Emerging evidence suggests that new cells, including neurons, can be generated within the adult hypothalamus, suggesting the existence of a local neural stem/progenitor cell niche. Here, we identify ...α-tanycytes as key components of a hypothalamic niche in the adult mouse. Long-term lineage tracing in vivo using a GLAST::CreER(T2) conditional driver indicates that α-tanycytes are self-renewing cells that constitutively give rise to new tanycytes, astrocytes and sparse numbers of neurons. In vitro studies demonstrate that α-tanycytes, but not β-tanycytes or parenchymal cells, are neurospherogenic. Distinct subpopulations of α-tanycytes exist, amongst which only GFAP-positive dorsal α2-tanycytes possess stem-like neurospherogenic activity. Fgf-10 and Fgf-18 are expressed specifically within ventral tanycyte subpopulations; α-tanycytes require fibroblast growth factor signalling to maintain their proliferation ex vivo and elevated fibroblast growth factor levels lead to enhanced proliferation of α-tanycytes in vivo. Our results suggest that α-tanycytes form the critical component of a hypothalamic stem cell niche, and that local fibroblast growth factor signalling governs their proliferation.
The existence of dark matter is undisputed, while the nature of it is still unknown. Explaining dark matter with the existence of a new unobserved particle is among the most promising possible ...solutions. Recently dark matter candidates in the MeV mass region received more and more interest. In comparison to the mass region between a few GeV to several TeV, this region is experimentally largely unexplored. We discuss the application of a RNDR DEPFET semiconductor detector for direct searches for dark matter in the MeV mass region. We present the working principle of the RNDR DEPFET devices and review the performance obtained by previously performed prototype measurements. The future potential of the technology as dark matter detector is discussed and the sensitivity for MeV dark matter detection with RNDR DEPFET sensors is presented. Under the assumption of six background events in the region of interest and an exposure of 1 kg year a sensitivity of about
σ
¯
e
=
10
-
41
cm
2
for dark matter particles with a mass of 10 MeV can be reached.
The world of photon science experiences significant advancements since the advent of synchrotron light sources with unprecedented brilliance, intensity and pulse repetition rates, with large ...implications on the detectors used for instrumentation. Here, an overview about the work on this field carried out at the semiconductor laboratory of the Max-Planck-Society (MPG HLL) is given. Main challenges are high dynamic range to resolve faint features at the fringes of scatter images as well as structures in bright peaks, and high bandwidth to fully exploit the fast timing capability of the source. A newly developed device to improve the signal-to-noise-ratio (SNR) at high bandwidths is the so-called MARTHA (Monolithic Array of Reach-Through Avalanche Photodiodes) structure, which integrates an array of APDs on a monolithic substrate. The reach-through architecture assures near 100% fill factor and allows implementing a thin entrance window with optimized quantum efficiency for low energy X-rays. The structures operate in proportional mode with adjustable gain, and can serve as a drop-in replacement for PAD detectors in hybrid pixel systems. A more sophisticated solution for low to medium frame rate applications with high contrast requirement are pnCCDs with high dynamic range in the pixel area featuring DEPFET based readout nodes with non-linear amplification (NLA). The high dynamic range mode has been demonstrated for pnCCD devices with a pixel size down to 75 μm
2
. Framerates of up to 1 kHz are possible for a 1 Megapixel detector. Small size prototypes of these structures have recently been manufactured. Modified DEPFET structures with build-in non-linear amplification are also used to implement active pixel detectors optimized for high dynamic range. Successfully prototyped for the DSSC sensors (DEPFET Sensor with Signal Compression) at the XFEL, these structures are increasingly being used in applications requiring high contrast and intensity, e.g., TEM imaging. Charge handling capability and output characteristics can be tailored to the requirements, as well as pixel geometry and size. The large intrinsic gain of the DEPFET provides excellent SNR even at fast timing. Pixels can be read with a speed of 100 ns, the resulting frame rate depends on the degree of readout parallelization.
Distinct olfactory bulb (OB) interneurons are thought to become specified depending on from which of the different subregions lining the lateral ventricle wall they originate, but the role of ...region-specific transcription factors (TFs) in the generation of OB interneurons diversity is still poorly understood. Despite the crucial roles of the Dlx family of TFs for patterning and neurogenesis in the ventral telencephalon during embryonic development, their role in adult neurogenesis has not yet been addressed. Here we show that in the adult brain, Dlx 1 and Dlx2 are expressed in progenitors of the lateral but not the dorsal subependymal zone (SEZ), thus exhibiting a striking regional specificity. Using retroviral vectors to examine the function of Dlx2 in a cell-autonomous manner, we demonstrate that this TF is necessary for neurogenesis of virtually all OB interneurons arising from the lateral SEZ. Beyond its function in generic neurogenesis, Dlx2 also plays a crucial role in neuronal subtype specification in the OB, promoting specification of adult-born periglomerular neurons (PGNs) toward a dopaminergic fate. Strikingly, Dlx2 requires interaction with Pax6, because Pax6 deletion blocks Dlx2-mediated PGN specification. Thus, Dlx2 wields a dual function by first instructing generic neurogenesis from adult precursors and subsequently specifying PGN subtypes in conjunction with Pax6.
Hippocampal neurogenesis has been proposed to participate in a myriad of behavioral responses, both in basal states and in the context of neuropsychiatric disorders. Here, we identify activating ...protein 2γ (AP2γ, also known as Tcfap2c), originally described to regulate the generation of neurons in the developing cortex, as a modulator of adult hippocampal glutamatergic neurogenesis in mice. Specifically, AP2γ is present in a sub-population of hippocampal transient amplifying progenitors. There, it is found to act as a positive regulator of the cell fate determinants Tbr2 and NeuroD, promoting proliferation and differentiation of new glutamatergic granular neurons. Conditional ablation of AP2γ in the adult brain significantly reduced hippocampal neurogenesis and disrupted neural coherence between the ventral hippocampus and the medial prefrontal cortex. Furthermore, it resulted in the precipitation of multimodal cognitive deficits. This indicates that the sub-population of AP2γ-positive hippocampal progenitors may constitute an important cellular substrate for hippocampal-dependent cognitive functions. Concurrently, AP2γ deletion produced significant impairments in contextual memory and reversal learning. More so, in a water maze reference memory task a delay in the transition to cognitive strategies relying on hippocampal function integrity was observed. Interestingly, anxiety- and depressive-like behaviors were not significantly affected. Altogether, findings open new perspectives in understanding the role of specific sub-populations of newborn neurons in the (patho)physiology of neuropsychiatric disorders affecting hippocampal neuroplasticity and cognitive function in the adult brain.
The KDK (potassium decay) experiment Di Stefano, P.C.F.; Brewer, N.; Fijałkowska, A. ...
Journal of physics. Conference series,
01/2020, Letnik:
1342, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Potassium-40 (40K) is a background in many rare-event searches and may well play a role in interpreting results from the DAMA dark-matter search. The electron-capture decay of 40K to the ground state ...of 40 Ar has never been measured and contributes an unknown amount of background. The KDK (potassium decay) collaboration will measure this branching ratio using a 40K source, an X-ray detector, and the Modular Total Absorption Spectrometer at Oak Ridge National Laboratory.
The focal-plane module is the key component of the DEPFET sensor with signal compression (DSSC) mega-pixel X-ray imager and handles the data of 128 <inline-formula> <tex-math ...notation="LaTeX">\times512 </tex-math></inline-formula> pixels. We report on assembly-related aspects, discuss the experimental investigation of bonding behavior of different adhesives, and present the metrology and electrical test results of the production. The module consists of two silicon (Si) sensors with flip-chip connected CMOS integrated circuits, a Si-heat spreader, a low-temperature co-fired ceramics circuit board, and a molybdenum frame. A low-modulus urethane-film adhesive fills the gaps between on-board components and frame. It is also used between board and heat spreader, reduces the misfit strain, and minimizes the module warpage very efficiently. The heat spreader reduces the on-board temperature gradient by about one order of magnitude. The placement precision of the bare modules to each other and the frame is characterized by a standard deviation below 10 and 65 <inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula>, respectively. The displacement due to the in-plane rotation and vertical tilting errors remains below 80 and 50 <inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula>, respectively. The deflection of the sensor plane shows a mean value below 30 <inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> with a standard deviation below 15 <inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula>. Less than 4% of the application-specified integrated circuits (ASICs) exhibit a malfunction. More than two-thirds of the sensors have a maximum leakage current below 1 <inline-formula> <tex-math notation="LaTeX">\mu \text{A} </tex-math></inline-formula>.
We present first significant limits on WIMP dark matter by the phonon-light technique, where combined phonon and light signals from a scintillating cryogenic detector are used. Data from early 2004 ...with two 300g CRESST-II prototype detector modules are presented, with a net exposure of 20.5kg days. The modules consist of a CaWO4 scintillating “target” crystal and a smaller cryogenic light detector. The combination of phonon and light signals leads to a strong suppression of non-nuclear recoil backgrounds. Using this information to define an acceptance region for nuclear recoils we have 16 events from the two modules, corresponding to a rate for nuclear recoils between 12 and 40keV of (0.87±0.22) events/(kgday). This is compatible with the rate expected from neutron background, and most of these events lie in the region of the phonon-light plane anticipated for neutron-induced recoils. A particularly strong limit for WIMPs with coherent scattering results from selecting a region of the phonon-light plane corresponding to tungsten recoils, where the best module shows zero events.
The mammalian brain contains few niches for neural stem cells (NSCs) capable of generating new neurons, whereas other regions are primarily gliogenic. Here we leverage the spatial separation of the ...sub-ependymal zone NSC niche and the olfactory bulb, the region to which newly generated neurons from the sub-ependymal zone migrate and integrate, and present a comprehensive proteomic characterization of these regions in comparison to the cerebral cortex, which is not conducive to neurogenesis and integration of new neurons. We find differing compositions of regulatory extracellular matrix (ECM) components in the neurogenic niche. We further show that quiescent NSCs are the main source of their local ECM, including the multi-functional enzyme transglutaminase 2, which we show is crucial for neurogenesis. Atomic force microscopy corroborated indications from the proteomic analyses that neurogenic niches are significantly stiffer than non-neurogenic parenchyma. Together these findings provide a powerful resource for unraveling unique compositions of neurogenic niches.
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•Proteomics define the NSC niche-specific extracellular matrix•Detergent-solubility profiling reveals extracellular matrix architecture•Transglutaminase 2 regulates neurogenesis•Stiffness is increased in the neurogenic niches of the brain
The physical properties of stem cell niches are thought to mediate important regulatory functions. Here we provide a proteomic resource of the neural stem cell niche in comparison to gliogenic brain parenchyma, highlighting stiffness and the enzyme transglutaminase 2 as key regulators of neurogenesis.
Endogenous opioids are synthesized in vivo to modulate pain mechanisms and inflammatory pathways. Endogenous and exogenous opioids mediate analgesia in response to painful stimuli by binding to ...opioid receptors on neuronal cells. However, wide distribution of opioid receptors on tissues and organ systems outside the CNS, such as the cells of the immune system, indicate that opioids are capable of exerting additional effects in the periphery, such as immunomodulation. The increased prevalence of infections in opioid abuser-based epidemiological studies further highlights the immunosuppressive effects of opioids. In spite of their many debilitating side effects, prescription opioids remain a gold standard for treatment of chronic pain. Therefore, given the prevalence of opioid use and abuse, opioid-mediated immune suppression presents a serious concern in our society today. It is imperative to understand the mechanisms by which exogenous opioids modulate immune processes. In this review, we will discuss the role of opioid receptors and their ligands in mediating immune-suppressive functions. We will summarize recent studies on direct and indirect opioid modulation of the cells of the immune system, as well as the role of opioids in exacerbation of certain disease states.
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