Non-response in surveys is a common problem faced by surveyors, this results in missing data. Missing values are often omitted when doing any statistical analysis, but this reduces the sample size and consequently decreases the precision of estimates. In such situations, imputation is a commonly used method to deal with missing data, this involves estimating the missing values based on the observed data.
View Article and Find Full Text PDFContext: Two-thirds of metastatic differentiated thyroid cancer (DTC) patients have radioiodine (RAI)-resistant disease, resulting in poor prognosis and high mortality. For rare NTRK and RET fusion-positive metastatic, RAI-resistant thyroid cancers, variable success of re-induction of RAI avidity during treatment with NTRK or RET inhibitors has been reported.
Case Presentation And Results: We report two cases with RAI-resistant lung metastases treated with larotrectinib: an 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.
E2-conjugating enzymes (E2s) play a central role in the enzymatic cascade that leads to the attachment of ubiquitin to a substrate. This process, termed ubiquitylation, is required to maintain cellular homeostasis and affects almost all cellular process. By interacting with multiple E3 ligases, E2s dictate the ubiquitylation landscape within the cell.
View Article and Find Full Text PDFIntroduction: Sleep paralysis is a prevalent phenomenon characterized by suffocation, immobility, and hallucinations. Its causes remain unknown, although the neurotransmitter imbalance is suggested as a potential factor. This condition is closely associated with hallucinations and a sense of intrusion, often observed in patients with narcolepsy, hypertension, and seizures.
View Article and Find Full Text PDFIn this study, we address the problem of estimating the finite population mean when the non-response occurs on the characteristics under study. We propose a class of Rao-regression type estimators when ranked set sampling (RSS) procedure is used to collect the data from non-response group only and from both, the response and non-response groups. The information provided on the auxiliary variable is used at both stages i.
View Article and Find Full Text PDFPulmonary hypertension (PH) is a rare condition associated with significant morbidity and mortality. The priorities for future research in PH according to patients, caregivers, and clinicians have not been established. We performed a James Lind Alliance priority setting partnership in Canada.
View Article and Find Full Text PDFCapital investment stimulates a sizable portion of petroleum consumption, especially in emerging economies. However, investment-embedded petroleum consumption (IEPC) and the socioeconomic factors that influence it are not well studied. Our study's objective is to close this research gap.
View Article and Find Full Text PDFOf the eight distinct polyubiquitin (polyUb) linkages that can be assembled, the roles of K48-linked polyUb (K48-polyUb) are the most established, with K48-polyUb modified proteins being targeted for degradation. MINDY1 and MINDY2 are members of the MINDY family of deubiquitinases (DUBs) that have exquisite specificity for cleaving K48-polyUb, yet we have a poor understanding of their catalytic mechanism. Here, we analyze the crystal structures of MINDY1 and MINDY2 alone and in complex with monoUb, di-, and penta-K48-polyUb, identifying 5 distinct Ub binding sites in the catalytic domain that explain how these DUBs sense both Ub chain length and linkage type to cleave K48-polyUb chains.
View Article and Find Full Text PDFO-acetylserine sulfhydrylase (OASS) and cystathionine β-synthase (CBS) are members of the PLP-II family, and involved in L-cysteine production. OASS produces L-cysteine via a de novo pathway while CBS participates in the reverse transsulfuration pathway. O-acetylserine-dependent CBS (OCBS) was previously identified as a new member of the PLP-II family, which are predominantly seen in bacteria.
View Article and Find Full Text PDFProtein ubiquitylation is a dynamic post-translational modification that can be reversed by deubiquitylating enzymes (DUBs). It is unclear how the small number (∼100) of DUBs present in mammalian cells regulate the thousands of different ubiquitylation events. Here, we analysed annotated transcripts of human DUBs and found ∼300 ribosome-associated transcripts annotated as protein coding, which thus increases the total number of DUBs.
View Article and Find Full Text PDFDeubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis.
View Article and Find Full Text PDFUnlabelled: The reverse transsulfuration pathway has been reported to produce cysteine from homocysteine in eukaryotes ranging from protozoans to mammals while bacteria and plants produce cysteine via a de novo pathway. Interestingly, the bacterium Bacillus anthracis includes enzymes of the reverse transsulfuration pathway viz. cystathionine β-synthase [BaCBS, previously annotated to be an O-acetylserine sulfhydrylase (OASS)] and cystathionine γ-lyase.
View Article and Find Full Text PDFThe eight different types of ubiquitin (Ub) chains that can be formed play important roles in diverse cellular processes. Linkage-selective recognition of Ub chains by Ub-binding domain (UBD)-containing proteins is central to coupling different Ub signals to specific cellular responses. The motif interacting with ubiquitin (MIU) is a small UBD that has been characterized for its binding to monoUb.
View Article and Find Full Text PDFDeubiquitinating enzymes (DUBs) remove ubiquitin (Ub) from Ub-conjugated substrates to regulate the functional outcome of ubiquitylation. Here we report the discovery of a new family of DUBs, which we have named MINDY (motif interacting with Ub-containing novel DUB family). Found in all eukaryotes, MINDY-family DUBs are highly selective at cleaving K48-linked polyUb, a signal that targets proteins for degradation.
View Article and Find Full Text PDFPolyubiquitin chains regulate diverse cellular processes through the ability of ubiquitin to form chains of eight different linkage types. Although detected in yeast and mammals, little is known about K29-linked polyubiquitin. Here we report the generation of K29 chains in vitro using a ubiquitin chain-editing complex consisting of the HECT E3 ligase UBE3C and the deubiquitinase vOTU.
View Article and Find Full Text PDFTo better understand the poor conservation of the helicase binding domain of primases (DnaGs) among the eubacteria, we determined the crystal structure of the Helicobacter pylori DnaG C-terminal domain (HpDnaG-CTD) at 1.78 Å. The structure has a globular subdomain connected to a helical hairpin.
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