.0% for chloramphenicol to 48.9% for rifampicin. The high prevalence and level of L. monocytogenes with numerous virulence factors in poultry underline how crucial it is to follow correct hygiene procedures during the processing of this foodstuff in order to reduce the risk of human listeriosis.

5.
World J Clin Cases ; 11(16): 3907-3914, 2023 Jun 06.
Article in English | MEDLINE | ID: mdl-37383141

ABSTRACT

BACKGROUND: Pyogenic granuloma (PG) is a localized, reddish and vascularized hyperplastic lesion of the connective tissue which occurs in the oral cavity. In most cases, the presence of this lesion does not show alveolar bone resorption. The pathology is diagnosed clinically with some caution. However, the diagnosis and treatment are usually corroborated with histopathological evidence. CASE SUMMARY: Three clinical cases of PG associated with bone loss were described in this study. The three patients presented tumor-like growth which bled on touch, and were associated with local irritant factors. Radiographs showed bone loss. All cases were treated with conservative surgical excision. The scarring was satisfactory, and there was no case of recurrence. The diagnoses were based on clinical findings, and were confirmed histopathologically. CONCLUSION: The occurrence of oral PG with bone loss is unusual. Therefore, clinical and radiographic evaluations are important for the diagnosis.

6.
Bull Environ Contam Toxicol ; 110(5): 87, 2023 Apr 29.
Article in English | MEDLINE | ID: mdl-37119338

ABSTRACT

Plastics enter the environment, amongst others, from synthetic textiles, which shed microplastic fibers (microfibers) during their production, use and disposal. We tested whether short- and long-term effects of microfibers on the aquatic worm, Lumbriculus variegatus, depend on the synthetic microfiber material. Microcosms containing L. variegatus were exposed to no microfibers (control) or one of three polymer treatments (nylon, polyester, or olefin) at 5 g of microfibers kg-1 of sediment for 48 h or 28 days. Following exposure, L. variegatus were counted, weighed, and the number of microfibers ingested determined. Polyester microfibers occurred in higher quantities (10-12) than nylon and olefin (< one) per individual after 48 h and 28 days. Only the olefin per individual doubled after 28 days compared to 48 h. These findings indicate that polyester microfibers are more likely to affect L. variegatus and have greater potential to be ingested by higher trophic levels than other polymers.


Subject(s)
Plastics , Water Pollutants, Chemical , Nylons , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/analysis , Textiles , Polyesters , Fresh Water , Polymers , Eating
7.
Eur J Sport Sci ; 23(6): 975-982, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35603722

ABSTRACT

The aim of this study was to compare gluteus maximus-to-hamstring (GM:H) co-activation, hamstrings-to-quadriceps (H:Q) co-activation, and mean muscle activity in the vastus lateralis (VL), vastus medialis (VM), rectus femoris (RM), gluteus maximus (GM), semitendinosus (ST), and bicep femoris (BF) muscles across a range of training loads (40%, 50%, 50%, 70%, 80% 90% 1RM) of the barbell back squat in resistance trained females. Surface electromyography (EMG) was observed in 18 healthy resistance trained females for the VL, VM, RM, GM, ST, and BF during the ascending and descending phase of the back squat. During the ascending phase, the VL, VM, RM, GM, ST, and BF displayed significantly more EMG activation at 90% 1RM compared to 40%-70% (p < .03). During the descending phase, there were no significant differences displayed in mean muscle activity at 40%-80% of 1RM compared to 90% of 1RM. There were no significant differences in H-Q co-activation and GM-H co-activation during the ascending or descending phase across external loads. These findings are similar to the results found in similar studies using male participants and support that higher training intensities (80%-90% 1RM) of the barbell back squat significantly activate muscles surrounding the hip compared to lower loads (40%-70%). The results of this study also suggest that training intensities of 80% 1RM and 90% 1RM elicits the similar musculature activation in the muscle surrounding the hip in resistance trained females.HighlightsDuring the back squat, mean muscle activity of the hip and leg muscles increased linearly with exercise intensity (40%-90% of one-repetition max) in resistance trained females.No significant difference in mean activity were noted between 80% and 90% of one-repetition max during the ascending and descending phases.During the ascending phase, 80% of one-repetition max generated the highest gluteus maximus to hamstring activity co-activation ratio.During the descending phase, 40% of one-repetition max produced a gluteus maximus to hamstring activity co-activation ratio closest to 1.0.


Subject(s)
Exercise , Resistance Training , Female , Humans , Male , Exercise/physiology , Resistance Training/methods , Muscle, Skeletal/physiology , Quadriceps Muscle/physiology , Electromyography
9.
Antibiotics (Basel) ; 11(12)2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36551484

ABSTRACT

Twenty samples of minced chicken meat procured from butcher's shops in León (Spain; 10 samples) and Vila Real (Portugal; 10 samples) were analyzed. Microbial concentrations (log10 cfu/g) of 7.53 ± 1.02 (viable aerobic microbiota), 7.13 ± 1.07 (psychrotrophic microorganisms), and 4.23 ± 0.88 (enterobacteria) were found. The detection method described in the UNE-EN ISO 11290-1 standard (based on isolation from the chromogenic medium OCLA) with confirmation by the polymerase chain reaction (PCR; lmo1030) (OCLA−PCR), revealed Listeria monocytogenes in 14 samples (70.0% of the total), nine of Spanish origin and five of Portuguese (p > 0.05). The levels of viable and inactivated L. monocytogenes in the samples were determined with a q-PCR using propidium monoazide (PMAxx) as a viability marker. Seven samples tested positive both with the OCLA−PCR and with the q-PCR, with estimated concentrations of viable cells varying between 2.15 log10 cfu/g (detection limit) and 2.94 log10 cfu/g. Three samples tested negative both with the OCLA−PCR and with the q-PCR. Seven samples were positive with the OCLA−PCR, but negative with the q-PCR, and three samples tested negative with the OCLA−PCR and positive with the q-PCR. The percentage of viable cells relative to the total ranged between 2.4% and 86.0%. Seventy isolates of L. monocytogenes (five from each positive sample) were classified in PCR serogroups with a multiplex PCR assay. L. monocytogenes isolates belonged to serogroups IIa (52 isolates; 74.3%), IIc (7; 10.0%), IVa (2; 2.9%), and IVb (9; 12.9%). The susceptibility of the 70 isolates to 15 antibiotics of clinical interest was tested. The strains presented resistance to between three and eight antibiotics. The average number of resistances was greater (p < 0.001) among strains isolated from Spanish samples (6.20 ± 1.08), than in those from Portugal (5.00 ± 1.08). In both groups of strains, a prevalence of resistance higher than 95% was observed for oxacillin, cefoxitin, cefotaxime, and cefepime. The need to handle minced chicken meat correctly, taking care to cook it sufficiently and to avoid cross-contamination, so as to reduce the danger of listeriosis, is emphasized. A combination of culture-dependent and culture-independent methods offers complementary routes for the detection in food of the cells of L. monocytogenes in various different physiological states.

10.
World J Clin Cases ; 10(34): 12750-12760, 2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36579122

ABSTRACT

BACKGROUND: Cyclosporine is an immunosuppressive agent used effectively for treatment of a rare haematological disorder known as medullary aplasia. This drug prevents several side effects, including gingival enlargement (GE) which compromises aesthetics, phonetics and chewing, and also predisposes patients to periodontitis. CASE SUMMARY: This clinical case reports a 41-year-old woman who presented with cyclosporine-induced GE with underlying periodontitis and medullary aplasia. The management of the disease was approached through multidisciplinary strategy which allowed for accurate diagnosis and a strategic treatment based on the systemic condition and severity of oral pathology. The diagnosis was confirmed through histopathological analysis. The treatment was carried out in phases: Initial (oral hygiene motivation, mechanical supragingival plaque control, and non-surgical therapy); systemic treatment, corrective treatment, and maintenance. CONCLUSION: Multidisciplinary management of cyclosporine-induced GE and medullary aplasia allows for correct diagnosis and effective treatment of this pathological expression through a phased therapeutic approach.

11.
Article in English | MEDLINE | ID: mdl-36429638

ABSTRACT

Cruciferous vegetables such as cauliflower and radish contain isothiocyanates exhibiting chemoprotective effects in vitro and in vivo. This research aimed to assess the impact of cauliflower (CIE) and radish (RIE) isothiocyanate extracts on the metabolic activity, intracellular reactive oxygen species (ROS), and LDH production of selected human colorectal adenocarcinoma cells (HCT116 and HT-29 for early and late colon cancer development, respectively). Non-cancerous colon cells (CCD-33Co) were used as a cytotoxicity control. The CIE samples displayed the highest allyl isothiocyanate (AITC: 12.55 µg/g) contents, whereas RIE was the most abundant in benzyl isothiocyanate (BITC: 15.35 µg/g). Both extracts effectively inhibited HCT116 and HT-29 metabolic activity, but the CIE impact was higher than that of RIE on HCT116 (IC50: 0.56 mg/mL). Assays using the half-inhibitory concentrations (IC50) of all treatments, including AITC and BITC, displayed increased (p < 0.05) LDH (absorbance: 0.25-0.40 nm) and ROS release (1190-1697 relative fluorescence units) in both cell lines. BITC showed the highest in silico binding affinity with all the tested colorectal cancer molecular markers (NF-kB, ß-catenin, and NRF2-NFE2). The theoretical evaluation of AITC and BITC bioavailability showed high values for both compounds. The results indicate that CIE and RIE extracts display chemopreventive effects in vitro, but additional experiments are needed to validate their effects.


Subject(s)
Brassica , Colorectal Neoplasms , Raphanus , Humans , Reactive Oxygen Species , Botrytis , Isothiocyanates/pharmacology , Colorectal Neoplasms/drug therapy
12.
Article in English | MEDLINE | ID: mdl-36141526

ABSTRACT

Pesticides are chemical substances used to control, prevent, or destroy agricultural, domestic, and livestock pests. These compounds produce adverse changes in health, and they have been associated with the development of multiple chronic diseases. This study aimed to present a detailed review of the effect of pesticides on the oral cavity and the oral microbiome. In the oral cavity, pesticides alter and/or modify tissues and the microbiome, thereby triggering imbalance in the ecosystem, generating an inflammatory response, and activating hydrolytic enzymes. In particular, the imbalance in the oral microbiome creates a dysbiosis that modifies the number, composition, and/or functions of the constituent microorganisms and the local response of the host. Pesticide exposure alters epithelial cells, and oral microbiota, and disrupts the homeostasis of the oral environment. The presence of pesticides in the oral cavity predisposes the appearance of pathologies such as caries, periodontal diseases, oral cancer, and odontogenic infections. In this study, we analyzed the effect of organochlorines, organophosphates, pyrethroids, carbamates, bipyridyls, and triazineson oral cavity health and ecosystems.


Subject(s)
Microbiota , Pesticides , Pyrethrins , Carbamates , Mouth , Organophosphates , Pesticides/toxicity
13.
Medicina (Kaunas) ; 58(9)2022 Sep 03.
Article in English | MEDLINE | ID: mdl-36143891

ABSTRACT

Oral manifestations are early and important clinical indicators of Human Immunodeficiency Virus (HIV) infection since they can occur in up to 50% of HIV-infected patients and in up to 80% of patients at the AIDS stage (<200 CD4+ T lymphocytes). Oral health is related to physical and mental well-being because the presence of some lesions can compromise dental aesthetics, and alter speech, chewing, and swallowing, thus impacting the quality of life of patients. For this reason, it is necessary to integrate, as part of the medical treatment of HIV-positive patients, the prevention, diagnosis, and control of oral health. It is essential that health professionals have the power to identify, diagnose, and treat oral pathologies through clinical characteristics, etiological agents, and risk factors, both local and systemic. A diagnosis at an early stage of injury allows optimizing and prioritizing oral treatments, especially in acute pathologies, such as gingivitis and necrotizing periodontitis. In this group of patients, the development of strategies for the prevention, control, and reduction of these pathologies must be prioritized in order to reduce morbidity and mortality in this group of patients.


Subject(s)
HIV Infections , Periodontitis , HIV Infections/complications , HIV Infections/diagnosis , Humans , Lymphocyte Count , Oral Health , Periodontitis/complications , Quality of Life
14.
Sci Rep ; 12(1): 14087, 2022 08 18.
Article in English | MEDLINE | ID: mdl-35982220

ABSTRACT

Immune checkpoint blockade (ICB) leads to durable and complete tumour regression in some patients but in others gives temporary, partial or no response. Accordingly, significant efforts are underway to identify tumour-intrinsic mechanisms underlying ICB resistance. Results from a published CRISPR screen in a mouse model suggested that targeting STUB1, an E3 ligase involved in protein homeostasis, may overcome ICB resistance but the molecular basis of this effect remains unclear. Herein, we report an under-appreciated role of STUB1 to dampen the interferon gamma (IFNγ) response. Genetic deletion of STUB1 increased IFNGR1 abundance on the cell surface and thus enhanced the downstream IFNγ response as showed by multiple approaches including Western blotting, flow cytometry, qPCR, phospho-STAT1 assay, immunopeptidomics, proteomics, and gene expression profiling. Human prostate and breast cancer cells with STUB1 deletion were also susceptible to cytokine-induced growth inhibition. Furthermore, blockade of STUB1 protein function recapitulated the STUB1-null phenotypes. Despite these encouraging in vitro data and positive implications from clinical datasets, we did not observe in vivo benefits of inactivating Stub1 in mouse syngeneic tumour models-with or without combination with anti-PD-1 therapy. However, our findings elucidate STUB1 as a barrier to IFNγ sensing, prompting further investigations to assess if broader inactivation of human STUB1 in both tumors and immune cells could overcome ICB resistance.


Subject(s)
Interferon-gamma , Neoplasms , Animals , Cytokines/metabolism , Disease Models, Animal , Humans , Interferon-gamma/metabolism , Interferon-gamma/pharmacology , Intracellular Space/metabolism , Male , Mice , Protein Binding , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
15.
Article in English | MEDLINE | ID: mdl-35886619

ABSTRACT

Dentists are health care workers with the highest risk of exposure to COVID-19, because the oral cavity is considered to be a reservoir for SARS-CoV-2 transmission. The identification of SARS-CoV-2 in saliva, the generation of aerosols, and the proximity to patients during dental procedures are conditions that have led to these health care workers implementing additional disinfection strategies for their protection. Oral antiseptics are widely used chemical substances due to their ability to reduce the number of microorganisms. Although there is still no evidence that they can prevent the transmission of SARS-CoV-2, some preoperative oral antiseptics have been recommended as control measures, by different health institutions worldwide, to reduce the number of microorganisms in aerosols and droplets during dental procedures. Therefore, this review presents the current recommendations for the use of oral antiseptics against SARS-CoV-2 and analyzes the different oral antiseptic options used in dentistry.


Subject(s)
Anti-Infective Agents, Local , COVID-19 , Aerosols , Anti-Infective Agents, Local/pharmacology , COVID-19/prevention & control , Health Personnel , Humans , SARS-CoV-2
16.
J Mycol Med ; 32(3): 101294, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35576772

ABSTRACT

OBJECTIVE: The objective of the present study was to determine the in vitro Azole antifungals susceptibility of Candida spp. strains isolated from HIV-positive patients with periodontitis. METHODS: Oral examination was performed in 500 HIV-positive patients, of which 228 were included in the study for having periodontitis which and separated in two groups based on their TCD4+ T-cells: (A) n = 110 (≤200 CD4+); (B) n = 118 (>200 CD4+). Candida spp. were isolated from the subgingival biofilm and crevicular fluid by seeding on CHROMagar plates and confirmed by endpoint PCR and MALDI-TOF. The susceptibility test in vitro for five antifungals was performed using the disc diffusion method. RESULTS: From the 228 HIV-positive patients with periodontitis, 174 were positive to Candida spp., and 204 isolations were obtained. 138 (67.64%) were C. albicans, and 66 (32.35%) were Candida non-albicans species. The most frequent Candida non-albicans species in order of frequency were C. glabrata with 48 (23.52%), C. tropicalis with 10 (4.9%), C. krusei with 7 (3.43%), and C. dubliniensis with 1 (0.49%). All species presented resistance to any antifungal: 149 to 5-fluorocytosine (73.0%), 149 to fluconazole (73.0%), and 144 to voriconazole (70.7%). Miconazole and econazole presented the highest susceptibility rates with 129 (63.2%) and 130 (63.7%) isolations, respectively. CONCLUSION: The Candida spp. involved in periodontitis of HIV-positive patients have a multi-resistant feature. It is necessary to implement recurrent research regarding the antifungal resistance of the Candida spp. that take part in periodontitis pathogenesis to promote an effective treatment in HIV patients.


Subject(s)
HIV Infections , Periodontitis , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Azoles/pharmacology , Candida , Candida albicans , Candida tropicalis , Drug Resistance, Fungal , Fluconazole , HIV Infections/complications , HIV Infections/drug therapy , Humans , Microbial Sensitivity Tests , Periodontitis/complications , Periodontitis/drug therapy
19.
Med Educ Online ; 27(1): 2010291, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34898403

ABSTRACT

Many U.S. medical schools conduct holistic review of applicants to enhance the socioeconomic and experiential diversity of the physician workforce. The authors examined the role of first-generation college-graduate status on U.S. medical school application, acceptance, and matriculation, hypothesizing that first-generation (vs. continuing-generation) college graduates would be less likely to apply and gain acceptance to medical school.Secondary analysis of de-identified data from a retrospective national-cohort study was conducted for individuals who completed the 2001-2006 Association of American Medical Colleges (AAMC) Pre-Medical College Admission Test Questionnaire (PMQ) and the Medical College Admissions Test (MCAT). AAMC provided medical school application, acceptance, and matriculation data through 06/09/2013. Multivariable logistic regression models identified demographic, academic, and experiential variables independently associated with each outcome and differences between first-generation and continuing-generation students. Of 262,813 PMQ respondents, 211,216 (80.4%) MCAT examinees had complete data for analysis and 24.8% self-identified as first-generation college graduates. Of these, 142,847 (67.6%) applied to U.S. MD-degree-granting medical schools, of whom 86,486 (60.5%) were accepted, including 14,708 (17.0%) first-generation graduates; 84,844 (98.1%) acceptees matriculated. Adjusting for all variables, first-generation (vs. continuing-generation) college graduates were less likely to apply (odds ratio [aOR] 0.84; 95% confidence interval [CI], 0.82-0.86) and be accepted (aOR 0.86; 95% CI, 0.83-0.88) to medical school; accepted first-generation college graduates were as likely as their continuing-generation peers to matriculate. Students with (vs. without) paid work experience outside hospitals/labs/clinics were less likely to apply, be accepted, and matriculate into medical school. Increased efforts to mitigate structural socioeconomic vulnerabilities that may prevent first-generation college students from applying to medical school are needed. Expanded use of holistic review admissions practices may help decision makers value the strengths first-generation college graduates and other underrepresented applicants bring to medical educationand the physician workforce.


Subject(s)
College Admission Test , Schools, Medical , Cohort Studies , Humans , Retrospective Studies , Universities
20.
Elife ; 102021 11 11.
Article in English | MEDLINE | ID: mdl-34761751

ABSTRACT

UCH37, also known as UCHL5, is a highly conserved deubiquitinating enzyme (DUB) that associates with the 26S proteasome. Recently, it was reported that UCH37 activity is stimulated by branched ubiquitin (Ub) chain architectures. To understand how UCH37 achieves its unique debranching specificity, we performed biochemical and Nuclear Magnetic Resonance (NMR) structural analyses and found that UCH37 is activated by contacts with the hydrophobic patches of both distal Ubs that emanate from a branched Ub. In addition, RPN13, which recruits UCH37 to the proteasome, further enhances branched-chain specificity by restricting linear Ub chains from having access to the UCH37 active site. In cultured human cells under conditions of proteolytic stress, we show that substrate clearance by the proteasome is promoted by both binding and deubiquitination of branched polyubiquitin by UCH37. Proteasomes containing UCH37(C88A), which is catalytically inactive, aberrantly retain polyubiquitinated species as well as the RAD23B substrate shuttle factor, suggesting a defect in recycling of the proteasome for the next round of substrate processing. These findings provide a foundation to understand how proteasome degradation of substrates modified by a unique Ub chain architecture is aided by a DUB.


Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Proteasome Endopeptidase Complex/metabolism , Ubiquitin/metabolism , Catalytic Domain , Gene Deletion , HCT116 Cells , HEK293 Cells , Humans , Inclusion Bodies , Intracellular Signaling Peptides and Proteins/genetics , Proteasome Endopeptidase Complex/genetics , Protein Binding , Proteolysis , Ubiquitin/genetics
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