Organ-Specific and Development Regulation of the Nopaline Synthase Promoter in Transgenic Tobacco Plants

Control regions of the nopaline synthase (nos) gene have been widely used to express foreign genes in plants since the promoter is active in a wide variety of plant tissues. We report here the characteristics of the nos promoter activity in transgenic tobacco (Nicotiana tabacum) plants at various developmental stages. The promoter was highly active in the lower parts of a plant and gradually decreased in the upper parts. This vertical gradient was maintained throughout plant growth until the flowering stage when the overall promoter strength decreased significantly in the vegetative organs. However, in various flower organs, the nos promoter activities increased dramatically. Higher activity was observed in calyx, corolla, and stamens although the maximum promoter activity in each organ was found at different stages of flower development. The promoter activity in pistils was low and gradually increased in the ovaries after anthesis. In developing fruits, the nos promoter activity was strongly induced during the mid-stage of embryogenesis. These results indicate that the expression of the nos promoter is developmentally regulated and organ specific in transgenic tobacco plants

Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks

The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection neuron (PN)-type resolution in real time during behavior. Combining genetic targeting and wide-field imaging, we monitored activity dynamics of subcortical-projecting (PTFezf2) and intratelencephalic-projecting (ITPlxnD1) types across dorsal cortex of mice during different brain states and behaviors. ITPlxnD1 and PTFezf2 neurons showed distinct activation patterns during wakeful resting, spontaneous movements, and upon sensory stimulation. Distinct ITPlxnD1 and PTFezf2 subnetworks were dynamically tuned to different sensorimotor components of a naturalistic feeding behavior, and optogenetic inhibition of subnetwork nodes disrupted specific components of this behavior. Lastly, ITPlxnD1 and PTFezf2 projection patterns are consistent with their subnetwork activation patterns. Our results show that, in addition to the concept of columnar organization, dynamic areal and PN type-specific subnetworks are a key feature of cortical functional architecture linking microcircuit components with global brain networks

Random walk with barriers: Diffusion restricted by permeable membranes

Restrictions to molecular motion by barriers (membranes) are ubiquitous in biological tissues, porous media and composite materials. A major challenge is to characterize the microstructure of a material or an organism nondestructively using a bulk transport measurement. Here we demonstrate how the long-range structural correlations introduced by permeable membranes give rise to distinct features of transport. We consider Brownian motion restricted by randomly placed and oriented permeable membranes and focus on the disorder-averaged diffusion propagator using a scattering approach. The renormalization group solution reveals a scaling behavior of the diffusion coefficient for large times, with a characteristically slow inverse square root time dependence. The predicted time dependence of the diffusion coefficient agrees well with Monte Carlo simulations in two dimensions. Our results can be used to identify permeable membranes as restrictions to transport in disordered materials and in biological tissues, and to quantify their permeability and surface area.Comment: 8 pages, 3 figures; origin of dispersion clarified, refs adde

Why are different estimates of the effective reproductive number so different? A case study on COVID-19 in Germany

The effective reproductive number R$_t$ has taken a central role in the scientific, political, and public discussion during the COVID-19 pandemic, with numerous real-time estimates of this quantity routinely published. Disagreement between estimates can be substantial and may lead to confusion among decision-makers and the general public. In this work, we compare different estimates of the national-level effective reproductive number of COVID-19 in Germany in 2020 and 2021. We consider the agreement between estimates from the same method but published at different time points (within-method agreement) as well as retrospective agreement across eight different approaches (between-method agreement). Concerning the former, estimates from some methods are very stable over time and hardly subject to revisions, while others display considerable fluctuations. To evaluate between-method agreement, we reproduce the estimates generated by different groups using a variety of statistical approaches, standardizing analytical choices to assess how they contribute to the observed disagreement. These analytical choices include the data source, data pre-processing, assumed generation time distribution, statistical tuning parameters, and various delay distributions. We find that in practice, these auxiliary choices in the estimation of R$_t$ may affect results at least as strongly as the selection of the statistical approach. They should thus be communicated transparently along with the estimates

SU(3) Gauge Family Symmetry and Prediction for the Lepton-Flavor Mixing and Neutrino Masses with Maximal Spontaneous CP Violation

A model for the lepton-flavor mixing and CP violation is proposed based on the SU$_F$(3) gauge family symmetry and the Majorana feature of neutrinos. A consistent prediction for the lepton-flavor mixing and masses is shown to be resulted from the appropriate vacuum structure of SU$_F$(3) gauge symmetry breaking. By choosing the SU$_F$(3) gauge fixing condition to possess a residual $Z_2$ symmetry and requiring the vacuum structure of spontaneous symmetry breaking to have approximate global U(1) family symmetries, we obtain naturally the tri-bimaximal mixing matrix and largely degenerate neutrino masses in the neutrino sector and the small mixing matrix in the charged-lepton sector. With a simple ansatz that all the smallness due to the approximate global U(1) family symmetries is characterized by a single Wolfenstein parameter $\lambda \simeq 0.22$, and the charged-lepton mixing matrix has a similar hierarchy structure as the CKM quark mixing matrix, we arrive at a consistent prediction for the MNSP lepton-flavor mixing with a maximal spontaneous CP violation: $\delta =\pi/2$, $\sin^2\theta_{13} \simeq 1/2\lambda^2 \simeq 0.024$ ($\sin^22\theta_{13} \simeq 0.094$), $\sin^2\theta_{12} \simeq 1/3{3}(1 - 2\lambda^3) \simeq 0.326$ and $\sin^2\theta_{23} \simeq 1/2(1 - \lambda^2) \simeq 0.48$, which agree well with the current experimental data. The CP-violating Jarlskog-invariant is obtained to be $J_{CP} \simeq 1/6\lambda(1-\lambda^2/2-\lambda^3)\sin\delta \simeq 0.035$, which is detectable in next generation neutrino experiment. The largely degenerate neutrino masses with the normal hierarchy and inverse hierarchy are discussed and found be at the order $m_{\nu_i} \simeq O(\lambda^2) \simeq 0.04\sim 0.06$ eV with a total mass $\sum m_{\nu} \sim 0.15$ eV, which is testable in future precision astrophysics and cosmology.Comment: 14 pages, it is explicitly shown that the smallness for both the charged-lepton mixing and neutrino masses with the standard seesaw mechanism can naturally be explained by the approximate global U(1) family symmetries of vacuum structure in the SU(3) gauge family model, references added, published version in PL

Propofol and Aminophylline Antagonize Each Other During the Mobilization of Intracellular Calcium in Human Umbilical Vein Endothelial Cells

This study examined whether propofol and aminophylline affect the mobilization of intracellular calcium in human umbilical vein endothelial cells. Intracellular calcium was measured using laser scanning confocal microscopy. Cultured and serum-starved cells on round coverslips were incubated with propofol or aminophylline for 30 min, and then stimulated with lysophosphatidic acid, propofol and aminophylline. The results were expressed as relative fluorescence intensity and fold stimulation. Propofol decreased the concentration of intracellular calcium, whereas aminophylline caused increased mobilization of intracellular calcium in a concentration-dependent manner. Propofol suppressed the lysophosphatidic acid-induced mobilization of intracellular calcium in a concentration-dependent manner. Propofol further prevented the aminophylline-induced increase of intracellular calcium at clinically relevant concentrations. However, aminophylline reversed the inhibitory effect of propofol on the elevation of intracellular calcium by lysophosphatidic acid. Our results suggest that propofol and aminophylline antagonize each other on the mobilization of intracellular calcium in human umbilical vein endothelial cells at clinically relevant concentrations. Serious consideration should be given to how this interaction affects mobilization of intracellular calcium when these two drugs are used together

Malaria and vitamin A deficiency in African children: a vicious circle?

Vitamin A deficiency and malaria are both highly prevalent health problems in Africa. Vitamin A deficiency affects over 30 million children, most of whom are in the age-group (under five years) most affected by malaria. Vitamin A deficiency increases all-cause mortality in this part of the population, and malaria is an important cause of death in children at this age. A low serum retinol concentration (a marker of vitamin A deficiency) is commonly found in children suffering from malaria, but it is not certain whether this represents pre-existing vitamin A deficiency, a contribution of malaria to vitamin A deficiency, or merely an acute effect of malaria on retinol metabolism or binding. In this paper, available evidence in support of a causal relationship in each direction between vitamin A deficiency and malaria is reviewed. If such a relationship exists, and especially if this is bidirectional, interventions against either disease may convey an amplified benefit for health

Mode shifting in school travel mode: examining the prevalence and correlates of active school transport in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Studies examining the correlates of school transport commonly fail to make the distinction between morning and afternoon school trips. The purpose of this study was to examine the prevalence and correlates of mode shift from passive in the morning to active in the afternoon among elementary and secondary school students in Ontario, Canada.</p> <p>Methods</p> <p>Data were derived from the 2009 cycle of the Ontario Student Drug Use and Health Survey (OSDUHS). 3,633 students in grades 7 through 12 completed self-administered questionnaires. Socio-demographic, behavioural, psychological, and environmental predictors of active school transport (AST) were assessed using logistic regression.</p> <p>Results</p> <p>Overall, 47% and 38% of elementary school students reported AST to and from school, respectively. The corresponding figures were 23% and 32% for secondary school students. The prevalence of AST varied temporarily and spatially. There was a higher prevalence of walking/biking found for elementary school students than for secondary school students, and there was an approximate 10% increase in AST in the afternoon. Different correlates of active school transport were also found across elementary and secondary school students. For all ages, students living in urban areas, with a shorter travel time between home and school, and having some input to the decision making process, were more likely to walk to and from school.</p> <p>Conclusions</p> <p>Future research examining AST should continue to make the analytic distinction between the morning and afternoon trip, and control for the moderating effect of age and geography in predicting mode choice. In terms of practice, these variations highlight the need for school-specific travel plans rather than 'one size fits all' interventions in promoting active school transport.</p

Mitochondrial Apoptosis and FAK Signaling Disruption by a Novel Histone Deacetylase Inhibitor, HTPB, in Antitumor and Antimetastatic Mouse Models

BACKGROUND: Compound targeting histone deacetylase (HDAC) represents a new era in molecular cancer therapeutics. However, effective HDAC inhibitors for the treatment of solid tumors remain to be developed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we propose a novel HDAC inhibitor, N-Hydroxy-4-(4-phenylbutyryl-amino) benzamide (HTPB), as a potential chemotherapeutic drug for solid tumors. The HDAC inhibition of HTPB was confirmed using HDAC activity assay. The antiproliferative and anti-migratory mechanisms of HTPB were investigated by cell proliferation, flow cytometry, DNA ladder, caspase activity, Rho activity, F-actin polymerization, and gelatin-zymography for matrix metalloproteinases (MMPs). Mice with tumor xenograft and experimental metastasis model were used to evaluate effects on tumor growth and metastasis. Our results indicated that HTPB was a pan-HDAC inhibitor in suppressing cell viability specifically of lung cancer cells but not of the normal lung cells. Upon HTPB treatment, cell cycle arrest was induced and subsequently led to mitochondria-mediated apoptosis. HTPB disrupted F-actin dynamics via downregulating RhoA activity. Moreover, HTPB inhibited activity of MMP2 and MMP9, reduced integrin-β1/focal adhesion complex formation and decreased pericellular poly-fibronectin assemblies. Finally, intraperitoneal injection or oral administration of HTPB efficiently inhibited A549 xenograft tumor growth in vivo without side effects. HTPB delayed lung metastasis of 4T1 mouse breast cancer cells. Acetylation of histone and non-histone proteins, induction of apoptotic-related proteins and de-phosphorylation of focal adhesion kinase were confirmed in treated mice. CONCLUSIONS/SIGNIFICANCE: These results suggested that intrinsic apoptotic pathway may involve in anti-tumor growth effects of HTPB in lung cancer cells. HTPB significantly suppresses tumor metastasis partly through inhibition of integrin-β1/FAK/MMP/RhoA/F-actin pathways. We have provided convincing preclinical evidence that HTPB is a potent HDAC targeted inhibitor and is thus a promising candidate for lung cancer chemotherapy

Regulatory T Cells Suppress T Cell Activation at the Pathologic Site of Human Visceral Leishmaniasis

Suppression of T cell response is thought to be involved in the pathogenesis of visceral leishmaniasis (VL). Regulatory T cell (Treg) mediated immune-suppression is reported in animal models of Leishmania infection. However, their precise role among human patients still requires pathologic validation. The present study is aimed at understanding the frequency dynamics and function of Treg cells in the blood and bone marrow (BM) of VL patients. The study included 42 parasitologically confirmed patients, 17 healthy contact and 9 normal bone marrow specimens (NBM). We show i) the selective accumulation of Treg cells at one of the disease inflicted site(s), the BM, ii) their in vitro expansion in response to LD antigen and iii) persistence after successful chemotherapy. Results indicate that the Treg cells isolated from BM produces IL-10 and may inhibit T cell activation in IL-10 dependent manner. Moreover, we observed significantly higher levels of IL-10 among drug unresponsive patients, suggesting their critical role in suppression of immunity among VL patients. Our results suggest that IL-10 plays an important role in suppression of host immunity in human VL and possibly determines the efficacy of chemotherapy