Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [Ga]Ga-ABY-025: Results from a Pilot Study.

Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [Ga]Ga-ABY-025 for visualization of HER2-low mBC.

Nitrogenase cofactor biosynthesis using proteins produced in mitochondria of .

Biological nitrogen fixation, the conversion of inert N to metabolically tractable NH, is only performed by certain microorganisms called diazotrophs and is catalyzed by the nitrogenases. A [7Fe-9S-C-Mo--homocitrate]-cofactor, designated FeMo-co, provides the catalytic site for N reduction in the Mo-dependent nitrogenase. Thus, achieving FeMo-co formation in model eukaryotic organisms, such as , represents an important milestone toward endowing them with a capacity for Mo-dependent biological nitrogen fixation.

Nodule-specific Cu -chaperone NCC1 is required for symbiotic nitrogen fixation in Medicago truncatula root nodules.

Cu -chaperones are a diverse group of proteins that allocate Cu ions to specific copper proteins, creating different copper pools targeted to specific physiological processes. Symbiotic nitrogen fixation carried out in legume root nodules indirectly requires relatively large amounts of copper, for example for energy delivery via respiration, for which targeted copper deliver systems would be required. MtNCC1 is a nodule-specific Cu -chaperone encoded in the Medicago truncatula genome, with a N-terminus Atx1-like domain that can bind Cu with picomolar affinities.

Differential transcript usage analysis incorporating quantification uncertainty via compositional measurement error regression modeling.

Differential transcript usage (DTU) occurs when the relative expression of multiple transcripts arising from the same gene changes between different conditions. Existing approaches to detect DTU often rely on computational procedures that can have speed and scalability issues as the number of samples increases. Here we propose a new method, CompDTU, that uses compositional regression to model the relative abundance proportions of each transcript that are of interest in DTU analyses.

Functional expression of the nitrogenase Fe protein in transgenic rice.

Engineering cereals to express functional nitrogenase is a long-term goal of plant biotechnology and would permit partial or total replacement of synthetic N fertilizers by metabolization of atmospheric N. Developing this technology is hindered by the genetic and biochemical complexity of nitrogenase biosynthesis. Nitrogenase and many of the accessory proteins involved in its assembly and function are O sensitive and only sparingly soluble in non-native hosts.

Nitrogenase Cofactor Maturase NifB Isolated from Transgenic Rice is Active in FeMo-co Synthesis.

The engineering of nitrogen fixation in plants requires assembly of an active prokaryotic nitrogenase complex, which is yet to be achieved. Nitrogenase biogenesis relies on NifB, which catalyzes the formation of the [8Fe-9S-C] metal cluster NifB-co. This is the first committed step in the biosynthesis of the iron-molybdenum cofactor (FeMo-co) found at the nitrogenase active site.

A colorimetric method to measure in vitro nitrogenase functionality for engineering nitrogen fixation.

Biological nitrogen fixation (BNF) is the reduction of N into NH in a group of prokaryotes by an extremely O-sensitive protein complex called nitrogenase. Transfer of the BNF pathway directly into plants, rather than by association with microorganisms, could generate crops that are less dependent on synthetic nitrogen fertilizers and increase agricultural productivity and sustainability. In the laboratory, nitrogenase activity is commonly determined by measuring ethylene produced from the nitrogenase-dependent reduction of acetylene (ARA) using a gas chromatograph.

Functional Nitrogenase Cofactor Maturase NifB in Mitochondria and Chloroplasts of .

Engineering plants to synthesize nitrogenase and assimilate atmospheric N will reduce crop dependency on industrial N fertilizers. This technology can be achieved by expressing prokaryotic nitrogen fixation gene products for the assembly of a functional nitrogenase in plants. NifB is a critical nitrogenase component since it catalyzes the first committed step in the biosynthesis of all types of nitrogenase active-site cofactors.

Environment and coordination of FeMo-co in the nitrogenase metallochaperone NafY.

In nitrogenase biosynthesis, the iron-molybdenum cofactor (FeMo-co) is externally assembled at scaffold proteins and delivered to the NifDK nitrogenase component by the NafY metallochaperone. Here we have used nuclear magnetic resonance, molecular dynamics, and functional analysis to elucidate the environment and coordination of FeMo-co in NafY. H stands as the key FeMo-co ligand.

Calcium oxalate urolithiasis in juvenile dogs.

Background: The features of juvenile-onset calcium oxalate urolithiasis in dogs have not been previously reported.

Methods: Calcium oxalate urolith submissions to the Minnesota Urolith Center between 2012 and 2016 were analyzed to identify those originating from juvenile (≤2 years, n = 510) or mature (7-9 years, n = 39,093) dogs. Breed, sex, urolith salt type and urolith location were compared between groups.

Methadone Access for Opioid Use Disorder During the COVID-19 Pandemic Within the United States and Canada.

Importance: Methadone access may be uniquely vulnerable to disruption during COVID-19, and even short delays in access are associated with decreased medication initiation and increased illicit opioid use and overdose death. Relative to Canada, US methadone provision is more restricted and limited to specialized opioid treatment programs.

Objective: To compare timely access to methadone initiation in the US and Canada during COVID-19.

Biosynthesis of cofactor-activatable iron-only nitrogenase in Saccharomyces cerevisiae.

Engineering nitrogenase in eukaryotes is hampered by its genetic complexity and by the oxygen sensitivity of its protein components. Of the three types of nitrogenases, the Fe-only nitrogenase is considered the simplest one because its function depends on fewer gene products than the homologous and more complex Mo and V nitrogenases. Here, we show the expression of stable Fe-only nitrogenase component proteins in the low-oxygen mitochondria matrix of S.

Compression of quantification uncertainty for scRNA-seq counts.

Motivation: Quantification estimates of gene expression from single-cell RNA-seq (scRNA-seq) data have inherent uncertainty due to reads that map to multiple genes. Many existing scRNA-seq quantification pipelines ignore multi-mapping reads and therefore underestimate expected read counts for many genes. alevin accounts for multi-mapping reads and allows for the generation of 'inferential replicates', which reflect quantification uncertainty.

Exploiting genetic diversity and gene synthesis to identify superior nitrogenase NifH protein variants to engineer N-fixation in plants.

Engineering nitrogen fixation in eukaryotes requires high expression of functional nitrogenase structural proteins, a goal that has not yet been achieved. Here we build a knowledge-based library containing 32 nitrogenase nifH sequences from prokaryotes of diverse ecological niches and metabolic features and combine with rapid screening in tobacco to identify superior NifH variants for plant mitochondria expression. Three NifH variants outperform in tobacco mitochondria and are further tested in yeast.

A Third Variant Causing Coat Color Dilution in Dogs.

Altered melanosome transport in melanocytes, resulting from variants in the melanophilin () gene, are associated with inherited forms of coat color dilution in many species. In dogs, the gene corresponds to the D locus and two variants, c.-22G > A (d) and c.

Use of synthetic biology tools to optimize the production of active nitrogenase Fe protein in chloroplasts of tobacco leaf cells.

The generation of nitrogen fixing crops is considered a challenge that could lead to a new agricultural 'green' revolution. Here, we report the use of synthetic biology tools to achieve and optimize the production of active nitrogenase Fe protein (NifH) in the chloroplasts of tobacco plants. Azotobacter vinelandii nitrogen fixation genes, nifH, M, U and S, were re-designed for protein accumulation in tobacco cells.

Biosynthesis of Nitrogenase Cofactors.

Nitrogenase harbors three distinct metal prosthetic groups that are required for its activity. The simplest one is a [4Fe-4S] cluster located at the Fe protein nitrogenase component. The MoFe protein component carries an [8Fe-7S] group called P-cluster and a [7Fe-9S-C-Mo--homocitrate] group called FeMo-co.

Biosynthesis of the nitrogenase active-site cofactor precursor NifB-co in .

The radical -adenosylmethionine (SAM) enzyme NifB occupies a central and essential position in nitrogenase biogenesis. NifB catalyzes the formation of an [8Fe-9S-C] cluster, called NifB-co, which constitutes the core of the active-site cofactors for all 3 nitrogenase types. Here, we produce functional NifB in aerobically cultured Combinatorial pathway design was employed to construct 62 strains in which transcription units driving different expression levels of mitochondria-targeted genes ( and ) were integrated into the chromosome.

Efficiency of HIV services in Nigeria: Determinants of unit cost variation of HIV counseling and testing and prevention of mother-to-child transmission interventions.

Background: Like most countries with a substantial HIV burden, Nigeria continues to face challenges in reaching coverage targets of HIV services. A fundamental problem is stagnated funding in recent years. Improving efficiency is therefore paramount to effectively scale-up HIV services.

Aerobic Training in Canadian Stroke Rehabilitation Programs.

Background And Purpose: Aerobic training (AT) is recommended for people after stroke, yet uptake and operationalization of AT in clinical practice in Canada have not been measured. We surveyed inclusion of structured AT and barriers to implementation in public inpatient/outpatient stroke rehabilitation programs across Canada.

Methods: A Web-based questionnaire was sent to 89 stroke rehabilitation program leads.