Prokineticin 2 Is a Target Gene of Proneural Basic Helix-Loop-Helix Factors for Olfactory Bulb Neurogenesis

Prokineticin 2, a cysteine-rich secreted protein, regulates diverse biological functions including the neurogenesis of olfactory bulb. Here we show that the PK2 gene is a functional target gene of proneural basic helix-loop-helix (bHLH) factors. Neurogenin 1 and MASH1 activate PK2 transcription by binding to E-box motifs on the PK2 promoter with the same set of E-boxes critical for another pair of bHLH factors, CLOCK and BMAL1, in the regulation of circadian clock. Our results establish PK2 as a common functional target gene for different bHLH transcriptional factors in mediating their respective functions

Retromer Is Essential for Autophagy-Dependent Plant Infection by the Rice Blast Fungus

We thank Dr. Yizhen Deng at the Temasek Life sciences Laboratory (TLL) for providing the RFP-MoAtg8 plasmid. We would like to thank Drs. Zhenbiao Yang (University of California, Riverside) and Xianying Dou (Fujian Agriculture and Forestry University) for helpful discussions.Author Summary The rice blast fungus Magnaporthe oryzae utilizes key infection structures, called appressoria, elaborated at the tips of the conidial germ tubes to gain entry into the host tissue. Development of the appressorium is accompanied with autophagy in the conidium leading to programmed cell death. This work highlights the significance of the Vps35/retromer membrane-trafficking machinery in the regulation of autophagy during appressorium-mediated host penetration, and thus sheds light on a novel molecular mechanism underlying autophagy-based membrane trafficking events during pathogen-host interaction in rice blast disease. Our findings provide the first genetic evidence that the retromer controls the initiation of autophagy in filamentous fungi.Yeshttp://www.plosgenetics.org/static/editorial#pee

Identification of state registers of FSM through full scan by data analytics

Finite-state machine (FSM) is widely used as control unit in most digital designs. Many intellectual property protection and obfuscation techniques leverage on the exponential number of possible states and state transitions of large FSM to secure a physical design with the reason that it is challenging to retrieve the FSM design from its downstream design or physical implementation without knowledge of the design. In this paper, we postulate that this assumption may not be sustainable with big data analytics. We demonstrate by applying a data mining technique to analyze sufficiently large amount of data collected from a full scan design to identify its FSM state registers. An impact metric is introduced to discriminate FSM state registers from other registers. A decision tree algorithm is constructed from the scan data for the regression analysis of the dependency of other registers on a chosen register to deduce its impact. The registers with the greater impact are more likely to be the FSM state registers. The proposed scheme is applied on several complex designs from OpenCores. The experiment results show the feasibility of our scheme in correctly identifying most FSM state registers with a high hit rate for a large majority of the designs.Ministry of Education (MOE)Accepted versionThis work was supported in part by the National Natural Science Foundation of China under Grant 61672182, the Guangdong Natural Science Foundation under Grant 2016A030313662, and in part by the Singapore Ministry of Education Tier 1 Grant MOE2018-T1-001-131 (RG87/18)

Identification of FSM state registers by analytics of scan-dump data

Big data analytics have gained tremendous successes in mining valuable information in various fields. However, its potential to solve complex problems in hardware security has not been adequately tapped. This paper presents a non-invasive approach to identify the state registers of a finite state machine (FSM) in an integrated chip. The state registers of the FSM are mined from the scan-dump data by exploiting the strongly connected property and chronologically correlated state codes of the FSM. The sequence of data scanned out of each scan register is partitioned into non-overlapping strings of high weighted frequencies by a string-matching algorithm. A coherency between a pair of registers is defined and computed based on the partitioned strings. The dimension of the coherency matrix is first reduced by pruning some registers of low influence by a regression analysis. The registers are then clustered to minimize the within-cluster variances based on their coherency values. The proposed scheme is applied to some IP cores from OpenCores. The experimental results show that our scheme can correctly identify the FSM state registers in most designs with high hit rate.Submitted/Accepted versionThis work was supported in part by the National Natural Science Foundation of China under Grant 62174045, in part by the Guangdong Basic and Applied Basic Research Foundation under Grant 2021A1515011862, and in part by the Shenzhen Fundamental Science Research Foundation under Project JCYJ20190806143203510 and Project GXWD20201230155427003-20200824112646001

Table_1_FgBud3, a Rho4-Interacting Guanine Nucleotide Exchange Factor, Is Involved in Polarity Growth, Cell Division and Pathogenicity of Fusarium graminearum.XLS

<p>Rho GTPases are signaling macromolecules that are associated with developmental progression and pathogenesis of Fusarium graminearum. Generally, enzymatic activities of Rho GTPases are regulated by Rho GTPase guanine nucleotide exchange factors (RhoGEFs). In this study, we identified a putative RhoGEF encoding gene (FgBUD3) in F. graminearum database and proceeded further by using a functional genetic approach to generate FgBUD3 targeted gene deletion mutant. Phenotypic analysis results showed that the deletion of FgBUD3 caused severe reduction in growth of FgBUD3 mutant generated during this study. We also observed that the deletion of FgBUD3 completely abolished sexual reproduction and triggered the production of abnormal asexual spores with nearly no septum in ΔFgbud3 strain. Further results obtained from infection assays conducted during this research revealed that the FgBUD3 defective mutant lost its pathogenicity on wheat and hence, suggests FgBud3 plays an essential role in the pathogenicity of F. graminearum. Additional, results derived from yeast two-hybrid assays revealed that FgBud3 strongly interacted with FgRho4 compared to the interaction with FgRho2, FgRho3, and FgCdc42. Moreover, we found that FgBud3 interacted with both GTP-bound and GDP-bound form of FgRho4. From these results, we subsequently concluded that, the Rho4-interacting GEF protein FgBud3 crucially promotes vegetative growth, asexual and sexual development, cell division and pathogenicity in F. graminearum.</p

Enhancement of Neural Salty Preference in Obesity

Background/Aims: Obesity and high salt intake are major risk factors for hypertension and cardiometabolic diseases. Obese individuals often consume more dietary salt. We aim to examine the neurophysiologic effects underlying obesity-related high salt intake. Methods: A multi-center, random-order, double-blind taste study, SATIETY-1, was conducted in the communities of four cities in China; and an interventional study was also performed in the local community of Chongqing, using brain positron emission tomography/computed tomography (PET/CT) scanning. Results: We showed that overweight/obese individuals were prone to consume a higher daily salt intake (2.0 g/day higher compared with normal weight individuals after multivariable adjustment, 95% CI, 1.2-2.8 g/day, P &#x3c; 0.001), furthermore they exhibited reduced salt sensitivity and a higher salt preference. The altered salty taste and salty preference in the overweight/obese individuals was related to increased activity in brain regions that included the orbitofrontal cortex (OFC, r = 0.44, P= 0.01), insula (r = 0.38, P= 0.03), and parahippocampus (r = 0.37, P= 0.04). Conclusion: Increased salt intake among overweight/obese individuals is associated with altered salt sensitivity and preference that related to the abnormal activity of gustatory cortex. This study provides insights for reducing salt intake by modifying neural processing of salty preference in obesity

Effects of resonant magnetic perturbations on neutral beam heating in a tokamak

Effects of resonant magnetic perturbations (RMPs) on tangential neutral beam heating in the EAST tokamak are studied numerically. RMPs with linear resistive magnetohydrodynamics response are used in the modeling. A variety of representing configurations of RMP coil currents are examined and their effects on the NBI heating efficiency are compared, in order to find a parameter window where deleterious effects of RMPs on NBI heating efficiency are minimized. It is found that the internal redistribution of fast ions by RMPs induces local accumulation of fast ions, resulting in higher local fast ion pressure than the case without RMPs. It is also found that the toroidal phasing of the RMP with respect to the fast ion source has slight effects on the steady-state radial profile of fast ions. The dependence of fast ion loss fraction on the RMP up-down phase difference shows similar behavior as the dependence of the radial width of chaotic magnetic field on the phase difference. A statistical method of identifying resonances between RMPs and lost fast ions is proposed and the results indicate that some resonances between RMPs and lost passing particles may be of non-integer fractional order, rather than the usual integer order

Sodium‐Glucose Cotransporter 2 Inhibitor Canagliflozin Antagonizes Salt‐Sensitive Hypertension Through Modifying Transient Receptor Potential Channels 3 Mediated Vascular Calcium Handling

Background Salt‐sensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that SGLT2 (sodium‐glucose cotransporter 2) inhibitors exert hypotensive effect and cardiorenal protective benefits in patients with hypertension with and without diabetes. However, the underlying mechanism remains elusive. Methods and Results Dahl salt‐sensitive rats and salt‐insensitive controls were fed with 8% high‐salt diet and some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, and vascular function were detected. Transient receptor potential channel 3 (TRPC3) knockout mice were used to explain the mechanism. Canagliflozin treatment significantly reduced high‐salt‐induced hypertension and this effect was not totally dependent on urinary sodium excretion in salt‐sensitive hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to high‐salt diet. High salt intake increased vascular expression of TRPC3 in salt‐sensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked salt‐induced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the antihypertensive effect of canagliflozin. Mechanistically, high‐salt‐induced activation of NCX1 (sodium‐calcium exchanger 1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin. Conclusions We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of high‐salt‐induced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize salt‐sensitive hypertension