Overcoming CD spectroscopy sample preparation challenges in protein structural analysis for biosimilars.

Circular dichroism (CD) spectroscopy is a valuable tool in the pharmaceutical industry for determining the secondary and tertiary structure, folding, stability, and interactions of proteins in biosimilars. However, protein aggregation due to its interaction with surfactants can introduce variations in CD spectra, leading to false interpretations. To investigate this effect, we prepared aqueous solutions of α-chymotrypsin with the same amount of surfactant but at different solution preparation steps. Interestingly, the CD spectra of these solutions showed slight differences despite having the same surfactant concentration. This suggests that the order of surfactant addition can influence protein conformation. To address this issue, we propose a method for preparing aqueous protein solutions that yields reproducible CD spectra. This method is expected to benefit the pharmaceutical industry by improving the accuracy of CD spectroscopy for protein structural analysis and evaluation of protein functionality

The role of fatty acid desaturases in epidermal metabolism

The lipid composition of skin is important to a variety of functions served by this organ. Therefore, skin expresses multiple enzymes that synthesize and metabolize lipids. An important class of lipid metabolism enzymes expressed in skin is the lipid desaturases. Various isoforms of stearoyl-CoA desaturase, a delta-9 desaturase, as well as a delta-6 desaturase alter the lipid composition of the skin, thereby affecting skin barrier homeostasis and consequently, whole body energy balance. This review will focus on the role of fatty acid desaturases in maintaining epidermal metabolism

Effects of Visual Locomotion and Tactile Stimuli Duration on the Emotional Dimensions of the Cutaneous Rabbit Illusion

In this study, we assessed the emotional dimensions (valence, arousal, and dominance) of the multimodal visual-cutaneous rabbit effect. Simultaneously to the tactile bursts on the forearm, visual silhouettes of saltatorial animals (rabbit, kangaroo, spider, grasshopper, frog, and flea) were projected on the left arm. Additionally, there were two locomotion conditions: taking-off and landing. The results showed that the valence dimension (happy-unhappy) was only affected by the visual stimuli with no effect of the tactile conditions nor the locomotion phases. Arousal (excited-calm) showed a significant difference for the three tactile conditions with an interaction effect with the locomotion condition. Arousal scores were higher when the taking-off condition was associated with the intermediate duration (24 ms) and when the landing condition was associated with either the shortest duration (12 ms) or the longest duration (48 ms). There was no effect for the dominance dimension. Similar to our previous results, the valence dimension seems to be highly affected by visual information reducing any effect of tactile information, while touch can modulate the arousal dimension. This can be beneficial for designing multimodal interfaces for virtual or augmented reality.acceptedVersionPeer reviewe

Spontaneous allelic variant in deafness–blindness gene \u3ci\u3eUsh1g\u3c/i\u3e resulting in an expanded phenotype

Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target-specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards-walking behavior in open-field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1gbw/bwnull mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner-ear hair-cell function, including a complete lack of auditory brainstem responses and vestibular-evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell\u27s kinocilial links. Consistent with other Usher type 1 models, Ush1gbw/bw mice had no substantial retinal degeneration compared with Ush1gbw/+ controls. In contrast to previously described Ush1g alleles, this new allele provides the first knockout model for this gene

Mitochondrial DNA Integrity: Role in Health and Disease

As the primary cellular location for respiration and energy production, mitochondria serve in a critical capacity to the cell. Yet, by virtue of this very function of respiration, mitochondria are subject to constant oxidative stress that can damage one of the unique features of this organelle, its distinct genome. Damage to mitochondrial DNA (mtDNA) and loss of mitochondrial genome integrity is increasingly understood to play a role in the development of both severe early-onset maladies and chronic age-related diseases. In this article, we review the processes by which mtDNA integrity is maintained, with an emphasis on the repair of oxidative DNA lesions, and the cellular consequences of diminished mitochondrial genome stability

Quasi-Resonant Converter for Electric Vehicle Charging Applications: Analysis, Design, and Markov Model Use for Reliability Estimation

This article presents a quasi-resonant converter (QRC) with multiple sources. A QRC has many benefits, such as high gain, constant current, and nominal voltage stress on MOSFET, with an up to 49% duty cycle with fewer switches. These features of the converter make it suitable for electrical vehicle (EV) off-board charging, which requires significant voltage gain. As the switch operates under soft switching condition, the converter has reduced power loss, improved efficiency, and increased reliability. To reduce grid dependency, the suggested QRC is housed with a grid and PV at the input ports. The proposed converter is modeled using mathematical equations and examined using the MATLAB platform under different operating conditions. In this work, analysis of the steady state, along with components design, estimation of the voltage and current stresses, are addressed. Further, the reliability of the QRC based on the probability of components failure is carried out using the Markov model. The hardware results are observed to validate the design, operation, efficiency, and suitability of the proposed QRC for EV off-board charging applications. A 400-watt test rig is designed to assess the performance of QRC

Designing an Intelligent Partner for Social Communication in Autism

This paper describes the Intelligent Engine (IE) of ECHOES, a serious game built for helping young children with Autism Spectrum Conditions acquire social communication skills. ECHOES IE’s main component is an autonomous virtual agent that acts as a credible social partner for children with autism by engaging them in interactive learning activities. The other IE components are a user model, a drama manager and a social communication engine. We discuss how AI technology allows us to satisfy the requirements for the design of the agent and the learning activities that we identified through consultations with children and carers and a review of best practices for autism intervention. We present experimental results pertaining to the agent’s effectiveness, which show encouraging improvements for a number of children