Medical Biophysics Commons^™

Identification Of Immune-Associated Biomarkers Of Diabetes Nephropathy Tubulointerstitial Injury Based On Machine Learning: A Bioinformatics Multi-Chip Integrated Analysis, Lin Wang, Jiaming Su, Zhongjie Liu, Shaowei Ding, Yaotan Li, Baoluo Hou, Yuxin Hu, Zhaoxi Dong, Jingyi Tang, Hongfang Liu, Weijing Liu

Faculty, Staff and Student Publications

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN.

METHODS: The …

Inter-Individual Variations In Circadian Misalignment-Induced Nafld Pathophysiology In Mice, Nobuya Koike, Yasuhiro Umemura, Hitoshi Inokawa, Isao Tokuda, Yoshiki Tsuchiya, Yuh Sasawaki, Atsushi Umemura, Naoko Masuzawa, Kazuya Yabumoto, Takashi Seya, Akira Sugimoto, Seung-Hee Yoo, Zheng Chen, Kazuhiro Yagita

Faculty, Staff and Student Publications

Pathological consequences of circadian misalignment, such as shift work, show considerable individual differences, but the lack of mechanistic understanding hinders precision prevention to prevent and mitigate disease symptoms. Here, we employed an integrative approach involving physiological, transcriptional, and histological phenotypes to examine inter-individual differences in pre-symptomatic pathological progression, preceding irreversible disease onset, in wild-type mice exposed to chronic jet-lag (CJL). We observed that CJL markedly increased the prevalence of hepatic steatosis with pronounced inter-individual differences. Stratification of individual mice based on CJL-induced hepatic transcriptomic signature, validated by histopathological analysis, pinpoints dysregulation of lipid metabolism. Moreover, the period and power of …

The Role Of Native Cysteine Residues In The Oligomerization Of Kcnq1 Channels, Alison Bates, Rebecca B Stowe, Elizabeth M Travis, Lauryn E Cook, Carole Dabney-Smith, Gary A Lorigan

Faculty, Staff and Student Publications

KCNQ1, the major component of the slow-delayed rectifier potassium channel, is responsible for repolarization of cardiac action potential. Mutations in this channel can lead to a variety of diseases, most notably long QT syndrome. It is currently unknown how many of these mutations change channel function and structure on a molecular level. Since tetramerization is key to proper function and structure of the channel, it is likely that mutations modify the stability of KCNQ1 oligomers. Presently, the C-terminal domain of KCNQ1 has been noted as the driving force for oligomer formation. However, truncated versions of this protein lacking the C-terminal …

Mechanosensitive Membrane Proteins: Usual And Unusual Suspects In Mediating Mechanotransduction, Miriam B Goodman, Elizabeth S Haswell, Valeria Vásquez

Faculty, Staff and Student Publications

This Viewpoint, which accompanies a Special Issue focusing on membrane mechanosensors, discusses unifying and unique features of both established and emerging mechanosensitive (MS) membrane proteins, their distribution across protein families and phyla, and current and future challenges in the study of these important proteins and their partners. MS membrane proteins are essential for tissue development, cellular motion, osmotic homeostasis, and sensing external and self-generated mechanical cues like those responsible for touch and proprioception. Though researchers' attention and this Viewpoint focus on a few famous ion channels that are considered the usual suspects as MS mechanosensors, we also discuss some of …

Structural Insights Into Cardiolipin Replacement By Phosphatidylglycerol In A Cardiolipin-Lacking Yeast Respiratory Supercomplex, Elena G Govorunova, Oleg A Sineshchekov, Leonid S Brown, Ana-Nicoleta Bondar, John L Spudich

Faculty, Staff and Student Publications

Potassium-selective channelrhodopsins (KCRs) are light-gated K+ channels recently found in the stramenopile protist Hyphochytrium catenoides. When expressed in neurons, KCRs enable high-precision optical inhibition of spiking (optogenetic silencing). KCRs are capable of discriminating K+ from Na+ without the conventional K+ selectivity filter found in classical K+ channels. The genome of H. catenoides also encodes a third paralog that is more permeable for Na+ than for K+. To identify structural motifs responsible for the unusual K+ selectivity of KCRs, we systematically analyzed a series of chimeras and mutants of this protein. We found that mutations of three critical residues in the …

Biophysical Characterization Of Light-Gated Ion Channels Using Planar Automated Patch Clamp, Elena G Govorunova, Oleg A Sineshchekov, Leonid S Brown, John L Spudich

Faculty, Staff and Student Publications

Channelrhodopsins (ChRs) are proteins that guide phototaxis in protists and exhibit light-gated channel conductance when their genes are heterologously expressed in mammalian cells. ChRs are widely used as molecular tools to control neurons and cardiomyocytes with light (optogenetics). Cation- and anion-selective ChRs (CCRs and ACRs, respectively) enable stimulation and inhibition of neuronal activity by depolarization and hyperpolarization of the membrane, respectively. More than 400 natural ChR variants have been identified so far, and high-throughput polynucleotide sequencing projects add many more each year. However, electrophysiological characterization of new ChRs lags behind because it is mostly done by time-consuming manual patch clamp …