The Role of Recombinant AAV in Precise Genome Editing

The replication-defective, non-pathogenic, nearly ubiquitous single-stranded adeno-associated viruses (AAVs) have gained importance since their discovery about 50 years ago. Their unique life cycle and virus-cell interactions have led to the development of recombinant AAVs as ideal genetic medicine tools that have evolved into effective commercialized gene therapies. A distinctive property of AAVs is their ability to edit the genome precisely. In contrast to all current genome editing platforms, AAV exclusively utilizes the high-fidelity homologous recombination (HR) pathway and does not require exogenous nucleases for prior cleavage of genomic DNA. Together, this leads to a highly precise editing outcome that preserves genomic integrity without incorporation of indel mutations or viral sequences at the target site while also obviating the possibility of off-target genotoxicity. The stem cell-derived AAV (AAVHSCs) were found to mediate precise and efficient HR with high on-target accuracy and at high efficiencies. AAVHSC editing occurs efficiently in post-mitotic cells and tissues in vivo. Additionally, AAV also has the advantage of an intrinsic delivery mechanism. Thus, this distinctive genome editing platform holds tremendous promise for the correction of disease-associated mutations without adding to the mutational burden. This review will focus on the unique properties of direct AAV-mediated genome editing and their potential mechanisms of action.

Olfactory Mucosal Auto-transplantation in Spinal Cord Injury: A Clinical Trial, Saudi Arabia

Introduction: Spinal cord injury (SCI) results in loss of nervous tissue and consequently loss of motor and sensory function. Despite significant improvements in the early medical and surgical management of SCI, there is no effective treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. Restoration of function and reversal of paralysis following SCI is among the most daunting challenges in all of neuroscience research. Methodology: We decided to study the outcomes in chronic SCI (CSCI) after autologous olfactory mucosal transplantation into the spinal cord following detethering of the cord. The human surgical procedure of autologous olfactory mucosal transplantation was first developed by Carlos Lima and his colleagues. These investigators provided guidance for the surgical procedures in this study and the procedures on the first six participants were performed in their presence. Result: Patients were screened at different centers in the kingdom. A stringent inclusion and exclusion criteria were applied. Patients for this clinical trial were selected from individuals that suffered an SCI at least 12 months before their assessment and were chronically paraplegic or tetraplegic. The final twenty participants were selected after screening more than 125 patients. While some of them were rejected for medical reasons, some refused to participate upon receiving a full briefing and some of them were unable to fulfill the required psychosocial criteria. Conclusion: The details of the patients and the changes observed in their conditions post olfactory mucosal auto-transplantation will be discussed in detail in oral presentation with graphic results with marked significant improvement in motor and sensory levels of SCI patients as compared to before transplantation of olfactory mucosa. Olfactory unsheathing cells (OECs) are glia cells and continuous axon extension and successful topographic targeting of the olfactory receptor neurons responsible for the sense of smell (olfaction). Due to this distinctive property, OECs have been trialed in human cell transplant therapies to assist in the repair of central nervous system injuries, particularly those of the spinal cord. Although many studies have reported neurological improvement, therapy remains inconsistent and requires further improvement.

Empirical Analysis Revealing Privileged Chemical Space of Cosmetic Preservatives

Most cosmetic products require preservation to prevent microbial contamination and to ensure consumer safety. Due to regulatory restrictions and rejection by consumers, preservative options have become limited and the development of novel solutions is needed. This search can be guided by knowledge about favorable chemical space for cosmetic preservatives. Therefore, we used preservatives allowed in the EU as training set and calculated various molecular properties. Empirical analysis revealed two separated areas of privileged chemical space with the net charge as distinctive property. The first area comprises the group of neutral and anionic preservatives and is characterized by low molecular size as well as limited hydrogen-bonding capacity, polarity, and flexibility. The second area includes cationic preservatives, which are rather diffusely distributed regarding molecular weight and hydrogen-bonding, however, all members share high flexibility. Both groups significantly differ from antibiotics, reflecting the specific requirement of cosmetic preservation. The molecular properties defining the privileged chemical space are easy to calculate, and thus, can provide guidance for the development of novel preservatives.

Critical Repetition Rates for Perceptual Segregation of Time-Varying Auditory, Visual and Vibrotactile Stimulation

What sound quality has led to exclude infrasound from sound in the conventional hearing range? We examined whether temporal segregation of pressure pulses is a distinctive property and evaluated this perceptual limit via an adaptive psychophysical procedure for pure tones and carriers of different envelopes. Further, to examine across-domain similarity and individual covariation of this limit, here called the critical segregation rate (CSR), it was also measured for various periodic visual and vibrotactile stimuli. Results showed that sequential auditory or vibrotactile stimuli separated by at least ~80‒90 ms (~11‒12-Hz repetition rates), will be perceived as perceptually segregated from one another. While this limit did not statistically differ between these two modalities, it was significantly lower than the ~150 ms necessary to perceptually segregate successive visual stimuli. For the three sensory modalities, stimulus periodicity was the main factor determining the CSR, which apparently reflects neural recovery times of the different sensory systems. Among all experimental conditions, significant within- and across-modality individual CSR correlations were observed, despite the visual CSR (mean: 6.8 Hz) being significantly lower than that of both other modalities. The auditory CSR was found to be significantly lower than the frequency above which sinusoids start to elicit a tonal quality (19 Hz; recently published for the same subjects). Returning to our initial question, the latter suggests that the cessation of tonal quality — not the segregation of pressure fluctuations — is the perceptual quality that has led to exclude infrasound (sound with frequencies < 20 Hz) from the conventional hearing range.

Accidental synthesis of a previously unknown quasicrystal in the first atomic bomb test

The first test explosion of a nuclear bomb, the Trinity test of 16 July 1945, resulted in the fusion of surrounding sand, the test tower, and copper transmission lines into a glassy material known as “trinitite.” Here, we report the discovery, in a sample of red trinitite, of a hitherto unknown composition of icosahedral quasicrystal, Si61Cu30Ca7Fe2. It represents the oldest extant anthropogenic quasicrystal currently known, with the distinctive property that its precise time of creation is indelibly etched in history. Like the naturally formed quasicrystals found in the Khatyrka meteorite and experimental shock syntheses of quasicrystals, the anthropogenic quasicrystals in red trinitite demonstrate that transient extreme pressure–temperature conditions are suitable for the synthesis of quasicrystals and for the discovery of new quasicrystal-forming systems.

On Proof Complexities Relations in Some Systems of Propositional Calculus

The number of linear proofs steps for some sets of formulas is compared in the folowing systems of propositional calculus: PK – seguent system with cut rule, PK— - the same system without cut rule, SPK – the same system with substitution rule, QPK – the same system with quantifier rules. The number of steps of tree-like proofs in the same systems for some considered set of formulas is compared from Alessandra Carbone in [1] and some distinctive property of the system QPK is revealed: QPK has an exponential speed-up over the systems SPK and PK, which, in their turn, have an exponential speed-up over the system PK—. This result drew the heavy interest for the study of the system QPK. In this work for linear proofs steps in the same systems the other relations are received: it is showed that the system QPK has no preference over the system SPK, it is showed also that for the considered formula sets the system PK has no preference over the system PK—, which, in its turn, has no preference over the monotone system PMon. It is proved also, that the same results are reliable for some other sets of formulas and for other systems as well.

Antimicrobial Activity of Biosynthesized Metal Nanoparticles

It has been well documented that microbes are able to create self-defense against conventional antibiotics. Such drug-resistant property of the microbes always inspired the researchers to develop an alternative strategy to control the growth of pathogenic microbes. Nanoparticles have received major importance because of their distinctive property over corresponding bulk material. For such unique property, from the recent past, research has been focused on the nanotechnology to uplift the biomedical sciences but hazardous byproducts of nanoparticle synthesis makes always retardation. In this review, we emphasized and elaborated the biosynthesis process of metal nanoparticles and how such particles can be considered for anti-microbial context.

Synthesis of Bioactive Silver Nanoparticles by a Pseudomonas Strain Associated with the Antarctic Psychrophilic Protozoon Euplotes focardii

The synthesis of silver nanoparticles (AgNPs) by microorganisms recently gained a greater interest due to its potential to produce them in various sizes and morphologies. In this study, for AgNP biosynthesis, we used a new Pseudomonas strain isolated from a consortium associated with the Antarctic marine ciliate Euplotes focardii. After incubation of Pseudomonas cultures with 1 mM of AgNO3 at 22 °C, we obtained AgNPs within 24 h. Scanning electron (SEM) and transmission electron microscopy (TEM) revealed spherical polydispersed AgNPs in the size range of 20–70 nm. The average size was approximately 50 nm. Energy dispersive X-ray spectroscopy (EDS) showed the presence of a high intensity absorption peak at 3 keV, a distinctive property of nanocrystalline silver products. Fourier transform infrared (FTIR) spectroscopy found the presence of a high amount of AgNP-stabilizing proteins and other secondary metabolites. X-ray diffraction (XRD) revealed a face-centred cubic (fcc) diffraction spectrum with a crystalline nature. A comparative study between the chemically synthesized and Pseudomonas AgNPs revealed a higher antibacterial activity of the latter against common nosocomial pathogen microorganisms, including Escherichia coli, Staphylococcus aureus and Candida albicans. This study reports an efficient, rapid synthesis of stable AgNPs by a new Pseudomonas strain with high antimicrobial activity.

Borromean Feshbach resonance in $^{11}$Li studied via $^{11}$Li($p$,$p'$)

A dipole resonance of $^{11}$Li is found by a $^9$Li + $n$ + $n$ three-body model analysis with the complex-scaling method. The resonance can be interpreted as a bound state in the $^{10}$Li + $n$ system, i.e., a Feshbach resonance in the $^9$Li + $n$ + $n$ system. As a characteristic feature of the Feshbach resonance of $^{11}$Li, the $^{10}$Li + $n$ threshold is open above the $^{9}$Li + $n$ + $n$ one, which reflects a distinctive property of the Borromean system. A microscopic four-body reaction calculation for the $^{11}$Li($p$,$p'$) reaction at 6 MeV/nucleon is performed by taking into account the resonant and nonresonant continuum states of the three-body system. The calculation of angular distributions of the elastic and inelastic scattering as well as the energy spectrum reproduced a recent experimental result. Furthermore, the $E1$ strength distribution from a Coulomb dissociation experiment was also reproduced in this framework. This means that the existence of the Borromean Feshbach resonance may consistently answer a long-standing open question of an excited state of $^{11}$Li.

Estimating the Mutual Information between Two Discrete, Asymmetric Variables with Limited Samples

Determining the strength of nonlinear, statistical dependencies between two variables is a crucial matter in many research fields. The established measure for quantifying such relations is the mutual information. However, estimating mutual information from limited samples is a challenging task. Since the mutual information is the difference of two entropies, the existing Bayesian estimators of entropy may be used to estimate information. This procedure, however, is still biased in the severely under-sampled regime. Here, we propose an alternative estimator that is applicable to those cases in which the marginal distribution of one of the two variables—the one with minimal entropy—is well sampled. The other variable, as well as the joint and conditional distributions, can be severely undersampled. We obtain a consistent estimator that presents very low bias, outperforming previous methods even when the sampled data contain few coincidences. As with other Bayesian estimators, our proposal focuses on the strength of the interaction between the two variables, without seeking to model the specific way in which they are related. A distinctive property of our method is that the main data statistics determining the amount of mutual information is the inhomogeneity of the conditional distribution of the low-entropy variable in those states in which the large-entropy variable registers coincidences.