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Full-Text Articles in Life Sciences

Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova Apr 2024

Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA–guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Leptotrichia shahii Cas13a expressed in Escherichia coli cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus …


Dysexecutive Difficulty And Subtle Everyday Functional Disabilities: The Digital Trail Making Test, David J Libon, Rod Swenson, Sean Tobyne, Ali Jannati, Daniel Schulman, Catherine C Price, Melissa Lamar, Alvaro Pascual-Leone Apr 2024

Dysexecutive Difficulty And Subtle Everyday Functional Disabilities: The Digital Trail Making Test, David J Libon, Rod Swenson, Sean Tobyne, Ali Jannati, Daniel Schulman, Catherine C Price, Melissa Lamar, Alvaro Pascual-Leone

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Digital neuropsychological tests reliably capture real-time, process-based behavior that traditional paper/pencil tests cannot detect, enabling earlier detection of neurodegenerative illness. We assessed relations between informant-based subtle and mild functional decline and process-based features extracted from the digital Trail Making Test-Part B (dTMT-B).

METHODS: A total of 321 community-dwelling participants (56.0% female) were assessed with the Functional Activities Questionnaire (FAQ) and the dTMT-B. Three FAQ groups were constructed: FAQ = 0 (unimpaired); FAQ = 1-4 (subtle impairment); FAQ = 5-8 (mild impairment).

Results: Compared to the FAQ-unimpaired group, other groups required longer pauses inside target circles (p < 0.050) and produced more total pen strokes to complete the test (p < 0.016). FAQ-subtle participants required more time to complete the entire test (p …


Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper Feb 2024

Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …


Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au Jan 2024

Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …


Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova Jan 2024

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …


Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang Jan 2024

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …