The glycerol-3-phosphate dehydrogenases GpsA and GlpD constitute the oxidoreductive metabolic linchpin for Lyme disease spirochete host infectivity and persistence in the tick.

We have identified GpsA, a predicted glycerol-3-phosphate dehydrogenase, as a virulence factor in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi: GpsA is essential for murine infection and crucial for persistence of the spirochete in the tick. B. burgdorferi has a limited biosynthetic and metabolic capacity; the linchpin connecting central carbohydrate and lipid metabolism is at the interconversion of glycerol-3-phosphate and dihydroxyacetone phosphate, catalyzed by GpsA and another glycerol-3-phosphate dehydrogenase, GlpD. Using a broad metabolomics approach, we found that GpsA serves as a dominant regulator of NADH and glycerol-3-phosphate levels in vitro, metabolic intermediates that reflect the cellular redox potential and serve as a precursor for lipid and lipoprotein biosynthesis, respectively. Additionally, GpsA was required for survival under nutrient stress, regulated overall reductase activity and controlled B. burgdorferi morphology in vitro. Furthermore, during in vitro nutrient stress, both glycerol and N-acetylglucosamine were bactericidal to B. burgdorferi in a GlpD-dependent manner. This study is also the first to identify a suppressor mutation in B. burgdorferi: a glpD deletion restored the wild-type phenotype to the pleiotropic gpsA mutant, including murine infectivity by needle inoculation at high doses, survival under nutrient stress, morphological changes and the metabolic imbalance of NADH and glycerol-3-phosphate. These results illustrate how basic metabolic functions that are dispensable for in vitro growth can be essential for in vivo infectivity of B. burgdorferi and may serve as attractive therapeutic targets.

Self-referenced single-electron quantized current source.

The future redefinition of the international system of units in terms of natural constants requires a robust, high-precision quantum standard for the electrical base unit ampere. However, the reliability of any single-electron current source generating a nominally quantized output current I=ef by delivering single electrons with charge e at a frequency f is eventually limited by the stochastic nature of the underlying quantum mechanical tunneling process. We experimentally explore a path to overcome this fundamental limitation by serially connecting clocked single-electron emitters with multiple in situ single-electron detectors. Correlation analysis of the detector signatures during current generation reveals erroneous pumping events and enables us to determine the deviation of the output current from the nominal quantized value ef. This demonstrates the concept of a self-referenced single-electron source for electrical quantum metrology.

Structured behavioral data format: An NWB extension standard for task-based behavioral neuroscience experiments.

Understanding brain function necessitates linking neural activity with corresponding behavior. Structured behavioral experiments are crucial for probing the neural computations and dynamics underlying behavior; however, adequately representing their complex data is a significant challenge. Currently, a comprehensive data standard that fully encapsulates task-based experiments, integrating neural activity with the richness of behavioral context, is lacking. We designed a data model, as an extension to the NWB neurophysiology data standard, to represent structured behavioral neuroscience experiments, spanning stimulus delivery, timestamped events and responses, and simultaneous neural recordings. This data format is validated through its application to a variety of experimental designs, showcasing its potential to advance integrative analyses of neural circuits and complex behaviors. This work introduces a comprehensive data standard designed to capture and store a spectrum of behavioral data, encapsulating the multifaceted nature of modern neuroscience experiments.

Counting statistics for electron capture in a dynamic quantum dot.

We report noninvasive single-charge detection of the full probability distribution P(n) of the initialization of a quantum dot with n electrons for rapid decoupling from an electron reservoir. We analyze the data in the context of a model for sequential tunneling pinch-off, which has generic solutions corresponding to two opposing mechanisms. One limit considers sequential "freeze-out" of an adiabatically evolving grand canonical distribution, the other one is an athermal limit equivalent to the solution of a generalized decay cascade model. We identify the athermal capturing mechanism in our sample, testifying to the high precision of our combined theoretical and experimental methods. The distinction between the capturing mechanisms allows us to derive efficient experimental strategies for improving the initialization.

Resin/Resin bonding: a new adhesive technology.

PURPOSE: Evaluation of a new surface treatment method to obtain a good bond strength between a luting composite and (1) a light-cured, (2) a heat-cured and (3) a thermoplastic resin. MATERIALS AND METHODS: Specimens were prepared and tests conducted according to ISO 10477, Amend. 1. The surfaces of Targis (light cured), SR Isosit (heat cured), and Dental D (thermoplastic) were ground under water cooling with 400-grit grinding paper, polished with 800-grit paper and air dried. Each resin material was divided into 3 groups of 10 specimens each. Group 1 was flame treated with a PyrosilPen for 5 s/2 cm2, group 2 for 10 s/2 cm2, and group 3 for 20 s/2 cm2. Subsequently, a methacryl silane was applied, followed by a luting composite. Prior to measuring shear bond strength, the specimens were thermocycled 5000 times in a water bath between 5 degrees C and 55 degrees C. SEM, FTIR investigations, and fracture analysis were also done. Etched and silanized Empress II - the gold standard - was used as a control. RESULTS: The following shear bond strengths were found: treatment time 5 s/2 cm2, Targis 25 (+/- 12) MPa, SR Isosit 17 (+/- 11) MPa; treatment time 10 s/2 cm2, Targis 23 (+/- 12) MPa, SR Isosit 26 (+/- 8) MPa; treatment time 20 s/2 cm2, Targis 29 (+/- 5) MPa, SR Isosit 26 (+/- 9) MPa. All Dental D specimens failed completely so that shear bond strength could not be measured. The control achieved 27 (+/- 6) MPa. No significant differences were found between the materials or the flaming times. On all flamed surfaces, Si was detected by FTIR. SEM showed that no heat destruction occurred at a flaming time of 5 s/2 cm2, a slight change at 10 s/2 cm2, and a significant change at 20 s/2 cm2. CONCLUSION: This new bonding technology is an effective method for surface-treating polymerized composite resin materials to obtain good bonding to luting composites. The method fails on thermoplastic resins.