Archives – ASSET

An engineered Cas9 fusion protein for the treatment of Gaucher disease type 1

admin — Thu, 22 Sep 2022 21:34:22 +0000

Gaucher disease is a genetic disorder caused by point mutations in the GBA gene encoding for glucocerebrosidase, an enzyme that breaks down the fat glucocerebroside. This work proposes the development of a Cas9-cytidine deaminase fusion protein to treat forms of Gaucher disease type 1 associated with an A1226G substitution on the GBA gene. This fusion protein would consist of the rAPOBEC1 cytidine deaminase, the Streptococcus pyogenes Cas9 nickase, and a uracil glycosylase inhibitor (UGI) connected with flexible serine/glycine linkers. This fusion protein, once complexed with an engineered guide RNA, would specifically bind to the mutated site near the Protospacer Adjacent Motif (PAM) and enzymatically convert the disease-associated cytosine base to thymine, reversing the disease mutation. The proposed system is unlikely to exhibit unintended edits; the designed guide RNA does not align with any other known locus on the human genome. Ultimately, we imagine expressing the fusion protein/guide RNA complex in vitro, encapsulating it in lipid nanoparticles, and injecting it into the body; to reach this goal, we propose three specific experimental aims: (1) expressing and purifying the fusion protein and guide RNA; (2) demonstrating consistent and on-target editing activity in human macrophage cell cultures; and (3) demonstrating successful delivery and on-target editing activity in a model organism. The completion of this project would put forth a vastly more accessible treatment for Gaucher disease type 1 and advance the precision of Cas9-based gene editing.

Authors List :

Arindam Bagga

Presenting Author :

Arindam Bagga

Affiliations :

251 Waltham St, Lexington, MA 02421

Email :

arindambagga@gmail.com

Key Words (5 Words Maximum) :

Gaucher disease type 1, CRISPR-Cas9, Cytidine Deaminase, Base editing

Peer Review Process and some Questionable Practices During COVID-19 Pandemic

admin — Fri, 27 Aug 2021 22:15:43 +0000

Editorial evaluations of manuscripts submitted to a journal first go through an initial screening by the editorial team who can reject the manuscript after screening or take it to the next step of peer review. Peer reviewers independently make a recommendation to the journal editor as to whether the manuscript should be rejected or accepted (with or without revisions). The journal editor considers all the feedback from peer reviewers and makes an informed decision and conveys to the authors. Peer review is the process by which journals scrutinize and regulate the quality of content they publish following strict ethical procedures and practices. However sadly, the COVID19 pandemic has exposed some questionable practices of top journals. We have seen many silent withdrawals and retractions of highly cited papers. In order to make literature available to public, in response to the COVID-19 pandemic many publishers and researchers have sped up their adoption of Open Access practices, sometimes embracing them fully and sometimes partially or in a sub-optimal manner, sharing of data, protocols, and standards. In some instances the use of COVID-19 literature /data has been badly reviewed ,and sometimes not reviewed (preprints) hence retracted, this has posed a public health risk because of misinformation. It is therefore concluded that to minimize such risks proper measures such as more transparency ,if the datasets, peer review reports , editorial comments and decisions, and authors’ responses to papers were released publicly.

Authors List :

Kaiser Jamil

Presenting Author :

Kaiser Jamil

Affiliations :

Fellow of the World Academy of Medical Sciences; Vice President of the Asian Council of Science Editors, & Head of Genetics Department, Bhagwan Mahavir medical Research centre, Hyderabad-India

Email :

kj.bmmrc@gmail.com

Key Words (5 Words Maximum) :

Publication, ethics, review, Covid-19

Food and Brain Health

admin — Fri, 27 Aug 2021 22:10:08 +0000

Brain health is very important as it can be vulnerable to various disorders and it can be damaged by the following trauma, degeneration, structural defects, infection, etc. World Health Organization (WHO) predicts that the brain diseases including neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) and neurodevelopmental disorders such as autism, ADHD, etc will be a global burden in the coming decade. These brain diseases could affect both early and elderly life. Even though, prevalence of these diseases increasing and causes are still remain elusive and the current therapeutic strategies are having less retention and costly. So there is a need to find out an alternative strategy to delay the progression of these diseases. Recently high attention towards nutritional prospects/benefits towards health and disease maintenance. Here, the role of food/nutrition in brain health and disease status will be discussed with the strong supporting data from our lab and other labs.

Authors List :

Musthafa Mohamed Essa

Presenting Author :

Musthafa Mohamed Essa

Affiliations :

Department of Food Science and Nutrition, CAMS; Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman; Visiting Professor, Biomedical Sciences Department, University of Pacific, Sacramento, CA, USA

Email :

drmdessa@gmail.com

Key Words (5 Words Maximum) :

Food, brain, nervous system, health, neurodevelopmental diseases, neurodegenerative diseases

Fluctuating Mindset of a High School Student: A Guiding Message from a Peer

admin — Fri, 27 Aug 2021 21:44:07 +0000

Attending college is a daunting, yet exciting landmark in a student’s journey for knowledge. The options that are available to a college student far exceeds those for a high school student. This depth of choice and freedom requires a certain level of maturity and sense of responsibility to transition into a well-adjusted contributor to the community and society at large. College brings about many choices, the most important being a focus of study. It is not mandated that a student need to know their future path as an incoming college freshman. The ideal path to take for a student to fulfill their own definition of success can be attributed to finding an occupation that satisfies their sense of duty and interest while being able to live a comfortable life. It is paramount to take responsibility for your own path to success, and college is the very first experience where that responsibility can be made into reality. It is important to look beyond the assignments and exams once in a while to gauge your long-term outlook and compare it with the surrounding reality. This can apply to a major which you find does not fit your interests anymore, or it can apply to a dream job which may not be as lucrative as you had expected. Navigating college is a balancing act which requires failure, learning and success.

Authors List :

Mohammed Faiz Khan

Presenting Author :

Mohammed Faiz Khan

Affiliations :

Merrimack College, North Andover, MA, USA

Email :

bazil0117@gmail.com

Key Words (5 Words Maximum) :

college, high school student, interest, decision

An In-Silico Study to Establish the Relation Between Ethanol and Morphine Co-Administration on Inflammatory Pathways

admin — Fri, 27 Aug 2021 21:21:28 +0000

Alcoholism and alcohol-related deaths are the third leading cause of preventable death in the US. A fourth of all Americans engage in some form of binge-drinking every week. Side effects of excessive or moderate alcohol use may include stupor, unconsciousness, or analgesia. The effects produced by alcohol (ethanol) mimic the effects produced by many analgesics and anesthetics commonly used by physicians for surgical procedures such as ketamine, morphine, or buprenorphine. Morphine specifically exerts its effect by activating the κ, δ and µ opioid receptors. Its effects include drowsiness, constipation, and most notably analgesia. Ethanol activates gamma aminobutyric acid (GABA), glutamate and glycine receptors. Although these receptors may be different, ethanol likely shares common downstream molecules with morphine that modulates its effects, because of their shared activity. To substantiate our interpretation, we have employed Ingenuity Pathway Analysis (IPA) from QIAGEN to establish any common pathways, receptors, or molecules associated with morphine- and ethanol-mediated effects. Existing literature shows that morphine and ethanol have pro-Inflammatory effects. Although ethanol at high concentrations is pro-inflammatory, at low concentrations it exhibits anti-Inflammatory activity. We thus predict, utilizing IPA, ethanol and morphine will share downstream molecules, which modulate the activity of pro-Inflammatory (IFNγ, TNFα) and anti-Inflammatory (IL-4, IL-13) cytokines. Our in-silico studies showed ethanol and morphine share 18 intermediary molecules in all cell types/lines including macrophages. At a systemic level, our findings support our hypothesis. Morphine showed to be pro-inflammatory, in addition to activating the µ receptor. Ethanol findings demonstrated an anti-inflammatory response, consistent to the findings in macrophages. In addition, we found that increasing levels of ethanol showed activation in each of the common 18 molecules except IL-12β and ITGAM. Ethanol activates the µ receptor, inhibits the δ receptor, and shares no connection to the κ receptor. In addition, the only cytokine inhibited was IFNγ, the rest were activated with increasing levels of ethanol. When the levels of both morphine and ethanol were increased, the molecules most significantly affected were IL-12β, IL-6, IL-10, TLR4, MAPK1 and IL-1β. In addition, all the common 18 molecules examined activated µ and inhibited δ, for the exception of IL-10, which inhibited both receptors. Based on our IPA analysis, any synergism between ethanol and morphine and the involvement of these 18 intermediary molecules in the regulation of IFNγ, TNFα, IL-4 and IL-13 can be established using in vitro studies.

Authors List :

Muhammad Zahid Asghar, Sulie Chang, Mohammed Akbar, Mohammed Khan

Presenting Author :

Muhammad Zahid Asghar

Affiliations :

Dow University of Health Sciences, Karachi, Pakistan; Department of Biological Science and Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ; Division of Neuroscience and Behavior, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, MD; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospital for Children, MA, USA

Email :

zahidasghar@hotmail.com

Key Words (5 Words Maximum) :

Morphine, Ethanol, IFN Gamma, TNF Alpha, IL-13, IL-4

The Effects of Metformin, AMPK, and ACE2 on Diabetes and COVID-19

admin — Wed, 25 Aug 2021 03:47:53 +0000

Diabetes has proven to significantly worsen the effects of COVID-19 by putting diabetic individuals at greater risk of infection and fatal outcomes. There is a bidirectionality between COVID and diabetes. Individuals suffering from COVID-19 as well as preexisting diabetes can have worsened side effects, leading to a worse prognosis. Furthermore, in some individuals with COVID-19, diabetes was reported even though they had no prior history of diabetes.
In order to decrease the impact of the virus, blood glucose control can help. Metformin is a drug prescribed to diabetic patients for its immune modulation, antiviral, and anti-inflammatory properties. Many of these are symptoms and side effects of COVID-19. In terms of its diabetic benefits, Metformin has a glucose-lowering effect due to the increased glucose uptake by the muscles which decreases the conversion of glycogen to glucose, leading to decreased absorption of glucose from the intestine. Metformin also has benefits towards the COVID-19 virus. Metformin may provide pulmonary protection following SARS-CoV-2 infection. Metformin’s molecular processes show its involvement in pathways controlling inflammation, glucose metabolism, vascular smooth muscle function, and in viral pathogenesis.
The explanation for this is found in the relationship between ACE2 (Angiotensin-converting enzyme 2) and AMPK (Adenosine monophosphate (AMP)-activated protein kinase). ACE2 is an enzyme attached to the membrane of cells located in the intestines, kidney, gallbladder, and heart. Metformin impacts glucose uptake within the intestine where it would interact with the ACE2 enzyme. ACE2 counterbalances the detrimental effect of the ACE/RAS pathway through its downstream axis. AMPK regulates metabolic homeostasis from cellular to whole body levels. AMPK phosphorylates are key molecules in regulating metabolism.
By using the Ingenuity Pathway Analysis tool, an affinity is shown by SARS-CoV-2 to bind to ACE2. The molecular basis for the beneficial effects of metformin on the pulmonary system likely involves metformin activation of AMPK. Metformin can activate AMPK, which phosphorylates ACE2 on Ser-680. This post-translational modification of ACE2 decreases its ubiquitination and therefore extends the half-life of ACE2, which may offer lung protection. Owing to similar interactions between ACE2 to SARS-CoV-1 and SARS-CoV-2, it is reasonable to suspect that metformin may offer similar lung protection in COVID-19.

Authors List :

(Maryam Khan, Robbinsville High School, 155 Robbinsville Edinburg Rd, Trenton, NJ 08691); (Dr. Sulie L. Chang, Ph.D. Institute of NeuroImmune Pharmacology, South Orange, NJ);( Dr. Mohammed A.S. Khan, Ph.D., Harvard Medical School, Shriners Hospital for Children, Boston, MA)

Presenting Author :

Maryam Khan

Affiliations :

(Dr. Sulie L. Chang, Ph.D. Institute of NeuroImmune Pharmacology, South Orange, NJ);( Dr. Mohammed A.S. Khan, Ph.D., Harvard Medical School, Shriners Hospital for Children, Boston, MA)

Email :

maryam.khan1916@gmail.com

Key Words (5 Words Maximum) :

Metformin, AMPK, ACE2, COVID, Diabetes

Coding and its Relevance

admin — Mon, 23 Aug 2021 01:02:49 +0000

Coding, or the process of writing computer programs, is a skill that has become vital in today’s industry. Not only does it expedite processes in the ever-growing world of technology, but also in various other fields of work. Based on twenty-five years of experience as a software engineer, as well as empirical data yielded from the advancements in coding-involved careers, a summary of coding in the industry was compiled. Among several topics discussed are motivations, challenges, careers, implications, and benefits of coding. The aim of the presentation is to inform and educate youths or those interested in entering the highly stimulating world of coding.

Authors List :

Zubeir Syed

Presenting Author :

Zubeir Syed

Affiliations :

Aliaswire, Burlington, MA, USA

Email :

zasyed786@gmail.com

Key Words (5 Words Maximum) :

computer programming, software development, coding

Radiology: Past Present and Future

admin — Sun, 22 Aug 2021 22:38:42 +0000

Radiology is the field of imaging. This was started in 1895 by William Rankin Ben he discovered X ray. This encompasses the modalities of imaging including X ray, ultrasound, Doppler, CT scan, MRI and PET scan. Over the course of time, the inquisitiveness of imagers led to image guided surgeries which at present is known as interventional radiology. There has been enormous development of the field which continues to this day. We introduce the field of Radiology to our students and provide an insight to the future of the field.

Authors List :

Shams Iqbal MD FSIR

Presenting Author :

Shams Iqbal MD FSIR

Affiliations :

Massachusetts General Hospital

Email :

siiqbal@mgh.harvard.edu

Key Words (5 Words Maximum) :

Radiology, Imaging, Intervention

Implementation of Cybersecurity in Public Domains

admin — Sun, 22 Aug 2021 21:17:23 +0000

Cybersecurity is the domain of networks, devices, and computer systems from unauthorized personnel to preserve the integrity of information. Cybersecurity is important because
it prevents data from being intercepted or altered. Data such as personal information and health information are especially sensitive and need to be protected from attempted theft. With the popularity of cloud services that store sensitive data on the rise, it is important as ever to maintain good cybersecurity. In this day and age, with almost every company out there having a website to promote their brand, cybercriminals have an easy time finding and taking advantage of poorly configured servers. Cybercrimes are dangerous because they can lead to severe economic repercussions. If private data were to be available for everyone, possession of intellectual property and trade secrets would be nonexistent. Additionally, companies with poor cybersecurity standards are in danger of leaking private customer information. Something like this would not only hurt the customers but the company itself, as they would lose consumer trust. As a result, it is vital to focus on cybersecurity. Companies can do this by educating themselves on the importance of cybersecurity and investing in tools to manage their cybersecurity. In order to truly strengthen the integrity of sensitive data, these are the measures that must be taken. This presentation will address the importance of implementing and maintaining good cybersecurity habits.

Presenting Author :

Abdul Khan

Email :

tanzil101614@gmail.com

Key Words (5 Words Maximum) :

Cybersecurity

How to Construct Scientific papers and Ethics in Publishing

admin — Thu, 19 Aug 2021 04:14:23 +0000

Due to various simple reasons most of the authors (new and less experienced) having novel data and results finding difficulty to publish in well-known peer reviewed international journals. Here, the best way to construct the manuscripts to attract the editors and the papers get published will be explained for better understanding. Further, the credibility of scientific is getting damaged many times due to ethical breaches in its research and publication practices. These unwanted practices come in place due to increased pressure to publish, conflicts of interest, and ethical committee restrictions on research and mostly these things happen due to a lack of knowledge rather than intentions. Here, I will be discussing the ethics in publishing as well.