Data from: Peroxisomal lactate dehydrogenase is generated by basal translational readthrough in mammals

Translational readthrough gives rise to low abundance proteins with C-terminal extensions beyond the stop codon. To identify functional translational readthrough, we estimated the readthrough propensity (RTP) of all stop codon contexts of the human genome by a new regression model in silico, identified a nucleotide consensus motif for high RTP by using this model, and analyzed all readthrough extensions in silico with a new predictor for peroxisomal targeting signal type 1 (PTS1). Lactate dehydrogenase B (LDHB) showed the highest combined RTP and PTS1 probability. Experimentally we show that at least 1.6% of the total cellular LDHB getting targeted to the peroxisome by a conserved hidden PTS1. The readthrough-extended lactate dehydrogenase subunit LDHBx can also co-import LDHA, the other LDH subunit into peroxisomes. Peroxisomal LDH is conserved in mammals and likely contributes to redox equivalent regeneration in peroxisomes

The CAREPAL-8: a short screening tool for multidimensional family caregiver burden in palliative care

Abstract Background Family caregivers of terminally ill and dying people do not only experience varying levels but also different dimensions of caregiver-related strain and burden. The aim of the study was to develop a short multidimensional screening tool for the detection of burden in family caregivers in palliative care. Methods Family caregivers of cancer patients newly admitted to specialist inpatient palliative care ( N  = 232) completed questionnaires on psychological burden, quality of life, social support and need fulfillment. A latent class mixture model was used to identify discrete classes of family caregivers related to their multidimensional caregiver burden. Multinomial logistic regression analyses were performed to identify the most predictive items from a set of established questionnaires. Results Four latent classes of family caregivers were identified: Currently stable caregivers (37%), Caregivers with unmet needs (20%), Psychologically burdened caregivers (30%), and High-risk caregivers (13%). Each of these classes describes a different risk profile of multidimensional family caregiver burden, although family caregivers exhibit high levels of distress across all classes. From a set of 48 items, we identified eight items that predicted the class membership best. These items represent the items of the novel multidimensional screening tool: The 8 -item Screening Tool for Family Care giver Burden in Pal liative Care (CAREPAL-8). Except for social support, the items maintained fidelity to the conceptualization of multidimensional caregiver burden used in this study. A preliminary classification system was developed, which has yet to be validated. Conclusions This study represents the first step in the establishment of a practical, self-administered screening tool that might help healthcare providers to tailor caregiver care according to their burden in daily practice. Brevity of the 8-item tool might facilitate its use in routine clinical care

Supportive care needs and service use during palliative care in family caregivers of patients with advanced cancer: a prospective longitudinal study

Purpose: This study aimed to investigate the supportive care needs of family caregivers (FCs) of advanced cancer patients and their support service use at the beginning of specialist inpatient palliative care (SIPC), near the patient's death, and during bereavement. Methods: FCs reported their needs using the Family Inventory of Needs (FIN), along with their utilization of psychosocial and bereavement support services at the beginning (N = 232) and 6-9 months after SIPC (N = 160). Results: At the beginning of SIPC, mean of 16.9 of 20 needs were reported to be highly important, and 12.2 were reported to be met. At the time of the patient's death, 16.8 needs were highly important, and 13.8 were met. At both time points, the highest ranked need was related to information about changes in the patient's condition (100% vs. 99%), and the most frequently unmet need was related to feeling hope (73% vs. 71%). Multivariate linear regression analysis revealed a low education level to be consistently related to a greater number of highly important needs. Higher satisfaction with care and better social support was related to a greater number of met needs. Twenty-five percent of FCs had accessed at least one psychosocial support service prior to SIPC, and 30% had done so during bereavement. Among non-users of support services, > 75% indicated sufficient informal support as a barrier to service use. Conclusions: The findings offer a useful guide for adequately addressing FCs' needs in an effort to optimize FC support. However, only a subgroup of the FCs used support services. Better information and provision of tailored services might improve FCs' situations in the future

Characterization of a novel Foxa (hepatocyte nuclear factor-3) site in the glucagon promoter that is conserved between rodents and humans

The pancreatic islet hormone glucagon stimulates hepatic glucose production and thus maintains blood glucose levels in the fasting state. Transcription factors of the Foxa [Fox (forkhead box) subclass A; also known as HNF-3 (hepatocyte nuclear factor-3)] family are required for cell-specific activation of the glucagon gene in pancreatic islet α-cells. However, their action on the glucagon gene is poorly understood. In the present study, comparative sequence analysis and molecular characterization using protein–DNA binding and transient transfection assays revealed that the well-characterized Foxa-binding site in the G2 enhancer element of the rat glucagon gene is not conserved in humans and that the human G2 sequence lacks basal enhancer activity. A novel Foxa site was identified that is conserved in rats, mice and humans. It mediates activation of the glucagon gene by Foxa proteins and confers cell-specific promoter activity in glucagon-producing pancreatic islet α-cell lines. In contrast with previously identified Foxa-binding sites in the glucagon promoter, which bind nuclear Foxa2, the novel Foxa site was found to bind preferentially Foxa1 in nuclear extracts of a glucagon-producing pancreatic islet α-cell line, offering a mechanism that explains the decrease in glucagon gene expression in Foxa1-deficient mice. This site is located just upstream of the TATA box (between −30 and −50), suggesting a role for Foxa proteins in addition to direct transcriptional activation, such as a role in opening the chromatin at the start site of transcription of the glucagon gene

A new Time-of-flight detector for the R 3 B setup

© 2022, The Author(s).We present the design, prototype developments and test results of the new time-of-flight detector (ToFD) which is part of the R3B experimental setup at GSI and FAIR, Darmstadt, Germany. The ToFD detector is able to detect heavy-ion residues of all charges at relativistic energies with a relative energy precision σΔE/ ΔE of up to 1% and a time precision of up to 14 ps (sigma). Together with an elaborate particle-tracking system, the full identification of relativistic ions from hydrogen up to uranium in mass and nuclear charge is possible.11Nsciescopu