Biology subjects

Klein, R. C.

Publications and source records attributed to Klein, R. C..

3 recordsLinked to original sources

bioRxiv2026

ARSA: an autonomous research scientist for target nomination in Alzheimer's disease and related dementias

Expanding therapeutic options for Alzheimer's disease and related dementias (ADRD) requires biologically grounded targets, yet nomination demands labor-intensive analysis and multidisciplinary evidence synthesis. To address this challenge, we present ARSA, an autonomous research scientist that transforms natural-language research interests and molecular data into prioritized, evidence-grounded target shortlists. ARSA formulates and audits hypotheses, adapts molecular analyses to observed results, and prioritizes targets using cross-cohort evidence and disease-specific knowledge, preserving the evidence and decisions underlying each nomination. Across three complementary evaluations, we show that ARSA generates hypotheses corresponding to subsequent research and identifies credible candidates within and beyond community nomination records. In structured assessment by 14 experts spanning all four technical cores of the Indiana University School of Medicine-Purdue University TREAT-AD Center, every expert assigned higher mean credibility to ARSA-retained candidates than to rejected comparators. ARSA enables systematic, transparent target exploration, opening opportunities to broaden the therapeutic mechanisms investigated in ADRD.

bioinformatics↗

bioRxiv2026

Acute Increase of Excitatory Activity in Pyramidal Neurons of Rat Motor Cortex under Static Magnetic Field

ObjectivesTranscranial application of a static magnetic field (SMF) was reported to result in subsequent modulation of neural excitability in the human motor cortex, but the acute mechanisms underlying this effect are unknown. We explore the mechanisms of this phenomenon with patch-clamp recording in rat brain slices during SMF exposure. Materials and MethodsPatch-clamp recording from layer II/III pyramidal neurons in motor cortex of acutely prepared brain slices were conducted during exposure to 0.20-0.35 T SMF or sham. ResultsDuring SMF exposure we observed an increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) as well as miniature excitatory post-synaptic currents (mEPSCs) recorded in the presence of TTX to suppress action potentials and thus also network effects. There was a significant acute increase in sEPSC frequency for SMF exposure duration of both 6 min and 10 min, but not for 10 min sham exposure. After SMF exposure, the sEPSC and mEPSC frequency returned to baseline. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was unaffected by SMF. The amplitude of the postsynaptic currents decreased with time for all recordings regardless of the condition, presumably due to the expected gradual deterioration of the patch clamp seal. ConclusionsThe acute effect of SMF exposure on sEPSC and mEPSC frequency, but not amplitude, is consistent with the assumption of a presynaptic or synaptic site mediating the effect. Furthermore, the consistency of the effect between sEPSCs and mEPSCs suggests that the effect is not related to action potential propagation in the presynaptic axon. The effect of SMF on EPSCs and not IPSCs may be related to the larger length of excitatory axons compared to inhibitory axons, or to effects on extracellular ionic gradients within the slice.

bioengineering↗

bioRxiv2024

Validation of RT-qPCR primers and probes for new and old variants of SARS-CoV-2 in a world scale

IntroductionThe demand for molecular diagnosis of pathogens has surged dramatically since the onset of the COVID-19 pandemic. In this context, different diagnostic tests have been developed to identify SARS-CoV-2 in patient samples. The emergence of new variants of SARS-CoV-2 raises questions about whether the molecular tests available for diagnosis continue to be effective in detecting the virus in biological samples. ObjectiveThis study analyzed the viability of molecular targets directed to N, E and RdRp genes available against the new variants of SARS-CoV-2. MethodologyFor this, we used bioinformatics tools to analyze SARS-CoV-2 genomic data of different variants deposited in GSAID and NCBI virus genomic databases to assess the accuracy of molecular tests available for the diagnosis of COVID-19. We also developed software for analyzing mutation frequencies in different molecular targets from the mutation database. ResultsMutation frequency analysis revealed a high rate of mutations in the N, E and RdRp genes and targets, although the target regions were more conserved. Only three SNPs were recurrent in the sequences of the variants identified in different continents and all in different targets. On the other hand, the registered mutations are not consistent and do not appear frequently in isolates of the same variant in all regions of the world. ConclusionOur data suggest that the molecular targets designed for the first SARS-CoV-2 variants remain valid for the identification of new virus variants despite the large number of identified haplotypes. However, false negative test failures can be identified by using more than one molecular target for the same sample. Genomic regions that are under evolutive selective pressure should be avoided in the use of the diagnostic, once the emergence of new variants may affect the efficiency of molecular testing on a global scale.

microbiology↗