Dynamic neuronal-glial interactions: an overview 20 years later

After commenting on some perceived reasons why our review may have been relatively frequently cited, a brief overview is presented that first summarizes what we knew 25 years ago about the dynamic neuronal-astroglial interactions that occur in response to changes in the physiological state of the animal. The brain system in which these dynamic interactions were studied was the magnocellular hypothalamo-neurohypophysial system (mHNS) of the rat. The mHNS developed as and continues to be the model system yielding the most coherent picture of dynamic morphological changes and insights into their functional consequences. Many other brain areas, however, have more recently come under scrutiny in the search for glial-neuronal dynamisms. Outlined next are some of the questions concerning this phenomenon that led to the research efforts immediately following the initial discoveries, along with the answers, both complete and incomplete, obtained to those research questions. The basis for this first wave of follow-up research can be characterized by the phrase "what we knew we didn't know at that time." The final section is an update and brief overview of highlights of both "what we know now" and "what we now know that we don't know" about dynamic neuronal-astroglial interactions in the mHNS.     

Why sex matters for neuroscience

A rapidly burgeoning literature documents copious sex influences on brain anatomy, chemistry and function. This article highlights some of the more intriguing recent discoveries and their implications. Consideration of the effects of sex can help to explain seemingly contradictory findings. Research into sex influences is mandatory to fully understand a host of brain disorders with sex differences in their incidence and/or nature. The striking quantity and diversity of sex-related influences on brain function indicate that the still widespread assumption that sex influences are negligible cannot be justified, and probably retards progress in our field.     

Observation and cogitation: how serendipity provides the building blocks of scientific discovery

The identification of serendipitous findings in field-based animal research is challenging in part because investigators are reluctant to declare a discovery accidental. Investigators recognize that many factors must be considered. For example, the impact of using carefully ordered observational search patterns in ecologic, pathologic, and epidemiologic investigations could result in findings being categorized as "sought" versus "unsought." Team collaborations are common in these types of investigations and have advantages related to the application of multiple paradigms, paradigm mixing, and paradigm shifting. This approach reduces the perception of serendipity. Issues of search image refinement and the co-discovery of sought and unsought discoveries additionally cloud the identification of a truly serendipitous finding. Nevertheless, basic curiosity and observation are necessary precursors to scientific discovery. It should be recognized that serendipitous discoveries are of significant value in the advancement of science and often present the foundation for important intellectual leaps of understanding.     

Drosophila models for cancer research

Drosophila is a model system for cancer research. Investigation with fruit flies has facilitated a number of important recent discoveries in the field: the hippo signaling pathway, which coordinates cell proliferation and death to achieve normal tissue size; 'social' behaviors of cells, including cell competition and apoptosis-induced compensatory proliferation, that help ensure normal tissue size; and a growing understanding of how oncogenes and tumor suppressors cooperate to achieve tumor growth and metastasis in situ. In the future, Drosophila models can be extended beyond basic research in the search for human therapeutics.     

Analysis of radicals and radical reaction products in cell signalling and biomolecular damage: the long hard road to gold-standard measures

The field of free radical biology and medicine continues to move at a tremendous pace, with a constant flow of ground-breaking discoveries. The following collection of papers in this issue of Biochemical Society Transactions highlights several key areas of topical interest, including the crucial role of validated measurements of radicals and reactive oxygen species in underpinning nearly all research in the field, the important advances being made as a result of the overlap of free radical research with the reinvigorated field of lipidomics (driven in part by innovations in MS-based analysis), the acceleration of new insights into the role of oxidative protein modifications (particularly to cysteine residues) in modulating cell signalling, and the effects of free radicals on the functions of mitochondria, extracellular matrix and the immune system. In the present article, we provide a brief overview of these research areas, but, throughout this discussion, it must be remembered that it is the availability of reliable analytical methodologies that will be a key factor in facilitating continuing developments in this exciting research area.     

Allospecific human T cell lines and clones which mediate HLA-DR restricted helper activity

In order to analyze the immunoregulatory activity of allospecific human T cells, we have combined the techniques of limiting dilution culture and IL-2 dependent T cell growth to generate cloned alloreactive T cell lines (TCL). These TCL have been expanded in continuous culture for greater than 8 mo with retention of stable phenotypic and functional characteristics. For example, phenotypic analysis of alloproliferative TCL, utilizing a panel of monoclonal antibodies, demonstrate that these cultures are comprised of T cells belonging exclusively to the T3+ T4+ T8- "helper" or "inducer" T cell subset. Coculture of cloned alloproliferative TCL cells with a panel of allogeneic stimulators reveals that these clones are specifically reactive against the HLA-DRw1 determinant. Of greater interest, coculture of selected alloproliferative TCL cells with DRw1+ but not DRw1- B cells results in a vigorous polyclonal response as measured by the reverse hemolytic plaque assay. Although major histocompatibility complex restriction of this T-B interaction operates at the inductive level, help is at least partially unrestricted at the effector level as alloantigen-activated TCL cells provide demonstrable, although not maximal, help for DRw1- B cells.     

Post Bleaching Assessment of Corals in Andaman and Nicobar Islands

Reefs of Andaman and Nicobar Islands harbour 418 species of scleractinian corals spread over an area of 2,000 km². In April to May, 2010, due to the delayed onset of the southwest monsoon the sea surface temperature of the coastal and oceanic region increased to 31.7 °C in respect to the earlier record of maximum 29.0 °C during the said period. This resulted in mass bleaching of hermatypic corals during May, 2010. Rapid under water surveys have been conducted in reefs of Andaman and Nicobar Islands to assess the health of corals between May 2010 and August 2011. It is estimated that 76.62 ± (SD) 10.83 % of coral species are bleached up to a water depth of 10–15 m. Species from the genus Acropora appeared more susceptible to bleaching than those belong to the genus Porites. During the month of June 2010 the sea surface temperature was reduced to 29 °C perhaps due to the rainfall which stimulated rebuilding of zooxanthellae population in bleached corals. Recovery of 85.54 ± (SD) 6.33 % of bleached corals was seen during the study period of 11 months after the bleaching event. Porites spp. showed a high recovery rate, while Acropora spp. had the highest mortality rate. Coral mortality can have profound ecological and socio-economical implications and highlights the need for sustained monitoring for coral reef conservation in India. Hence, steps must be taken to improve management tools to protect these resources of global significance.     

Next steps after 15 stimulating years of human gut microbiome research

Gut microbiome research has bloomed over the past 15 years. We have learnt a lot about the complex microbial communities that colonize our intestine. Promising avenues of research and microbiome-based applications are being implemented, with the goal of sustaining host health and applying personalized disease management strategies. Despite this exciting outlook, many fundamental questions about enteric microbial ecosystems remain to be answered. Organizational measures will also need to be taken to optimize the outcome of discoveries happening at an extremely rapid pace. This article highlights our own view of the field and perspectives for the next 15 years.     

Mass Spectral Analysis of Synthetic Peptides: Implications in Proteomics

Sequence determination of peptides is a crucial step in mass spectrometry–based proteomics. Peptide sequences are determined either by database search or by de novo sequencing using tandem mass spectrometry. Determination of all the theoretical expected peptide fragments and eliminating false discoveries remains a challenge in proteomics. Developing standards for evaluating the performance of mass spectrometers and algorithms used for identification of proteins is important for proteomics studies. The current study is focused on these aspects by using synthetic peptides. A total of 599 peptides were designed from in silico tryptic digest with 1 or 2 missed cleavages from 199 human proteins, and synthetic peptides corresponding to these sequences were obtained. The peptides were mixed together, and analysis was carried out using liquid chromatography–electrospray ionization tandem mass spectrometry on a Q-Exactive HF mass spectrometer. The peptides and proteins were identified with SEQUEST program. The analysis was carried out using the proteomics workflows. A total of 573 peptides representing 196 proteins could be identified, and a spectral library was created for these peptides. Analysis parameters such as “no enzyme selection” gave the maximum number of detected peptides as compared with trypsin in the selection. False discoveries could be identified. This study highlights the limitations of peptide detection and the need for developing powerful algorithms along with tools to evaluate mass spectrometers and algorithms. It also shows the limitations of peptide detection even with high-end mass spectrometers. The mass spectral data are available in ProteomeXchange with accession no. PXD017992.     

Inherited connexin mutations associated with hearing loss

One of the most dramatic discoveries in the field of hereditary hearing loss is the association of this sensory defect with connexin mutations. Most significant is the large proportion, 30-50%, of inherited hearing loss that is due to mutations in connexin 26. The proteins these genes encode are expressed in the cochlear duct, in regions containing gap junctions. Together, these findings suggest a crucial role for gap junction proteins in the mammalian inner ear. Mouse models with specific connexin mutations leading to deafness will help resolve the many questions regarding the role of these gap junction proteins in the inner ear.     

Collagen fibril biosynthesis in tendon: a review and recent insights

The development and evolution of multicellular animals relies on the ability of certain cell types to synthesise an extracellular matrix (ECM) comprising very long collagen fibrils that are arranged in very ordered 3-dimensional scaffolds. Tendon is a good example of a highly ordered ECM, in which tens of millions of collagen fibrils, each hundreds of microns long, are synthesised parallel to the tendon long axis. This review highlights recent discoveries showing that the assembly of collagen fibrils in tendon is hierarchical, and involves the formation of fairly short "collagen early fibrils" that are the fusion precursors of the very long fibrils that occur in mature tendon.     

Is the kinetome conserved?

Computational biologists have labored for decades to produce kinetic models to mechanistically explain complex metabolic phenomena. The estimation of numerical values for the large number of kinetic parameters required for constructing large‐scale models has been a major challenge. This collection of kinetic constants has recently been termed the kinetome (Nilsson et al, 2017). In this Commentary, we discuss the recent advances in the field that suggest that the kinetome may be more conserved than expected. A conserved kinetome will accelerate the development of future kinetic models of integrated cellular functions and expand their scope and usability in many fields of biology and biomedicine.Subject Categories: Computational Biology, Metabolism

This Commentary highlights recent discoveries suggesting that the kinetome (a collection of kinetic parameters) can be conserved and discusses how a conserved kinetome will accelerate the development of future kinetic models.     

The incredible elastic brain: how neural stem cells expand our minds

Brain development was thought to be largely hardwired and accomplished by birth, and the brain was thought to have essentially no regenerative capacity. The remarkable discovery of adult neurogenesis and neural stem cells (NSCs) existing in the mature CNS changed that, allowing us to think optimistically about CNS repair. These discoveries helped to generate a robust field of neural progenitor cell biology, with relevance to CNS development, pathogenesis, the search for novel neurological therapies, as well as our understanding of how the brain works.     

CD38 and CD157: biological observations to clinical therapeutic targets

The application of molecular knowledge for developing new medical technologies is the goal of molecular medicine. Success in this area is highly dependent on the interaction of investigators from fields as diverse as biochemistry, cell biology, immunology, physiology, epidemiology, and physics, with an eye toward applying their insights and discoveries to improving human health. Such interdisciplinary approaches rarely find the common ground and language necessary to achieve this goal. Recently, a meeting of researchers studying the ectoenzymes CD38 and CD157 brought together insights into the regulation of calcium signaling, the metabolism of pyridine nucleotides by CD38 and CD157, and subsequent effects on immune function. Together, these discoveries were being applied to the development of novel therapeutics and diagnostics for myeloma and chronic lymphocytic leukemia. This issue of Molecular Medicine, featuring several short reviews based on a conference held in Turin, Italy, 10-12 June 2006, showcases the current state of this field and highlights some recent progress in molecular medicine.     

The lens in focus: a comparison of lens development in Drosophila and vertebrates

The evolution of the eye has been a major subject of study dating back centuries. The advent of molecular genetics offered the surprising finding that morphologically distinct eyes rely on conserved regulatory gene networks for their formation. While many of these advances often stemmed from studies of the compound eye of the fruit fly, Drosophila melanogaster, and later translated to discoveries in vertebrate systems, studies on vertebrate lens development far outnumber those in Drosophila. This may be largely historical, since Spemann and Mangold's paradigm of tissue induction was discovered in the amphibian lens. Recent studies on lens development in Drosophila have begun to define molecular commonalities with the vertebrate lens. Here, we provide an overview of Drosophila lens development, discussing intrinsic and extrinsic factors controlling lens cell specification and differentiation. We then summarize key morphological and molecular events in vertebrate lens development, emphasizing regulatory factors and networks strongly associated with both systems. Finally, we provide a comparative analysis that highlights areas of research that would help further clarify the degree of conservation between the formation of dioptric systems in invertebrates and vertebrates.     

Probiotics: from bench to market

"Probiotics: From Bench to Market" was a one-day conference convened by the New York Academy of Sciences on June 11, 2010, with the goal of stimulating discussion of the physiological effects of probiotics on the gastrointestinal, nervous, and immune systems. The program included speakers from academia, industry, and government to give conference participants a full understanding of the state of the field of probiotics. The overall goal of the program was to increase communication and collaboration among these groups to advance probiotic research and probiotic contributions to public health. The conference was divided into three sessions and included both oral and visual presentations as well as panel discussions.     

Professor Howard Mason and oxygen activation

Our understanding of the classification, function, mechanism, and structure of the enzymes which incorporate atoms of oxygen from atmospheric molecular oxygen during catalysis is based on the thoughtful and technically challenging experiments of two giants in the field of Biochemistry, Howard Mason and Osamu Hayaishi. This volume celebrates the 50th anniversary of the discovery and characterization of these "oxygenase" enzymes and provides a broad view of how far this area of research has advanced. Professor Hayaishi describes herein his perspective on the background and major discoveries which led to the development of this field. Regrettably Howard Mason passed away at age 88 in 2003. I am indeed fortunate to have been a Ph.D. student with Howard and to have the opportunity to briefly review his role in the development of this field for this special commemorative issue of BBRC.