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Accumulating evidence shows that most chronic neurological diseases have a link with sleep disturbances, and that patients with chronically poor sleep undergo an accelerated cognitive decline. Indeed, a single-night of sleep deprivation may increase metabolic waste levels in cerebrospinal fluid. However, it remains unknown how chronic sleep disturbances in isolation from an underlying neurological disease may affect the glymphatic system. Clearance of brain interstitial waste by the glymphatic system occurs primarily during sleep, driven by multiple oscillators including arterial pulsatility, and vasomotion. Herein, we induced sleep fragmentation in young wildtype mice and assessed the effects on glymphatic activity and cognitive functions. Chronic sleep fragmentation reduced glymphatic function and impaired cognitive functions in healthy mice. A mechanistic analysis showed that the chronic sleep fragmentation suppressed slow vasomotion, without altering cardiac-driven pulsations. Taken together, results of this study document that chronic sleep fragmentation suppresses brain metabolite clearance and impairs cognition, even in the absence of disease. [ABSTRACT FROM AUTHOR]

The cell nucleus is the main site for the storage and replication of genetic material, and the synthesis of substances in the nucleus is rhythmic, regular and strictly regulated by physiological processes. However, whether exogenous substances, such as nanoparticles, can be synthesized in situ in the nucleus of live cells has not been reported. Here, we have achieved in-situ synthesis of CdS x Se1−x quantum dots (QDs) in the nucleus by regulation of the glutathione (GSH) metabolic pathway. High enrichment of GSH in the nucleus can be accomplished by the addition of GSH with the help of the Bcl-2 protein. Then, high-valence Se is reduced to low-valence Se by glutathione-reductase-catalyzed GSH, and interacts with the Cd precursor formed through Cd and thiol-rich proteins, eventually generating QDs in the nucleus. Our work contributes to a new understanding of the syntheses of substances in the cell nucleus and will pave the way for the development of advanced 'supercells'. [ABSTRACT FROM AUTHOR]

The western Hunan–eastern Guizhou Zn‐Pb metallogenic belt is one of the important Zn‐Pb mineralization regions in China. The Dadongla deposit, located in the northeast of Guizhou Province, is one of the typical Zn‐Pb deposits in the region and has estimated resources more than 12 million metric tons (Mt) with an average grade of 4.11 wt% Zn+Pb. Its orebodies are hosted in the lower Cambrian Aoxi Formation dolomite, occurring as bedded, para‐bedded in shape, and in conformity with the wall rock. The ore mineral assemblage is simple, dominated by sphalerite with minor pyrite and galena, and the gangue minerals are composed of dolomite, calcite with minor bitumen and barite. In view of the lack of geological and geochemical researches, the genesis of Zn‐Pb ore is still unclear. Laser ablation‐inductively coupled plasma mass spectrometry (LA‐ICPMS) spot and mapping analyses were used to obtain sphalerite trace element chemistry in the Dadongla Zn‐Pb deposit in Guizhou, China, aiming to constrain its ore genesis. The results show that sphalerite is characterized by the enrichment of Cd, Fe, Ge and Hg, corresponding with that of typical MVT deposits. Four zones were identified in the sphalerite crystal from Dadongla from the center to margin according to the color bands, in which the zone in the center, representing the early ore‐stage sphalerite, is characterized by enrichment of Cd relatively, while the zone forming at late ore‐stage is enriched in Ge and Hg relatively. The finding was controlled by differential leached metals content in ore‐forming fluid from its source rock. Notably, critical element Ge trends to be enriched at the late ore‐stage and follows a substitution of 2Zn2+↔ Ge4++□ (vacancy). Moreover, the calculated ore‐forming temperature ranges from 79.9°C to 177.6°C by the empirical formula, which is similar to that of typical Mississippi Valley‐type (MVT) deposits. Compared with the features of trace elements in sphalerite from different types of deposits, together with the geology, the Dadongla deposit belongs to an MVT Zn‐Pb deposit. [ABSTRACT FROM AUTHOR]

The Sichuan–Yunnan–Guizhou (SYG) Pb–Zn metallogenic province is one of the most productive areas of Pb–Zn resources in China. The Fule deposit occurs in Permian carbonate and contains Pb–Zn reserves exceeding 1 Mt. To investigate the sulphur source, in situ S isotopic analysis of sphalerite and pyrite was carried out using nanoscale secondary-ion mass spectrometry. The results show that the δ34S values of the sulphide minerals range from +16.1‰ to +23.0‰, higher than that of marine sulphates hosted in Permian carbonate rocks (+11‰), but similar to that of sulphates over a broader area (+12.9‰ to +25.9‰). The sulphates in the regional rocks could therefore represent an important source of S for the Fule deposit via thermochemical sulphate reduction. The S source of the Fule deposit is different from those of most other Pb–Zn deposits in the SYG Pb–Zn mineralization province, which were mainly derived from the ore-bearing strata. The δ34S values of the early to late generations and some single sulphide crystals from the cores to rims show a slight increasing trend, implying that partial Rayleigh fractionation took place in the Fule deposit. It is suggested that the Fule sulphide precipitation resulted from the mixing of a metalliferous fluid with a H2S-rich fluid derived from the regional strata. Combining the geology, mineralogy and S isotope results with previous Pb isotope studies, it is suggested that the Fule deposit should be attributed to a Mississippi Valley type deposit. [ABSTRACT FROM AUTHOR]

The Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province (SYGMP) is an important region for Pb-Zn resources in China. However, considerable controversy remains as to whether the Pb-Zn deposits are Mississippi Valley Type (MVT). The Maozu deposit, a typical example of the carbonate-hosted Pb-Zn deposits in the SYGMP, occurs in the late Ediacaran Dengying Formation and its ore bodies are divided into three types: lower layer (LL), vein layer (VL), and upper layer (UL) ore bodies based on their spatial relationship. In this study, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used to systematically analyze the trace-element compositions of sphalerite and galena in these three ore bodies. The results show that sphalerite is characterized by Cd and Ge enrichment; Fe, Mn, and Co depletion; and local In and Sn enrichment. Most of these elements likely appear as solid solutions in sphalerite and show a wide compositional variation, which is probably related to the medium- and low-temperature mixing of the ore-forming fluids. The local enrichment of In and Sn is likely attributed to the long-distance migration of ore-forming fluids through In-Sn-bearing volcaniclastic rocks. In vs. Sn and (Cu + Sb) vs. (Ag + Ge) show strong correlations and similar element distribution in the mapped images, indicating that these elements may be incorporated into sphalerite via a coupled substitution for Zn as 2In3+ + Sn4+ + 2 5Zn2+ (= vacancies) and 4(Cu+ + Sb3+) + (Ge4+ + 2Ag+) + 2 13Zn2+. Galena is enriched in Ag and Sb with minor Cd and Se and depleted in Bi, and most of the elements may occur as solid solutions. Ag vs. Sb in galena displays a strong positive correlation, implying the coupled substitution of Ag+ + Sb3+ 2Pb2+. Notably, the majority of the trace-element concentrations gradually decrease in the order LL UL except Fe, Co, Cu, and Ge, while Fe, In, and Sn in sphalerite and Ag and Sb in galena have the highest concentration in the VL, indicating that the VL is a secondary migration channel for the ore-forming fluids. Furthermore, the trace-element compositions of the sulfides in the Maozu Pb-Zn deposit are consistent with the typical MVT deposit (hosted in the carbonate sequence) but are markedly different from sedimentary exhalative (SEDEX), volcanogenic massive sulfide (VMS) and skarn-type deposits. Based on these results, as well as the geological and geochemical characteristics of the deposit, the Maozu Pb-Zn deposit is an MVT deposit. [ABSTRACT FROM AUTHOR]

The Laochang Ag-Pb-Zn-Cu deposit, located in the southern margin of the Sanjiang Tethys Metallogenic Belt (STMB), is the typical Ag-Pb-Zn-Cu deposit in this region. Its orebodies are hosted in the Carboniferous Yiliu Formation volcanic-sedimentary cycle and occur as stratiform, stratoid and lenticular. Whether or not the stratabound ore belong to the volcanogenic massive sulfide (VMS) deposit remains unclear and controversial. In this paper, the whole rock geochemistry, trace elements in sphalerite, U-Pb zircon chronology and Pb isotopes were investigated, aiming to provide significant insights into the genesis and geodynamic setting of the Laochang deposit. Lead isotope ratios of pyrite and sphalerite from the stratabound ore are 18.341 to 18.915 for 206Pb/204Pb; 15.376 to 15.770 for 207Pb/204Pb; and 38.159 to 39.200 for 208Pb/204Pb—which display a steep linear trend on Pb-Pb diagrams. This indicates a binary mixing of lead components derived from leaching between the host volcanic rock and mantle reservoir. Sphalerite from stratabound ores is relatively enriched in Fe, Mn, In, Sn, and Ga—similar to typical VMS deposits. Moreover, the Carboniferous volcanic rock hosting the stratabound Ag-Pb-Zn-Cu ores has a zircon U-Pb age of 312 ± 4 Ma; together with previous geochronological and geological evidences, thus, we consider that the stratabound mineralization occur in the Late Paleozoic (~323–308 Ma). Collectively, these geologic, geochemical, and isotopic data confirm that the stratabound ores should be assigned to Carboniferous VMS mineralization. In addition, volcanic rocks hosting the stratabound ore exhibit elevated high field strength elements (HFSEs, Nb, Ta, Zr and Hf) abundance, slight enrichment of light rare earth element (LREE), and depletion of Ba and Sr with obvious Nb-Ta anomalies. Such characteristics suggest that their magma is similar to typical oceanic island basalt. In addition, the oceanic island basalt (OIB)-like volcanic rocks were formed at Late Paleozoic, which could be approximately synchronous with the VMS mineralization at Laochang. Thus, it is suggested that the Laochang VMS mineralization was generated in the oceanic island setting prior to the initial subduction of the Changning-Menglian Paleo-Tethys Ocean. [ABSTRACT FROM AUTHOR]

The Nayongzhi Zn-Pb deposit, located in the southeastern margin of the Sichuan-Yunnan-Guizhou (S-Y-G) Zn-Pb metallogenic province, China, has been recently discovered in this region and has an estimated resource of 1.52 Mt of metal at average grades of 4.82 wt % Zn and 0.57 wt % Pb. The ore bodies are hosted in the Lower Cambrian Qingxudong Formation dolostone and occur as stratiform, stratoid and steeply dipping veins. The predominant minerals are sphalerite, galena, dolomite, calcite with minor pyrite, and barite. In this paper, the inductively coupled plasma mass spectrometry (ICP-MS) technique has been used to investigate the concentrations of Fe, Cd, Ge, Ga, Cu, Pb, Ag, In, Sn, Sb, Co and Mn in bulk grain sphalerite from the Nayongzhi deposit, in an effort to provide significant insights into the element substitution mechanisms, ore-forming temperature and genesis of the deposit. This study shows that those trace elements (i.e., Cd, In, Sn, Sb, Fe, Mn, Cu, Ga, Ge, Ag, and Co) are present in the form of isomorphism in sphalerite, and strong binary correlation among some elements suggests direct substitution as Zn2+↔Fe2+ and coupled substitutions as Zn2+↔Ga3+ + (Cu, Ag)+ and Zn2+↔In3+ + Sn3+ + □ (vacancy), despite there being no clear evidence for the presence of Sn3+. Sphalerite from the Nayongzhi deposit is enriched in Cd, Ge and Ga and depleted in Fe, Mn, In and Co, which is similar to that of the Mississippi Valley-type (MVT) deposit and significantly different from that of the Volcanogenic Massive Sulfide (VMS) deposit, Sedimentary-exhalative (Sedex) deposit, skarn, and epithermal hydrothermal deposit. Moreover, the ore-forming temperature is relatively low, ranging from 100.5 to 164.4 °C, as calculated by the GGIMFis geothermometer. Geological characteristics, mineralogy and trace element contents of sphalerite suggest that the Nayongzhi deposit is a MVT deposit. In addition, according to the geological characteristics, Ag content in sphalerite, and Pb isotope evidence, the Nayongzhi deposit is distinct from the deposits associated with the Indosinian Orogeny in S-Y-G Zn-Pb metallogenic province (e.g., Huize, Daliangzi, Tianbaoshan and Tianqiao deposits), thus, suggesting that multi-stage Zn-Pb mineralization may have occurred in this region. [ABSTRACT FROM AUTHOR]

Summary Activation of class I phosphatidylinositol 3-kinase (PI3K) leads to formation of phosphatidylinositol-3,4,5-trisphophate (PIP 3) and phosphatidylinositol-3,4-bisphophate (PI34P 2), which spatiotemporally coordinate and regulate a myriad of cellular processes. By simultaneous quantitative imaging of PIP 3 and PI34P 2 in live cells, we here show that they have a distinctively different spatiotemporal distribution and history in response to growth factor stimulation, which allows them to selectively induce the membrane recruitment and activation of Akt isoforms. PI34P 2 selectively activates Akt2 at both the plasma membrane and early endosomes, whereas PIP 3 selectively stimulates Akt1 and Akt3 exclusively at the plasma membrane. These spatiotemporally distinct activation patterns of Akt isoforms provide a mechanism for their differential regulation of downstream signaling molecules. Collectively, our studies show that different spatiotemporal dynamics of PIP 3 and PI34P 2 and their ability to selectively activate key signaling proteins allow them to mediate class I PI3K signaling pathways in a spatiotemporally specific manner. Graphical Abstract Highlights • PIP 3 and PI34P 2 after PI3K activation are quantitatively determined in live cells • PIP 3 and PI34P 2 have distinctively different spatiotemporal history and dynamics • PIP 3 and PI34P 2 induce site- and isoform-specific activation of Akt proteins PI3K signaling is mediated by two lipids, PIP 3 and PI34P 2. By means of quantitative lipid imaging, we determined the spatiotemporal dynamics of PIP 3 and PI34P 2 in live cells and elucidated how they specifically control the cellular activities of different Akt isoforms and their downstream signaling proteins. [ABSTRACT FROM AUTHOR]

Astrocytes, the multi-functional glial cells with the most abundant population in the brain, integrate information across their territories to regulate neuronal synaptic and cerebrovascular activities. Astrocytic calcium (Ca 2+ ) signaling is the major readout of cellular functional state of astrocytes. The conventional two-photon in vivo imaging usually focuses on a single horizontal focal plane to capture the astrocytic Ca 2+ signals, which leaves >80% spatial information undetected. To fully probe the Ca 2+ activity across the whole astrocytic territory, we developed a pipeline for imaging and visualizing volumetric astrocytic Ca 2+ time-lapse images. With the pipeline, we discovered a new signal distribution pattern from three-dimensional (3D) astrocytic Ca 2+ imaging data of mice under isoflurane anesthetic states. The tools developed in this study enable a better understanding of the spatiotemporal patterns of astrocytic activity in 3D space.

Membrane-protein interaction plays key roles in a wide variety of biological processes. To facilitate rapid and sensitive measurement of membrane binding of soluble proteins, we developed a fluorescence-based quantitative assay that is universally applicable to all proteins. This fluorescence-quenching assay employs fluorescence protein (FP)-tagged proteins whose fluorescence intensity is greatly decreased when they bind vesicles containing synthetic lipid dark quenchers, such as N-dimethylaminoazobenzenesulfonylphosphatidylethanolamine (dabsyl-PE). This simple assay can be performed with either a spectrofluorometer or a plate reader and optimized for different proteins with various combinations of FPs and quenching lipids. The assay allows rapid, sensitive, and accurate determination of lipid specificity and affinity for various lipid binding domains and proteins, and also high-throughput screening of small molecules that modulate membrane binding of proteins.