Quality of Life Changes Following Peripheral Blood Stem Cell Transplantation and Participation in a Mixed-Type, Moderate-intensity, Exercise Program

Summary:The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and to determine the effect of participating in a mixed-type, moderate-intensity exercise program on QoL. It was also an objective to determine the relationship between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test, pretransplant (PI), post transplant (PII) and following a 12-week intervention period (PIII). At PII, 12 patients were divided equally into a control or exercise intervention group. Undergoing a PBST was associated with a statistically but not clinically significant decline in QoL (P<0.05). Following the intervention, exercising patients demonstrated an improved QoL when compared with pretransplant ratings (P<0.01) and nonexercising transplant patients (P<0.05). Moreover, peak aerobic capacity and QoL were correlated (P<0.05). The findings demonstrated that exercise participation following oncology treatment is associated with a reduction in the number and severity of endorsed problems, which in turn leads to improvements in global, physical and psychosocial QoL. Furthermore, a relationship between fitness and QoL exists, with those experiencing higher levels of fitness also demonstrating higher QoL.Bone Marrow Transplantation (2004) 33, 553-558. doi:10.1038/sj.bmt.1704378 Published online 12 January 200

The signalling channel of Central Bank interventions:modelling the Yen/US dollar exchange rate

This paper presents a theoretical framework analysing the signalling channel of exchange rate interventions as an informational trigger. We develop an implicit target zone framework with learning in order to model the signalling channel. The theoretical premise of the model is that interventions convey signals that communicate information about the exchange rate objectives of the central bank. The model is used to analyse the impact of Japanese FX interventions during the period 1999--2011 on the yen/US dollar dynamics

Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD

Background: Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that the clinical manifestation of FSHD1 can be modified by mutations in the SMCHD1 gene within a given family. The absence of either D4Z4 contraction or SMCHD1 mutations in a small cohort of patients suggests that the disease could also be due to disruption of gene regulation. In this study, we postulated that mutations responsible for exerting a modifier effect on FSHD might reside within remotely acting regulatory elements that have the potential to interact at a distance with their cognate gene promoter via chromatin looping. To explore this postulate, genome-wide Hi-C data were used to identify genomic fragments displaying the strongest interaction with the SMCHD1 gene. These fragments were then narrowed down to shorter regions using ENCODE and FANTOM data on transcription factor binding sites and epigenetic marks characteristic of promoters, enhancers and silencers

Mass Spectrometry Reveals that Oxysterols are Secreted from Non-Alcoholic Fatty Liver Disease Induced Organoids

Oxysterols are potential biomarkers for liver metabolism that are altered under disease conditions such as non-alcoholic fatty liver disease (NAFLD). We here apply sterolomics to organoids used for disease modeling of NAFLD. Using liquid chromatography-mass spectrometry with on-line sample clean-up and enrichment, we establish that liver organoids produce and secrete oxysterols. We find elevated levels of 26-hydroxycholesterol, an LXR agonist and the first oxysterol in the acidic bile acid synthesis, in medium from steatotic liver organoids compared to untreated organoids. Other upregulated sterols in medium from steatotic liver organoids are dihydroxycholesterols, such as 7α,26–dihydroxycholesterol, and 7α,25-dihydroxycholesterol. Through 26-hydroxycholesterol exposure to human stem cell-derived hepatic stellate cells, we observe a trend of expressional downregulation of the pro-inflammatory cytokine CCL2, suggesting a protective role of 26-hydroxycholesterol during early-phased NAFLD disease development. Our findings support the possibility of oxysterols serving as NAFLD indicators, demonstrating the usefulness of combining organoids and mass spectrometry for disease modeling and biomarker studies

Localization of AQP5 during development of the mouse submandibular salivary gland

Aquaporin 5 (AQP5) is known to be central for salivary fluid secretion. A study of the temporal-spatial distribution of AQP5 during submandibular gland (SMG) development and in adult tissues might offer further clues to its unknown role during development. In the present work, SMGs from embryonic day (E) 14.5–18.5 and postnatal days (P) 0, 2, 5, 25, and 60 were immunostained for AQP5 and analyzed using light microscopy. Additional confocal and transmission electron microscopy were performed on P60 glands. Our results show that AQP5 expression first occurs in a scattered pattern in the late canalicular stage and becomes more prominent and organized in the terminal tubuli/pro-acinar cells towards birth. Additional apical membrane staining in the entire intralobular duct is found just prior to birth. During postnatal development, AQP5 is expressed in both the luminal and lateral membrane of pro-acinar/acinar cells. AQP5 is also detected in the basal membrane of acinar cells at P25 and P60. In the intercalated ducts at P60, the male glands show apical staining in the entire segment, while only the proximal region is positive in the female glands. These results demonstrate an evolving distribution of AQP5 during pre- and postnatal development in the mouse SMGs

Generalized scaling function from light-cone gauge AdS_5 x S^5 superstring

We revisit the computation of the 2-loop correction to the energy of a folded spinning string in AdS_5 with an angular momentum J in S^5 in the scaling limit log S, J >>1 with J / log S fixed. This correction gives the third term in the strong-coupling expansion of the generalized scaling function. The computation, using the AdS light-cone gauge approach developed in our previous paper, is done by expanding the AdS_5 x S^5 superstring partition function near the generalized null cusp world surface associated to the spinning string solution. The result corrects and extends the previous conformal gauge result of arXiv:0712.2479 and is found to be in complete agreement with the corresponding terms in the generalized scaling function as obtained from the asymptotic Bethe ansatz in arXiv:0805.4615 (and also partially from the quantum O(6) model and the Bethe ansatz data in arXiv:0809.4952). This provides a highly nontrivial strong coupling comparison of the Bethe ansatz proposal with the quantum AdS_5 x S^5 superstring theory, which goes beyond the leading semiclassical term effectively controlled by the underlying algebraic curve. The 2-loop computation we perform involves all the structures in the AdS light-cone gauge superstring action of hep-th/0009171 and thus tests its ultraviolet finiteness and, through the agreement with the Bethe ansatz, its quantum integrability. We do most of the computations for a generalized spinning string solution or the corresponding null cusp surface that involves both the orbital momentum and the winding in a large circle of S^5.Comment: 50 pages, late

Natural Islands for a 125 GeV Higgs in the scale-invariant NMSSM

We study whether a 125 GeV standard model-like Higgs boson can be accommodated within the scale-invariant NMSSM in a way that is natural in all respects, i.e., not only is the stop mass and hence its loop contribution to Higgs mass of natural size, but we do not allow significant tuning of NMSSM parameters as well. We pursue as much as possible an analytic approach which gives clear insights on various ways to accommodate such a Higgs mass, while conducting complementary numerical analyses. We consider both scenarios with singlet-like state being heavier and lighter than SM-like Higgs. With A-terms being small, we find for the NMSSM to be perturbative up to GUT scale, it is not possible to get 125 GeV Higgs mass, which is true even if we tune parameters of NMSSM. If we allow some of the couplings to become non-perturbative below the GUT scale, then the non-tuned option implies that the singlet self-coupling, kappa, is larger than the singlet-Higgs coupling, lambda, which itself is order 1. This leads to a Landau pole for these couplings close to the weak scale, in particular below ~10^4 TeV. In both the perturbative and non-perturbative NMSSM, allowing large A_lambda, A_kappa gives "more room" to accommodate a 125 GeV Higgs, but a tuning of these A-terms may be needed. In our analysis we also conduct a careful study of the constraints on the parameter space from requiring global stability of the desired vacuum fitting a 125 GeV Higgs, which is complementary to existing literature. In particular, as the singlet-Higgs coupling lambda increases, vacuum stability becomes more serious of an issue.Comment: 34 pages, 4 figures, references added, minor corrections to text and figures, version to be published in JHE

Association between average daily gain, faecal dry matter content and concentration of Lawsonia intracellularis in faeces

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to investigate the association between average daily gain and the number of <it>Lawsonia intracellularis</it> bacteria in faeces of growing pigs with different levels of diarrhoea.</p> <p>Methods</p> <p>A longitudinal field study (<it>n</it> = 150 pigs) was performed in a Danish herd from day 29 to 47 post weaning. Every third day all pigs were weighed, subjected to a clinical examination and faecal samples were obtained. Faecal samples were subjected to dry matter determination and absolute quantification by PCR for <it>L. intracellularis</it> and porcine circovirus type 2 (PCV2). Association between average daily gain, faecal dry matter content, numbers of <it>L. intracellularis</it> bacteria and PCV2 genome copies in faeces was investigated in a multilevel mixed-effects linear model.</p> <p>Results</p> <p>Increasing numbers of <it>L. intracellularis</it> log₁₀ bacteria/g faeces were significantly associated with decreasing average daily gain (<it>P</it> < 0.001). The association was decreasing with increasing faecal dry matter content (<it>P</it> < 0.01). The number of PCV2 log₁₀ copies/g faeces was not significantly associated with average daily gain of the pigs (<it>P</it> > 0.5).</p> <p>Conclusion</p> <p>The results suggest a potential application of a PCR quantifying <it>L. intracellularis</it> in growing pigs. Faecal dry matter content must be taken into consideration in interpretation of such test results.</p

A Small Conductance Calcium-Activated K⁺ Channel in C. elegans, KCNL-2, Plays a Role in the Regulation of the Rate of Egg-Laying

In the nervous system of mice, small conductance calcium-activated potassium (SK) channels function to regulate neuronal excitability through the generation of a component of the medium afterhyperpolarization that follows action potentials. In humans, irregular action potential firing frequency underlies diseases such as ataxia, epilepsy, schizophrenia and Parkinson's disease. Due to the complexity of studying protein function in the mammalian nervous system, we sought to characterize an SK channel homologue, KCNL-2, in C. elegans, a genetically tractable system in which the lineage of individual neurons was mapped from their early developmental stages. Sequence analysis of the KCNL-2 protein reveals that the six transmembrane domains, the potassium-selective pore and the calmodulin binding domain are highly conserved with the mammalian homologues. We used widefield and confocal fluorescent imaging to show that a fusion construct of KCNL-2 with GFP in transgenic lines is expressed in the nervous system of C. elegans. We also show that a KCNL-2 null strain, kcnl-2(tm1885), demonstrates a mild egg-laying defective phenotype, a phenotype that is rescued in a KCNL-2-dependent manner. Conversely, we show that transgenic lines that overexpress KCNL-2 demonstrate a hyperactive egg-laying phenotype. In this study, we show that the vulva of transgenic hermaphrodites is highly innervated by neuronal processes and by the VC4 and VC5 neurons that express GFP-tagged KCNL-2. We propose that KCNL-2 functions in the nervous system of C. elegans to regulate the rate of egg-laying. © 2013 Chotoo et al