Full-Privacy Secured Search Engine Empowered by Efficient Genome-Mapping Algorithms.

Since the 90s, keyword-based search engines have been the only option for people to locate relevant web content through a simple query comprising one to a few keywords. These engines, whether free or paid, retained users' search queries and preferences, often to deliver targeted ads. Additionally, user-uploaded articles for plagiarism detection can further be stored as part of service providers' expanding databases for profit. Essentially, users could not search without exposing their queries to these providers. We present a new solution here: a method for searching the internet using a full article as a query without disclosing the content. Our Sapiens Aperio Veritas Engine (S.A.V.E.) uses an encoding scheme and an FM-index search, borrowed from next-generation human genome sequencing. Each word in a user's query is transformed into one of 12 "amino acids" to create a pseudo-biological sequence (PBS) on the user's device. Plagiarism checks are done by users submitting their locally created PBSs to our cloud service. This detects identical content in our database, which includes all English and Chinese Wikipedia articles and Open Access journals up to April 2021. PBSs, longer than 12 "amino acids", show accurate results with less than 0.8% false positives. Performance-wise, S.A.V.E. runs at a similar genome-mapping speed as Bowtie and is >5 orders faster than BLAST. With both standard and private modes, S.A.V.E. offers a revolutionary, privacy-first search and plagiarism check system. We believe this sets an exciting precedent for future search engines prioritizing user confidentiality. S.A.V.E. can be accessed at https://dyn.life.nthu.edu.tw/SAVE/.

LM-GVP: an extensible sequence and structure informed deep learning framework for protein property prediction.

Proteins perform many essential functions in biological systems and can be successfully developed as bio-therapeutics. It is invaluable to be able to predict their properties based on a proposed sequence and structure. In this study, we developed a novel generalizable deep learning framework, LM-GVP, composed of a protein Language Model (LM) and Graph Neural Network (GNN) to leverage information from both 1D amino acid sequences and 3D structures of proteins. Our approach outperformed the state-of-the-art protein LMs on a variety of property prediction tasks including fluorescence, protease stability, and protein functions from Gene Ontology (GO). We also illustrated insights into how a GNN prediction head can inform the fine-tuning of protein LMs to better leverage structural information. We envision that our deep learning framework will be generalizable to many protein property prediction problems to greatly accelerate protein engineering and drug development.

The Impairment of TorsinA's Binding to and Interactions With Its Activator: An Atomistic Molecular Dynamics Study of Primary Dystonia.

Primary dystonia's prolonged muscle contractions and the associated abnormal postures and twisting movements remain incurable. Genetic mutation/deletion of GAG from TorsonA's gene resulting in ΔE303 (which weakens the binding between TorsinA and its activator, such as LULL1) primarily cause this neurodegenerative disorder. We studied TorsinA-LULL1 (or TorsinAΔE303-LULL1) bindings and interactions. For the first time, we show the atomic details of TorsinA-LULL1 dynamic interactions and TorsinAΔE303-LULL1 dynamic interactions and their binding affinities. Our results show extensive effects of ΔE303 on TorsinAΔE303-LULL1 interactions, and suggest that the differences between TorsinA-LULL1 interactions and TorsinAΔE303-LULL1 interactions are non-subtle. ΔE303 significantly weakens TorsinAΔE303-LULL1's binding affinity. We present pieces of evidence proving that the effects of ΔE303 (on the differences between TorsinA-LULL1 interactions and TorsinAΔE303-LULL1 interactions) are more pronounced than previously suggested, and that the nanobody used for achieving the X-ray crystallization in the previous study attenuated the differences between TorsinA-LULL1 and TorsinAΔE303-LULL1 interactions. Our accounts of the dynamic interactions between "TorsinA and LULL1" and between "TorsinAΔE303 and LULL1" and the detailed effects of ΔE303 on TorsinA-/TorsinAΔE303-LULL1 build on previous findings and offer new insights for a better understanding of the molecular basis of Primary Dystonia. Our results have long-term potentials of guiding the development of medications for the disease.

Lycopersicon esculentum (Tomato) Prevents Adverse Effects of Lead on Blood Constituents.

BACKGROUND: Lead is known for its adverse effects on various organs and systems. In this study, the ability of lead to adversely affect blood parameters was investigated, and Lycopersicon esculentum, or commonly known as tomato (a source of antioxidants), was administered orally in the form of tomato paste (TP) to reduce the adverse effects of lead. METHODS: The study involved 56 Wistar rats divided equally into 4 groups of 14 rats each: Control, LA(G), TP(G), and LA+TP(G). Control and TP(G) rats were given distilled water ad libitum, while LA(G) and LA+TP(G) rats were given 1% lead (II) acetate (LA) per day. TP(G) and LA+TP(G) rats were additionally treated with 1.5 ml of TP per day. All treatments lasted for 10 weeks, after which the rats were weighed and sacrificed, and haematological and biochemical parameters were measured. The independent samples t test was used to analyse the results. RESULTS: LEAD CAUSED SIGNIFICANT REDUCTIONS IN THE FOLLOWING PARAMETERS: weight; packed cell volume; red blood cell and white blood cell counts; the percentages of lymphocytes and monocytes; total serum protein, albumin, and globulin levels; and plasma superoxide dismutase and catalase activities. In contrast, lead caused a significant increase in the percentage of neutrophils and the plasma malondialdehyde concentration. TP, however, significantly prevented the adverse effects of LA. CONCLUSION: The oral administration of TP prevents the adverse effects of lead on blood constituents.

Tomato (Lycopersicon esculentum) prevents lead-induced testicular toxicity.

BACKGROUND: Lead, an example of heavy metals, has, for decades, being known for its adverse effects on various body organs and systems such that their functions are compromised. AIM: In the present study, the ability of lead to adversely affect the male reproductive system was investigated and tomato (Lycopersicon esculentum: Source of antioxidants) paste (TP) was administered orally to prevent the adverse effects of Pb. MATERIALS AND METHODS: Fifteen Sprague Dawley rats, randomised into three groups (n = 5), were used for this study. Animals in Group A served as the control and were drinking distilled water. Animals in Groups B and C were drinking 1% Pb (II) acetate (LA). Group C animals were, in addition to drinking LA, treated with 1.5 ml of TP/day. All treatments were for 8 weeks. STATISTICAL ANALYSIS USED: A Mann-Whitney U-test was used to analyse the results obtained. RESULTS: The obtained results showed that Pb caused a significant reduction in the testicular weight, sperm count, life-death ratio, sperm motility, normal sperm morphology, and plasma and tissue superoxide dismutase and catalase activity, but a significant increase in plasma and tissue malondialdehyde concentration. But, Pb did not cause any significant change in the serum testosterone level. TP, however, significantly reduced these adverse effects of Pb. CONCLUSION: These findings lead to the conclusion that TP significantly lowered the adverse effects of Pb exposure on the kidney as well as Pb-induced oxidative stress.