Clonality contributes to the spread of Avrainvillea lacerata (Bryopsidales, Chlorophyta) in Hawai'i.

The relative rates of sexual versus asexual reproduction influence the partitioning of genetic diversity within and among populations. During range expansions, asexual reproduction often facilitates colonization and establishment. The arrival of the green alga Avrainvillea lacerata has caused shifts in habitat structure and community assemblages since its discovery in 1981 offshore of O'ahu, Hawai'i.

Prophylactic Local Antibiotics for Tissue Expansion (PLATE) Improve Breast Reconstruction Outcomes.

Introduction: Infection following tissue expander (TE) breast reconstruction is frequent and impactful. Preliminary reports demonstrate value of local antibiotic delivery for implant salvage and prophylactic potential. Herein is a multi-institutional retrospective study employing surgeon-crafted tobramycin-vancomycin PMMA plates (PLATE) during TE implantation for infection prophylaxis.

Evidence for the translocation of fixed N in the N-fixing lichen Stereocaulon vesuvianum.

The fruticose lichen Stereocaulon vesuvianum is among the most abundant and widespread lichens in upland Britain. It typically produces cephalodia (nodules) that contain the cyanobacterium Stigonema, which can fix atmospheric nitrogen. However, over much of England, Wales, and southern Scotland S.

Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9.

Thermostable clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas9) enzymes could improve genome-editing efficiency and delivery due to extended protein lifetimes. However, initial experimentation demonstrated Geobacillus stearothermophilus Cas9 (GeoCas9) to be virtually inactive when used in cultured human cells. Laboratory-evolved variants of GeoCas9 overcome this natural limitation by acquiring mutations in the wedge (WED) domain that produce >100-fold-higher genome-editing levels.

Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9.

Thermostable CRISPR-Cas9 enzymes could improve genome editing efficiency and delivery due to extended protein lifetimes. However, initial experimentation demonstrated Geobacillus stearothermophilus Cas9 (GeoCas9) to be virtually inactive when used in cultured human cells. Laboratory-evolved variants of GeoCas9 overcome this natural limitation by acquiring mutations in the wedge (WED) domain that produce >100-fold higher genome editing levels.

CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes.

CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities.

Revisiting the Landscape of Potential Small and Drug Substance Related Nitrosamines in Pharmaceuticals.

N-Nitrosamines are a class of indirect acting mutagens, as their metabolic degradation leads to the formation of the DNA-alkylating diazonium ion. Following up on the in-silico identification of thousands of nitrosamines that can potentially be derived from small molecule drugs and their known impurities described in a previous publication, we have now re-analyzed this dataset to apply EMA's Carcinogenic Potency Categorization Approach (CPCA) introduced with the 16th revision of their Q&A document for Marketing Authorization Holders. We find that the majority of potential nitrosamines from secondary amine precursors belongs to potency categories 4 and 5, corresponding to an acceptable daily intake of 1500 ng, whereas nitrosamines from tertiary amine precursors distribute more evenly among all categories, resulting in a substantial number of structures that are assigned the more challenging acceptable intakes of 18 ng/day and 100 ng/day for potency categories 1 and 2, respectively.

Multimodal image and spectral feature learning for efficient analysis of water-suspended particles.

We have developed a method to combine morphological and chemical information for the accurate identification of different particle types using optical measurement techniques that require no sample preparation. A combined holographic imaging and Raman spectroscopy setup is used to gather data from six different types of marine particles suspended in a large volume of seawater. Unsupervised feature learning is performed on the images and the spectral data using convolutional and single-layer autoencoders.

Use of Antibiotic-impregnated Polymethylmethacrylate (PMMA) Plates for Prevention of Periprosthetic Infection in Breast Reconstruction.

Unlabelled: Periprosthetic infections remain a major challenge for breast reconstruction. Local antibiotic delivery systems, such as antibiotic beads and spacers, have been widely used within other surgical fields, but their use within plastic surgery remains scarce. In this study, we demonstrate the use of antibiotic-impregnated polymethylmethacrylate (PMMA) plates for infection prophylaxis in tissue expander (TE)-based breast reconstruction.

Risk stratification in subpectoral to prepectoral pocket conversion to reduce post-reconstruction animation deformity.

Background: Animation deformity is a morbid complication that impacts women undergoing subpectoral implant-based breast reconstruction. Transferring implants from the subpectoral to prepectoral space, pocket conversion, can be performed to minimize this issue. While prior literature has evaluated outcomes associated with this procedure, we investigated the risk factors most commonly associated with post-conversion complications.

Does Higher Intraoperative Fraction of Inspired Oxygen Improve Complication Rates Following Implant-Based Breast Reconstruction?

Background: The surgical literature debates about whether an average intraoperative fractional inspired level of oxygen (FiO) greater than 80% confers lower postsurgical complication rates. Although some evidence demonstrates minimal or no difference in short-term mortality or surgical site infections, few studies suggest negative long-term outcomes.

Objectives: To the best of our knowledge, this is the first study examining the relationship between intraoperative FiO levels and postoperative outcomes in the setting of immediate prepectoral implant-based breast reconstruction.

An Exploratory Study Using Electronic Medical Records to Assess the Feasibility of Establishing Cohorts of Patients with Genetic Causes of Parkinson's Disease.

Background: More efficient screening methods are needed to improve the ability to identify and follow genetic cohorts in Parkinson's disease (PD).

Objective: To explore the use of the electronic medical records (EMRs) to identify participants with PD.

Methods: Using an algorithm previously developed in collaboration with Maccabi Healthcare Services (MHS), approximately 5,200 participants with PD were identified, more than 3,200 were screened, and 837 participants were enrolled and genotyped for leucine-rich repeat kinase 2 (LRRK2) and beta-glucocerebrosidase (GBA) variants.

Incorporating protein precipitation to resolve hybrid IP-LC-MS assay interference for ultrasensitive quantification of intact therapeutic insulin dimer in human plasma.

For pharmacokinetics characterization of a therapeutic insulin dimer, an ultrasensitive plasma method was required due to the expected low circulating levels in humans. A bioanalytical strategy combining immunoprecipitation enrichment with liquid chromatography - tandem mass spectrometry (LC-MS/MS) analysis of the intact protein offers the opportunity to resolve the analyte from endogenous and exogenous insulin and insulin analogs. Nonetheless, interference from complex background matrix was observed limiting reliable measurements at the low concentration range.

An EPA database on the effects of engineered nanomaterials-NaKnowBase.

The US EPA Office of Research and Development (ORD) has conducted a research program assessing potential risks of emerging materials and technologies, including engineered nanomaterials (ENM). As a component of that program, a nanomaterial knowledge base, termed "NaKnowBase", was developed containing the results of published ORD research relevant to the potential environmental and biological actions of ENM. The experimental data address issues such as ENM release into the environment; fate, transport and transformations in environmental media; exposure to ecological species or humans; and the potential for effects on those species.

Guiding Labelling Effort for Efficient Learning With Georeferenced Images.

We describe a novel semi-supervised learning method that reduces the labelling effort needed to train convolutional neural networks (CNNs) when processing georeferenced imagery. This allows deep learning CNNs to be trained on a per-dataset basis, which is useful in domains where there is limited learning transferability across datasets. The method identifies representative subsets of images from an unlabelled dataset based on the latent representation of a location guided autoencoder.

A New Paradigm for KIM-PTP Drug Discovery: Identification of Allosteric Sites with Potential for Selective Inhibition Using Virtual Screening and LEI Analysis.

The kinase interaction motif protein tyrosine phosphatases (KIM-PTPs), HePTP, PTPSL and STEP, are involved in the negative regulation of mitogen-activated protein kinase (MAPK) signalling pathways and are important therapeutic targets for a number of diseases. We have used VSpipe, a virtual screening pipeline, to identify a ligand cluster distribution that is unique to this subfamily of PTPs. Several clusters map onto KIM-PTP specific sequence motifs in contrast to the cluster distribution obtained for PTP1B, a classic PTP that mapped to general PTP motifs.

Unsupervised feature learning and clustering of particles imaged in raw holograms using an autoencoder.

Digital holography is a useful tool to image microscopic particles. Reconstructed holograms give high-resolution shape information that can be used to identify the types of particles. However, the process of reconstructing holograms is computationally intensive and cannot easily keep up with the rate of data acquisition on low-power sensor platforms.

Accelerated RNA detection using tandem CRISPR nucleases.

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided RNA recognition that triggers cleavage and release of a fluorescent reporter molecule, but long reaction times hamper their detection sensitivity and speed. Here, we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 molecules per µl of RNA in 20 min.

Accelerated RNA detection using tandem CRISPR nucleases.

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided recognition of RNA that triggers cleavage and release of a fluorescent reporter molecule, but long reaction times hamper sensitivity and speed when applied to point-of-care testing. Here we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 RNA copies/microliter in 20 minutes.

The carbon partitioning of glucose and DIC in mixotrophic, heterotrophic and photoautotrophic cultures of Tetraselmis suecica.

Objective: Changes in the partitioning of dissolved inorganic (DIC) and glucose were elucidated by utilising C labelled DIC or glucose, and quantifying the biochemical profile of mixotrophic, heterotrophic and photoautotrophic cultures of the microalga Tetraselmis suecica.

Results: Mixotrophic cultivation increases microalgal productivity and changes their biochemical profile, due to an alteration in the partitioning of carbon within the cell. When cultured mixotrophically and heterotrophically, there is enhanced incorporation of carbon into shorter chain saturated fatty acids and non-lipid biomass, compared to photoautotrophic cultivation.

Targeting Methionine Synthase in a Fungal Pathogen Causes a Metabolic Imbalance That Impacts Cell Energetics, Growth, and Virulence.

There is an urgent need to develop novel antifungals to tackle the threat fungal pathogens pose to human health. Here, we have performed a comprehensive characterization and validation of the promising target methionine synthase (MetH). We show that in the absence of this enzymatic activity triggers a metabolic imbalance that causes a reduction in intracellular ATP, which prevents fungal growth even in the presence of methionine.