Notes

Visual image of Chromatin from the Fungus Nucleus along with Nucleolus Using Hyperosmotic Jolt.
Whereas mild, antibody-based immunologic conditioning concepts might be appropriate for benign hematological disorders in which incomplete replacement of diseased cells is sufficient, higher efficacy will be required for treatment and elimination of hematologic stem cell malignancies such as acute myeloid leukemia and myelodysplastic syndrome. Antibody-drug conjugates, bispecific T-cell engaging and activating antibodies (TEAs), or chimeric antigen receptor (CAR) T cells might offer increased efficacy compared with naked antibodies and yet higher tolerability and safety compared with current genotoxic conditioning approaches. Here, we summarize the current state regarding immunologic conditioning concepts for the treatment of HSC disorders and outline potential future developments.Caregivers modify their speech when talking to infants, a specific type of speech known as infant-directed speech (IDS). This speaking style facilitates language learning compared to adult-directed speech (ADS) in infants with normal hearing (NH). While infants with NH and those with cochlear implants (CIs) prefer listening to IDS over ADS, it is yet unknown how CI processing may affect the acoustic distinctiveness between ADS and IDS, as well as the degree of intelligibility of these. This study analyzed speech of seven female adult talkers to model the effects of simulated CI processing on (1) acoustic distinctiveness between ADS and IDS, (2) estimates of intelligibility of caregivers' speech in ADS and IDS, and (3) individual differences in caregivers' ADS-to-IDS modification and estimated speech intelligibility. Results suggest that CI processing is substantially detrimental to the acoustic distinctiveness between ADS and IDS, as well as to the intelligibility benefit derived from ADS-to-IDS modifications. Moreover, the observed variability across individual talkers in acoustic implementation of ADS-to-IDS modification and the estimated speech intelligibility was significantly reduced due to CI processing. The findings are discussed in the context of the link between IDS and language learning in infants with CIs.The proteostasis network guarantees successful protein synthesis, folding, transportation, and degradation. Mounting evidence has revealed that this network maintains proteome integrity and is linked to cellular physiology, pathology, and virus infection. Human enterovirus A71 (EV-A71) and EV-D68 are suspected causative agents of acute flaccid myelitis, a severe poliomyelitis-like neurologic syndrome with no known cure. In this context, further clarification of the molecular mechanisms underlying EV-A71 and EV-D68 infection is paramount. Here, we summarize the components of the proteostasis network that are intercepted by EV-A71 and EV-D68, as well as antivirals that target this network and may help develop improved antiviral drugs.Tumor neovascularization may occur via both angiogenic and vasculogenic events. In order to investigate the vessel formation during tumor growth, we developed a novel experimental model that takes into account the differentiative and tumorigenic properties of Embryonic Stem cells (ESCs). Leukemia Inhibitory Factor-deprived murine ESCs were grafted on the top of the chick embryo chorionallantoic membrane (CAM) in ovo. Cell grafts progressively grew, forming a vascularized mass within 10 days. At this stage, the grafts are formed by cells with differentiative features representative of all three germ layers, thus originating teratomas, a germinal cell tumor. In addition, ESC supports neovascular events by recruiting host capillaries from surrounding tissue that infiltrates the tumor mass. Moreover, immunofluorescence studies demonstrate that perfused active blood vessels within the tumor are of both avian and murine origin because of the simultaneous occurrence of angiogenic and vasculogenic events. In conclusion, the chick embryo ESC/CAM-derived teratoma model may represent a useful approach to investigate both vasculogenic and angiogenic events during tumor growth and for the study of natural and synthetic modulators of the two processes.Recording neural activities over large populations is critical for a better understanding of the functional mechanisms of animal brains. Traditional optical imaging technologies for in vivo neural activity recording are usually limited in throughput and cannot cover a large imaging volume at high speed. Light-field microscopy features a highly parallelized imaging collection mechanism and can simultaneously record optical signals from different depths. Therefore, it can potentially increase the imaging throughput substantially. Furthermore, its unique instantaneous volumetric imaging capability enables the capture of highly dynamic processes, such as recording whole-animal neural activities in freely moving Caenorhabditis elegans and whole-brain neural activity in freely swimming larval zebrafish during prey capture. Here, we summarize the principles of and considerations in the practical implementation of light-field microscopy as currently applied in biological imaging experiments. We also discuss the strategies that light-field microscopy can employ when imaging thick tissues in the presence of scattering and background interference. Finally, we present a few examples of applying light-field microscopy in neuroscientific studies in several important animal models.
Recent anthropomorphic disturbances are occurring at an increasing rate leading to organisms facing a variety of challenges. This change is testing the information processing capacity (IPC) of all animals. Brain function is widely accepted to be influenced by a variety of factors, including relative size, number of neurons and neuronal densities. Therefore, in order to understand what drives an animals IPC, a methodological approach to analyze these factors must be established.

Here we created a protocol that allowed for high-throughput, non-biased quantification of neuronal density and size across six regions of the brain. We used the Isotropic Fractionator method in combination with flow cytometry to identify neuronal and non-neuronal cells in the brains of adult rats.

The results obtained were comparable to those identified using stereological counting methods.

By employing this new method, the number of nuclei in a specific brain region can be compared between replicate animals within an experiment. By calibrating the forward scatter channel of the flow cytometer with size standard beads, neuronal and non-neuronal nuclear sizes can be estimated simultaneously with nuclei enumeration. These techniques for nuclear counting and size estimation are technically and biologically reproducible.

Use of flow cytometry provides a methodological approach that allows for consistency in research, so that information on brain morphology, and subsequent function, will become comparable across taxa.
Use of flow cytometry provides a methodological approach that allows for consistency in research, so that information on brain morphology, and subsequent function, will become comparable across taxa.
In the context of signal analysis and pattern matching, alignment of 1D signals for the comparison of signal morphologies is an important problem. For image processing and computer vision, 2D optical flow (OF) methods find wide application for motion analysis and image registration and variational OF methods have been continuously improved over the past decades.

We propose a variational method for the alignment and displacement estimation of 1D signals. We pose the estimation of non-flat displacements as an optimization problem with a similarity and smoothness term similar to variational OF estimation. To this end, we can make use of efficient optimization strategies that allow real-time applications on consumer grade hardware.

We apply our method to two applications from functional neuroimaging The alignment of 2-photon imaging line scan recordings and the denoising of evoked and event-related potentials in single trial matrices. We can report state of the art results in terms of alignment quality and computing speeds.

Existing methods for 1D alignment target mostly constant displacements, do not allow native subsample precision or precise control over regularization or are slower than the proposed method.

Our method is implemented as a MATLAB toolbox and is online available. It is suitable for 1D alignment problems, where high accuracy and high speed is needed and non-constant displacements occur.
Our method is implemented as a MATLAB toolbox and is online available. It is suitable for 1D alignment problems, where high accuracy and high speed is needed and non-constant displacements occur.Phototrophic biofilms produce a matrix of extracellular polymeric substances (EPS), which holds the cells together and functions inter alia as nutrient storage and protection layer. EPS mainly consist of water, polysaccharides, proteins, lipids and nucleic acids as well as lysis and hydrolysis products which makes the composition very complex. Thus, rough simplifications are used and commonly one or at most two components of the EPS are examined. In this work a new procedure for separation and analysis of EPS in the main components (i) polysaccharides, (ii) proteins and (iii) lipids is presented with recovery rates of nearly 100 %. The method was established with synthetic EPS, which based on the composition of real EPS described in literature. Afterwards, the method was transferred to real EPS samples allowing a deeper insight in the composition of EPS from only one sample. The composition of EPS-extracts from Nostoc spec, cultivated under heterotrophic and mixotrophic batch and fed-batch conditions, was analysed during a cultivation period of 14 days. It was observed that mixotrophic cultivation led to higher amounts of carbohydrates, lipids and proteins than heterotrophic cultivation respectively, regardless of batch or fed-batch culture. While the amount of proteins in the EPS increased during the cultivation period, carbohydrates and lipids were dominant in the beginning and decreased afterwards.The adrenal cortex is the main steroid producing organ of the human body. Studies on adrenal tissue renewal have been neglected for many years, but recent intensified research has seen tremendous progress in our understanding of the formation and homeostasis of this organ. However, cell turnover of the adrenal cortex appears to be complex and several cell populations have been identified that can differentiate into steroidogenic cells and contribute to adrenal cortex renewal. The purpose of this review is to provide an overview of how the adrenal cortex develops and how stem cell populations relate to its developmental progenitors. Finally, we will summarize present and future approaches to harvest the potential of progenitor/stem cells for future cell replacement therapies.The syndromes of mineralocorticoid excess describe a heterogeneous group of clinical manifestations leading to endocrine hypertension, typically either through direct activation of mineralocorticoid receptors or indirectly by impaired pre-receptor enzymatic regulation or through disturbed renal sodium homeostasis. The phenotypes of these disorders can be caused by inherited gene variants and somatic mutations or may be acquired upon exposures to exogenous substances. Regarding the latter, the symptoms of an acquired mineralocorticoid excess have been reported during treatment with azole antifungal drugs. The current review describes the occurrence of mineralocorticoid excess particularly during the therapy with posaconazole and itraconazole, addresses the underlying mechanisms as well as inter- and intra-individual differences, and proposes a therapeutic drug monitoring strategy for these two azole antifungals. Moreover, other therapeutically used azole antifungals and ongoing efforts to avoid adverse mineralocorticoid effects of azole compounds are shortly discussed.
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