Gamma motor neurons express distinct genetic markers at birth and require muscle spindle-derived GDNF for postnatal survival

<p>Abstract</p> <p>Background</p> <p>Gamma motor neurons (γ-MNs) selectively innervate muscle spindle intrafusal fibers and regulate their sensitivity to stretch. They constitute a distinct subpopulation that differs in morphology, physiology and connectivity from α-MNs, which innervate extrafusal muscle fibers and exert force. The mechanisms that control the differentiation of functionally distinct fusimotor neurons are unknown. Progress on this question has been limited by the absence of molecular markers to specifically distinguish and manipulate γ-MNs. Recently, it was reported that early embryonic γ-MN precursors are dependent on GDNF. Using this knowledge we characterized genetic strategies to label developing γ-MNs based on GDNF receptor expression, showed their strict dependence for survival on muscle spindle-derived GDNF and generated an animal model in which γ-MNs are selectively lost.</p> <p>Results</p> <p>In mice heterozygous for both the <it>Hb9::GFP </it>transgene and a tau-lacZ-labeled (<it>TLZ</it>) allele of the GDNF receptor Gfrα1, we demonstrated that small motor neurons with high Gfrα1-TLZ expression and lacking Hb9::GFP display structural and synaptic features of γ-MNs and are selectively lost in mutants lacking target muscle spindles. Loss of muscle spindles also results in the downregulation of Gfrα1 expression in some large diameter MNs, suggesting that spindle-derived factors may also influence populations of α-MNs with β-skeletofusimotor collaterals. These molecular markers can be used to identify γ-MNs from birth to the adult and to distinguish γ- from β-motor axons in the periphery. We also found that postnatal γ-MNs are also distinguished by low expression of the neuronal nuclear protein (NeuN). With these markers of γ-MN identity, we show after conditional elimination of GDNF from muscle spindles that the survival of γ-MNs is selectively dependent on spindle-derived GDNF during the first 2 weeks of postnatal development.</p> <p>Conclusion</p> <p>Neonatal γ-MNs display a unique molecular profile characterized by the differential expression of a series of markers - Gfrα1, Hb9::GFP and NeuN - and the selective dependence on muscle spindle-derived GDNF. Deletion of GDNF expression from muscle spindles results in the selective elimination of γ-MNs with preservation of the spindle and its sensory innervation. This provides a mouse model with which to explore the specific role of γ-fusimotor activity in motor behaviors.</p

Southern Massive Stars at High Angular Resolution: Observational Campaign and Companion Detection

Multiplicity is one of the most fundamental observable properties of massive O-type stars and offers a promising way to discriminate between massive star formation theories. Nevertheless, companions at separations between 1 and 100 mas remain mostly unknown due to intrinsic observational limitations. [...] The Southern MAssive Stars at High angular resolution survey (SMASH+) was designed to fill this gap by providing the first systematic interferometric survey of Galactic massive stars. We observed 117 O-type stars with VLTI/PIONIER and 162 O-type stars with NACO/SAM, respectively probing the separation ranges 1-45 and 30-250mas and brightness contrasts of Delta H < 4 and Delta H < 5. Taking advantage of NACO's field-of-view, we further uniformly searched for visual companions in an 8''-radius down to Delta H = 8. This paper describes the observations and data analysis, reports the discovery of almost 200 new companions in the separation range from 1mas to 8'' and presents the catalog of detections, including the first resolved measurements of over a dozen known long-period spectroscopic binaries. Excluding known runaway stars for which no companions are detected, 96 objects in our main sample (DEC < 0 deg; H<7.5) were observed both with PIONIER and NACO/SAM. The fraction of these stars with at least one resolved companion within 200mas is 0.53. Accounting for known but unresolved spectroscopic or eclipsing companions, the multiplicity fraction at separation < 8'' increases to f_m = 0.91 +/- 0.03. The fraction of luminosity class V stars that have a bound companion reaches 100% at 30mas while their average number of physically connected companions within 8'' is f_c = 2.2 +/- 0.3. This demonstrates that massive stars form nearly exclusively in multiple systems. Additionally, the nine non-thermal (NT) radio emitters observed by SMASH+ are all resolved [...]Comment: 57 pages, 20 figures, 7 tables; accepted for publication in ApJ

Le tourisme, agent d&#039;interculturation sociospatial ? Le cas des pratiques touristiques littorales indonésiennes à Bali et à Java

A new interpretation of social relationships emerged in the 1990 in cultural psychology; based on the concept of interculturation, it helps to understand a co-constituted and yet contradictory phenomena: the transformation of existing cultures under the influence of social interactions and their persistance, fueled by the desire to preserve one\u27s identity. Yet, geographers have not yet claimed this concept, deeply associated to mobilities and site-specific cultural encounters. Using the case of the Indonesian touristic practices on the seaside in Bali and Java, this paper aims to indicate how the study of touristic phenomena can favor the appropriation of the concept of interculturation

Expériences touristiques et ludiques sur les littoraux en Indonésie : des vecteurs de mutation du rapport au corps ? Etude de cas des plages de Bali, Yogyakarta, Jakarta et Manado

Le littoral est, au travers de l\u27expérience touristique, un lieu d\u27innovation du rapport au corps qui a permis, sur le socle  de deux siècles d\u27histoire contemporaine, l\u27affranchissement des normes en place et la constitution de nouvelles. La complexité de ce phénomène a été abondamment étudiée en Occident, mais demeure en grande partie à découvrir en Indonésie.  L\u27objet de cette étude est donc d\u27analyser l\u27expérience touristique et ludique indonésienne du littoral et du rapport au corps qu\u27elle induit, entre reproduction des pratiques occidentales et particularismes culturels et relgieux locaux, permettant l\u27affirmation de modèle singulier indonésien

Global Health Needs Modernized Containment Strategies to Prepare for the Next Pandemic

COVID-19 continues to be a public health crisis, while severely impacting global financial markets causing significant economic and social hardship. As with any emerging disease, pharmaceutical interventions required time, emphasizing the initial and continuing need for non-pharmaceutical interventions. We highlight the role of anthropological and historical perspectives to inform approaches to non-pharmaceutical interventions for future preparedness. The National Academy of Medicine, a not-for-profit, non-governmental US-based medical watchdog organization, published a key document early in the COVID-19 pandemic which points to inadequate quarantine and containment infrastructure as a significant obstacle to an effective pandemic response. In considering how to implement effective quarantine policies and infrastructure, we argue that it is essential to take a longitudinal approach to assess interventions that have been effective in past pandemics while simultaneously addressing and eliminating the negative socio-historical legacies of ineffective quarantine practices. Our overview reinforces the need for social equity and compassion when implementing containment

C1B domain peptide of protein kinase Cγ significantly suppresses growth of human colon cancer cells in vitro and in an in vivo mouse xenograft model through induction of cell cycle arrest and apoptosis

Two peptides derived from the C1B domain of protein kinase Cγ (PKCγ) were shown to associate with classical PKC isozymes and modulate their activities. These C1B peptides are designated C1B1 (amino acid residues 101-112) and C1B5 (residues 141-151). Since PKC enzyme activity is shown to be involved in colon cancer development, the effect of C1B peptides on the growth of various human colon cancer cell lines was examined in vitro and in vivo. Sub-micromolar to micromolar levels of both C1B peptides induced approximately 60-70% growth attenuation in multiple colon cancer cell lines in a soft agar tumor colony assay; however, C1B5 peptide was not cytotoxic to normal colon epithelial cells in two dimensional culture. The effect of C1B5 peptide on colony growth of COLO205 cells was reversed by treatment with the PKCα/β inhibitor, Ro-32-0432. C1B peptide treatment attenuated COLO205 cells via two mechanisms: 1) cell cycle arrest and 2) stimulation of apoptosis. This is evident in G[subscript 2] arrest and increases in levels of cleaved caspase 3 and p53 phosphorylated at serine 20. Intratumoral injection of C1B5 peptide (20 mg/kg/day, every three days) markedly attenuated the growth of subcutaneous xenografts of COLO205 cells in SCID mice by 76% compared to the control. Taken together, these results strongly suggest that C1B peptides have negligible effects on normal tissues but are potentially effective chemotherapeutic agents for colon cancer

All the Brain\u27s a Stage for Serotonin: The Forgotten Story of Serotonin Diffusion across Cell Membranes

In the conventional model of serotonin neurotransmission, serotonin released by neurons in the midbrain raphe nuclei exerts its actions on forebrain neurons by interacting with a large family of post-synaptic receptors. The actions of serotonin are terminated by active transport of serotonin back into the releasing neuron, which is mediated by the serotonin reuptake transporter (SERT). Because SERT is expressed pre-synaptically and is widely thought to be the only serotonin transporter in the forebrain, the conventional model does not include serotonin transport into post-synaptic neurons. However, a large body of evidence accumulating since the 1970s has shown that serotonin, despite having a positive charge, can cross cell membranes through a diffusion-like process. Multiple low-affinity, high-capacity, sodium-independent transporters, widely expressed in the brain, allow the carrier-mediated diffusion of serotonin into forebrain neurons. The amount of serotonin crossing cell membranes through this mechanism under physiological conditions is considerable. Most prominent textbooks fail to include this alternative method of serotonin uptake in the brain, and even most neuroscientists are unaware of it. This failure has limited our understanding of a key regulator of serotonergic neurotransmission, impeded research on the potential intracellular actions of serotonin in post-synaptic neurons and glial cells, and may have impeded our understanding of the mechanism by which antidepressant medications reduce depressive symptoms

Modelling charge storage in Euclid CCD structures

The primary aim of ESA's proposed Euclid mission is to observe the distribution of galaxies and galaxy clusters, enabling the mapping of the dark architecture of the universe [1]. This requires a high performance detector, designed to endure a harsh radiation environment. The e2v CCD204 image sensor was redesigned for use on the Euclid mission [2]. The resulting e2v CCD273 has a narrower serial register electrode and transfer channel compared to its predecessor, causing a reduction in the size of charge packets stored, thus reducing the number of traps encountered by the signal electrons during charge transfer and improving the serial Charge Transfer Efficiency (CTE) under irradiation [3]. The proposed Euclid CCD has been modelled using the Silvaco TCAD software [4], to test preliminary calculations for the Full Well Capacity (FWC) and the channel potential of the device and provide indications of the volume occupied by varying signals. These results are essential for the realisation of the mission objectives and for radiation damage studies, with the aim of producing empirically derived formulae to approximate signal-volume characteristics in the devices. These formulae will be used in the radiation damage (charge trapping) models. The Silvaco simulations have been tested against real devices to compare the experimental measurements to those predicted in the models. Using these results, the implications of this study on the Euclid mission can be investigated in more detail

Tryptophan metabolism and bacterial commensals prevent fungal dysbiosis in Arabidopsis roots

In nature, roots of healthy plants are colonized by multikingdom microbial communities that include bacteria, fungi, and oomycetes. A key question is how plants control the assembly of these diverse microbes in roots to maintain host–microbe homeostasis and health. Using microbiota reconstitution experiments with a set of immunocompromised Arabidopsis thaliana mutants and a multikingdom synthetic microbial community (SynCom) representative of the natural A. thaliana root microbiota, we observed that microbiota-mediated plant growth promotion was abolished in most of the tested immunocompromised mutants. Notably, more than 40% of between-genotype variation in these microbiota-induced growth differences was explained by fungal but not bacterial or oomycete load in roots. Extensive fungal overgrowth in roots and altered plant growth was evident at both vegetative and reproductive stages for a mutant impaired in the production of tryptophan-derived, specialized metabolites (cyp79b2/b3). Microbiota manipulation experiments with single- and multikingdom microbial SynComs further demonstrated that 1) the presence of fungi in the multikingdom SynCom was the direct cause of the dysbiotic phenotype in the cyp79b2/b3 mutant and 2) bacterial commensals and host tryptophan metabolism are both necessary to control fungal load, thereby promoting A. thaliana growth and survival. Our results indicate that protective activities of bacterial root commensals are as critical as the host tryptophan metabolic pathway in preventing fungal dysbiosis in the A. thaliana root endosphere