Targeting genomic SARS-CoV-2 RNA with siRNAs allows efficient inhibition of viral replication and spread.

A promising approach to tackle the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) could be small interfering (si)RNAs. So far it is unclear, which viral replication steps can be efficiently inhibited with siRNAs. Here, we report that siRNAs can target genomic RNA (gRNA) of SARS-CoV-2 after cell entry, and thereby terminate replication before start of transcription and prevent virus-induced cell death.

Molecular Prognostic Factors for Distant Metastases in Premenopausal Patients with HR+/HER2- Early Breast Cancer.

Molecular factors that drive metastasis in premenopausal patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), early breast cancer (EBC) are largely unknown. To identify markers/signatures contributing to metastasis, we analyzed molecular changes in tumors from premenopausal patients who developed metastasis (M1) and who did not (M0). Ninety-seven premenopausal patients with HR+/HER2- EBC were included (M1, = 48, median distant metastasis-free survival (DMFS): 54 (7-184) months; M0, = 49, median follow-up: 149 (121-191) months).

Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'.

The in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients.

Biomarkers for Comorbidities Modulate the Activity of T-Cells in COPD.

In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by comorbidities.

Prevention of COVID-19 in Thoracic Surgery Patients: Lessons Learned during the First Pandemic Wave.

Background:  The aim of this retrospective study was to investigate the implementation of measures to prevent perioperative COVID-19 in thoracic surgery during the first wave of the COVID-19 pandemic 2020 allowing a continued surgical treatment of patients.

Methods:  The implemented preventive measures in patient management of the thoracic surgery department of the Asklepios Lung Clinic Munich-Gauting, Germany were retrospectively analyzed. Postoperative COVID-19 incidence before and after implementation of preventive measures was investigated.

Regulation of the microsomal proteome by salicylic acid and deficiency of phosphatidylinositol-4-kinases β1 and β2 in Arabidopsis thaliana.

Phosphatidylinositol-4-kinases β1 and β2 (PI4Kβ1/PI4Kβ2), which are responsible for phosphorylation of phosphatidylinositol to phosphatidylinositol-4-phosphate, have important roles in plant vesicular trafficking. Moreover, PI4Kβ1/PI4Kβ2 negatively regulates biosynthesis of phytohormone salicylic acid (SA), a key player in plant immune responses. The study focused on the effect of PI4Kβ1/PI4Kβ2 deficiency and SA level on the proteome of microsomal fraction.

Switch from IL-5 to IL-5-Receptor α Antibody Treatment in Severe Eosinophilic Asthma.

Background: Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5Rα therapy in patients with inadequate response to anti-IL-5 therapy.

Methods: In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5Rα therapy due to inadequate response or intolerability.

Intra-Individual Behavioural Variability: A Trait under Genetic Control.

When individuals are measured more than once in the same context they do not behave in exactly the same way each time. The degree of predictability differs between individuals, with some individuals showing low levels of variation around their behavioural mean while others show high levels of variation. This intra-individual variability in behaviour has received much less attention than between-individual variability in behaviour, and very little is known about the underlying mechanisms that affect this potentially large but understudied component of behavioural variation.

Dupilumab Improves Asthma Control and Lung Function in Patients with Insufficient Outcome During Previous Antibody Therapy.

Background: Biological treatments directed against IgE and IL-5 have largely improved outcomes for patients with severe type 2-high asthma. However, a fraction of patients with severe asthma show insufficient treatment outcome under anti-IgE and anti-IL-5/IL-5 receptor α antibodies.

Objective: To evaluate whether switching to dupilumab was of benefit in patients with insufficient outcome under previous anti-IgE or anti-IL-5/IL-5 receptor α therapy.

Exposure to welding fumes suppresses the activity of T-helper cells.

Welders have an increased susceptibility to airway infections with non-typeable Haemophilus influenzae (NTHi), which implicates immune defects and might promote pneumonia and chronic obstructive pulmonary disease (COPD). We hypothesized that welding-fume exposure suppresses Th1-lymphocyte activity. Non-effector CD4 T-cells from blood of 45 welders (n = 23 gas metal arc welders, GMAW; n = 16 tungsten inert gas welders, TIG; n = 6 others) and 25 non-welders were ex vivo activated towards Th1 via polyclonal T-cell receptor stimulation and IL-12 (first activation step) and then stimulated with NTHi extract or lipopolysaccharide (LPS) (second activation step).

Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab?

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a severe hypersensitivity reaction to aspergillus species colonizing the airways of patients with asthma or cystic fibrosis. Biologics including anti-IgE and anti-IL5 antibodies have strongly changed the treatment of severe asthmatics and have partly been reported to be effective in the treatment of ABPA. Recently, dupilumab, an anti-IL4-Rα antibody which inhibits signaling by the Th2-cytokines IL4 and IL13, has been approved for the treatment of severe asthma.

Triangulating Neanderthal cognition: A tale of not seeing the forest for the trees.

The inference of Neanderthal cognition, including their cultural and linguistic capabilities, has persisted as a fiercely debated research topic for decades. This lack of consensus is substantially based on inherent uncertainties in reconstructing prehistory out of indirect evidence as well as other methodological limitations. Further factors include systemic difficulties within interdisciplinary discourse, data artifacts, historic research biases, and the sheer scope of the relevant research.

A combined and model shows specific predictors of individual trans-generational diabetic programming.

Diabetic pregnancies are cleary associated with maternal type 2 diabetes and metabolic syndrome as well as atherosclerotic diseases in the offspring. The global prevalence of hyperglycemia in pregnancy was estimated as 15.8% of live births to women in 2019, with an upward trend.

Impact of SARS-CoV-2 pandemic on pulmonary hypertension out-patient clinics in Germany: a multi-centre study.

Pulmonary hypertension is frequently underdiagnosed, and referral is delayed with subsequent impact on outcomes. During the SARS-CoV-2 pandemic, restrictions on daily life and changes in hospitals' daily routine care were introduced in Germany. This multi-centre study provides evidence for a negative influence of these restrictions on patient care in pulmonary hypertension expert referral centres.

CLUE: a bioinformatic and wet-lab pipeline for multiplexed cloning of custom sgRNA libraries.

The systematic perturbation of genomes using CRISPR/Cas9 deciphers gene function at an unprecedented rate, depth and ease. Commercially available sgRNA libraries typically contain tens of thousands of pre-defined constructs, resulting in a complexity challenging to handle. In contrast, custom sgRNA libraries comprise gene sets of self-defined content and size, facilitating experiments under complex conditions such as in vivo systems.

An inverted U-shaped curve relating farmland vulnerability to biological disasters: Implications for sustainable intensification in China.

Sustainable farmland intensification is necessary in order to harmonize relationships between food security, socioeconomic development, and ecological civilization. However, the degradation of farmland sustainability because of biological disasters represents a major challenge if we are to achieve this intensification. Our understanding of farmland vulnerability to biological disasters (FVBD) remains relatively rudimentary and subjective, limiting its effectiveness as a tool for farmland sustainability analysis.

Disrupted actin: a novel player in pathogen attack sensing?

The actin cytoskeleton is widely involved in plant immune responses. The majority of studies show that chemical disruption of the actin cytoskeleton increases plant susceptibility to pathogen infection. Similarly, several pathogens have adopted this as a virulence strategy and produce effectors that affect cytoskeleton integrity.

An ocular glymphatic clearance system removes β-amyloid from the rodent eye.

Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified an ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve in rodents. β-amyloid (Aβ) was cleared from the retina and vitreous via a pathway dependent on glial water channel aquaporin-4 (AQP4) and driven by the ocular-cranial pressure difference.

Aquaporin 1 and the Na/K/2Cl cotransporter 1 are present in the leptomeningeal vasculature of the adult rodent central nervous system.

Background: The classical view of cerebrospinal fluid (CSF) production posits the choroid plexus as its major source. Although previous studies indicate that part of CSF production occurs in the subarachnoid space (SAS), the mechanisms underlying extra-choroidal CSF production remain elusive. We here investigated the distributions of aquaporin 1 (AQP1) and Na/K/2Cl cotransporter 1 (NKCC1), key proteins for choroidal CSF production, in the adult rodent brain and spinal cord.

Age- and sex-dependent differences in patients with severe asthma included in the German Asthma Net cohort.

Background: Severe asthma affects less than 5% of asthmatics, but is associated with high costs and increased mortality. The aim of this study was to assess age- and sex-dependent differences in this patient group.

Methods: Retrospective analysis of 1317 children and adults with severe asthma who are included in the German Asthma Net registry.

"Salicylic Acid Mutant Collection" as a Tool to Explore the Role of Salicylic Acid in Regulation of Plant Growth under a Changing Environment.

The phytohormone salicylic acid (SA) has a crucial role in plant physiology. Its role is best described in the context of plant response to pathogen attack. During infection, SA is rapidly accumulated throughout the green tissues and is important for both local and systemic defences.

LABAs and p38MAPK Inhibitors Reverse the Corticosteroid-Insensitivity of IL-8 in Airway Smooth Muscle Cells of COPD.

Airway inflammation in chronic obstructive pulmonary disease (COPD) is partially insensitive/resistant to inhaled corticosteroids (ICS). ICS plus bronchodilator therapy has been discussed for COPD phenotypes with frequent exacerbations and participation of corticosteroid-sensitive type 2/eosinophilic inflammation. Neutralization of non-type 2/IL-8-associated airway inflammation by reversion of its corticosteroid-resistance might be a future strategy for other phenotypes.

Distinct metabolic adaptation of liver circadian pathways to acute and chronic patterns of alcohol intake.

Binge drinking and chronic exposure to ethanol contribute to alcoholic liver diseases (ALDs). A potential link between ALDs and circadian disruption has been observed, though how different patterns of alcohol consumption differentially impact hepatic circadian metabolism remains virtually unexplored. Using acute versus chronic ethanol feeding, we reveal differential reprogramming of the circadian transcriptome in the liver.