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ABSTRACT Lipids play a fundamental role in fungal cell biology, being essential cell membrane components and major targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here, we built a comprehensive map of the Histoplasma capsulatum lipid metabolic pathway by incorporating proteomic and lipidomic analyses. We performed genetic complementation and overexpression of H. capsulatum genes in Saccharomyces cerevisiae to validate reactions identified in the map and to determine enzymes responsible for catalyzing orphan reactions. The map led to the identification of both the fatty acid desaturation and the sphingolipid biosynthesis pathways as targets for drug development. We found that the sphingolipid biosynthesis inhibitor myriocin, the fatty acid desaturase inhibitor thiocarlide, and the fatty acid analog 10-thiastearic acid inhibit H. capsulatum growth in nanomolar to low-micromolar concentrations. These compounds also reduced the intracellular infection in an alveolar macrophage cell line. Overall, this lipid metabolic map revealed pathways that can be targeted for drug development. IMPORTANCE It is estimated that 150 people die per hour due to the insufficient therapeutic treatments to combat fungal infections. A major hurdle to developing antifungal therapies is the scarce knowledge on the fungal metabolic pathways and mechanisms of virulence. In this context, fungal lipid metabolism is an excellent candidate for developing drugs due to its essential roles in cellular scaffolds, energy storage, and signaling transductors. Here, we provide a detailed map of Histoplasma capsulatum lipid metabolism. The map revealed points of this fungus lipid metabolism that can be targeted for developing antifungal drugs.

BackgroundAs psychotherapy involves at least two individuals, it is essential to include the interaction perspective research. During interaction, synchrony, i.e., the occurrence of simultaneous responses, can be observed at the physiological, neural, and behavioral level. Physiological responses include heart rate and electrodermal activity; neural markers can be measured using electroencephalogram. Emotionally arousing stimuli are allocated more attentional resources (motivated attention), which is reflected in physiological activation and brain potentials. Here we present a protocol for a pilot study implementing a new research methodology, and replication of the motivated attention to emotion effect in in dyads. There is evidence that higher synchrony is associated with more positive (therapeutic) relationships. Thus, the secondary outcome will be the association between physiological and neural synchrony and subjective ratings.Methods and designIndividuals (18−30 years) will participate in same-sex pairs in two experiments. In the first experiment (triadic interaction), both participants attentively watch unpleasant, neutral and pleasant pictures, and read/listen to standardized scripts (unpleasant, neutral, and pleasant, respectively) for the imagination task. In the second experiment, participants will read out three scripts (unpleasant, neutral, pleasant) to each other, followed by a joint imagination period. Stimuli will be presented in counterbalanced orders. After each picture and imagination, participants rate their subjective arousal and valence. In the beginning and in the end of the procedure, dyads rate their relationship, sympathy, and bonds (Working Alliance Inventory subscale). Heart rate, electrodermal activity and electroencephalogram will be continuously measured during both experiments using portable devices (EcgMove4 and EdaMove4, nine-channel B-Alert X-Series mobile-wireless EEG). Synchrony analyses will include the dual electroencephalography analysis pipeline, correlational analyses and Actor–Partner Interdependence Models.DiscussionThe present study protocol provides an experimental approach to investigate interpersonal synchrony during emotion processing, allowing for the establishment of research methods in a pilot study, which can later be translated into real-life psychotherapy research. In the future, fundamental understanding of such mechanisms in dyadic interactions is essential in order to promote therapeutic relationships, and thus, treatment effectiveness and efficiency.

Several species of the Helichrysum genus have been used ethnobotanically to treat conditions that we today know have been caused by viral infections. Since HIV is a modern disease with no ethnobotanical history, we commenced with a study on the anti-HIV activity of several Helichrysum species. Drug discovery of small molecules from natural resources that is based on the integration of chemical and biological activity by means of metabolomical analyses, enables faster and a more cost-effective path to identify active compounds without the need for a long process of bioassay-guided fractionation. This study used metabolomics to identify anti-HIV compounds as biomarkers from 57 Helichrysum species in a combined study of the chemical and biological data of two previous studies. In the OPLS-DA and hierarchical cluster analyses, anti-HIV activity data was included as a secondary observation, which assisted in the correlation of the phytochemical composition and biological activity of the samples. Clear grouping revealed similarity in chemical composition and bioactivity of the samples. Based on the biological activity of polar extracts, there was a distinct phytochemical difference between active and non-active groups of extracts. This NMR-based metabolomic investigation showed that the chlorogenic acids, compounds with cinnamoyl functional groups, and quinic acid were the most prominent compounds in the Helichrysum species with anti-HIV activity. This study further revealed that the chlorogenic acid type compounds and quinic acid are biomarkers for anti-HIV activity.

Cu-doped hydroxyapatite (CuHAp) thin films were obtained using spin coating method. To make these thin films, CuHAp suspensions obtained by sol-gel method were used. The coatings obtained were thermally treated at 500 °C. After the thermal treatment, the thin films were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM). Moreover, the stability of the suspensions before being used to obtain the thin films was certified by dynamic light scattering (DLS), zeta potential methods and ultrasound measurements. In the XRD patterns, the peaks associated with hexagonal hydroxyapatite were identified in accordance with JCPDS no. 09-0432. EDS and XPS results confirmed the presence of Cu ions in the samples. Data about the morphological features and chemical composition of CuHAp thin films were obtained by performing scanning electron microscopy (SEM) measurements. Our results suggest that the CuHAp thin films surface is continuous and homogenous. The presence of the functional groups in the CuHAp thin films was confirmed by Fourier-transform infrared spectroscopy (FTIR) and Raman spectroscopy studies. Information about the surface topography of the CuHAp thin films has been obtained using atomic force microscopy (AFM). The AFM images determined that the surface topography of the CuHAp thin layer is homogenous and continuous without presenting any unevenness or fissures. The cytotoxicity of CuHAp thin films was assessed using human gingival fibroblasts (HGF-1) cells. The results of the cell viability assays demonstrated that the thin films presented good biocompatible properties towards the HGF-1 cells. Additionally, the adherence and development of HGF-1 cells on the surface of CuHAp thin films were determined using AFM. The AFM surface topographies highlighted that the CuHAp thin film's surface favored the attachment and proliferation of HGF-1 cells on their surface., (© 2024. The Author(s).)

The industrialization of agriculture has led to an increasing dependence on non-locally sourced agricultural inputs. Hence, shocks in the availability of agricultural inputs can be devastating to food crop production. There is also a pressure to decrease the use of synthetic fertilizers and pesticides in many areas. However, the combined impact of the agricultural input shocks on crop yields has not yet been systematically assessed globally. Here we modelled the effects of agricultural input shocks using a random forest machine learning algorithm. We show that shocks in fertilizers cause the most drastic yield losses. Under the scenario of 50% shock in all studied agricultural inputs, global maize production could decrease up to 26%, and global wheat production up to 21%, impacting particularly the high-yielding 'breadbasket' areas of the world. Our study provides insights into global food system resilience and can be useful for preparing for potential future shocks or agricultural input availability decreases at local and global scales., (© 2023. The Author(s).)

Despite being a topical issue in public debate and on the political agenda for many countries, a global-scale, high-resolution quantification of migration and its major drivers for the recent decades remained missing. We created a global dataset of annual net migration between 2000 and 2019 (~10 km grid, covering the areas of 216 countries or sovereign states), based on reported and downscaled subnational birth (2,555 administrative units) and death (2,067 administrative units) rates. We show that, globally, around 50% of the world's urban population lived in areas where migration accelerated urban population growth, while a third of the global population lived in provinces where rural areas experienced positive net migration. Finally, we show that, globally, socioeconomic factors are more strongly associated with migration patterns than climatic factors. While our method is dependent on census data, incurring notable uncertainties in regions where census data coverage or quality is low, we were able to capture migration patterns not only between but also within countries, as well as by socioeconomic and geophysical zonings. Our results highlight the importance of subnational analysis of migration-a necessity for policy design, international cooperation and shared responsibility for managing internal and international migration., (© 2023. The Author(s).)

Food chain contamination by soil lead (Pb), beginning with Pb uptake by leafy vegetables, is a threat to food safety and poses a potential risk to human health. This study highlights the importance of two ecologically different earthworm species (the anecic species Amynthas aspergillum and the epigeic species Eisenia fetida ) as the driving force of microbial hotspots to enhance Pb accumulation in the leafy vegetable Brassica campestris at different Pb contamination levels (0, 100, 500, and 1,000 mg·kg -1 ). The fingerprints of phospholipid fatty acids (PLFAs) were employed to reveal the microbial mechanism of Pb accumulation involving earthworm-plant interaction, as PLFAs provide a general profile of soil microbial biomass and community structure. The results showed that Gram-positive (G + ) bacteria dominated the microbial community. At 0 mg·kg -1 Pb, the presence of earthworms significantly reduced the total PLFAs. The maximum total of PLFAs was found at 100 mg·kg -1 Pb with E. fetida inoculation. A significant shift in the bacterial community was observed in the treatments with E. fetida inoculation at 500 and 1,000 mg·kg -1 Pb, where the G + /G - bacteria ratio was significantly decreased compared to no earthworm inoculation. Principal component analysis (PCA) showed that E. fetida had a greater effect on soil microbial hotspots than A. aspergillum , thus having a greater effect on the Pb uptake by B. campestris . Redundancy analysis (RDA) showed that soil microbial biomass and structure explained 43.0% (R 2  = 0.53) of the total variation in Pb uptake by B. campestris , compared to 9.51% of microbial activity. G - bacteria explained 23.2% of the total variation in the Pb uptake by B. campestris , significantly higher than the other microbes. The Mantel test showed that microbial properties significantly influenced Pb uptake by B. campestris under the driving force of earthworms. E. fetida inoculation was favorable for the G - bacterial community, whereas A. aspergillum inoculation was favorable for the fungal community. Both microbial communities facilitated the entry of Pb into the vegetable food chain system. This study delivers novel evidence and meaningful insights into how earthworms prime the microbial mechanism of Pb uptake by leafy vegetables by influencing soil microbial biomass and community composition. Comprehensive metagenomics analysis can be employed in future studies to identify the microbial strains promoting Pb migration and develop effective strategies to mitigate Pb contamination in food chains., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tibihenda, Zhong, Liu, Dai, Lin, Motelica-Heino, Hou, Zhang, Lu, Xiao and Zhang.)

Although extreme weather events recur periodically everywhere, the impacts of their simultaneous occurrence on crop yields are globally unknown. In this study, we estimate the impacts of combined hot and dry extremes as well as cold and wet extremes on maize, rice, soybean, and wheat yields using gridded weather data and reported crop yield data at the global scale for 1980-2009. Our results show that co-occurring extremely hot and dry events have globally consistent negative effects on the yields of all inspected crop types. Extremely cold and wet conditions were observed to reduce crop yields globally too, although to a lesser extent and the impacts being more uncertain and inconsistent. Critically, we found that over the study period, the probability of co-occurring extreme hot and dry events during the growing season increased across all inspected crop types; wheat showing the largest, up to a six-fold, increase. Hence, our study highlights the potentially detrimental impacts that increasing climate variability can have on global food production., (© 2023. The Author(s).)

Drinking water contamination has become a worldwide problem due to the highly negative effects that pollutants can have on human organisms and the environment. Hydroxyapatite (HAp) has the appropriate properties for the immobilization of various pollutants, being considered amongst the most cost-effective materials for water decontamination. The main objective of this study was to use synthesized hydroxyapatite for the elimination of Sr 2+ ions from contaminated solutions. The hydroxyapatite used in the decontamination process was synthesized in the laboratory using an adapted method. The hydroxyapatite powder (HAp) resulting from the synthesis was analyzed both before and after the elimination of Sr 2+ ions from contaminated solutions. The efficiency of the HAp nanoparticles in removing Sr 2+ ions from contaminated solution was determined by batch adsorption experiments. X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to study the HAp samples before and after the removal of Sr 2+ ions. The ability of HAp nanoparticles to eliminate strontium ions from contaminated solutions was established. Moreover, the removal of Sr 2+ ions from the contaminated aqueous solutions was highlighted by ultrasound measurements. The value of the stability parameter calculated by ultrasonic measurements after the removal of Sr 2+ ions from the contaminated solution was similar to that of double distilled water whose stability was used as reference. The outcomes of the batch experiments and the parameters obtained from Langmuir and Freundlich models indicated that the HAp nanoparticles had a strong affinity for the elimination of Sr 2+ ions from polluted solutions. These results emphasized that HAp nanoparticles could be excellent candidates in the development of new technologies for water remediation. More than that, the outcomes of the cytotoxic assays proved that HAp nanoparticles did not induce any noticeable harmful effects against HeLa cells and did not affect their proliferation after 1 day and 7 days of incubation.

In this White Paper, we outline recommendations from the perspective of health psychology and behavioural science, addressing three research gaps: (1) What methods in the health psychology research toolkit can be best used for developing and evaluating digital health tools? (2) What are the most feasible strategies to reuse digital health tools across populations and settings? (3) What are the main advantages and challenges of sharing (openly publishing) data, code, intervention content and design features of digital health tools? We provide actionable suggestions for researchers joining the continuously growing Open Digital Health movement, poised to revolutionise health psychology research and practice in the coming years. This White Paper is positioned in the current context of the COVID-19 pandemic, exploring how digital health tools have rapidly gained popularity in 2020-2022, when world-wide health promotion and treatment efforts rapidly shifted from face-to-face to remote delivery. This statement is written by the Directors of the not-for-profit Open Digital Health initiative (n = 6), Experts attending the European Health Psychology Society Synergy Expert Meeting (n = 17), and the initiative consultant, following a two-day meeting (19-20th August 2021).

Actin is a central mediator between mechanical force and cellular phenotype. In tendons, it is speculated that mechanical stress deprivation regulates gene expression by reducing filamentous (F)-actin. However, the mechanisms regulating tenocyte F-actin remain unclear. Tropomyosins (Tpms) are master regulators of F-actin. There are more than 40 Tpm isoforms, each having the unique capability to stabilize F-actin subpopulations. We investigated F-actin polymerization in stress-deprived tendons and tested the hypothesis that stress fiber-associated Tpm(s) stabilize F-actin to regulate cellular phenotype. Stress deprivation of mouse tail tendon down-regulated tenogenic and up-regulated protease (matrix metalloproteinase-3) mRNA levels. Concomitant with mRNA modulation were increases in G/F-actin, confirming reduced F-actin by tendon stress deprivation. To investigate the molecular regulation of F-actin, we identified that tail, Achilles, and plantaris tendons express three isoforms in common: Tpm1.6, 3.1, and 4.2. Tpm3.1 associates with F-actin in native and primary tenocytes. Tpm3.1 inhibition reduces F-actin, leading to decreases in tenogenic expression, increases in chondrogenic expression, and enhancement of protease expression in mouse and human tenocytes. These expression changes by Tpm3.1 inhibition are consistent with tendinosis progression. A further understanding of F-actin regulation in musculoskeletal cells could lead to new therapeutic interventions to prevent alterations in cellular phenotype during disease progression.

High crop yield variation between years-caused by extreme shocks on the food production system such as extreme weather-can have substantial effects on food production. This in turn introduces vulnerabilities into the global food system. To mitigate the effects of these shocks, there is a clear need to understand how different adaptive capacity measures link to crop yield variability. While existing literature provides many local-scale studies on this linkage, no comprehensive global assessment yet exists. We assessed reported crop yield variation for wheat, maize, soybean, and rice for the time period 1981-2009 by measuring both yield loss risk (variation in negative yield anomalies considering all years) and changes in yields during "dry" shock and "hot" shock years. We used the machine learning algorithm XGBoost to assess the explanatory power of selected gridded indicators of anthropogenic factors globally (i.e., adaptive capacity measures such as the human development index, irrigation infrastructure, and fertilizer use) on yield variation at a 0.5° resolution within climatically similar regions (to rule out the role of average climate conditions). We found that the anthropogenic factors explained 40%-60% of yield loss risk variation across the whole time period, whereas the factors provided noticeably lower (5%-20%) explanatory power during shock years. On a continental scale, especially in Europe and Africa, the factors explained a high proportion of the yield loss risk variation (up to around 80%). Assessing crop production vulnerabilities on global scale provides supporting knowledge to target specific adaptation measures, thus contributing to global food security., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2022. The Authors.)

Harvesting is typically size-selective, targeting large individuals. This is expected to lead to reduced average body size and earlier maturation (i.e. faster life histories). Such changes can also affect traits seemingly unrelated to harvesting, including immunocompetence. Here we test four hypotheses on how harvesting affects immunocompetence based on the pace-of-life syndrome, habitat area limitation and energy allocation and acquisition, respectively. We empirically evaluate these hypotheses using an experimental system consisting of the ectoparasite Gyrodactylus turnbulli and lines of guppies Poecilia reticulata that had been subjected to either small, random or large size-selective harvest for over 12 years. We followed the infection progression of individually infected fish for 15 days. We found significant differences between the harvested lines: fish from the small-harvested lines had the highest parasite loads. During the early phase of the infection, parasite loads were the lowest in the large-harvested lines, whereas the terminal loads were the lowest for the random-harvested lines. These results agree with the predictions from the energetic trade-off and surface area hypotheses. To our knowledge, this is the first demonstration of the consequences of size-selective harvesting on immunocompetence.

This study was aimed to evaluate the potential of four earthworm species commonly found in South China for the bioremediation of soils contaminated by Cu, Cd, Pb and Zn. Survival rates and metal accumulation of Eisenia fetida, Amynthas morrisi, A. robustus and A. corticis and changes in soil physico-chemical properties were investigated in a 60-day incubation experiment with a metal-polluted soil. At the end of the experiment, the survival rates of E. fetida, A. morrisi and A. robustus were significantly higher than that of A. corticis. Principal component analysis showed that earthworm activity improved soil quality with the averaging soil quality index being 0.66, 0.64, 0.56, 0.53, and 0.12 for the A. corticis, A. morrisi, A. robustus, E. fetida, and control treatments, respectively. The highest total available Cd, Cu, and Pb in casts were found in the treatment with A. morrisi, and this species accumulated the smallest amount of metals. Results indicate that A. morrisi may be the best candidate for earthworm-assisted bioremediation of metal contaminated soils in South China., 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 © 2022 Elsevier B.V. All rights reserved.)

Sulfur related prokaryotes residing in hot spring present good opportunity for exploring the limitless possibilities of integral ecosystem processes. Metagenomic analysis further expands the phylogenetic breadth of these extraordinary sulfur (S) metabolizing microorganisms as well as their complex metabolic networks and syntrophic interactions in environmental biosystems. Through this study, we explored and expanded the microbial genetic repertoire with focus on S cycling genes through metagenomic analysis of S contaminated hot spring, located at the Northern Himalayas. The analysis revealed rich diversity of microbial consortia with established roles in S cycling such as Pseudomonas , Thioalkalivibrio , Desulfovibrio , and Desulfobulbaceae ( Proteobacteria ). The major gene families inferred to be abundant across microbial mat, sediment, and water were assigned to Proteobacteria as reflected from the reads per kilobase (RPKs) categorized into translation and ribosomal structure and biogenesis. An analysis of sequence similarity showed conserved pattern of both dsrAB genes ( n = 178) retrieved from all metagenomes while other S disproportionation proteins were diverged due to different structural and chemical substrates. The diversity of S oxidizing bacteria (SOB) and sulfate reducing bacteria (SRB) with conserved (r) dsrAB suggests for it to be an important adaptation for microbial fitness at this site. Here, (i) the oxidative and reductive dsr evolutionary time-scale phylogeny proved that the earliest (but not the first) dsrAB proteins belong to anaerobic Thiobacillus with other ( rdsr ) oxidizers, also we confirm that (ii) SRBs belongs to δ- Proteobacteria occurring independent lateral gene transfer (LGT) of dsr genes to different and few novel lineages. Further, the structural prediction of unassigned DsrAB proteins confirmed their relatedness with species of Desulfovibrio (TM score = 0.86, 0.98, 0.96) and Archaeoglobus fulgidus (TM score = 0.97, 0.98). We proposed that the genetic repertoire might provide the basis of studying time-scale evolution and horizontal gene transfer of these genes in biogeochemical S cycling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nagar, Talwar, Motelica-Heino, Richnow, Shakarad, Lal and Negi.)

Aim and Objective: The aim of the study was to investigate how the sleep improvement interventions developed for the wards were associated with patients' sleep. The objective was to promote patients' sleep., Background: The quality of sleep is vital for patients' health and recovery from illness. However, patients generally sleep poorly during hospitalisation. Sleep-disturbing factors are connected to the hospital environment, patients' physical illness, emotional state and the activities of the staff. Many sleep-disturbing factors can be influenced by appropriate nursing interventions., Design: A two-group intervention study including the development of nursing interventions aimed at supporting patients' sleep. One group received a sleep promotion intervention and the other received standard care. Both groups evaluated their sleep in the morning., Methods: A survey of participants' sleep evaluations was collected with the five-item Richards-Campbell Sleep Questionnaire. The data were analysed statistically. The STROBE checklist was used to report the study., Results: From the participants' perspective, sleep was better in the intervention group, even though statistically significantly only among men. The pain intensity correlated with sleep quality. The number of patients in the room or whether participants had had an operation had no effect on their sleep evaluations., Conclusions: Interventions targeted at supporting and promoting the sleep quality of hospital inpatients may be effective. They should be developed in collaboration with patients and nurses. Several nursing interventions can be proposed to promote better sleep among patients; however, more research is needed to confirm the results. Sleep promotion should include both standardised protocols and individualised sleep support., Relevance to Clinical Practice: Investing in nursing interventions to promote patients' sleep is important. Patients' individual sleep-related needs should be part of their care plan. Training programmes that support nurses' knowledge and skills of patients' sleep promotion should be part of nursing education in healthcare organisations., (© 2021 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

In the context of climate change and biodiversity loss, rehabilitation of degraded urban soils is a means of limiting artificialization of terrestrial ecosystems and preventing further degradation of soils. Ecological rehabilitation approaches are available to reinitiate soil functions and enhance plant development. However, little is known about the long-term stability of rehabilitated soils in terms of soil functions when further natural or anthropogenic perturbations occur. Based on rehabilitated urban soils, the present study sought to evaluate the resistance and resilience of soil functions linked to carbon cycling and phosphate dynamics in addition to nitrogen cycling and related microbial communities after a heat and drought stress. A laboratory experiment was conducted in microcosms under controlled temperature conditions, with four contrasted soils collected from a rehabilitated urban brownfield; an initial, non-rehabilitated soil (IS), a technosol with a high organic matter level (HO), and two technosols with less organic matter (LO1 and LO2), together with their respective controls (no stress). Changes in potential denitrification (PDR), nitrification (PNR) rates, and their interactive relationships with soil microbial activities and soil physicochemical properties were determined following a combined heat (40°C) and drought stress period of 21 days. Measurements were carried out immediately after the stress (resistance), and then also 5, 30, and 92 days after soil rewetting at 60% water holding capacity (resilience). Microbial activities involved in soil functions such as carbon cycling and phosphate dynamics proved to be of low resistance in all soils except for IS; however, they were resilient and recovered rapidly after rewetting. On the other hand, the microbial activities and gene abundances that were measured in relation to nitrogen cycling processes showed that for denitrification, activities were more rapidly resilient than gene abundances whereas for nitrification the activities and gene abundances were resilient in the same way. Results suggest that, unless the soils contain high amounts of organic matter, microbial communities in imported soils can be more vulnerable to environmental pressures such as drought and heat than communities already present. This should be considered when rehabilitating degraded soils., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fikri, Joulian, Motelica-Heino, Norini and Hellal.)