Discovery of the Interstellar Chiral Molecule Propylene Oxide (CH3_3CHCH2_2O)

Life on Earth relies on chiral molecules, that is, species not superimposable on their mirror images. This manifests itself in the selection of a single molecular handedness, or homochirality, across the biosphere. We present the astronomical detection of a chiral molecule, propylene oxide (CH$_3$CHCH$_2$O), in absorption toward the Galactic Center. Propylene oxide is detected in the gas phase in a cold, extended molecular shell around the embedded, massive protostellar clusters in the Sagittarius B2 star-forming region. This material is representative of the earliest stage of solar system evolution in which a chiral molecule has been found

Retinal Architecture in ​\u3cem\u3eRGS9-\u3c/em\u3e and ​\u3cem\u3eR9AP\u3c/em\u3e-Associated Retinal Dysfunction (Bradyopsia)

Purpose To characterize photoreceptor structure and mosaic integrity in subjects with RGS9- and R9AP-associated retinal dysfunction (bradyopsia) and compare to previous observations in other cone dysfunction disorders such as oligocone trichromacy. Design Observational case series. Methods setting: Moorfields Eye Hospital (United Kingdom) and Medical College Wisconsin (USA). study population: Six eyes of 3 subjects with disease-causing variants in RGS9 or R9AP. main outcome measures: Detailed retinal imaging using spectral-domain optical coherence tomography and confocal adaptive-optics scanning light ophthalmoscopy. Results Cone density at 100 μm from foveal center ranged from 123 132 cones/mm2to 140 013 cones/mm2. Cone density ranged from 30 573 to 34 876 cones/mm2 by 600 μm from center and from 15 987 to 16,253 cones/mm2 by 1400 μm from center, in keeping with data from normal subjects. Adaptive-optics imaging identified a small, focal hyporeflective lesion at the foveal center in both eyes of the subject with RGS9-associated disease, corresponding to a discrete outer retinal defect also observed on spectral-domain optical coherence tomography; however, the photoreceptor mosaic remained intact at all other observed eccentricities. Conclusions Bradyopsia and oligocone trichromacy share common clinical symptoms and cannot be discerned on standard clinical findings alone. Adaptive-optics imaging previously demonstrated a sparse mosaic of normal wave-guiding cones remaining at the fovea, with no visible structure outside the central fovea in oligocone trichromacy. In contrast, the subjects presented in this study with molecularly confirmed bradyopsia had a relatively intact and structurally normal photoreceptor mosaic, allowing the distinction between these disorders based on the cellular phenotype and suggesting different pathomechanisms

CSO and CARMA Observations of L1157. I. A Deep Search for Hydroxylamine (NH2_2OH)

A deep search for the potential glycine precursor hydroxylamine (NH$_2$OH) using the Caltech Submillimeter Observatory (CSO) at $\lambda = 1.3$ mm and the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at $\lambda = 3$ mm is presented toward the molecular outflow L1157, targeting the B1 and B2 shocked regions. We report non-detections of NH$_2$OH in both sources. We a perform non-LTE analysis of CH$_3$OH observed in our CSO spectra to derive kinetic temperatures and densities in the shocked regions. Using these parameters, we derive upper limit column densities of NH$_2$OH of $\leq1.4 \times 10^{13}$~cm$^{-2}$ and $\leq1.5 \times 10^{13}$~cm$^{-2}$ toward the B1 and B2 shocks, respectively, and upper limit relative abundances of $N_{NH_2OH}/N_{H_2} \leq1.4 \times 10^{-8}$ and $\leq1.5 \times 10^{-8}$, respectively.Comment: Accepted in the Astrophysical Journa

Detecting co-cultivation induced chemical diversity via 2D NMR fingerprints

Rediscovery of already known compounds is a major issue in microbial natural product drug discovery. In recent years, progress has been made in developing more efficient analytical approaches that quickly identify known compounds in a sample to minimise rediscovery. In parallel, whole genome sequencing of microorganisms has revealed their immense potential to produce secondary metabolites, yet the majority of biosynthetic genes remain silent under common laboratory culturing conditions. Therefore, increased research has focused on optimising culturing methods to activate the silent biosynthetic gene clusters. Co-cultivation of different microbial strains can activate biosynthetic gene clusters that remain silent under standard laboratory fermentations involving monocultures, hence, the technique has great potential for natural product drug discovery. However, innovative methods are still needed to evaluate the success of any cocultured fermentation end-product. Here, the application of HSQC-TOCSY NMR spectra and subsequent PCoA to identify changes in the metabolite diversity induced through co-cultivation is described

Out of equilibrium: understanding cosmological evolution to lower-entropy states

Despite the importance of the Second Law of Thermodynamics, it is not absolute. Statistical mechanics implies that, given sufficient time, systems near equilibrium will spontaneously fluctuate into lower-entropy states, locally reversing the thermodynamic arrow of time. We study the time development of such fluctuations, especially the very large fluctuations relevant to cosmology. Under fairly general assumptions, the most likely history of a fluctuation out of equilibrium is simply the CPT conjugate of the most likely way a system relaxes back to equilibrium. We use this idea to elucidate the spacetime structure of various fluctuations in (stable and metastable) de Sitter space and thermal anti-de Sitter space.Comment: 27 pages, 11 figure

Dark Energy or Apparent Acceleration Due to a Relativistic Cosmological Model More Complex than FLRW?

We use the Szekeres inhomogeneous relativistic models in order to fit supernova combined data sets. We show that with a choice of the spatial curvature function that is guided by current observations, the models fit the supernova data almost as well as the LCDM model without requiring a dark energy component. The Szekeres models were originally derived as an exact solution to Einstein's equations with a general metric that has no symmetries and are regarded as good candidates to model the true lumpy universe that we observe. The null geodesics in these models are not radial. The best fit model found is also consistent with the requirement of spatial flatness at CMB scales. The first results presented here seem to encourage further investigations of apparent acceleration using various inhomogeneous models and other constraints from CMB and large structure need to be explored next.Comment: 6 pages, 1 figure, matches version published in PR

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness and Oguchi Disease

Purpose To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. Design Prospective, observational case series. Methods We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. Results Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. Conclusions The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus

α-Synuclein aggregation inhibitory activity of the bromotyrosine derivatives aerothionin and aerophobin-2 from the subtropical marine sponge Aplysinella sp

The neuronal protein α-synuclein (α-syn) is one of the main constituents of intracellular amyloid aggregations found in the post-mortem brains of Parkinson’s disease (PD) patients. Recently, we screened the MEOH extracts obtained from 300 sub-tropical marine invertebrates for α-syn binding activity using affinity MS and this resulted in the extract of the Verongida marine sponge Aplysinella sp. 1194, (QM G339263) displaying molecules that bind to the protein. The subsequent bioassay-guided separation of the Aplysinella sp. extract led to the isolation of the known bromotyrosine derivatives (+)-aerothionin (1) and (+)-aerophobin-2 (2). Both compounds bind to α-syn as detected by a MS affinity assay and inhibit α-syn aggregation in an assay that uses the fluorescence probe, thioflavin T, to detect aggregation. (+)-Aerothionin (1) was toxic to primary dopaminergic neurons at its expected α-syn aggregation inhibitory concentration and so could not be tested for pSyn aggregates in this functional assay. (+)-Aerophobin-2 (2) was not toxic and shown to weakly inhibit pSyn aggregation in primary dopaminergic neurons at 10 µM.Peer reviewe

Characterization of Retinal Structure in ATF6-Associated Achromatopsia.

PurposeMutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM.MethodsSeven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM.ResultsFoveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports.ConclusionsOur data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM