ESCRT machinery mediates selective microautophagy of endoplasmic reticulum in yeast

ER-phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER-phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro-ER-phagy has been discovered, the molecules and mechanisms mediating micro-ER-phagy remain unknown. Here, we first show that micro-ER-phagy in yeast involves the conversion of stacked cisternal ER into multilamellar ER whorls during microautophagic uptake into lysosomes. Second, we identify the conserved Nem1-Spo7 phosphatase complex and the ESCRT machinery as key components for micro-ER-phagy. Third, we demonstrate that macro- and micro-ER-phagy are parallel pathways with distinct molecular requirements. Finally, we provide evidence that the ESCRT machinery directly functions in scission of the lysosomal membrane to complete the microautophagic uptake of ER. These findings establish a framework for a mechanistic understanding of micro-ER-phagy and, thus, a comprehensive appreciation of the role of autophagy in ER homeostasis

Effect of a physical activity intervention on lower body bone health in childhood cancer survivors: A randomized controlled trial (SURfit)

It remains controversial whether physical activity promotes bone health in childhood cancer survivors (CCS). We aimed to assess the effect of a one-year general exercise intervention on lower body bone parameters of CCS. CCS ≥16 years at enrollment, -1. A nonstandardized personalized exercise programs might not be specific enough to promote bone health in CCS, although those compliant and those most in need may benefit. Future trials should include bone stimulating exercise programs targeting risk groups with reduced bone health and motivational features to maximize compliance

Measurements in two bases are sufficient for certifying high-dimensional entanglement

High-dimensional encoding of quantum information provides a promising method of transcending current limitations in quantum communication. One of the central challenges in the pursuit of such an approach is the certification of high-dimensional entanglement. In particular, it is desirable to do so without resorting to inefficient full state tomography. Here, we show how carefully constructed measurements in two bases (one of which is not orthonormal) can be used to faithfully and efficiently certify bipartite high-dimensional states and their entanglement for any physical platform. To showcase the practicality of this approach under realistic conditions, we put it to the test for photons entangled in their orbital angular momentum. In our experimental setup, we are able to verify 9-dimensional entanglement for a pair of photons on a 11-dimensional subspace each, at present the highest amount certified without any assumptions on the state.Comment: 11+14 pages, 2+7 figure

Experimental non-classicality of an indivisible quantum system

Quantum theory demands that, in contrast to classical physics, not all properties can be simultaneously well defined. The Heisenberg Uncertainty Principle is a manifestation of this fact. Another important corollary arises that there can be no joint probability distribution describing the outcomes of all possible measurements, allowing a quantum system to be classically understood. We provide the first experimental evidence that even for a single three-state system, a qutrit, no such classical model can exist that correctly describes the results of a simple set of pairwise compatible measurements. Not only is a single qutrit the simplest system in which such a contradiction is possible, but, even more importantly, the contradiction cannot result from entanglement, because such a system is indivisible, and it does not even allow the concept of entanglement between subsystems.Comment: 11 pages, 4 figures, 2 table

First Evidence for Adoption in California Sea Lions

Demographic parameters such as birth and death rates determine the persistence of populations. Understanding the mechanisms that influence these rates is essential to developing effective management strategies. Alloparental behavior, or the care of non-filial young, has been documented in many species and has been shown to influence offspring survival. However, the role of alloparental behavior in maintaining population viability has not been previously studied. Here, we provide the first evidence for adoption in California sea lions and show that adoption potentially works to maintain a high survival rate of young and may ultimately contribute to population persistence. Alloparental behavior should have a positive effect on the population growth rate when the sum of the effects on fitness for the alloparent and beneficiary is positive

Effects of a partially supervised conditioning programme in cystic fibrosis: an international multi-centre randomised controlled trial (ACTIVATE-CF): study protocol

Physical activity (PA) and exercise have become an accepted and valued component of cystic fibrosis (CF) care. Regular PA and exercise can positively impact pulmonary function, improve physical fitness, and enhance health-related quality of life (HRQoL). However, motivating people to be more active is challenging. Supervised exercise programs are expensive and labour intensive, and adherence falls off significantly once supervision ends. Unsupervised or partially supervised programs are less costly and more flexible, but compliance can be more problematic. The primary objective of this study is to evaluate the effects of a partially supervised exercise intervention along with regular motivation on forced expiratory volume in 1 s (FEV1) at 6 months in a large international group of CF patients. Secondary endpoints include patient reported HRQoL, as well as levels of anxiety and depression, and control of blood sugar.; It is planned that a total of 292 patients with CF 12 years and older with a FEV1 ≥ 35% predicted shall be randomised. Following baseline assessments (2 visits) patients are randomised into an intervention and a control group. Thereafter, they will be seen every 3 months for assessments in their centre for one year (4 follow-up visits). Along with individual counselling to increase vigorous PA by at least 3 h per week on each clinic visit, the intervention group documents daily PA and inactivity time and receives a step counter to record their progress within a web-based diary. They also receive monthly phone calls from the study staff during the first 6 months of the study. After 6 months, they continue with the step counter and web-based programme for a further 6 months. The control group receives standard care and keeps their PA level constant during the study period. Thereafter, they receive the intervention as well.; This is the first large, international multi-centre study to investigate the effects of a PA intervention in CF with motivational feedback on several health outcomes using modern technology. Should this relatively simple programme prove successful, it will be made available on a wider scale internationally.; ClinicalTrials.gov Identifier: NCT01744561 ; Registration date: December 6, 2012

On-chip generation of high-dimensional entangled quantum states and their coherent control

Optical quantum states based on entangled photons are essential for solving questions in fundamental physics and are at the heart of quantum information science1. Specifically, the realization of high-dimensional states (D-level quantum systems, that is, qudits, with D > 2) and their control are necessary for fundamental investigations of quantum mechanics2, for increasing the sensitivity of quantum imaging schemes3, for improving the robustness and key rate of quantum communication protocols4, for enabling a richer variety of quantum simulations5, and for achieving more efficient and error-tolerant quantum computation6. Integrated photonics has recently become a leading platform for the compact, cost-efficient, and stable generation and processing of non-classical optical states7. However, so far, integrated entangled quantum sources have been limited to qubits (D = 2)8, 9, 10, 11. Here we demonstrate on-chip generation of entangled qudit states, where the photons are created in a coherent superposition of multiple high-purity frequency modes. In particular, we confirm the realization of a quantum system with at least one hundred dimensions, formed by two entangled qudits with D = 10. Furthermore, using state-of-the-art, yet off-the-shelf telecommunications components, we introduce a coherent manipulation platform with which to control frequency-entangled states, capable of performing deterministic high-dimensional gate operations. We validate this platform by measuring Bell inequality violations and performing quantum state tomography. Our work enables the generation and processing of high-dimensional quantum states in a single spatial mode