Search

Mutuality, the positive quality of the relationship between the family caregiver and care receiver, is an important variable in family care for frail older adults. It has been shown to be associated with lower levels of caregiver strain and higher levels of caregiving rewards. However, the concept and measure of mutuality were developed with non-Hispanic White samples. The purpose of this article is to describe the development of an instrument—the Spanish Version of the Mutuality Scale. We determined for Mexican American families: (a) the functional equivalence of mutuality, (b) a comparative descriptive framework for mutuality, and (c) the language equivalence of the Mutuality Scale and the Spanish Version of the Mutuality Scale. Evaluating mutuality levels for Mexican American older adults and caregivers, especially in view of their strong cultural norm of familism, is essential. [ABSTRACT FROM AUTHOR]

BACKGROUND: Family caregiving researchers have explored the moderating or stress-buffering effects of variables such as coping and social support. However, the quality of the family caregiver-patient relationship and preparedness for caregiving have received little attention as potential moderators. OBJECTIVE: To explore whether relationship quality and preparedness moderate the effects of caregiving demand on caregiver outcomes during cancer treatment. METHODS: Eighty-seven family caregivers of patients receiving treatment for cancer completed the Demand and Difficulty subscales of the Caregiving Burden Scale, Mutuality and Preparedness Scales of the Family Care Inventory, and the short form of the Profile of Mood States. Using hierarchical multiple regression analyses, caregiving difficulty and total mood disturbance were regressed on two- and three-way interaction terms for demand, mutuality, and preparedness, controlling for caregiver age and gender, and the simple effect of each independent variable. RESULTS: Negligible effects for two-way interactions were found. However, the three-way interaction between demand, mutuality, and preparedness explained statistically significant variance in both perceived difficulty of caregiving and total mood disturbance. High mutuality in combination with high preparedness protected caregivers from adverse outcomes when demand was high. When either mutuality or preparedness was low, caregivers were at greater risk for negative outcomes when demand was high, but not when demand was low. When both mutuality and preparedness were low, caregivers were at risk for mood disturbance even when demand was low. DISCUSSION: Analysis of three-way interactions provided new theoretical insights into the protective effects of mutuality and preparedness and demonstrated conditions under which caregivers are at increased risk for negative outcomes. [ABSTRACT FROM AUTHOR]

Mutuality is a protective factor in family care situations, but little is known about changes in care-dyad mutuality. In this study, we examined mutuality in 103 care dyads over 20 months, and the enduring and contextual impact of older adult and family caregiver health on changes in mutuality. Care dyads consisted of frail older adults and their family caregiver. Older adults reported higher levels of mutuality than family caregivers, but their mutuality declined significantly faster over time. Although changes in physical health were more important than mean health for both older adults and family caregivers, mean depression was more important than changes in depression for older adults. This study shows the importance of examining time-varying covariates in the care dyad. [ABSTRACT FROM AUTHOR]

Conclusion: Both tinnitus masking (TM) and tinnitus retraining therapy (TRT) can be effective therapies for amelioration of tinnitus. TM may be more effective for patients in the short term, but with continued treatment TRT may produce the greatest effects. Objectives: Although TM and TRT have been used for many years, research has not documented definitively the efficacy of these methods. The present study was a controlled clinical trial to prospectively evaluate the clinical efficacy of these two methods for US military veterans with severe tinnitus. Subjects and methods: Over 800 veterans were screened to ensure that enrolled patients had tinnitus of sufficient severity to justify 18 months of individualized treatment. Qualifying patients (n=123) were placed quasi-randomly (alternating placement) into treatment with either TM or TRT. Treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated primarily using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index). Results: Findings are presented from the three written questionnaires with respect to three categories of patients: describing tinnitus as a 'moderate,' 'big,' and 'very big' problem at baseline. Based on effect sizes, both groups showed considerable improvement overall. In general, TM effects remained fairly constant over time while TRT effects improved incrementally. For the patients with a 'moderate' and 'big' problem, TM provided the greatest benefit at 3 and 6 months; benefit to these TRT patients was slightly greater at 12 months, and much greater at 18 months. For patients with a 'very big' problem, TM provided the greatest benefit at 3 months. For these latter patients, results were about the same between groups at 6 months, and improvement for TRT was much greater at 12 months, with further gains at 18 months. [ABSTRACT FROM AUTHOR]

In this validity study, using factor analysis, the authors identified three dimensions (affection, skill, and attentiveness) of the Care Receiver View of Caregiver Role Enactment Scale, a self-report measure designed to elicit an elderly care receiver's evaluation of how well their family member carried out the role of caregiver. The scale is a revision of the Satisfaction With Caregiving Scale. This study was a secondary analysis of data from PREP: Family-based Care for Frail Older Persons. Care receiver mutuality was the variable most highly correlated with caregiver role enactment. Other variables related to good quality care were higher care receiver positive affect, better caregiver physical health, and lower caregiver role strain; husband caregivers were rated as giving poorer quality care. [ABSTRACT FROM AUTHOR]

While some authors believe that testing for glucose in suctioned tracheal secretions can be used to detect aspiration of glucose-containing formula, others disagree. Previous evaluative studies of the glucose method's efficacy have lacked adequate statistical power and a gold standard for aspiration. In this animal study, a gold standard for aspiration was used and possessed sufficient statistical power to address the glucose method's sensitivity and specificity. As such, the results from the study provide the clinician with useful data to decide if the glucose method is appropriate for use in clinical settings. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of the analysis reported here was to develop the concept of family caregiving skill through qualitative analysis of interviews with caregivers of family members with cancer. DESIGN: Qualitative, grounded theory. SETTING: In-home interviews with patients recruited from private medical oncology practices and clinics in the San Francisco Bay Area. POPULATION: The majority of the caregivers were women, white, and spouses of the ill person. Caregivers had a mean age of 53 years. The majority of the persons with cancer were also women and white. Their mean age was 60. All were being treated with chemotherapy for the first time for solid tumors of lymphoma. INTERVENTIONS: The database consisted of interviews conducted by the first author in the course of two larger studies. Data collection included in-home interviews after each of the first four cycles of chemotherapy to ask about strategies used to manage side effects. MAIN OUTCOME MEASURE(S): Caregivers' accounts of how they managed specific care problems and procedures constituted the units of analysis for constant comparison. Comparing one account with others across the data set allowed us to analyze caregiving processes in relation to their results and to identify variations in these processes that appeared to be related to outcomes. The variations in how caregiving processes were carried out eventually formed the basis for indicators of caregiving skill. Sixty-three indicators of caregiving skill were identified and categorized into one of nine caregiving processes: monitoring, interpreting, making decisions, taking action, making adjustments, providing hands-on care, accessing resources, working together with the ill person, and negotiating the health care system. RESULTS/CONCLUSIONS: The indicators of caregiving skill identified in this study will comprise items for future instrument development. Conceptualization of family caregiving skill is greatly needed in nursing. The results of this study suggest an approach to clinical assessment that differs from the usual practice of determining whether caregivers are correctly following instructions. Our results suggest that brief periods of nursing instruction may not be sufficient for the development of caregiving skill. Rather, coaching for skill development may be needed. [CINAHL abstract] [ABSTRACT FROM AUTHOR]

This report presents a typology of family care actions (what family members actually say or do to help an older relative in the hospital) that was developed using Lofland and Lofland's qualitative approach. This typology provides a conceptual foundation for developing measures to assess family care actions for hospitalized elders. DESIGN: Qualitative. SETTING: Data were collected in two hospitals in a Northwest city. The interviews with older patients and their family caregivers took place in both hospital and home settings. Nurse interviews took place in the hospital. POPULATION: The purposive sample of 16 participants comprised 6 older patients, 6 family members, and 4 registered nurses. Patients included were 65 years of age or older. Family caregivers were 18 years of age or older. Nurses who worked in the study units either had more than one shift experience in caring for the patient participants or were identified by the unit nurse managers as experienced nurses who had worked with older patients and their families. INTERVENTIONS: Altogether 25 semi-structured interviews were conducted. The interviews with older patients and their family caregivers took place in both hospital and home settings. Probes were used to elicit the details of family care during different phases in various hospital settings. Patients were asked to describe the nature of the help received from their family members. Participant observation took place in the hospital setting. Transcribed interviews and participant observation notes were analyzed for descriptive comments. MAIN OUTCOME MEASURE(S): Analysis revealed three conceptually distinct dimensions of family care actions and eight categories of caregiving within the dimensions. Only one of the three dimensions, providing care to patients, includes categories of what generally has been considered in the literature to be caregiving for hospitalized elders. The other two dimensions - working together with HCT (health care team) and taking care of self, are somewhat 'invisible' or hidden behaviors that are not emphasized as dimensions or categories of family care in existing literature. However, our findings suggested that they might be processes crucial to an understanding of family care for hospitalized elders and to establishing partnerships between family caregivers and hospital caregivers. RESULTS/CONCLUSIONS: On the basis of these findings, a self-report method has been selected to measure the type and extent of Family Care Actions. Future studies are needed to compare family care for hospitalized elders with care for those who are in the young-old and old-old age groups as well as for ethnically diverse families. Findings about the nature of family care for hospitalized elders may enable nurses to improve the way they work together with families in the acute care setting. [CINAHL abstract] [ABSTRACT FROM AUTHOR]

The study reported here explored similarities and differences between 103 family caregivers of older persons who had been discharged from the hospital and 70 caregivers of terminally ill older persons receiving hospice care. Caregiving variables were selected for examination based on role theory. Major findings include: hospice caregivers provided significantly more personal care and medically related tasks, significantly fewer transportation tasks, and worried less than the post-hospitalized sample. Otherwise, the two groups were strikingly similar. Similar patterns of correlations for the two groups were also found. [ABSTRACT FROM AUTHOR]

Nonhuman primates (NHPs) are pivotal for unlocking the complexities of human cognition, yet traditional cognitive studies remain constrained to specialized laboratories. To revolutionize this paradigm, we present CalliCog : an open-source, scalable in-cage platform tailored for freely behaving experiments in small primate species such as the common marmoset ( Callithrix jacchus ). CalliCog includes modular operant chambers that operate autonomously and integrate seamlessly with home cages, eliminating human intervention. Our results showcase the power of CalliCog to train experimentally naïve marmosets in touchscreen-based cognitive tasks. Remarkably, across two independent facilities, marmosets achieved touchscreen proficiency within two weeks and successfully completed tasks probing behavioral flexibility and working memory. Moreover, CalliCog enabled precise synchronization of behavioral data with electrocorticography (ECoG) recordings from freely moving animals, opening new frontiers for neurobehavioral research. By making CalliCog openly accessible, we aim to democratize cognitive experimentation with small NHPs, narrowing the translational gap between preclinical models and human cognition., Motivation: Cognitive neuroscience research involving nonhuman primates (NHPs) has traditionally been confined to a few highly specialized laboratories equipped with advanced infrastructure, expert knowledge, and specialized resources for housing and testing these animals. The common marmoset ( Callithrix jacchus ), a small NHP species, has gained popularity in cognitive research due to its ability to address some of these challenges. However, behavioral studies in marmosets remain labor-intensive and restricted mainly to experts in the field, making them less accessible to the broader scientific community. To address these barriers, we introduce an open and accessible platform designed for automated cognitive experiments in home cage settings with marmosets. This system supports the integration of cognitive behavioral analysis with wireless neural recordings, is cost-effective, and requires minimal technical expertise to build and operate.

Organ shortage is a major challenge in kidney transplantation but the use of older donors, often with co-morbidities, is hampered by inconsistent outcomes. Methods of accurately stratifying marginal donor organs by clinical and histological assessment are lacking. To better understand organ variability, we profiled the transcriptomes of 271 kidneys from deceased donors at retrieval. Following correction for biopsy composition, we assessed molecular pathways that associated with delayed, and sub-optimal one-year graft function. Analysis of cortical biopsies identified an adaptive immune gene-rich module that significantly associated with increasing age and worse outcomes. Cellular deconvolution using human kidney reference single cell transcriptomes confirmed an increase in kidney-specific B and T cell signatures, as well as kidney macrophage, myofibroblast and fibroblast gene sets in this module. Surprisingly, innate immune pathway and neutrophil gene signature enrichment was associated with better outcomes. Thus, our work uncovers cellular molecular features of pathological organ ageing, identifiable at kidney retrieval, with translational potential., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Many studies have attempted to determine methodology for interpreting change on outcome instruments that result from an intervention. The objective of these studies has been to devise methods to identify the minimal level of change that would be consistent with actual benefit perceived by the patient, and not just statistically significant change. With respect to intervention for bothersome tinnitus, the authors of the original study to develop and validate the Tinnitus Functional Index (TFI) suggested that a minimum 13-point reduction in the TFI score was likely to reflect a change perceived as meaningful to an individual. The 13-point estimation of meaningful change for an individual is appropriate for use with any adult seeking care for tinnitus. However, it cannot be relied upon in isolation to determine if an individual believes that there has been a noticeable, or meaningful improvement in their quality of life. It is important to use subjective impressions elicited from the patient to assist in interpreting the meaning of TFI data for an individual. For clinicians engaging in care for tinnitus, we recommend using the TFI and pairing it with the patient's belief/impression as to whether they are doing better than they were before care for tinnitus was provided. Ideally, the outcome assessment would be conducted by someone other than the clinician who provided the intervention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

During kidney development, nephron epithelia arise de novo from fate-committed mesenchymal progenitors through a mesenchymal-to-epithelial transition (MET). Downstream of fate specification, transcriptional mechanisms that drive establishment of epithelial morphology are poorly understood. We used human iPSC-derived renal organoids, which recapitulate nephrogenesis, to investigate mechanisms controlling renal MET. Multi-ome profiling via snRNA-seq and ATAC-seq of organoids identified dynamic changes in gene expression and chromatin accessibility driven by activators and repressors throughout MET. CRISPR interference identified that paired box 8 (PAX8) is essential for initiation of MET in human renal organoids, contrary to in vivo mouse studies, likely by activating a cell-adhesion program. While Wnt/β-catenin signaling specifies nephron fate, we find that it must be attenuated to allow hepatocyte nuclear factor 1-beta (HNF1B) and TEA-domain (TEAD) transcription factors to drive completion of MET. These results identify the interplay between fate commitment and morphogenesis in the developing human kidney, with implications for understanding both developmental kidney diseases and aberrant epithelial plasticity following adult renal tubular injury., Competing Interests: Declaration of interests J.M.W. is an employee and stockholder of AstraZeneca., (Copyright © 2024 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.)

Harmonizing cell types across the single-cell community and assembling them into a common framework is central to building a standardized Human Cell Atlas. Here, we present CellHint, a predictive clustering tree-based tool to resolve cell-type differences in annotation resolution and technical biases across datasets. CellHint accurately quantifies cell-cell transcriptomic similarities and places cell types into a relationship graph that hierarchically defines shared and unique cell subtypes. Application to multiple immune datasets recapitulates expert-curated annotations. CellHint also reveals underexplored relationships between healthy and diseased lung cell states in eight diseases. Furthermore, we present a workflow for fast cross-dataset integration guided by harmonized cell types and cell hierarchy, which uncovers underappreciated cell types in adult human hippocampus. Finally, we apply CellHint to 12 tissues from 38 datasets, providing a deeply curated cross-tissue database with ∼3.7 million cells and various machine learning models for automatic cell annotation across human tissues., Competing Interests: Declaration of interests S.A.T. is a remunerated member of the Scientific Advisory Board, Foresite Labs, and Qiagen. She is co-founder and equity holder of Transition Bio., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ensuring the validity of results from funded programs is a critical concern for agencies that sponsor biological research. In recent years, the open science movement has sought to promote reproducibility by encouraging sharing not only of finished manuscripts but also of data and code supporting their findings. While these innovations have lent support to third-party efforts to replicate calculations underlying key results in the scientific literature, fields of inquiry where privacy considerations or other sensitivities preclude the broad distribution of raw data or analysis may require a more targeted approach to promote the quality of research output. Methods: We describe efforts oriented toward this goal that were implemented in one human performance research program, Measuring Biological Aptitude, organized by the Defense Advanced Research Project Agency's Biological Technologies Office. Our team implemented a four-pronged independent verification and validation (IV&V) strategy including 1) a centralized data storage and exchange platform, 2) quality assurance and quality control (QA/QC) of data collection, 3) test and evaluation of performer models, and 4) an archival software and data repository. Results: Our IV&V plan was carried out with assistance from both the funding agency and participating teams of researchers. QA/QC of data acquisition aided in process improvement and the flagging of experimental errors. Holdout validation set tests provided an independent gauge of model performance. Conclusions: In circumstances that do not support a fully open approach to scientific criticism, standing up independent teams to cross-check and validate the results generated by primary investigators can be an important tool to promote reproducibility of results., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Drocco JA et al.)

Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here, we show that individuals 70 years or older (median age 73, range 70-75) who received a primary two-dose schedule with AZD1222 and booster third dose with mRNA vaccine achieve significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared with those younger than 70 (median age 66, range 54-69) at 1 month post booster. Impaired neutralization potency and breadth post third dose in the elderly is associated with circulating "atypical" spike-specific B cells expressing CD11c and FCRL5. However, when considering individuals who received three doses of mRNA vaccine, we did not observe differences in neutralization or enrichment in atypical B cells. This work highlights the finding that AdV and mRNA COVID-19 vaccine formats differentially instruct the memory B cell response., Competing Interests: Declaration of interests R.K.G. has received honoraria for consulting and educational activities from Gilead, GSK, Janssen, and Moderna., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The binding of transcription factors at proximal promoters and distal enhancers is central to gene regulation. Identifying regulatory motifs and quantifying their impact on expression remains challenging. Using a convolutional neural network trained on single-cell data, we infer putative regulatory motifs and cell type-specific importance. Our model, scover, explains 29% of the variance in gene expression in multiple mouse tissues. Applying scover to distal enhancers identified using scATAC-seq from the developing human brain, we identify cell type-specific motif activities in distal enhancers. Scover can identify regulatory motifs and their importance from single-cell data where all parameters and outputs are easily interpretable., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSCs) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) in the vicinity of HRSCs express similar regulatory mechanisms in parallel, and their presence in tissue is associated with inferior patient outcomes. MNPs in cHL have hitherto been identified by a small number of canonical markers and are usually described as tumor-associated macrophages. The organization of MNP networks and interactions with HRSCs remains unexplored at high resolution. Here, we defined the global immune-cell composition of cHL and nonlymphoma lymph nodes, integrating data across single-cell RNA sequencing, spatial transcriptomics, and multiplexed immunofluorescence. We observed that MNPs comprise multiple subsets of monocytes, macrophages, and dendritic cells (DCs). Classical monocytes, macrophages and conventional DC2s were enriched in the vicinity of HRSCs, but plasmacytoid DCs and activated DCs were excluded. Unexpectedly, cDCs and monocytes expressed immunoregulatory checkpoints PD-L1, TIM-3, and the tryptophan-catabolizing protein IDO, at the same level as macrophages. Expression of these molecules increased with age. We also found that classical monocytes are important signaling hubs, potentially controlling the retention of cDC2 and ThExh via CCR1-, CCR4-, CCR5-, and CXCR3-dependent signaling. Enrichment of the cDC2-monocyte-macrophage network in diagnostic biopsies is associated with early treatment failure. These results reveal unanticipated complexity and spatial polarization within the MNP compartment, further demonstrating their potential roles in immune evasion by cHL., (© 2023 by The American Society of Hematology.)

In family caregiving interventions for adults with health problems, tailoring has become the norm. Studies that evaluate tailored interventions, however, have rarely included intentional variation in dosage or explored the dosage-outcome association. In this Part 1 secondary analysis, we examine dosage and outcomes in intervention families ( N = 116) who participated in the Oregon Health & Science University/Kaiser Permanente Northwest Region Family Care Study. The Family Care Study was a randomized controlled trial to evaluate the preparedness, skill, enrichment, and predictability (PREP) intervention with caregiving families of frail older adults referred for skilled home health. Tailoring of PREP began with assessment by the PREP nurse. Families then identified and selected care-related issues to work on with their PREP nurse; family needs and preferences guided the number and timing of nurse visits and calls. Families selected a median of 3 (range = 0 to 10) care-related issues in five categories: direct care (chosen by 57% of families), transitions (40%), caregiver strain and health (40%), arranging care (33%), and enrichment (22%). The number of issues strongly predicted number of PREP nurse visits and calls, whereas nurse visits in turn predicted caregivers' reports of improved family care and usefulness of home health assistance, highlighting the importance of visits for achieving outcomes. [ Research in Gerontological Nursing, 16 (2), 57-70.].

Family caregivers frequently use health and social services to support their caregiving. In evaluating care-giving interventions, however, researchers rarely examine the influences of such concurrent services on intervention effectiveness. In this Part 2 secondary analysis of data from the Oregon Health & Science University/Kaiser Permanente Northwest Region Family Care Study, we examined the moderating influences of concurrent services on intervention effectiveness. The Family Care Study was a randomized controlled trial to evaluate the preparedness, skill, enrichment, and predictability (PREP) intervention with caregivers of frail older adults referred for skilled home health. Compared with control caregivers receiving usual home health care ( n = 103), PREP intervention caregivers ( n = 104) reported greater improvements in family care (effect size, d = 0.58). We conducted follow-up analyses to determine whether PREP was differentially effective depending on whether dyads received concurrent Social Health Maintenance Organization (SHMO) services, concurrent hospice services, or neither. In the 55% of dyads not receiving SHMO or hospice, we found that PREP's effects were large compared to usual care ( d = 1.16, p < 0.001). PREP's effects were not significant for dyads receiving concurrent SHMO or hospice services. Results highlight the strong benefits of hospice for control dyads, but reveal difficulties in evaluating intervention effectiveness when dyads receive concurrent services. [ Research in Gerontological Nursing, 16 (2), 71-83.].

Accelerator mass spectrometry (AMS) is the method of choice for quantitation of low amounts of 14 C-labeled biomolecules. Despite exquisite sensitivity, an important limitation of AMS is its inability to provide structural information about the analyte. This limitation is not critical when the labeled compounds are well-characterized prior to AMS analysis. However, analyte identity is important in other experiments where, for example, a compound is metabolized and the structures of its metabolites are not known. We previously described a moving wire interface that enables direct AMS measurement of liquid sample in the form of discrete drops or HPLC eluent without the need for individual fraction collection, termed liquid sample-AMS (LS-AMS). We now report the coupling of LS-AMS with a molecular mass spectrometer, providing parallel accelerator and molecular mass spectrometry (PAMMS) detection of analytes separated by liquid chromatography. The repeatability of the method was examined by performing repeated injections of 14 C-labeled tryptophan, and relative standard deviations of the 14 C peak areas were ≤10.57% after applying a normalization factor based on a standard. Five 14 C-labeled amino acids were separated and detected to provide simultaneous quantitative AMS and structural MS data, and AMS results were compared with solid sample-AMS (SS-AMS) data using Bland-Altman plots. To demonstrate the utility of the workflow, yeast cells were grown in a medium with 14 C-labeled tryptophan. The cell extracts were analyzed by PAMMS, and 14 C was detected in tryptophan and its metabolite kynurenine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Inborn errors of immunity (IEIs) unveil regulatory pathways of human immunity. We describe a new IEI caused by mutations in the GTPase of the immune-associated protein 6 (GIMAP6) gene in patients with infections, lymphoproliferation, autoimmunity, and multiorgan vasculitis. Patients and Gimap6-/- mice show defects in autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)-containing lipids. We find that GIMAP6 complexes with GABARAPL2 and GIMAP7 to regulate GTPase activity. Also, GIMAP6 is induced by IFN-γ and plays a critical role in antibacterial immunity. Finally, we observed that Gimap6-/- mice died prematurely from microangiopathic glomerulosclerosis most likely due to GIMAP6 deficiency in kidney endothelial cells., (This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.)

There is an increasing appreciation that many innate and adaptive immune cell subsets permanently reside within non-lymphoid organs, playing a critical role in tissue homeostasis and defense. The best characterized are macrophages and tissue-resident T lymphocytes that work in concert with organ structural cells to generate appropriate immune responses and are functionally shaped by organ-specific environmental cues. The interaction of tissue epithelial, endothelial and stromal cells is also required to attract, differentiate, polarize and maintain organ immune cells in their tissue niche. All of these processes require dynamic regulation of cellular transcriptional programmes, with epigenetic mechanisms playing a critical role, including DNA methylation and post-translational histone modifications. A failure to appropriately regulate immune cell transcription inevitably results in inadequate or inappropriate immune responses and organ pathology. Here, with a focus on the mammalian kidney, an organ which generates differing regional environmental cues (including hypersalinity and hypoxia) due to its physiological functions, we will review the basic concepts of tissue immunity, discuss the technologies available to profile epigenetic modifications in tissue immune cells, including those that enable single-cell profiling, and consider how these mechanisms influence the development, phenotype, activation and function of different tissue immune cell subsets, as well as the immunological function of structural cells., (© 2021 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.)

Parallel accelerator and molecular mass spectrometry (PAMMS) is a powerful analytical technique capable of simultaneous quantitation of carbon-14 tracer and structural characterization of 14 C-labeled biomolecules. Here we describe the use of PAMMS for the analysis of biological molecules separated by high-performance liquid chromatography. This protocol is intended to serve as a guide for researchers who need to perform PAMMS experiments using instrumentation available at resource centers such as the National User Resource for Biological Accelerator Mass Spectrometry at Lawrence Livermore National Laboratory., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Langerhans cells (LC) are skin-resident antigen-presenting cells that regulate immune responses to epithelial microorganisms. Human papillomavirus (HPV) infection can promote malignant epithelial transformation. As LCs are considered important for controlling HPV infection, we compared the transcriptome of murine LCs from skin transformed by K14E7 oncoprotein and from healthy skin. We identified transcriptome heterogeneity at the single cell level amongst LCs in normal skin, associated with ontogeny, cell cycle, and maturation. We identified a balanced co-existence of immune-stimulatory and immune-inhibitory LC cell states in normal skin that was significantly disturbed in HPV16 E7-transformed skin. Hyperplastic skin was depleted of immune-stimulatory LCs and enriched for LCs with an immune-inhibitory gene signature, and LC-keratinocyte crosstalk was dysregulated. We identified reduced expression of interleukin (IL)-34, a critical molecule for LC homeostasis. Enrichment of an immune-inhibitory LC gene signature and reduced levels of epithelial IL-34 were also found in human HPV-associated cervical epithelial cancers., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)