Multiway modeling and analysis in stem cell systems biology

<p>Abstract</p> <p>Background</p> <p>Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.). A number of deterministic, probabilistic, and statistical learning models are used to understand sophisticated cellular behaviors such as protein expression during cellular differentiation and the activity of signaling networks. However, many of these models are bimodal i.e., they only consider row-column relationships. In contrast, multiway modeling techniques (also known as tensor models) can analyze multimodal data, which capture much more information about complex behaviors such as cell differentiation. In particular, tensors can be very powerful tools for modeling the dynamic activity of biological networks over time. Here, we review the application of systems biology to stem cells and illustrate application of tensor analysis to model collagen-induced osteogenic differentiation of human mesenchymal stem cells.</p> <p>Results</p> <p>We applied Tucker1, Tucker3, and Parallel Factor Analysis (PARAFAC) models to identify protein/gene expression patterns during extracellular matrix-induced osteogenic differentiation of human mesenchymal stem cells. In one case, we organized our data into a tensor of type protein/gene locus link × gene ontology category × osteogenic stimulant, and found that our cells expressed two distinct, stimulus-dependent sets of functionally related genes as they underwent osteogenic differentiation. In a second case, we organized DNA microarray data in a three-way tensor of gene IDs × osteogenic stimulus × replicates, and found that application of tensile strain to a collagen I substrate accelerated the osteogenic differentiation induced by a static collagen I substrate.</p> <p>Conclusion</p> <p>Our results suggest gene- and protein-level models whereby stem cells undergo transdifferentiation to osteoblasts, and lay the foundation for mechanistic, hypothesis-driven studies. Our analysis methods are applicable to a wide range of stem cell differentiation models.</p

U potrazi za optimalnom psihoaktivacijom – stimulansi kao pojačivači kognitivne funkcije

An increasing number of people, students in particular, seek substances that improve their cognitive functioning. The most popular group of pharmacological cognitive enhancers (PCEs) are stimulants. Available studies suggest a small beneficial effect of methylphenidate and amphetamine on memory, executive functions, and processing speed. However small, this effect can make the difference between success and failure. In recent years, research has focused on the additional beneficial effect on the emotional state, increased motivation, and placebo-induced cognitive enhancement. This paper briefly reviews the latest and most important research on the relationship between popular stimulants and cognitive enhancement. One cannot understand this relationship without understanding the Yerkes-Dodson law, which explains the relationship between the degree of arousal and performance. It suggests that the effect of stimulants is a dose-dependent continuum. This law has repeatedly been confirmed by studies in which an optimal level of psychoactivation for cognitive enhancement was obtained with low stimulant doses, whereas exceeding the effective dose resulted in cognitive deficits, psychomotor agitation, and addiction. A separate section has been devoted to modafinil, an increasingly popular stimulant that differs from the rest in neurochemical profile and behavioural effects.Sve više ljudi, napose studenata, traži tvari kojima će poboljšati svoju kognitivnu funkciju. Najpopularniji među farmakološkim pojačivačima kognitivne funkcije jesu stimulansi. Rezultati dostupnih istraživanja pokazuju blago, povoljno djelovanje metilfenidata i amfetamina na pamćenje, izvršne funkcije i brzinu obrade (procesiranja). Premda je poboljšanje blago, ono u studenata može značiti razliku između uspjeha i neuspjeha. Posljednjih se je godina istraživanje usmjerilo na dodatne povoljne učinke stimulansa na emocionalno stanje, povećanu motivaciju, pa i na kognitivna poboljšanja povezana s placebom. U ovom se radu daje kratki pregled najnovijih i najvažnijih istraživanja odnosa između popularnih stimulansa i poboljšanja kognitivne funkcije. Taj se odnos ne može razumjeti bez poznavanja Yerkes-Dodsonova zakona, koji objašnjava odnos između razine uzbuđenosti i izvedbe (performanse) te govori o tome da stimulansi djeluju u kontinuumu koji je ovisan o dozi. Zakon je opetovano potvrđivan istraživanjima u kojima je optimalna razina psihoaktivacije za poboljšanje kognitivne funkcije postignuta niskim dozama stimulansa, a previsoke razine dovodile su do pada kognitivnih deficita, psihomotorne agitacije i ovisnosti. Dio je teksta posvećen modafinilu, sve popularnijem stimulansu koji se svojim neurokemijskim svojstvima i djelovanjem na ponašanje razlikuje od ostalih

Developmental history and stress responsiveness are related to response inhibition, but not judgement bias, in a cohort of European starlings (Sturnus vulgaris)

Judgement bias tasks are designed to provide markers of affective states. A recent study of European starlings (Sturnus vulgaris) demonstrated modest familial effects on judgement bias performance, and found that adverse early experience and developmental telomere attrition (an integrative marker of biological age) both affected judgement bias. Other research has shown that corticosterone levels affect judgement bias. Here, we investigated judgement bias using a modified Go/No Go task in a new cohort of starlings (n = 31) hand-reared under different early-life conditions. We also measured baseline corticosterone and the corticosterone response to acute stress in the same individuals. We found evidence for familial effects on judgement bias, of a similar magnitude to the previous study. We found no evidence that developmental treatments or developmental telomere attrition were related to judgement bias per se. We did, however, find that birds that experienced the most benign developmental conditions, and birds with the greatest developmental telomere attrition, were significantly faster to probe the learned unrewarded stimulus. We also found that the birds whose corticosterone levels were faster to return towards baseline after an acute stressor were slower to probe the learned unrewarded stimulus. Our results illustrate the potential complexities of relationships between early-life experience, stress and affectively mediated decision making. For judgement bias tasks, they demonstrate the importance of clearly distinguishing factors that affect patterns of responding to the learned stimuli (i.e. response inhibition in the case of the Go/No Go design) from factors that influence judgements under ambiguity

Epitopes of Bordetella pertussis lipopolysaccharides as potential markers for typing of isolates with monoclonal antibodies: Microbiology.

NRC publication: Ye

Specific and cross-reacting monoclonal antibodies to Bordetella parapertussis and Bordetella bronchiseptica lipopolysaccharides: Microbiology.

NRC publication: Ye

Overlapping network meta-analyses on psoriasis systemic treatments: an overview, quantity does not make quality

International audienceBACKGROUND: Network Meta-analyses (NMAs) have become successful in addressing gaps in the comparative effectiveness of systemic treatments in moderate-to-severe psoriasis. However, their increasing number carries both a risk of overlap and reproducibility issues that can hamper clinical decision-making. In this overview, we aimed to assess redundancy across these NMAs and to describe their characteristics. METHODS: We considered all systematic reviews with NMAs of randomized controlled trials that included adult patients with moderate-to-severe psoriasis and that evaluated the efficacy and/or safety of systemic treatments compared with placebo or with an active comparator. PubMed/MEDLINE, Epistemonikos, PROSPERO and the Evidence Update of the Centre of Evidence-Based Dermatology of the University of Nottingham were searched up to 25 February 2021. Our main outcome was the number per year of redundant NMAs and the extent of their overlap. We also described their features, especially, the confidence in the results of the reviews, the studies’ funding and the presence of spin (a description that overstates efficacy and/or understates harm), reporting issues and methodological characteristics. RESULTS: In total, 47 redundant NMAs were included. Only 2/47 (4%) included all available treatments. Both efficacy and safety were evaluated in 14/47 (30%) NMAs and both short and long-term evaluations were assessed in 5/47 (11 %). Confidence in the results was critically low for 39/47 (83%) NMAs and only 10/47 (23 %) registered a protocol. 26/47 NMAs (55%) received pharmaceutical funding. CROs were involved in 19/47 (40%) NMAs. Reporting was poor across most of the NMAs’ abstracts and spin was present in all of the abstracts. Almost half of the NMA failed to consider important limitations such as heterogeneity (32%) or consistency (66%). DISCUSSION: In addition to a duplication of efforts, our overview showed heterogeneous methods and poor confidence in the results in a majority of the included NMAs, further distorted by reporting issues and spin. Clinicians need to interpret NMAs with caution when looking for the most reliable and comprehensive evidence

Chemical and Serological Characterization of the Bordetella hinzii Lipopolysaccharides: FEBS Lett.

In press: YesNRC publication: Ye