Excitation and tailoring of diffractive spin-wave beams in NiFe using nonuniform microwave antennas

We experimentally demonstrate by time-resolved scanning magneto-optical Kerr microscopy the possibility to locally excite multiple spin-wave beams in the dipolar-dominated regime in metallic NiFe films. For this purpose we employ differently shaped nonuniform microwave antennas consisting of several coplanar waveguide sections different in size, thereby adapting an approach for the generation of spin-wave beams in the exchange-dominated regime suggested by Gruszecki et al. [Sci. Rep. 6, 22367 (2016)]. The occurring spin-wave beams are diffractive and we show that the width of the beam and its widening as it propagates can be tailored by the shape and the length of the nonuniformity. Moreover, the propagation direction of the diffractive beams can be manipulated by changing the bias field direction

Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210

Background Autophagy participates in innate immunity by eliminating intracellular pathogens. Consequently, numerous microorganisms have developed strategies to impair the autophagic machinery in phagocytes. In the current study, interactions between Leishmania major (L. m.) and the autophagic machinery of bone marrow-derived macrophages (BMDM) were analyzed. Methods BMDM were generated from BALB/c mice, and the cells were infected with L. m. promastigotes. Transmission electron microscopy (TEM) and electron tomography were used to investigate the ultrastructure of BMDM and the intracellular parasites. Affymetrix® chip analyses were conducted to identify autophagy-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The protein expression levels of autophagy related 5 (ATG5), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), cathepsin E (CTSE), mechanistic target of rapamycin (MTOR), microtubule-associated proteins 1A/1B light chain 3B (LC3B), and ubiquitin (UB) were investigated through western blot analyses. BMDM were transfected with specific small interfering RNAs (siRNAs) against autophagy-related genes and with mimics or inhibitors of autophagy-associated miRNAs. The infection rates of BMDM were determined by light microscopy after a parasite-specific staining. Results The experiments demonstrated autophagy induction in BMDM after in vitro infection with L. m.. The results suggested a putative MTOR phosphorylation-dependent counteracting mechanism in the early infection phase and indicated that intracellular amastigotes were cleared by autophagy in BMDM in the late infection phase. Transcriptomic analyses and specific downregulation of protein expression with siRNAs suggested there is an association between the infection-specific over expression of BNIP3, as well as CTSE, and the autophagic activity of BMDM. Transfection with mimics of mmu-miR-101c and mmu-miR-129-5p, as well as with an inhibitor of mmu-miR-210-5p, demonstrated direct effects of the respective miRNAs on parasite clearance in L. m.-infected BMDM. Furthermore, Affymetrix® chip analyses revealed a complex autophagy-related RNA network consisting of differentially expressed mRNAs and miRNAs in BMDM, which indicates high glycolytic and inflammatory activity in the host macrophages. Conclusions Autophagy in L. m.-infected host macrophages is a highly regulated cellular process at both the RNA level and the protein level. Autophagy has the potential to clear parasites from the host. The results obtained from experiments with murine host macrophages could be translated in the future to develop innovative and therapeutic antileishmanial strategies for human patients

Magnetic properties of spin waves in thin yttrium iron garnet films

We report spin wave propagation experiments in thin yttrium iron garnet (YIG) films. Using time-resolved scanning Kerr microscopy we extract the mode structure of the spin waves. For quasi-single-mode excitation, the spin wave decay can be fitted with a damped harmonic oscillator function providing us with information about the attenuation length. We measure values of about 2.7 and 3.6 μm for the spin wave decay length of 38- and 49-nm-thick YIG samples, respectively. Micromagnetic simulations are performed to compare experimental and simulated modes. The data are in very good agreement with these simulations

DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons

Disturbed motor control is a hallmark of Parkinson's disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats. DRD1 activation causes enhanced TrkB translocation to the cell surface and increased sensitivity for BDNF. In contrast, dopamine depletion in cultured dSPN neurons, 6-OHDA-treated rats, and postmortem brain of patients with PD reduces BDNF responsiveness and causes formation of intracellular TrkB clusters. These clusters associate with sortilin related VPS10 domain containing receptor 2 (SORCS-2) in multivesicular-like structures, which apparently protects them from lysosomal degradation. Thus, impaired TrkB processing might contribute to disturbed motor function in PD.This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) project 424778381 (TRR295, A05, A06, and A01), project SE697/7-1, and project 218894895 (INST93/761-1FUGG). R.L.M.was supported by the Alexander von Humboldt-Stiftung. V.P. and C.S.were supported by GRK2581 (P6) SPHINGOINF of the DFG.Work in the lab of R.M. was supported by grant PID2019-111693RB-100 from MICIN/AEI/10.13039/501100011033, the European Union’s Horizon 2020 research and innovation program, AND-PD (grant 84800),Next Generation EU/PRTR (MICIN/CSIC/PTI+NeuroAging), and CIBERNED, Instituto de Salud Carlos III. The graphical abstract was created with BioRender.com. We thank Drs.James Surmeier, Moses Chao, and Esther Asan for critical comments and suggestions

Cell-Autonomous Requirement for Rx Function in the Mammalian Retina and Posterior Pituitary

Rx is a paired-like homeobox gene that is required for vertebrate eye formation. Mice lacking Rx function do not develop eyes or the posterior pituitary. To determine whether Rx is required cell autonomously in these tissues, we generated embryonic chimeras consisting of wild type and Rx−/− cells. We found that in the eye, Rx-deficient cells cannot participate in the formation of the neuroretina, retina pigment epithelium and the distal part of the optic stalk. In addition, in the ventral forebrain, Rx function is required cell autonomously for the formation of the posterior pituitary. Interestingly, Rx−/− and wild type cells segregate before the morphogenesis of these two tissues begins. Our observations suggest that Rx function is not only required for the morphogenesis of the retina and posterior pituitary, but also prior to morphogenesis, for the sorting out of cells to form distinct fields of retinal/pituitary cells

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Specification, maintenance and fate determination of neural progenitor pools in the zebrafish central nervous system.

This thesis contributes to the deeper understanding of the processes of specification and maintenance of neural progenitor pools and to the mechanisms of fate determination in the central nervous system of the zebrafish. The focus of this work lies on the progenitor pools of the eye field and the midbrain-hindbrain boundary. E(Spl) genes and microRNA 9 could be identified as factors that are crucially implicated in the control of the progenitor status. Furthermore, molecular and cellular differences of progenitors within the midbrain-hindbrain domain and the role of a timer mechanism in cell fate determination were analyzed. With the help of comparative studies parallels and differences between progenitor pools in the embryonic and adult brain could be identified