Machine Learning Ensemble Directed Engineering of Genetically Encoded Fluorescent Calcium Indicators.

In this study, we focused on the transformative potential of machine learning in the engineering of genetically encoded fluorescent indicators (GEFIs), protein-based sensing tools that are critical for real-time monitoring of biological activity. GEFIs are complex proteins with multiple dynamic states, rendering optimization by trial-and-error mutagenesis a challenging problem. We applied an alternative approach using machine learning to predict the outcomes of sensor mutagenesis by analyzing established libraries that link sensor sequences to functions.

Intestinal parasitic infections in a community from Pampa del Indio, Chaco (Argentina) and their association with socioeconomic and environmental factors.

Neglected tropical diseases are a group of 20 disabling diseases, which, in particular, are the most common chronic infections in the most vulnerable people. This study aimed to characterize the infection by intestinal parasites (IPs) in dwellings from a peri-urban neighborhood in Pampa del Indio, Chaco (Argentina), and its association with socioeconomic and environmental variables. Single stool samples were collected from all individuals older than 1 year through household visits and processed using coprological sedimentation and flotation techniques.

Loss of hypothalamic MCH decreases food intake in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is associated with impaired energy metabolism, including weight loss and decreased appetite which are negatively correlated with survival. Neural mechanisms underlying metabolic impairment in ALS remain unknown. ALS patients and presymptomatic gene carriers have early hypothalamic atrophy.

Leukemia-associated truncation of granulocyte colony-stimulating factor receptor impacts granulopoiesis throughout the life-course.

Introduction: The granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the gene, is involved in the production and function of neutrophilic granulocytes. Somatic mutations in leading to truncated G-CSFR forms are observed in acute myeloid leukemia (AML), particularly those subsequent to severe chronic neutropenia (SCN), as well as in a subset of patients with other leukemias.

Methods: This investigation introduced equivalent mutations into the zebrafish gene genome editing and used a range of molecular and cellular techniques to understand the impact of these mutations on immune cells across the lifespan.

Design of a metal-based deformable mirror for orthogonal beam deflection and highly dynamic beam oscillation.

We report on an opto-mechanical metal mirror design for highly dynamic, diffraction-limited focus shifting. Here, the mechanical geometry of the membrane is of crucial interest as it must provide sufficient optical performance to allow for diffraction limited focussing and have a high mechanical eigenfrequency to provide dynamic motions. The approach is the analytical consideration of the plate theory and provides the basis for a parameterized finite element model.

Evaluation of a 5-HT receptor agonist in a murine model of amyotrophic lateral sclerosis.

Degeneration of brainstem serotonin neurons has been demonstrated in ALS patients and mouse models and was found responsible for the development of spasticity. Consistent with involvement of central serotonin pathways, 5-HT receptor (5-HTR) was upregulated in microglia of ALS mice. Its deletion worsened disease outcome in the Sod1 mouse model and led to microglial degeneration.

Circulatory and Urinary B-Vitamin Responses to Multivitamin Supplement Ingestion Differ between Older and Younger Adults.

Multivitamin and mineral (MVM) supplements are frequently used amongst older populations to improve adequacy of micronutrients, including B-vitamins, but evidence for improved health outcomes are limited and deficiencies remain prevalent. Although this may indicate poor efficacy of supplements, this could also suggest the possibility for altered B-vitamin bioavailability and metabolism in older people. This open-label, single-arm acute parallel study, conducted at the Liggins Institute Clinical Research Unit in Auckland, compared circulatory and urinary B-vitamer responses to MVM supplementation in older (70.

Robotic automation of a UHPLC/MS-MS method profiling one-carbon metabolites, amino acids, and precursors in plasma.

Amino acids (AAs) and one-carbon (1-C) metabolism compounds are involved in a range of key metabolic pathways, and mediate numerous health and disease processes in the human body. Previous assays have quantified a limited selection of these compounds and typically require extensive manual handling. Here, we describe the robotic automation of an analytical method for the simultaneous quantification of 37 1-C metabolites, amino acids, and precursors using reversed-phase ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS-MS).

FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis.

Neuromuscular junction (NMJ) disruption is an early pathogenic event in amyotrophic lateral sclerosis (ALS). Yet, direct links between NMJ pathways and ALS-associated genes such as FUS, whose heterozygous mutations cause aggressive forms of ALS, remain elusive. In a knock-in Fus-ALS mouse model, we identified postsynaptic NMJ defects in newborn homozygous mutants that were attributable to mutant FUS toxicity in skeletal muscle.

Sex-Specific Associations of Blood-Based Nutrient Profiling With Body Composition in the Elderly.

The intake of adequate amounts and types of nutrients is key for sustaining health and a good quality of life, particularly in the elderly population. There is considerable evidence suggesting that physiological changes related to age and sex modify nutritional needs, and this may be related to age-associated changes in body composition (BC), specifically in lean and fat body mass. However, there is a clear lack of understanding about the association of nutrients in blood and BC parameters in the elderly.

Development of a prototype active optics system for future space telescopes.

It is envisaged that future large space telescopes will be lightweight and employ active optics to maintain optical quality throughout the mission lifetime. We have proposed a 4 m, two-mirror space telescope with an active optics system based on reimaging the telescope primary mirror onto a small active mirror (110 mm optical pupil). Using Zemax, we demonstrate the feasibility of using this mirror to correct low-order Zernike aberrations and show that the aberration is well corrected across the 2.

Temporally-stable active precision mount for large optics.

We present a temporally-stable active mount to compensate for manufacturing-induced deformations of reflective optical components. In this paper, we introduce the design of the active mount, and its evaluation results for two sample mirrors: a quarter mirror of 115 × 105 × 9 mm, and a full mirror of 228 × 210 × 9 mm. The quarter mirror with 20 actuators shows a best wavefront error rms of 10 nm.

Real-time adaptive optics testbed to investigate point-ahead angle in pre-compensation of Earth-to-GEO optical communication.

We explore adaptive optics (AO) pre-compensation for optical communication between Earth and geostationary (GEO) satellites in a laboratory experiment. Thus, we built a rapid control prototyping breadboard with an adjustable point-ahead angle where downlink and uplink can operate both at 1064 nm and 1550 nm wavelength. With our real-time system, beam wander resulting from artificial turbulence was reduced such that the beam hits the satellite at least 66% of the time as compared to merely 3% without correction.

Dietary salt regulates uroguanylin expression and signaling activity in the kidney, but not in the intestine.

The peptide uroguanylin (Ugn) is expressed at significant levels only in intestine and kidney, and is stored in both tissues primarily (perhaps exclusively) as intact prouroguanylin (proUgn). Intravascular infusion of either Ugn or proUgn evokes well-characterized natriuretic responses in rodents. Furthermore, Ugn knockout mice display hypertension and salt handling deficits, indicating that the Na(+) excretory mechanisms triggered when the peptides are infused into anesthetized animals are likely to operate under normal physiological conditions, and contribute to electrolyte homeostasis in conscious animals.

Reactivation of Chagas Disease in a Patient With Follicular Lymphoma Diagnosed by Means of Quantitative Real-Time Polymerase Chain Reaction.

We report a case of Chagas disease reactivation in a patient with stage IIb follicular lymphoma in the cecum. He was admitted to the hospital with neutropenia and fever. He had a history of right hemicolectomy 6 months earlier and had received the sixth cycle of chemotherapy with cyclophosphamide/doxorubicin/vincristine/prednisone/rituximab.

Mounting with compliant cylinders for deformable mirrors.

A method is presented to mount large aperture unimorph deformable mirrors by compliant cylinders (CC). The CCs are manufactured from a soft silicone, and shear testing is performed in order to evaluate the Young's modulus. A scale mirror model is assembled to evaluate mount-induced change of piezoelectric deformation, and its applicability for tightly focusing mirrors.

Performance of a thermal-piezoelectric deformable mirror under 6.2 kW continuous-wave operation.

The thermal-piezoelectric deformable mirror (TPDM) is a device employed to compensate for laser-induced mirror deformation and thermal lensing in high-power optical systems. The TPDM setup is a unimorph deformable mirror with thermal and piezoelectric actuation properties. Laser-induced thermal lensing is compensated for by heating of the TPDM.

The rat kidney contains high levels of prouroguanylin (the uroguanylin precursor) but does not express GC-C (the enteric uroguanylin receptor).

The peptide uroguanylin (Ugn) regulates enteric and renal electrolyte transport. Previous studies have shown that Ugn and its receptor GC-C (a ligand-activated guanylate cyclase) are abundant in the intestine. Less is known about Ugn and GC-C expression in the kidney.

Natriuretic and antikaliuretic effects of uroguanylin and prouroguanylin in the rat.

The peptide uroguanylin (Ugn) is stored and released as a propeptide (proUgn) by enterochromaffin cells in the intestine, and converted to Ugn and other metabolites in the renal tubules. Both proUgn and Ugn are natriuretic, although the response to proUgn is thought to depend on its conversion to Ugn within nephrons. To assess the efficiency of intrarenal conversion of proUgn to Ugn, we measured urinary Ugn excretion in rats following intravenous infusions of proUgn or Ugn.

The natriuretic peptide uroguanylin elicits physiologic actions through 2 distinct topoisomers.

The peptide uroguanylin regulates electrolyte transport in the intestine and kidney. Human uroguanylin has 2 conformations that can be stably isolated because of their slow interconversion rate. The A isomer potently activates the guanylate cyclase C receptor found primarily in the intestine.

Circulating prouroguanylin is processed to its active natriuretic form exclusively within the renal tubules.

The intestine and kidney are linked by a mechanism that increases salt excretion in response to salt intake. The peptide uroguanylin (UGn) is thought to mediate this signaling axis. Therefore, it was surprising to find (as reported in a companion publication) that UGn is stored in the intestine and circulates in the plasma almost exclusively in the form of its biologically inactive propeptide precursor, prouroguanylin (proUGn), and, furthermore, that infused proUGn leads to natriuretic activity.

Uroguanylin, an intestinal natriuretic peptide, is delivered to the kidney as an unprocessed propeptide.

Orally delivered salt stimulates renal salt excretion more effectively than does iv delivered salt. Although the mechanisms that underlie this "postprandial natriuresis" are poorly understood, the peptide uroguanylin (UGn) is thought to be a key mediator. However, the lack of selective assays for UGn gene products has hindered rigorous testing of this hypothesis.

Mass spectral characterization of peptide transmitters/hormones in the nervous system and neuroendocrine organs of the American lobster Homarus americanus.

The American lobster Homarus americanus is a decapod crustacean with both high economic and scientific importance. To facilitate physiological investigations of peptide transmitter/hormone function in this species, we have used matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nanoscale liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem mass spectrometry (nanoLC-ESI-Q-TOF MS/MS) to elucidate the peptidome present in its nervous system and neuroendocrine organs. In total, 84 peptides were identified, including 27 previously known H.

Identification of neuropeptides from the decapod crustacean sinus glands using nanoscale liquid chromatography tandem mass spectrometry.

Neurosecretory systems are known to synthesize and secrete a diverse class of peptide hormones which regulate many physiological processes. The crustacean sinus gland (SG) is a well-defined neuroendocrine site that produces numerous hemolymph-borne agents including the most complex class of endocrine signaling molecules--neuropeptides. As an ongoing effort to define the peptidome of the crustacean SG, we determine the neuropeptide complements of the SG of the Jonah crab, Cancer borealis, and the Maine lobster, Homarus americanus, using nanoflow liquid chromatography electrospray ionization quadrupole time-of-flight (ESI-QTOF) MS/MS.

Nitric oxide: an inhibitory retrograde modulator in the crustacean heart.

The nervous system innervates most of the organs in the body, and controls and coordinates their activities. Effective coordination depends on accurate feedback from target organs. Recent studies have identified a target-based feedback mechanism that regulates a simple neural circuit, the cardiac ganglion-a network of nine neurons whose rhythmic bursts of action potentials drive the contractions of the crustacean heart.