Learning Spectral Fractional Anisotropy and Mean Diffusivity Features as Neuroimaging Biomarkers for Tracking White Matter Integrity Changes in Myotonic Dystrophy Type 1 Patients using Deep Convolutional Neural Networks.

Myotonic dystrophy type 1 (DM1) is a genetic neuromuscular progressive multisystem disease that results in a broad spectrum of clinical central nervous system (CNS) involvement, including problems with memory, attention, executive functioning, and social cognition. Fractional anisotropy and mean diffusivity along-tract data calculated using diffusion tensor imaging techniques play a vital role in assessing white matter microstructural changes associated with neurodegeneration caused by DM1. In this work, a novel spectrogram-based deep learning method is proposed to characterize white matter network alterations in DM1 with the goal of building a deep learning model as neuroimaging biomarkers of DM1.

USP30 sets a trigger threshold for PINK1-PARKIN amplification of mitochondrial ubiquitylation.

The mitochondrial deubiquitylase USP30 negatively regulates the selective autophagy of damaged mitochondria. We present the characterisation of an N-cyano pyrrolidine compound, FT3967385, with high selectivity for USP30. We demonstrate that ubiquitylation of TOM20, a component of the outer mitochondrial membrane import machinery, represents a robust biomarker for both USP30 loss and inhibition.

A constant light-genetic screen identifies KISMET as a regulator of circadian photoresponses.

Circadian pacemakers are essential to synchronize animal physiology and behavior with the dayrationight cycle. They are self-sustained, but the phase of their oscillations is determined by environmental cues, particularly light intensity and temperature cycles. In Drosophila, light is primarily detected by a dedicated blue-light photoreceptor: CRYPTOCHROME (CRY).

Interactions between circadian neurons control temperature synchronization of Drosophila behavior.

Most animals rely on circadian clocks to synchronize their physiology and behavior with the day/night cycle. Light and temperature are the major physical variables that can synchronize circadian rhythms. Although the effects of light on circadian behavior have been studied in detail in Drosophila, the neuronal mechanisms underlying temperature synchronization of circadian behavior have received less attention.

PER-TIM interactions with the photoreceptor cryptochrome mediate circadian temperature responses in Drosophila.

Drosophila cryptochrome (CRY) is a key circadian photoreceptor that interacts with the period and timeless proteins (PER and TIM) in a light-dependent manner. We show here that a heat pulse also mediates this interaction, and heat-induced phase shifts are severely reduced in the cryptochrome loss-of-function mutant cry(b). The period mutant per(L) manifests a comparable CRY dependence and dramatically enhanced temperature sensitivity of biochemical interactions and behavioral phase shifting.

A subset of dorsal neurons modulates circadian behavior and light responses in Drosophila.

A fundamental property of circadian rhythms is their ability to persist under constant conditions. In Drosophila, the ventral Lateral Neurons (LNvs) are the pacemaker neurons driving circadian behavior under constant darkness. Wild-type flies are arrhythmic under constant illumination, but flies defective for the circadian photoreceptor CRY remain rhythmic.

Ectopic CRYPTOCHROME renders TIM light sensitive in the Drosophila ovary.

The period (per) and timeless (tim) genes play a central role in the Drosophila circadian clock mechanism. PERIOD (PER) and TIMELESS (TIM) proteins periodically accumulate in the nuclei of pace-making cells in the fly brain and many cells in peripheral organs. In contrast, TIM and PER in the ovarian follicle cells remain cytoplasmic and do not show daily oscillations in their levels.

Diurnal, circadian and photic regulation of calcium/calmodulin-dependent kinase II and neuronal nitric oxide synthase in the hamster suprachiasmatic nuclei.

Mammalian circadian rhythms are entrained by light pulses that induce phosphorylation events in the suprachiasmatic nuclei (SCN). Ca(2+)-dependent enzymes are known to be involved in circadian phase shifting. In this paper, we show that calcium/calmodulin-dependent kinase II (CaMKII) is rhythmically phosphorylated in the SCN both under entrained and free-running (constant dark) conditions while neuronal nitric oxide synthase (nNOS) is rhythmically phosphorylated in the SCN only under entrained conditions.

From light to genes: moving the hands of the circadian clock.

Mammalian circadian rhythms are generated by the hypothalamic suprachiasmatic nuclei and finely tuned to environmental periodicities by neurochemical responses to the light-dark cycle. Light reaches the clock through a direct retinohypothalamic tract, primarily through glutamatergic innervation, and its action is probably regulated by a variety of other neurotransmitters. A key second messenger in circadian photic entrainment is calcium, mobilized through membrane channels or intracellular reservoirs, which triggers the activation of several enzymes, including a calcium/calmodulin-dependent protein kinase and nitric oxide synthase.