Nunchaku: optimally partitioning data into piece-wise contiguous segments.

MOTIVATION: When analyzing 1D time series, scientists are often interested in identifying regions where one variable depends linearly on the other. Typically, they use an ad hoc and therefore often subjective method to do so. RESULTS: Here, we develop a statistically rigorous, Bayesian approach to infer the optimal partitioning of a dataset not only into contiguous piece-wise linear segments, but also into contiguous segments described by linear combinations of arbitrary basis functions. We therefore present a general solution to the problem of identifying discontinuous change points. Focusing on microbial growth, we use the algorithm to find the range of optical density where this density is linearly proportional to the number of cells and to automatically find the regions of exponential growth for both Escherichia coli and Saccharomyces cerevisiae. For budding yeast, we consequently are able to infer the Monod constant for growth on fructose. Our algorithm lends itself to automation and high throughput studies, increases reproducibility, and should facilitate data analyses for a broad range of scientists. AVAILABILITY AND IMPLEMENTATION: The corresponding Python package, entitled Nunchaku, is available at PyPI: https://pypi.org/project/nunchaku.

A robust method for simultaneous determination of eight B vitamins in human serum by liquid chromatography tandem mass spectrometry.

The level of vitamin B group in human serum is an important index of human health. Among B vitamins, cyanocobalamin in serum is unstable and its content is extremely low. Rapid and simultaneous detection of multiple B vitamins including cyanocobalamin is a challenge. Herein, we have developed a rapid and stable method that can realize the determination of thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin simultaneously in 6 min. The method was established based on protein precipitation with methanol and then chromatographic separation was achieved using Waters acquity ultra-high-performance liquid chromatography high strength silica T3 column, which was stable and sensitive especially for cyanocobalamin. Limit of quantification, precision, trueness, and matrix effect were validated according to the European Medicines Agency and United States Food and Drug guidelines and Clinical and Laboratory Standards Institute guidelines on bioanalytical method. The limit of quantification for thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin was 0.4, 0.4, 0.8, 2.0, 0.4, 0.1, 0.4, and 0.04 ng/mL separately, respectively. Intra- and interday precisions were 1.1%-12.4% and 2.0%-13.5%, respectively. The relative errors were between 0.3% and 13.3%, and the matrix effects were between 2.6% and 10.4%.

Efficient Suppression of Dendrites and Side Reactions by Strong Electrostatic Shielding Effect via the Additive of Rb2 SO4 for Anodes in Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) have attracted considerable attention due to their low cost and environmental friendliness. However, the rampant dendrite growth and severe side reactions during plating/stripping on the surface of zinc (Zn) anode hinder the practicability of AZIBs. Herein, an effective and non-toxic cationic electrolyte additive of Rb2 SO4 is proposed to address the issues. The large cation of Rb+ is preferentially adsorbed on the surface of Zn metal to induce a strong shielding effect for realizing the lateral deposition of Zn2+ ions along the Zn surface and isolating water from Zn metal to effectively inhibit side reactions. Consequently, the Zn||Zn symmetric cell with the addition of 1.5 mm Rb2 SO4 can cycle more than 6000 h at 0.5 mA cm-2 /0.25 mAh cm-2 , which is 20 times longer than that without Rb2 SO4 . Besides, the Zn||Cu asymmetric cell with Rb2 SO4 achieves a very high average Coulombic efficiency of 99.16% up to 500 cycles. Moreover, the electrolyte with Rb2 SO4 well matches with the VO2 cathode, achieving high initial capacity of 412.7 mAh g-1 at 5 A g-1 and excellent cycling stability with a capacity retention of 71.6% at 5 A g-1 after 500 cycles for the Zn//VO2 full cell.

Homologous Heterostructured NiS/NiS2 @C Hollow Ultrathin Microspheres with Interfacial Electron Redistribution for High-Performance Sodium Storage.

Nickel sulfides with high theoretical capacity are considered as promising anode materials for sodium-ion batteries (SIBs); however, their intrinsic poor electric conductivity, large volume change during charging/discharging, and easy sulfur dissolution result in inferior electrochemical performance for sodium storage. Herein, a hierarchical hollow microsphere is assembled from heterostructured NiS/NiS2 nanoparticles confined by in situ carbon layer (H-NiS/NiS2 @C) via regulating the sulfidation temperature of the precursor Ni-MOFs. The morphology of ultrathin hollow spherical shells and confinement of in situ carbon layer to active materials provide rich channels for ion/electron transfer and alleviate the effects of volume change and agglomeration of the material. Consequently, the as-prepared H-NiS/NiS2 @C exhibit superb electrochemical properties, satisfactory initial specific capacity of 953.0 mA h g-1 at 0.1 A g-1 , excellent rate capability of 509.9 mA h g-1 at 2 A g-1 , and superior longtime cycling life with 433.4 mA h g-1 after 4500 cycles at 10 A g-1 . Density functional theory calculation shows that heterogenous interfaces with electron redistribution lead to charge transfer from NiS to NiS2 , and thus favor interfacial electron transport and reduce ion-diffusion barrier. This work provides an innovative idea for the synthesis of homologous heterostructures for high-efficiency SIB electrode materials.

Analysing and meta-analysing time-series data of microbial growth and gene expression from plate readers.

Responding to change is a fundamental property of life, making time-series data invaluable in biology. For microbes, plate readers are a popular, convenient means to measure growth and also gene expression using fluorescent reporters. Nevertheless, the difficulties of analysing the resulting data can be a bottleneck, particularly when combining measurements from different wells and plates. Here we present omniplate, a Python module that corrects and normalises plate-reader data, estimates growth rates and fluorescence per cell as functions of time, calculates errors, exports in different formats, and enables meta-analysis of multiple plates. The software corrects for autofluorescence, the optical density's non-linear dependence on the number of cells, and the effects of the media. We use omniplate to measure the Monod relationship for the growth of budding yeast in raffinose, showing that raffinose is a convenient carbon source for controlling growth rates. Using fluorescent tagging, we study yeast's glucose transport. Our results are consistent with the regulation of the hexose transporter (HXT) genes being approximately bipartite: the medium and high affinity transporters are predominately regulated by both the high affinity glucose sensor Snf3 and the kinase complex SNF1 via the repressors Mth1, Mig1, and Mig2; the low affinity transporters are predominately regulated by the low affinity sensor Rgt2 via the co-repressor Std1. We thus demonstrate that omniplate is a powerful tool for exploiting the advantages offered by time-series data in revealing biological regulation.

Heteroatom-Modulated Assembly of Hexalanthanoid-Containing Polyoxometalate-Based Coordination Networks.

Two series of lanthanoid (Ln)-containing polyoxometalates (POMs) {[Ln6(ampH)4(H2O)24-n(ampH2)n(PW11O39)2]·21H2O (Ln = Tb, n = 0 (1), Ln = Er, n = 1 (2)) and K2[Ln6(ampH)4(H2O)22(SiW11O39)2]·23H2O (Ln = Tb (3), Er (4)) (ampH2 = (aminomethyl) phosphonic acid)} have been synthesized with tri-lacunary Keggin-type POMs containing different types of heteroatoms. Compounds 1 and 2 display neutral organic-inorganic hybrid POM molecules containing {Ln6(ampH)4} ({Ln6}) cores sandwiched by two {PW11O39} units. By changing the heteroatoms from PV to SiIV, the extended 2D networks of 3 and 4 were successfully isolated where the adjacent {Ln6} clusters were connected by {SiW11O39} moieties. Luminescence performances and magnetic properties of 1-4 have been systematically surveyed. The solid-state fluorescence spectra of 1-4 display characteristic emissions of Ln components resulting from the 4f-4f transitions, and energy transfer from the POM segments to Ln3+ centers in 1 and 3 has been observed based on the lifetime decay behaviors. Furthermore, all compounds can be utilized as electrocatalysts toward reduction of nitrite with high stability.

Copper Hexacyanoferrate Solid-State Electrolyte Protection Layer on Zn Metal Anode for High-Performance Aqueous Zinc-Ion Batteries.

Zinc (Zn) metal possesses broad prospects as an anode for aqueous zinc-ion batteries (AZIBs) due to its considerable theoretical capacity of 820 mAh g-1 . However, the Zn anode suffers from dendrite growth and side reactions during Zn stripping/plating. Herein, a Prussian blue analog of copper hexacyanoferrate (CuHCF) with a 3D open structure and rich polar groups (CN) is coated on Zn foil as a solid-state electrolyte (SSE) protection layer to protect the Zn anode. The CuHCF protection layer possesses low activation energy of 26.49 kJ mol-1 , the high ionic conductivity of 7.6 mS cm-1 , and a large Zn2+ transference number of 0.74. Hence, the Zn@CuHCF||Zn@CuHCF symmetric cell delivers high cycling stability over 1800 h at 5 mA cm-2 , an excellent depth of discharge of 51.3%, and the accumulative discharge capacity over 3000 mAh cm-2 . In addition, the Zn//Ti@CuHCF asymmetric cell achieves the coulombic efficiency (CE) of 99.87% after 2000 cycles. More importantly, the Zn@CuHCF//V2 O5 full cell presents outstanding capacity retention of 87.6% at 10 A g-1 after 3000 cycles. This work develops a type of material to form an artificial protection layer for high-performance AZIBs.

GsMTx-4 normalizes the exercise pressor reflex evoked by intermittent muscle contraction in early stage type 1 diabetic rats.

Emerging evidence suggests the exercise pressor reflex is exaggerated in early stage type 1 diabetes mellitus (T1DM). Piezo channels may play a role in this exaggeration, as blocking these channels attenuates the exaggerated pressor response to tendon stretch in T1DM rats. However, tendon stretch constitutes a different mechanical and physiological stimuli than that occurring during muscle contraction. Therefore, the purpose of this study was to determine the contribution of Piezo channels in evoking the pressor reflex during an intermittent muscle contraction in T1DM. In unanesthetized decerebrate rats, we compared the pressor and cardioaccelerator responses to intermittent muscle contraction before and after locally injecting grammostola spatulata mechanotoxin 4 (GsMTx-4, 0.25 µM) into the hindlimb vasculature. Although GsMTx-4 has a high potency for Piezo channels, it has also been suggested to block transient receptor potential cation (TRPC) channels. We, therefore, performed additional experiments to control for this possibility by also injecting SKF 96365 (10 µM), a TRPC channel blocker. We found that local injection of GsMTx-4, but not SKF 96365, attenuated the exaggerated peak pressor (ΔMAP before: 33 ± 3 mmHg, after: 22 ± 3 mmHg, P = 0.007) and pressor index (ΔBPi before: 668 ± 91 mmHg·s, after: 418 ± 81 mmHg·s, P = 0.021) response in streptozotocin (STZ) rats (n = 8). GsMTx-4 attenuated the exaggerated early onset pressor and the pressor response over time, which eliminated peak differences as well as those over time between T1DM and healthy controls. These data suggest that Piezo channels are an effective target to normalize the exercise pressor reflex in T1DM.NEW & NOTEWORTHY This is the first study to demonstrate that blocking Piezo channels is effective in ameliorating the exaggerated exercise pressor reflex evoked by intermittent muscle contraction, commonly occurring during physical activity, in T1DM. Thus, these findings suggest Piezo channels may serve as an effective therapeutic target to reduce the acute and prolonged cardiovascular strain that may occur during dynamic exercise in T1DM.

pH-Controlled Assembly of Two Polynuclear Dy(III)-Containing Polytungstoarsenates with Magnetic and Luminescence Properties.

Two novel polynuclear dysprosium (Dy)-containing polytungstoarsenates, CsK7Na16[(AsW9O33)6Dy6W10O24(H2O)23]·40H2O (1) and Cs2K18Na18[(AsW9O33)7Dy7W8O21(H2O)17(µ3-OH)(OH)]·78H2O (2), have been synthesized via the reaction of the preformed polyoxometalate (POM) precursor [As2W19O67(H2O)]14- and Dy3+ ions through controlling pH. The polyanion of 1 can be described as a dimer of two similar trimers {(AsW9O33)3Dy2W5O12(H2O)6} that are linked by Dy cation and two µ2-oxo groups, and the Dy(III) ions in 1 are arranged in a linear fashion. Compound 2 presenting an interesting W-shaped structure, assembly composed of a dimeric {(AsW9O33)2W3Dy2O8(H2O)7}, a trimer {(AsW9O33)3W4Dy2O11(OH)(H2O)3}, and a particular sandwiched {(AsW9O33)2WDy3O4(µ3-OH)(H2O)7} segment concatenated by µ2-oxo groups. The solid-state luminescence performances and lifetime decay behaviors of 1 and 2 were systematically researched at ambient temperature, and time-resolved fluorescence spectra of 1 and 2 indicate energy transfer (ET) from the photoexcitation O → M ligand to the metal charge-transfer (LMCT) bands of the POM ligands to Dy3+ ions. Moreover, the dynamic magnetic measurement indicates that 1 and 2 exhibit slow relaxation of the magnetization.

Metal-Organic Framework-Derived ZnSe- and Co0.85Se-Filled Porous Nitrogen-Doped Carbon Nanocubes Interconnected by Reduced Graphene Oxide for Sodium-Ion Battery Anodes.

Transition-metal selenides have been considered as one of the most promising anode materials for sodium-ion batteries (SIBs) due to their high theoretical capacity and excellent rate performance. However, rapid capacity decay and poor cycling stability limit their practical application as the anode for SIBs. Carbon coating is one of the most effective ways to solve the above problems, but the thickness and uniformity of the coating layer are difficult to control. Herein, we successfully synthesize metal-organic framework (MOF)-derived porous N-doped carbon nanocubes homogeneously filled with ZnSe and Co0.85Se and interconnected by reduced graphene oxide (ZCS@NC@rGO). ZCS@NC@rGO with more active sites and the synergistic effect of the ZnSe and Co0.85Se heterojunction can enhance the sodium storage performance. The porous carbon nanocubes effectively prevent the agglomeration of active particles, and the rGO acting as a carbon network can significantly buffer the inevitable volume changes. At the same time, carbon nanocubes and the rGO are interconnecting to form a conductive network to accelerate electron transfer. Based on the aforementioned advantages, the ZCS@NC@rGO electrode shows an excellent sodium storage performance. Our investigation opens up a new horizon for the rational design of transition-metal selenide anodes for SIBs with a unique structure.

Light curve VMD-MI: simultaneous estimation of precession and spin rates of space targets using light curves.

Optical data are important data sources for operating state estimation of space targets. Inversion of the rotation rate of tumbling targets via light curves can help us perform on-orbit services. However, previous methods cannot estimate the precession and spin rates of tumbling targets from light curves simultaneously. To solve the problem, an efficient precession and spin rate estimation algorithm for tumbling targets is proposed in this paper. The method combines the variational mode decomposition (VMD) method and mutual information (MI). Specifically, VMD is utilized to decompose each light curve into discrete frequency intrinsic mode functions (IMFs). Then, the MI between each IMF and light curve is generated, and the IMF frequencies corresponding to the two maximum MI values are extracted as spin and precession frequencies. Finally, the two frequencies are converted into spin and precession rates. Experimental results show that the estimation accuracy of the precession and spin rates is no less than 97% for a small nutation angle (no greater than 20º). The method provides a simple way to invert a space target state and mine more information from light curves.

177 Saponins, Including 11 New Compounds in Wild Ginseng Tentatively Identified via HPLC-IT-TOF-MSn, and Differences among Wild Ginseng, Ginseng under Forest, and Cultivated Ginseng.

Wild ginseng (W-GS), ginseng under forest (F-GS, planted in mountain forest and growing in natural environment), and cultivated ginseng (C-GS) were compared via HPLC-DAD and HPLC-IT-TOF-MSn. A total of 199 saponins, including 16 potential new compounds, were tentatively identified from 100 mg W-GS (177 saponins in W-GS with 11 new compounds), F-GS (56 saponins with 1 new compound), and C-GS (60 saponins with 6 new compounds). There were 21 saponins detected from all the W-GS, F-GS, and C-GS. Fifty saponins were only detected from W-GS, including 23 saponins found in ginseng for the first time. Contents of ginsenosides Re (12.36-13.91 mg/g), Rh1 (7.46-7.65 mg/g), Rd (12.94-12.98 mg/g), and the total contents (50.52-55.51 mg/g) of Rg1, Re, Rf, Rb1, Rg2, Rh1, and Rd in W-GS were remarkably higher than those in F-GS (Re 1.22-3.50 mg/g, Rh1 0.15-1.49 mg/g, Rd 0.19-1.49 mg/g, total 5.69-18.74 mg/g), and C-GS (Re 0.30-3.45 mg/g, Rh1 0.05-3.42 mg/g, Rd 0.17-1.68 mg/g, total 2.99-19.55 mg/g). Contents of Re and Rf were significantly higher in F-GS than those in C-GS (p < 0.05). Using the contents of Re, Rf, or Rb1, approximately a half number of cultivated ginseng samples could be identified from ginseng under forest. Contents of Rg1, Re, Rg2, Rh1, as well as the total contents of the seven ginsenosides were highest in ginseng older than 15 years, middle-high in ginseng between 10 to 15 years old, and lowest in ginseng younger than 10 years. Contents of Rg1, Re, Rf, Rb1, Rg2, and the total of seven ginsenosides were significantly related to the growing ages of ginseng (p < 0.10). Similarities of chromatographic fingerprints to W-GS were significantly higher (p < 0.05) for F-GS (median: 0.824) than C-GS (median: 0.745). A characteristic peak pattern in fingerprint was also discovered for distinguishing three types of ginseng. Conclusively, wild ginseng was remarkably superior to ginseng under forest and cultivated ginseng, with ginseng under forest slightly closer to wild ginseng than cultivated ginseng. The differences among wild ginseng, ginseng under forest, and cultivated ginseng in saponin compositions and contents of ginsenosides were mainly attributed to their growing ages.

[Application of objective performance criteria in post-marketing evaluation schemes of traditional Chinese medicine].

Traditional Chinese medicines(TCMs) have certain limitations in the clinical research design in their post-marketing evaluation, so that randomized controlled programs cannot be strictly implemented in some studies, while the objective performance criteria is a reasonable external controlled research method that has been gradually recognized at home and abroad in recent years in addition to randomized controlled trial(RCT) method. It is more mature in medical devices, surgery and other research fields, but there is no relevant report in the field of post-marketing evaluation of Chinese patent medicines. In this paper, the application prospect of the objective performance criteria and the problems were discussed in the field of post-marketing evaluation of TCM. The characteristics of as TCM are more consistent with the scope of the objective performance criteria, the application of the objective performance criteria in post-marketing evaluation of Chinese patent medicines, especially in single arm research, can break through the limitations of existing conventional clinical research methods, and improve the level of evidence, with good feasibility and advantages. However, in the application process, we should pay attention to the key issues such as the selection of index, research population, follow-up period and the reference selection, to ensure the quality of research. This research group has carried out some exploration and practice in the field of post-marketing evaluation of TCM injections by using single arm combined with the objective performance criteria, hoping to establish the key technology in this field, and provide certain research and design reference for the secondary development of Chinese patent medicines.

Effects of type 1 diabetes on reflexive cardiovascular responses to intermittent muscle contraction.

Studies have shown that early-stage type 1 diabetes mellitus (T1DM) leads to an exaggerated reflex pressor response to both static muscle contraction and tendon stretch. However, whether similar responses are present during dynamic exercise (i.e., intermittent contraction) is not known. Therefore, the purpose of this study was to determine whether T1DM leads to an exaggerated reflex pressor response to intermittent muscle contraction. We measured the exercise pressor reflex in unanesthetized, decerebrated T1DM (50 mg/kg streptozotocin; STZ) and healthy control (CTL) Sprague-Dawley rats by intermittently contracting the hindlimb muscles for 30 s while measuring mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). Intermittently contracting the hindlimb muscles evoked exaggerated mean RSNA (STZ: Δ109 ± 21%, n = 4 rats; CTL: Δ61 ± 8%, n = 5 rats, P < 0.05), peak MAP (STZ: Δ32 ± 2 mmHg, n = 9 rats; CTL: Δ12 ± 2 mmHg, n = 6 rats, P < 0.05), blood pressure index (STZ: Δ625 ± 60 mmHg/s, n = 9 rats; CTL: Δ241 ± 46 mmHg/s, n = 6 rats, P < 0.05), and HR (STZ: Δ24 ± 3 beats/min, n = 9 rats; CTL: Δ9 ± 3 beats/min, n = 6 rats, P < 0.05) responses to similar developed tensions (P > 0.05) in T1DM compared with CTL rats. T1DM rats also exhibited exaggerated early-onset sympathetic (onset: 1 s) and pressor (onset: 5 s) responses. These data show that early-stage T1DM leads to an exaggerated pressor reflex evoked by intermittent muscle contraction. The early onset and greater blood pressure index suggest that cardiovascular strain during dynamic exercise may be significantly higher in individuals with T1DM.NEW & NOTEWORTHY This is the first study to provide evidence that early-stage type 1 diabetes mellitus (T1DM) leads to an exaggerated exercise pressor reflex evoked by intermittent muscle contraction, resulting in substantially higher cardiovascular strain. These findings are significant as they indicate that interventions targeting the exercise pressor reflex may work to alleviate the increased cardiovascular strain and overall burden during exercise in T1DM.

Hollow Porous MnFe2 O4 Sphere Grown on Elm-Money-Derived Biochar towards Energy-Saving Full Water Electrolysis.

The development of inexpensive and efficient bifunctional electrocatalysts is significant for widespread practical applications of overall water splitting technology. Herein, a one-pot solvothermal method is used to prepare hollow porous MnFe2 O4 spheres, which are grown on natural-abundant elm-money-derived biochar material to construct MnFe2 O4 /BC composite. When the overpotential is 156 mV for both the oxygen evolution reaction and the hydrogen evolution reaction, the current density reaches up to 10 mA cm-2 , and its duration is 10 h. At 1.51 V, the overall water decomposition current density of 10 mA cm-2 can be obtained in 1 m KOH. This work proves that elm-money-derived biochar is a valid substrate for growing hollow porous spheres. MnFe2 O4 /BC give a promising general strategy for preparing the effective and stable bifunctional catalysis that can be expand to multiple transition metal oxide.

Connectivity on Underwater MI-Assisted Acoustic Cooperative MIMO Networks.

In traditional underwater wireless sensor networks (UWSNs), it is difficult to establish reliable communication links as the acoustic wave experiences severe multipath effect, channel fading, and ambient noise. Recently, with the assistance of magnetic induction (MI) technique, cooperative multi-input-multi-output (MIMO) is utilized in UWSNs to enable the reliable long range underwater communication. Compared with the acoustic-based UWSNs, the UWSNs adopting MI-assisted acoustic cooperative MIMO are referred to as heterogeneous UWSNs, which are able to significantly improve the effective cover space and network throughput. Due to the complex channel characteristics and the heterogeneous architecture, the connectivity of underwater MI-assisted acoustic cooperative MIMO networks is much more complicated than that of acoustic-based UWSNs. In this paper, a mathematical model is proposed to analyze the connectivity of the networks, which considers the effects of channel characteristics, system parameters, and synchronization errors. The lower and upper bounds of the connectivity probability are also derived, which provide guidelines for the design and deployment of underwater MI-assisted acoustic cooperative MIMO networks. Monte Carlo simulations were performed, and the results validate the accuracy of the proposed model.

Exaggerated cardiovascular responses to muscle contraction and tendon stretch in UCD type-2 diabetes mellitus rats.

Patients with type-2 diabetes mellitus (T2DM) have exaggerated sympathetic activity and blood pressure responses to exercise. However, the underlying mechanisms for these responses, as well as how these responses change throughout disease progression, are not completely understood. For this study, we examined the effect of the progression of T2DM on the exercise pressor reflex, a critical neurocardiovascular mechanism that functions to increase sympathetic activity and blood pressure during exercise. We also aimed to examine the effect of T2DM on reflexive cardiovascular responses to static contraction, as well as those responses to tendon stretch when an exaggerated exercise pressor reflex was present. We evoked the exercise pressor reflex and mechanoreflex by statically contracting the hindlimb muscles and stretching the Achilles tendon, respectively, for 30 s. We then compared pressor and cardioaccelerator responses in unanesthetized, decerebrated University of California Davis (UCD)-T2DM rats at 21 and 31 wk following the onset of T2DM to responses in healthy nondiabetic rats. We found that the pressor response to static contraction was greater in the 31-wk T2DM [change in mean arterial pressure (∆MAP) = 39 ± 5 mmHg] but not in the 21-wk T2DM (∆MAP = 24 ± 5 mmHg) rats compared with nondiabetic rats (∆MAP = 18 ± 2 mmHg; P < 0.05). Similarly, the pressor and the cardioaccelerator responses to tendon stretch were significantly greater in the 31-wk T2DM rats [∆MAP = 69 ± 6 mmHg; change in heart rate (∆HR) = 28 ± 4 beats/min] compared with nondiabetic rats (∆MAP = 14 ± 2 mmHg; ∆HR = 5 ± 3 beats/min; P < 0.05). These findings suggest that the exercise pressor reflex changes as T2DM progresses and that a sensitized mechanoreflex may play a role in exaggerating these cardiovascular responses.NEW & NOTEWORTHY This is the first study to provide evidence that as type-2 diabetes mellitus (T2DM) progresses, the exercise pressor reflex becomes exaggerated, an effect that may be due to a sensitized mechanoreflex. Moreover, these findings provide compelling evidence suggesting that impairments in the reflexive control of circulation contribute to exaggerated blood pressure responses to exercise in T2DM.

Hybrid Two-Component Sensors for Identification of Bacterial Chemoreceptor Function.

Soil bacteria adapt to diverse and rapidly changing environmental conditions by sensing and responding to environmental cues using a variety of sensory systems. Two-component systems are a widespread type of signal transduction system present in all three domains of life and typically are comprised of a sensor kinase and a response regulator. Many two-component systems function by regulating gene expression in response to environmental stimuli. The bacterial chemotaxis system is a modified two-component system with additional protein components and a response that, rather than regulating gene expression, involves behavioral adaptation and results in net movement toward or away from a chemical stimulus. Soil bacteria generally have 20 to 40 or more chemoreceptors encoded in their genomes. To simplify the identification of chemoeffectors (ligands) sensed by bacterial chemoreceptors, we constructed hybrid sensor proteins by fusing the sensor domains of Pseudomonas putida chemoreceptors to the signaling domains of the Escherichia coli NarX/NarQ nitrate sensors. Responses to potential attractants were monitored by ß-galactosidase assays using an E. coli reporter strain in which the nitrate-responsive narG promoter was fused to lacZ Hybrid receptors constructed from PcaY, McfR, and NahY, which are chemoreceptors for aromatic acids, tricarboxylic acid cycle intermediates, and naphthalene, respectively, were sensitive and specific for detecting known attractants, and the ß-galactosidase activities measured in E. coli correlated well with results of chemotaxis assays in the native P. putida strain. In addition, a screen of the hybrid receptors successfully identified new ligands for chemoreceptor proteins and resulted in the identification of six receptors that detect propionate.IMPORTANCE Relatively few of the thousands of chemoreceptors encoded in bacterial genomes have been functionally characterized. More importantly, although methyl-accepting chemotaxis proteins, the major type of chemoreceptors present in bacteria, are easily identified bioinformatically, it is not currently possible to predict what chemicals will bind to a particular chemoreceptor. Chemotaxis is known to play roles in biodegradation as well as in host-pathogen and host-symbiont interactions, but many studies are currently limited by the inability to identify relevant chemoreceptor ligands. The use of hybrid receptors and this simple E. coli reporter system allowed rapid and sensitive screening for potential chemoeffectors. The fusion site chosen for this study resulted in a high percentage of functional hybrids, indicating that it could be used to broadly test chemoreceptor responses from phylogenetically diverse samples. Considering the wide range of chemical attractants detected by soil bacteria, hybrid receptors may also be useful as sensitive biosensors.

Exaggerated mechanoreflex in early-stage type 1 diabetic rats: role of Piezo channels.

Recent findings have shown that muscle contraction evokes an exaggerated pressor response in type 1 diabetes mellitus (T1DM) rats; however, it is not known whether the mechanoreflex, which is commonly stimulated by stretching the Achilles tendon, contributes to this abnormal response. Furthermore, the role of mechano-gated Piezo channels, found on thin-fiber afferent endings, in evoking the mechanoreflex in T1DM is also unknown. Therefore, in male and female streptozotocin (STZ, 50 mg/kg)-induced T1DM and healthy control (CTL) rats, we examined the pressor and cardioaccelerator responses to tendon stretch during the early stage of the disease. To determine the role of Piezo channels, GsMTx-4, a selective Piezo channel inhibitor, was injected into the arterial supply of the hindlimb. At 1 wk after STZ injection in anesthetized, decerebrate rats, we stretched the Achilles tendon for 30 s and measured pressor and cardioaccelerator responses. We then compared pressor and cardioaccelerator responses to tendon stretch before and after GsMTx-4 injection (10 µg/100 ml). We found that the pressor (change in mean arterial pressure) response [41 ± 5 mmHg (n = 15) for STZ and 18 ± 3 mmHg (n = 11) for CTL (P < 0.01)] and cardioaccelerator (change in heart rate) response [18 ± 4 beats/min for STZ (n = 15) and 8 ± 2 beats/min (n = 11) for CTL (P < 0.05)] to tendon stretch were exaggerated in STZ rats. Local injection of GsMTx-4 attenuated the pressor [55 ± 7 mmHg (n = 6) before and 27 ± 9 mmHg (n = 6) after GsMTx-4 (P < 0.01)], but not the cardioaccelerator, response to tendon stretch in STZ rats and had no effect on either response in CTL rats. These data suggest that T1DM exaggerates the mechanoreflex response to tendon stretch and that Piezo channels play a role in this exaggeration.

Effect of Bridging Ligands on Magnetic Behavior in Dinuclear Dysprosium Cores Supported by Polyoxometalates.

A family of dinuclear dysprosium cores bridged by different ligands within a polyoxometalates (POMs) framework, (TBA)8.5H1.5[(PW11O39)2Dy2X2(H2O)2]·6H2O (X = OH (1), F (2), OAc (3); TBA = tetra- n-butylammonium), was successfully synthesized and structurally characterized. Magnetic studies indicate that the bridging ligands can significantly affect the magnetic behaviors, with 1 and 3 showing antiferromagnetic coupling and 2 bridged by fluoride ions showing ferromagnetic interaction. 1 and 2 behaved as single-molecule magnets (SMMs) with the thermally activated energy barrier of 98(5) and 74(6) cm-1 under zero dc filed, respectively, whereas no SMM behavior was observed for 3 bridged by two µ-η1:η2-acetato ligands. Notably, the low-temperature fluorescence spectra of 1-3 provide valuable information on the energy levels, which are consistent with the anisotropic barriers determined by magnetic measurements. These results offer an insight into the magneto-optical correlation. Furthermore, the effective energy barrier of 1 reaches a breakthrough among all POM-based SMMs.