EHMT2 as a Candidate Gene for an Autosomal Recessive Neurodevelopmental Syndrome.

Neurodevelopmental disorders (NDD) comprise clinical conditions with high genetic heterogeneity and a notable enrichment of genes involved in regulating chromatin structure and function. The EHMT1/2 epigenetic complex plays a crucial role in repression of gene transcription in a highly tissue- and temporal-specific manner. Mutations resulting in heterozygous loss-of-function (LoF) of EHMT1 are implicated in Kleefstra syndrome 1 (KS1).

Skipping of Exon 20 in EP300: A Novel Variant Linked to Rubinstein-Taybi Syndrome With Atypical and Severe Clinical Manifestations.

Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder linked to haploinsufficiency of CREBBP (RSTS1) and EP300 (RSTS2) genes. Characteristic features often include distinctive facial traits, broad thumbs and toes, short stature, and various degrees of intellectual disability. The clinical presentation of RSTS is notably variable, making it challenging to establish a clear genotype-phenotype correlation, except for specific variants which cause the allelic Menke-Hennekam syndrome.

Epigenomic and phenotypic characterization of DEGCAGS syndrome.

Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities syndrome (DEGCAGS, MIM #619488) is caused by biallelic, loss-of-function (LoF) ZNF699 variants, and is characterized by variable neurodevelopmental disability, discordant organ anomalies among full siblings and infant mortality. ZNF699 encodes a KRAB zinc finger protein of unknown function. We aimed to investigate the genotype-phenotype spectrum of DEGCAGS and the possibility of a diagnostic DNA methylation episignature, to facilitate the diagnosis of a highly variable condition lacking pathognomonic clinical findings.

Saliva-STAT: Sample-to-answer saliva test for COVID-19.

Highly accessible and highly accurate diagnostics are necessary to combat rapidly-spreading infectious diseases, such as the recent COVID-19 pandemic. While lateral flow antigen tests have become pervasive, they are insufficiently sensitive to detect early or asymptomatic disease. Nucleic acid amplification tests provide the needed sensitivity, but accessibility of these tests continues to be a challenge due to the need for precise sample processing steps.

Identification of a DNA methylation episignature for recurrent constellations of embryonic malformations.

The term "recurrent constellations of embryonic malformations" (RCEM) is used to describe a number of multiple malformation associations that affect three or more body structures. The causes of these disorders are currently unknown, and no diagnostic marker has been identified. Consequently, providing a definitive diagnosis in suspected individuals is challenging.

Congenital hyperinsulinism and novel KDM6A duplications -resolving pathogenicity with genome and epigenetic analyses.

Context: Hyperinsulinemic hypoglycemia (HI) can be the presenting feature of Kabuki syndrome (KS), which is caused by loss-of-function variants in KMT2D or KDM6A. As these genes play a critical role in maintaining methylation status in chromatin, individuals with pathogenic variants have a disease-specific epigenomic profile -an episignature.

Objective: We evaluated the pathogenicity of three novel partial KDM6A duplications identified in three individuals presenting with neonatal-onset HI without typical features of KS at the time of genetic testing.

Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features.

Heterozygous missense variants and in-frame indels in SMC3 are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with SMC3 loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in SMC3, and analyzed population databases to characterize mutational intolerance in this gene.

Diagnostic utility and reporting recommendations for clinical DNA methylation episignature testing in genetically undiagnosed rare diseases.

Purpose: This study aims to assess the diagnostic utility and provide reporting recommendations for clinical DNA methylation episignature testing based on the cohort of patients tested through the EpiSign Clinical Testing Network.

Methods: The EpiSign assay utilized unsupervised clustering techniques and a support vector machine-based classification algorithm to compare each patient's genome-wide DNA methylation profile with the EpiSign Knowledge Database, yielding the result that was reported. An international working group, representing distinct EpiSign Clinical Testing Network health jurisdictions, collaborated to establish recommendations for interpretation and reporting of episignature testing.

Redox-enabled electronic interrogation and feedback control of hierarchical and networked biological systems.

Microelectronic devices can directly communicate with biology, as electronic information can be transmitted via redox reactions within biological systems. By engineering biology's native redox networks, we enable electronic interrogation and control of biological systems at several hierarchical levels: proteins, cells, and cell consortia. First, electro-biofabrication facilitates on-device biological component assembly.

Heterozygous loss-of-function variants are associated with variable and incompletely penetrant growth and developmental features.

Heterozygous missense variants and in-frame indels in are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in , and analyzed population databases to characterize mutational intolerance in this gene.

Network-based redox communication between abiotic interactive materials.

Recent observations that abiotic materials can engage in redox-based interactive communication motivates the search for new redox-active materials. Here we fabricated a hydrogel from a four-armed thiolated polyethylene glycol (PEG-SH) and the bacterial metabolite, pyocyanin (PYO). We show that: (i) the PYO-PEG hydrogel is reversibly redox-active; (ii) the molecular-switching and directed electron flow within this PYO-PEG hydrogel requires both a thermodynamic driving force (i.

Pediatric Otoscopy Video Screening With Shift Contrastive Anomaly Detection.

Ear related concerns and symptoms represent the leading indication for seeking pediatric healthcare attention. Despite the high incidence of such encounters, the diagnostic process of commonly encountered diseases of the middle and external presents a significant challenge. Much of this challenge stems from the lack of cost effective diagnostic testing, which necessitates the presence or absence of ear pathology to be determined clinically.

Real-time ultra-sensitive detection of SARS-CoV-2 by quasi-freestanding epitaxial graphene-based biosensor.

We report the rapid detection of SARS-CoV-2 in infected patients (mid-turbinate swabs and exhaled breath aerosol samples) in concentrations as low as 60 copies/mL of the virus in seconds by electrical transduction of the SARS-CoV-2 S1 spike protein antigen via SARS-CoV-2 S1 spike protein antibodies immobilized on bilayer quasi-freestanding epitaxial graphene without gate or signal amplification. The sensor demonstrates the spike protein antigen detection in a concentration as low as 1 ag/mL. The heterostructure of the SARS-CoV-2 antibody/graphene-based sensor is developed through a simple and low-cost fabrication technique.

Association of acute psychosocial stress with oxidative stress: Evidence from serum analysis.

Growing evidence implicates an association between psychosocial stress and oxidative stress (OxSt) although there are not yet reliable biomarkers to study this association. We used a Trier Social Stress Test (TSST) and compared the response of a healthy control group (HC; N=10) against the response of a schizophrenia group (SCZ; N=10) that is expected to have higher levels of OxSt. Because our previous study showed inconsistent changes in conventional molecular markers for stress responses in the neuroendocrine and immune systems, we analyzed the same serum samples using a separate reducing capacity assay that provides a more global measurement of OxSt.

Light field camera study of near-ground turbulence anisotropy and observation of small outer-scales.

Understanding turbulence effects on laser beam propagation is critical to the emerging design, study, and test of many long-range free space optical (FSO) communication and directed energy systems. Conventional studies make the prevalent assumption of isotropic turbulence, while more recent results suggest anisotropic turbulence for atmospheric channels within a few meters elevation above the ground. As countless FSO systems have been and continue to be deployed in such channels, analysis of anisotropic modelings has become one of the fastest growing areas in FSO research.

Dynamics of analog logic-gate networks for machine learning.

We describe the continuous-time dynamics of networks implemented on Field Programable Gate Arrays (FPGAs). The networks can perform Boolean operations when the FPGA is in the clocked (digital) mode; however, we run the programed FPGA in the unclocked (analog) mode. Our motivation is to use these FPGA networks as ultrafast machine-learning processors, using the technique of reservoir computing.

Measuring the turbulence profile in the lower atmospheric boundary layer.

Optical turbulence can have a severe effect on the propagation of laser beams through the atmosphere. In free space optics and directed energy applications, these laser beams quite often propagate along a slant or vertical path. In these cases, the refractive index structure function parameter cannot be assumed constant, since it varies with height.

Phase and amplitude beam shaping with two deformable mirrors implementing input plane and Fourier plane phase modifications.

We find that ideas in optical image encryption can be very useful for adaptive optics in achieving simultaneous phase and amplitude shaping of a laser beam. An adaptive optics system with simultaneous phase and amplitude shaping ability is very desirable for atmospheric turbulence compensation. Atmospheric turbulence-induced beam distortions can jeopardize the effectiveness of optical power delivery for directed-energy systems and optical information delivery for free-space optical communication systems.

Using turbulence scintillation to assist object ranging from a single camera viewpoint.

Image distortions caused by atmospheric turbulence are often treated as unwanted noise or errors in many image processing studies. Our study, however, shows that in certain scenarios the turbulence distortion can be very helpful in enhancing image processing results. This paper describes a novel approach that uses the scintillation traits recorded on a video clip to perform object ranging with reasonable accuracy from a single camera viewpoint.

Multi-aperture laser transmissometer system for long-path aerosol extinction rate measurement.

We present the theory, design, simulation, and experimental evaluations of a new laser transmissometer system for aerosol extinction rate measurement over long paths. The transmitter emits an ON/OFF modulated Gaussian beam that does not require strict collimation. The receiver uses multiple point detectors to sample the sub-aperture irradiance of the arriving beam.

Omnidirectional beacon-localization using a catadioptric system.

We present a catadioptric beacon localization system that can provide mobile network nodes with omnidirectional situational awareness of neighboring nodes. In this system, a receiver composed of a hyperboloidal mirror and camera is used to estimate the azimuth, elevation, and range of an LED beacon. We provide a general framework for understanding the propagation of error in the angle-of-arrival estimation and then present an experimental realization of such a system.

Long-range vibration detection system using heterodyne interferometry.

We present the design and performance of an extremely sensitive coherent remote vibration detection system using optical heterodyne vibration of phase shifts produced by laser light scattered off a remote target. The resulting phase-modulated intermediate RF of 200 MHz, which carries the vibrational motion of the target, is demodulated down to baseband using an RF in-phase and quadrature demodulator. Acquisition and calculation of the target phase angle is carried out on a custom-made control board which utilizes high-resolution A/D converters, variable gain amplifiers, and a Spartan-6 field programmable gate array.

Effect of growth hormone on basal and LH-stimulated steroid secretion by chicken yellow ovarian follicles. An in vitro study.

The aim of the present study was to determine the effect of growth hormone (GH) on basal and LH-regulated steroid secretion by yellow hierarchical follicles before and after maturation, and the granulosa and theca layers of the largest preovulatory follicles during the ovulatory cycle in the chicken. In the first experiment, whole yellow follicles (8-12 mm, 12-18 mm, 18-24 mm and 24-30 mm) isolated from 15 and 17-18 week-old chickens were used. In the second experiment, the granulosa and theca layers of the 3 largest yellow preovulatory follicles (F3 View Article and Find Full Text PDF

Independent, non-IGF-I mediated, GH action on estradiol secretion by prehierarchical ovarian follicles in chicken. In vitro study.

Information concerning the role of growth hormone (GH) in the local regulation of ovarian activity in birds is limited. Therefore, the aim of the present study was to determine whether in the domestic hen GH influences in vitro estradiol secretion by prehierarchical ovarian follicles. Moreover, the interaction between GH and IGF-I on estradiol secretion was examined.