Investigating the functionality of an OCT4-short response element in human induced pluripotent stem cells.

Pluripotent stem cells offer great therapeutic promise for personalized treatment platforms for numerous injuries, disorders, and diseases. Octamer-binding transcription factor 4 (OCT4) is a key regulatory gene maintaining pluripotency and self-renewal of mammalian cells. With site-specific integration for gene correction in cellular therapeutics, use of the OCT4 promoter may have advantages when expressing a suicide gene if pluripotency remains. However, the human OCT4 promoter region is 4 kb in size, limiting the capacity of therapeutic genes and other regulatory components for viral vectors, and decreasing the efficiency of homologous recombination. The purpose of this investigation was to characterize the functionality of a novel 967bp OCT4-short response element during pluripotency and to examine the OCT4 titer-dependent response during differentiation to human derivatives not expressing OCT4. Our findings demonstrate that the OCT4-short response element is active in pluripotency and this activity is in high correlation with transgene expression in vitro, and the OCT4-short response element is inactivated when pluripotent cells differentiate. These studies demonstrate that this shortened OCT4 regulatory element is functional and may be useful as part of an optimized safety component in a site-specific gene transferring system that could be used as an efficient and clinically applicable safety platform for gene transfer in cellular therapeutics

Stump Appendicitis: An Uncompleted Surgery, a Rare but Important Entity with Potential Problems

Appendicectomy for appendicitis is one of the commonest surgical procedures performed worldwide. The residual appendiceal stump left after an initial appendectomy risks the development of stump appendicitis. Stump appendicitis is a real recognized entity but not often considered when evaluating patients with right lower quadrant abdominal pain, especially those with past history of appendectomy. It remains a clinical challenge with the result that its diagnosis and effective treatment are often delayed with possible attendant morbidity or mortality. Stump appendicitis results from obstruction of the lumen of the remaining appendix stump, usually by a faecolith. This increases intraluminal pressure, impairing venous drainage and allowing subsequent bacterial infection. We present the case of a twenty-five (25)-year-old female who underwent laparoscopic appendicectomy and presented four and half (4(1/2)) months later with fever, right lower quadrant abdominal pain, and tenderness associated with repeated vomiting. Exploratory laparotomy was carried out after clinical and imaging studies which revealed big inflammatory mass with abscess at the right iliac fossa and recurrent appendicitis of the appendiceal stump. Surgical treatment is easy but recognition of this important entity but potentially dangerous condition should always be borne in mind in order to avoid delay in its diagnosis and treatment

Optimization of Furfural Production from Corncobs using p-Toluene Sulphonic Acid

Furfural is a promising renewable platform compound derived from lignocellulosic biomass that can be further converted to bio-based industrial chemicals. About 90% of what is used in Nigeria is imported, translating to hundreds of millions of Dollars in foreign exchange. Hence, this research aim was to optimize the production process of furfural from corncobs, a lignocellulosic biomass using a three steps methods which includes; pretreatment of raw materials, acid hydrolysis and distillation according to standard methods. The corncobs were grind to powdered form and then hydrolysed in a stirred reactor using p-toluene sulphonic acid (p-TsOH) by varying parameters which includes; temperature (60, 65 and 70 oC), reaction time (1, 2 and 3hrs) and concentration (30 ml, 40 ml and 50 ml). Analysis using FTIR was conducted to identify the functional group present in the furfural produced. The results showed yield of furfural increased from 23.66 % to 28 %, and the highest yield of furfural production was obtained using 50 ml p-TsOH at 70 oC for 3 h

EVALUATION OF ANALGESIC, ANTICONVULSANT AND HYPNOTIC ACTIVITIES OF PYRENACANTHIA STAUNDTII

An Aqueous leaf extract of Pyrenacanthia Staundtii (AqPs) was studied for central nervous activities. The extract (100.0 – 400.0 mg/kg i. p). significantly (

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon

We report the first measurement of coherent elastic neutrino-nucleus scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer \cevns over the background-only null hypothesis with greater than $3\sigma$ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2 $\pm$ 0.7) $\times$10$^{-39}$ cm$^2$ -- consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the \cevns process and provides improved constraints on non-standard neutrino interactions.Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3: fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6: fix Eq 1, new fig 3, V7 final version, updated with final revision