An alcove at the acetyl-CoA synthase nickel active site is required for productive substrate CO binding and anaerobic carbon fixation.

One of the seven natural CO fixation pathways, the anaerobic Wood-Ljungdahl pathway (WLP) is unique in generating CO as a metabolic intermediate, operating through organometallic intermediates, and in conserving (versus utilizing) net ATP. The key enzyme in the WLP is acetyl-CoA synthase (ACS), which uses an active site [2Ni-4Fe-4S] cluster (A-cluster), a CO tunnel, and an organometallic (Ni-CO, Ni-methyl, and Ni-acetyl) reaction sequence to generate acetyl-CoA. Here, we reveal that an alcove, which interfaces the tunnel and the A-cluster, is essential for CO fixation and autotrophic growth by the WLP.

Inversin (NPHP2) and Vangl2 are required for normal zebrafish cloaca formation.

Nephronophthisis (NPH), an autosomal recessive ciliopathy, results from mutations in more than 20 different genes (NPHPs). These gene products form protein complexes that regulate trafficking within the cilium, a microtubular structure that plays a crucial role in developmental processes. Several NPHPs, including NPHP2/Inversin, have been linked to extraciliary functions.

Clock genes rescue nphp mutations in zebrafish.

The zebrafish pronephros model, using morpholino oligonucleotides (MO) to deplete target genes, has been extensively used to characterize human ciliopathy phenotypes. Recently, discrepancies between MO and genetically defined mutants have questioned this approach. We analyzed zebrafish with mutations in the nphp1-4-8 module to determine the validity of MO-based results.

Lessons from COVID-19 syndromic surveillance through emergency department activity: a prospective time series study from western Switzerland.

Objective: We aimed to assess if emergency department (ED) syndromic surveillance during the first and second waves of the COVID-19 outbreak could have improved our surveillance system.

Design And Settings: We did an observational study using aggregated data from the ED of a university hospital and public health authorities in western Switzerland.

Participants: All patients admitted to the ED were included.

Impact of N-Aryl- and NHC Core-Substituents on the Coupling of Alkylzinc Nucleophiles: Is Bigger always Better?

Bulky Pd-N-heterocyclic carbene (NHC) catalysts (e. g., N-(di-2,6-(3-pentyl)phenyl), IPent) have been shown to have significantly higher reactivity in a wide variety of cross-coupling applications (i.

Loss of central mineralocorticoid or glucocorticoid receptors impacts auditory nerve processing in the cochlea.

The key auditory signature that may associate peripheral hearing with central auditory cognitive defects remains elusive. Suggesting the involvement of stress receptors, we here deleted the mineralocorticoid and glucocorticoid receptors ( and ) using a CaMKIIα-based tamoxifen-inducible Cre/ approach to generate mice with single or double deletion of central but not cochlear MR and GR. Hearing thresholds of MRGR conditional knockouts () were unchanged, whereas auditory nerve fiber () responses were larger and faster and auditory steady state responses were improved.

Improving nutritional therapy of persistent critically ill patients by organisational measures: A before and after study.

Background & Aims: Critically ill patients requiring prolonged intensive care (ICU) treatment are at high risk of malnutrition, which latter contributes to worsening outcome. Having observed that despite the presence of a nutrition protocol and dieticians, the patients with persistent critical illness (PCI) had been underfed during their ICU stay and particularly during the first 10 days, the aim was to analyse the impact of the organisational changes that were proposed to prevent the observed malnutrition.

Methods: Before (Period A) and after (Period B) study enrolling critically ill patients consecutively admitted, requiring >10 days of ICU treatment.

Corpuscles of Stannius development requires FGF signaling.

The corpuscles of Stannius (CS) represent a unique endocrine organ of teleostean fish that secrets stanniocalcin-1 (Stc1) to maintain calcium homeostasis. Appearing at 20-25 somite stage in the distal zebrafish pronephros, stc1-expressing cells undergo apical constriction, and are subsequently extruded to form a distinct gland on top of the distal pronephric tubules at 50 ​h post fertilization (hpf). Several transcription factors (e.

The Na-activated K channel Slack contributes to synaptic development and plasticity.

Human mutations of the Na-activated K channel Slack (KCNT1) are associated with epilepsy and intellectual disability. Accordingly, Slack knockout mice (Slack) exhibit cognitive flexibility deficits in distinct behavioral tasks. So far, however, the underlying causes as well as the role of Slack in hippocampus-dependent memory functions remain enigmatic.

Spectroscopic and computational investigations of organometallic complexation of group 12 transition metals by methanobactins from Methylocystis sp. SB2.

Methanotrophic bacteria catalyze the aerobic oxidation of methane to methanol using Cu-containing enzymes, thereby exerting a modulating influence on the global methane cycle. To facilitate the acquisition of Cu ions, some methanotrophic bacteria secrete small modified peptides known as "methanobactins," which strongly bind Cu and function as an extracellular Cu recruitment relay, analogous to siderophores and Fe. In addition to Cu, methanobactins form complexes with other late transition metals, including the Group 12 transition metals Zn, Cd, and Hg, although the interplay among solution-phase configurations, metal interactions, and the spectroscopic signatures of methanobactin-metal complexes remains ambiguous.

Organ donation in the ICU - a survey on next of kin response in two Swiss academic centres.

Aim Of The Study: In the Swiss population, attitudes to organ donation are mostly positive. However, a high refusal rate by the next of kin may be observed. We aimed to investigate potential underlying reasons.

Deletion of BDNF in Pax2 Lineage-Derived Interneuron Precursors in the Hindbrain Hampers the Proportion of Excitation/Inhibition, Learning, and Behavior.

Numerous studies indicate that deficits in the proper integration or migration of specific GABAergic precursor cells from the subpallium to the cortex can lead to severe cognitive dysfunctions and neurodevelopmental pathogenesis linked to intellectual disabilities. A different set of GABAergic precursors cells that express Pax2 migrate to hindbrain regions, targeting, for example auditory or somatosensory brainstem regions. We demonstrate that the absence of BDNF in Pax2-lineage descendants of KOs causes severe cognitive disabilities.

International Delphi Expert Consensus on Safe Return to Surgical and Endoscopic Practice: From the Coronavirus Global Surgical Collaborative.

Objective: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities.

Background: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled.

Video fluoroscopy for pulmonary artery catheter insertion in high-risk situation of knotting or misplacement.

Pulmonary artery catheter (PAC) insertion in patients with severe pulmonary hypertension, right heart dilation and failure, is very challenging. Misplacement and knotting are rare but could be serious complications leading to a delay of the monitoring and sometimes an emergent not expected intervention. Here we report a case of a patient admitted to Intensive Care Unit (ICU) with an acute hypoxemic respiratory failure.

Neonatal tooth infection resulting in subperiosteal orbital abscess: A case report.

Neonatal orbital infections are quite rare, and are most often attributed to ethmoid sinusitis. This report describes a case of subperiosteal orbital abscess in a neonate secondary to an infected neonatal tooth. Although there have been two cases reported in the literature describing odontogenic infection resulting in orbital abscess in neonates, these cases were due to infected tooth buds rather than an infected neonatal tooth.

Surgery for non-Covid-19 patients during the pandemic.

Background: In the early phase of the Covid-19 pandemic, mainly data related to the burden of care required by infected patients were reported. The aim of this study was to illustrate the timeline of actions taken and to measure and analyze their impact on surgical patients.

Method: This is a retrospective review of actions to limit Covid-19 spread and their impact on surgical activity in a Swiss tertiary referral center.

Salt to Taste: The Critical Roles Played by Inorganic Salts in Organozinc Formation and in the Negishi Reaction.

The first cross-coupling of organozinc nucleophiles with aryl halides was reported in 1977 by Negishi. Unknown to all at the time was the importance of salt additives that were often present as a byproduct from the organozinc preparation. For decades, these salt additives were overlooked until 2006 when it was discovered that two different, yet effective methods for preparing organozinc solutions (i.

Adequacy of stress ulcer prophylaxis prescription in the intensive care unit: an observational study.

Purpose: Stress ulcer prophylaxis prescriptions might not be sufficiently challenged throughout a patient's stay in an intensive care unit (ICU) and might be erroneously maintained after ICU discharge. This study aimed to determine (1) stress ulcer prophylaxis adequacy in ICU and (2) the proportion of patients receiving inappropriate stress ulcer prophylaxis after ICU discharge.

Material And Methods: This was an observational, single centre study (University Hospital Lausanne, Switzerland).

[Adequacy of intensive care admission in cirrhotic patients not eligible for transplantation].

Decompensated cirrhosis corresponds to the end stage of chronic liver disease. It is associated with poor outcomes, in particular, in patients who are not candidate for a liver transplantation. Those patients require frequent hospital admissions to manage complications.

SPHN/PHRT: Forming a Swiss-Wide Infrastructure for Data-Driven Sepsis Research.

Sepsis is a highly heterogenous syndrome with variable causes and outcomes. As part of the SPHN/PHRT funding program, we aim to build a highly interoperable, interconnected network for data collection, exchange and analysis of patients on intensive care units in order to predict sepsis onset and mortality earlier. All five University Hospitals, Universities, the Swiss Institute of Bioinformatics and ETH Zurich are involved in this multi-disciplinary project.

Guanylyl Cyclase A/cGMP Signaling Slows Hidden, Age- and Acoustic Trauma-Induced Hearing Loss.

In the inner ear, cyclic guanosine monophosphate (cGMP) signaling has been described as facilitating otoprotection, which was previously observed through elevated cGMP levels achieved by phosphodiesterase 5 inhibition. However, to date, the upstream guanylyl cyclase (GC) subtype eliciting cGMP production is unknown. Here, we show that mice with a genetic disruption of the gene encoding the cGMP generator GC-A, the receptor for atrial and B-type natriuretic peptides, display a greater vulnerability of hair cells to hidden hearing loss and noise- and age-dependent hearing loss.

In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP.

Colobomata, persistent optic fissures, frequently cause congenital blindness. Here, we focused on optic fissure fusion using in vivo time-lapse imaging in zebrafish. We identified the fusion initiating cells, which we termed "pioneer cells.

A Path to More Sustainable Catalysis: The Critical Role of LiBr in Avoiding Catalyst Death and its Impact on Cross-Coupling.

The role that LiBr plays in the lifetime of Pd-NHC complexes has been investigated. A bromide ion is proposed to coordinate to Pd thereby preventing beta hydride elimination (BHE) (to form NHC-H ) of the reductive elimination (RE) intermediate that normally completes with the desired cross-coupling catalytic cycle. Coordinating groups, such as anilines, are able to bind suitably well to Pd to prevent this pathway from occurring, thus reducing the need for the added salt.

Complications of Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy: An Observational Study.

Introduction: Regional citrate anticoagulation (RCA) is the recommended anticoagulation modality for continuous renal replacement therapy (CRRT). RCA was associated with a low rate of complications in randomized controlled trials. However, little is known about the type and rate of complications in real life.