TYK2 as a novel therapeutic target in Alzheimer's Disease with TDP-43 inclusions.

Neuroinflammation is a pathological feature of many neurodegenerative diseases, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), raising the possibility of common therapeutic targets. We previously established that cytoplasmic double-stranded RNA (cdsRNA) is spatially coincident with cytoplasmic pTDP-43 inclusions in neurons of patients with C9ORF72-mediated ALS. CdsRNA triggers a type-I interferon (IFN-I)-based innate immune response in human neural cells, resulting in their death.

From microbiome composition to functional engineering, one step at a time.

SUMMARYCommunities of microorganisms (microbiota) are present in all habitats on Earth and are relevant for agriculture, health, and climate. Deciphering the mechanisms that determine microbiota dynamics and functioning within the context of their respective environments or hosts (the microbiomes) is crucially important. However, the sheer taxonomic, metabolic, functional, and spatial complexity of most microbiomes poses substantial challenges to advancing our knowledge of these mechanisms.

Optimal enzyme utilization suggests that concentrations and thermodynamics determine binding mechanisms and enzyme saturations.

Deciphering the metabolic functions of organisms requires understanding the dynamic responses of living cells upon genetic and environmental perturbations, which in turn can be inferred from enzymatic activity. In this work, we investigate the optimal modes of operation for enzymes in terms of the evolutionary pressure driving them toward increased catalytic efficiency. We develop a framework using a mixed-integer formulation to assess the distribution of thermodynamic forces and enzyme states, providing detailed insights into the enzymatic mode of operation.

Genome-encoded cytoplasmic double-stranded RNAs, found in ALS-FTD brain, propagate neuronal loss.

Triggers of innate immune signaling in the CNS of patients with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD) remain elusive. We report the presence of cytoplasmic double-stranded RNA (cdsRNA), an established trigger of innate immunity, in ALS-FTD brains carrying intronic hexanucleotide expansions that included genomically encoded expansions of the GC repeat sequences. The presence of cdsRNA in human brains was coincident with cytoplasmic TAR DNA binding protein 43 (TDP-43) inclusions, a pathologic hallmark of ALS/FTD.

Controlling optical return loss in production silicon photonic metamaterial fiber couplers.

A cost-efficient and low-complexity optical input/output (I/O) packaging solution is a substantial challenge for volume production of photonic integrated circuits. To address this, metamaterial fiber couplers are an attractive solution for integrated photonic devices especially for optical I/O, interfacing standard optical fibers to photonic chips. They offer the advantages of refractive index engineering to achieve better mode match as well as higher fabrication tolerances.

Age-dependent degeneration of an identified adult leg motor neuron in a SOD1 model of ALS.

Mutations in superoxide dismutase 1 (SOD1) cause familial amyotrophic lateral sclerosis (ALS) in humans. ALS is a neurodegenerative disease characterized by progressive motor neuron loss leading to paralysis and inevitable death in affected individuals. Using a gene replacement strategy to introduce disease mutations into the orthologous () gene, here, we characterize changes at the neuromuscular junction using longer-lived mutant adults.

Circuit Dysfunction in Model First Detected in Sensory Feedback Prior to Motor Neuron Degeneration Is Alleviated by BMP Signaling.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which the origin and underlying cellular defects are not fully understood. Although motor neuron degeneration is the signature feature of ALS, it is not clear whether motor neurons or other cells of the motor circuit are the site of disease initiation. To better understand the contribution of multiple cell types in ALS, we made use of a knock-in model, in which all cells harbor the disease allele.

Human SOD1 ALS Mutations in a Drosophila Knock-In Model Cause Severe Phenotypes and Reveal Dosage-Sensitive Gain- and Loss-of-Function Components.

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage.

Can pregnancy-associated plasma protein-A be a marker for the assessment of atherosclerosis risk in patients with chronic plaque psoriasis?

Introduction: Psoriasis is an immune-mediated chronic inflammatory dermatosis. Several studies have shown that patients with psoriasis have a much greater risk of cardiovascular diseases than the normal population. The chronic inflammation observed in psoriasis is thought to have a role in the development of atherosclerosis and vascular endothelial injury.

A New Approach in the Treatment of Keloids: UVA-1 Laser.

Keloids are scars that grow beyond the boundaries of a cutaneous injury, inflammation, surgical incision, or burn. They are the result of an overgrowth of dense fibrous tissue that usually develops after healing of a skin injury, and do not usually regress spontaneously. In addition to symptomatic relief, cosmetic concern is the primary reason patients seek medical intervention.

Biomass production from electricity using ammonia as an electron carrier in a reverse microbial fuel cell.

The storage of renewable electrical energy within chemical bonds of biofuels and other chemicals is a route to decreasing petroleum usage. A critical challenge is the efficient transfer of electrons into a biological host that can covert this energy into high energy organic compounds. In this paper, we describe an approach whereby biomass is grown using energy obtained from a soluble mediator that is regenerated electrochemically.

Auto-regulatory RNA editing fine-tunes mRNA re-coding and complex behaviour in Drosophila.

Auto-regulatory feedback loops are a common molecular strategy used to optimize protein function. In Drosophila, many messenger RNAs involved in neuro-transmission are re-coded at the RNA level by the RNA-editing enzyme, dADAR, leading to the incorporation of amino acids that are not directly encoded by the genome. dADAR also re-codes its own transcript, but the consequences of this auto-regulation in vivo are unclear.

Engineered alterations in RNA editing modulate complex behavior in Drosophila: regulatory diversity of adenosine deaminase acting on RNA (ADAR) targets.

Select proteins involved in electrical and chemical neurotransmission are re-coded at the RNA level via the deamination of particular adenosines to inosine by adenosine deaminases acting on RNA (ADARs). It has been hypothesized that this process, termed RNA editing, acts to "fine-tune" neurophysiological properties in animals and potentially downstream behavioral outputs. However, the extreme phenotypes resulting from deletions of adar loci have precluded investigations into the relationship between ADAR levels, target transcripts, and complex behaviors.

Effects of the acute exposure to the electromagnetic field of mobile phones on human auditory brainstem responses.

The purpose of this study was to evaluate the short-term effects of the electromagnetic fields (EMF) of mobile phones on human auditory brainstem responses. This prospective study of healthy adults evaluated the influence of EMF. Eighteen healthy adult volunteers participated in this study.

Marble impaction in the nasopharynx following oral ingestion.

Foreign body ingestion is an important emergency occurring in childhood. In this article, we report the case of a 5-year-old girl with marble impaction in the nasopharynx, which had not been discovered by routine X-rays of the chest and abdomen at the time of ingestion. The patient presented 4 months after the event with typical symptoms of adenoid hypertrophy and sinusitis, and the diagnosis was established on the basis of a plain film of the nasopharynx.