Identification of potent HSV antivirals using 3D bioprinted human skin equivalents.

Herpes simplex virus (HSV) infection has worldwide public health concerns and lifelong medical impacts. The standard therapy, acyclovir, has limited efficacy in preventing HSV subclinical virus shedding, and drug resistance occurs in immunocompromised patients, highlighting the need for novel therapeutics. HSV infection manifests in the skin epidermal layer, but current drug discovery utilizes Vero cells and fibroblasts monolayer cultures, capturing neither relevance nor tissue environment.

The use of ectopic volar fibroblasts to modify skin identity.

Skin identity is controlled by intrinsic features of the epidermis and dermis and their interactions. Modifying skin identity has clinical potential, such as the conversion of residual limb and stump (nonvolar) skin of amputees to pressure-responsive palmoplantar (volar) skin to enhance prosthesis use and minimize skin breakdown. Greater keratin 9 () expression, higher epidermal thickness, keratinocyte cytoplasmic size, collagen length, and elastin are markers of volar skin and likely contribute to volar skin resiliency.

Regional variation in the organization and connectivity of the first synapse in the primate night vision pathway.

Sensitivity of primate daylight vision varies across the visual field. This is attributed to regional variations in cone photoreceptor density and synaptic connectivity of the underlying circuitry. In contrast, we have limited understanding of how synapse organization of the primate night vision pathway changes across space.

Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration.

Age-related macular degeneration (AMD), a leading cause of blindness, initiates in the outer-blood-retina-barrier (oBRB) formed by the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. The mechanisms of AMD initiation and progression remain poorly understood owing to the lack of physiologically relevant human oBRB models. To this end, we engineered a native-like three-dimensional (3D) oBRB tissue (3D-oBRB) by bioprinting endothelial cells, pericytes, and fibroblasts on the basal side of a biodegradable scaffold and establishing an RPE monolayer on top.

Pattern Electroretinogram Parameters and their Associations with Optical Coherence Tomography in Glaucoma Suspects.

Aim: To investigate whether steady state pattern electroretinogram (ssPERG) could identify retinal ganglion cell (RGC) dysfunction, and to assess the relationship between ssPERG with optical coherence tomography (OCT) measurements in glaucoma suspects (GS).

Materials And Methods: This was a prospective cohort study of GS, identified based on suspicious optic disk appearance and glaucoma risk factors. Complete eye exam, Standard automated perimetry, OCT, and ssPERG were performed.

Pattern Electroretinogram Parameters Are Associated with Optic Nerve Morphology in Preperimetric Glaucoma after Adjusting for Disc Area.

Purpose: We examined the relationships between pattern electroretinogram and optical coherence tomography derived optic nerve head measurements, after controlling for disc area.

Methods: Thirty-two eyes from 20 subjects with preperimetric glaucoma underwent pattern electroretinogram and optical coherence tomography. Pattern electroretinogram parameters (Magnitude, MagnitudeD, and MagnitudeD/Magnitude ratio) and optic nerve head measurements (rim area, average cup to disc ratio, vertical cup to disc ratio, cup volume, retinal nerve fiber layer thickness sectors, and Bruch's membrane opening-minimum rim width thickness sectors) were analyzed after controlling for disc area.

A dual role for Ca1.4 Ca channels in the molecular and structural organization of the rod photoreceptor synapse.

Synapses are fundamental information processing units that rely on voltage-gated Ca (Ca) channels to trigger Ca-dependent neurotransmitter release. Ca channels also play Ca-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Ca1.

A 3D biofabricated cutaneous squamous cell carcinoma tissue model with multi-channel confocal microscopy imaging biomarkers to quantify antitumor effects of chemotherapeutics in tissue.

Cutaneous squamous cell carcinoma (cSCC) causes approximately 10,000 deaths annually in the U. S. Current therapies are largely ineffective against metastatic and locally advanced cSCC.

Fully Three-Dimensional Bioprinted Skin Equivalent Constructs with Validated Morphology and Barrier Function.

This article describes a method for the biofabrication of skin tissue equivalents in a multiwell plate format. The technique and results overcome shortcomings of previously published engineering methods, and show good architecture and barrier function from well to well; thus it may be used for compound functional testing and for the development of disease tissue models for screening.

An improved high cell density cultivation-iHCDC-strategy for leucine auxotrophic K12 ER2507.

Fed-batch processes are commonly used tools in high cell density cultivation of . However, the setup of a fed-batch process can be challenging, especially when working with genetically modified strains. This work deals with the design of a specific strategy for the leucine auxotrophic strain K12 ER2507 that is of interest for arabinose-inducible gene expression systems due to its mutation.

Sensitivity and specificity of short-duration transient visual evoked potentials (SD-tVEP) in discriminating normal from glaucomatous eyes.

Purpose: To evaluate the ability of the short-duration transient visual evoked potential (SD-tVEP) to discriminate between healthy eyes and eyes with early to advanced glaucomatous visual field loss.

Methods: We tested 30 eyes of 30 healthy controls and 45 eyes of 35 glaucoma patients. Normal eyes had 20/30 or better visual acuity and normal 24-2 Swedish interactive thresholding algorithm (SITA) Standard visual fields.

Short duration transient visual evoked potentials in glaucomatous eyes.

Purpose: To investigate the correlation between structural and functional damage in patients with asymmetric glaucoma using a newly developed short duration transient visual evoked potential (SD-tVEP) device.

Methods: Twenty-five patients with visual acuity ≥20/30 and asymmetric visual field (VF) loss [inter-eye difference in mean deviation index (MD) of at least 3 dB] were enrolled. Patients underwent optical coherence tomography (OCT) for macular thickness measurement, scanning laser polarimetry with variable corneal compensation for retinal nerve fiber layer measurement, and SD-tVEP (10% and 85% Michelson contrast, acquisition time of 20 s) in both eyes within 2 months.

Repeatability of short-duration transient visual evoked potentials in normal subjects.

To evaluate the within-session and inter-session repeatability of a new, short-duration transient visual evoked potential (SD-tVEP) device on normal individuals, we tested 30 normal subjects (20/20 visual acuity, normal 24-2 SITA Standard VF) with SD-tVEP. Ten of these subjects had their tests repeated within 1-2 months from the initial visit. Synchronized single-channel EEG was recorded using a modified Diopsys Enfant System (Diopsys, Inc.

Engineered single- and multi-cell chemotaxis pathways in E. coli.

We have engineered the chemotaxis system of Escherichia coli to respond to molecules that are not attractants for wild-type cells. The system depends on an artificially introduced enzymatic activity that converts the target molecule into a ligand for an E. coli chemoreceptor, thereby enabling the cells to respond to the new attractant.

Demonstration of a multichannel optical interconnection by use of imaging fiber bundles butt coupled to optoelectronic circuits.

Through five experiments, we demonstrate and characterize the basic functionality of imaging fiber bundles for optoelectronic chip-level interconnections. We demonstrate the transmission of spot arrays with spot sizes and a spot pitch roughly equal to 2 and 4 times the core pitch, respectively. We show that optoelectronic integrated circuits, including sources and detectors, can be butt coupled directly to fiber bundles without any additional optical elements.

Changing the specificity of a bacterial chemoreceptor.

The methyl-accepting chemotaxis proteins are a family of receptors in bacteria that mediate chemotaxis to diverse signals. To explore the plasticity of these proteins, we have developed a simple method for selecting cells that swim to target attractants. The procedure is based on establishing a diffusive gradient in semi-soft agar plates and does not require that the attractant be metabolized or degraded.

Novel antimicrobial peptide of human epididymal duct origin.

HE2, a gene expressed specifically in human epididymis, gives rise to multiple mRNAs that encode a group of small cationic secretory peptides. Localization of HE2 within the defensin gene cluster and prediction that beta-defensin-like modules exist suggest that these peptides have antimicrobial activity and represent components of the innate epithelial defense system of the epididymal duct. Reverse transcription-polymerase chain reaction analysis confirmed the occurrence of eight human HE2-derived transcripts, including minor mRNA variants, that had previously been shown only in animal species.

Extraction and modeling of the Oscillatory Potential: signal conditioning to obtain minimally corrupted Oscillatory Potentials.

A method of extracting a temporally bounded component of a composite signal has been developed which minimizes data corruption in signal processing. The composite signal is windowed in the time domain, padding signals are attached, and finally, the conditioned signal is filtered to extract the component of interest. The method has been utilized to extract the Oscillatory Potential (OP) from the Electroretinogram (ERG).

Synthesis and glycosylation of CD52, the major 'maturation-associated' antigen of rat spermatozoa, in the cauda epididymidis.

A western and lectin blot analysis was performed of the major 'maturation-associated' antigen of rat spermatozoa, which is the rat counterpart of human CD52. In the absence of a suitable antibody, direct study of this approximately 26 kDa antigen, named previously SMemG, had been difficult. In the present study, these problems were overcome by raising a polyclonal antibody against a chemosynthetic peptide predicted from the cDNA sequence of the antigen.

Male-specific modification of human CD52.

CD52 is an unusually short, bipolar glycopeptide bearing a highly charged N-linked carbohydrate moiety and a glycosylphosphatidylinositol membrane anchor. It is exclusively expressed on lymphocytes and in the male genital tract where it is shed into the seminal plasma and inserts into the sperm membrane. The sperm surface molecule has potential significance as a target for antibodies that inhibit sperm function and gamete interaction.

Regionalized expression of CD52 in rat epididymis is related to mRNA poly(A) tail length.

The regional pattern of CD52 expression in the rat epididymis was followed by Northern analyses and carbohydrate-labelling of glycoconjugates on Western blots. CD52 mRNA showed a novel aspect of regionalization, namely region-dependent length differences in its poly(A) tail. 'Short' CD52 mRNA molecules were present in all parts of this organ and also in the seminal vesicles.

The molecular biology of the sperm surface. Post-testicular membrane remodelling.

The membrane of testicular spermatozoa undergoes extensive changes in the epididymis, including rearrangement, modification and loss of pre-existing components, addition of new glycoproteins from epididymal secretions, and exchange of lipid constituents. As a result, the membrane of cauda epididymidal spermatozoa has a different composition and different properties, which collectively contribute to male fertility. Special significance has been attributed to sperm surface structures that only appear post-testicularly in the epididymis, the so-called "maturation antigens".

Ethical considerations in fitness and risk evaluations.

Physicians and other health care workers involved in the delivery of occupational health care can be confronted with difficult questions about fairness, justice and professional ethics. These issues and other ethical considerations are discussed.