A study of families from southern Tunisia affected by general pustular psoriasis uncovered the genetic cause of their disease: a mutation affecting the function of the interleukin-36–receptor ...antagonist.
Psoriasis is a chronic inflammatory skin disease affecting 2 to 3% of persons of European descent.
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Psoriasis vulgaris, the most common form of the disease, accounts for 80% of cases and has a strong, albeit complex, genetic component.
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Numerous chromosomal loci have been implicated in genomewide association studies, but analyses of these loci have yielded only a few candidate genes, which mediate inflammatory cytokine signaling and adaptive immune responses.
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The disease follows mendelian transmission in a small minority of families.
Generalized pustular psoriasis is a life-threatening, multisystemic inflammatory disease involving repeated flare-ups of sudden onset, which are characterized by . . .
We report here the selection and characterization of a novel peptide ligand using phage display targeted against the cancer-specific epidermal growth factor tyrosine kinase receptor mutation variant ...III (EGFRvIII). This receptor is expressed in several kinds of cancer: ovarian cancer, breast cancer and glioblastoma, but not in normal tissues. A 12-mer random peptide library was screened against EGFRvIII. Phage-selected peptides were sequenced in high-throughput by next generation sequencing (NGS), and their diversity was studied to identify highly abundant clones expected to bind with the highest affinities to EGFRvIII. The enriched peptides were characterized and their binding capacity towards stable cell lines expressing EGFRvIII, EGFR wild type (EGFR WT), or a low endogenous level of EGFR WT was confirmed by flow cytometry analysis. The best peptide candidate, VLGREEWSTSYW, was synthesized, and its binding specificity towards EGFRvIII was validated in vitro. Additionally, computational docking analysis suggested that the identified peptide binds selectively to EGFRvIII. The novel VLGREEWSTSYW peptide is thus a promising EGFRvIII-targeting agent for future applications in cancer diagnosis and therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The introduction of thermostable polymerases revolutionized the polymerase chain reaction (PCR) and biotechnology. However, many GC-rich genes cannot be PCR-amplified with high efficiency in water, ...irrespective of temperature. Although polar organic cosolvents can enhance nucleic acid polymerization and amplification by destabilizing duplex DNA and secondary structures, nature has not selected for the evolution of solvent-tolerant polymerase enzymes. Here, we used ultrahigh-throughput droplet-based selection and deep sequencing along with computational free-energy and binding affinity calculations to evolve Taq polymerase to generate enzymes that are both stable and highly active in the presence of organic cosolvents, resulting in up to 10% solvent resistance and over 100-fold increase in stability at 97.5 °C in the presence of 1,4-butanediol, as well as tolerance to up to 10 times higher concentrations of the potent cosolvents sulfolane and 2-pyrrolidone. Using these polymerases, we successfully amplified a broad spectrum of GC-rich templates containing regions with over 90% GC content, including templates recalcitrant to amplification with existing polymerases, even in the presence of cosolvents. We also demonstrated dramatically reduced GC bias in the amplification of genes with widely varying GC content in quantitative polymerase chain reaction (qPCR). By expanding the scope of solvent systems compatible with nucleic acid polymerization, these organic solvent-resistant polymerases enable a dramatic reduction of sequence bias not achievable through thermal resistance alone, with significant implications for a wide range of applications including sequencing and synthetic biology in mixed aqueous-organic media.
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IJS, KILJ, NUK, PNG, UL, UM
Antibody (Ab) validation is the procedure in which an Ab is thoroughly assayed for sensitivity and specificity in a given application. Validation of Abs against post-translationally modified (PTM) ...targets is particularly challenging because it requires specifically prepared antigen. Here we describe a novel validation method using surrogate proteins in a Western blot. The surrogate protein, which we termed ‘MILKSHAKE,’ is a modified maltose binding protein enzymatically conjugated to a peptide from the chosen target that is either modified or nonmodified at the residue of interest. The certainty of the residue’s modification status can be used to confirm Ab specificity. This method also allows for Ab validation even in the absence or limited availability of treated cell lysates.
We have developed a novel method for validating Abs in a Western blot using modified maltose-binding protein enzymatically conjugated to a target peptide mixed with mammalian cell lysate as the antigen. This method can be used to confirm the primary antibody’s specificity for the target sequence and as a Western blot process control specific to the primary antibody used. We will demonstrate the utility of MILKSHAKE for post-translationally modified (PTM) targets and for determining specificity at an amino acid polymorphic site, but it should be apparent that it can also be used for non-PTMs.
The study attempts to evaluate the relationship, if any, between interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. The results indicate such a form of deficiency did ...lead to generalized pustular psoriasis.
The COVID-19 pandemic has presented various challenges, one of which is the discovery that after the acute episode, around 30% of patients experience persistent symptoms or develop new ones, now ...known as long COVID. This new disease has significant social and financial impacts. The objective is to determine the prevalence of long COVID in the Tunisian population and identify its predictive factors.
This was a cross-sectional study conducted among Tunisians who were infected with COVID-19 between March 2020 and February 2022. An online self-administered questionnaire was distributed through social media, radio, and television channels over the course of one month (February 2022). Long COVID was defined as the persistence of existing symptoms or the development of new symptoms within three months after onset, lasting for at least two months, and with no differential diagnosis. We performed univariate and multivariate analyses using binary stepwise logistic regression with a significance level set at 5%.
A total of 1911 patients participated in our study, and the prevalence of long COVID was 46.5%. The two most frequent categories were general and neurological post-COVID syndrome, with a prevalence of 36.7% each. The most commonly observed symptoms were fatigue (63.7%) and memory problems (49.1%). In the multivariate analysis, the predictive factors for long COVID were female gender and age of 60 years or older, while complete anti-COVID vaccination was found to be a protective factor.
Our study found that complete vaccination was a protective factor against long COVID, while female gender and age of 60 years or older were identified as the main risk factors. These findings are consistent with studies conducted on other ethnic groups. However, many aspects of long COVID remain unclear, including its underlying mechanisms, the identification of which could guide the development of potential effective treatments.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Distal vessel occlusions represent about 25-40% of acute ischemic stroke (AIS), either as primary occlusion or secondary occlusion complicating mechanical thrombectomy (MT) for large vessel ...occlusion.
Our aim was to evaluate safety and effectiveness of MT associated with the best medical treatment (BMT) in the management of AIS patients with distal vessel occlusion in comparison with the BMT alone.
Retrospective analysis was conducted on AIS patients treated by MT+BMT for primary distal vessel occlusion between 2015 and 2020, and were compared with a historic cohort managed by BMT alone between 2006 and 2015 selected based on the same inclusion criteria. A secondary analysis was conducted using propensity score matching (PSM) including the following: NIHSS, age and treatment with intravenous thrombolysis (IVT) as covariates.
Of 650 patients screened, 44 patients with distal vessel occlusions treated by MT+BMT were selected and compared with 36 patients who received BMT alone. After PSM, 28 patients in each group were matched without significant difference. Good clinical outcome defined as mRS≤2 was achieved by 53.6% of the MT+BMT group and 57% of the BMT group (OR, 0.87; 95%CI, 0.3–2.4; p = 1.00). The mortality rate was comparable in both groups (7% vs. 10.7% in MT+BMT and BMT patients, respectively; OR=0.64; 95%CI, 0.1-4; p = 1.00). Symptomatic intracranial hemorrhage (ICH) was seen in only one patient treated by MT+BMT (3.6%).
Mechanical thrombectomy seems to be comparable with the best medical treatment regarding the effectiveness and safety in the management of patients with distal vessel occlusions.
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•Distal vessel occlusions (DVOs) represent about 25 - 40% of acute ischemic stroke.•There are insufficient data to ascertain whether mechanical thrombectomy (MT) plus best medical treatment (BMT) is superior to BMT alone in DVOs.•In our study, MT+BMT and BMT alone were found to achieve similar rates of good clinical outcome despite higher final successful recanalisation rate in MT+BMT group.•The 3-months mortality rate was comparable between both groups.•Despite that MT and BMT seem to be comparable in the management of DVOs, larger-sample randomised studies are warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This meeting abstract was removed due to the OA licensing requirements of this journal. The full abstract is listed here
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https://www.svin.org/files/SVIN_2021_Abstracts_for_Web.pdf
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