Exploring hierarchical and overlapping modular structure in the yeast protein interaction network

<p>Abstract</p> <p>Background</p> <p>Developing effective strategies to reveal modular structures in protein interaction networks is crucial for better understanding of molecular mechanisms of underlying biological processes. In this paper, we propose a new density-based algorithm (ADHOC) for clustering vertices of a protein interaction network using a novel subgraph density measurement.</p> <p>Results</p> <p>By statistically evaluating several independent criteria, we found that ADHOC could significantly improve the outcome as compared with five previously reported density-dependent methods. We further applied ADHOC to investigate the hierarchical and overlapping modular structure in the yeast PPI network. Our method could effectively detect both protein modules and the overlaps between them, and thus greatly promote the precise prediction of protein functions. Moreover, by further assaying the intermodule layer of the yeast PPI network, we classified hubs into two types, module hubs and inter-module hubs. Each type presents distinct characteristics both in network topology and biological functions, which could conduce to the better understanding of relationship between network architecture and biological implications.</p> <p>Conclusions</p> <p>Our proposed algorithm based on the novel subgraph density measurement makes it possible to more precisely detect hierarchical and overlapping modular structures in protein interaction networks. In addition, our method also shows a strong robustness against the noise in network, which is quite critical for analyzing such a high noise network.</p

Coding or Noncoding, the Converging Concepts of RNAs

Technological advances over the past decade have unraveled the remarkable complexity of RNA. The identification of small peptides encoded by long non-coding RNAs (lncRNAs) as well as regulatory functions mediated by non-coding regions of mRNAs have further complicated our understanding of the multifaceted functions of RNA. In this review, we summarize current evidence pointing to dual roles of RNA molecules defined by their coding and non-coding potentials. We also discuss how the emerging roles of RNA transform our understanding of gene expression and evolution

Clustered microRNAs' coordination in regulating protein-protein interaction network

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs), a growing class of small RNAs with crucial regulatory roles at the post-transcriptional level, are usually found to be clustered on chromosomes. However, with the exception of a few individual cases, so far little is known about the functional consequence of this conserved clustering of miRNA loci. In animal genomes such clusters often contain non-homologous miRNA genes. One hypothesis to explain this heterogeneity suggests that clustered miRNAs are functionally related by virtue of co-targeting downstream pathways.</p> <p>Results</p> <p>Integrating of miRNA cluster information with protein protein interaction (PPI) network data, our research supports the hypothesis of the functional coordination of clustered miRNAs and links it to the topological features of miRNAs' targets in PPI network. Specifically, our results demonstrate that clustered miRNAs jointly regulate proteins in close proximity of the PPI network. The possibility that two proteins yield to this coordinated regulation is negatively correlated with their distance in PPI network. Guided by the knowledge of this preference, we found several network communities enriched with target genes of miRNA clusters. In addition, our results demonstrate that the variance of this propensity can also partly be explained by protein's connectivity and miRNA's conservation.</p> <p>Conclusion</p> <p>In summary, this work supports the hypothesis of intra-cluster coordination and investigates the extent of this coordination.</p

MicroRNA-encoding long non-coding RNAs

© 2008 He et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

NONCODE: an integrated knowledge database of non-coding RNAs

NONCODE is an integrated knowledge database dedicated to non-coding RNAs (ncRNAs), that is to say, RNAs that function without being translated into proteins. All ncRNAs in NONCODE were filtered automatically from literature and GenBank, and were later manually curated. The distinctive features of NONCODE are as follows: (i) the ncRNAs in NONCODE include almost all the types of ncRNAs, except transfer RNAs and ribosomal RNAs. (ii) All ncRNA sequences and their related information (e.g. function, cellular role, cellular location, chromosomal information, etc.) in NONCODE have been confirmed manually by consulting relevant literature: more than 80% of the entries are based on experimental data. (iii) Based on the cellular process and function, which a given ncRNA is involved in, we introduced a novel classification system, labeled process function class, to integrate existing classification systems. (iv) In addition, some 1100 ncRNAs have been grouped into nine other classes according to whether they are specific to gender or tissue or associated with tumors and diseases, etc. (v) NONCODE provides a user-friendly interface, a visualization platform and a convenient search option, allowing efficient recovery of sequence, regulatory elements in the flanking sequences, secondary structure, related publications and other information. The first release of NONCODE (v1.0) contains 5339 non-redundant sequences from 861 organisms, including eukaryotes, eubacteria, archaebacteria, virus and viroids. Access is free for all users through a web interface at http://noncode.bioinfo.org.cn

The Promotion of Mechanical Properties by Bone Ingrowth in Additive-Manufactured Titanium Scaffolds

Although the initial mechanical properties of additive-manufactured (AM) metal scaffolds have been thoroughly studied and have become a cornerstone in the design of porous orthopaedic implants, the potential promotion of the mechanical properties of the scaffolds by bone ingrowth has barely been studied. In this study, the promotion of bone ingrowth on the mechanical properties of AM titanium alloy scaffolds was investigated through in vivo experiments and numerical simulation. On one hand, the osseointegration characteristics of scaffolds with architectures of body-centred cubic (BCC) and diamond were compared through animal experiments in which the mechanical properties of both scaffolds were not enhanced by the four-week implantation. On the other hand, the influences of the type and morphology of bone tissue in the BCC scaffolds on its mechanical properties were investigated by the finite element model of osseointegrated scaffolds, which was calibrated by the results of biomechanical testing. Significant promotion of the mechanical properties of AM metal scaffolds was only found when cortical bone filled the pores in the scaffolds. This paper provides a numerical prediction method to investigate the effect of bone ingrowth on the mechanical properties of AM porous implants, which might be valuable for the design of porous implants

Efficacy and safety of Argatroban in patients with acute ischemic stroke: a systematic review and meta-analysis

ObjectiveArgatroban is a highly promising drug for the treatment of acute ischemic stroke (AIS), but there is currently insufficient strong evidence regarding the efficacy and safety of using Argatroban in the treatment of AIS. Therefore, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of Argatroban in the treatment of AIS.MethodsArticles on PubMed, Embase and the Cochrane Library databases were searched from these websites’ inceptions to 2th February 2023. Randomized controlled trials and observational studies on Argatroban therapy for acute ischemic stroke were included. Meta-analyses were conducted using a random-effects model.ResultsFourteen studies involving 10,315 patients were included in the meta-analysis. The results showed a significant reduction in the rate of early neurological deterioration (END) in the Argatroban group compared with the control group (OR = 0.47, 95% CI: 0.31–0.73, I2 = 15.17%). The rates of adverse events were no significant difference between the two groups (ICH: OR = 1.02, 95% CI: 0.68–1.51, I2 = 0.00%; major extracranial bleeding: OR = 1.22, 95% CI: 1.01–1.48, I2 = 0.00%; mortality: OR = 1.16, 95% CI: 0.84–1.59, I2 = 0.00%). However, the rates of mRS score of 0–1 (OR = 1.38, 95% CI: 0.71–2.67, I2 = 77.56%) and mRS score of 0–2 (OR = 1.18, 95% CI: 0.98–1.42, I2 = 0.00%) during the 90 days did not significantly improved in the Argatroban group. Subgroup analyses showed that the rate of END (OR = 0.41, 95% CI: 0.26–0.65, I2 = 2.77%) and mRS score of 0–2 (OR = 1.38, 95% CI: 1.06–1.81, I2 = 0.00%) had significantly improved when the intervention group adopted Argatroban plus Antiplatelet.ConclusionArgatroban can improve neurological deterioration, with a low incidence of adverse events such as bleeding and death, and general analysis showed no improvement in mRS. However, subgroup analysis suggests that compared to mono-antiplatelet therapy, combination therapy of Argatroban combined with antiplatelet therapy significantly reduced the incidence of END and improved mRS scores. After using Argatroban, there was no increase in the risk and mortality of intracranial hemorrhage and other bleeding sites

Fused Deposition Modeling PEEK Implants for Personalized Surgical Application: From Clinical Need to Biofabrication

Three-dimensional printing (3DP) technology is suitable for manufacturing personalized orthopedic implants for reconstruction surgery. Compared with traditional titanium, polyether-ether-ketone (PEEK) is the ideal material for 3DP orthopedic implants due to its various advantages, including thermoplasticity, thermal stability, high chemical stability, and radiolucency suitable elastic modulus. However, it is challenging to develop a well-designed method and manufacturing technique to meet the clinical needs because it requires elaborate details and interplays with clinical work. Furthermore, establishing surgical standards for new implants requires many clinical cases and an accumulation of surgical experience. Thus, there are few case reports on using 3DP PEEK implants in clinical practice. Herein, we formed a team with a lot of engineers, scientists, and doctors and conducted a series of studies on the 3DP PEEK implants for chest wall reconstruction. First, the thoracic surgeons sort out the specific types of chest wall defects. Then, the engineers designed the shape of the implant and performed finite element analysis for every implant. To meet the clinical needs and mechanical requirements of implants, we developed a new fused deposition modeling technology to make personalized PEEK implants. Overall, the thoracic surgeons have used 114 personalized 3DP PEEK implants to reconstruct the chest wall defect and further established the surgical standards of the implants as part of the Chinese clinical guidelines. The surface modification technique and composite process are developed to overcome the new clinical problems of implant-related complications after surgery. Finally, the major challenges and possible solutions to translating 3DP PEEK implants into a mature and prevalent clinical product are discussed in the paper

Dynamic Changes in Subgraph Preference Profiles of Crucial Transcription Factors

Transcription factors with a large number of target genes—transcription hub(s), or THub(s)—are usually crucial components of the regulatory system of a cell, and the different patterns through which they transfer the transcriptional signal to downstream cascades are of great interest. By profiling normalized abundances (A(N)) of basic regulatory patterns of individual THubs in the yeast Saccharomyces cerevisiae transcriptional regulation network under five different cellular states and environmental conditions, we have investigated their preferences for different basic regulatory patterns. Subgraph-normalized abundances downstream of individual THubs often differ significantly from that of the network as a whole, and conversely, certain over-represented subgraphs are not preferred by any THub. The THub preferences changed substantially when the cellular or environmental conditions changed. This switching of regulatory pattern preferences suggests that a change in conditions does not only elicit a change in response by the regulatory network, but also a change in the mechanisms by which the response is mediated. The THub subgraph preference profile thus provides a novel tool for description of the structure and organization between the large-scale exponents and local regulatory patterns

Stress Shielding and Bone Resorption of Press-Fit Polyether–Ether–Ketone (PEEK) Hip Prosthesis: A Sawbone Model Study

Stress shielding secondary to bone resorption is one of the main causes of aseptic loosening, which limits the lifespan of the hip prostheses and increases the rates of revision surgery. This study proposes a low stiffness polyether–ether–ketone (PEEK) hip prostheses, produced by fused deposition modelling to minimize the stress difference after the hip replacement. The stress shielding effect and the potential bone resorption of the PEEK implant was investigated through both experimental tests and FE simulation. A generic Ti6Al4V implant was incorporated in this study to allow fair comparison as control group. Attributed to the low stiffness, the proposed PEEK implant showed a more natural stress distribution, less stress shielding (by 104%), and loss in bone mass (by 72%) compared with the Ti6Al4V implant. The stiffness of the Ti6Al4V and the PEEK implant were measured through compression tests to be 2.76 kN/mm and 0.276 kN/mm. The factor of safety for the PEEK implant in both static and dynamic loading scenarios were obtained through simulation. Most of the regions in the PEEK implant were tested to be safe (FoS larger than 1) in terms of representing daily activities (2300 N), while the medial neck and distal restriction point of the implant attracts large von Mises stress 82 MPa and 76 MPa, respectively, and, thus, may possibly fail during intensive activities by yield and fatigue. Overall, considering the reduction in stress shielding and bone resorption in cortical bone, PEEK could be a promising material for the patient–specific femoral implants