EUV spectral analysis of ns-laser produced bismuth plasmas at 8-17 nm.

Extreme ultraviolet (EUV) spectra from laser produced bismuth plasmas were recorded in the 8-17 nm spectral region using a Nd:YAG laser with a pulse length of 8 ns operating at a range of laser power densities. Due to the broad-band emission at 8-17 nm, bismuth plasmas show promise as sources of quasicontinuous radiation in the extreme ultraviolet. When varying the incident laser power density, ionic populations of Bi ions at different power densities were estimated by the collisional-radiative (CR) model for explanation of changes in the spectral profile. Comparison of experimental spectra with atomic structure calculations using the Hartree-Fock with configuration interaction (HFCI) code of Cowan was performed in order to identify most of the features in the spectra.

A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome.

GOAL: To examine dementia characteristics, age at onset and associated co-morbidities in persons with Down syndrome. METHOD: A total of 77 people with Down syndrome aged 35 years and older were followed up from 1996 to 2015. The diagnosis of dementia was established using the modified ICD 10 Criteria and a combination of objective and informant-based tests. Cognitive tests included the Test for Severe Impairment and the Down Syndrome Mental Status Examination; adaptive behaviour was measured using the Daily Living Skills Questionnaire, and data from the Dementia Questionnaire for People with Intellectual Disabilities have been available since 2005. RESULTS: Over the 20-year period, 97.4% (75 of 77) persons developed dementia with a mean age of dementia diagnosis of 55 years (SD = 7.1, median = 56 years). Clinical dementia was associated with cognitive and function decline and seizure activity. Risk for dementia increased from 23% in those aged 50 years to 80% in those aged 65 years and above. There were no differences by level of ID. CONCLUSION: The previously reported high risk levels for dementia among people with Down syndrome were confirmed in this data as was the relationship with late onset epilepsy. The value of the instruments utilised in tracking decline and helping to confirm diagnosis is further highlighted.

Mapping of the congenital generalized hypertrichosis locus to chromosome Xq24-q27.1.

Congenital generalized hypertrichosis (CGH) is a rare, fully penetrant X-linked dominant trait previously described in a single, multigenerational Mexican family. CGH is a visually striking phenotype characterized by excessive facial and upper torso hair in males and by less severe asymmetric hairiness in females. We have found significant evidence for linkage with several markers from the long arm of the X chromosome. Recombinant chromosomes place the CGH gene within a 22 cM interval between DXS425 and DXS1227 in Xq24-Xq27.1. The localization of a gene for CGH represents the first step towards the isolation of genes involved in hair growth pattern, particularly those involved in restriction of areas in humans.

Solvothermal synthesis of soluble, surface modified anatase and transition metal doped anatase hybrid nanocrystals.

Titanium dioxide, or titania, is perhaps the most well-known and widely studied photocatalytic material, with myriad applications, due to a high degree of tunability achievable through the incorporation of dopants and control of phase composition and particle size. Many of the applications of titanium dioxide require particular forms, such as gels, coatings, or thin films, making the development of hybrid solution processable nanoparticles increasingly attractive. Here we report a simple solvothermal route to highly dispersible anatase phase titanium dioxide hybrid nanoparticles from amorphous titania. Solvothermal treatment of the amorphous titania in trifluoroacetic acid leads to the formation of anatase phase nanoparticles with a high degree of size control and near complete surface functionalisation. This renders the particles highly dispersible in simple organic solvents such as acetone. Dopant ions may be readily incorporated into the amorphous precursor by co-precipitation, with no adverse effect on subsequent crystallisation and surface modification.

MLH1 mediates PARP-dependent cell death in response to the methylating agent N-methyl-N-nitrosourea.

BACKGROUND: Methylating agents such as N-methyl-N-nitrosourea (MNU) can cause cell cycle arrest and death either via caspase-dependent apoptosis or via a poly(ADP-ribose) polymerase (PARP)-dependent form of apoptosis. We wished to investigate the possible role of MLH1 in signalling cell death through PARP. METHODS: Fibroblasts are particularly dependent on a PARP-mediated cell death response to methylating agents. We used hTERT-immortalised normal human fibroblasts (WT) to generate isogenic MLH1-depleted cells, confirmed by quantitative PCR and western blotting. Drug resistance was measured by clonogenic and cell viability assays and effects on the cell cycle by cell sorting. Damage signalling was additionally investigated using immunostaining. RESULTS: MLH1-depleted cells were more resistant to MNU, as expected. Despite having an intact G(2)/M checkpoint, the WT cells did not initially undergo cell cycle arrest but instead triggered cell death directly by PARP overactivation and nuclear translocation of apoptosis-inducing factor (AIF). The MLH1-depleted cells showed defects in this pathway, with decreased staining for phosphorylated H2AX, altered PARP activity and reduced AIF translocation. Inhibitors of PARP, but not of caspases, blocked AIF translocation and greatly decreased short-term cell death in both WT and MLH1-depleted cells. This MLH1-dependent response to MNU was not blocked by inhibitors of ATM/ATR or p53. CONCLUSION: These novel data indicate an important role for MLH1 in signalling PARP-dependent cell death in response to the methylating agent MNU.

An unstable triplet repeat in a gene related to myotonic muscular dystrophy.

Synthetic oligonucleotides containing GC-rich triplet sequences were used in a scanning strategy to identify unstable genetic sequences at the myotonic dystrophy (DM) locus. A highly polymorphic GCT repeat was identified and found to be unstable, with an increased number of repeats occurring in DM patients. In the case of severe congenital DM, the paternal triplet allele was inherited unaltered while the maternal, DM-associated allele was unstable. These studies suggest that the mutational mechanism leading to DM is triplet amplification, similar to that occurring in the fragile X syndrome. The triplet repeat sequence is within a gene (to be referred to as myotonin-protein kinase), which has a sequence similar to protein kinases.

Colour of bovine subcutaneous adipose tissue: A review of contributory factors, associations with carcass and meat quality and its potential utility in authentication of dietary history.

The colour of bovine subcutaneous (sc) adipose tissue (carcass fat) depends on the age, gender and breed of cattle. Diet is the most important extrinsic factor but its influence depends on the duration of feeding. Cattle produced under extensive grass-based production systems generally have carcass fat which is more yellow than their intensively-reared, concentrate-fed counterparts and this is caused by carotenoids from green forage. Although yellow carcass fat is negatively regarded in many countries, evidence suggests it may be associated with a healthier fatty acid profile and antioxidant content in beef, synonymous with grass feeding. Nonetheless, management strategies to reduce fat colour of grass-fed cattle are sought after. Current research suggests that yellow colour of this tissue is reduced if pasture-fed cattle are converted to a grain-based diet, which results in accretion of adipose tissue and dilution of carotenoids. Colour changes may depend on the initial yellow colour, the carotene and utilisable energy in the finishing diet, the duration of finishing, the amount of fat accumulated during finishing and the rate of utilisation of carotene from body fat. Differences in nutritional strategies which cause differences in fatty acid composition may be reflected by differences in fat colour and carotenoid concentration. Fat colour and carotenoids are prominent among a panoply of measurements which can aid the authentication of the dietary history and thus to some extent, the origin of beef, although this potential utility is complicated by the simultaneous rather than discrete use of forages and concentrates in real production systems.

Effect of concentrate feeding pattern in a grass silage/concentrate beef finishing system on performance, selected carcass and meat quality characteristics.

Steers were offered grass silage ad libitum and 6.4 kg concentrates daily for 126 days or silage ad libitum for 35 days, followed by concentrates ad libitum (Experiment 1). Steers were offered grass silage ad libitum and 6 kg concentrates daily for 154 days, concentrates ad libitum or grass silage ad libitum for 112 days followed by concentrates ad libitum (Experiment 2). All treatments received the same total concentrate allowance. In Experiment 1, there was no difference in any measurement of meat quality. In Experiment 2, ad libitum concentrate feeding per se, decreased redness and increased shear force of muscle at 2 days post-mortem. Delaying concentrate feeding decreased fat yellowness, decreased shear force at 7 and 14 days post-mortem and increased muscle redness at 14 days post-mortem. Modifications of the beef production system examined had minor effects on beef quality which are unlikely to be of commercial significance.

Colour, composition and quality of M. longissimus dorsi and M. extensor carpi radialis of steers housed on straw or concrete slats or accommodated outdoors on wood-chips.

Forty-five Charolais crossbred steers were offered a common diet and accommodated either outside on wood-chips (OWP, 18m(2)/head) or in a naturally-ventilated building in slatted-floor pens (SLA, 2.5m(2)/500kg bodyweight) or in straw-bedded pens (STR, 4m(2)/head) for 132 days. Carcass weight averaged 351, 362, and 372 (sed 6.63)kg (P<0.05), for SLA, STR and OWP, respectively. Accommodation system did not affect the colour, drip loss, shear force or composition of Musculus longissimus dorsi (LD) or Musculus extensor carpi radialis (ECR) muscles or the sensory characteristics of LD. The ultimate pH of ECR was highest (P<0.05) for OWP steers, while their LD was darker at 2 days post-mortem than LD from STR steers. It is concluded that accommodating cattle on OWP had a minor transient effect on beef colour and no impact on beef composition or eating quality.

Transcriptional subtyping and CD8 immunohistochemistry identifies poor prognosis stage II/III colorectal cancer patients who benefit from adjuvant chemotherapy.

PURPOSE: Transcriptomic profiling of colorectal cancer (CRC) has led to identification of four consensus molecular subtypes (CMS1-4), which have prognostic value in stage II/III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system has helped to define the biology specific to the epithelial component of colorectal tumors. However, the clinical value of these classifications in predicting response to standard-of-care adjuvant chemotherapy remains unknown. PATIENTS AND METHODS: Using samples from 4 European sites, we assembled a novel stage II/III CRC patient cohort and performed transcriptomic profiling on 156 samples, targeted sequencing and generated a tissue microarray to enable integrated "multi-omics" analyses. We also accessed data from 2 published stage II/III CRC patient cohorts: GSE39582 and GSE14333 (479 and 185 samples respectively). RESULTS: The epithelial-rich CMS2 subtype of CRC benefitted significantly from adjuvant chemotherapy treatment in both stage II and III disease (p=0.02 and p<0.0001 respectively), while the CMS3 subtype significantly benefitted in stage III only (p=0.00073). Following CRIS sub-stratification of CMS2, we observed that only the CRIS-C subtype significantly benefitted from adjuvant chemotherapy in stage II and III disease (p=0.0081 and p<0.0001 respectively), while CRIS-D significantly benefitted in stage III only (p=0.0034). We also observed that CRIS-C patients with low levels of CD8+ tumor-infiltrating lymphocytes were most at risk of relapse in both stage II and III disease (p=0.0031). CONCLUSION: Patient stratification using a combination of transcriptional subtyping and CD8 immunohistochemistry analyses is capable of identifying poor prognostic stage II/III patients who benefit from adjuvant standard-of-care chemotherapy. These findings are particularly relevant for stage II disease, where the overall benefit of adjuvant chemotherapy is marginal.

Review article: recent insights into clinical decision-making in severe alcoholic hepatitis.

BACKGROUND: Alcoholic hepatitis is a severe acute manifestation of alcoholic liver disease with a high mortality. Management of patients with this condition has been a matter of controversy for many years; however, recent clinical studies have sought to improve the clinical approach to these patients. AIM: To use these recent studies in order to guide clinical management. METHODS: A MeSH search of Medline was performed to specifically identify recent studies which influenced clinical diagnosis, assessment and management of alcoholic hepatitis. RESULTS: Fulfilment of clear clinical criteria including a minimum threshold of bilirubin, defined periods of jaundice and alcohol ingestion negates the need for liver biopsy in most patients. Corticosteroids improve short-term mortality only (28 day) with other factors such as abstinence likely to be significant in long-term outcome. Pentoxifylline is not an effective treatment. The Glasgow Alcoholic Hepatitis Score (GAHS) score can identify those patients likely to benefit from corticosteroids, but scores that include the evolution of bilirubin over 1 week of such treatment (such as the Lille Score) define "response". Underlying infection may contribute towards corticosteroid nonresponse and needs to be actively sought out and treated. Liver transplant remains controversial; however, it has been shown to be feasible in alcoholic hepatitis. CONCLUSIONS: Recent studies have helped to define patients who may benefit from corticosteroid treatment. However, there remains a need for more accurate scores of prognosis and treatment response, and a clear need for alternative treatments for those patients not responding to corticosteroid therapy.

Synthesis of CaCO3 nano- and micro-particles by dry ice carbonation.

Here we report a new low temperature dry ice carbonation approach for the synthesis of carbonate-based nano- and micro-particulate materials, which enables the preparation of monodispersed calcium carbonate nanoparticles and microspheres with very high purity phases.

Compensatory growth in crossbred Aberdeen Angus and Belgian Blue steers: Effects on the colour, shear force and sensory characteristics of longissimus muscle.

The effect of feed restriction (99days) followed by compensatory growth during a 200day re-alimentation period on the colour and sensory characteristics of meat from Aberdeen Angus×Holstein-Friesian (AN) and Belgian Blue×Holstein-Friesian (BB) steers was examined. Compensatory growth had no effect on muscle pH and temperature decline, chemical composition, drip loss, fat colour, or juiciness, but increased (P=0.009) Warner-Bratzler shear force and decreased tenderness (P=0.08) and overall liking (P=0.09). Compared to meat from BB steers, meat from AN steers had a higher intramuscular fat concentration and was rated similarly for tenderness, but higher for many of the flavour characteristics examined. While adjustment for intramuscular fat concentration removed some of these differences, genotype-specific flavour differences remained. It is concluded that genotype had greater effects on meat quality than the compensatory growth feeding regime imposed in this study.

Changes in colour characteristics and pigmentation of subcutaneous adipose tissue and M. longissimus dorsi of heifers fed grass, grass silage or concentrate-based diets.

The objective of this experiment was to determine the effect of dietary composition and duration of feeding on subcutaneous (s.c.) adipose tissue and M. longissimus dorsi (LD) colour and pigment concentrations of heifers. Fifteen heifers were permanently housed and fed a concentrate diet (PH-CON). Fifty-four heifers were grazed on pasture (PAS) for 90d, housed and offered concentrates (PAS-CON), 200g grass silage (GS)/kg dry matter (DM) (PAS-GS20), 500g GS/kgDM (PAS-GS50) or zero-grazed grass (PAS-GRA). To facilitate assessment of the temporal pattern of tissue colour, 3 heifers/treatment were slaughtered at housing (following 7d adjustment to diets) and 28, 56, 91 and 120 days thereafter. Yellowness ('b' value) of s.c. adipose tissue and lightness ('L' value) and redness ('a' value) of LD were recorded 48h post-mortem. ß-Carotene and lutein contents of s.c. adipose tissue and total LD haem pigments were determined. At housing, s.c. adipose tissue 'b' values of the PAS group (mean=13.47) were higher (P<0.01) than those of the PH-CON group (mean=10.35) but there was no difference in ß-carotene or lutein concentrations. The change in s.c. adipose tissue 'b' for each diet following housing was best described by the following equations: PH-CON: y=-0.087 (SE 0.0347) X+0.0005 (SE 0.00029) X(2)+10.06 (SE 0.600), MSE 1.94, R(2) 0.57, P<0.01. PAS-CON: y=-0.102 (SE 0.0286) X+0.0006 (SE 0.00024) X(2)+13.32 (SE 0.598), MSE 2.30, R(2) 0.62, P<0.001. PAS-GS20: y=-0.106 (SE 0.0296) X+0.0008 (SE 0.00025) X(2)+13.10 (SE 0.618), MSE 2.46, R(2) 0.47, P<0.01. PAS-GS50: y=-0.077 (SE 0.0269) X+0.0006 (SE 0.00023) X(2)+13.29 (SE 0.552) MSE 1.95, R(2) 0.38, P<0.05. PAS-GRA: y=-0.018 (SE 0.0079) X+13.77 (SE 0.528), MSE 2.28, R(2) 0.24, P<0.05, where y='b' value, x=days post-housing (d96-d216) and MSE=mean square error. Treatment had a significant effect on s.c. adipose tissue ß-carotene and lutein (both P<0.001) with PAS-GRA and PH-CON tending to have the highest and lowest concentrations, respectively. PH-CON heifers tended (P=0.058) to have lower LD haem pigments and lighter LD than other heifers. It is concluded that, while concentrate feeding led to the greatest decrease in s.c. adipose tissue yellowness relative to PAS-GRA, choice of dietary ingredients and duration of feeding will depend on the stringency of the colour criteria in particular markets.

Colour stability, under simulated retail display conditions, of M. longissimus dorsi and M. semimembranosus from steers given long-term daily exercise and supplemented with vitamin E.

The objective was to determine if exercise has a negative impact on the colour stability of beef and if dietary vitamin E (VE) supplementation could counteract any negative effect. Steers were not exercised or were walked 4.41km/day for 18 weeks. Within exercise treatment animals consumed, on average, either 450 or 1050IU/day of VE. Muscle α-tocopherol increased (P=0.004) from 2.35 to 3.15µg/g with VE supplementation. Following ageing M. longissimus dorsi (LD) and M. semimembranosus (SM) steaks were packaged under 80%O(2):20%CO(2) and stored at 4°C. The LD of exercised steers was more red and more saturated (both P<0.05) after 0 and 2 days of storage than LD of unexercised steers. While redness of both muscles decreased over the display period, LD retained a higher redness than SM from day 2 to 7 (P<0.05). Colour shelf-life of LD was extended by 0.75 days, to 3.25 days, due to VE supplementation.

Colour of muscle from 18-month-old steers given long-term daily exercise.

Darker beef from pasture-fed compared with grain-fed cattle may result from differences in physical activity rather than differences in nutrition. The objective was to determine if steers that were exercised produced darker meat than non-exercised steers and whether any effect was muscle-related. Exercised steers were walked 4.41 km daily in a single bout, six days per week for 18 weeks at an average speed of 5.2 kmh(-1). All steers were fed grass silage on an ad libitum basis plus 6 kg concentrates. Following slaughter, muscle colour coordinates ('L' (lightness), 'a' (redness) and 'b' (yellowness) values) of M. longissimus dorsi (LD), M. semimembranosus (SM) and M. extensor carpi radialis (ECR) were recorded at 48 h postmortem and redness and yellowness were used to calculate muscle hue ('H') and colour intensity/saturation ('C'). The pH of all muscles was measured at 1.5, 3, 6, 22 and 48 h postmortem and LD samples were recovered (90 min postmortem) for glycolytic potential (GP) assessment. Exercise did not affect muscle lightness, yellowness, hue or colour intensity. However, LD was the darkest (P<0.001) and SM the most saturated (P<0.001) muscle. Exercise affected muscle redness in a muscle-dependent manner (muscle×exercise, P=0.038) whereby ECR became more red with exercise but LD and SM were unaffected. There were muscle×time (P<0.001) and time×exercise (P=0.045) interactions for muscle pH. The ECR muscle had the highest pH at all times. The exercised steers had higher (P<0.05) LD muscle pH than control steers at 3 and 6 h postmortem. Exercise did not affect myoglobin concentration, which was muscle dependent, decreasing in the order: SM (6.72 mg/g)>ECR (6.33 mg/g)>LD (5.48 mg/g), which were all different (P<0.001). Exercise had no effect on GP in LD muscle (111 vs. 99 µmol/g for control and exercised steers, respectively; SED=6.6 µmol/g). It was concluded that although application of exercise did not affect muscle lightness and thus, did not cause 'darker' meat, it did affect muscle redness in a muscle-dependent manner.

Large-scale continuous hydrothermal production and activation of ZIF-8.

A new method for the large-scale hydrothermal production and activation of ZIF-8 is presented in this communication. Activated ZIF-8 has been produced, at lab-scale and pilot-scale, at a rate of 27 g h(-1) and 810 g h(-1) respectively with the activated material showing a surface area of 1800 m(2) g(-1).

Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase.

Myotonic dystrophy protein kinase (DMPK) is a serine-threonine protein kinase encoded by the myotonic dystrophy (DM) locus on human chromosome 19q13.3. It is a close relative of other kinases that interact with members of the Rho family of small GTPases. We show here that the actin cytoskeleton-linked GTPase Rac-1 binds to DMPK, and coexpression of Rac-1 and DMPK activates its transphosphorylation activity in a GTP-sensitive manner. DMPK can also bind Raf-1 kinase, the Ras-activated molecule of the MAP kinase pathway. Purified Raf-1 kinase phosphorylates and activates DMPK. The interaction of DMPK with these distinct signals suggests that it may play a role as a nexus for cross-talk between their respective pathways and may partially explain the remarkable pleiotropy of DM.

Effects of the sex of myotonic dystrophy patients on the unstable triplet repeat in their affected offspring.

The mutation responsible for myotonic dystrophy (DM) is an unstable expansion of the CTG repeat within the myotonin protein kinase gene. To examine whether the parental origin of the expanded repeat influences the repeat size in offspring, we studied 51 father-child and 59 mother-child pairs with DM. Small expansions in fathers resulted in larger size expansions in their offspring, while large paternal expansions resulted in less size change in their offspring. However, there was no correlation between maternal size expansion and size increase in offspring for either congenital or noncongenital DM. These data suggest that the sex of the affected parent influences the unstable expansion of the repeat in DM offspring. While some evidence suggests that DNA methylation status cannot explain this observation, the mechanism for differential maternal/paternal transmission expansion is currently unknown.

Driving safety in Parkinson's disease.

In this study, 39 patients with PD and 25 control subjects without neurologic disease completed testing in a driving simulator. PD patients had more total collisions on the driving simulator than control subjects (t = -3.7, p < 0.01). In PD patients, collisions were associated with Hoehn and Yahr stage (chi(2) = 12.4, p = 0.006) and correlated with Unified Parkinson's Disease Rating Scale score (r = 0.5, p < 0.01).