The evolutionary history of infectious disease in the ancient Americas and the pathogenic consequences of European contact

The increasing availability of next generation sequencing techniques in recent decades has led to new discoveries, and sometimes the redefinition of conventional hypotheses, regarding many complex human-pathogen evolutionary relationships. These new discoveries are particularly poignant in studies of the Americas, where research into Indigenous ancestry and migration has historically been ignored. As a result, conventional hypotheses regarding the origin of global pathogens like tuberculosis, syphilis, and malaria in the Americas and their spread within the continents have been mischaracterized. Fortunately, recent studies using molecular techniques have now superseded these missteps, which were often based in anecdotal accounts from colonial missionary reports rather than rigorous scientific study. It is now clear that there was not a unidirectional pipeline of pathogen introduction that began with European contact; instead, a rich and varied microbiological landscape already existed in the Americas. This synthesis of research regarding the origin and spread of pathogens in the Americas examines the scope of this changing perception within the fields of paleogenomics and paleomicrobiology.     

A plethora of painful molecules

Pain is a fundamental experience with a complex and multi-layered neurobiological basis. In recent years a powerful battery of techniques has been brought to bear to unravel the mechanisms by which painful stimuli are transduced and processed. There have been several recent discoveries regarding the molecular transduction mechanisms in nociceptors and novel molecular and cellular mechanisms underlying the spinal processing of painful stimuli. The mechanisms by which sensory neurons initiate hyperalgesia and touch evoked pain (allodynia) have been addressed particularly successfully in recent studies. The rich variety of key molecular players that have emerged in physiological and pathophysiological pain states reflects the sophistication and uniqueness of this vitally important sense.     

Molecular mechanisms of metal toxicity and carcinogenesis

Many metals and metal-containing compounds have been identified to be potent mutagens and carcinogens. Recently, a new sub-discipline of molecular toxicology and carcinogenesis has been developed. The combination of newly developed molecular techniques and free radical approach makes it possible to insightfully examine metal-induced carcinogenesis in precise molecular terms so that intricate biological interrelationships can be elucidated. In consideration of the increased amount of new findings deciphered by utilizing these new methods, the 1st Conference on Molecular Mechanisms of Metal Toxicity and Carcinogenesis was held. In this conference, more than 50 scientists from nine countries presented their novel discoveries concerning metal-induced carcinogenesis, delineated molecular mechanism of metal carcinogenesis, and proposed novel therapeutic intervention and prevention strategies. This article reviewes some of the state-of-the-art information presented at the meeting regarding the molecular mechanisms of metal cytotoxicity and carcinogenesis.     

Developments in aquatic microbiology.

Major discoveries in marine microbiology over the past 4-5 decades have resulted in the recognition of bacteria as a major biomass component of marine food webs. Such discoveries include chemosynthetic activities in deep-ocean ecosystems, survival processes in oligotrophic waters, and the role of microorganisms in food webs coupled with symbiotic relationships and energy flow. Many discoveries can be attributed to innovative methodologies, including radioisotopes, immunofluorescent-epifluorescent analysis, and flow cytometry. The latter has shown the key role of marine viruses in marine system energetics. Studies of the components of the "microbial loop" have shown the significance of various phagotrophic processes involved in grazing by microinvertebrates. Microbial activities and dissolved organic carbon are closely coupled with the dynamics of fluctuating water masses. New biotechnological approaches and the use of molecular biology techniques still provide new and relevant information on the role of microorganisms in oceanic and estuarine environments. International interdisciplinary studies have explored ecological aspects of marine microorganisms and their significance in biocomplexity. Studies on the origins of both life and ecosystems now focus on microbiological processes in the marine environment. This paper describes earlier and recent discoveries in marine (aquatic) microbiology and the trends for future work, emphasizing improvements in methodology as major catalysts for the progress of this broadly-based field.     

Biodesulfurization.

Microbial sulfur-specific transformations have been identified that selectively desulfurize organic sulfur compounds in fossil fuels. Recent discoveries related to biodesulfurization mechanisms may lead to commercial applications of biodesulfurization through engineering recombinant strains for over-expression of biodesulfurization genes, removal of end product repression, and/or by combining relevant industrial and environmental traits with improvements in bioprocess design.     

Celebrating Plant Cells： A Special Issue on Plant Cell Biology

A special issue on plant cell biology is long overdue for JIPB! In the last two decades or so, the plant biology community has been thrilled by explosive discoveries regarding the molecular and genetic basis of plant growth, development, and responses to the environment, largely owing to recent maturation of model systems like Arabidopsis thaliana and the rice Oryza sativa, as well as the rapid development of high throughput technologies associated with qenomics and proteomics.     

Vascular endothelial growth factor: biology and therapeutic applications

While the development of anti-angiogenic therapy, as it pertains to cancer treatment, may still be in its infancy relative to well-established modalities such as chemotherapy, radiation, and surgery, major strides made in the past several decades have allowed translation of basic science discoveries in this field into clinical reality. The discovery of key molecular modulators of angiogenesis, notably vascular endothelial growth factor (VEGF), has catalyzed the development of numerous neutralizing therapeutic agents. The validity of VEGF inhibition as a therapeutic strategy has been well supported in randomized clinical trials, as well as U.S. Food and Drug Administration approval of the VEGF antagonists bevacizumab, sunitinib malate, sorafenib, pegaptinib and ranibizumab. Accordingly, this review will (1) briefly review the basic molecular biology of VEGF and (2) summarize recent progress in targeting the VEGF molecular pathway as therapy for angiogenic diseases such as cancer and age-related macular degeneration.     

High-performance size-exclusion chromatography of peptides

Gel filtration on soft gels has been employed for over 40 years for the separation, desalting and molecular weight estimation of peptides and proteins. Technical improvements have given rise to high-performance size-exclusion chromatography (HPSEC) on rigid supports, giving more rapid run times and increased resolution. Initially, these packings were more suitable for the separation of proteins than of peptides, but supports that operate in the fractionation range <10,000 Daltons (Da) are now available. In this report, HPSEC is described in relation to its application to peptides, especially regarding purification, estimation of molecular weight and study of molecular associations.     

From fate to function: the Drosophila trachea and salivary gland as models for tubulogenesis

Tube formation is a ubiquitous process required to sustain life in multicellular organisms. The tubular organs of adult mammals include the lungs, vasculature, digestive and excretory systems, as well as secretory organs such as the pancreas, salivary, prostate, and mammary glands. Other tissues, including the embryonic heart and neural tube, have requisite stages of tubular organization early in development. To learn the molecular and cellular basis of how epithelial cells are organized into tubular organs of various shapes and sizes, investigators have focused on the Drosophila trachea and salivary gland as model genetic systems for branched and unbranched tubes, respectively. Both organs begin as polarized epithelial placodes, which through coordinated cell shape changes, cell rearrangement, and cell migration form elongated tubes. Here, we discuss what has been discovered regarding the details of cell fate specification and tube formation in the two organs; these discoveries reveal significant conservation in the cellular and molecular events of tubulogenesis.     

Towards a molecular understanding of cytokinesis

In this review, we focus on recent discoveries regarding the molecular basis of cleavage furrow positioning and contractile ring assembly and contraction during cytokinesis. However, some of these mechanisms might have different degrees of importance in different organisms. This synthesis attempts to uncover common themes and to reveal potential relationships that might contribute to the biochemical and mechanical aspects of cytokinesis. Because the information about cytokinesis is still fairly rudimentary, our goal is not to present a definitive model but to present testable hypotheses that might lead to a better mechanistic understanding of the process.     

Programming and reprogramming neuronal subtypes in the central nervous system

Recent discoveries in nuclear reprogramming have challenged the dogma that the identity of terminally differentiated cells cannot be changed. The identification of molecular mechanisms that reprogram differentiated cells to a new identity carries profound implications for regenerative medicine across organ systems. The central nervous system (CNS) has historically been considered to be largely immutable. However, recent studies indicate that even the adult CNS is imparted with the potential to change under the appropriate stimuli. Here, we review current knowledge regarding the capability of distinct cells within the CNS to reprogram their identity and consider the role of developmental signals in directing these cell fate decisions. Finally, we discuss the progress and current challenges of using developmental signals to precisely direct the generation of individual neuronal subtypes in the postnatal CNS and in the dish.     

The Indonesian Homo erectus brain endocasts revisited

New brain endocast reconstructions of Homo erectus discoveries from Indonesia since 1963 (H. erectus VI, 1963; VII, 1965; VIII, 1969) have been made and their volumes determined. In addition, older discoveries (H. erectus I, 1891; II, 1937; IV, 1937–38) have been reendocast and reconstructed, and have yielded volumes considerably different from those previously published. This is particularly so in the case of Dubois's original discovery, which yields a volume of 940 ml rather than the widely quoted volume of 750 ml. In addition, a number of morphological observations regarding hemispheric asymmetries (petalias) are provided, which suggest a condition similar to modern Homo sapiens.     

2001: a year of major advances in anthrax toxin research

Anthrax is caused when spores of Bacillus anthracis enter a host and germinate. The bacteria multiply and secrete a tripartite toxin causing local edema and, in systemic infection, death. In nature, anthrax is primarily observed in cattle and other herbivores; humans are susceptible but rarely affected. In 2001, anthrax spores were used effectively for the first time in bioterrorist attacks, resulting in 11 confirmed cases of human disease and five deaths. These events have underscored the need for improved prophylaxis, therapeutics and a molecular understanding of the toxin. The good news about anthrax is that several decisive discoveries regarding the toxin have been reported recently. Most notably, the toxin receptor was identified, the 3-D structures of two of the toxin subunits were solved and potent in vivo inhibitors were designed. These findings have improved our understanding of the intoxication mechanism and are stimulating the design of strategies to fight disease in the future.     

Proline-directed protein phosphorylation and cell cycle regulation.

Recent discoveries have converged on the emerging enzymology that governs the G1-S phase transition of the mammalian somatic cell cycle. These discoveries have led to an appreciation of the regulatory role of proline-directed protein phosphorylation in molecular signalling, and have resulted in the identification of a putative proto-oncogene.     

Radiation Research Society. 1952-2002. Historical and current highlights in radiation biology: has anything important been learned by irradiating cells?

Around 30 years ago, a very prominent molecular biologist confidently proclaimed that nothing of fundamental importance has ever been learned by irradiating cells! The poor man obviously did not know about discoveries such as DNA repair, mutagenesis, connections between mutagenesis and carcinogenesis, genomic instability, transposable genetic elements, cell cycle checkpoints, or lines of evidence historically linking the genetic material with nucleic acids, or origins of the subject of oxidative stress in organisms, to name a few things of fundamental importance learned by irradiating cells that were well known even at that time. Early radiation studies were, quite naturally, phenomenological. They led to the realization that radiations could cause pronounced biological effects. This was followed by an accelerating expansion of investigations of the nature of these radiobiological phenomena, the beginnings of studies aimed toward better understanding the underlying mechanisms, and a better appreciation of the far-reaching implications for biology, and for society in general. Areas of principal importance included acute tissue and tumor responses for applications in medicine, whole-body radiation effects in plants and animals, radiation genetics and cytogenetics, mutagenesis, carcinogenesis, cellular radiation responses including cell reproductive death, cell cycle effects and checkpoint responses, underlying molecular targets leading to biological effects, DNA repair, and the genetic control of radiosensitivity. This review summarizes some of the highlights in these areas, and points to numerous examples where indeed, many things of considerable fundamental importance have been learned by irradiating cells.     

Mapping of phospholipids by MALDI imaging (MALDI-MSI): realities and expectations

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has emerged as a novel powerful MS methodology that has the ability to generate both molecular and spatial information within a tissue section. Application of this technology as a new type of biochemical lipid microscopy may lead to new discoveries of the lipid metabolism and biomarkers associated with area-specific alterations or damage under stress/disease conditions such as traumatic brain injury or acute lung injury, among others. However there are limitations in the range of what it can detect as compared with liquid chromatography-MS (LC-MS) of a lipid extract from a tissue section. The goal of the current work was to critically consider remarkable new opportunities along with the limitations and approaches for further improvements of MALDI-MSI. Based on our experimental data and assessments, improvements of the spectral and spatial resolution, sensitivity and specificity towards low abundance species of lipids are proposed. This is followed by a review of the current literature, including methodologies that other laboratories have used to overcome these challenges.     

The evolution of lipidomics through space and time

Although the foundations of mass spectrometry-based lipidomics have been practiced for over 30 years, recent technological advances in ionization modalities in conjunction with robust increases in mass accuracy and resolution have greatly accelerated the emergence, growth and importance of the field of lipidomics. Moreover, advances in the separation sciences, bioinformatic strategies and the availability of robust databases have been synergistically integrated into modern lipidomic technologies leading to unprecedented improvements in the depth, penetrance and precision of lipidomic analyses and identification of their biological and mechanistic significance. The purpose of this "opinion" article is to briefly review the evolution of lipidomics, critique the platforms that have evolved and identify areas that are likely to emerge in the years to come. Through seamlessly integrating a rich repertoire of mass spectrometric, chemical and bioinformatic strategies, the chemical identities and quantities of tens of thousands to hundreds of thousands of different lipid molecular species and their metabolic alterations during physiologic or pathophysiologic perturbations can be obtained. Thus, the field of lipidomics which already has a distinguished history of exciting new discoveries in many disease states holds unparalleled potential to identify the pleiotropic roles of lipids in health and disease at the chemical level. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.