Pichia stipitis xylose reductase helps detoxifying lignocellulosic hydrolysate by reducing 5-hydroxymethyl-furfural (HMF)

<p>Abstract</p> <p>Background</p> <p><it>Pichia stipitis </it>xylose reductase (Ps-XR) has been used to design <it>Saccharomyces cerevisiae </it>strains that are able to ferment xylose. One example is the industrial <it>S. cerevisiae </it>xylose-consuming strain TMB3400, which was constructed by expression of <it>P. stipitis </it>xylose reductase and xylitol dehydrogenase and overexpression of endogenous xylulose kinase in the industrial <it>S. cerevisiae </it>strain USM21.</p> <p>Results</p> <p>In this study, we demonstrate that strain TMB3400 not only converts xylose, but also displays higher tolerance to lignocellulosic hydrolysate during anaerobic batch fermentation as well as 3 times higher <it>in vitro </it>HMF and furfural reduction activity than the control strain USM21. Using laboratory strains producing various levels of Ps-XR, we confirm that Ps-XR is able to reduce HMF both <it>in vitro </it>and <it>in vivo</it>. Ps-XR overexpression increases the <it>in vivo </it>HMF conversion rate by approximately 20%, thereby improving yeast tolerance towards HMF. Further purification of Ps-XR shows that HMF is a substrate inhibitor of the enzyme.</p> <p>Conclusion</p> <p>We demonstrate for the first time that xylose reductase is also able to reduce the furaldehyde compounds that are present in undetoxified lignocellulosic hydrolysates. Possible implications of this newly characterized activity of Ps-XR on lignocellulosic hydrolysate fermentation are discussed.</p

Probabilistic Clustering of Time-Evolving Distance Data

We present a novel probabilistic clustering model for objects that are represented via pairwise distances and observed at different time points. The proposed method utilizes the information given by adjacent time points to find the underlying cluster structure and obtain a smooth cluster evolution. This approach allows the number of objects and clusters to differ at every time point, and no identification on the identities of the objects is needed. Further, the model does not require the number of clusters being specified in advance -- they are instead determined automatically using a Dirichlet process prior. We validate our model on synthetic data showing that the proposed method is more accurate than state-of-the-art clustering methods. Finally, we use our dynamic clustering model to analyze and illustrate the evolution of brain cancer patients over time

Visualizing sound emission of elephant vocalizations: evidence for two rumble production types

Recent comparative data reveal that formant frequencies are cues to body size in animals, due to a close relationship between formant frequency spacing, vocal tract length and overall body size. Accordingly, intriguing morphological adaptations to elongate the vocal tract in order to lower formants occur in several species, with the size exaggeration hypothesis being proposed to justify most of these observations. While the elephant trunk is strongly implicated to account for the low formants of elephant rumbles, it is unknown whether elephants emit these vocalizations exclusively through the trunk, or whether the mouth is also involved in rumble production. In this study we used a sound visualization method (an acoustic camera) to record rumbles of five captive African elephants during spatial separation and subsequent bonding situations. Our results showed that the female elephants in our analysis produced two distinct types of rumble vocalizations based on vocal path differences: a nasally- and an orally-emitted rumble. Interestingly, nasal rumbles predominated during contact calling, whereas oral rumbles were mainly produced in bonding situations. In addition, nasal and oral rumbles varied considerably in their acoustic structure. In particular, the values of the first two formants reflected the estimated lengths of the vocal paths, corresponding to a vocal tract length of around 2 meters for nasal, and around 0.7 meters for oral rumbles. These results suggest that African elephants may be switching vocal paths to actively vary vocal tract length (with considerable variation in formants) according to context, and call for further research investigating the function of formant modulation in elephant vocalizations. Furthermore, by confirming the use of the elephant trunk in long distance rumble production, our findings provide an explanation for the extremely low formants in these calls, and may also indicate that formant lowering functions to increase call propagation distances in this species'

Mathematics and Medicine: How mathematics, modelling and simulations can lead to better diagnosis and treatments

Starting with the discovery of X-rays by Röntgen in 1895, the progress in medical imaging has been extraordinary and immensely beneficial to diagnosis and therapy. Parallel to the increase of imaging accuracy, there is the quest of moving from qualitative to quantitative analysis and patient-tailored therapy. Mathematics, modelling and simulations are increasing their importance as tools in this quest. In this paper we give an overview of relations between mathematical modelling and imaging and focus particularly on the estimation of perfusion in the brain. In the forward model, the brain is treated as a porous medium and a two compartment model (arterial/venous) is used. Motivated by the similarity with techniques in reservoir modelling, we propose an ensemble Kalman filter to perform the parameter estimation and apply the method to a simple example as an illustrative example.acceptedVersio

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

Differences between patients' and clinicians' report of sleep disturbance: a field study in mental health care in Norway

<p>Abstract</p> <p>Background</p> <p>The aims of the study was to assess the prevalence of diagnosed insomnia and the agreement between patient- and clinician-reported sleep disturbance and use of prescribed hypnotic medication in patients in treatment for mental disorders.</p> <p>Methods</p> <p>We used three cross-sectional, multicenter data-sets from 2002, 2005, and 2008. Data-set 1 included diagnostic codes from 93% of all patients receiving treatment in mental health care in Norway (<it>N </it>= 40261). Data-sets 2 (<it>N </it>= 1065) and 3 (<it>N </it>= 1181) included diagnostic codes, patient- and clinician-reported sleep disturbance, and use of prescribed hypnotic medication from patients in 8 mental health care centers covering 10% of the Norwegian population.</p> <p>Results</p> <p>34 patients in data-set 1 and none in data-sets 2 and 3 had a diagnosis of insomnia as a primary or comorbid diagnosis. In data-sets 2 and 3, 42% and 40% of the patients reported sleep disturbance, whereas 24% and 13% had clinician-reported sleep disturbance, and 7% and 9% used hypnotics. Patients and clinicians agreed in 29% and 15% of the cases where the patient or the clinician or both had reported sleep disturbance. Positive predictive value (PPV) of clinicians' evaluations of patient sleep disturbance was 62% and 53%. When the patient reported sleep disturbance as one of their most prominent problems PPV was 36% and 37%. Of the patients who received hypnotic medication, 23% and 29% had neither patient nor clinician-rated sleep disturbance.</p> <p>Conclusion</p> <p>When patients meet the criteria for a mental disorder, insomnia is almost never diagnosed, and sleep disturbance is imprecisely recognized relative to the patients' experience of sleep disturbance.</p

Exploiting physico-chemical properties in string kernels

<p>Abstract</p> <p>Background</p> <p>String kernels are commonly used for the classification of biological sequences, nucleotide as well as amino acid sequences. Although string kernels are already very powerful, when it comes to amino acids they have a major short coming. They ignore an important piece of information when comparing amino acids: the physico-chemical properties such as size, hydrophobicity, or charge. This information is very valuable, especially when training data is less abundant. There have been only very few approaches so far that aim at combining these two ideas.</p> <p>Results</p> <p>We propose new string kernels that combine the benefits of physico-chemical descriptors for amino acids with the ones of string kernels. The benefits of the proposed kernels are assessed on two problems: MHC-peptide binding classification using position specific kernels and protein classification based on the substring spectrum of the sequences. Our experiments demonstrate that the incorporation of amino acid properties in string kernels yields improved performances compared to standard string kernels and to previously proposed non-substring kernels.</p> <p>Conclusions</p> <p>In summary, the proposed modifications, in particular the combination with the RBF substring kernel, consistently yield improvements without affecting the computational complexity. The proposed kernels therefore appear to be the kernels of choice for any protein sequence-based inference.</p> <p>Availability</p> <p>Data sets, code and additional information are available from <url>http://www.fml.tuebingen.mpg.de/raetsch/suppl/aask</url>. Implementations of the developed kernels are available as part of the Shogun toolbox.</p

Similar decline in mortality rate of older persons with and without type 2 diabetes between 1993 and 2004 the Icelandic population-based Reykjavik and AGES-Reykjavik cohort studies.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.A decline in mortality rates due to cardiovascular diseases and all-cause mortality has led to increased life expectancy in the Western world in recent decades. At the same time, the prevalence of type 2 diabetes, a disease associated with a twofold excess risk of cardiovascular disease and mortality, has been increasing. The objective of this study was to estimate the secular trend of cardiovascular and all-cause mortality rates in two population-based cohorts of older persons, with and without type 2 diabetes, examined 11 years apart.1506 participants (42% men) from the population-based Reykjavik Study, examined during 1991-1996 (median 1993), mean age 75.0 years, and 4814 participants (43% men) from the AGES-Reykjavik Study, examined during 2002-2006 (median 2004), mean age 77.2 years, age range in both cohorts 70-87 years. The main outcome measures were age-specific mortality rates due to cardiovascular disease and all causes, over two consecutive 5.7- and 5.3-year follow-up periods.A 32% decline in cardiovascular mortality rate and a 19% decline in all-cause mortality rate were observed between 1993 and 2004. The decline was greater in those with type 2 diabetes, as illustrated by the decline in the adjusted hazard ratio of cardiovascular mortality in individuals with diabetes compared to those without diabetes, from 1.88 (95% CI 1.24-2.85) in 1993 to 1.46 (95% CI 1.11-1.91) in 2004. We also observed a concurrent decrease in major cardiovascular risk factors in both those with and without diabetes. A higher proportion of persons with diabetes received glucose-lowering, hypertensive and lipid-lowering medication in 2004.A decline in cardiovascular and all-cause mortality rates was observed in older persons during the period 1993-2004, in both those with and without type 2 diabetes. This decline may be partly explained by improvements in cardiovascular risk factors and medical treatment over the period studied. However, type 2 diabetes still persists as an independent risk factor for cardiovascular mortality.National Institute of Health/N01-AG-1-2100 NIA Intramural Research Program Icelandic Heart Association (Hjartavernd) Icelandic Parliament (Althingi

Evidence for waning of latency in a cohort study of tuberculosis

<p>Abstract</p> <p>Background</p> <p>To investigate how the risk of active tuberculosis disease is influenced by time since original infection and to determine whether the risk of reactivation of tuberculosis increases or decreases with age.</p> <p>Methods</p> <p>Cohort analysis of data for the separate ten year birth cohorts of 1876-1885 to 1959-1968 obtained from Statistics Norway and the National Tuberculosis Registry. These data were used to calculate the rates and the changes in the rates of bacillary (or active) tuberculosis. Data on bacillary tuberculosis for adult (20+) age groups were obtained from the National Tuberculosis Registry and Statistics Norway from 1946 to 1974. Most cases during this period arose due to reactivation of remote infection. Participants in this part of the analysis were all reported active tuberculosis cases in Norway from 1946 to 1974 as recorded in the National Tuberculosis Registry.</p> <p>Results</p> <p>Tuberculosis decreased at a relatively steady rate when following individual birth cohorts, but with a tendency of slower decline as time passed since infection. A mean estimate of this rate of decline was 57% in a 10 year period.</p> <p>Conclusions</p> <p>The risk of reactivation of latent tuberculosis decreases with age. This decline may reflect the rate at which latent tuberculosis is eliminated from a population with minimal transmission of tubercle bacilli. A model for risk of developing active tuberculosis as a function of time since infection shows that the rate at which tuberculosis can be eliminated from a society can be quite substantial if new infections are effectively prevented. The findings clearly indicate that preventative measures against transmission of tuberculosis will be the most effective. These results also suggest that the total population harbouring live tubercle bacilli and consequently the future projection for increased incidence of tuberculosis in the world is probably overestimated.</p