Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases

Polyketide synthases (PKSs) are biosynthetic factories that produce natural products with important biological and pharmacological activities1, 2, 3. Their exceptional product diversity is encoded in a modular architecture. Modular PKSs (modPKSs) catalyse reactions colinear to the order of modules in an assembly line3, whereas iterative PKSs (iPKSs) use a single module iteratively as exemplified by fungal iPKSs (fiPKSs)3. However, in some cases non-colinear iterative action is also observed for modPKSs modules and is controlled by the assembly line environment4, 5. PKSs feature a structural and functional separation into a condensing and a modifying region as observed for fatty acid synthases6. Despite the outstanding relevance of PKSs, the detailed organization of PKSs with complete fully reducing modifying regions remains elusive. Here we report a hybrid crystal structure of Mycobacterium smegmatis mycocerosic acid synthase based on structures of its condensing and modifying regions. Mycocerosic acid synthase is a fully reducing iPKS, closely related to modPKSs, and the prototype of mycobacterial mycocerosic acid synthase-like7, 8 PKSs. It is involved in the biosynthesis of C20–C28 branched-chain fatty acids, which are important virulence factors of mycobacteria9. Our structural data reveal a dimeric linker-based organization of the modifying region and visualize dynamics and conformational coupling in PKSs. On the basis of comparative small-angle X-ray scattering, the observed modifying region architecture may be common also in modPKSs. The linker-based organization provides a rationale for the characteristic variability of PKS modules as a main contributor to product diversity. The comprehensive architectural model enables functional dissection and re-engineering of PKSs

Exploring the status of and demand for palliative day-care clinics and day hospices in Germany: a protocol for a mixed-methods study

Background: To date, the establishment and development of palliative day-care clinics and day hospices in Germany have been completely unsystematic. Research is needed to gain insight into these services and to ensure their accessibility and quality. Accordingly, the ABPATITE research project aims at: (1) identifying the characteristics of palliative day-care clinics and day hospices in Germany, (2) determining demand and preferences for these services, and (3) proposing recommendations (with expert agreement) for the needs-based establishment and development of these services. Methods: The research is a multi-perspective, prospective, observational study following a mixed-methods approach across three study phases. In phase 1a, qualitative expert interviews will be conducted to capture the facility-related characteristics of palliative day-care clinics and day hospices in Germany; the results will feed into a questionnaire sent to all such institutions identified nationwide. In phase 1b, a questionnaire will be sent to local statutory health insurance providers, to gain insight into their contracts and accounting and remuneration models. In phase 2a, a service preference survey will be conducted with patients and family caregivers. In phase 2b, semi-structured interviews with management staff will explore the factors that promote and hinder the provision of service. In phase 2c, the external perspective will be surveyed via focus groups with local actors involved in hospice and palliative care. In phase 3a, focus groups with representatives from relevant areas will be conducted to develop recommendations. Finally, in phase 3b, recommendations will be agreed upon through a Delphi survey. Discussion: The empirically developed recommendations should enable the establishment and development of day hospices and palliative day-care clinics in Germany to be better managed, more oriented to actual demand, and more effectively integrated into wider health care services. Importantly, the findings are expected to optimize the overall development of hospice and palliative care services. Trial registratio

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world\u27s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world’s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Experiences and support needs of informal long-distance caregivers at the end of life: a scoping review

Objectives There is a lack of research on the specific experiences and needs of geographically distant kin caregivers in end-of-life situations. Clinicians and researchers would benefit from a systematic overview. The scoping review aimed at examining the international literature on the experiences and needs of informal long-distance (LD) caregivers at the end of life, to address gaps in the evidence base, and to make recommendations for further research.Design The scoping review was conducted according to the methodological framework of Arksey and O’Malley. Studies of various designs involving kin caregivers were analysed narratively.Data sources A highly sensitive strategy was used to search CINAHL, Google Scholar, PsycInfo, PubMed and Web of Science Core Collection, from inception to 8 November 2021, with searches rerun in CINAHL, PsycInfo and PubMed on 31 January 2023. An additional hand search of the reference lists of the identified articles was performed.Results Two authors independently assessed the titles and abstracts of 3827 scientific papers. As a result, 89 full texts were reviewed and 20 articles plus one review were included in the review. Five major themes were identified: (1) LD as a barrier to caregiving, (2) communication difficulties and the role of video and telephone calls, (3) the burdens and benefits of LD caregiving, (4) interaction and conflict with local caregivers and (5) LD caregivers’ wishes and needs for support.Conclusions Further quantitative and mixed-methods studies should be undertaken to improve our understanding of LD caregiving for relatives at the end of life. Studies to explore the feasibility and implementation of communication technologies in end-of-life LD caregiving are also needed

Consensus-based recommendations for psychosocial support measures for parents and adult children at the end of life: results of a Delphi study in Germany

The availability of psychosocial support measures has a significant impact on the quality of life of terminally ill and dying patients and the burden experienced by their relatives. To date, no intervention has specifically focused on promoting interaction within the dyads of the following: (1) terminally ill adult children and their parents and (2) terminally ill parents and their adult children. A national Delphi study was conducted to provide appropriate recommendations for dyadic psychosocial support measures.Recommendations were formulated from qualitative interview data on the experiences and wishes of patients and family caregivers within these two dyads. Experts from palliative and hospice care providers rated the relevance and feasibility of 21 recommendations on two 4-point Likert-type scales, respectively. Additional suggestions for improvement were captured via free text fields. Individual items were considered consented when >= 80% of participants scored 1 (strongly agree) or 2 (somewhat agree) regarding both relevance and feasibility. A total of 27 experts (35% response rate) completed two Delphi rounds. Following the first round, 13 recommendations were adjusted according to participants' comments. After the second round, consensus was achieved for all 21 of the initially presented recommendations.The Delphi-consented recommendations for parents and adult children at the end of life provide the first guidance for hands-on dyadic psychosocial support measures for parent-adult child relationships, specifically. The next step could involve the structured implementation of the recommendations, accompanied by scientific research

Exploring end-of-life interaction in dyads of parents and adult children: a protocol for a mixed-methods study

Background: A considerable number of terminally-ill adult children are outlived by at least one parent and receive palliative care prior to their death. At the same time, adult children continue to be confronted with their parents' terminal illnesses and end-of-life situations. The current study explores the specifics of dyadic interaction at the end of life between a) adult children suffering from a life-threatening disease and their parents, and b) terminally ill parents and their adult children. Methods: This prospective observational study aims at filling the existing gap on adult child-parent interaction specifics at the end of life using an exploratory mixed-methods framework. The mixed-methods framework combines a qualitative face-to face interview and quantitative self-report questionnaires to study the topic at hand. The qualitative interview will focus on experiences, expectations, and wishes with regard to dyadic communication, information about illness and prognosis, expressed and perceived burden and support as well as caregiving role at the end of life. The questionnaires will cover socio-demographics, loneliness, attachment style, social support, and emotional closeness. Discussion: The research group is currently adjusting a semi-structured interview guide and questionnaire instructions based on the results of a multiprofessional scientific advisory board meeting (Jan. 2018). In a next step, and prior to qualitative and quantitative data collection, the questionnaires will be piloted on patients and their family members in a palliative care setting. The main expected results are i) a description of the specifics of the interaction within and between both dyads, ii) the development of hypotheses and a theoretical framework on the specifics, similarities, and differences for both study groups, and iii) clinical conclusions on specific psychosocial care needs of both groups.German Federal Ministry of Education and Research (BMBF) [01GY1711]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) at a palliative care unit: A prospective single service analysis

Background The emergence of multidrug-resistant bacterial microorganisms is a particular challenge for the health care systems. Little is known about the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Gram-negative bacteria (MDRGNB) in patients of palliative care units (PCU). Aim The primary aim of this study was to determine the carriage of MRSA among patients of a PCU at a German University Hospital and to assess whether the positive cases would have been detected by a risk-factor-based screening-approach. Design Between February 2014 and January 2015 patients from our PCU were tested for MRSA carriage within 48 hours following admission irrespective of pre-existing risk factors. In addition, risk factors for MRSA colonization were assessed. Samples from the nostrils and, if applicable, from pre-existing wounds were analysed by standardized culture-based laboratory techniques for the presence of MRSA and of other bacteria and fungi. Results from swabs taken prior to admission were also recorded if available. Results 297 out of 317 patients (93.7%) fulfilled one or more MRSA screening criteria. Swabs from 299 patients were tested. The detection rate was 2.1% for MRSA. All MRSA cases would have been detected by a risk-factor-based screening-approach. Considering the detected cases and the results from swabs taken prior to admission, 4.1% of the patients (n = 13) were diagnosed with MRSA and 4.1% with MDRGNB (n = 13), including two patients with MRSA and MDRGNB (0.6%). The rate of MRSA carriage in PCU patients (4.1%) was elevated compared to the rate seen in the general cohort of patients admitted to our University Hospital (2.7%). Conclusions PCU patients have an increased risk to carry MRSA compared to other hospitalized patients. Although a risk factor-based screening is likely to detect all MRSA carriers amongst PCU patients, we rather recommend a universal screening to avoid the extra effort to identify the few risk factor-negative patients (<7%). As we did not perform a systematic MDRGNB screening, further studies are needed to determine the true prevalence of MDRGNB amongst PCU patients