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The amygdala, or an amygdala-like structure, is found in the brains of all vertebrates and plays a critical role in survival and reproduction. However, the cellular architecture of the amygdala and how it has evolved remain elusive. Here, we generated single-nucleus RNA-sequencing data for more than 200,000 cells in the amygdala of humans, macaques, mice, and chickens. Abundant neuronal cell types from different amygdala subnuclei were identified in all datasets. Cross-species analysis revealed that inhibitory neurons and inhibitory neuron-enriched subnuclei of the amygdala were well-conserved in cellular composition and marker gene expression, whereas excitatory neuron-enriched subnuclei were relatively divergent. Furthermore, LAMP5+ interneurons were much more abundant in primates, while DRD2+ inhibitory neurons and LAMP5+SATB2+ excitatory neurons were dominant in the human central amygdalar nucleus (CEA) and basolateral amygdalar complex (BLA), respectively. We also identified CEA-like neurons and their species-specific distribution patterns in chickens. This study highlights the extreme cell-type diversity in the amygdala and reveals the conservation and divergence of cell types and gene expression patterns across species that may contribute to species-specific adaptations.

The low-voltage activated T-type calcium channels regulate cellular excitability and oscillatory behavior of resting membrane potential which trigger many physiological events and have been implicated with many diseases. Here, we determine structures of the human T-type CaV3.3 channel, in the absence and presence of antihypertensive drug mibefradil, antispasmodic drug otilonium bromide and antipsychotic drug pimozide. CaV3.3 contains a long bended S6 helix from domain III, with a positive charged region protruding into the cytosol, which is critical for T-type CaV channel activation at low voltage. The drug-bound structures clearly illustrate how these structurally different compounds bind to the same central cavity inside the CaV3.3 channel, but are mediated by significantly distinct interactions between drugs and their surrounding residues. Phospholipid molecules penetrate into the central cavity in various extent to shape the binding pocket and play important roles in stabilizing the inhibitor. These structures elucidate mechanisms of channel gating, drug recognition, and actions, thus pointing the way to developing potent and subtype-specific drug for therapeutic treatments of related disorders.

Cenpj is a centrosomal protein located at the centrosomes and the base of cilia, it plays essential roles in regulating neurogenesis and cerebral cortex development. Although centrosomal and cilium dysfunction are one of the causes of obesity, insulin resistance, and type 2 diabetes, the role that Cenpj plays in the regulation of body weight remains unclear. Here, we deleted Cenpj by crossing Cenpjflox/flox mice with Nkx2.1-Cre mice. Loss of the centrosomal protein Cenpj in Nkx2.1-expressing cells causes morbid obesity in mice at approximately 4 months of age with expended brain ventricles but no change of brain size. We found that hypothalamic cells exhibited reduced proliferation and increased apoptosis upon Cenpj depletion at the embryonic stages, resulting in a dramatic decrease in the number of Proopiomelanocortin (POMC) neurons and electrophysiological dysfunction of NPY neurons in the arcuate nucleus (ARC) in adults. Furthermore, depletion of Cenpj also reduced the neuronal projection from the ARC to the paraventricular nucleus (PVN), with decreased melanocortin-4 receptors (MC4R) expression in PVN neurons. The study defines the roles that Cenpj plays in regulating hypothalamus development and body weight, providing a foundation for further understanding of the pathological mechanisms of related diseases.

Mounting evidence suggests that function and connectivity of the striatum is disrupted in schizophrenia1–5. We have developed a new hypothesis-driven neuroimaging biomarker for schizophrenia identification, prognosis and subtyping based on functional striatal abnormalities (FSA). FSA scores provide a personalized index of striatal dysfunction, ranging from normal to highly pathological. Using inter-site cross-validation on functional magnetic resonance images acquired from seven independent scanners (n = 1,100), FSA distinguished individuals with schizophrenia from healthy controls with an accuracy exceeding 80% (sensitivity, 79.3%; specificity, 81.5%). In two longitudinal cohorts, inter-individual variation in baseline FSA scores was significantly associated with antipsychotic treatment response. FSA revealed a spectrum of severity in striatal dysfunction across neuropsychiatric disorders, where dysfunction was most severe in schizophrenia, milder in bipolar disorder, and indistinguishable from healthy individuals in depression, obsessive-compulsive disorder and attention-deficit hyperactivity disorder. Loci of striatal hyperactivity recapitulated the spatial distribution of dopaminergic function and the expression profiles of polygenic risk for schizophrenia. In conclusion, we have developed a new biomarker to index striatal dysfunction and established its utility in predicting antipsychotic treatment response, clinical stratification and elucidating striatal dysfunction in neuropsychiatric disorders. A new cross-validated neuroimaging biomarker that reflects striatal dysfunctioning can be used to distinguish patients with schizophrenia from healthy controls, and is associated with treatment response to antipsychotics.

Quasi-Monte Carlo (QMC) method is a useful numerical tool for pricing and hedging of complex financial derivatives. These problems are usually of high dimensionality and discontinuities. The two factors may significantly deteriorate the performance of the QMC method. This paper develops an integrated method that overcomes the challenges of the high dimensionality and discontinuities concurrently. For this purpose, a smoothing method is proposed to remove the discontinuities for some typical functions arising from financial engineering. To make the smoothing method applicable for more general functions, a new path generation method is designed for simulating the paths of the underlying assets such that the resulting function has the required form. The new path generation method has an additional power to reduce the effective dimension of the target function. Our proposed method caters for a large variety of model specifications, including the Black-Scholes, exponential normal inverse Gaussian L\'evy, and Heston models. Numerical experiments dealing with these models show that in the QMC setting the proposed smoothing method in combination with the new path generation method can lead to a dramatic variance reduction for pricing exotic options with discontinuous payoffs and for calculating options' Greeks. The investigation on the effective dimension and the related characteristics explains the significant enhancement of the combined procedure.

The cellular complexity of human brain development has been intensively investigated, although a regional characterization of the entire human cerebral cortex based on single-cell transcriptome analysis has not been reported. Here, we performed RNA-seq on over 4,000 individual cells from 22 brain regions of human mid-gestation embryos. We identified 29 cell sub-clusters, which showed different proportions in each region and the pons showed especially high percentage of astrocytes. Embryonic neurons were not as diverse as adult neurons, although they possessed important features of their destinies in adults. Neuron development was unsynchronized in the cerebral cortex, as dorsal regions appeared to be more mature than ventral regions at this stage. Region-specific genes were comprehensively identified in each neuronal sub-cluster, and a large proportion of these genes were neural disease related. Our results present a systematic landscape of the regionalized gene expression and neuron maturation of the human cerebral cortex.

Many problems in derivative pricing can be formulated as high-dimensional integrals. Many of them do not have closed-form solutions and have to be estimated by numerical integrations such as Monte Carlo or quasi-Monte Carlo (QMC) methods. Since the quasi-random points used for QMC simulation have perfect projections at the first few dimensions, reducing the effective dimension of the integrands can improve the efficiency of QMC. In this paper, based on the first-order Taylor approximations of the functions at Gaussian sample points, we propose a new general method based on principal component analysis (PCA) to reduce the effective dimensions of the functions. Rather than aiming at decomposing the covariance matrix of the Brownian motions as in the traditional PCA, the new method implements PCA on the gradients of the functions at sample points and then an orthogonal transformation is found to reduce the effective dimensions. Numerical experiments show that by using the new dimension reduction method, a significant efficient improvement of QMC can be achieved on pricing exotic options and mortgage-backed securities.

Endothelial cell apoptosis induced by oxidative stress is an early event in the development of atherosclerosis. Several antioxidant enzymes which can cope with oxidative stress are up-regulated by the anti-atherogenic laminar blood flow often seen in straight or unbranched regions of blood vessels. However, the molecular mechanism responsible for flow-induced beneficial effects is incompletely understood. Here we report the role of glutaredoxin 1 (Grx1), an antioxidant enzyme, in flow-mediated protective effect in endothelial cells. Specifically, we found that Grx1 is markedly up-regulated by the steady laminar flow. Increasing Grx1 reduces the pro-apoptotic protein Bim expression through regulating Akt-FoxO1 signaling and also attenuates H2O2-induced Bim activation via inhibiting JNK phosphorylation, subsequently preventing the apoptosis of endothelial cells. Grx1 knockdown abolishes the inhibitory effect of steady laminar flow on Bim. The inhibitory effect of Grx1 on Bim is dependent on Grx1′s thioltransferase activity. These findings indicate that Grx1 induction plays a key role in mediating the protective effect of laminar blood flow and suggest that Grx1 may be a potential therapeutic target for atherosclerosis.

Super P carbon black (SPCB) has been widely used as a conducting additive in Li/Na ion batteries to improve the electronic conductivity. However, there has not yet been a comprehensive study on its structure and electrochemical properties for Li/Na ion uptake, though it is important to characterize its contribution in any study of active materials that uses this additive in non-negligible amounts. In this article the structure of SPCB has been characterized and a comprehensive study on the electrochemical Li/Na ion uptake capability and reaction mechanisms are reported. SPCB exhibits a considerable lithiation capacity (up to 310 mAh g–1) from the Li ion intercalation in the graphite structure. Sodiation in SPCB undergoes two stages: Na ion intercalation into the layers between the graphene sheets and the Na plating in the pores between the nano-graphitic domains, and a sodiation capacity up to 145 mAh g–1 has been achieved. Moreover, the influence of the type and content of binders on the lithiation and sodiation properties has been investigated. The cycling stability is much enhanced with sodium carboxymethyl cellulose (NaCMC) binder in the electrode and fluoroethylene carbonate (FEC) in the electrolyte; and a higher content of binder improves the Coulombic efficiency during dis-/charge.

Montmorillonite supported titanium (Ti-MMT) or antimony catalyst (Sb-MMT) has been a hot area of research on preparing polyethylene terephthalate/montmorillonite (PET/MMT) nanocomposites by in situ polymerization. So removal of Ti or Sb from Ti-MMT or Sb-MMT is not expected during in situ polymerization. Studies on immobilization of Ti or Sb on Ti-MMT or Sb-MMT are seldom reported. In this work, a series of montmorillonite supported catalysts of titanium (Ti-MMT) or antimony (Sb-MMT) and cointercalated montmorillonite of titanium and antimony (Ti/Sb-MMT) were prepared by (1) the reaction of sodium bentonite suspension with intercalating solution containing titanium tetrachloride and/or antimony chloride, and (2) drying or calcinating the products at different temperature (100, 150, 240, 350 and 450 °C). The physicochemical properties of these MMT supported catalysts were studied by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), inductively coupled plasma optical emission spectrometer (ICPOES), N2 adsorption/desorption isotherms, UV-visible diffuse reflectance spectroscopy(UV-vis) and transmission electron microscopy (TEM). The immobile character of Ti or Sb on MMT supported catalysts was evaluated by a two-step method in deionized water or ethylene glycol. Several results were obtained, i e, (a) during the preparation, with an increase in drying or calcinating temperature, the amount of titanium and/or antimony species remained on these MMT supported catalysts decreased, (b) the experiments about immobile character of Ti or/and Sb showed that with an increase in drying or calcinating temperature, the immobilization of Ti and/or Sb species remained on these MMT supported catalysts increased gradually, (c) Ti-MMT calcinated at 450 °C had the biggest pore volume, which means Ti-MMT had the best adsorption application prospect.

Both of quaternary ammonium and quaternary phosphonium salts of bis-hydroxyethyl terephthalate (BHET) were successfully synthesized and characterized by fourier transform infrared spectroscopy (FT-IR). These two kinds of salts were used to intercalate Na-MMT to yield two kinds of respective organo-modified MMTs. Basal spacing and thermal stability were investigated by using X-ray diffraction (XRD) and thermogravimetric analysis (TGA), respectively. The experimental results show that, as compared with Na-MMT, basal spacings of both of MMTs modified by the quaternary phosphonium salt of BHET (BHETPP) and the quaternary ammonium salt of BHET (BHEA), increase from 12.4 A to 19.7 A and 31.3 A, respec-tively. Thermal stability of BHETPP-modified MMT is much better than that of BHEA-modified MMT, i e, T onset of BHETPP-modified MMT is around 400 °C while T onset of BHEA-modified MMT is near 250 °C. Therefore, with en-larged basal spacing and excellent thermal stability, BHETPP-modified MMT is a promising organo-modified MMT which may be used to prepare polyethylene terephthalate/MMT nanocomposite with high thermal and mechanical performance.

Continuous variable measurement-device-independent quantum key distribution (CV MDI-QKD) where legitimate communication parties, Alice and Bob, do not connect to each other directly but to an untrusted relay where the detection is performed can defend attacks that aim at measurement devices. It was recently shown that the preparation noise, although being trusted, was breaking the security of CV QKD. Hence, we study the security of continuous variable measurement-device-independent quantum key distribution based on noisy modulation of coherent states and investigate how the preparation noise influences the maximum transmission distance of the system. We propose a scheme of using a variable attenuator to attenuate decoder’s (Bob’s) mode to purify the coherent states he sends out under two-mode coherent attack. The simulation results show that when taking preparation noise into consideration the maximum transmission distance decreases seriously and our scheme can effectively compensate the detrimental effect of the preparation noise and improve the maximum transmission distance.

Few studies have explored the change in thermal stability of poly(oxypropylene) (POP) ammonium ions after intercalation, even though several studies have focused on the modification of montmorillonite (Mt) with POP amine hydrochloride. The purpose of the present study was to understand the effect of chain length of POP amine hydrochlorides on the basal spacing of modified Mt, and the amount and thermal stability of the ammonium ions intercalated. The relations between basal spacing, organic fraction, and thermal stability of the ammonium ions intercalated were also explored. Series of modified Mt were prepared via ion-exchange between Na-montmorillonite (Na + -Mt) and POP diammonium ions or POP triammonium ions with different chain lengths, and were then characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, and simultaneous differential scanning calorimetry-thermogravimetric analysis. The results revealed that the basal spacing of modified Mt increased with the hydrophobic chain length of the POP ammonium ions. The amount of triammonium ions intercalated was close to the theoretical amount, while the organic fraction of modified Mt was directly proportional to the basal spacing of modified Mt. The intercalated ammonium ions were, therefore, contained within the interlayer space of Mt. After intercalation, the thermal stability of the POP ammonium ions with various chain lengths was reduced; i.e. T onset was reduced by 7–60oC for short-chain POP ammonium ions (D400 and T403) and by 177–192oC for long-chain ions (D2000, D4000, T3000, and T5000).

Thermoelectric coolers (TECs) were used to cool a low-temperature chemical reactor (LTR). A combined theoretical/experimental study of the heat transfer in LTR with TECs was undertaken. First, two models of a TEC with a LTR junction were developed to evaluate the equilibrium and transient temperatures of the reactor inner wall. Next, two methods were used to determine the parameters of these models. Finally, the relationship between the transient temperatures of the reactor inner wall and cooling times was established. The results show that the calculated results of transient temperatures are in good agreement with the corresponding experimental data.

Asymmetric divisions of radial glia progenitors produce self-renewing radial glia and differentiating cells simultaneously in the ventricular zone (VZ) of the developing neocortex. Whereas differentiating cells leave the VZ to constitute the future neocortex, renewing radial glia progenitors stay in the VZ for subsequent divisions. The differential behaviour of progenitors and their differentiating progeny is essential for neocortical development; however, the mechanisms that ensure these behavioural differences are unclear. Here we show that asymmetric centrosome inheritance regulates the differential behaviour of renewing progenitors and their differentiating progeny in the embryonic mouse neocortex. Centrosome duplication in dividing radial glia progenitors generates a pair of centrosomes with differently aged mother centrioles. During peak phases of neurogenesis, the centrosome retaining the old mother centriole stays in the VZ and is preferentially inherited by radial glia progenitors, whereas the centrosome containing the new mother centriole mostly leaves the VZ and is largely associated with differentiating cells. Removal of ninein, a mature centriole-specific protein, disrupts the asymmetric segregation and inheritance of the centrosome and causes premature depletion of progenitors from the VZ. These results indicate that preferential inheritance of the centrosome with the mature older mother centriole is required for maintaining radial glia progenitors in the developing mammalian neocortex.

We study the problem of multivariate integration and the construction of good lattice rules in weighted Korobov spaces with general weights. These spaces are not necessarily tensor products of spaces of univariate functions. Sufficient conditions for tractability and strong tractability of multivariate integration in such weighted function spaces are found. These conditions are also necessary if the weights are such that the reproducing kernel of the weighted Korobov space is pointwise non-negative. The existence of a lattice rule which achieves the nearly optimal convergence order is proven. A component-by-component (CBC) algorithm that constructs good lattice rules is presented. The resulting lattice rules achieve tractability or strong tractability error bounds and achieve nearly optimal convergence order for suitably decaying weights. We also study special weights such as finite-order and order-dependent weights. For these special weights, the cost of the CBC algorithm is polynomial. Numerical computations show that the lattice rules constructed by the CBC algorithm give much smaller worst-case errors than the mean worst-case errors over all quasi-Monte Carlo rules or over all lattice rules, and generally smaller worst-case errors than the best Korobov lattice rules in dimensions up to hundreds. Numerical results are provided to illustrate the efficiency of CBC lattice rules and Korobov lattice rules (with suitably chosen weights), in particular for high-dimensional finance problems.

Tillering in rice (Oryza sativa L.) is an important agronomic trait for grain production, and also a model system for the study of branching in monocotyledonous plants. Rice tiller is a specialized grain-bearing branch that is formed on the unelongated basal internode and grows independently of the mother stem (culm) by means of its own adventitious roots. Rice tillering occurs in a two-stage process: the formation of an axillary bud at each leaf axil and its subsequent outgrowth. Although the morphology and histology and some mutants of rice tillering have been well described, the molecular mechanism of rice tillering remains to be elucidated. Here we report the isolation and characterization of MONOCULM 1 (MOC1), a gene that is important in the control of rice tillering. The moc1 mutant plants have only a main culm without any tillers owing to a defect in the formation of tiller buds. MOC1 encodes a putative GRAS family nuclear protein that is expressed mainly in the axillary buds and functions to initiate axillary buds and to promote their outgrowth.