Highly nondegenerate four-wave mixing and gain nonlinearity in a strained multiple-quantum-well optical amplifier

Highly nondegenerate four-wave mixing was investigated in a 1.5 µm compressively strained multi-quantum-well semiconductor traveling-wave optical amplifier at detuning frequencies up to 600 GHz. A gain nonlinearity with a characteristic relaxation time of 650 fs was determined from the data, and the nonlinear gain coefficient was estimated to be 4.3×10^–23 m^3. Dynamic carrier heating is believed to be the major source of nonlinear gain in this device at the wavelengths investigated

Effect of testosterone metabolites on ABC half-transporter relative gene expression in X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder associated with reduced very long-chain fatty acid beta-oxidation, mainly affecting the nervous system, the adrenal cortex and the testes. The clinical manifestations of hypogonadism, alopecia and the impairment of the enzyme 5alpha-reductase, which converts testosterone into dihydrotestosterone, clearly point to an involvement of androgens in this pathology. The disease is characterized by mutations in the ABCD1 gene, which codes for the peroxisomal ABC half-transporter ALDP, and by a broad range of clinical manifestations. The altered function of ALDP can be compensated by the overexpression of proteins belonging to the same family of ABC half-transporters. A promising therapeutic approach is represented by the activation of these proteins by specific agonists. In this study we evaluated the effect of the testosterone metabolite dihydrotestosterone (DHT) and 5alpha-androstan-3alpha,17beta-diol (3alpha-diol) on the expression of the ABC half-transporters encoded by the ABCD2 and ABCD3 genes, in fibroblasts drawn from controls and from two affected brothers. The two patients presented the same mutation in exon 9 but had different clinical manifestations, one patient being asymptomatic and the second one severely affected. When the cells were stimulated with testosterone metabolites, only the severely affected patient showed a significant increase in ABCD2 mRNA levels, while the ABCD3 expression remained unchanged in both patients

hypomyelination and congenital cataract neuroimaging features of a novel inherited white matter disorder

BACKGROUND AND PURPOSE: Hypomyelination and congenital cataract (HCC) is an autosomal recessive white matter disease caused by deficiency of hyccin, a membrane protein implicated in both central and peripheral myelination. We aimed to describe the neuroimaging features of this novel entity. MATERIALS AND METHODS: A systematic analysis of patients with unclassified leukoencephalopathies admitted to our institutions revealed 10 children with congenital cataract, slowly progressive neurologic impairment, and diffuse white matter abnormalities on neuroimaging. Psychomotor developmental delay was evident after the first year of life. Peripheral neuropathy was demonstrated by neurophysiologic studies in 9 children. The available neuroimaging studies were retrospectively reviewed. RESULTS: In all patients, neuroimaging revealed diffuse involvement of the supratentorial white matter associated with preservation of both cortical and deep gray matter structures. Supratentorial white matter hypomyelination was detected in all patients; 7 patients also had evidence of variably extensive areas of increased white matter water content. Deep cerebellar white matter hypomyelination was found in 6 patients. Older patients had evidence of white matter bulk loss and gliosis. Proton MR spectroscopy showed variable findings, depending on the stage of the disease. Sural nerve biopsy revealed hypomyelinated nerve fibers. Mutations in the DRCTNNB1A gene on chromosome 7p15.3, causing complete or severe deficiency of hyccin, were demonstrated in all patients. CONCLUSIONS: HCC is characterized by a combined pattern of primary myelin deficiency and secondary neurodegenerative changes. In the proper clinical setting, recognition of suggestive neuroimaging findings should prompt appropriate genetic investigations

Encephalitozoon cuniculi

This is the first confirmed report of Encephalitozoon cuniculi (E. cuniculi) in farm meat rabbits located in Northern Mexico. Eighty young rabbits exhibited clinical signs of this zoonotic emerging disease, like torticollis, ataxia, paresis, circling, and rolling. Samples of brain, kidney, and liver were examined for histology lesions. For the first time the lesions caused by E. cuniculi were graded according to their severity (I, II, and III) and the size of the granulomas (Types A, B, and C). The main cerebral injuries were Grade III, coinciding with the presence of Type C granulomas. The cerebral lesions were located in the cortex, brain stem, and medulla. The renal lesions were also Grade III distributed throughout cortex and renal medulla, with no granuloma formation. The involvement of hypersensitivity Types III and IV is suggested. All of the rabbits were seropositive to E. cuniculi by CIA testing, suggesting that this zoonotic and emerging pathogen is widely distributed among animals intended for human consumption. We believe this work could be used as a guide when examining E. cuniculi and will provide direction to confirm the diagnosis of this pathogen

Telomere shortening may be associated with human keloids

<p>Abstract</p> <p>Background</p> <p>Keloids are benign skin tumors that are the effect of a dysregulated wound-healing process in genetically predisposed patients. They are inherited with an autosomal dominant mode with incomplete clinical penetrance and variable expression. Keloids are characterized by formation of excess scar tissue beyond the boundaries of the wound. The exact etiology is still unknown and there is currently no appropriate treatment for keloid disease.</p> <p>Methods</p> <p>We analyzed sample tissues were obtained from 20 patients with keloid skin lesions and normal skin was obtained from 20 healthy donors. The telomeres were measured by Terminal Restriction Fragment (TRF) analysis and Real-Time PCR assay. Quantitative Real-Time RT-PCR analysis of hTERT gene expression was performed and intracellular ROS generation was measured.</p> <p>Results</p> <p>In this study, we determined whether telomeric shortening and the expression of human telomerase reverse transcriptase (hTERT) occurs in keloid patients. Using Terminal Restriction Fragment (TRF) analysis and Real-Time PCR assay, we detected a significant telomere shortening of 30% in keloid specimens compared to normal skin. Using quantitative Real-Time RT-PCR, telomerase activity was found absent in the keloid tissues. Moreover, an increase in ROS generation was detected in fibroblasts cell cultures from keloid specimens as more time elapsed compared to fibroblasts from normal skin.</p> <p>Conclusion</p> <p>Telomere shortening has been reported in several metabolic and cardiovascular diseases. We found that telomere shortening can also be associated with human keloids. Chronic oxidative stress plays a major role in the pathophysiology of several chronic inflammatory diseases. Here we found increased ROS generation in fibroblasts from keloid fibroblasts cell cultures when compared to normal skin fibroblasts. Hence we conclude that oxidative stress might be an important modulator of telomere loss in keloid because of the absence of active telomerase that counteracts telomere shortening.</p

The miR-17 similar to 92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma

Medulloblastomas (MBs) are the most common brain tumors in children. Some are thought to originate from cerebellar granule neuron progenitors (GNPs) that fail to undergo normal cell cycle exit and differentiation. Because microRNAs regulate numerous aspects of cellular physiology and development, we reasoned that alterations in miRNA expression might contribute to MB. We tested this hypothesis using 2 spontaneous mouse MB models with specific initiating mutations, Ink4c(-/-); Ptch1(+/-) and Ink4c(-/-); p53(-/-). We found that 26 miRNAs showed increased expression and 24 miRNAs showed decreased expression in proliferating mouse GNPs and MBs relative to mature mouse cerebellum, regardless of genotype. Among the 26 overexpressed miRNAs, 9 were encoded by the miR-17 similar to 92 cluster family, a group of microRNAs implicated as oncogenes in several tumor types. Analysis of human MBs demonstrated that 3 miR-17 similar to 92 cluster miRNAs (miR-92, miR-19a, and miR-20) were also overexpressed in human MBs with a constitutively activated Sonic Hedgehog (SHH) signaling pathway, but not in other forms of the disease. To test whether the miR-17 similar to 92 cluster could promote MB formation, we enforced expression of these miRNAs in GNPs isolated from cerebella of postnatal (P) day P6 Ink4c(-/-); Ptch1(+/-) mice. These, but not similarly engineered cells from Ink4c(-/-); p53(-/-) mice, formed MBs in orthotopic transplants with complete penetrance. Interestingly, orthotopic mouse tumors ectopically expressing miR-17 similar to 92 lost expression of the wild-type Ptch1 allele. Our findings suggest a functional collaboration between the miR-17 similar to 92 cluster and the SHH signaling pathway in the development of MBs in mouse and man

Anisotropic flow at RHIC: How unique is the number-of-constituent-quark scaling?

The transverse momentum dependence of the anisotropic flow $v_2$ for $\pi$, $K$, nucleon, $\Lambda$, $\Xi$ and $\Omega$ is studied for Au+Au collisions at $\sqrt{s_{\rm NN}} = 200$ GeV within two independent string-hadron transport approaches (RQMD and UrQMD). Although both models reach only 60% of the absolute magnitude of the measured $v_2$, they both predict the particle type dependence of $v_2$, as observed by the RHIC experiments: $v_2$ exhibits a hadron-mass hierarchy (HMH) in the low $p_T$ region and a number-of-constituent-quark (NCQ) dependence in the intermediate $p_T$ region. The failure of the hadronic models to reproduce the absolute magnitude of the observed $v_2$ indicates that transport calculations of heavy ion collisions at RHIC must incorporate interactions among quarks and gluons in the early, hot and dense phase. The presence of an NCQ scaling in the string-hadron model results suggests that the particle-type dependencies observed in heavy-ion collisions at intermediate $p_T$ might be related to the hadronic cross sections in vacuum rather than to the hadronization process itself.Comment: 10 pages, 5 figures; A new author (H. Petersen) is added; A new figure (fig.1) on time evolution of elliptic flow and number of collisions is added; Version accepted for publication in J. Phys.