A cell-free transcription-translation pipeline for recreating methylation patterns boosts DNA transformation in bacteria.

The bacterial world offers diverse strains for understanding medical and environmental processes and for engineering synthetic biological chassis. However, genetically manipulating these strains has faced a long-standing bottleneck: how to efficiently transform DNA. Here, we report imitating methylation patterns rapidly in TXTL (IMPRINT), a generalized, rapid, and scalable approach based on cell-free transcription-translation (TXTL) to overcome DNA restriction, a prominent barrier to transformation.

Epilepsy panel testing criteria: A clinical assessment.

Epilepsy is a common, and often genetic, neurological disorder. Few guidelines exist to help medical providers or insurance companies decide when to order or cover epilepsy panels for patients with epilepsy. The most recent guidelines were published by NSGC after this study's data collection.

Treatment of Refractory Metastatic Renal Cell Carcinoma.

First-line treatment for metastatic renal cell carcinoma (mRCC) rapidly shifted in recent years with the advent of combination therapies, including immune checkpoint inhibitor (ICI) doublets and combinations of an ICI with a vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitor (TKI). Despite improvements in overall survival and many durable responses, there exists a significant number of patients who fail to respond to these agents, and many patients eventually progress. Given the rapid changes in the front-line setting, it is essential to understand treatment options in refractory mRCC.

Engineered cell differentiation and sexual reproduction in probiotic and mating yeasts.

G protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. GPCRs comprise the largest class of cell surface receptors in eukaryotes, and for more than three decades the pheromone-induced mating pathway in baker's yeast Saccharomyces cerevisiae has served as a model for studying heterologous GPCRs (hGPCRs). Here we report transcriptome profiles following mating pathway activation in native and hGPCR-signaling yeast and use a model-guided approach to correlate gene expression to morphological changes.

Beneficial commensal bacteria promote Drosophila growth by downregulating the expression of peptidoglycan recognition proteins.

Commensal bacteria are known to promote host growth. Such effect partly relies on the capacity of microbes to regulate the host's transcriptional response. However, these evidences mainly come from comparing the transcriptional response caused by commensal bacteria with that of axenic animals, making it difficult to identify the animal genes that are specifically regulated by beneficial microbes.

Genome Editing with Cas9 in Lactobacilli.

The bacterial genus Lactobacillus comprises a vast range of strains with varying metabolic and probiotic traits, with genome editing representing an essential tool to probe genotype-phenotype relationships and enhance their beneficial properties. Currently, one of the most effective means of genome editing in bacteria couples low-efficiency recombineering with high-efficiency counterselection by nucleases from CRISPR-Cas systems. In lactobacilli, several CRISPR-based genome editing methods exist that have shown varying success in different strains.

Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.

Background: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations.

Competitive Exclusion Is a Major Bioprotective Mechanism of Lactobacilli against Fungal Spoilage in Fermented Milk Products.

A prominent feature of lactic acid bacteria (LAB) is their ability to inhibit growth of spoilage organisms in food, but hitherto research efforts to establish the mechanisms underlying bioactivity focused on the production of antimicrobial compounds by LAB. We show, in this study, that competitive exclusion, i.e.

Barriers to genome editing with CRISPR in bacteria.

Genome editing is essential for probing genotype-phenotype relationships and for enhancing chemical production and phenotypic robustness in industrial bacteria. Currently, the most popular tools for genome editing couple recombineering with DNA cleavage by the CRISPR nuclease Cas9 from Streptococcus pyogenes. Although successful in some model strains, CRISPR-based genome editing has been slow to extend to the multitude of industrially relevant bacteria.

PD-L1 detection using Zr-atezolizumab immuno-PET in renal cell carcinoma tumorgrafts from a patient with favorable nivolumab response.

Background: Programmed death-ligand 1 (PD-L1) expression in metastatic renal cell carcinoma (RCC) correlates with a worse prognosis, but whether it also predicts responsiveness to anti-PD-1/PD-L1 therapy remains unclear. Most studies of PD-L1 are limited by evaluation in primary rather than metastatic sites, and in biopsy samples, which may not be representative. These limitations may be overcome with immuno-positron emission tomography (iPET), an emerging tool allowing the detection of cell surface proteins with radiolabeled antibodies.

Genome Editing with CRISPR-Cas9 in Lactobacillus plantarum Revealed That Editing Outcomes Can Vary Across Strains and Between Methods.

Lactic-acid bacteria such as Lactobacillus plantarum are commonly used for fermenting foods and as probiotics, where increasingly sophisticated genome-editing tools are employed to elucidate and enhance these microbes' beneficial properties. The most advanced tools to date utilize an oligonucleotide or double-stranded DNA donor for recombineering and Cas9 for targeted DNA cleavage. As the associated methods are often developed in isolation for one strain, it remains unclear how different Cas9-based editing methods compare across strains.

Ms L: a case of a reversible phenotypic and brain function equivalent of frontotemporal dementia.

Frontotemporal dementia (FTD) is second only to Alzheimer's disease in individuals younger than 65 years of age. Behavioral variant FTD (bvFTD) presents with nonspecific symptoms such as disinhibition, apathy, or emotional blunting. Although neuropsychological testing and structural neuroimaging are not very helpful in diagnosing bvFTD in its initial stages, newer quantitative structural methods and functional neuroimaging have better sensitivity and specificity.

Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations.

We describe an MRI phenotype seen in a series of patients with mutations in PTEN who have clinical features consistent with PTEN hamartoma tumor syndrome (PHTS). Retrospective review of clinical data and MRI was performed in 23 subjects evaluated in four different tertiary care centers with clinical programs in inherited disorders of the white matter. Patients were referred due to abnormal MRI features and abnormal PTEN sequencing was identified.

The mitochondrial solute carrier SLC25A5 at Xq24 is a novel candidate gene for non-syndromic intellectual disability.

Loss-of-function mutations in several different neuronal pathways have been related to intellectual disability (ID). Such mutations often are found on the X chromosome in males since they result in functional null alleles. So far, microdeletions at Xq24 reported in males always have been associated with a syndromic form of ID due to the loss of UBE2A.

Mitochondrial disease in childhood: nuclear encoded.

Primary mitochondrial disorders are clinically and genetically heterogeneous, caused by an alteration(s) in either mitochondrial DNA or nuclear DNA, and affect the respiratory chain's ability to undergo oxidative phosphorylation, leading to decreased production of adenosine triphosphophate and subsequent energy failure. These disorders may present at any age, but children tend to have an acute onset of disease compared with subacute or slowly progressive presentation in adults. Varying organ involvement also contributes to the phenotypic spectrum seen in these disorders.

Genetic counseling in mitochondrial disease.

Mitochondrial diseases are a genetically and clinically diverse group of disorders that arise as a result of dysfunction of the mitochondria. Mitochondrial disorders can be caused by alterations in nuclear DNA and/or mitochondrial DNA. Although some mitochondrial syndromes have been described clearly in the literature many others present as challenging clinical cases with multisystemic involvement at variable ages of onset.

Family history of autoimmune disease in patients with Aicardi-Goutières syndrome.

Purpose: The purpose of this study was to explore anecdotal evidence for an increase in the prevalence of autoimmune diseases in family members of patients with Aicardi-Goutières syndrome (AGS).

Methods: Pedigrees of patients and controls were analyzed using chi-square and logistic regression to assess differences in reports of autoimmune disease among family members of cases and controls. Data was collected at Children's National Medical Center in Washington, DC, USA and at the International Aicardi-Goutières Syndrome Association Scientific Headquarters, C.

Update on nuclear mitochondrial genes and neurologic disorders.

The majority of primary mitochondrial disorders are due to nuclear gene mutations, not aberrations within the mitochondrial genome. The nervous system is frequently involved due to its high-energy demands. Many nonspecific neurologic symptoms may be present in mitochondrial disease; however, there are well-recognized red flags that should alert the clinician to the possibility of mitochondrial disease.

Genetic testing in child neurology.

Integration of genetic and genomic information into the clinical practice of child neurologists is revolutionizing how diagnosis, prognosis, and treatment of neurogenetic diseases are approached. Genetic testing technology, informatics, and interpretation are rapidly expanding. High-throughput next-generation sequencing has changed the landscape of many fields of medicine by enabling new diagnoses and gene/disease associations.

Family history: a guide for neurologists in the age of genomic medicine.

The field of neurogenetics has expanded dramatically over recent years. Neurogenetics has developed from a distinct subspecialty within neurology to something that transcends most of the common presenting conditions for neurologists. The importance of understanding the genetic contribution to conditions like epilepsy, neurodevelopmental disorders, and metabolic diseases has become very evident in neurology.

Carbon nanotube-nanocup hybrid structures for high power supercapacitor applications.

Here, we design and develop high-power electric double-layer capacitors (EDLCs) using carbon-based three dimensional (3-D) hybrid nanostructured electrodes. 3-D hybrid nanostructured electrodes consisting of vertically aligned carbon nanotubes (CNTs) on highly porous carbon nanocups (CNCs) were synthesized by a combination of anodization and chemical vapor deposition techniques. A 3-D electrode-based supercapacitor showed enhanced areal capacitance by accommodating more charges in a given footprint area than that of a conventional CNC-based device.

SPECT brain imaging in chronic Lyme disease.

Objectives: Lyme disease is an infectious disease that frequently involves the central nervous system, leading to cognitive and/or mood dysfunction. The basis for these symptoms remains to be defined but may be the result of a vasculitis or metabolic abnormality secondary to the infection. SPECT scans of the brain might provide an objective measure of abnormalities present in patients with otherwise difficult to objectify clinical findings.

Structural and functional neuroimaging methods in the diagnosis of dementias: a retrospective chart and brain imaging review.

Objective: Assess the contribution of structural and functional neuroimaging methods to the diagnosis of dementia.

Methods: This was a retrospective chart and imaging review. Participants were 24 inpatient dementia cases from a general hospital-based, university medical psychiatry unit.

Potential role of a hybrid intraoperative probe based on OCT and positron detection for ovarian cancer detection and characterization.

Ovarian cancer has the lowest survival rate of the gynecologic cancers because it is predominantly diagnosed in the late stages due to the lack of reliable symptoms and efficacious screening techniques. A novel hybrid intraoperative probe has been developed and evaluated for its potential role in detecting and characterizing ovarian tissue. The hybrid intraoperative dual-modality device consists of multiple scintillating fibers and an optical coherence tomography imaging probe for simultaneously mapping the local activities of (18)F-FDG uptake and imaging of local morphological changes of the ovary.

Neuroimaging findings and brain-behavioral correlates in a former boxer with chronic traumatic brain injury.

Chronic traumatic brain injury (CTBI) is associated with contact sports such as boxing. CTBI results from repetitive blows to the head rather than from a single impact. CTBI individuals present with motor symptoms (incoordination, spasticity, parkinsonism), cognitive impairment (executive dysfunction, memory deficits) and neuropsychiatric symptoms (irritability, affective disturbances).