Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration

Acute skeletal muscle injury is followed by an inflammatory response, removal of damaged tissue, and the generation of new muscle fibers by resident muscle stem cells, a process well characterized in murine injury models. Inflammatory cells are needed to remove the debris at the site of injury and provide signals that are beneficial for repair. However, they also release chemokines, reactive oxygen species as well as enzymes for clearance of damaged cells and fibers, which muscle stem cells have to withstand in order to regenerate the muscle. We show here that MET and CXCR4 cooperate to protect muscle stem cells against the adverse environment encountered during muscle repair. This powerful cyto-protective role was revealed by the genetic ablation of Met and Cxcr4 in muscle stem cells of mice, which resulted in severe apoptosis during early stages of regeneration. TNFα neutralizing antibodies rescued the apoptosis, indicating that TNFα provides crucial cell-death signals during muscle repair that are counteracted by MET and CXCR4. We conclude that muscle stem cells require MET and CXCR4 to protect them against the harsh inflammatory environment encountered in an acute muscle injury

Mid-circuit qubit measurement and rearrangement in a 171^{171}Yb atomic array

Measurement-based quantum error correction relies on the ability to determine the state of a subset of qubits (ancillae) within a processor without revealing or disturbing the state of the remaining qubits. Among neutral-atom based platforms, a scalable, high-fidelity approach to mid-circuit measurement that retains the ancilla qubits in a state suitable for future operations has not yet been demonstrated. In this work, we perform imaging using a narrow-linewidth transition in an array of tweezer-confined $^{171}$Yb atoms to demonstrate nondestructive state-selective and site-selective detection. By applying site-specific light shifts, selected atoms within the array can be hidden from imaging light, which allows a subset of qubits to be measured while causing only percent-level errors on the remaining qubits. As a proof-of-principle demonstration of conditional operations based on the results of the mid-circuit measurements, and of our ability to reuse ancilla qubits, we perform conditional refilling of ancilla sites to correct for occasional atom loss, while maintaining the coherence of data qubits. Looking towards true continuous operation, we demonstrate loading of a magneto-optical trap with a minimal degree of qubit decoherence.Comment: 9 pages, 6 figure

Structure and microstructure evolution of Al-Mg-Si alloy processed by equal-channel angular pressing

An ultrafine grained Al–Mg–Si alloy was prepared by severe plastic deformation using the equal-channel angular pressing (ECAP) method. Samples were ECAPed through a die with an inner angle of F = 90° and outer arc of curvature of ¿ = 37° from 1 to 12 ECAP passes at room temperature following route Bc. To analyze the evolution of the microstructure at increasing ECAP passes, X-ray diffraction and electron backscatter diffraction analyses were carried out. The results revealed two distinct processing regimes, namely (i) from 1 to 5 passes, the microstructure evolved from elongated grains and sub-grains to a rather equiaxed array of ultrafine grains and (ii) from 5 to 12 passes where no change in the morphology and average grain size was noticed. In the overall behavior, the boundary misorientation angle and the fraction of high-angle boundaries increase rapidly up to 5 passes and at a lower rate from 5 to 12 passes. The crystallite size decreased down to about 45 nm with the increase in deformation. The influence of deformation on precipitate evolution in the Al–Mg–Si alloy was also studied by differential scanning calorimetry. A significant decrease in the peak temperature associated to the 50% of recrystallization was observed at increasing ECAP passes.Peer ReviewedPreprin

COVAD survey 2 long-term outcomes: unmet need and protocol

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups

Investigating the effect of meta-cognitive scaffolding for learning by teaching

This paper investigates the effect of meta-cognitive help in the context of learning by teaching. Students learned to solve algebraic equations by tutoring a teachable agent, called SimStudent, using an online learning environment, called APLUS. A version of APLUS was developed to provide meta-cognitive help on what problems students should teach, as well as when to quiz SimStudent. A classroom study comparing APLUS with and without the meta-cognitive help was conducted with 173 seventh to ninth grade students. The data showed that students with the meta-cognitive help showed better problem selection and scored higher on the post-test than those who tutored SimStudent without the meta-cognitive help. These results suggest that, when carefully designed, learning by teaching can support students to not only learn cognitive skills but also employ meta-cognitive skills for effective tutoring. © 2014 Springer International Publishing Switzerland

Colonization of the satellite cell niche by skeletal muscle progenitor cells depends on notch signals

Skeletal muscle growth and regeneration rely on myogenic progenitor and satellite cells, the stem cells of postnatal muscle. Elimination of Notch signals during mouse development results in premature differentiation of myogenic progenitors and formation of very small muscle groups. Here we show that this drastic effect is rescued by mutation of the muscle differentiation factor MyoD. However, rescued myogenic progenitors do not assume a satellite cell position and contribute poorly to myofiber growth. The disrupted homing is due to a deficit in basal lamina assembly around emerging satellite cells and to their impaired adhesion to myofibers. On a molecular level, emerging satellite cells deregulate the expression of basal lamina components and adhesion molecules like integrin {alpha}7, collagen XVIII{alpha}1, Megf10, and Mcam. We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers

The Effects of Androgens on Bovine and Human Granulosa Cells

A subpopulation of cows in the Physiology herd has been identified as subfertile due to sporadic or chronic anovulation. This decrease in fertility could be lost profits for farmers and raises questions about ovulation disorders in women. Granulosa cells, a type of cell that is essential to ovarian follicle development, was investigated to determine if high concentrations of a hormone, androstenedione, could impact the follicular environment enough to cause anovulation disorders. Previous studies suggested that excess androgen may decrease the number of functioning granulosa cells by preventing them from proliferating within the follicle. Fewer granulosa cells mean fewer cells that are available to convert androstenedione to estrogen; and estrogen is required for the development of the follicle and ovulation. This research experience determined that when primary granulosa cells are subjected to high concentrations of androstenedione the rate of proliferation decreases based on the reduced proliferation promoting genes within the cells. These tests were done on primary granulosa cells from bovine as well as an immortalized granulosa cell line from humans