Kirstin R.W. Matthews

Bio: Kirstin R.W. Matthews is an academic researcher from Rice University. The author has contributed to research in topics: Science policy & Stem cell. The author has an hindex of 13, co-authored 50 publications receiving 731 citations. Previous affiliations of Kirstin R.W. Matthews include University of Texas Health Science Center at Houston.

Cutting Edge: Targeted Disruption of the C3a Receptor Gene Demonstrates a Novel Protective Anti-Inflammatory Role for C3a in Endotoxin-Shock

Abstract: The complement anaphylatoxin C3a, on binding the C3aR, mediates numerous proinflammatory activities. In addition, recent in vitro studies with C3a have implicated C3aR as a possible anti-inflammatory receptor. Because of its possible dual role in modulating the inflammatory response, it is uncertain whether C3aR contributes to the pathogenesis of endotoxin shock. Here, the targeted-disruption of the C3aR in mice is reported. These mice exhibit an enhanced lethality to endotoxin shock with a pronounced gene dosage effect. In addition, the plasma concentration of IL-1beta was significantly elevated in the C3aR(-/-) mice compared with their littermates following LPS challenge. These findings demonstrate an important protective role for the C3aR in endotoxin shock and indicate that, in addition to its traditionally accepted functions in mediating inflammation, the C3aR also acts in vivo as an anti-inflammatory receptor by attenuating LPS-induced proinflammatory cytokine production.

Religion among Scientists in International Context: A New Study of Scientists in Eight Regions

Abstract: Scientists have long been associated with religion’s decline around the world. But little data permit analysis of the religiosity of scientists or their perceptions of the science-faith interface. ...

Revisiting the Warnock rule

Abstract: The seminal 1984 Warnock Report1 established that research on human embryos should be limited to the first 14 days of development (Box 1). Since that time, the rule has been broadly adopted and adhered to across the research community. With the introduction of new methodologies into human embryology, however, our ability to culture human embryos in vitro has progressed rapidly, to the point where we now are reaching the 14-day Rubicon. In August 2016, two groups in the UK and in the US reported experiments on human embryos that were sustained in culture for 12–13 days after fertilization2,3. To comply with British law, the UK lab destroyed its embryo on the 13th day. In the following article, Nature Biotechnology brings together a group of experts to discuss whether, in the light of these advances, it is now time to reassess the 14-day rule.

International Stem Cell Collaboration: How Disparate Policies between the United States and the United Kingdom Impact Research

Abstract: As the scientific community globalizes, it is increasingly important to understand the effects of international collaboration on the quality and quantity of research produced. While it is generally assumed that international collaboration enhances the quality of research, this phenomenon is not well examined. Stem cell research is unique in that it is both politically charged and a research area that often generates international collaborations, making it an ideal case through which to examine international collaborations. Furthermore, with promising medical applications, the research area is dynamic and responsive to a globalizing science environment. Thus, studying international collaborations in stem cell research elucidates the role of existing international networks in promoting quality research, as well as the effects that disparate national policies might have on research. This study examined the impact of collaboration on publication significance in the United States and the United Kingdom, world leaders in stem cell research with disparate policies. We reviewed publications by US and UK authors from 2008, along with their citation rates and the political factors that may have contributed to the number of international collaborations. The data demonstrated that international collaborations significantly increased an article's impact for UK and US investigators. While this applied to UK authors whether they were corresponding or secondary, this effect was most significant for US authors who were corresponding authors. While the UK exhibited a higher proportion of international publications than the US, this difference was consistent with overall trends in international scientific collaboration. The findings suggested that national stem cell policy differences and regulatory mechanisms driving international stem cell research in the US and UK did not affect the frequency of international collaborations, or even the countries with which the US and UK most often collaborated. Geographical and traditional collaborative relationships were the predominate considerations in establishing international collaborations.

Harmful molecular mechanisms in sepsis

Abstract: Sepsis and sepsis-associated multi-organ failure are major challenges for scientists and clinicians and are a tremendous burden for health-care systems. Despite extensive basic research and clinical studies, the pathophysiology of sepsis is still poorly understood. We are now beginning to understand that sepsis is a heterogeneous, dynamic syndrome caused by imbalances in the 'inflammatory network'. In this Review, we highlight recent insights into the molecular interactions that occur during sepsis and attempt to unravel the nature of the dysregulated immune response during sepsis.

Complement System Part I - Molecular Mechanisms of Activation and Regulation

Abstract: Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins and the membrane attack complex. We will also discuss the importance of structure-function relationships using the example of atypical hemolytic uremic syndrome. Lastly we will discuss the development and benefits of therapies using complement inhibitors.

The complement system in regulation of adaptive immunity.

Abstract: The serum complement system, which represents a chief component of innate immunity, not only participates in inflammation but also acts to enhance the adaptive immune response. Specific activation of complement via innate recognition proteins or secreted antibody releases cleavage products that interact with a wide range of cell surface receptors found on myeloid, lymphoid and stromal cells. This intricate interaction among complement activation products and cell surface receptors provides a basis for the regulation of both B and T cell responses. This review highlights fundamental events, explaining how complement links innate and adaptive immunity as well as describing more recent studies on how this large family of proteins functions locally in peripheral lymph nodes to enhance B and T cell responses.

Plant Growth-Promoting Rhizobacteria: Context, Mechanisms of Action, and Roadmap to Commercialization of Biostimulants for Sustainable Agriculture.

Abstract: Microbes of the phytomicrobiome are associated with every plant tissue and, in combination with the plant form the holobiont. Plants regulate the composition and activity of their associated bacterial community carefully. These microbes provide a wide range of services and benefits to the plant; in return, the plant provides the microbial community with reduced carbon and other metabolites. Soils are generally a moist environment, rich in reduced carbon which supports extensive soil microbial communities. The rhizomicrobiome is of great importance to agriculture owing to the rich diversity of root exudates and plant cell debris that attract diverse and unique patterns of microbial colonization. Microbes of the rhizomicrobiome play key roles in nutrient acquisition and assimilation, improved soil texture, secreting, and modulating extracellular molecules such as hormones, secondary metabolites, antibiotics, and various signal compounds, all leading to enhancement of plant growth. The microbes and compounds they secrete constitute valuable biostimulants and play pivotal roles in modulating plant stress responses. Research has demonstrated that inoculating plants with plant-growth promoting rhizobacteria (PGPR) or treating plants with microbe-to-plant signal compounds can be an effective strategy to stimulate crop growth. Furthermore, these strategies can improve crop tolerance for the abiotic stresses (e.g., drought, heat, and salinity) likely to become more frequent as climate change conditions continue to develop. This discovery has resulted in multifunctional PGPR-based formulations for commercial agriculture, to minimize the use of synthetic fertilizers and agrochemicals. This review is an update about the role of PGPR in agriculture, from their collection to commercialization as low-cost commercial agricultural inputs. First, we introduce the concept and role of the phytomicrobiome and the agricultural context underlying food security in the 21st century. Next, mechanisms of plant growth promotion by PGPR are discussed, including signal exchange between plant roots and PGPR and how these relationships modulate plant abiotic stress responses via induced systemic resistance. On the application side, strategies are discussed to improve rhizosphere colonization by PGPR inoculants. The final sections of the paper describe the applications of PGPR in 21st century agriculture and the roadmap to commercialization of a PGPR-based technology.

Complement System Part II: Role in Immunity.

Abstract: The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target.