Mechanical model for a collagen fibril pair in extracellular matrix

In this paper, we model the mechanics of a collagen pair in the connective tissue extracellular matrix that exists in abundance throughout animals, including the human body. This connective tissue comprises repeated units of two main structures, namely collagens as well as axial, parallel and regular anionic glycosaminoglycan between collagens. The collagen fibril can be modeled by Hooke's law whereas anionic glycosaminoglycan behaves more like a rubber-band rod and as such can be better modeled by the worm-like chain model. While both computer simulations and continuum mechanics models have been investigated the behavior of this connective tissue typically, authors either assume a simple form of the molecular potential energy or entirely ignore the microscopic structure of the connective tissue. Here, we apply basic physical methodologies and simple applied mathematical modeling techniques to describe the collagen pair quantitatively. We find that the growth of fibrils is intimately related to the maximum length of the anionic glycosaminoglycan and the relative displacement of two adjacent fibrils, which in return is closely related to the effectiveness of anionic glycosaminoglycan in transmitting forces between fibrils. These reveal the importance of the anionic glycosaminoglycan in maintaining the structural shape of the connective tissue extracellular matrix and eventually the shape modulus of human tissues. We also find that some macroscopic properties, like the maximum molecular energy and the breaking fraction of the collagen, are also related to the microscopic characteristics of the anionic glycosaminoglycan

A Non-Specific Effect Associated with Conditional Transgene Expression Based on Cre-loxP Strategy in Mice

Transgenes flanked by loxP sites have been widely used to generate transgenic mice where the transgene expression can be controlled spatially and temporally by Cre recombinase. Data from this approach has led to important conclusions in cancer, neurodevelopment and neurodegeneration. Using this approach to conditionally express micro RNAs (miRNAs) in mice, we found that Cre-mediated recombination in neural progenitor cells caused microcephaly in five of our ten independent transgenic lines. This effect was not associated with the types or the quantity of miRNAs being expressed, nor was it associated with specific target knockdown. Rather, it was correlated with the presence of multiple tandem transgene copies and inverted (head-to-head or tail-to-tail) transgene repeats. The presence of these inverted repeats caused a high level of cell death in the ventricular zone of the embryonic brain, where Cre was expressed. Therefore, results from this Cre-loxP approach to generate inducible transgenic alleles must be interpreted with caution and conclusions drawn in previous reports may need reexamination

Trypanosoma brucei PUF9 Regulates mRNAs for Proteins Involved in Replicative Processes over the Cell Cycle

Many genes that are required at specific points in the cell cycle exhibit cell cycle–dependent expression. In the early-diverging model eukaryote and important human pathogen Trypanosoma brucei, regulation of gene expression in the cell cycle and other processes is almost entirely post-transcriptional. Here, we show that the T. brucei RNA-binding protein PUF9 stabilizes certain transcripts during S-phase. Target transcripts of PUF9—LIGKA, PNT1 and PNT2—were identified by affinity purification with TAP-tagged PUF9. RNAi against PUF9 caused an accumulation of cells in G2/M phase and unexpectedly destabilized the PUF9 target mRNAs, despite the fact that most known Puf-domain proteins promote degradation of their target mRNAs. The levels of the PUF9-regulated transcripts were cell cycle dependent, peaking in mid- to late- S-phase, and this effect was abolished when PUF9 was targeted by RNAi. The sequence UUGUACC was over-represented in the 3′ UTRs of PUF9 targets; a point mutation in this motif abolished PUF9-dependent stabilization of a reporter transcript carrying the PNT1 3′ UTR. LIGKA is involved in replication of the kinetoplast, and here we show that PNT1 is also kinetoplast-associated and its over-expression causes kinetoplast-related defects, while PNT2 is localized to the nucleus in G1 phase and redistributes to the mitotic spindle during mitosis. PUF9 targets may constitute a post-transcriptional regulon, encoding proteins involved in temporally coordinated replicative processes in early G2 phase

Does Foreign Direct Investment Stimulate New Firm Creation? In Search of Spillovers through Industrial and Geographical Linkages

This paper examines the spillover effects of inward foreign direct investment (FDI) on the entrepreneurial activities of new firm creation through both industrial and geographical linkages. Using a dataset of 44,434 newly created small firms in 234 regions of South Korea in 2000–2004, this study finds that while the spillover impacts of FDI in the low-tech industry are positive and significant across almost all four possible combinations of the intra-/inter-regional and intra-/inter-sectoral channels, the impacts in the high-tech industry are largely intra-sectoral within the host region and across neighboring regions. Moreover, all statistically significant spillover effects follow an inverted ‘U’-shaped curvilinear trend

Effect of rehabilitation exercise durations on the dynamic bone repair process by coupling polymer scaffold degradation and bone formation

Implantation of biodegradable scaffold is considered as a promising method to treat bone disorders, but knowledge of the dynamic bone repair process is extremely limited. In this study, based on the representative volume cell of a periodic scaffold, the influence of rehabilitation exercise duration per day on the bone repair was investigated by a computational framework. The framework coupled scaffold degradation and bone remodeling. The scaffold degradation was described by a function of stochastic hydrolysis independent of mechanical stimulation, and the bone formation was remodeled by a function of the mechanical stimulation, i.e., strain energy density. Then, numerical simulations were performed to study the dynamic bone repair process. The results showed that the scaffold degradation and the bone formation in the process were competitive. An optimal exercise duration per day emerged. All exercise durations promoted the bone maturation with a final Young's modulus of 1.9 ± 0.3 GPa. The present study connects clinical rehabilitation and fundamental research, and is helpful to understand the bone repair process and further design bone scaffold for bone tissue engineering

Cleavage modification did not alter blastomere fates during bryozoan evolution

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The study was funded by the core budget of the Sars Centre and by The European Research Council Community’s Framework Program Horizon 2020 (2014–2020) ERC grant agreement 648861 to A

The clinical course of pain and disability following surgery for spinal stenosis: a systematic review and meta-analysis of cohort studies

Purpose: The aim of this study was to assess the clinical course of pain and disability in patients with lumbar spinal stenosis following surgery. Methods: Electronic databases were searched to July 2014 and only prospective cohort studies assessing pain or disability following surgery for lumbar spinal stenosis were included. Two independent reviewers extracted data and assessed study quality. Estimates of pain and disability (expressed as 0–100 point scales) as well as 95 % confidence intervals were obtained using meta-regression. The effect of time was clearly non-linear, so it was modelled using fractional polynomial regression. Results: From a total of 10,741 titles, 69 publications (64 cohort studies) were included in the review. Pooled estimate for pain pre-operatively was 63.4 (95 % CI 56.5; 70.3), reducing to 33.1 (95 % CI 24.2; 41.9) at 3 months and 19.2 points (95 % CI 9.2; 29.3) at 60 months. Pre-operative estimates of disability were 36.9 (95 % CI 32.6; 41.3), reducing to 16.3 (95 % CI 11.8; 20.9) at 3 months and 12.4 (95 % CI 7.7; 17.2) at 60 months. Conclusion: Patients with lumbar spinal stenosis experience rapid symptom reduction after surgery, but should still expect to experience mild-to-moderate pain and disability 60 months later

Measuring adherence to unsupervised, conservative treatment for knee osteoarthritis: A systematic review

Objective To describe the measurement of adherence to unsupervised, conservative treatments for knee osteoarthritis (OA), including the methods of adherence measurement, parameters for assessing adherence and any values used to quantify adherence. Methods A systematic review with search terms related to knee OA, conservative treatments and adherence was conducted. The protocol was registered with the International Prospective Register of Systematic Reviews (registration number CRD42020158188). Seven electronic databases (MEDLINE, AMED, EMBASE, CINAHL, SportDiscus, PsychINFO, PEDro) were searched from inception to February 02, 2021. Studies that included unsupervised, conservative treatment(s) for knee OA measuring adherence were eligible. Studies were independently screened for inclusion by two researchers. Data was extracted by one researcher and verified by a second researcher. Extracted data included: study type, population, type of treatment, adherence measurement methods, time-points, recall, parameters and values used to quantify adherence. Results Of 5033 references identified, 242 studies comprising of 261 treatments were included in the review. The majority of studies were randomised controlled trials investigating therapeutic exercise (n ​= ​107, 41.0%). The most common adherence measurement across all treatments was through self-reported diary (n ​= ​137, 52.5%) and the most common parameter was assessing the frequency of the treatment (n ​= ​79, 30.3%). Only a small number of studies provided values for quantifying satisfactory adherence (n ​= ​26, 9.3%). Conclusion There is a wide variety in the reporting of adherence to conservative treatments for knee OA and standardised methods for measuring and reporting adherence are needed. Developing a tool to measure adherence to conservative treatments for knee OA is a priority

Family-based Interventions Benefit Individuals with Musculoskeletal Pain in the Short-term but not in the Long Term: A Systematic Review and Meta-analysis.

INTRODUCTION: The benefits of family-based interventions for patients with musculoskeletal pain have been previously shown in individual randomised controlled trials (RCTs), but no systematic review has summarised their effects. MATERIALS AND METHODS: A systematic review was conducted to assess the effectiveness of family-based interventions on clinical and biopsychosocial outcomes in people with musculoskeletal pain (PROSPERO CRD42018118442). Meta-analyses were performed for the outcomes of pain intensity, disability, mood, self-efficacy, and marital adjustment. RESULTS: Of 1,223 records identified, 18 reports representing 15 RCTs were included in the qualitative review and 10 in the meta-analyses. Family-based interventions were more effective to reduce pain [Mean difference (MD): -3.55/100; 95%CI -4.03, -3.06], and disability (MD: -1.51/100; 95%CI -1.98, -1.05) than individual-focused interventions at short-term, but not at mid or long-term. There were no effects on other outcomes. Family-based interventions were more effective to reduce pain (MD: -6.05/100; 95%CI -6.78, -5.33) compared to usual care only at short-term. No effects were found on disability and other outcomes. DISCUSSION: There is moderate-quality evidence that family-based interventions result in small, significantly better pain and disability outcomes in the short-term compared to individual-focused interventions in patients with musculoskeletal pain. Based on low-quality evidence, family-based interventions result in small improvements on pain in the short-term compared to usual care. Future studies should review the content and optimise the mechanisms underpinning family-based interventions in musculoskeletal pain so that the approach could be further tested in adequately powered RCTs