Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy

<p>Abstract</p> <p>Background</p> <p>It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson's disease (PD). Mitochondria supply the adenosine triphosphate (ATP) needed to support axonal transport and contribute to many other cellular functions essential for the survival of neuronal cells. Furthermore, mitochondria in PD tissues are metabolically and functionally compromised. To address this hypothesis, we measured the velocity of mitochondrial movement in human transmitochondrial cybrid "cytoplasmic hybrid" neuronal cells bearing mitochondrial DNA from patients with sporadic PD and disease-free age-matched volunteer controls (CNT). The absorption of low level, near-infrared laser light by components of the mitochondrial electron transport chain (mtETC) enhances mitochondrial metabolism, stimulates oxidative phosphorylation and improves redox capacity. PD and CNT cybrid neuronal cells were exposed to near-infrared laser light to determine if the velocity of mitochondrial movement can be restored by low level light therapy (LLLT). Axonal transport of labeled mitochondria was documented by time lapse microscopy in dopaminergic PD and CNT cybrid neuronal cells before and after illumination with an 810 nm diode laser (50 mW/cm²) for 40 seconds. Oxygen utilization and assembly of mtETC complexes were also determined.</p> <p>Results</p> <p>The velocity of mitochondrial movement in PD cybrid neuronal cells (0.175 +/- 0.005 SEM) was significantly reduced (p < 0.02) compared to mitochondrial movement in disease free CNT cybrid neuronal cells (0.232 +/- 0.017 SEM). For two hours after LLLT, the average velocity of mitochondrial movement in PD cybrid neurites was significantly (p < 0.003) increased (to 0.224 +/- 0.02 SEM) and restored to levels comparable to CNT. Mitochondrial movement in CNT cybrid neurites was unaltered by LLLT (0.232 +/- 0.017 SEM). Assembly of complexes in the mtETC was reduced and oxygen utilization was altered in PD cybrid neuronal cells. PD cybrid neuronal cell lines with the most dysfunctional mtETC assembly and oxygen utilization profiles were least responsive to LLLT.</p> <p>Conclusion</p> <p>The results from this study support our proposal that axonal transport is reduced in sporadic PD and that a single, brief treatment with near-infrared light can restore axonal transport to control levels. These results are the first demonstration that LLLT can increase axonal transport in model human dopaminergic neuronal cells and they suggest that LLLT could be developed as a novel treatment to improve neuronal function in patients with PD.</p

Two Biexciton Types Coexisting in Coupled Quantum Dot Molecules

Coupled colloidal quantum dot molecules (CQDMs) are an emerging class of nanomaterials, manifesting two coupled emission centers and thus introducing additional degrees of freedom for designing quantum-dot-based technologies. The properties of multiply excited states in these CQDMs are crucial to their performance as quantum light emitters, but they cannot be fully resolved by existing spectroscopic techniques. Here we study the characteristics of biexcitonic species, which represent a rich landscape of different configurations essentially categorized as either segregated or localized biexciton states. To this end, we introduce an extension of Heralded Spectroscopy to resolve the different biexciton species in the prototypical CdSe/CdS CQDM system. By comparing CQDMs with single quantum dots and with nonfused quantum dot pairs, we uncover the coexistence and interplay of two distinct biexciton species: A fast-decaying, strongly interacting biexciton species, analogous to biexcitons in single quantum dots, and a long-lived, weakly interacting species corresponding to two nearly independent excitons. The two biexciton types are consistent with numerical simulations, assigning the strongly interacting species to two excitons localized at one side of the quantum dot molecule and the weakly interacting species to excitons segregated to the two quantum dot molecule sides. This deeper understanding of multiply excited states in coupled quantum dot molecules can support the rational design of tunable single- or multiple-photon quantum emitters.U.B. and D.O. acknowledge the support of the Israel Science Foundation (ISF) and the Directorate for Defense Research and Development (DDR&D), grant No. 3415/21. J.I.C. and J.P. acknowledge support from UJI project B-2021-06. E.S., A.L., Y.E.P., and Y.O. acknowledge support from the Hebrew University Center for Nanoscience and Nanotechnology

Low-energy laser irradiation enhances de novo protein synthesis via its effects on translation-regulatory proteins in skeletal muscle myoblasts

AbstractLow-energy laser irradiation (LELI) drives quiescent skeletal muscle satellite cells into the cell cycle and enhances their proliferation, thereby promoting skeletal muscle regeneration. Ongoing protein synthesis is a prerequisite for these processes. Here, we studied the signaling pathways involved in the LELI regulation of protein synthesis. High levels of labeled [35S]methionine incorporation were detected in LELI cells as early as 20 min after irradiation, suggesting translation of pre-existing mRNAs. Induced levels of protein synthesis were detected up until 8 h after LELI implying a role for LELI in de novo protein synthesis. Elevated levels of cyclin D1, associated with augmented phosphorylation of the eukaryotic initiation factor 4E (eIF4E) and its inhibitory binding protein PHAS-I, suggested the involvement of LELI in the initiation steps of protein translation. In the presence of the MEK inhibitor, PD98059, eIF4E phosphorylation was abolished and levels of cyclin D1 were dramatically reduced. The LELI-induced PHAS-I phosphorylation was abolished after preincubation with the PI3K inhibitor, Wortmannin. Concomitantly, LELI enhanced Akt phosphorylation, which was attenuated in the presence of Wortmannin. Taken together, these results suggest that LELI induces protein translation via the PI3K/Akt and Ras/Raf/ERK pathways

Photon Correlations in Spectroscopy and Microscopy

Measurements of photon temporal correlations have been the mainstay of experiments in quantum optics. Over the past several decades, advancements in detector technologies have supported further extending photon correlation techniques to give rise to novel spectroscopy and imaging methods. This Perspective reviews the evolution of these techniques from temporal autocorrelations through multidimensional photon correlations to photon correlation imaging. State-of-the-art single-photon detector technologies are discussed, highlighting the main challenges and the unique current perspective of photon correlations to usher in a new generation of spectroscopy and imaging modalities.publishe

Monumental megalithic burial and rock art tell a new story about the Levant Intermediate Bronze "Dark Ages".

The Intermediate Bronze Age (IB) in the Southern Levant (ca. 2350-2000 BCE) is known as the "Dark Ages," following the collapse of Early Bronze urban society and predating the establishment of the Middle Bronze cities. The absence of significant settlements and monumental building has led to the reconstruction of IB social organization as that of nomadic, tribal society inhabiting rural villages with no central governmental system. Excavation in the Shamir Dolmen Field (comprising over 400 dolmens) on the western foothills of the Golan Heights was carried out following the discovery of rock art engravings on the ceiling of the central chamber inside one of the largest dolmens ever recorded in the Levant. Excavation of this multi-chambered dolmen, covered by a basalt capstone weighing some 50 tons, revealed a secondary multi-burial (of both adults and children) rarely described in a dolmen context in the Golan. Engraved into the rock ceiling above the multi-burial is a panel of 14 forms composed of a vertical line and downturned arc motif. 3D-scanning by structured-light technology was used to sharpen the forms and revealed the technique employed to create them. Building of the Shamir dolmens required a tremendous amount of labor, architectural mastery, and complex socio-economic organization well beyond the capacity of small, rural nomadic groups. The monumental megalithic burial of the Shamir dolmens indicates a hierarchical, complex, non-urban governmental system. This new evidence supports a growing body of recent criticism stemming from new discoveries and approaches that calls for rethinking our views of the Levantine IB "Dark Ages.