A closer look at ARSA activity in a patient with metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease mainly caused by a deficiency of arylsulfatase A activity. The typical clinical course of patients with the late infantile form includes a regression in motor skills with progression to dysphagia, seizures, hypotonia and death. We present a case of a 4-year-old female with rapidly progressive developmental regression with loss of motor milestones, spasticity and dysphagia. MRI showed volume loss and markedly abnormal deep white matter. Enzymatic testing in one laboratory showed arylsulfatase A activity in their normal range. However, extraction of urine showed a large increase in sulfatide excretion in a second laboratory. Measurement of arylsulfatase A in that laboratory showed a partial decrease in arylsulfatase A activity measured under typical conditions (about 37% of the normal mean). When the concentration of substrate in the assay was lowered to one quarter of that normally used, this individual had activity \u3c10% of controls. The patient was found to be homozygous for an unusual missense mutation in the arylsulfatase A gene confirming the diagnosis of MLD. This case illustrates the importance of careful biochemical and molecular testing for MLD if there is suspicion of this diagnosis

Correlation of the middle Eocene Kellogg Shale of northern California

The Kellogg Shale of northern California has traditionally been considered to be late Eocene in age on the basis of benthic foraminifer, radiolarian, and diatom correlations. The 30-m-thick Kellogg section exposed west of Byron, California, however, contains middle Eocene planktonic foraminifers (Zone P12), coccoliths (Subzones CP13c and CP14a), silicoflagellates (Dictyocha hexacantha Zone), and diatoms. Quantitative studies of the silicoflagellates and diatoms show a general cooling trend through the section which is consistent with paleoclimatic trends for this part of the middle Eocene (ca. 42-45 Ma) from elsewhere in the world. Seven new silicoflagellate taxa (Corbisema angularis. C, exilis, C, hastate miranda, C. inermis ballantina, C. regina, Dictyocha byronalis, Naviculopsis Americana) and one new coccolithophorid species (Helicosphaera neolophota) are described

Chiral discrimination in optical binding

The laser-induced intermolecular force that exists between two or more particles in the presence of an electromagnetic field is commonly termed “optical binding.” Distinct from the single-particle forces that are at play in optical trapping at the molecular level, the phenomenon of optical binding is a manifestation of the coupling between optically induced dipole moments in neutral particles. In other, more widely known areas of optics, there are many examples of chiral discrimination—signifying the different response a chiral material has to the handedness of an optical input. In the present analysis, extending previous work on chiral discrimination in optical binding, a mechanism is identified using a quantum electrodynamical approach. It is shown that the optical binding force between a pair of chiral molecules can be significantly discriminatory in nature, depending upon both the handedness of the interacting particles and the polarization of the incident light, and it is typically several orders of magnitude larger than previously reported

Chiral discrimination in optical trapping and manipulation

When circularly polarized light interacts with chiral molecules or nanoscale particles powerful symmetry principles determine the possibility of achieving chiral discrimination, and the detailed form of electrodynamic mechanisms dictate the types of interaction that can be involved. The optical trapping of molecules and nanoscale particles can be described in terms of a forward-Rayleigh scattering mechanism, with trapping forces being dependent on the positioning within the commonly non-uniform intensity beam profile. In such a scheme, nanoparticles are commonly attracted to local potential energy minima, ordinarily towards the centre of the beam. For achiral particles the pertinent material response property usually entails an electronic polarizability involving transition electric dipole moments. However, in the case of chiral molecules, additional effects arise through the engagement of magnetic counterpart transition dipoles. It emerges that, when circularly polarized light is used for the trapping, a discriminatory response can be identified between left- and right-handed polarizations. Developing a quantum framework to accurately describe this phenomenon, with a tensor formulation to correctly represent the relevant molecular properties, the theory leads to exact analytical expressions for the associated energy landscape contributions. Specific results are identified for liquids and solutions, both for isotropic media and also where partial alignment arises due to a static electric field. The paper concludes with a pragmatic analysis of the scope for achieving enantiomer separation by such methods

The origin of the parrotfish species Scarus compressus in the Tropical Eastern Pacific: region-wide hybridization between ancient species pairs

BACKGROUND: In the Tropical Eastern Pacific (TEP), four species of parrotfishes with complex phylogeographic histories co-occur in sympatry on rocky reefs from Baja California to Ecuador: Scarus compressus, S. ghobban, S. perrico, and S. rubroviolaceus. The most divergent, S. perrico, separated from a Central Indo-Pacific ancestor in the late Miocene (6.6 Ma). We tested the hypothesis that S. compressus was the result of ongoing hybridization among the other three species by sequencing four nuclear markers and a mitochondrial locus in samples spanning 2/3 of the latitudinal extent of the TEP. RESULTS: A Structure model indicated that K = 3 fit the nuclear data and that S. compressus individuals had admixed genomes. Our data could correctly detect and assign pure adults and F1 hybrids with > 0.90 probability, and correct assignment of F2s was also high in some cases. NewHybrids models revealed that 89.8% (n = 59) of the S. compressus samples were F1 hybrids between either S. perrico × S. ghobban or S. perrico × S. rubroviolaceus. Similarly, the most recently diverged S. ghobban and S. rubroviolaceus were hybridizing in small numbers, with half of the admixed individuals assigned to F1 hybrids and the remainder likely > F1 hybrids. We observed strong mito-nuclear discordance in all hybrid pairs. Migrate models favored gene flow between S. perrico and S. ghobban, but not other species pairs. CONCLUSIONS: Mating between divergent species is giving rise to a region-wide, multispecies hybrid complex, characterized by a high frequency of parental and F1 genotypes but a low frequency of > F1 hybrids. Trimodal structure, and evidence for fertility of both male and female F1 hybrids, suggest that fitness declines sharply in later generation hybrids. In contrast, the hybrid population of the two more recently diverged species had similar frequencies of F1 and > F1 hybrids, suggesting accelerating post-mating incompatibility with time. Mitochondrial genotypes in hybrids suggest that indiscriminate mating by male S. perrico is driving pre-zygotic breakdown, which may reflect isolation of this endemic species for millions of years resulting in weak selection for conspecific mate recognition. Despite overlapping habitat use and high rates of hybridization, species boundaries are maintained by a combination of pre- and post-mating processes in this complex

Coronary artery caliber in normal children and patients with Kawasaki disease but without aneurysms: An echocardiographic and angiographic study

A total of 110 children aged 3 months to 16 years underwent two-dimensional echocardiography of the coronary arteries. Forty-two normal subjects and 68 patients with Kawasaki disease were evaluated. All 68 patients with Kawasaki disease underwent selective coronary arteriography. The objectives of this study were to 1) develop a normal profile of the proximal left and right coronary arteries as to caliber and shape in infants, toddlers and children using echocardiography; 2) compare the dimensions and shape of the coronary arteries of patients with Kawasaki disease but no obvious aneurysms with those of the coronary arteries of normal children; and 3) develop criteria that would permit distinguishing a large but normal coronary artery from a true aneurysm in patients with Kawasaki disease.In the normal subjects and patients with Kawasaki disease, the caliber of the coronary arteries showed little variability from the ostium to 10 mm distally, and ranged in size from 2 mm in infants to 5 mm in teenagers. There was no significant difference between male and female subjects. The feature that distinguished the large but normal coronary artery without aneurysm from that with an aneurysm was its uniformity of caliber. Also, the caliber of the opposite coronary artery was generally at the lower limits of normal. It appears that the proximal coronary arteries of infants and children can be accurately assessed using high resolution two-dimensional echocardiography, and that sequential evaluation of subtle changes over time may be performed

Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

<p>Abstract</p> <p>Background</p> <p>It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis.</p> <p>Methods</p> <p>We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body ¹⁸F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression.</p> <p>Results</p> <p>No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.</p

Spin-orbit interactions and chiroptical effects engaging orbital angular momentum of twisted light in chiral and achiral media

There is recurrent interest in the orbital angular momentum (OAM) conveyed by optical vortices, which are structured beams with a helically twisted wave front. Particular significance is attached to the issue of how material interactions with light conveying OAM might prove sensitive to the handedness and degree of twist in the optical wave front. As a result of recent experimental and theoretical studies, the supposition that beams with OAM might enable spectroscopic discrimination between oppositely handed forms of matter has become a renewed focus of attention. Some of the tantalizing conclusions that are beginning to emerge from this research have, however, not yet established a definitive basis for a supporting mechanism. To resolve this problem requires the development of theory to support a faithful representation, and a thorough understanding, of the fundamental molecule-photon physics at play in such optical processes - even for processes as basic as absorption. The present analysis establishes mechanisms at play that entail an unconventional manifestation of optical spin-orbit interactions, engaging transition electric-quadrupole moments. Powerful symmetry principles prove to render distinctively different criteria governing the exhibition of two-dimensional (2D) and 3D chirality. These results elucidate the operation of such effects, identifying their responsibility for discriminatory optical interactions of various forms in both chiral and achiral media