Transient receptor potential melastatin 7 cation channel kinase new player in angiotensin II–induced hypertension

Transient receptor potential melastatin 7 (TRPM7) is a bifunctional protein comprising a magnesium (Mg2+)/cation channel and a kinase domain. We previously demonstrated that vasoactive agents regulate vascular TRPM7. Whether TRPM7 plays a role in the pathophysiology of hypertension and associated cardiovascular dysfunction is unknown. We studied TRPM7 kinase–deficient mice (TRPM7Δkinase; heterozygous for TRPM7 kinase) and wild-type (WT) mice infused with angiotensin II (Ang II; 400 ng/kg per minute, 4 weeks). TRPM7 kinase expression was lower in heart and aorta from TRPM7Δkinase versus WT mice, effects that were further reduced by Ang II infusion. Plasma Mg2+ was lower in TRPM7Δkinase versus WT mice in basal and stimulated conditions. Ang II increased blood pressure in both strains with exaggerated responses in TRPM7Δkinase versus WT groups (P<0.05). Acetylcholine-induced vasorelaxation was reduced in Ang II–infused TRPM7Δkinase mice, an effect associated with Akt and endothelial nitric oxide synthase downregulation. Vascular cell adhesion molecule–1 expression was increased in Ang II–infused TRPM7 kinase–deficient mice. TRPM7 kinase targets, calpain, and annexin-1, were activated by Ang II in WT but not in TRPM7Δkinase mice. Echocardiographic and histopathologic analysis demonstrated cardiac hypertrophy and left ventricular dysfunction in Ang II–treated groups. In TRPM7 kinase–deficient mice, Ang II–induced cardiac functional and structural effects were amplified compared with WT counterparts. Our data demonstrate that in TRPM7Δkinase mice, Ang II–induced hypertension is exaggerated, cardiac remodeling and left ventricular dysfunction are amplified, and endothelial function is impaired. These processes are associated with hypomagnesemia, blunted TRPM7 kinase expression/signaling, endothelial nitric oxide synthase downregulation, and proinflammatory vascular responses. Our findings identify TRPM7 kinase as a novel player in Ang II–induced hypertension and associated vascular and target organ damage

Drawing Graphs within Restricted Area

We study the problem of selecting a maximum-weight subgraph of a given graph such that the subgraph can be drawn within a prescribed drawing area subject to given non-uniform vertex sizes. We develop and analyze heuristics both for the general (undirected) case and for the use case of (directed) calculation graphs which are used to analyze the typical mistakes that high school students make when transforming mathematical expressions in the process of calculating, for example, sums of fractions

A Chronic Care Model Program Incorporating Group Office Visits for Obesity Treatment in Primary Care

Background. Obesity is a chronic disease of epidemic proportions. Primary care providers are on the front line of diagnosing and treating obesity and need better tools to deliver top-notch obesity care. Methods. A pilot randomized trial was conducted to test a chronic care model (CCM) program for obesity compared to usual care. Primary care patients, 18 years and older, with a body mass index (BMI) between 27 and 45 were enrolled. Sixteen weekly 90-minute group office visits were structured with the first 30 minutes encompassing individualized clinical assessments and the final 60 minutes containing the group-based standardized intensive lifestyle training. The primary outcome was weight change at 16 weeks. Secondary outcomes were weight change at 24 weeks, change in diet and physical activity behaviors, self-efficacy for weight control behaviors, and physiologic markers of cardiovascular risk at 16 and 24 weeks. Results. The participants (19 in the active arm and 10 in the control arm) were 49.8 ± 11.5 years old (mean ± SD), 97% women, 55% white, and 41% black. Weight change in the control arm at week 16 was 0.25+ 2.21 kg (mean + SD) and that for the active arm was -5.74 + 4.50 kg (n=16). The difference between the two arms was significant (p = 0.0002). Both the intent-to-treat analysis using the last observation carried forward approach and the analysis including completers only provided similar siginificant results. Conclusions. This study demonstrated that a CCM program incorporating group office visits was feasible and effective for obesity treatment in primary care settings

Optimization and measurement of a smoothly profiled horn for a W-band gyro-TWA

In this paper, a smoothly profiled horn was designed and manufactured to replace a corrugated output horn for a W-band gyro-TWA with improved ultra-high vacuum compatibility. It was optimized for high vacuum integrity, low reflection, high fundamental Gaussian mode content, low side lobe levels and high directivity over the frequency bandwidth of 90 - 100 GHz. Over this operating frequency band the reflectivity was better than -37 dB and the coupling to a fundamental Gaussian mode was above 97%. The far field pattern showed a directivity of approximately 27 dB in the measurement with side lobes lower than -30 dB

Analysis of LIN28A in early human ovary development and as a candidate gene for primary ovarian insufficiency

Lin28 proteins are emerging as important regulators of microRNAs in endocrine systems. Lin28a regulates primordial germ cell development and puberty timing in mice, whereas the related protein LIN28B is associated with age at menarche in genome-wide association studies in humans. Here, we studied expression of LIN28A and LIN28B in early human gonad development. LIN28A increased in the developing ovary between 6 and 9 weeks post conception, but not in the developing testis. Immunohistochemistry demonstrated LIN28A in peripheral germ cells. LIN28B was expressed at lower levels in both tissues and did not increase with time. As disruption of Lin28a affects germ cell development in mice, LIN28A was considered a candidate gene for primary ovarian insufficiency (POI) in humans. However, no significant changes were found in 50 women studied. These findings show LIN28A is strongly expressed in germ cells during early human ovary development, but disruption of LIN28A is not a common cause of POI

An output coupler for a W-band high power wideband gyro-amplifier

This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) U.K. under Research Grant EP/K029746/1, and Science and Technology Facilities Council (STFC) U.K. under Research Grants ST/K006673/1 & ST/K006703/1, ST/N002326/1 & ST/N002318/1.An output coupler for a W-band high power wideband gyro-amplifier has been designed, manufactured and experimentally measured. It consists of a high performance sin2-parallel corrugated horn integrated with a broadband multi-layer window. The major design requirements are that the horn/window combination must have an input return loss lower than -30 dB over a 10 GHz bandwidth, provide a high quality output beam pattern, and operate under ultra-high vacuum conditions. The coupler converts a circular wave guide TE11 mode into the free space Laguerre Gaussian LG00 mode over the frequency band of 90–100 GHz with a measured return loss of between -30 and -40 dB and a simulated Gaussian coupling efficiency of over 99% at 94 GHz.PostprintPeer reviewe

Quantum phase transitions in Bose-Einstein condensates from a Bethe ansatz perspective

We investigate two solvable models for Bose-Einstein condensates and extract physical information by studying the structure of the solutions of their Bethe ansatz equations. A careful observation of these solutions for the ground state of both models, as we vary some parameters of the Hamiltonian, suggests a connection between the behavior of the roots of the Bethe ansatz equations and the physical behavior of the models. Then, by the use of standard techniques for approaching quantum phase transition - gap, entanglement and fidelity - we find that the change in the scenery in the roots of the Bethe ansatz equations is directly related to a quantum phase transition, thus providing an alternative method for its detection.Comment: 26 pages, 13 figure

Modulating attentional load affects numerosity estimation: evidence against a pre-attentive subitizing mechanism

Traditionally, the visual enumeration of a small number of items (1 to about 4), referred to as subitizing, has been thought of as a parallel and pre-attentive process and functionally different from the serial attentive enumeration of larger numerosities. We tested this hypothesis by employing a dual task paradigm that systematically manipulated the attentional resources available to an enumeration task. Enumeration accuracy for small numerosities was severely decreased as more attentional resources were taken away from the numerical task, challenging the traditionally held notion of subitizing as a pre-attentive, capacity-independent process. Judgement of larger numerosities was also affected by dual task conditions and attentional load. These results challenge the proposal that small numerosities are enumerated by a mechanism separate from large numerosities and support the idea of a single, attention-demanding enumeration mechanism

Plant responses to photoperiod

Photoperiod controls many developmental responses in animals, plants and even fungi. The response to photoperiod has evolved because daylength is a reliable indicator of the time of year, enabling developmental events to be scheduled to coincide with particular environmental conditions. Much progress has been made towards understanding the molecular mechanisms involved in the response to photoperiod in plants. These mechanisms include the detection of the light signal in the leaves, the entrainment of circadian rhythms, and the production of a mobile signal which is transmitted throughout the plant. Flowering, tuberization and bud set are just a few of the many different responses in plants that are under photoperiodic control. Comparison of what is known of the molecular mechanisms controlling these responses shows that, whilst common components exist, significant differences in the regulatory mechanisms have evolved between these responses

Walks4work: Rationale and study design to investigate walking at lunchtime in the workplace setting

Background: Following recruitment of a private sector company, an 8week lunchtime walking intervention was implemented to examine the effect of the intervention on modifiable cardiovascular disease risk factors, and further to see if walking environment had any further effect on the cardiovascular disease risk factors. Methods. For phase 1 of the study participants were divided into three groups, two lunchtime walking intervention groups to walk around either an urban or natural environment twice a week during their lunch break over an 8week period. The third group was a waiting-list control who would be invited to join the walking groups after phase 1. In phase 2 all participants were encouraged to walk during their lunch break on self-selecting routes. Health checks were completed at baseline, end of phase 1 and end of phase 2 in order to measure the impact of the intervention on cardiovascular disease risk. The primary outcome variables of heart rate and heart rate variability were measured to assess autonomic function associated with cardiovascular disease. Secondary outcome variables (Body mass index, blood pressure, fitness, autonomic response to a stressor) related to cardiovascular disease were also measured. The efficacy of the intervention in increasing physical activity was objectively monitored throughout the 8-weeks using an accelerometer device. Discussion. The results of this study will help in developing interventions with low researcher input with high participant output that may be implemented in the workplace. If effective, this study will highlight the contribution that natural environments can make in the reduction of modifiable cardiovascular disease risk factors within the workplace. © 2012 Brown et al.; licensee BioMed Central Ltd