Description and pathology of a new genus and species of fish blood fluke (Digenea: Aporocotylidae Odhner, 1912) infecting white mullet, Mugil curema Valenciennes, 1836 (Mugiliformes: Mugilidae) in Mobile Bay (northern Gulf of Mexico) with a phylogenetic analysis.

Three fish blood flukes (Aporocotylidae Odhner, 1912) infect mullets (Mugiliformes: Mugilidae): Cardicola mugilis Yamaguti, 1970 and Plethorchis acanthus Martin, 1975 infect striped mullet, Mugil cephalus Linnaeus, 1758 in the Central Pacific Ocean (Hawaiian Islands) and Brisbane River (Australia), respectively; Cardicola brasiliensis Knoff & Amato, 1992 infects Lebranche mullet, Mugil liza Valenciennes, 1836 from the Southwestern Atlantic Ocean (Brazil). White mullets were cast-netted from the mouth of Deer River, a coastal saltmarsh of Mobile Bay, in the north-central Gulf of Mexico and examined for blood fluke infections. Specimens of Mugilitrema labowskiae Warren & Bullard n. gen., n. sp. were found infecting the endocardial surface and inter-trabecular spaces of the atrium, ventricle, and bulbous arteriosus. The new genus and species differ from all other aporocotylids by having the combination of two post-caecal testes, a uterus with straight ascending and descending portions, and a common genital pore. The 28S analysis recovered the new species and P.acanthus as sister taxa and Aporocotylidae as monophyletic. Carditis associated with intense infections comprised endocardial hyperplasia, resulting in a thickened cardiac endothelium. Probable dead or deteriorating eggs in the myocardium were encapsulated by granulomas composed of epithelioid histiocytes. Live eggs infected the afferent artery of gill filaments and were associated with varied hyperplasia of the overlying epithelium and haemorrhaging from the afferent artery in high-intensity infections. The new species is the first aporocotylid infecting a mullet from the northwestern Atlantic Ocean and only the second description of demonstrable endocarditis attributed to an adult fish blood fluke infection.

ON than OFF pathway disruption leads to greater deficits in visual function and retinal dopamine signaling.

The visual system uses ON and OFF pathways to signal luminance increments and decrements. Increasing evidence suggests that ON and OFF pathways have different signaling properties and serve specialized visual functions. However, it is still unclear the contribution of ON and OFF pathways to visual behavior. Therefore, we examined the effects on optomotor response and the retinal dopamine system in nob mice with ON pathway dysfunction and Vsx1-/- mice with partial OFF pathway dysfunction. Spatial frequency and contrast sensitivity thresholds were determined, and values were compared to age-matched wild-type controls. Retinas were collected immediately after visual testing to measure levels of dopamine and its metabolite, DOPAC. At 4 weeks of age, we found that nob mice had significantly reduced spatial frequency (19%) and contrast sensitivity (60%) thresholds compared to wild-type mice. Vsx1-/- mice also exhibited reductions in optomotor responses (3% in spatial frequency; 18% in contrast sensitivity) at 4 weeks, although these changes were significantly smaller than those found in nob mice. Furthermore, nob mice had significantly lower DOPAC levels (53%) and dopamine turnover (41%) compared to controls while Vsx1-/- mice displayed a transient increase in DOPAC levels at 4 weeks of age (55%). Our results show that dysfunction of ON pathways leads to reductions in contrast sensitivity, spatial frequency threshold, and retinal dopamine turnover whereas partial loss of the OFF pathway has minimal effect. We conclude that ON pathways play a critical role in visual reflexes and retinal dopamine signaling, highlighting a potential association for future investigations.

Saccocoelioides kirchneri n. sp. (Digenea: Haploporidae) from the killifish Cnesterodon decemmaculatus (Cyprinodontiformes: Poeciliidae) from Argentina, morphological and molecular description.

This paper presents a new haploporid digenean that expands the number of species of Saccoccoelioides to 27. The new species, Saccocoelioides kirchneri n. sp. was collected from the intestine of Cnesterodon decemmaculatus (Poeciliidae: Cyprinodontiformes) from Lago del Bosque, La Plata, Argentina. The new species possesses the diagnostic features for Saccocoelioides: a sac like ceca; the vitellarium confined in two irregular groups of follicles distributed between the ventral sucker and the anterior margin of the testis; and a uterus confined largely in the hind-body, but encroaching into the range of the ventral sucker. The new species is differentiated from the 26 congeners by the body size, pharynx size, ventral sucker size, posterior extent of ceca, posterior extent of uterus and egg size. S. kirchneri n. sp. also is supported by the molecular analysis.

Prosthenhystera gattii n. sp. (Digenea: Callodistomidae), a gallbladder parasite of Bryconamericus ikaa from the lower Iguazú River, described based on combined molecular and morphological evidence.

Adult forms of members of the Callodistomidae always parasitize the gallbladder of freshwater fishes and occur in Africa and America. This study provides a description of a new South American species belonging in Prosthenhystera from the gallbladder of a characid fish (Bryconamericus ikaa), and ribosomal gene sequences (28S rDNA and ITS1-5.8S-ITS2) are used to demonstrate molecular differences between the new species and congeners as well as explore interrelationships among congeners. Additionally, the first cytological analysis is conducted for a member of the family to determine chromosome number and arrangement. Prosthenhystera gattii n. sp. most closely resembles Prosthenhystera caballeroi in morphology, but the vitellarium is more extensive reaching anterior to the caecal bifurcation in the new species and the uterus is confined to the hindbody in P. gattii n. sp., whereas it extends to the level of the pharynx in P. caballeroi. Also, the testes, cirrus sac, seminal receptacle and the ratio of body length to width are larger in P. gattii n. sp. Independent Bayesian inference analyses of 28S rDNA and ITS1-5.8S-ITS2 sequence fragments produced phylograms that showed P. gattii n. sp. is more similar to Prosthenhystera obesa + Prosthenhystera oonastica than P. caballeroi + two unidentified species of Prosthenhystera, but with poor posterior probability support for the node in the ITS1-5.8S-ITS2-based phylogram. Further, the genetic distance between P. oonastica and P. gattii n. sp. are the largest among Prosthenhystera spp. Cytological analysis revealed ten metacentric chromosomes, which is fewer than the 12-18 chromosomes present in species from the closely related Gorgoderidae.

IRBP deficiency permits precocious ocular development and myopia.

PURPOSE: Interphotoreceptor retinoid-binding protein (IRBP) is abundant in the subretinal space and binds retinoids and lipophilic molecules. The expression of IRBP begins precociously early in mouse eye development. IRBP-deficient (KO) mice show less cell death in the inner retinal layers of the retina before eyelid opening compared to wild-type C57BL/6J (WT) controls and eventually develop profound myopia. Thus, IRBP may play a role in eye development before visually-driven phenomena. We report comparative observations during the course of the natural development of eyes in WT and congenic IRBP KO mice that suggest IRBP is necessary at the early stages of mouse eye development for correct function and development to exist in later stages. METHODS: We observed the natural development of congenic WT and IRBP KO mice, monitoring several markers of eye size and development, including haze and clarity of optical components in the eye, eye size, axial length, immunohistological markers of differentiation and eye development, visually guided behavior, and levels of a putative eye growth stop signal, dopamine. We conducted these measurements at several ages. Slit-lamp examinations were conducted at post-natal day (P)21. Fundus and spectral domain optical coherence tomography (SD-OCT) images were compared at P15, P30, P45, and P80. Enucleated eyes from P5 to P10 were measured for weight, and ocular dimensions were measured with a noncontact light-emitting diode (LED) micrometer. We counted the cells that expressed tyrosine hydroxylase (TH-positive cells) at P23-P36 using immunohistochemistry on retinal flatmounts. High-performance liquid chromatography (HPLC) was used to analyze the amounts of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) at P7-P60. Monocular form deprivation in the right eye was induced using head-mounted goggles from P28 to P56. RESULTS: Eye elongation and eye size in the IRBP KO mice began to increase at P7 compared to the WT mice. This difference increased until P12, and the difference was maintained thereafter. SD-OCT images in live mice confirmed previously reported retinal thinning of the outer nuclear layer in the IRBP KO mice compared to the WT mice from P15 to P80. Slit-lamp and fundoscopy examination outcomes did not differ between the WT and KO mice. SD-OCT measurements of the optical axis components showed that the only factor contributing to excess optical axis length was the depth of the vitreous body. No other component of optical axis length (including corneal thickness, anterior chamber depth, and lens thickness) was different from that of the WT mouse. The refractive power of the IRBP KO mice did not change in response to form deprivation. The number of retinal TH-positive cells was 28% greater in the IRBP KO retinas compared to the WT mice at P30. No significant differences were observed in the steady-state retinal DA or DOPAC levels or in the DOPAC/DA ratios between the WT and IRBP KO mice. CONCLUSIONS: The IRBP KO mouse eye underwent precocious development and rapid eye size growth temporally about a day sooner than the WT mouse eye. Eye size began to differ between the WT and KO mice before eyelid opening, indicating no requirement for focus-dependent vision, and suggesting a developmental abnormality in the IRBP KO mouse eye that precedes form vision-dependent emmetropization. Additionally, the profoundly myopic KO eye did not respond to form deprivation compared to the non-deprived contralateral eye. Too much growth occurred in some parts of the eye, possibly upsetting a balance among size, differentiation, and focus-dependent growth suppression. Thus, the loss of IRBP may simply cause growth that is too rapid, possibly due to a lack of sequestration or buffering of morphogens that normally would bind to IRBP but are unbound in the IRBP KO eye. Despite the development of profound myopia, the DA levels in the IRBP KO mice were not statistically different from those in the WT mice, even with the excess of TH-positive cells in the IRBP KO mice compared to the WT mice. Overall, these data suggest that abnormal eye elongation in the IRBP KO mouse is independent of, precedes, and is epistatic to the process(es) of visually-driven refractive development.

ON pathway mutations increase susceptibility to form-deprivation myopia.

The ON pathway mutation in nob mice is associated with altered refractive development, and an increased susceptibility to form-deprivation (FD) myopia. In this study, we used mGluR6-/- mice, another ON pathway mutant, to determine whether the nob phenotype was due to the Nyx mutation or abnormal ON pathway transmission. Refractive development under a normal visual environment for mGluR6-/- and age-matched wild-type (WT) mice was measured every 2 weeks from 4 to 16 weeks of age. The response to monocular FD from 4 weeks of age was measured weekly in a separate cohort of mice. Refraction and ocular biometry were obtained using a photorefractor and optical coherence tomography. Retinas were harvested at 16 weeks, and analyzed for dopamine (DA) and DOPAC using high-performance liquid chromatography. Under normal conditions, mGluR6-/- mice were significantly more myopic than their WT controls (refraction at 12 weeks; WT: 9.40 ± 0.16 D, mGluR6-/-: 6.91 ± 0.38 D). Similar to nob mice, two weeks of FD resulted in a significant myopic shift of -5.57 ± 0.72 D in mGluR6-/- mice compared to -1.66 ± 0.19 D in WT animals. No significant axial length changes were observed with either normal or FD visual conditions. At 16 weeks, mGluR6-/- retinas showed significantly lower DOPAC levels (111.2 ± 33.0 pg/mg) compared to their WT counterparts (197.5 ± 11.2 pg/mg). Retinal DA levels were similar between the different genotypes. Our results indicate that reduced retinal DA metabolism/turnover may be associated with increased susceptibility to myopia in mice with ON pathway defect mutations.

Comparison of refractive development and retinal dopamine in OFF pathway mutant and C57BL/6J wild-type mice.

PURPOSE: Proper visual transmission depends on the retinal ON and OFF pathways. We used Vsx1-/- mice with a retinal OFF visual pathway defect to determine the role of OFF pathway signaling in refractive development (RD) of the eye. METHODS: Refractive development was measured every 2 weeks in Vsx1-/-, Vsx1+/+ (both on 129S1/Sv background), and commonly used C57BL/6J mice from 4 to 12 weeks of age. Form deprivation (FD) was induced monocularly from 4 weeks of age using head-mounted diffuser goggles. Refractive state, corneal curvature, and ocular biometry were obtained weekly using photorefraction, keratometry, and 1310 nm spectral-domain optical coherence tomography. Retinal dopamine and its metabolite, 3,4-dihydroxyphenylacetate (DOPAC), were measured using high-performance liquid chromatography (HPLC). RESULTS: During normal development, the Vsx1-/- and Vsx1+/+ mice showed similar myopic refractions at younger ages (4 weeks, Vsx1-/-: -5.28±0.75 diopter (D); WT: -4.73±0.98 D) and became significantly hyperopic by 12 weeks of age (Vsx1-/-: 3.28±0.82 D; WT: 5.33±0.81 D). However, the C57BL/6J mice were relatively hyperopic at younger ages (mean refraction at 4 weeks, 3.40±0.43 D), and developed more hyperopic refractions until about 7 weeks of age (8.07±0.55 D) before stabilizing. Eight weeks of FD did not induce a myopic shift in the 129S1/Sv animals (0.16±0.85 D), as opposed to a significant shift of -4.29±0.42 D in the C57BL/6J mice. At 4 weeks of visual development, dopamine turnover (the DOPAC/dopamine ratio) was significantly greater in the 129S1/Sv mice compared to the C57BL/6J mice. FD did not alter the levels of dopamine between the goggled and opposite eyes for any genotype or strain. CONCLUSIONS: OFF pathway signaling may not be critically important for normal refractive development in mice. Elevated retinal dopamine turnover in early refractive development may prevent FD myopia in 129S1/Sv mice compared to C57BL/6J mice.

Relative validity of a food frequency questionnaire to assess nutrient intake in pregnant women.

BACKGROUND: To date, there are no food frequency questionnaires that have been validated to assess nutrient intakes in pregnant women in Ireland. The present study aimed to assess the relative validity of a self-administered food frequency questionnaire during pregnancy. METHODS: The food frequency questionnaire was administered once during pregnancy between 12 and 34 weeks. Participants also completed a 3-day food diary during each trimester of pregnancy (reference method) and intakes from both the food frequency questionnaire and the mean of the 3-day food diaries were compared in a sample of 130 participants from the control arm of an intervention study. RESULTS: Energy-adjusted Pearson's correlation coefficients ranged from 0.24 (riboflavin) to 0.59 (magnesium) and were all statistically significant (P < 0.05). The food frequency questionnaire tended to report higher energy and nutrient intakes compared to the food diaries. On average, 74% of participants were classified into the same ± 1 quartile and 7% into opposing quartiles by the two methods. CONCLUSIONS: Overall, our food frequency questionnaire showed good relative validity. We conclude that a single administration of a food frequency questionnaire is a valid tool for ranking women in accordance with their nutrient intakes during pregnancy.

Relationship between vitamin D knowledge and 25-hydroxyvitamin D levels amongst pregnant women.

BACKGROUND: Pregnant women living at northerly latitudes are at risk of suboptimal vitamin D status. There is a paucity of studies correlating knowledge, attitudes and practices of vitamin D with serum levels amongst pregnant women. We aimed to determine the prevalence of suboptimal vitamin D status in pregnant women of various ethnicities attending two Dublin maternity hospitals and to assess levels of knowledge, attitudes and practices concerning vitamin D. METHODS: We conducted a cross-sectional study of 116 pregnant women of Irish, Asian, Sub-Saharan African and Middle Eastern and North African (MENA) origin. Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D (25OHD). We examined knowledge, attitudes and practices concerning vitamin D using an interview-assisted questionnaire. RESULTS: The median (interquartile range) 25OHD level was 25.9 (16.5-44.7) nmol L(-1). Using a cut-off point of <30 nmol L(-1) , the proportion at risk of deficiency was significantly higher among MENA (88%; P < 0.001) and Sub-Saharan African women (68%; P = 0.019) than Irish women (36%). Eighty-two women (71%) reported they had insufficient knowledge about vitamin D and its sources. Vitamin D containing supplement usage was the strongest predictor of 25OHD levels ≥30 nmol L(-1) (odds ratio = 18.03, 95% confidence interval = 5.7256.8, P < 0.001). CONCLUSIONS: Suboptimal vitamin D status is common in this cohort of pregnant women, especially among those of Sub-Saharan African and MENA origin. Awareness of vitamin D dietary sources is poor among all subgroups. Recommending vitamin D containing supplements may be the best strategy at present for improving vitamin D status with a need for increased vitamin D education.

The influence of ankle joint mobility when using an orthosis on stability in patients with spinal cord injury: a pilot study.

OBJECTIVES: Perceived risk of falling is an important factor for people with spinal cord injury (SCI). This study investigated the influence of ankle joint motion on postural stability and walking in people with SCI when using an orthosis. METHODS: Volunteer subjects with SCI (n=5) participated in this study. Each subject was fitted with an advanced reciprocating gait orthosis (ARGO) equipped with either solid or dorsiflexion-assist type ankle-foot orthosis (AFOs) and walked at their self-selected speed along a flat walkway to enable the comparison of walking speed, cadence and endurance. A force plate system and a modified Falls Efficacy Scale (MFES) were utilized to measure postural sway and the perceived fear of falling, respectively. RESULTS: There were significant differences in the mean MFES scores between two types of orthosis (P=0.023). When using two crutches, there was no significant difference in static standing postural sway in the medio-lateral (M/L) direction (P=0.799), but significant difference in the antero-posterior (A/P) direction (P=0.014). However, during single crutch support, there was a significant difference in both M/L (P=0.019) and A/P (P=0.022) directions. Walking speed (7%) and endurance (5%) significantly increased when using the ARGO with dorsi flexion assisted AFOs. There was no significant deference between two types of orthoses in cadence (P=0.54). CONCLUSIONS: Using an ARGO with dorsiflexion-assisted AFOs increased the fear of falling, but improved static postural stability and increased walking speed and endurance, and should therefore be considered as an effective orthosis during the rehabilitation of people with SCI.

Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study.

BACKGROUND: Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype. METHOD: We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender. RESULTS: VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome. CONCLUSIONS: Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.

Drug-associated linear IgA disease mimicking toxic epidermal necrolysis.

Linear IgA disease (LAD) is an uncommon, acquired, autoimmune blistering disorder with a characteristic linear IgA deposition along the basement membrane zone. LAD can be idiopathic or drug-induced. Drug-related LAD most commonly occurs after exposure to vancomycin, but phenytoin and other medications have been implicated. A small number of cases of drug-induced LAD clinically resembling TEN have been reported. We report a case of phenytoin-associated LAD clinically mimicking TEN in a 57-year-old woman. This case shows the necessity of investigating TEN patients for autoimmune bullous diseases, using immunofluorescence studies.

Assessment of the effectiveness of group education on knowledge for women with newly diagnosed gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is identified in pregnancy and resolves following delivery. It increases maternal and foetal morbidity and may increase risk of future type 2 diabetes. Women diagnosed with GDM need high-quality multidisciplinary education in order to apply necessary changes to their diet and lifestyle. There is a paucity of information on the effectiveness of group education for women with GDM. AIMS: The aim of this study was to assess the effect of a multidisciplinary group intervention delivered by a specialist midwife and dietitian on women's knowledge of GDM. METHODS: All women with a diagnosis of GDM were invited to attend a multidisciplinary group educational session on lifestyle and GDM management. Participants were invited to complete a questionnaire before and after the educational intervention; only individuals who completed both questionnaires were included. The questionnaire reviewed knowledge of suitable diet, implications of GDM diagnosis and management of GDM. RESULTS: A total of 716 women completed both questionnaires; mean age of the participants was 34 years. Just under half of women (46.9%, n = 333) were primiparous. The majority of the women (62.5%, n = 439) were Irish; 53.4% (n = 382) had a family history of diabetes. There was a significant increase in median score for knowledge following the educational intervention (pre-intervention score 8 (-2-12); post-intervention score 12 (1-12); p < 0.001). CONCLUSIONS: This study demonstrates the benefit of a multidisciplinary group educational session delivered by a specialized midwife and a dietitian on pregnant women's knowledge and understanding of GDM.

Transcriptional Changes in the Mouse Retina after Ocular Blast Injury: A Role for the Immune System.

Ocular blast injury is a major medical concern for soldiers and explosion victims due to poor visual outcomes. To define the changes in gene expression following a blast injury to the eye, we examined retinal ribonucleic acid (RNA) expression in 54 mouse strains 5 days after a single 50-psi overpressure air wave blast injury. We observe that almost 40% of genes are differentially expressed with a false discovery rate (FDR) of <0.001, even though the nominal changes in RNA expression are rather small. Moreover, we find through machine learning approaches that genetic networks related to the innate and acquired immune system are activated. Accompanied by lymphocyte invasion into the inner retina, blast injury also results in progressive loss of visual function and retinal ganglion cells (RGCs). Collectively, these data demonstrate how systems genetics can be used to put meaning to the transcriptome changes following ocular blast injury that eventually lead to blindness.

Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina.

Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia.

The essential function of the small Tim proteins in the TIM22 import pathway does not depend on formation of the soluble 70-kilodalton complex.

The TIM22 protein import pathway of the yeast mitochondrion contains several components, including a family of five proteins (Tim8p, -9p, -10p, -12p, and -13p [Tim, for translocase of inner membrane]) that are located in the intermembrane space and are 25% identical. Tim9p and Tim10p have dual roles in mediating the import of inner membrane proteins. Like the Tim8p-Tim13p complex, the Tim9p-Tim10p complex functions as a putative chaperone to guide hydrophobic precursors across the intermembrane space. Like membrane-associated Tim12p, they are members of the Tim18p-Tim22p-Tim54p membrane complex that mediates precursor insertion into the membrane. To understand the role of this family in protein import, we have used a genetic approach to manipulate the complement of the small Tim proteins. A strain has been constructed that lacks the 70-kDa soluble Tim8p-Tim13p and Tim9p-Tim10p complexes in the intermembrane space. Instead, a functional version of Tim9p (Tim9(S67C)p), identified as a second-site suppressor of a conditional tim10 mutant, maintains viability. Characterization of this strain revealed that Tim9(S67C)p and Tim10p were tightly associated with the inner membrane, the soluble 70-kDa Tim8p-Tim13p and Tim9p-Tim10p complexes were not detectable, and the rate of protein import into isolated mitochondria proceeded at a slower rate. An arrested translocation intermediate bound to Tim9(S67C)p was located in the intermembrane space, associated with the inner membrane. We suggest that the 70-kDa complexes facilitate import, similar to the outer membrane receptors of the TOM (hetero-oligomeric translocase of the outer membrane) complex, and the essential role of Tim9p and Tim10p may be to mediate protein insertion in the inner membrane with the TIM22 complex.

Electron spin resonance and raman scattering spectroscopy of multi-walled carbon nanotubes: a function of acid treatment.

We compare the fundamental transport mechanism in multi-walled carbon nanotubes (MWNTs) by means of electron spin resonance (ESR) and Raman spectroscopy as a function of acid treatment. The ESR and Raman results show that the acid treatment reduces the density of states at the Fermi level. Defects introduced through the acid treatment move the Fermi level closer to the K points in the valence band, and consequently conduction is reduced. These defects are identified as Stone-Wales type from the Raman results.

Expression of cell cycle control proteins in primary colorectal tumors does not always predict expression in lymph node metastases.

Analysis of tumor markers focuses on expression in primary tumors with the assumption that this is representative of metastatic tumor, against which treatment is targeted. Few studies have compared the expression of such markers in primary and secondary tumors. In this study, several key genes involved in cell cycle regulation were investigated in colorectal tumors and corresponding lymph node metastases. The cell cycle regulators p53, cyclin D1, p21, p27, retinoblastoma protein (Rb), and proliferating cell nuclear antigen (PCNA) were examined in a series of 42 paired samples of primary colorectal and secondary lymph node tumors by immunohistochemistry. Expression of p53, p27, and Rb was similar in virtually all paired samples (p53, 38 of 42; p27, 39 of 42; Rb, 40 of 42), indicating that the pattern of these proteins in colorectal tumors may be used to predict that in lymph node tumors. It also suggests a lack of direct involvement in the metastatic process. A lower concordance for p21 and cyclin D1 staining was observed between primary and secondary tumors (p21, 19 of 42; cyclin D1, 22 of 42). p21 expression was more often observed in primary colorectal cancers, whereas cyclin D1 expression was more frequently seen in lymph node metastases, in keeping with the contrasting roles of these proteins as a cell cycle inhibitor (p21) and activator (cyclin D1). The PCNA-labeling index was found to vary considerably in a number of cases, thus limiting the ability to predict expression of this protein in lymph node metastases from the primary tumor. In addition, PCNA-labeling indices between paired samples were neither consistently higher nor lower, suggesting that the proliferative capacity of tumor cells is not directly related to their ability to metastasize.