Early induction of neural crest cells: lessons learned from frog,fish and chick

The identification of genes in Xenopus, chick and zebrafish expressed early in prospective neural crest (NC) cells has challenged the previous view that the NC is induced during the closure of the neural tube. We compare here the early inductive molecular mechanisms in different organisms and, despite observed differences, propose a general common model for NC induction.     

Tuberculin immunotherapy: its history and lessons to be learned

The use of tuberculin for the therapy of tuberculosis was attempted more than 100 years ago and abandoned because of its adverse reactions. In this historical review we point out that some of the intensive efforts to avoid the reactions were based on the best scientific rationale available at that time. Balancing the dosage and intervals of tuberculin delivery with clinical and laboratory monitoring of patients achieved a limited success, with implications, toward current research in the field. The role of economical and social aspects at that time is also a lesson to be learned toward current approaches to tuberculosis control.     

The core-binding factor leukemias: lessons learned from murine models

The recent development of murine models of core-binding factor leukemias has provided important insights into the underlying molecular pathology of this common subtype of acute myeloid leukemia. Evidence from these models supports the idea that acute myeloid leukemia 1/core-binding factor beta-subunit (AML1/CBFbeta) has a critical role in the control of the self-renewal capacity of hematopoietic stem cells and their progeny. Moreover, the accumulated data demonstrate that the expression of translocation-encoded AML1 or CBFbeta fusion proteins are insufficient by themselves to induce a full leukemic phenotype. The models that have been developed should prove to be of value for defining the range of mutations that can cooperate with AML1/CBFbeta fusion proteins, and for assessing novel therapies targeted toward the pathways that are altered by the expression of these fusion proteins.     

The Global Environment Facility and biodiversity conservation: lessons to date and suggestions for future action

The last five years in particular have seen increasing attention paid to biodiversity. This culminated at the Earth Summit last June with the completion of Agenda 21 and a major international Convention on Biological Diversity, a document signed by some 165 nations. Concurrent with the Convention negotiations was the development of a global fund for biodiversity conservation and other environmental priorities, the Global Environment Facility (GEF). The GEF is the largest fund to data put forward by the international community to address biodiversity loss, but, so far, it has failed to set adequate priorities for biodiversity conservation. It has also yet to recognize the full range of biodiversity values and uses and, in general, GEF projects have not taken advantage of existing non-governmental capacity for biodiversity conservation. 1993 is a critical year for the GEF, one in which the GEF can become a critical element of global efforts to conserve biodiversity or remain an important initialive that realized only a fraction of its potential.     

Iron and protein biofortification of cassava: lessons learned

Over two hundred and fifty million Africans rely on the starchy root crop cassava (Manihot esculenta) as their primary source of calories. Cassava roots, however, have the lowest protein:energy ratio of all the world's major staple crops. Furthermore, a typical cassava-based diet provides less than 10-20% of the required amounts of iron, zinc, vitamin A and vitamin E. The BioCassava Plus program employed modern biotechnologies to improve the health of Africans through development and delivery of novel cassava germplasm with increased nutrient levels. Here we describe the development of molecular strategies and their outcomes to meet minimum daily allowances for protein and iron in cassava based diets. We demonstrate that cyanogens play a central role in cassava nitrogen metabolism and that strategies employed to increase root protein levels result in reduced cyanogen levels in roots. We also demonstrate that enhancing root iron uptake has an impact on the expression of genes that regulate iron homeostasis in multiple tissues. These observations demonstrate the complex metabolic interactions involved in enhancing targeted nutrient levels in plants and identify potential new strategies for further enhancing nutrient levels in cassava.     

Development and cancer: lessons learned in the pancreas

Cancer progression and organ development are similar phenomena. Both involve rapid bursts of proliferation, angiogenesis, tissue remodeling, and cell migration. Therefore, it is not surprising that both processes utilize similar signaling machinery. In fact, many recent studies have suggested that cancer is a disease triggered by the erroneous re-activation of signaling pathways that are typically downregulated after the completion of embryonic development. This link between embryonic development and cancer is particularly exciting because it suggests that we might be able to exploit the knowledge gained in studies of Developmental Biology to obtain novel insights into tumor biology. Our evolving understanding of pancreatic adenocarcinoma is an excellent example of this relationship between development and cancer. Here we discuss recent studies have indicated important roles for two major developmental signaling pathways in pancreatic cancer: Notch and Hedgehog (Hh).     

Amazonia and the modern carbon cycle: lessons learned

In this paper, we review some critical issues regarding carbon cycling in Amazonia, as revealed by several studies conducted in the Large Scale Biosphere Atmosphere Experiment in Amazonia (LBA). We evaluate both the contribution of this magnificent biome for the global net primary productivity/net ecosystem exchange (NPP/NEE) and the feedbacks of climate change on the dynamics of Amazonia. In order to place Amazonia in a global perspective and make the carbon flux obtained through the LBA project comparable with global carbon budgets, we extrapolated NPP/NEE values found by LBA studies to the entire area of the Brazilian Amazon covered by rainforest. The carbon emissions due to land use changes for the tropical regions of the world produced values from 0.96 to 2.4 Pg C year⁻¹, while atmospheric CO₂ inversion models have recently indicated that tropical lands in the Americas could be exchanging a net 0.62±1.15 Pg C year⁻¹ with the atmosphere. The difference calculated from these two methods would imply a local sink of approximately 1.6–1.7 Pg C year⁻¹, or a source of 0.85 ton C ha⁻¹ year⁻¹. Using our crude extrapolation of LBA values for the Amazon forests (5 million km²) we estimate a range for the C flux in the region of −3.0 to 0.75 Pg C year⁻¹. The exercise here does not account for environmental variability across the region, but it is an important driver for present and future studies linking local process (i.e. nutrient availability, photosynthetic capacity, and so forth) to global and regional dynamic approaches.     

Barriers to fish passage and barriers to fish passage assessments: the impact of assessment methods and assumptions on barrier identification and quantification of watershed connectivity

Barriers (culverts and dams) can impede fish passage and affect the overall habitat connectivity of rivers. However, a challenge lies in how to conceptualize and adequately measure passability at barriers. We hypothesize that estimates of barrier and watershed connectivity are dependent on assumptions about the nature of passability, and how it is measured. Specifically, we compare passability estimates in Terra Nova National Park, Canada for individual barriers for two barrier assessment methods (a rapid assessment and one based on FishXing software), two salmonid species, different fish sizes and swimming speeds, and varying hydrological conditions. Watershed connectivity was calculated using the Dendritic Connectivity Index (DCI). Lastly, we test to see what the impact of the various factors is on the practical goal: prioritizing barriers for restoration. Our results show that barrier passability estimates can vary drastically for some barriers (0–100%). In general, the rapid field-based assessment tended to give more conservative estimates of passability than those based on FishXing. Estimates of watershed connectivity were not as sensitive to the assumptions and methods used (DCI: 40–83). Fish size had the greatest effect on DCI. Importantly, variation in DCI had little impact on the restoration priorities. The same barrier was retained as the top priority >96% of the time. Thus, managers wishing to assess barriers for restoration need to carefully consider how passability is to be measured, but can reduce the impact of these decisions by considering barriers in their watershed context using a connectivity index such as the DCI.     

A national fish passage barrier inventory to support fish passage policy implementation and estimate river connectivity in New Zealand

Fragmentation of river systems is a key driver of freshwater biodiversity loss. Instream structure inventories are an essential component of delivering a strategic approach to restoring river connectivity. We used a range of data sources to collate the best available information on fish passage barriers and instream structures across the whole of New Zealand. To support implementation of new national policy objectives to maintain and improve river connectivity, the structure inventory has been integrated with a new fish passage assessment mobile application that allows river managers and asset owners to ground-truth, update and add records to the database. The data are provided open access and are being used for environmental reporting and to support strategic prioritisation of barrier mitigation actions. We used these data to quantify river connectivity at regional and national scales and demonstrated that at least half of New Zealand's river network is upstream of fish migration barriers. Limitations to our calculation of upstream river connectivity included the unknown influence of unrecorded structures, particularly on private land, missing information within recorded data, the large number of instream structures that have been identified but not yet assessed for their risk to fish passage, and spatial errors in the automated pairing of structures to a digital river network. A critical challenge for river managers is understanding the consequences of these uncertainties in the data for prioritisation and decision-making regarding barrier removal or mitigation.     

大熊猫国家公园体制试点的经验与挑战

大熊猫国家公园试点于2016年8月由四川、陕西、甘肃三省人民政府联合上报《大熊猫国家公园体制试点方案》;2016年12月5日,习近平总书记主持召开中央全面深化改革领导小组第三十次会议审议通过《大熊猫国家公园体制试点方案》;2017年1月31日,中共中央办公厅、国务院办公厅印发《大熊猫国家公园体制试点方案》;2018年10月29日,大熊猫国家公园管理局正式挂牌;2018年11月,大熊猫祁连山国家公园甘肃省管理局、大熊猫国家公园四川省管理局、大熊猫国家公园陕西省管理局相继挂牌;2020年3月17日,大熊猫国家公园管理局印发《大熊猫国家公园管理办法(试行)》;2020年6月,国家林业和草原局(国家公园管理局)印发《大熊猫国家公园总体规划(试行)》。在试点过程中,初步建立起由大熊猫国家公园管理局、省管理局、管理分局、管护站(管护总站)构成的实际管理体系,其中省管理局3个、管理分局14个。     

Regulation of immunity to malaria: valuable lessons learned from murine models

A major advance in immunology has been the establishment of a framework for analysing how certain immune responses dominate following exposure to a particular pathogen or antigen. CD4(+) T helper (Th) cells can be separated into two major subsets which mediate qualitatively distinct cell-mediated (Th1) and humoral (Th2) immune responses. Immunity to most pathogens can be broadly categorized into a predominant protective response of either type. A characteristic of murine malarias is that primary infections with asexual erythrocytic parasites (the pathogenic stage of the malaria life cycle) generate a host protective immune response with a broad spectrum of Th1- and Th2-type CD4(+) T-cell involvement and so can be examined as models of the interaction of Th1 and Th2 cells during an immune response to an infectious agent. Andrew Taylor-Robinson here describes recent events in the dissection of the mechanisms responsible for the generation of protective immunity to Plasmodium chabaudi chabaudi and other experimental malarias in mice.     

Origin of resistance to Imatinib mesylate: lessons learned from this experience

For drug development and pharmaceutical research, targeting the molecular abnormalities is considered as a new challenge. A number of diseases including cancer are linked to perturbation of tyrosine kinase (TK). Imatinib (Glivec or Gleevec, Novartis), the most potent inhibitor of c-abl TK, was recently developed. This molecule has been approved in the treatment of chronic myeloid leukemia (CML). However, emergence of clinical resistance regarding a low rate of CML patients leads to intensive research. In the current article, we discuss the data and the mechanism of the resistance phenomenon. This review illustrates the important requirement to transfer back the information from patient to laboratory in order to improve future drug design.     

Introduction: microbiology and immunology: lessons learned from Salmonella.

Salmonella enterica, a Gram-negative bacterium, causes significant morbidity and mortality worldwide, and is an excellent model to study bacterial pathogenesis and cellular immune responses. With the development of powerful new technologies, there has been a fusion of research on immunology, molecular biology and cellular microbiology of S. enterica infections. This multidisciplinary research will enhance our understanding of the basic mechanisms of bacterial infections and immunity; it also provides new approaches towards therapeutic and control measures.     

Protein folding diseases and neurodegeneration: lessons learned from yeast

Budding yeast Saccharomyces cerevisiae has proven to be a valuable model organism for studying fundamental cellular processes across the eukaryotic kingdom including man. In this respect, complementation assays, in which the yeast protein is replaced by a homologous protein from another organism, have been very instructive. A newer trend is to use the yeast cell factory as a toolbox to understand cellular processes controlled by proteins for which the yeast lacks functional counterparts. An increasing number of studies have indicated that S. cerevisiae is a suitable model system to decipher molecular mechanisms involved in a variety of neurodegenerative disorders caused by aberrant protein folding. Here we review the current knowledge gained by the use of so-called humanized yeasts in the field of Huntington's, Parkinson's and Alzheimer's diseases.     

Protozoa and pathogenic bacteria: lessons learned from Legionella pneumophila

Bacterivorous protozoa and bacteria have been in co-existence since the origin of life. This co-existence has led unequivocally to the evolution of many different co-interactions. Most bacteria are ingested and digested, but many escape ingestion for various reasons. Others are ingested but evade digestion, and a few, notoriously Legionella pneumophila , even have the capacity of multiplying within the protozoan host. The aims of this study were to elucidate the interactions of various multi-drug-resistant Staphylococcus aureus (MRSA) strains, Listeria monocytogenes sv4b, and Escherichia coli K12 with the amoeba, Acanthamoeba polyphaga . To evaluate the interactions, we set up co-cultures in Neffs' amoebic saline, at a multiplicity of invasion (MOI) of 1:100 of amoeba to bacteria, and a temperature of 37°C, although the effects of MOI and temperature were also assessed. Survival of bacteria and amoeba was checked at regular intervals, coupled with microscopy. It was discovered under our test conditions, that E. coli was ingested and digested by A. polyphaga , but in contrast, L. monocytogenes , had the capacity to flourish in the presence of A. polyphaga . We also report, for the first time, that all six MRSA isolates tested, survived and replicated in association with A. polyphaga , in comparison to conditions where amoebae were absent. Indeed, we also have evidence suggesting that increases in MRSA, in the presence of A. polyphaga , may be attributable to intracellular survival and replication. These findings have profound implications for the hospital environment, where Acanthamoeba sp., are also commonly isolated. In conclusion, this study illustrates the significance of protozoa as vehicles augmenting the survival of MRSA and L. monocytogenes in the environment.     

Clinical trials in systemic sclerosis: lessons learned and outcomes

The pathogenesis of systemic sclerosis (SSc) is complex and largely unclear. The clinical heterogeneity of the disease and its progression over a number of years makes the choice of endpoints in the design of clinical trials difficult. The overwhelming need in this disease is to diagnose it early and identify those patients who will benefit most from early, aggressive treatment that potentially can alter the clinical disease course. To achieve this, innumerable challenges must be overcome. This article reviews data from recent clinical trials and the lessons derived from retrospective observational studies, databases, and patient registries. Taken together, these observations will help to improve our understanding of the diverse clinical course of SSc and permit refinement of existing outcome measures for the design of future clinical trials, in which the likelihood of observing a positive treatment effect with the drugs at our disposal will be maximized.