Best be(e) on low fat: linking nutrient perception, regulation and fitness.

Preventing malnutrition through consuming nutritionally appropriate resources represents a challenge for foraging animals. This is due to often high variation in the nutritional quality of available resources. Foragers consequently need to evaluate different food sources. However, even the same food source can provide a plethora of nutritional and non-nutritional cues, which could serve for quality assessment. We show that bumblebees, Bombus terrestris, overcome this challenge by relying on lipids as nutritional cue when selecting pollen. The bees 'prioritised' lipid perception in learning experiments and avoided lipid consumption in feeding experiments, which supported survival and reproduction. In contrast, survival and reproduction were severely reduced by increased lipid contents. Our study highlights the importance of fat regulation for pollen foraging bumblebees. It also reveals that nutrient perception, nutrient regulation and reproductive fitness can be linked, which represents an effective strategy enabling quick foraging decisions that prevent malnutrition and maximise fitness.

Possible Effects of Volcanic Eruptions on the Modern Atmosphere of Venus.

This work reviews possible signatures and potential detectability of present-day volcanically emitted material in the atmosphere of Venus. We first discuss the expected composition of volcanic gases at present time, addressing how this is related to mantle composition and atmospheric pressure. Sulfur dioxide, often used as a marker of volcanic activity in Earth's atmosphere, has been observed since late 1970s to exhibit variability at the Venus' cloud tops at time scales from hours to decades; however, this variability may be associated with solely atmospheric processes. Water vapor is identified as a particularly valuable tracer for volcanic plumes because it can be mapped from orbit at three different tropospheric altitude ranges, and because of its apparent low background variability. We note that volcanic gas plumes could be either enhanced or depleted in water vapor compared to the background atmosphere, depending on magmatic volatile composition. Non-gaseous components of volcanic plumes, such as ash grains and/or cloud aerosol particles, are another investigation target of orbital and in situ measurements. We discuss expectations of in situ and remote measurements of volcanic plumes in the atmosphere with particular focus on the upcoming DAVINCI, EnVision and VERITAS missions, as well as possible future missions.

A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in cancer.

Linking the molecular aberrations of cancer to drug responses could guide treatment choice and identify new therapeutic applications. However, there has been no systematic approach for analyzing gene-drug interactions in human cells. Here we establish a multiplexed assay to study the cellular fitness of a panel of engineered isogenic cancer cells in response to a collection of drugs, enabling the systematic analysis of thousands of gene-drug interactions. Applying this approach to breast cancer revealed various synthetic-lethal interactions and drug-resistance mechanisms, some of which were known, thereby validating the method. NOTCH pathway activation, which occurs frequently in breast cancer, unexpectedly conferred resistance to phosphoinositide 3-kinase (PI3K) inhibitors, which are currently undergoing clinical trials in breast cancer patients. NOTCH1 and downstream induction of c-MYC over-rode the dependency of cells on the PI3K-mTOR pathway for proliferation. These data reveal a new mechanism of resistance to PI3K inhibitors with direct clinical implications.

Psoriasis and Psoriatic Arthritis Have a Major Impact on Quality of Life and Depressive Symptoms: A Cross-Sectional Study of 300 Patients.

INTRODUCTION: Psoriasis (Pso) and psoriatic arthritis (PsA) can reduce the quality of life (QoL) and are known to be associated with depression. Within this study, we aimed to assess the burden of disease, functional capacity, quality of life, and depressive symptoms and identify factors predicting functional impairment and depression in patients with psoriatic disease. METHODS: A cross-sectional survey was conducted in a cohort of 300 patients with psoriatic disease including 150 patients from a university hospital dermatology outpatient clinic and 150 patients from a university hospital rheumatology outpatient clinic. Questionnaire-based assessment of signs of arthritis (Psoriasis Epidemiology Screening Tool; PEST), functional status (Functional Questionnaire Hannover; FFbH), quality of life (World Health Organization Quality of Life Brief Version; WHOQOL-BREF), and depressive symptoms (Patient health questionnaire 9; PHQ-9) and retrospective medical chart analysis were performed. RESULTS: Despite treatment, burden of disease was high. Joint pain was reported in multiple regions in patients with Pso (n = 111) and patients with PsA (n = 189), but with differences in frequency and distribution patterns of symptoms. Functional impairment in everyday life was independently associated with diagnosis of PsA (odds ratio [OR] 9.56, p = 0.005), depressive symptoms (OR 5.44, p < 0.001) and age (OR 1.04, p = 0.033). At least mild depressive symptoms were demonstrated in 54% and 69% of patients with Pso and PsA, respectively. In a logistic regression model, depressive symptoms were independently associated with functional impairment (OR 4.50, p = 0.003), axial complaints (OR 2.80, p = 0.030), diagnosis of psoriatic arthritis (OR 2.69, p = 0.046), and number of joint regions with complaints (OR 1.10, p = 0.032). CONCLUSION: Functional impairment, QoL, and depressive symptoms are mutually interdependent. Early diagnosis of PsA and initiation of anti-inflammatory therapy are essential to avoid long-term damage, disability, and mental health complications. However, despite therapy many patients with PsA, and especially female patients, report a substantial residual disease burden due to their psoriatic disease which will need to be addressed by a more patient-centered approach.

Adding Amino Acids to a Sucrose Diet Is Not Sufficient to Support Longevity of Adult Bumble Bees.

Dietary macro-nutrients (i.e., carbohydrates, protein, and fat) are important for bee larval development and, thus, colony health and fitness. To which extent different diets (varying in macro-nutrient composition) affect adult bees and whether they can thrive on nectar as the sole amino acid source has, however, been little investigated. We investigated how diets varying in protein concentration and overall nutrient composition affected consumption, longevity, and breeding behavior of the buff-tailed bumble bee, Bombus terrestris (Hymenoptera: Apidae). Queenless micro-colonies were fed either natural nutrient sources (pollen), nearly pure protein (i.e., the milk protein casein), or sucrose solutions with low and with high essential amino acid content in concentrations as can be found in nectar. We observed micro-colonies for 110 days. We found that longevity was highest for pure pollen and lowest for pure sucrose solution and sucrose solution supplemented with amino acids in concentrations as found in the nectar of several plant species. Adding higher concentrations of amino acids to sucrose solution did only slightly increase longevity compared to sucrose alone. Consequently, sucrose solution with the applied concentrations and proportions of amino acids or other protein sources (e.g., casein) alone did not meet the nutritional needs of healthy adult bumble bees. In fact, longevity was highest and reproduction only successful in micro-colonies fed pollen. These results indicate that, in addition to carbohydrates and protein, adult bumble bees, like larvae, need further nutrients (e.g., lipids and micro-nutrients) for their well-being. An appropriate nutritional composition seemed to be best provided by floral pollen, suggesting that pollen is an essential dietary component not only for larvae but also for adult bees.

COVID-19 in a Severely Immunosuppressed Patient With Life-Threatening Eosinophilic Granulomatosis With Polyangiitis.

Immunosuppressive therapies increase the susceptibility of patients to infections. The current pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compels clinicians to develop recommendations for successful clinical management and surveillance of immunocompromised patients at high risk for severe disease progression. With only few case studies published on SARS-CoV-2 infection in patients with rheumatic diseases, we report a 25-year-old male who developed moderate coronavirus disease 2019 (COVID-19) with fever, mild dyspnea, and no major complications despite having received high-dose prednisolone, cyclophosphamide, and rituximab for the treatment of highly active, life-threatening eosinophilic granulomatosis with polyangiitis (EGPA).

Modeling MyD88 Deficiency In Vitro Provides New Insights in Its Function.

Inherited defects in MyD88 and IRAK4, two regulators in Toll-like receptor (TLR) signaling, are clinically highly relevant, but still incompletely understood. MyD88- and IRAK4-deficient patients are exceedingly susceptible to a narrow spectrum of pathogens, with ∼50% lethality in the first years of life. To better understand the underlying molecular and cellular characteristics that determine disease progression, we aimed at modeling the cellular response to pathogens in vitro. To this end, we determined the immunophenotype of monocytes and macrophages derived from MyD88- and IRAK4-deficient patients. We recognized that macrophages derived from both patients were particularly poorly activated by streptococci, indicating that both signaling intermediates are essential for the immune response to facultative pathogens. To characterize this defect in more detail, we generated induced pluripotent stem cells (iPSCs) of fibroblasts derived from an MyD88-deficient patient. The underlying genetic defect was corrected using Sleeping Beauty transposon vectors encoding either the long (L) or the short (S) MYD88 isoform, respectively. Macrophages derived from these iPSC lines (iMacs) expressed typical macrophage markers, stably produced either MyD88 isoform, and showed robust phagocytic activity. Notably, iMacs expressing MyD88-L, but not MyD88-S, exhibited similar responses to external stimuli, including cytokine release patterns, as compared to genetically normal iMacs. Thus, the two MyD88 isoforms assume distinct functions in signaling. In conclusion, iPSC technology, in combination with efficient myeloid differentiation protocols, provides a valuable and inexhaustible source of macrophages, which can be used for disease modeling. Moreover, iPSC-derived macrophages may eventually aid in stabilizing MyD88-deficient patients during pyogenic infections.

Merci mechanical thrombectomy retriever for acute ischemic stroke therapy: literature review.

BACKGROUND: Mechanical thrombectomy is a promising adjuvant or stand-alone therapy for acute ischemic stroke (AIS) caused by occlusion of a large vessel in patients beyond the systemic thrombolysis therapeutic window. This review focuses on the clinical and angiographic outcomes of mechanical thrombectomy with use of the Merci retriever device. METHODS: Available literature published to date on the major trials and observational studies involving the Merci retriever was reviewed. In addition to the review, results from studies involving the Merci retriever were compared to results from Prolyse in Acute Cerebral Thromboembolism II (PROACT II) and the Penumbra device studies. The predictors for favorable outcome following revascularization with the Merci device were reviewed on the basis of published stratified analyses. Favorable clinical outcome was defined in the Merci experience by a modified Rankin Scale (mRS) score of ≤ 2 at 90 days following AIS. RESULTS: Presented in this review are a total of 1,226 patients treated with the Merci device; 305 patients are from 2 pivotal trials involving the device, and the remaining 921 patients are from observational studies in the Merci registry. The 90-day mRS of ≤ 2 was achieved in 32% of the patient group, with an overall mortality rate of 35.2%. Symptomatic intracerebral hemorrhage was identified in 7.3% of patients treated with Merci retriever, a result comparable to that in the PROACT II and Penumbra thrombectomy trials. Successful recanalization, lower NIH Stroke Scale score, and younger age were identified as the strongest predictors of favorable outcomes. CONCLUSION: Mechanical thrombectomy with the Merci retriever device is a safe treatment modality for AIS patients presenting with a large-vessel occlusion within 8 hours of symptom onset. Although the Merci retriever showed a good recanalization rate, there are currently no randomized clinical trials to assess its clinical efficacy in comparison with systemic thrombolysis within a window of 3 to 4.5 hours or with standard of care beyond a 4.5-hour window.

Recent hotspot volcanism on Venus from VIRTIS emissivity data.

The questions of whether Venus is geologically active and how the planet has resurfaced over the past billion years have major implications for interior dynamics and climate change. Nine "hotspots"--areas analogous to Hawaii, with volcanism, broad topographic rises, and large positive gravity anomalies suggesting mantle plumes at depth--have been identified as possibly active. This study used variations in the thermal emissivity of the surface observed by the Visible and Infrared Thermal Imaging Spectrometer on the European Space Agency's Venus Express spacecraft to identify compositional differences in lava flows at three hotspots. The anomalies are interpreted as a lack of surface weathering. We estimate the flows to be younger than 2.5 million years and probably much younger, about 250,000 years or less, indicating that Venus is actively resurfacing.

Cardiac glycosides induce cell death in human cells by inhibiting general protein synthesis.

BACKGROUND: Cardiac glycosides are Na(+)/K(+)-pump inhibitors widely used to treat heart failure. They are also highly cytotoxic, and studies have suggested specific anti-tumor activity leading to current clinical trials in cancer patients. However, a definitive demonstration of this putative anti-cancer activity and the underlying molecular mechanism has remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: Using an unbiased transcriptomics approach, we found that cardiac glycosides inhibit general protein synthesis. Protein synthesis inhibition and cytotoxicity were not specific for cancer cells as they were observed in both primary and cancer cell lines. These effects were dependent on the Na(+)/K(+)-pump as they were rescued by expression of a cardiac glycoside-resistant Na(+)/K(+)-pump. Unlike human cells, rodent cells are largely resistant to cardiac glycosides in vitro and mice were found to tolerate extremely high levels. CONCLUSIONS/SIGNIFICANCE: The physiological difference between human and mouse explains the previously observed sensitivity of human cancer cells in mouse xenograft experiments. Thus, published mouse xenograft models used to support anti-tumor activity for these drugs require reevaluation. Our finding that cardiac glycosides inhibit protein synthesis provides a mechanism for the cytotoxicity of CGs and raises concerns about ongoing clinical trials to test CGs as anti-cancer agents in humans.