ATM phosphorylates subunit A of PP2A resulting in its nuclear export and spatiotemporal regulation of the DNA damage response

Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and major regulator of the DNA damage response (DDR). One critical ATM target is protein phosphatase 2A (PP2A) known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylation of many proteins during the recovery from the DDR while returning the cell to normalcy. Interestingly, ATM and PP2A are known to form an auto-regulatory yin-yang kinase-phosphatase relationship. Herein, we show that the phosphorylation of the PP2A-Aα structural subunit at S401 by ATM results in nuclear export, which regulates the DDR at multiple levels and affects genomic stability and cell growth. We generated PP2A-Aα conditional knockout mouse embryonic fibroblasts expressing PP2A-Aα-WT, S401A (cannot be phosphorylated), or S401D phosphomimetic) transgenes by floxing out the endogenous PP2A-Aα alleles with Cre. The S401D mutant cells displayed increased ERK and AKT signaling, resulting in an enhanced growth rate. Phosphorylation of PP2A-Aα at S401 caused the dissociation of ATM with the holoenzyme, an effect that could be recapitulated with S401D. Additionally, the S401A and S401D mutants exhibited significantly more chromosomal aberrations and underwent increased mitotic catastrophe after radiation. Both the S401A and the S401D cells showed impaired DSB repair (Non-homologous end joining and Homologous recombination repair) and exhibited delayed DNA damage recovery, which was reflected in reduced radiation survival. Time-lapse video and cellular localization experiments showed that the PP2A-Aα subunit was exported to the cytoplasm after radiation possibly by CRM1, a nuclear export protein, in line with the very rapid pleiotropic effects seen. In conclusion, our study demonstrates using a genetically defined system that ATM phosphorylation of a single, critical amino acid S401 is essential for regulating DDR. To study how the interplay between ATM and PP2A affects DDR in the brain, we are in the process of generating a brain specific PP2A-Aα conditional knockout mouse. Loss of many DDR related proteins like ATM and PP2A can lead to severe neuropathological effects. This model will be helpful in dissecting the PP2A-Aα/ATM regulatory circuit in the brain in response to DDR

Assessment of Dry and Wet Milling using Fabricated Burr Mill

Size reduction processes are utilized to produce watery paste vegetables common in most developing countries. The research was executed in two parts; the first part was a survey of workers and owners of pepper grinding machine in 3 markets Nigeria, to obtain information on experience working with the machine and functionality of burr mills using Structured questionnaire .The second part involved physical measurement of the dimensions, and other engineering parameters on five randomly selected pepper grinding machines from a lot in each market, About 25.4% of the respondents has being working with burr mill for 11-15 years, 23.7% has 16-20 years’ experience while 10% of the respondents have spent above 20 years in business while 93.22% of the respondents use the machine more than three times daily. In view of this it could be deduced that the interaction of the working parts of the machine is un-ending in the sense that increase in the numbers of usage of the burr mill increases the level of wear of the working parts. The physical measurement of the component parts of the burr mill of existing machine compared to that of new machine showed that the level of wear and tear of the machines varies which is due to age of machine and frequency of usage. Keywords: burr-mill, grinder, dry milling, wet milling

Enterotoxicity of Staphylococcus aureus isolated from beans pudding

36 samples of beans pudding from selected sources were analysed for Staphylococcus aureus and Bacillus cereus using standard protocols aimed at assessing its bacteriological quality. Samples obtained from restaurant showed slightly lower value for total plate count (1.3 x 104 - 1.6 x 106 cfu/gm) compared to samples from cafeteria (2.7 x 104 - 2.6 x 106 cfu/gm) and hawkers (3.1 x 104 - 3.2 x 106 cfu/gm). Count of S. aureus from samples obtained from hawkers varied between 1.2 x 103 - 2.0 x 106 cfu/gm while those of cafeteria and restaurant showed counts varying between 1.3 x 103 - 1.0 x 105 cfu/gm and 2.2 x 103 - 1.1 x 105 cfu/gm respectively. The counts for B. cereus from samples obtained from hawker ranged from 1.0 x 102 - 1.3 x 104 cfu/gm, while those from cafeteria and restaurant ranged from 1.0 x 102 - 2.10 x 104 cfu/gm and 1.0 x 102 - 1.0 x 104 cfu/gm respectively. 53% of the 13 isolates of S. aureus produced enterotoxin A but non produced enterotoxins C and D. The results from this study showed that S. aureus is common in vended beans capable of producing pathogenic enterotoxin A. Keywords: Staphylococcus aureus, moin-moin, enterotoxin, enterotoxicity, cellophan

Cellulase production from waste paper using Trichoderma species isolated from rhizospheric soil

The recent interest in bioconversion of cellulosic wastes to value added chemicals has led to extensive studies on microorganisms capable of producing the enzyme. The possibility of using waste paper for the production of cellulase by Trichoderma species isolated from the soil was investigated using submerged fermentation technique. The fermentation temperature and pH were varied. Results indicated that maximum cellulase production of 0.18 IU/ml/min was obtained at 96 h. Maximal enzyme activity was at pH 5 when compared to the activity obtained at pH of 6.0 (0.11 IU/ml/min) and 7.0 (0.06 IU/ml/min). Incubation temperature influenced the cellulase production greatly with about 50% of the cellulase activity lost when the temperature was switched from 28 to 37°C. The cultivation and application of the organism in cellulose hydrolysis will lead to efficient conversion of cellulose materials to other important products.Key words: Cellulose, Trichoderma, cellulase, submerged, fermentation, wastepaper

Four Compounds Suppressing Growth of Mycobacterium tuberculosis

Aims: To demonstrate the efficacy of several small molecular weight compounds having hydrazide groups, for inhibiting the growth of Mycobacterium tuberculosis. To show these same compounds have favorable drug-likeness properties. Study Design: To synthesize tuberculostats and test their antibacterial activity in-vitro. Place and Duration of Study: University of Nebraska, Durham Science Center, 6001 Dodge Street, Omaha NE 68182, and Texas A&M Health Science Center, Department of Microbial Pathogenesis and Immunology, 8447 State Hwy 47, Medical Research and Education Building, Room #3012, Bryan, TX 7780. From January 2015 to June 2015. Methodology: Hydrazide groups were formed by covalently bonding hydrazine onto small molecules having a single aromatic ring by utilizing microwave excitation and evaluating for antibacterial activity. These compounds were placed into tissue culture media at various concentrations and then tuberculosis bacteria were added to determine the level of growth inhibition. Growth inhibition of the bacteria was measured as a function of compound concentration for assessment and comparison. Results: Compounds A, B, C, and D carry hydrazide groups with various substituents that are bonded to a single aromatic ring. All four compounds show zero violations of Rule of 5, indicating favorable absorption and membrane permeation. All four compounds showed greater than 85% growth inhibition of bacteria at concentrations below 50 micrograms per milliliter, while assayed by colony forming units and luminescence. Values of Log BB suggests compounds A and C will have greater penetration into the central nervous system than isoniazid. Conclusion: These four hydrazide compounds induced substantial inhibition of bacterial growth. Microwave excitation for the synthesis of hydrazide compounds is effective. These compounds have favorable drug-likeness properties and are highly effective inhibiting growth of Mycobacterium tuberculosis

Aromatic Hydrazide Compounds that Inhibit the Growth of Mycobacterium Tuberculosis

Aims: To demonstrate the efficacy of aromatic hydrazide compounds to inhibit growth of Mycobacterium tuberculosis. Study Design: To synthesize tuberculostats and test their antibacterial activity in-vitro. Place and Duration of Study: University of Nebraska, Durham Science Center, 6001 Dodge Street, Omaha NE 68182, and Texas A&M Health Science Center, Department of Microbial Pathogenesis and Immunology, 8447 State Hwy 47, Medical Research and Education Building, Room #3012, Bryan, TX 7780. From March 2019 to October 2019. Methodology: Hydrazide functional groups were formed by covalently bonding hydrazine onto a carbonyl carbon that is a substituent of a single aromatic ring. Microwave excitation was utilized for synthesis, followed by evaluation of antibacterial activity. These compounds were placed into tissue culture media at various concentrations and then Mycobacterium tuberculosis bacteria was added, in order to determine the level of growth inhibition. Growth inhibition of the bacteria was measured as a function of compound concentration versus growth inhibition. Results: Compounds A, B, C, and D carry hydrazide groups as a substituent to a single aromatic ring. All four compounds show zero violations of Rule of 5, indicating favorable drug-likeness. All four compounds showed greater than 50% growth inhibition of bacteria at concentrations below 50 micrograms per milliliter. Growth inhibition was measured by colony forming units and luminescence. Polar surface area, Log P, molecular volume, and other molecular properties were determined for these four compounds. Conclusion: These four hydrazide compounds induced substantial inhibition of bacterial growth. Microwave excitation for the synthesis of hydrazide compounds is effective. These compounds have favorable drug-likeness properties and are highly effective inhibiting the growth of Mycobacterium tuberculosis

Novel Tuberculostatic Agents Suitable for Treatment of Mycobacterium tuberculosis Infections of the Central Nervous System

Aims: To demonstrate the efficacy of five small molecule compounds for inhibiting the growth of Mycobacterium tuberculosis. To present evidence that these compounds will penetrate into the central nervous system. Study Design: Five small molecule compounds bearing a hydrazide group were synthesized utilizing microwave excitation. These compounds were then placed into tissue culture with Mycobacterium tuberculosis at various concentrations for evaluation of bacterial growth inhibition. Place and Duration of Study: The compounds to be tested were prepared at the University of Nebraska Chemistry Department August 2013. The evaluation of antibacterial activity was determined at the Texas A&M Health Science Center during October to December of 2013. Methodology: Applying microwave excitation for generation of hydrazide groups within the structure of small molecule carboxylic acids, five agents were prepared for evaluation of bacterial growth inhibition. These agents were dissolved into tissue culture media at various concentrations. Having various levels of tuberculostatic agents, then tuberculosis bacteria were added to determine level of growth inhibition. Growth inhibition of the bacteria was achieved and measured by compound concentration for comparison and evaluation. Results: Five compounds having a hydrazide functional group greatly inhibited the growth of Mycobacterium tuberculosis. All five agents had molecular weight less than 215 grams/mole and polar surface area of less than 70 Angstroms2. Values of Log P ranged from -0.226 to 0.998. Values of Log BB (Log [Cbrain/Cblood]) ranged from -0.711 to - 0.525, with a range in central nervous system penetration Cbrain/Cblood of 0.195 to 0.299. All compounds showed zero violations of the Rule of 5. Substantial inhibition of bacterial growth was observed at concentrations as low as 30 micrograms/mL, as measured by optical density and colony forming units. Conclusion: These five hydrazide compounds substantially decreased the proliferation of tuberculosis bacteria at concentrations as low as 30 micrograms/mL. In addition, their physicochemical properties are shown to allow high levels of penetration into the central nervous system

Intraoperative colonic irrigation in the management of left sided large bowel emergecies in Jos University Teaching Hospital, Nigeria

Objectives: To evaluate the safety and benefits of antegrade intraoperative colonic irrigation (lavage) and primary anastomosis, after colonic resection, in the treatment of left sided large bowel emergencies.Design: A prospective descriptive study.Setting: Jos University Teaching Hospital, Jos, Nigeria.Participants: Thirty seven patients with an average age of 44.86 ± 16.15 years.Intervention: Sigmoid colectomy was performed in twenty two sigmoid volvulus, five sigmoid cancer, two faecal fistulae and one sigmoid injury. Left hemicolectomy was offered in four descending colon cancer, one descending colon injury, while anterior resection was carriedout in two rectal cancers. Primary anastomosis was performed after intraoperative colonic lavage.Results: The operative mortality was 2.7%, anastomotic leakage rate 2.7% and superficial wound infection occurred in 10.81%. The average duration of hospital stay was 22.76 ± 11.26 days. Intraoperative colonic lavage added 35.79 ± 7.25 minutes to the operating time.Conclusion: The results of this study suggest that intraoperative colonic lavage is an effective method enabling the surgeon to perform a primary anastomosis with reasonable safety after emergency resection of selected distal colonic lesions

Personalized Health Assessment and Recommendations Through Iot and Mlp Classifier Algorithms

Procuring a healthy lifestyle involves a holistic approach of personalized dietary and exercise recommendations dependent on individual health statuses. In this study, we present a new paradigm for examining individual health statuses for easy self-assessment without specialist help. The heart is a full kit of assessing instruments that can align critical climacterics of body temperature, pulse rate, blood oxygen level, and body max index that could be run with minor medic assistance. The research abides a dataset obtained through a broad scope of volunteers aged 17 to 24 including both males and females. Vital signs such as SpO2, BPM, temperature, and BMI are mediated utilizing incorporated Internet of Things units. The dataset is then cautiously preprocessed and balanced using machine learning algorithms before examination. The basis of this model is a two-tier state classifier system that designs autonomous dietary and exercise responsibilities varying from examined health clots. It is exploited for adulthood healthcare systems across multiple machines learning techniques, including Decision Tree, KNN, and some classifiers with the MLP classifier being the exemplary worthy model. The MLP classifier demonstrates unbelievable outcomes through approximately 86% accuracy when the trainings and testing datasets are 70:30 ratios apart