Chiral Isotropic Liquids from Achiral Molecules Hough, L.E; Spannuth, M; Nakata, M ...
Science (American Association for the Advancement of Science),
07/2009, Volume:
325, Issue:
5939
Journal Article
Peer reviewed
A variety of simple bent-core molecules exhibit smectic liquid crystal phases of planar fluid layers that are spontaneously both polar and chiral in the absence of crystalline order. We found that ...because of intralayer structural mismatch, such layers are also only marginally stable against spontaneous saddle splay deformation, which is incompatible with long-range order. This results in macroscopically isotropic fluids that possess only short-range orientational and positional order, in which the only macroscopically broken symmetry is chirality--even though the phases are formed from achiral molecules. Their conglomerate domains exhibit optical rotatory powers comparable to the highest ever found for isotropic fluids of chiral molecules.
The Transforming Growth Factor-Beta (TGF-β) family is involved in regulating a variety of cellular processes such as apoptosis, differentiation, and proliferation. TGF-β binding to a Serine/Threonine ...kinase receptor complex causes the recruitment and subsequent activation of transcription factors known as smad2 and smad3. These proteins subsequently translocate into the nucleus to negatively or positively regulate gene expression. In this study, we define a second signaling pathway leading to TGF-β receptor activation of Extracellular Signal Regulated Kinase (Erk) in a cell-type dependent manner. TGF-β induced Erk activation was found in phenotypically normal mesenchymal cells, but not normal epithelial cells. By activating phosphotidylinositol 3-kinase (PI3K), TGF-β stimulates p21-activated kinase2 (Pak2) to phosphorylate c-Raf, ultimately resulting in Erk activation. Activation of Erk was necessary for TGF-β induced fibroblast replication. In addition, Erk phosphorylated the linker region of nuclear localized smads, resulting in increased half-life of C-terminal phospho-smad 2 and 3 and increased duration of smad target gene transcription. Together, these data show that in mesenchymal cell types the TGF-β/PI3K/Pak2/Raf/MEK/Erk pathway regulates smad signaling, is critical for TGF-β-induced growth and is part of an integrated signaling web containing multiple interacting pathways rather than discrete smad/non-smad pathways.
It is now widely accepted that most galaxies undergo an active phase, during which a central super-massive black hole generates vast radiant luminosities through the gravitational accretion of gas. ...Winds launched from a rotating accretion disk surrounding the black hole are thought to play a critical role, allowing the disk to shed angular momentum that would otherwise inhibit accretion. Such winds are capable of depositing large amounts of mechanical energy in the host galaxy and its environs, profoundly affecting its formation and evolution, and perhaps regulating the formation of large-scale cosmological structures in the early Universe. Although there are good theoretical grounds for believing that outflows from active galactic nuclei originate as disk winds, observational verification has proven elusive. Here we show that structures observed in polarized light across the broad H emission line in the quasar PG 1700+518 originate close to the accretion disk in an electron scattering wind. The wind has large rotational motions (∼4,000 km s-1), providing direct observational evidence that outflows from active galactic nuclei are launched from the disks. Moreover, the wind rises nearly vertically from the disk, favouring launch mechanisms that impart an initial acceleration perpendicular to the disk plane.
Invasive mechanical ventilation is often initiated in the ED, and mechanically ventilated patients may be kept in the ED for hours before ICU transfer. Although lung-protective ventilation is ...beneficial, particularly in ARDS, it remains uncertain how often lung-protective tidal volumes are used in the ED, and whether lung-protective ventilation in this setting impacts patient outcomes.
What is the association between the use of lung-protective ventilation in the ED and outcomes among invasively ventilated patients?
A retrospective analysis (2011-2017) of a prospective registry from eight EDs enrolling consecutive adult patients (≥ 18 years) who received invasive mechanical ventilation in the ED was performed. Lung-protective ventilation was defined by use of tidal volumes ≤ 8 mL/kg predicted body weight. The primary outcome was hospital mortality. Secondary outcomes included development of ARDS, hospital length of stay, and total hospital costs.
The study included 4,174 patients, of whom 2,437 (58.4%) received lung-protective ventilation in the ED. Use of lung-protective ventilation was associated with decreased odds of hospital death (adjusted OR aOR, 0.91; 95% CI, 0.84-0.96) and development of ARDS (aOR, 0.87; 95% CI, 0.81-0.92). Patients who received lung-protective ventilation in the ED had shorter median duration of mechanical ventilation (4 vs 5 days; P < 0.01), shorter median hospital length of stay (11 vs 14 days; P < .001), and reduced total hospital costs (Can$44,348 vs Can$52,484 US$34,153 vs US$40,418; P = .03) compared with patients who received higher tidal volumes.
Use of lung-protective ventilation in the ED was associated with important patient- and system-centered outcomes, including lower hospital mortality, decreased incidence of ARDS, lower hospital length of stay, and decreased total costs. Protocol development promoting the regular use of lung-protective ventilation in the ED may be of value.
We present optical spectropolarimetry of the nuclei of 36 Seyfert 1 galaxies, obtained with the William Herschel and the Anglo-Australian Telescopes from 1996 to 1999. In 20 of these, the optical ...emission from the active nucleus is intrinsically polarized. We have measured a significant level of polarization in a further seven objects but these may be heavily contaminated by Galactic interstellar polarization. The intrinsically polarized Seyfert 1 galaxies exhibit a variety of characteristics, with the average polarization ranging from <0.5 to 5 per cent and with many showing variations in both the degree and position angle of polarization across the broad Hα emission line. We identify a small group of Seyfert 1 galaxies that exhibit polarization properties similar to those of Seyfert 2 galaxies in which polarized broad lines have been discovered. These objects represent direct observational evidence that a Seyfert 2-like far-field polar scattering region is also present in Seyfert 1 galaxies. Several other objects have features that can be explained in terms of equatorial scattering of line emission from a rotating disc. We propose that much of the diversity in the polarization properties of Seyfert galaxies can be understood in terms of a model involving both equatorial and polar scattering, the relative importance of the two geometries as sources of polarized light being determined principally by the inclination of the system axis to the line of sight.
We demonstrated recently that two protons are involved in reduction of nitrite to nitric oxide through a proton-coupled electron transfer (ET) reaction catalyzed by the blue Cu-dependent nitrite ...reductase (Cu NiR) of Alcaligenes xylosoxidans (AxNiR). Here, the functionality of two putative proton channels, one involving Asn90 and the other His254, is studied using single (N90S, H254F) and double (N90S–H254F) mutants. All mutants studied are active, indicating that protons are still able to reach the active site. The H254F mutation has no effect on the catalytic activity, while the N90S mutation results in ∼70% decrease in activity. Laser flash-photolysis experiments show that in H254F and wild-type enzyme electrons enter at the level of the T1Cu and then redistribute between the two Cu sites. Complete ET from T1Cu to T2Cu occurs only when nitrite binds at the T2Cu site. This indicates that substrate binding to T2Cu promotes ET from T1Cu, suggesting that the enzyme operates an ordered mechanism. In fact, in the N90S and N90S–H254F variants, where the T1Cu site redox potential is elevated by ∼60 mV, inter-Cu ET is only observed in the presence of nitrite. From these results it is evident that the Asn90 channel is the main proton channel in AxNiR, though protons can still reach the active site if this channel is disrupted. Crystallographic structures provide a clear structural rationale for these observations, including restoration of the proton delivery via a significant movement of the loop connecting the T1Cu ligands Cys130 and His139 that occurs on binding of nitrite. Notably, a role for this loop in facilitating interaction of cytochrome c 551 with Cu NiR has been suggested previously based on a crystal structure of the binary complex.
•Emotional reactivity was reduced in late puberty with testosterone suppression.•GnRHa + testosterone led to greater approach and less avoidance behavior.•Familiarity preferences increased ...post-puberty with GnRHa + testosterone treatment.•Peripubertal GnRH + testosterone modulated motivation to approach/avoid objects.
Chronic gonadotropin-releasing hormone agonist (GnRHa) treatment is effective for the medical suppression of the hypothalamic-pituitary-gonadal axis in situations like central precocious puberty and gender dysphoria. However, its administration during the peripubertal period could influence normal brain development and function because GnRH receptors are expressed in brain regions that regulate emotions, cognition, motivation and memory. This study used an ovine model to determine whether chronic peripubertal GnRHa-treatment affected the developmental shift from preference of familiarity to novelty. Experimental groups included Controls and GnRHa-treated rams. To differentiate between effects of altered GnRH signaling and those associated with the loss of sex steroids, a group was also included that received testosterone replacement as well as GnRHa (GnRHa + T). Preference for a novel versus familiar object was assessed during 5-min social isolation at 8, 28 and 46 weeks of age. Approach behavior was measured as interactions with and time spent near the objects, whereas avoidance behavior was measured by time spent in the entrance zone and attempts to escape the arena via the entry point. Emotional reactivity was measured by the number of vocalizations, escape attempts and urinations. As Control and GnRHa-treated rams aged, their approach behaviors showed a shift from preference for familiarity (8 weeks) to novelty (46 weeks). In contrast, relative to the Controls the GnRHa + T rams exhibited more approach behaviors towards both objects, at 28 and 46 weeks of age and preferred familiarity at 46 weeks of age. Vocalisation rate was increased in GnRHa treated rams in late puberty (28 weeks) compared to both Control and GnRHa + T rams but this effect was not seen in young adulthood (46 weeks). These results suggest that the specific suppression of testosterone during a developmental window in late puberty may reduce emotional reactivity and hamper learning a flexible adjustment to environmental change. The results also suggest that disruption of either endogenous testosterone signalling or a synergistic action between GnRH and testosterone signalling, may delay maturation of cognitive processes (e.g. information processing) that affects the motivation of rams to approach and avoid objects.
Highlights • Peripubertal GnRHa impaired long-term spatial reference memory. • This GnRHa-effect was not counteracted with testosterone replacement in rams. • Traverse times of spatial orientation ...and learning tasks were unaffected by GnRHa. • GnRHa exaggerated emotional reactivity during these spatial tasks. • Testosterone replacement decreased emotional reactivity and motivation in tasks.
Little information exists about mobile phone usage or preferences for tuberculosis (TB) related health communications in Uganda.
We surveyed household contacts of TB patients in urban Kampala, ...Uganda, and clinic patients in rural central Uganda. Questions addressed mobile phone access, usage, and preferences for TB-related communications. We collected qualitative data about messaging preferences.
We enrolled 145 contacts and 203 clinic attendees. Most contacts (58%) and clinic attendees (75%) owned a mobile phone, while 42% of contacts and 10% of clinic attendees shared one; 94% of contacts and clinic attendees knew how to receive a short messaging service (SMS) message, but only 59% of contacts aged 45 years (vs. 96% of contacts aged <45 years, P = 0.0001) did so. All contacts and 99% of clinic attendees were willing and capable of receiving personal-health communications by SMS. Among contacts, 55% preferred detailed messages disclosing test results, while 45% preferred simple messages requesting a clinic visit to disclose results.
Most urban household TB contacts and rural clinic attendees reported having access to a mobile phone and willingness to receive TB-related personal-health communications by voice call or SMS. However, frequent phone sharing and variable messaging abilities and preferences suggest a need to tailor the design and monitoring of mHealth interventions to target recipients.
Highlights • Peripubertal GnRHa impaired long-term spatial memory. • This impairment was not reversed after discontinuing GnRHa-treatment. • Spatial orientation and learning performance remained ...unaffected following GnRHa withdrawal. • Speed of progression through these spatial tasks was altered after discontinuing GnRHa. • GnRH irreversibly alters these cognitive functions during critical window of development
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