Chemical Space for Peptide-based Antimicrobials.

Multidrug-resistant (MDR) bacteria represent a global public health threat, and antimicrobial peptides (AMPs), derived from naturally occurring linear or cyclic peptides, can provide the solution. However, most AMPs are sensitive to proteases and have poor pharmacokinetics. The EU-funded ERC Advanced Grant SPACE4AMPS aims to identify new AMPs by applying the concepts of chemical space and ligand-based virtual screening, which are well known for small molecule drug discovery, to the world of peptides.

Stereorandomized Oncocins with Preserved Ribosome Binding and Antibacterial Activity.

We recently showed that solid-phase peptide synthesis using racemic amino acids yields stereorandomized peptides comprising all possible diastereomers as homogeneous, single-mass products that can be purified by HPLC and that stereorandomization modulates activity, toxicity, and stability of membrane-disruptive cyclic and linear antimicrobial peptides (AMPs) and dendrimers. Here, we tested if stereorandomization might be compatible with target binding peptides with the example of the proline-rich AMP oncocin, which inhibits the bacterial ribosome. Stereorandomization of up to nine -terminal residues preserved ribosome binding and antibacterial effects including activities against drug-resistant bacteria and protected against serum degradation.

Let the dust settle: Impact of enhanced rock weathering on soil biological, physical, and geochemical fertility.

Terrestrial enhanced rock weathering (ERW) is a promising carbon dioxide removal technology that consists in applying ground silicate rock such as basalt on agricultural soils. On top of carbon sequestration, ERW has the potential to raise the soil pH and release nutrients, thereby improving soil fertility. Despite these possible co-benefits, concerns such as heavy metal pollution or soil structure damage have also been raised.

Patient-Reported Experiences of Persistent Post-COVID-19 Conditions After Hospital Discharge During the Second and Third Waves of the Pandemic in Switzerland: Cross-Sectional Questionnaire Study.

Background: Hospitalized patients infected with SARS-CoV-2 should recover within a few weeks. However, even those with mild versions can experience symptoms lasting 4 weeks or longer. These post-COVID-19 condition (PCC) comprise various new, returning, or ongoing symptoms that can last for months or years and cause disability.

State Expansion of a Levitated Nanoparticle in a Dark Harmonic Potential.

We spatially expand and subsequently contract the motional thermal state of a levitated nanoparticle using a hybrid trapping scheme. The particle's center-of-mass motion is initialized in a thermal state (temperature 155 mK) in an optical trap and then expanded by subsequent evolution in a much softer Paul trap in the absence of optical fields. We demonstrate expansion of the motional state's standard deviation in position by a factor of 24.

Bulk-suppressed and surface-sensitive Raman scattering by transferable plasmonic membranes with irregular slot-shaped nanopores.

Raman spectroscopy enables the non-destructive characterization of chemical composition, crystallinity, defects, or strain in countless materials. However, the Raman response of surfaces or thin films is often weak and obscured by dominant bulk signals. Here we overcome this limitation by placing a transferable porous gold membrane, (PAuM) on the surface of interest.

Antimicrobial Peptide-Peptoid Hybrids with and without Membrane Disruption.

Among synthetic analogues of antimicrobial peptides (AMPs) under investigation to address antimicrobial resistance, peptoids (-alkylated oligoglycines) have been reported to act both by membrane disruption and on intracellular targets. Here we gradually introduced peptoid units into the membrane-disruptive undecapeptide KKLLKLLKLLL to test a possible transition toward intracellular targeting. We found that selected hybrids containing up to five peptoid units retained the parent AMP's α-helical folding, membrane disruption, and antimicrobial effects against Gram-negative bacteria including multidrug-resistant (MDR) strains of and while showing reduced hemolysis and cell toxicities.

Relatives' experiences of visiting restrictions during the COVID-19 pandemic's first wave: a PREMs study in Valais Hospital, Switzerland.

Background: During the COVID-19 pandemic, most countries introduced temporary visiting restrictions on the relatives of acute care hospital patients, whether or not they were infected with SARS-CoV-2. This affected relatives' psychological and emotional states and how closely they could be involved in their loved one's hospitalization.

Study Aims: Investigate relatives' experiences of visiting restrictions during the COVID-19 pandemic's first wave and the support offered by Valais Hospital's healthcare staff.

Perceived stress, trust, safety and severity of SARS-CoV-2 infection among patients discharged from hospital during the COVID-19 pandemic's first wave: a PREMs survey.

Aim: To investigate experiences of stress, feelings of safety, trust in healthcare staff and perceptions of the severity of a SARS-CoV-2 infection among inpatients discharged from Valais Hospital, Switzerland, during the COVID-19 pandemic's first wave.

Methods: Discharged patients aged 18 years or more (n=4665), hospitalised between 28 February and 11 May 2020, whether they had been infected by SARS-CoV-2 or not, were asked to complete a self-reporting questionnaire, as were their informal caregivers, if available (n=866). Participants answered questions from Cohen's Perceived Stress Scale (PSS) (0=no stress, 40=severe stress), Krajewska-Kułak 's Trust in Nurses Scale and Anderson and Dedrick's Trust in Physician Scale (10=no trust, 50=complete trust), the severity of a SARS-CoV-2 infection (1=not serious, 5=very serious), as well as questions on their perceived feelings of safety (0=not safe, 10=extremely safe).

Reciprocal Regulation of BRN2 and NOTCH1/2 Signaling Synergistically Drives Melanoma Cell Migration and Invasion.

Phenotypic plasticity drives cancer progression, impacts treatment response, and is a major driver of therapeutic resistance. In melanoma, a regulatory axis between the MITF and BRN2 transcription factors has been reported to promote tumor heterogeneity by mediating switching between proliferative and invasive phenotypes, respectively. Despite strong evidence that subpopulations of cells that exhibit a BRN2/MITF expression profile switch to a predominantly invasive phenotype, the mechanisms by which this switch is propagated and promotes invasion remain poorly defined.

New Method for Efficient siRNA Delivery in Retina Explants: Reverse Magnetofection.

The prevalence of retinal disorders associated with visual impairment and blindness is increasing worldwide, while most of them remain without effective treatment. Pharmacological and molecular therapy development is hampered by the lack of effective drug delivery into the posterior segment of the eye. Among molecular approaches, RNA-interference (RNAi) features strong advantages, yet delivering it to the inner layer of the retina appears extremely challenging.

Protocol for a patient-reported experience measures (PREMs) survey of patients discharged during the COVID-19 pandemic and their family caregivers.

Introduction: In the Swiss canton of Valais, the first cases of SARS-CoV-2 were detected on 28 February 2020. Discharged patients' and their family caregivers' experiences in relation to safety, quality of care, trust and communication during the COVID-19 hospitalisation period remain unexplored. The study aims to collect the patient-reported experience measures (PREMs) survey of patients discharged during the COVID-19 pandemic and their family caregivers.

Classification and Grading of Melanocytic Lesions in a Mouse Model of -driven Melanomagenesis.

The mouse line carrying the Tg(Tyr-NRAS*Q61K)1Bee transgene is widely used to model in vivo -driven melanomagenesis. Although the pathological features of this model are well described, classification and interpretation of the resulting proliferative lesions-including their origin, evolution, grading, and pathobiological significance-are still unclear and not supported by molecular and biological evidence. Focusing on their classification and grading, this work combines histopathology and expression analysis (using both immunohistochemistry [IHC] and quantitative PCR) of selected biomarkers to study the full spectrum of cutaneous and lymph nodal melanocytic proliferations in the Tg(Tyr-NRAS*Q61K)1Bee mouse.

Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation.

Tet-enzyme-mediated 5-hydroxymethylation of cytosines in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies.

Removal of trace organic contaminants from wastewater by superfine powdered activated carbon (SPAC) is neither affected by SPAC dispersal nor coagulation.

Powdered activated carbon (PAC) is increasingly used as tertiary treatment for the removal of trace organic contaminants (TrOCs) from wastewater (WW). To enhance the sorption kinetics and capacity, the PAC particles can be milled down to superfine powdered activated carbon (SPAC). However, the small-grained SPAC particles are prone to aggregation, which may impact their treatment performance.

One-Dimensional Edge Contacts to a Monolayer Semiconductor.

Integration of electrical contacts into van der Waals (vdW) heterostructures is critical for realizing electronic and optoelectronic functionalities. However, to date no scalable methodology for gaining electrical access to buried monolayer two-dimensional (2D) semiconductors exists. Here we report viable edge contact formation to hexagonal boron nitride (hBN) encapsulated monolayer MoS.

TET2-Dependent Hydroxymethylome Plasticity Reduces Melanoma Initiation and Progression.

Although numerous epigenetic aberrancies accumulate in melanoma, their contribution to initiation and progression remain unclear. The epigenetic mark 5-hydroxymethylcytosine (5hmC), generated through TET-mediated DNA modification, is now referred to as the sixth base of DNA and has recently been reported as a potential biomarker for multiple types of cancer. Loss of 5hmC is an epigenetic hallmark of melanoma, but whether a decrease in 5hmc levels contributes directly to pathogenesis or whether it merely results from disease progression-associated epigenetic remodeling remains to be established.

Healthcare professionals' sources of knowledge of complementary medicine in an academic center.

Background: Complementary medicine (CM) is utilized in a growing number of academic centers despite the debate concerning its value, risks and benefits. Healthcare professionals often feel uncomfortable discussing CM with patients, and little is known about their sources of knowledge in the field of CM.

Objective: To assess healthcare professionals' sources of knowledge and attitude toward CM in an academic hospital.

The Attitudes of Physicians, Nurses, Physical Therapists, and Midwives Toward Complementary Medicine for Chronic Pain: A Survey at an Academic Hospital.

Objective: To assess the attitudes of physicians, nurses, physical therapists, and midwives toward complementary medicine (CM) at a Swiss academic hospital and toward its use for treating chronic pain.

Design: The cross-sectional survey took place from October to December 2013.

Setting: An e-mail sent to 4925 healthcare professionals (1969 physicians, 2372 nurses, 145 physical therapists, and 111 midwives) working at Lausanne University Hospital, Switzerland, invited them to answer a web-based questionnaire.

Ultrasensitive 1D field-effect phototransistors: CH3NH3PbI3 nanowire sensitized individual carbon nanotubes.

Field-effect phototransistors were fabricated based on individual carbon nanotubes (CNTs) sensitized by CH3NH3PbI3 nanowires (MAPbI3NWs). These devices represent light responsivities of R = 7.7 × 10(5) A W(-1) under low-lighting conditions in the nW mm(-2) range, unprecedented among CNT-based photodetectors.

RNA biochemistry. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine.

Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identify consensus sites for hydroxymethylation.