Use of osteogenic bone matrix in patients with traumatic long bone defects: An open label, single center study.

Background: Osteogenic Bone Matrix (Altis™ OBM) is a tissue-engineered, porcine-derived demineralized bone matrix prepared using a humanization processing technology that confers biocompatibility and improved osteoinductivity. The objective of this study was to determine the safety and efficacy of OBM in patients with traumatic long bone defects in an open-label, non-randomized single-center study.

Methods: Diagnosis and main criteria for inclusion were open long bone fractures graded as Gustilo-Anderson Grade II, IIIA or IIIB.

Cell immunity to SARS-CoV-2 after natural infection and/or different vaccination regimens.

Background: The aim of the study was to evaluate the humoral and cellular immunity after SARS-CoV-2 infection and/or vaccination according to the type of vaccine, number of doses and combination of vaccines.

Methods: Volunteer subjects were sampled between September 2021 and July 2022 in Hospital Clínico San Carlos, Madrid (Spain). Participants had different immunological status against SARS-CoV-2: vaccinated and unvaccinated, with or without previous COVID-19 infection, including healthy and immunocompromised individuals.

Exploring New Strategies for Optimizing the Production of Poly(3-hydroxybutyrate--3-hydroxyvalerate) from Methane and VFAs in Synthetic Cocultures and Mixed Methanotrophic Consortia.

In this work, the potential of a synthetic coculture and a mixed methanotrophic consortium to synthesize poly(3-hydroxybutyrate--3-hydroxyvalerate) (PHBV) from renewable and waste-based feedstocks was assessed batchwise. cocultivated with and a -enriched culture previously grown on methane were subjected to nutrient starvation in a medium enriched with valeric acid (30% w w of ) or with a VFAs mixture containing acetic, propionic, butyric, and valeric acids (15% w w of ) under a CH:O or air atmosphere. For all test series, pH was adjusted to 7 after adding the cosubstrates, and a negligible substrate consumption or polymer production was considered the end point of the trial.

The structural landscape of the immunoglobulin fold by large-scale de novo design.

De novo designing immunoglobulin-like frameworks that allow for functional loop diversification shows great potential for crafting antibody-like scaffolds with fully customizable structures and functions. In this work, we combined de novo parametric design with deep-learning methods for protein structure prediction and design to explore the structural landscape of 7-stranded immunoglobulin domains. After screening folding of nearly 4 million designs, we have assembled a structurally diverse library of ~50,000 immunoglobulin domains with high-confidence AlphaFold2 predictions and structures diverging from naturally occurring ones.

Resistance of soil bacterial communities from montane heathland ecosystems in the Cantabrian mountains (NW Spain) to a gradient of experimental nitrogen deposition.

Elevated atmospheric nitrogen (N) deposition on terrestrial ecosystems has become one of the most important drivers of microbial diversity loss on a global scale, and has been reported to alter the soil function of nutrient-poor, montane Calluna vulgaris heathlands in the context of global change. In this work we analyze for the first time the shifts of bacterial communities in response to experimental addition of N in Calluna heathlands as a simulation of atmospheric deposition. Specifically, we evaluated the effects of five N addition treatments (0, 10, 20, and 50 kg N ha yr for 3-years; and 56 kg N ha yr for 10-years) on the resistance of soil bacterial communities as determined by changes in their composition and alpha and beta diversities.

Carving out a Glycoside Hydrolase Active Site for Incorporation into a New Protein Scaffold Using Deep Network Hallucination.

Enzymes are indispensable biocatalysts for numerous industrial applications, yet stability, selectivity, and restricted substrate recognition present limitations for their use. Despite the importance of enzyme engineering in overcoming these limitations, success is often challenged by the intricate architecture of enzymes derived from natural sources. Recent advances in computational methods have enabled the de novo design of simplified scaffolds with specific functional sites.

Single-chain dimers from de novo immunoglobulins as robust scaffolds for multiple binding loops.

Antibody derivatives have sought to recapitulate the antigen binding properties of antibodies, but with improved biophysical attributes convenient for therapeutic, diagnostic and research applications. However, their success has been limited by the naturally occurring structure of the immunoglobulin dimer displaying hypervariable binding loops, which is hard to modify by traditional engineering approaches. Here, we devise geometrical principles for de novo designing single-chain immunoglobulin dimers, as a tunable two-domain architecture that optimizes biophysical properties through more favorable dimer interfaces.

Loss of Pla2r1 decreases cellular senescence and age-related alterations caused by aging and Western diets.

Cellular senescence is induced by many stresses including telomere shortening, DNA damage, oxidative, or metabolic stresses. Senescent cells are stably cell cycle arrested and they secrete many factors including cytokines and chemokines. Accumulation of senescent cells promotes many age-related alterations and diseases.

Quantification and Whole Genome Characterization of SARS-CoV-2 RNA in Wastewater and Air Samples.

Wastewater-based epidemiology has emerged as a promising and efficacious surveillance system for SARS-CoV-2 and other infectious diseases in many nations. The process typically involves wastewater concentration, nucleic acid extraction, amplification of selected genomic segments, and detection and quantification of the amplified genomic segment. This methodology can similarly be leveraged to detect and quantify infectious agents, such as SARS-CoV-2, in air samples.

Short-term responses of ecosystem multifunctionality to fire severity are modulated by fire-induced impacts on plant and soil microbial communities.

This study represents a first attempt to shed light into the mechanisms that modulate the response of ecosystem multifunctionality (EMF) to fire severity in post-fire landscapes. We specifically investigated the role played by fire-induced changes on above and belowground communities in the modulation of EMF responses at short-term after fire. For this purpose, we estimated EMF using an averaging approach from three ecosystem functions (carbon regulation, decomposition and soil fertility) and their standardized functional indicators in field plots burned at low and high fire severity 1-year after a wildfire occurred in a Mediterranean ecosystem in the central region of Spain.

Alcohol-induced damage to the fimbria/fornix reduces hippocampal-prefrontal cortex connection during early abstinence.

Alcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC).

Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.

Background: Senescent cells (SCs) are involved in proliferative disorders, but their role in pulmonary hypertension remains undefined. We investigated SCs in patients with pulmonary arterial hypertension and the role of SCs in animal pulmonary hypertension models.

Methods: We investigated senescence (p16, p21) and DNA damage (γ-H2AX, 53BP1) markers in patients with pulmonary arterial hypertension and murine models.

Identifying well-folded proteins in the new era of accurate structure prediction.

Computational protein design tailors proteins for target structures and oligomerisation states with high stability, which allows overcoming many limitations of natural proteins when redesigned for new functions. Despite significant advances in the field over the past decade, it remains challenging to predict sequences that will fold as stable monomers in solution or binders to a particular protein target; thereby requiring substantial experimental resources to identify proteins with the desired properties. To overcome this, here we leveraged the large amount of design data accumulated in the last decade, and the breakthrough in protein structure prediction from last year to investigate on improved ways of selecting promising designs before experimental testing.

De novo design of immunoglobulin-like domains.

Antibodies, and antibody derivatives such as nanobodies, contain immunoglobulin-like (Ig) β-sandwich scaffolds which anchor the hypervariable antigen-binding loops and constitute the largest growing class of drugs. Current engineering strategies for this class of compounds rely on naturally existing Ig frameworks, which can be hard to modify and have limitations in manufacturability, designability and range of action. Here, we develop design rules for the central feature of the Ig fold architecture-the non-local cross-β structure connecting the two β-sheets-and use these to design highly stable Ig domains de novo, confirm their structures through X-ray crystallography, and show they can correctly scaffold functional loops.

The Influence of Culture and Art Management on the Healthy Development of Cultural Economy Industry under the Background of Sustainable Ecological Environment.

In the context of sustainable ecological environment, strengthening the scientific management of cultural industry can promote the rapid development of China's cultural industry and further promote the construction of spiritual civilization in China. Starting from culture and art management, this study expounds its position in the development of cultural economy industry and its impact on the development of cultural economy. Through two different methods of culture and art management and conventional management, this paper discusses the social and economic market benefit value, the demand for the healthy development of industry, and the impact of innovative cultural industry resources on the development of cultural industry.

Analysis of Adverse Effects of COVID-19 Vaccines in Spain following Booster Dose.

The present study evaluates the adverse effects of three vaccines: AstraZeneca (Vaxzevria), Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax) according to the dose. From 733 participants collected, the vaccine schedule was as follows: 330 (45%) received a double dose of the AstraZeneca vaccine, 382 (52.1%) received a double dose of Pfizer, 18 (2.

Short-term effects of burn severity on ecosystem multifunctionality in the northwest Iberian Peninsula.

Severe wildfires cause important changes in vegetation and soil properties in Mediterranean ecosystems. The aim of this work was to evaluate ecosystem multifunctionality through the study of burn severity short-term effects on different ecosystem functions and services. We selected the Cabrera wildfire (2017) in northwest Spain.

ALOS-2 L-band SAR backscatter data improves the estimation and temporal transferability of wildfire effects on soil properties under different post-fire vegetation responses.

Remote sensing techniques are of particular interest for monitoring wildfire effects on soil properties, which may be highly context-dependent in large and heterogeneous burned landscapes. Despite the physical sense of synthetic aperture radar (SAR) backscatter data for characterizing soil spatial variability in burned areas, this approach remains completely unexplored. This study aimed to evaluate the performance of SAR backscatter data in C-band (Sentinel-1) and L-band (ALOS-2) for monitoring fire effects on soil organic carbon and nutrients (total nitrogen and available phosphorous) at short term in a heterogeneous Mediterranean landscape mosaic made of shrublands and forests that was affected by a large wildfire.

Nootropic effects of LSD: Behavioral, molecular and computational evidence.

The therapeutic use of classical psychedelic substances such as d-lysergic acid diethylamide (LSD) surged in recent years. Studies in rodents suggest that these effects are produced by increased neural plasticity, including stimulation of the mTOR pathway, a key regulator of metabolism, plasticity, and aging. Could psychedelic-induced neural plasticity be harnessed to enhance cognition? Here we show that LSD treatment enhanced performance in a novel object recognition task in rats, and in a visuo-spatial memory task in humans.

An engineered protein-based submicromolar competitive inhibitor of the virulence factor aureolysin.

Aureolysin, a secreted metallopeptidase (MP) from the thermolysin family, functions as a major virulence factor in . No specific aureolysin inhibitors have yet been described, making this an important target for the development of novel antimicrobial drugs in times of rampant antibiotic resistance. Although small-molecule inhibitors are currently more common in the clinic, therapeutic proteins and peptides (TPs) are favourable due to their high selectivity, which reduces off-target toxicity and allows dosage tuning.

Predicting potential wildfire severity across Southern Europe with global data sources.

The large environmental and socioeconomic impacts of wildfires in Southern Europe require the development of efficient generalizable tools for fire danger analysis and proactive environmental management. With this premise, we aimed to study the influence of different environmental variables on burn severity, as well as to develop accurate and generalizable models to predict burn severity. To address these objectives, we selected 23 wildfires (131,490 ha) across Southern Europe.

The importance of urgency in decision making based on dynamic information.

A standard view in the literature is that decisions are the result of a process that accumulates evidence in favor of each alternative until such accumulation reaches a threshold and a decision is made. However, this view has been recently questioned by an alternative proposal that suggests that, instead of accumulated, evidence is combined with an urgency signal. Both theories have been mathematically formalized and supported by a variety of decision-making tasks with constant information.