The lectin chaperones calreticulin (CRT) and calnexin (CNX) contribute to the folding of glycoproteins in the ER by recruiting foldases such as the protein disulfide isomerase ERp57 and the peptidyl ...prolyl cis-trans isomerase CypB. Recently, CRT was shown to interact with the chaperone ERp29. Here, we show that ERp29 directly binds to the P domain of CNX. Crystal structures of the D domain of ERp29 in complex with the P domains from CRT and calmegin, a tissue-specific CNX homolog, reveal a commonality in the mechanism of binding whereby the tip of the P domain functions as a plurivalent adapter to bind a variety of folding factors. We show that mutation of a single residue, D348 in CNX, abrogates binding to ERp29 as well as ERp57 and CypB. The structural diversity of the accessory factors suggests that these chaperones became specialized for glycoprotein folding through convergent evolution of their P-domain binding sites.
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•Calnexin/calreticulin enlist various chaperones for glycoprotein folding•P domain acts as an adaptor for binding different ER chaperones•Crystal structures reveal convergent evolution of chaperone P-domain binding sites
Kozlov et al. show that lectin chaperones in the ER use a multipurpose adapter to recruit different proteins, a protein disulfide isomerase, a peptidyl prolyl isomerase, and a general chaperone, to promote the folding of newly synthesized glycoproteins.
La memoria del cuerpo es textil Muñoz-Toro, Juliana
CS (Universidad Icesi. Facultad de Derecho y Ciencias Sociales),
09/2022
38
Journal Article, Book Review
Odprti dostop
En mis manos unas manos. Las manos bordan, reparan o juntan fragmentos. Las manos también escriben con hilo y tinta: Gestos textiles. Un acercamiento material a las etnografías, los cuerpos y los ...tiempos, el más reciente libro de Tania Pérez-Bustos, docente e investigadora. Esta es una conversación no solo académica, sino también pensada como la suma de voces que narran sus tramas.
The UBR‐box is a 70‐residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N‐terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is ...an UBR‐box containing E3 ubiquitin ligase that does not bind N‐terminal signals. Here, we present the crystal structure of the UBR‐box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR‐box fold. Analysis of the structure suggests that the absence of N‐terminal residue binding arises from the lack of an amino acid binding pocket.
PDB Code(s): 5VMD
Atrazine is a pesticide used to control weeds in both in pre- and post-emergence crops. The chronic exposure to atrazine can lead to severe damage in animals, especially in the endocrine and ...reproduction systems, leading to the inclusion of this pesticide into the endocrine disrupting chemicals group. Studies with rats showed that atrazine exposure during lactation in dams caused changes in the juvenile offspring, however; there is still limited information regarding the effects of atrazine during puberty. Thus, the aim of this study is to evaluate the effects of peripubertal exposure of atrazine in rats, assessing motor activity, social behavior and neurochemical alterations. Juvenile rats were treated with different doses of atrazine (0, 10, 30 or 100 mg/kg) by gavage from postnatal day 22 to 41. Behavioral tests were conducted for the evaluation of motor activity and social behavior, and neurochemical evaluation was done in order to assess monoamine levels. Atrazine caused behavioral alterations, evidenced by decrease in the exploratory activity (p values variation between 0.05 and 0.0001) and deficits in the social behavior of both male and females as adults (p values variation between 0.01 and 0.0001). As for the monoaminergic neurotransmission, atrazine led to very few alterations on the dopamine and serotonin systems that were limited to the females (p < 0.05). Altogether, the results suggests that peripubertal exposure of atrazine cause behavioral and neurochemical alterations. More studies need to be conducted to fully understand the differences in atrazine's effects and its use should be considered carefully.
•Peripubertal exposure of atrazine cause alterations on the exploratory activity.•Peripubertal exposure of atrazine cause deficits in social behavior.•Atrazine caused few neurochemical alterations but limited only to the females.
E3 ubiquitin ligases catalyze the transfer of ubiquitin from an E2-conjugating enzyme to a substrate. UBR5, homologous to the E6AP Cterminus (HECT)-type E3 ligase, mediates the ubiquitination of ...proteins involved in translation regulation, DNA damage response, and gluconeogenesis. In addition, UBR5 functions in a ligase-independent manner by prompting protein/protein interactions without ubiquitination of the binding partner. Despite recent functional studies, the mechanisms involved in substrate recognition and selective ubiquitination of its binding partners remain elusive. The C terminus of UBR5 harbors the HECT catalytic domain and an adjacent MLLE domain. MLLE domains mediate protein/protein interactions through the binding of a conserved peptide motif, termed PAM2. Here, we characterize the binding properties of the UBR5 MLLE domain to PAM2 peptides from Paip1 and GW182. The crystal structure with a Paip1 PAM2 peptide reveals the network of hydrophobic and ionic interactions that drive binding. In addition, we identify a novel interaction of the MLLE domain with the adjacent HECT domain mediated by a PAM2-like sequence. Our results confirm the role of the MLLE domain of UBR5 in substrate recruitment and suggest a potential role in regulating UBR5 ligase activity.
Background: Paip2 and GW182 are translation effectors that interact with the E3 ubiquitin ligase UBR5.
Results: The MLLE domain of UBR5 interacts with GW182, recruits Paip2 for ubiquitination, and interacts with the catalytic HECT domain of UBR5.
Conclusion: The MLLE domain of UBR5 regulates inter- and intramolecular interactions in UBR5.
Significance: The MLLE/HECT interaction in UBR5 may regulate ubiquitin transfer catalyzed by the HECT domain.
Thyroid eye disease is an autoimmune disorder of the orbital retrobulbar tissue commonly associated with dysthyroid status. The most frequent condition is hyperthyroidism, although it is also present ...in hypothyroid and euthyroid patients. The prevalence of thyroid conditions in patients with thyroid eye disease had been previously evaluated; however, there is no consensus on a global prevalence. The study aims to estimate the prevalence of hyperthyroidism, hypothyroidism, and euthyroidism in patients with TED, through a systematic review of literature.
We conducted a systematic review of the literature following the PRISMA guidelines, in MEDLINE, COCHRANE, EMBASE, Science Direct, and LILACS databases. Inclusion criteria were primary studies of patients with a diagnosis of thyroid eye disease made by an ophthalmologist or with diagnosis criteria, with measurement of thyroid function (TSH, T3, and free T4), and diagnosis of the primary thyroid condition. A quality assessment was made through the Joanna Briggs Institute Quality tools. Finally, we extracted relevant details about the design, the results, and the prevalence of thyroid disorders in thyroid eye disease.
The initial search revealed 916 studies, of which finally thirteen met inclusion criteria. Six studies were performed in Europe (Germany, Wales, and Spain), five in Asia (Iran, South Korea, Japan, and Singapore), one in North America (USA), and one in Africa (Ghana). The global prevalence, in patients of thyroid eye disease, was 10.36% for hypothyroidism, 7.9% for euthyroidism, and 86.2% for hyperthyroidism.
Professionals should be aware that thyroid eye disease can be present in patients with a normal thyroid function. The assessment for these patients is based on orbital images; serum TSH, T3, and free T4; antibody levels as thyrotropin receptor antibodies; and thyroperoxidase levels. Additionally, we want to encourage research in this field in other regions of the world such as Latin America.
PROSPERO ID CRD42020107167.
The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis.
...A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis.
A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon β, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon β was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case.
Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach.
PROSPERO ID CRD42020106886.
Abstract
Background
Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, which leads to visual impairment in a large proportion of patients. Antibiotics and corticosteroids lower ...the risk of permanent visual loss by controlling infection and inflammation. However, there remains disagreement regarding optimal antibiotic therapy for OT. Therefore, this systematic review and meta-analysis were performed to determine the effects and safety of existing antibiotic treatment regimens for OT.
Methods
MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, LILACS, WHO International Clinical Trials Registry Platform portal, ClinicalTrials.gov, and Gray Literature in Europe (“OpenGrey”) were searched for relevant studies; manual searches of reference lists were performed for studies identified by other methods. All published and unpublished randomized controlled trials that compared antibiotic schemes known to be effective in OT at any dosage, duration, and administration route were included. Studies comparing antibiotics with placebo were excluded. This review followed standard methodological procedures recommended by the Cochrane group.
Results
Ten studies were included in the narrative summary, of which four were included for quantitative synthesis (meta-analysis). Interventions were organized into three groups: intravitreal clindamycin versus pyrimethamine + sulfadiazine, trimethoprim + sulfamethoxazole versus other antibiotics, and other interventions. The first comparison favored intravitreal clindamycin (Mean difference (MD) = 0.10 logMAR; 95% confidence interval = 0.01 to 0.22). However, this finding lacks clinical relevance. Other outcomes showed no statistically significant differences between the treatment groups. In general, the risk of performance bias was high in evaluated studies, and the quality of the evidence found was low to very low.
Conclusions
No antibiotic scheme was superior to others, and the selection of a treatment regimen depends on multiple factors; therefore, treatment should be chosen based on safety, sulfa allergies, and availability.
Down syndrome (DS) is a chromosomal anomaly that is characterized by an extra chromosome 21. Ophthalmological manifestations have a high prevalence in patients with DS.
To review the scientific ...evidence and estimate the prevalence of ophthalmological manifestations in the pediatric population with DS.
Electronic databases including MEDLINE, Cochrane Library, EMBASE, ScienceDirect, and LILACS.
Published observational studies with available and original data were included. Articles were excluded if the study design was a review, letter to the editor, case report, case series, or systematic review and if the subjects had ophthalmological manifestations secondary to other conditions.
Pediatric and adolescent population with DS and with ophthalmological evaluation.
A data collection form was designed in Excel. Five reviewers extracted relevant details about the design and results of each study. The quality of the studies was assessed by applying the tools for systematic reviews of prevalence and incidence from the Joanna Briggs Institute. We calculated the weighted prevalence of ophthalmological manifestations, considering only the studies reporting the measurement of each manifestation.
Twenty-two articles (from 15 countries, published during 1994-2020) were included in the present systematic review. Ocular manifestations were observed in 85% of the studied pediatric and adolescent populations with DS. The most frequent ones were slanting fissures, oblique fissures, epicanthus, and epiblepharon.
The ocular manifestations in the pediatric and adolescent populations with DS are varied, and some can irreversibly affect visual development. Screening of the pediatric population with DS should be conducted from the first months of age and continued annually.
PROSPERO CRD42019127717.
We report a case of white circular spots of iridian atrophy, which we will call "polka dots" pattern, as a rare ophthalmological finding associated with uveitis secondary to varicella-zoster virus ...and Toxoplasma gondii coinfection in a male patient in Bogotá, Colombia.
We present de case of a 53-year-old Colombian male patient with a diagnosis of anterior uveitis in his left eye due to varicella-zoster virus and Toxoplasma gondii coinfection documented by polymerase chain reaction analysis. He presented with multiple areas of superficial white circular spots of iridian atrophy in 360º, some with deeper atrophy where the stroma fibers were visualized and only a small punctate defect of transillumination was evident. This rare pattern of iridian atrophy has not been previously described in cases of uveitis in the literature.
This is the first case reporting the findings of superficial "polka dots" pattern iridian atrophy in 360° secondary to anterior uveitis due to the coinfection of a virus and a parasite. The identification of similar clinical cases may lead to early initiation of systemic treatment in these patients.
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