Complement membrane attack and tumourigenesis: a systems biology approach.

J Biol Chem. 2016 May 19;

Authors: Towner LD, Wheat RA, Hughes TR, Morgan BP

Abstract
Tumour development driven by inflammation is now an established phenomenon but the role that complement plays remains uncertain. Recent evidence has suggested that various components of the complement (C) cascade may influence tumour development in disparate ways; however, little attention has been paid to that of the membrane attack complex (MAC). This is despite abundant evidence documenting the effects of this complex on cell behaviour, including cell activation, protection from/induction of apoptosis, release of inflammatory cytokines, growth factors and ECM components and regulators and the triggering of the NLRP3 inflammasome. Here we present a novel approach to this issue by using global gene expression studies in conjunction with a systems biology analysis. Using network analysis of MAC responsive expression changes we demonstrated a cluster of co-regulated genes known to have their impact in the extracellular space and on the supporting stroma and with well-characterized tumour promoting roles. Network analysis highlighted the central role for EGFR activation in mediating the observed responses to MAC exposure. Overall, the study sheds light on the mechanisms by which sublytic MAC causes tumour cell responses and exposes a gene expression signature that implicates MAC as a driver of tumour progression. These findings have implications for understanding of the roles of C and the MAC in tumour development and progression which in turn will inform future therapeutic strategies in cancer.

PMID: 27226542 [PubMed - as supplied by publisher]

Redox regulation of vascular remodeling.

Cell Mol Life Sci. 2016 Jan;73(2):349-63

Authors: Karimi Galougahi K, Ashley EA, Ali ZA

Abstract
Vascular remodeling is a dynamic process of structural and functional changes in response to biochemical and biomechanical signals in a complex in vivo milieu. While inherently adaptive, dysregulation leads to maladaptive remodeling. Reactive oxygen species participate in homeostatic cell signaling in tightly regulated- and compartmentalized cellular circuits. It is well established that perturbations in oxidation-reduction (redox) homeostasis can lead to a state of oxidative-, and more recently, reductive stress. We provide an overview of the redox signaling in the vasculature and review the role of oxidative- and reductive stress in maladaptive vascular remodeling. Particular emphasis has been placed on essential processes that determine phenotype modulation, migration and fate of the main cell types in the vessel wall. Recent advances in systems biology and the translational opportunities they may provide to specifically target the redox pathways driving pathological vascular remodeling are discussed.

PMID: 26483132 [PubMed - indexed for MEDLINE]

Systems Metabolic Engineering of Escherichia coli.

EcoSal Plus. 2016 May;7(1)

Authors: Choi KR, Shin JH, Cho JS, Yang D, Lee SY

Abstract
Systems metabolic engineering, which recently emerged as metabolic engineering integrated with systems biology, synthetic biology, and evolutionary engineering, allows engineering of microorganisms on a systemic level for the production of valuable chemicals far beyond its native capabilities. Here, we review the strategies for systems metabolic engineering and particularly its applications in Escherichia coli. First, we cover the various tools developed for genetic manipulation in E. coli to increase the production titers of desired chemicals. Next, we detail the strategies for systems metabolic engineering in E. coli, covering the engineering of the native metabolism, the expansion of metabolism with synthetic pathways, and the process engineering aspects undertaken to achieve higher production titers of desired chemicals. Finally, we examine a couple of notable products as case studies produced in E. coli strains developed by systems metabolic engineering. The large portfolio of chemical products successfully produced by engineered E. coli listed here demonstrates the sheer capacity of what can be envisioned and achieved with respect to microbial production of chemicals. Systems metabolic engineering is no longer in its infancy; it is now widely employed and is also positioned to further embrace next-generation interdisciplinary principles and innovation for its upgrade. Systems metabolic engineering will play increasingly important roles in developing industrial strains including E. coli that are capable of efficiently producing natural and nonnatural chemicals and materials from renewable nonfood biomass.

PMID: 27223822 [PubMed - as supplied by publisher]

Cox process representation and inference for stochastic reaction-diffusion processes.

Nat Commun. 2016;7:11729

Authors: Schnoerr D, Grima R, Sanguinetti G

Abstract
Complex behaviour in many systems arises from the stochastic interactions of spatially distributed particles or agents. Stochastic reaction-diffusion processes are widely used to model such behaviour in disciplines ranging from biology to the social sciences, yet they are notoriously difficult to simulate and calibrate to observational data. Here we use ideas from statistical physics and machine learning to provide a solution to the inverse problem of learning a stochastic reaction-diffusion process from data. Our solution relies on a non-trivial connection between stochastic reaction-diffusion processes and spatio-temporal Cox processes, a well-studied class of models from computational statistics. This connection leads to an efficient and flexible algorithm for parameter inference and model selection. Our approach shows excellent accuracy on numeric and real data examples from systems biology and epidemiology. Our work provides both insights into spatio-temporal stochastic systems, and a practical solution to a long-standing problem in computational modelling.

PMID: 27222432 [PubMed - in process]

Data Mining for Identification of Molecular Targets in Ovarian Cancer.

Asian Pac J Cancer Prev. 2016;17(4):1691-9

Authors: Villegas-Ruiz V, Juarez-Mendez S

Abstract
Ovarian cancer is possibly the sixth most common malignancy worldwide, in Mexico representing the fourth leading cause of gynecological cancer death more than 70% being diagnosed at an advanced stage and the survival being very poor. Ovarian tumors are classified according to histological characteristics, epithelial ovarian cancer as the most common (~80%). We here used high-density microarrays and a systems biology approach to identify tissue-associated deregulated genes. Non-malignant ovarian tumors showed a gene expression profile associated with immune mediated inflammatory responses (28 genes), whereas malignant tumors had a gene expression profile related to cell cycle regulation (1,329 genes) and ovarian cell lines to cell cycling and metabolism (1,664 genes).

PMID: 27221839 [PubMed - in process]

Genomic Landscape of Colorectal Mucosa and Adenomas.

Cancer Prev Res (Phila). 2016 May 24;

Authors: Borras E, San Lucas FA, Chang K, Zhou R, Masand G, Fowler J, Mork ME, You YN, Taggart MW, McAllister F, Jones DA, Davies GE, Edelmann W, Ehli EA, Lynch PM, Hawk ET, Capella G, Scheet P, Vilar E

Abstract
The molecular basis of the adenoma-to-carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances (AI) in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer driver genes (APC, KRAS, FBXW7, TCF7L2) and AIs in chromosomes 5, 7, and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis. Cancer Prev Res; 9(6); 1-11. ©2016 AACR.

PMID: 27221540 [PubMed - as supplied by publisher]

[Deepening the idea of systems biology and promoting the development of pan-vascular medical science].

Zhonghua Xin Xue Guan Bing Za Zhi. 2016 May 24;44(5):373-4

Authors: Ge JB

PMID: 27220570 [PubMed - in process]

The bovine milk microbiota: insights and perspectives from -omics studies.

Mol Biosyst. 2016 May 24;

Authors: Addis MF, Tanca A, Uzzau S, Oikonomou G, Bicalho RC, Moroni P

Abstract
Recent significant progress in culture-independent techniques, together with the parallel development of -omics technologies and data analysis capabilities, have led to a new perception of the milk microbiota as a complex microbial community with great diversity and multifaceted biological roles, living in an environment that was until recently believed to be sterile. In this review, we summarize and discuss the latest findings on the milk microbiota in dairy cows, with a focus on the role it plays in bovine physiology and health. Following an introduction on microbial communities and the importance of their study, we present an overview of the -omics methods currently available for their characterization, and outline the potential offered by a systems biology approach encompassing metatranscriptomics, metaproteomics, and metametabolomics. Then, we review the recent discoveries on the dairy cow milk microbiome enabled by the application of -omics approaches. Learning from studies in humans and in the mouse model, and after a description of the endogenous route hypothesis, we discuss the role of the milk microbiota in the physiology and health of both the mother and the offspring, and report how it can be changed by farming practices and during infection. In conclusion, we shortly outline the impact of the milk microbiota on the quality of milk and of dairy products.

PMID: 27216801 [PubMed - as supplied by publisher]

Drug Design based on Protein Structure Network.

Mini Rev Med Chem. 2016 May 24;

Authors: Liang Z, Hu G

Abstract
Although structure-based drug design (SBDD) has become an indispensable tool in drug discovery for a long time, it continues to pose major challenges to date. With the advancement of "omics" techniques, systems biology has enriched SBDD into a new era, called polypharmacology, in which multi-targets drug or drug combination is designed to fight complex diseases. As a preliminary tool in systems biology, protein structure networks (PSNs) treat a protein as a set of residues linked by edges corresponding to the intramolecular interactions existing in folded structures between the residues. The PSN offers a computationally efficient tool to study the structure and function of proteins, and thus may facilitate structure-based drug design. Herein, we provide an overview of recent advances in PSNs, from predicting functionally important residues, to charactering protein-protein interactions and allosteric communication paths. Furthermore, we discuss potential pharmacological applications of PSN concepts and tools, and highlight the application to two families of drug targets, GPCRs and Hsp90. Although the application of PSNs as a framework for computer-aided drug discovery has been limited to date, we put forward the potential utility value in the near future and propose the PSNs could also serve as a new tool for polypharmacology research.

PMID: 27215941 [PubMed - as supplied by publisher]

[Big Biology : Supersizing Wissenschaft zu Beginn des 21. Jahrhunderts].

NTM. 2016 May 23;

Authors: Vermeulen N

PMID: 27215209 [PubMed - as supplied by publisher]

Systems biology in kidney transplantation: The application of multi-omics to a complex model.

Am J Transplant. 2016 May 23;

Authors: Bontha SV, Maluf DG, Mueller TF, Mas VR

Abstract
In spite of reduction of rejection rates and improvement in short term survival post kidney transplantation, modest progress has occurred in long-term graft attrition over the years. Timely identification of molecular events that precede clinical and histopathological changes might help in early intervention and thereby increase the graft half-life. Evolution of -omics tools has enabled systemic investigation of the influence of whole genome, epigenome, transcriptome, proteome, microbiome on transplant function and survival. In this 'omics' era, systemic approaches, in-depth clinical phenotyping and use of strict validation methods is the key for further understanding of the complex mechanisms associated with graft function. Systems biology is an inter-disciplinary holistic approach that focuses on complex and dynamic interactions within biological systems. The complexity of human kidney transplant is unlikely to be captured by a reductionist approach. It appears essential to integrate multi - omics data that can elucidate the multidimensional and multilayered regulation of the underlying heterogeneous and complex kidney transplant model. Here, we discuss studies which focus on genetic biomarkers, emerging technologies and systems biology approaches, which should increase the ability to discover biomarkers, understand mechanisms and stratify patients and responses post kidney transplantation. This article is protected by copyright. All rights reserved.

PMID: 27214826 [PubMed - as supplied by publisher]

Characterization of physiological responses to 22 gene knockouts in Escherichia coli central carbon metabolism.

Metab Eng. 2016 May 19;

Authors: Long CP, Gonzalez JE, Sandoval NR, Antoniewicz MR

Abstract
Understanding the impact of gene knockouts on cellular physiology, and metabolism in particular, is centrally important to quantitative systems biology and metabolic engineering. Here, we present a comprehensive physiological characterization of wild-type Escherichia coli and 22 knockouts of enzymes in the upper part of central carbon metabolism, including the PTS system, glycolysis, pentose phosphate pathway and Entner-Doudoroff pathway. Our results reveal significant metabolic changes that are affected by specific gene knockouts. Analysis of collective trends and correlations in the data using principal component analysis (PCA) provide new, and sometimes surprising, insights into E. coli physiology. Additionally, by comparing the data-to-model predictions from constraint-based approaches such as FBA, MOMA and RELATCH we demonstrate the important role of less well-understood kinetic and regulatory effects in central carbon metabolism.

PMID: 27212692 [PubMed - as supplied by publisher]

Multi-Omics of Single Cells: Strategies and Applications.

Trends Biotechnol. 2016 May 19;

Authors: Bock C, Farlik M, Sheffield NC

Abstract
Most genome-wide assays provide averages across large numbers of cells, but recent technological advances promise to overcome this limitation. Pioneering single-cell assays are now available for genome, epigenome, transcriptome, proteome, and metabolome profiling. Here, we describe how these different dimensions can be combined into multi-omics assays that provide comprehensive profiles of the same cell.

PMID: 27212022 [PubMed - as supplied by publisher]

Characterizing Strain Variation in Engineered E. coli Using a Multi-Omics-Based Workflow.

Cell Syst. 2016 May 19;

Authors: Brunk E, George KW, Alonso-Gutierrez J, Thompson M, Baidoo E, Wang G, Petzold CJ, McCloskey D, Monk J, Yang L, O'Brien EJ, Batth TS, Martin HG, Feist A, Adams PD, Keasling JD, Palsson BO, Lee TS

Abstract
Understanding the complex interactions that occur between heterologous and native biochemical pathways represents a major challenge in metabolic engineering and synthetic biology. We present a workflow that integrates metabolomics, proteomics, and genome-scale models of Escherichia coli metabolism to study the effects of introducing a heterologous pathway into a microbial host. This workflow incorporates complementary approaches from computational systems biology, metabolic engineering, and synthetic biology; provides molecular insight into how the host organism microenvironment changes due to pathway engineering; and demonstrates how biological mechanisms underlying strain variation can be exploited as an engineering strategy to increase product yield. As a proof of concept, we present the analysis of eight engineered strains producing three biofuels: isopentenol, limonene, and bisabolene. Application of this workflow identified the roles of candidate genes, pathways, and biochemical reactions in observed experimental phenomena and facilitated the construction of a mutant strain with improved productivity. The contributed workflow is available as an open-source tool in the form of iPython notebooks.

PMID: 27211860 [PubMed - as supplied by publisher]

Systems toxicology-based assessment of the candidate modified risk tobacco product THS2.2 for the adhesion of monocytic cells to human coronary arterial endothelial cells.

Toxicology. 2016 Jan 2;339:73-86

Authors: Poussin C, Laurent A, Peitsch MC, Hoeng J, De Leon H

Abstract
Alterations of endothelial adhesive properties by cigarette smoke (CS) can progressively favor the development of atherosclerosis which may cause cardiovascular disorders. Modified risk tobacco products (MRTPs) are tobacco products developed to reduce smoking-related risks. A systems biology/toxicology approach combined with a functional in vitro adhesion assay was used to assess the impact of a candidate heat-not-burn technology-based MRTP, Tobacco Heating System (THS) 2.2, on the adhesion of monocytic cells to human coronary arterial endothelial cells (HCAECs) compared with a reference cigarette (3R4F). HCAECs were treated for 4h with conditioned media of human monocytic Mono Mac 6 (MM6) cells preincubated with low or high concentrations of aqueous extracts from THS2.2 aerosol or 3R4F smoke for 2h (indirect treatment), unconditioned media (direct treatment), or fresh aqueous aerosol/smoke extracts (fresh direct treatment). Functional and molecular investigations revealed that aqueous 3R4F smoke extract promoted the adhesion of MM6 cells to HCAECs via distinct direct and indirect concentration-dependent mechanisms. Using the same approach, we identified significantly reduced effects of aqueous THS2.2 aerosol extract on MM6 cell-HCAEC adhesion, and reduced molecular changes in endothelial and monocytic cells. Ten- and 20-fold increased concentrations of aqueous THS2.2 aerosol extract were necessary to elicit similar effects to those measured with 3R4F in both fresh direct and indirect exposure modalities, respectively. Our systems toxicology study demonstrated reduced effects of an aqueous aerosol extract from the candidate MRTP, THS2.2, using the adhesion of monocytic cells to human coronary endothelial cells as a surrogate pathophysiologically relevant event in atherogenesis.

PMID: 26655683 [PubMed - indexed for MEDLINE]

Network Modeling Reveals Cross Talk of MAP Kinases during Adaptation to Caspofungin Stress in Aspergillus fumigatus.

PLoS One. 2015;10(9):e0136932

Authors: Altwasser R, Baldin C, Weber J, Guthke R, Kniemeyer O, Brakhage AA, Linde J, Valiante V

Abstract
Mitogen activated protein kinases (MAPKs) are highly conserved in eukaryotic organisms. In pathogenic fungi, their activities were assigned to different physiological functions including drug adaptation and resistance. Aspergillus fumigatus is a human pathogenic fungus, which causes life-threatening invasive infections. Therapeutic options against invasive mycoses are still limited. One of the clinically used drugs is caspofungin, which specifically targets the fungal cell wall biosynthesis. A systems biology approach, based on comprehensive transcriptome data sets and mathematical modeling, was employed to infer a regulatory network and identify key interactions during adaptation to caspofungin stress in A. fumigatus. Mathematical modeling and experimental validations confirmed an intimate cross talk occurring between the cell wall-integrity and the high osmolarity-glycerol signaling pathways. Specifically, increased concentrations of caspofungin promoted activation of these signalings. Moreover, caspofungin affected the intracellular transport, which caused an additional osmotic stress that is independent of glucan inhibition. High concentrations of caspofungin reduced this osmotic stress, and thus decreased its toxic activity. Our results demonstrated that MAPK signaling pathways play a key role during caspofungin adaptation and are contributing to the paradoxical effect exerted by this drug.

PMID: 26356475 [PubMed - indexed for MEDLINE]

Clinical decision-making and secondary findings in systems medicine.

BMC Med Ethics. 2016;17(1):32

Authors: Fischer T, Brothers KB, Erdmann P, Langanke M

Abstract
BACKGROUND: Systems medicine is the name for an assemblage of scientific strategies and practices that include bioinformatics approaches to human biology (especially systems biology); "big data" statistical analysis; and medical informatics tools. Whereas personalized and precision medicine involve similar analytical methods applied to genomic and medical record data, systems medicine draws on these as well as other sources of data. Given this distinction, the clinical translation of systems medicine poses a number of important ethical and epistemological challenges for researchers working to generate systems medicine knowledge and clinicians working to apply it.
DISCUSSION: This article focuses on three key challenges: First, we will discuss the conflicts in decision-making that can arise when healthcare providers committed to principles of experimental medicine or evidence-based medicine encounter individualized recommendations derived from computer algorithms. We will explore in particular whether controlled experiments, such as comparative effectiveness trials, should mediate the translation of systems medicine, or if instead individualized findings generated through "big data" approaches can be applied directly in clinical decision-making. Second, we will examine the case of the Riyadh Intensive Care Program Mortality Prediction Algorithm, pejoratively referred to as the "death computer," to demonstrate the ethical challenges that can arise when big-data-driven scoring systems are applied in clinical contexts. We argue that the uncritical use of predictive clinical algorithms, including those envisioned for systems medicine, challenge basic understandings of the doctor-patient relationship. Third, we will build on the recent discourse on secondary findings in genomics and imaging to draw attention to the important implications of secondary findings derived from the joint analysis of data from diverse sources, including data recorded by patients in an attempt to realize their "quantified self." This paper examines possible ethical challenges that are likely to be raised as systems medicine to be translated into clinical medicine. These include the epistemological challenges for clinical decision-making, the use of scoring systems optimized by big data techniques and the risk that incidental and secondary findings will significantly increase. While some ethical implications remain still hypothetical we should use the opportunity to prospectively identify challenges to avoid making foreseeable mistakes when systems medicine inevitably arrives in routine care.

PMID: 27209083 [PubMed - as supplied by publisher]

Text mining, a race against time? An attempt to quantify possible variations in text corpora of medical publications throughout the years.

Comput Biol Med. 2016 Apr 20;73:173-185

Authors: Wagner M, Vicinus B, Muthra ST, Richards TA, Linder R, Frick VO, Groh A, Rubie C, Weichert F

Abstract
BACKGROUND: The continuous growth of medical sciences literature indicates the need for automated text analysis. Scientific writing which is neither unitary, transcending social situation nor defined by a timeless idea is subject to constant change as it develops in response to evolving knowledge, aims at different goals, and embodies different assumptions about nature and communication. The objective of this study was to evaluate whether publication dates should be considered when performing text mining.
METHODS: A search of PUBMED for combined references to chemokine identifiers and particular cancer related terms was conducted to detect changes over the past 36 years. Text analyses were performed using freeware available from the World Wide Web. TOEFL Scores of territories hosting institutional affiliations as well as various readability indices were investigated. Further assessment was conducted using Principal Component Analysis. Laboratory examination was performed to evaluate the quality of attempts to extract content from the examined linguistic features.
RESULTS: The PUBMED search yielded a total of 14,420 abstracts (3,190,219 words). The range of findings in laboratory experimentation were coherent with the variability of the results described in the analyzed body of literature. Increased concurrence of chemokine identifiers together with cancer related terms was found at the abstract and sentence level, whereas complexity of sentences remained fairly stable.
CONCLUSIONS: The findings of the present study indicate that concurrent references to chemokines and cancer increased over time whereas text complexity remained stable.

PMID: 27208610 [PubMed - as supplied by publisher]

Members of BTB gene family regulate negatively nitrate uptake and nitrogen use efficiency in Arabidopsis thaliana and Oryza sativa.

Plant Physiol. 2016 Apr 27;

Authors: Araus V, Vidal EA, Puelma T, Alamos S, Mieulet D, Guiderdoni E, Gutiérrez RA

Abstract
Development of crops with improved nitrogen use efficiency (NUE) is essential for sustainable agriculture. However, achieving this goal has proven difficult due to NUE is a complex trait encompassing physiological and developmental processes. We thought to tackle this problem by taking a systems biology approach to identify candidate target genes. First, we used a supervised machine-learning algorithm to predict a NUE gene network in Arabidopsis thaliana. Second, we identified BT2, a member of the Bric-a-Brac/Tramtrack/Broad (BTB) gene family, as the most central and connected gene in the NUE network. Third, we experimentally tested BT2 for a role in NUE. We found NUE decreased in plants overexpressing BT2 gene as compared to wild-type plants under limiting nitrate conditions. Additionally, NUE increased as compared to wild-type plants under low nitrate conditions in double mutant plants in bt2 and its closely related homolog bt1, indicating a functional redundancy of BT1 and BT2 for NUE. Expression of the nitrate transporter genes NRT2.1 and NRT2.4 increased in the bt1/bt2 double mutant as compared to wild-type plants, with a concomitant 65% increase in nitrate uptake under low nitrate conditions. Similar to Arabidopsis, we found that mutation of the BT1/BT2 ortholog gene in rice OsBT increased NUE by 20% as compared to wild-type rice plants under low nitrogen conditions. These results indicate BT gene family members act as conserved negative regulators of nitrate uptake genes and NUE in plants and highlight them as prime targets for future strategies to improve NUE in crops.

PMID: 27208309 [PubMed - as supplied by publisher]

It may Seem Inflammatory, but Some T Cells are Innately Healing to the Bone.

J Bone Miner Res. 2016 May 21;

Authors: Kalyan S

Abstract
Among the most significant developments to have taken place in osteology over the last few decades is an evolution from treating and viewing bone disorders primarily through an endocrine lens to instead seeing them as metabolic disorders that interface at the molecular and cellular level with the immune system. Osteoimmunology was officially born in response to accumulating evidence that the immune system is integrally involved in bone remodelling, but much of the early work focused on the role of conventional αβ T cells in driving bone loss. There is, however, emerging data indicating that innate lymphocytes, in particular γδ T cells, may in fact be important for bone regeneration. We first observed that bisphosphonate-associated osteonecrosis of the jaw (ONJ), a rare but serious adverse drug effect characterized by non-healing necrotic bone tissue of the mandible or maxilla, was linked to a deficiency in a subset of γδ T cells found in human peripheral blood. Patients who developed ONJ while on bisphosphonate therapy not only lacked the main subset of circulating γδ T cells, but they also all had underlying conditions that compromised their immune integrity. A number of recent studies have unraveled the role of γδ T cells (and lymphocytes sharing their characteristics) in bone regeneration - particularly for fracture healing. These findings seem to contradict the prevailing view of such "inflammatory" T cells as being bone degenerative rather than restorative. This viewpoint melds together the emerging evidence of these so-called inflammatory T cells in bone remodeling and healing - showing that they are not in fact "all bad to the bone". This article is protected by copyright. All rights reserved.

PMID: 27207251 [PubMed - as supplied by publisher]