MINFLUX reveals dynein stepping in live neurons.

Dynein is the primary molecular motor responsible for retrograde intracellular transport of a variety of cargoes, performing successive nanometer-sized steps within milliseconds. Due to the limited spatiotemporal precision of established methods for molecular tracking, current knowledge of dynein stepping is essentially limited to slowed-down measurements in vitro. Here, we use MINFLUX fluorophore localization to directly track CRISPR/Cas9-tagged endogenous dynein with nanometer/millisecond precision in living primary neurons.

Uncovering kinesin dynamics in neurites with MINFLUX.

Neurons grow neurites of several tens of micrometers in length, necessitating active transport from the cell body by motor proteins. By tracking fluorophores as minimally invasive labels, MINFLUX is able to quantify the motion of those proteins with nanometer/millisecond resolution. Here we study the substeps of a truncated kinesin-1 mutant in primary rat hippocampal neurons, which have so far been mainly observed on polymerized microtubules deposited onto glass coverslips.

MINFLUX dissects the unimpeded walking of kinesin-1.

We introduce an interferometric MINFLUX microscope that records protein movements with up to 1.7 nanometer per millisecond spatiotemporal precision. Such precision has previously required attaching disproportionately large beads to the protein, but MINFLUX requires the detection of only about 20 photons from an approximately 1-nanometer-sized fluorophore.

A humanized mouse model of liver fibrosis following expansion of transplanted hepatic stellate cells.

Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo.

TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is upregulated during hepatic fibrogenesis and considered to promote fibrosis in the injured liver by inhibition of matrix metalloproteases (MMP) and degradation of extracellular matrix. Moreover, TIMP-1 displays anti-apoptotic properties, in patients with hepatocellular carcinoma (HCC) TIMP-1 serum levels are elevated and high TIMP-1 expression levels in HCC are associated with a poor prognosis. Therefore, TIMP-1 could functionally link fibrogenesis and carcinogenesis in the liver.

Asymmetric dimethylarginine and progression of chronic kidney disease: a one-year follow-up study.

Background/aims: Asymmetric dimethylarginine (ADMA) is a prognostic factor in patients with chronic kidney disease (CKD). However, the relationships among factors influencing the metabolism of ADMA and the CKD progression are not fully understood.

Methods: Serum ADMA, and variables related to the metabolism of ADMA were measured in 181 non-dialysis patients (CKD stages 3-5) and in 46 controls.

Induction of heme oxygenase 1 prevents progression of liver fibrosis in Mdr2 knockout mice.

Unlabelled: Induction or overexpression of the heme-degrading enzyme, heme oxygenase 1 (HO-1), has been shown to protect mice from liver damage induced by acute inflammation. We have investigated the effects of HO-1 induction in a mouse model of chronic liver inflammation and fibrogenesis with progression to hepatocellular carcinoma (HCC) (Mdr2ko; FVB.129P2-Abcb4(tm1Bor)).

Cell-free plasma DNA during Hemodialysis.

Purpose: Cell-free plasma DNA (cfDNA) levels originating predominantly from apoptotic leukocytes were found to rise during hemodialysis (HD) session, and as such are considered a marker of HD membrane biocompatibility. The purpose of our study was to determine the changes of cfDNA during two consecutive high-flux polysulphone HD sessions after a long (HD-L) and short (HD-S) interdialytic interval.

Methods: A total of 17 HD patients were examined.

Cell-free plasma DNA during peritoneal dialysis and hemodialysis and in patients with chronic kidney disease.

The mechanisms of clearance of circulating plasma DNA are not fully understood, and so we aimed to examine it in patients with impaired renal function compared with healthy individuals. We also assessed the effect of peritoneal dialysis and hemodialysis on circulating plasma cell-free DNA (cfDNA) in our treated patients. Overall, 20 healthy volunteers, 20 patients with chronic kidney disease (CKD), 18 patients undergoing peritoneal dialysis (PD), and 17 patients on hemodialysis (HD; high-flux polysulfone membrane) were examined.

Citrate anticoagulation control by ionized calcium levels does not prevent hemostasis and complement activation during hemodialysis.

The purpose of this study was to determine whether or not regional citrate anticoagulation (RCA) controlled by ionized calcium (iCa(2+)) would overcome thrombogenicity, prevent hemostasis, and complement activation during hemodialysis (HD). RCA was performed in 10 patients during 10 HD sessions using a polysulfone membrane in an effort to keep iCa(2+) at dialyzer outlet at < or =0.4 mmol/L.