A new multiple regression approach for the construction of genetic regulatory networks

Objective: Re-construction of a genetic regulatory network from a given time-series gene expression data is an important research topic in systems biology. One of the main difficulties in building a genetic regulatory network lies in the fact that practical data set has a huge number of genes vs. a small number of sampling time points. In this paper, we propose a new linear regression model that may overcome this difficulty for uncovering the regulatory relationship in a genetic network. Methods: The proposed multiple regression model makes use of the scale-free property of a real biological network. In particular, a filter is constructed by using this scale-free property and some appropriate statistical tests to remove redundant interactions among the genes. A model is then constructed by minimizing the gap between the observed and the predicted data. Results: Numerical examples based on yeast gene expression data are given to demonstrate that the proposed model fits the practical data very well. Some interesting properties of the genes and the underlying network are also observed. Conclusions: In conclusion, we propose a new multiple regression model based on the scale-free property of real biological network for genetic regulatory network inference. Numerical results using yeast cell cycle gene expression dataset show the effectiveness of our method. We expect that the proposed method can be widely used for genetic network inference using high-throughput gene expression data from various species for systems biology discovery. © 2009 Elsevier B.V.postprin

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study

BACKGROUND: The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. METHODS: This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. RESULTS: Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. CONCLUSIONS: There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02586-9

Mapping Cosmic Dawn and Reionization: Challenges and Synergies

Cosmic dawn and the Epoch of Reionization (EoR) are among the least explored observational eras in cosmology: a time at which the first galaxies and supermassive black holes formed and reionized the cold, neutral Universe of the post-recombination era. With current instruments, only a handful of the brightest galaxies and quasars from that time are detectable as individual objects, due to their extreme distances. Fortunately, a multitude of multi-wavelength intensity mapping measurements, ranging from the redshifted 21 cm background in the radio to the unresolved X-ray background, contain a plethora of synergistic information about this elusive era. The coming decade will likely see direct detections of inhomogenous reionization with CMB and 21 cm observations, and a slew of other probes covering overlapping areas and complementary physical processes will provide crucial additional information and cross-validation. To maximize scientific discovery and return on investment, coordinated survey planning and joint data analysis should be a high priority, closely coupled to computational models and theoretical predictions.Comment: 5 pages, 1 figure, submitted to the Astro2020 Decadal Survey Science White Paper cal

Cosmology with the Highly Redshifted 21cm Line

In addition to being a probe of Cosmic Dawn and Epoch of Reionization astrophysics, the 21cm line at $z>6$ is also a powerful way to constrain cosmology. Its power derives from several unique capabilities. First, the 21cm line is sensitive to energy injections into the intergalactic medium at high redshifts. It also increases the number of measurable modes compared to existing cosmological probes by orders of magnitude. Many of these modes are on smaller scales than are accessible via the CMB, and moreover have the advantage of being firmly in the linear regime (making them easy to model theoretically). Finally, the 21cm line provides access to redshifts prior to the formation of luminous objects. Together, these features of 21cm cosmology at $z>6$ provide multiple pathways toward precise cosmological constraints. These include the "marginalizing out" of astrophysical effects, the utilization of redshift space distortions, the breaking of CMB degeneracies, the identification of signatures of relative velocities between baryons and dark matter, and the discovery of unexpected signs of physics beyond the $\Lambda$CDM paradigm at high redshifts.Comment: Science white paper submitted to Decadal 2020 surve

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

Ganoderma lucidum polysaccharides can induce human monocytic leukemia cells into dendritic cells with immuno-stimulatory function

<p>Abstract</p> <p>Background</p> <p>Previous studies demonstrated <it>Ganoderma lucidum </it>polysaccharides (GL-PS), a form of bioactive β-glucan can stimulate the maturation of monocyte-derived dendritic cells (DC). The question of how leukemic cells especially in monocytic lineage respond to GL-PS stimuli remains unclear.</p> <p>Results</p> <p>In this study, we used <it>in vitro</it> culture model with leukemic monocytic cell-lines THP-1 and U937 as monocytic effectors cells for proliferation responses and DCs induction. We treated the THP-1 and U937 cells with purified GL-PS (100 μg/mL) or GL-PS with GM-CSF/IL-4. GL-PS alone induced proliferative response on both THP-1 and U937 cells but only THP-1 transformed into typical DC morphology when stimulated with GL-PS plus GM-CSF/IL-4. The transformed THP-1 DCs had significant increase expression of HLA-DR, CD40, CD80 and CD86 though not as high as the extent of normal monocyte-derived DCs. They had similar antigen-uptake ability as the normal monocyte-derived DCs positive control. However, their potency in inducing allogeneic T cell proliferation was also less than that of normal monocyte-derived DCs.</p> <p>Conclusion</p> <p>Our findings suggested that GL-PS could induce selected monocytic leukemic cell differentiation into DCs with immuno-stimulatory function. The possible clinical impact of using this commonly used medicinal mushroom in patients with monocytic leukemia (AML-M4 and M5) deserved further investigation.</p

Proteomics analysis of serum protein profiling in pancreatic cancer patients by DIGE: up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer has significant morbidity and mortality worldwide. Good prognosis relies on an early diagnosis. The purpose of this study was to develop techniques for identifying cancer biomarkers in the serum of patients with pancreatic cancer.</p> <p>Methods</p> <p>Serum samples from five individuals with pancreatic cancer and five individuals without cancer were compared. Highly abundant serum proteins were depleted by immuno-affinity column. Differential protein analysis was performed using 2-dimensional differential in-gel electrophoresis (2D-DIGE).</p> <p>Results</p> <p>Among these protein spots, we found that 16 protein spots were differently expressed between the two mixtures; 8 of these were up-regulated and 8 were down-regulated in cancer. Mass spectrometry and database searching allowed the identification of the proteins corresponding to the gel spots. Up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2, which have not previously been implicated in pancreatic cancer, were observed. In an independent series of serum samples from 16 patients with pancreatic cancer and 16 non-cancer-bearing controls, increased levels of mannose-binding lectin 2 and myosin light chain kinase 2 were confirmed by western blot.</p> <p>Conclusions</p> <p>These results suggest that affinity column enrichment and DIGE can be used to identify proteins differentially expressed in serum from pancreatic cancer patients. These two proteins 'mannose-binding lectin 2 and myosin light chain kinase 2' might be potential biomarkers for the diagnosis of the pancreatic cancer.</p