Current status and future prospects of transforming growth factor-β as a potential prognostic and therapeutic target in the treatment of breast cancer

The transforming growth factor-β (TGF-β) signaling pathway is one of the important pathways involved in the cancer cell proliferation, invasion, migration, angiogenesis, apoptosis, as well as in metastasis by agitation or invasion of metastasis-related factors, including matrix metalloproteinase (MMP), epithelial-to-mesenchymal transition (EMT), tumor microenvironment (TME), cancer stem cells (CSCs), and cell adhesion molecules (CAMs). These data suggest its potential value as a therapeutic object in the treatment of malignancies including breast cancer. Several pharmacological approaches have been established to suppress TGF-β pathway; such as vaccines, small molecular inhibitors, antisense oligonucleotides, and monoclonal antibodies. Some of these are now approved by the US Food and Drug Administration for targeting the TGF-β signaling pathway. This study attempts to summarize the current data about the functions of TGF-β in cancer cells, and their probable application in the cancer therapy with a specific emphasis on recent preclinical and clinical research in the treatment of breast cancer and its prognostic value.     

TNF-α and insulin resistance: Summary and future prospects

While the causes of obesity remain elusive, the relationship between obesity and insulin resistance is a well-established fact [1]. Insulin resistance is defined as a smaller than normal response to a certain dose of insulin, and contributes to several pathological problems of obese patients such as hyperlipidemia, arteriosclerosis and hypertension. Several pieces of evidence indicate that the cytokine tumor necrosis factor a (TNF-) is an important player in the state of insulin resistance observed during obesity. In this review we will try to summarize what is known about the function of TNF-a in insulin resistance during obesity and how TNF- interferes with insulin signaling.     

Novel associations between ophiostomatoid fungi,insects and tree hosts: current status—future prospects

Associations between fungal tree pathogens and insects have been recognized for at least 100 years. An important group of these fungi, termed ‘ophiostomatoid fungi’ on account of their morphological similarity, are represented by genera in the families Ceratocystidaceae and Ophiostomataceae. Associations between these fungi, tree-colonizing insects, and host trees have been actively researched since their first discovery. Human activities have led to the global movement of fungi from both families, resulting in the establishment of new and sometimes damaging associations between these fungi, insects and trees. Recent ‘black swan’ events have resulted in an unprecedented increase of ambrosia and bark beetle-associated diseases of forest and fruit trees. We revisit some of the most important emergent diseases caused by the ophiostomatoid fungi, outline the reasons behind the emergence of these diseases, and consider long-term prospects regarding the threats that they pose to forestry and agriculture.     

Changes in the Alyki Kitrous wetland in northern Greece: 1990–1999, and future prospects

The Alyki wetland in northern Greece is a site of notable herpetological and ornithological importance. A large population of the tortoise Testudo hermanni began to recover slowly (r = 0.016) between 1990 and 1999, following catastrophic habitat destruction in 1980 and slow decline from 1980–1990. Heathland vegetation showed signs of desiccation, probably due to increased drainage by the salt works, including deterioration of Crataegus, Ruscus and Asphodelus, and loss of formerly important food plants of tortoises. Activity and body mass condition of tortoises were reduced in summer in grassy heath habitats. Predation of artificial (chicken egg) tortoise nests increased, and the relative frequency of juveniles (about 1 % of samples) was lower than after severe habitat destruction or pesticide damage. These changes were attributed to an increasing population of badgers, Meles meles. Population levels of waders were lower in 1998/1999 than in 1988/1989, especially avocets (Recurvirostra avosetta) for which the site was internationally important. Breeding populations of most waders and larids also declined. Mediterranean gulls, for which Alyki was formerly the most important breeding area outside Russia, did not nest from 1990 to 1998, and nests were unsuccessful in 1999. Changes in breeding populations were due to falling lagoon levels, exposure to predators and vegetation encroachment on islet breeding sites. Midwinter waterfowl populations remained high or increased, however, as alternative feeding areas were available in the lagoon. Preservation of the habitats against development of the salt works and increasing desiccation are necessary to maintain the long-term conservation value of the Alyki site.     

International Symposium on Chemistry and Biology of Municipal Water Treatment: Current status and future directions October 24–29, 1993 Call for papers

Aquatic Ecosystem Health and Management Society

International Symposium on Chemistry and Biology of Municipal Water Treatment: Current status and future directions October 24–29, 1993 Call for papers     

Evolutionary morphology of the male reproductive system,spermatozoa and seminal fluid of spiders (Araneae,Arachnida) – Current knowledge and future directions

The male reproductive system and spermatozoa of spiders are known for their high structural diversity. Spider spermatozoa are flagellate and males transfer them to females in a coiled and encapsulated state using their modified pedipalps. Here, we provide a detailed overview of the present state of knowledge of the primary male reproductive system, sperm morphology and the structural diversity of seminal fluids with a focus on functional and evolutionary implications. Secondly, we conceptualized characters for the male genital system, spermiogenesis and spermatozoa for the first time based on published and new data. In total, we scored 40 characters for 129 species from 56 families representing all main spider clades. We obtained synapomorphies for several taxa including Opisthothelae, Araneomorphae, Dysderoidea, Scytodoidea, Telemidae, Linyphioidea, Mimetidae, Synotaxidae and the Divided Cribellum Clade. Furthermore, we recovered synspermia as a synapomorphy for ecribellate Haplogynae and thus propose Synspermiata as new name for this clade. We hope that these data will not only contribute to future phylogenetic studies but will also stimulate much needed evolutionary studies of reproductive systems in spiders.     

An emerging role of the 5′ termini of mature tRNAs in human diseases: Current situation and prospects

The fundamental biological roles of a class of small noncoding RNAs (sncRNAs), derived from mature tRNAs or pre-tRNAs, in human diseases have received increasing attention in recent years. These ncRNAs are called tRNA-derived fragments (tRFs) or tRNA-derived small RNAs (tsRNAs). tRFs mainly include tRF-1, tRF-5, tRF-3 and tRNA halves (tiRNAs or tRHs), which are produced by enzyme-specific cleavage of tRNAs. Here, we classify tRF-5 and 5′ tiRNAs into the same category: 5′-tRFs and review the biological functions and regulatory mechanisms of 5′-tRFs in cancer and other diseases (metabolic diseases, neurodegenerative diseases, pathological stress injury and virus infection) to provide a new theoretical basis for the diagnosis and treatment of diseases.     

Acetone–butanol–ethanol fermentation of corn stover by Clostridium species: present status and future perspectives

Sustainable vehicle fuel is indispensable in future due to worldwide depletion of fossil fuel reserve, oil price fluctuation and environmental degradation. Microbial production of butanol from renewable biomass could be one of the possible options. Renewable biomass such as corn stover has no food deficiency issues and is also cheaper in most of the agricultural based countries. Thus it can effectively solve the existing issue of substrate cost. In the last 30 years, a few of Clostridium strains have been successfully implemented for biobutanol fermentation. However, the commercial production is hindered due to their poor tolerance to butanol and inhibitors. Metabolic engineering of Clostridia strains is essential to solve above problems and ultimately enhance the solvent production. An effective and efficient pretreatment of raw material as well as optimization of fermentation condition could be another option. Furthermore, biological approaches may be useful to optimize both the host and pathways to maximize butanol production. In this context, this paper reviews the existing Clostridium strains and their ability to produce butanol particularly from corn stover. This study also highlights possible fermentation pathways and biological approaches that may be useful to optimize fermentation pathways. Moreover, challenges and future perspectives are also discussed.     

Contamination of air systems: 1987–88 assessment and prospects of the Grenoble intervention group

Summary In order to evaluate bacterial and fungal contamination, the authors used a qualitative and quantitative procedure and investigated 47 air conditioning and humidifying units. Air samples were studied using Biotest RCS biocollector (160×6 liters on 6 different selective media), whilst dust samples were analysed after spreading 10 mg onto fungal media. Selective research ofLegionella and fungi were performed using water filtrates and specific media. Even though, the most frequently identified species were quite common environmental fungi, mainlyPenicillium, Alternaria andAspergillus fumigatus (36 out of 47 collections), the health effects of intense exposure to these common moulds are not really known.Staphylococcus aureus was identified 6 times and thermophilic actinomyces species (A. candidus) once. From the quantitative analysis a significant relationship was found between some risk factors and airborne contamination. Indeed bacteria and fungi number depends on the humidifying system (steam or washer), efficiency of secondary filters, relative humidity percentage (< or >60%), installation maintenance, industrial activity and complaints of people at risk. The presence of air recycling and biocide use seems only to have an influence on fungal flora. Having determined a global risk score for each air conditioning unit, the authors underline the fact that bacterial and fungal airborne contamination increases with score. Moreover, for a global, metrological, medical and technical evaluation, a multidisciplinary approach has proved itself to be indispensable.     

The social and economic origins of genetic determinism: a case history of the American Eugenics Movement, 1900–1940 and its lessons for today

Eugenics, the attempt to improve the genetic quality of the human species by ‘better breeding’, developed as a worldwide movement between 1900 and 1940. It was particularly prominent in the United States, Britain and Germany, and in those countries was based on the then-new science of Mendelian genetics. Eugenicists developed research programs to determine the degree to which traits such as Huntington's chorea, blindness, deafness, mental retardation (feeblemindedness), intelligence, alcoholism, szhiophrenia, manic depression, rebelliousness, nomadism, prostitution and feeble-inhibition were genetically determined. Eugenicists were also active in the political arena, lobbying in the United States for immigration restriction and compulsory sterilization laws for those deemed genetically unfit; in Britain they lobbied for incarceration of genetically unfit and in Germany for sterilization and eventually euthanasia. In all these countries one of the major arguments was that of efficiency: that it was inefficient to allow genetic defects to be multiplied and then have to try and deal with the consequences of state care for the offspring. National Socialists called genetically defective individuals ‘useless eaters’ and argued for sterilization or euthanasia on economic grounds. Similar arguments appeared in the United States and Britain as well. At the present time (1997) much research and publicity is being given to claims about a genetic basis for all the same behaviors (alcoholism, manic depression, etc), again in an economic context – care for people with such diseases is costing too much. There is an important lesson to learn from the past: genetic arguments are put forward to mask the true – social and economic – causes of human behavioral defects. This revised version was published online in August 2006 with corrections to the Cover Date.     

Current status of the role of Cl− ion in the oxygen-evolving complex

This minireview summarizes the current state of knowledge concerning the role of Cl⁻ in the oxygen-evolving complex (OEC) of photosystem II (PSII). The model that proposes that Cl⁻ is a Mn ligand is discussed in light of more recent work. Studies of Cl⁻ specificity, stoichiometry, kinetics, and retention by extrinsic polypeptides are discussed, as are the results that fail to detect Cl⁻ ligation to Mn and results that show a lack of a requirement for Cl⁻ in PSII-catalyzed H₂O oxidation. Mutagenesis experiments in cyanobacteria and higher plants that produce evidence for a correlation between Cl⁻ retention and stable interactions among intrinsic and extrinsic polypeptides are summarized, and spectroscopic data on the interaction between PSII and Cl⁻ are discussed. Lastly, the question of the site of Cl⁻ action in PSII is discussed in connection with the current crystal structures of the enzyme.     

Success factors and future prospects of Ponto–Caspian peracarid (Crustacea: Malacostraca) invasions: Is ‘the worst over’?

Ponto–Caspian peracarids (amphipods, isopods, mysids and cumaceans) represent one of the most successful groups of aquatic invaders comprising several high-impact species, such as Chelicorophium curvispinum, Dikerogammarus villosus, or Hemimysis anomala. In the present study we made the first attempt to compare biological traits and the environmental preferences of invasive and non-invasive members of the group based on both literature and field data (Joint Danube Survey 3, 2013) with the goal of identifying factors linked to invasion success and drawing conclusions on future invasion risks. Both datasets indicated substrate preference as an important factor in spontaneous range expansion; all invasive species are lithophilous, whereas the majority of non-invasives are psammo-pelophilous. The remaining seven presently non-invasive lithophilous species deserve special attention when considering potential future invaders; however, due to their rarity and possible negative interactions with earlier colonists we consider the probability of their expansion in the foreseeable future as low. Their potential expansion could most likely be of minor consequence anyway, since no considerable functional novelty can be attributed to them in addition to species already present. In this limited context (regarding habitats dominated by hard substrates and not considering the potential further spread of already invasive species) it might be justified to conclude that ‘the worst is over’. Nevertheless, impending navigation development projects both in the Danube–Main–Rhine and Dnieper–Pripyat–Bug–Vistula systems might favour the future spread of non-lithophilous species, which might imply a new invasion wave of Ponto–Caspian peracarids.     

Modelling interactions of acid–base balance and respiratory status in the toxicity of metal mixtures in the American oyster Crassostrea virginica

Heavy metals, such as copper, zinc and cadmium, represent some of the most common and serious pollutants in coastal estuaries. In the present study, we used a combination of linear and artificial neural network (ANN) modelling to detect and explore interactions among low-dose mixtures of these heavy metals and their impacts on fundamental physiological processes in tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001–0.400 μM), Zn (0.001–3.059 μM) or Cu (0.002–0.787 μM), either alone or in combination for 1 to 27 days. We measured indicators of acid–base balance (hemolymph pH and total CO₂), gas exchange (Po₂), immunocompetence (total hemocyte counts, numbers of invasive bacteria), antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative membrane damage from tissue accumulation of environmental metals was correlated with impaired acid–base balance in oysters. ANN analysis revealed interactions of metals with hemolymph acid–base chemistry in predicting oxidative damage that were not evident from linear analyses. These results highlight the usefulness of machine learning approaches, such as ANNs, for improving our ability to recognize and understand the effects of sub-acute exposure to contaminant mixtures.     

Painting the chromosomes of <Emphasis Type="Italic">Brachypodium</Emphasis>—current status and future prospects

Chromosome painting is one of the most powerful and spectacular tools of modern molecular cytogenetics, enabling complex analyses of nuclear genome structure and evolution. For many years, this technique was restricted to the study of mammalian chromosomes, as it failed to work in plant genomes due mainly to the presence of large amounts of repetitive DNA common to all the chromosomes of the complement. The availability of ordered, chromosome-specific BAC clones of Arabidopsis thaliana containing relatively little repetitive genomic DNA enabled the first chromosome painting in dicotyledonous plants. Here, we show for the first time chromosome painting in three different cytotypes of a monocotyledonous plant—the model grass, Brachypodium distachyon. Possible directions of further detailed studies are proposed, such as the evolution of grass karyotypes, the behaviour of meiotic chromosomes, and the analysis of chromosome distribution at interphase.     

American geneticists and the eugenics movement: 1905–1935

Conclusion I have attempted to show that between 1905 and 1935, both internal and external factors were important in producing and influencing geneticists' attitudes toward the eugenics movement. Internal factors operated in several ways during this period. In the first decade of the century, discoveries within genetics supplied geneticists a mode of expression to evoke their already existing social concern by providing a new vocabulary with which to present eugenic proposals. In addition, because these findings were relatively easy to explain to the layman, it became an easy matter for geneticists to popularize eugenics. After 1915, by suggesting the complexity of inheritance, other developments within genetics helped dim their initial enthusiasm for the movement. During this period, factors external to the science of genetics also were important. By producing a general interest in social affairs among many geneticists, the intellectual and social milieu of the late 1800's lay the foundations for their early participation in the eugenics movement. In the 1920's and 1930's the subjection of genetic theory to support preconceived social and political doctrines prompted them to renounce the movement publicly.While both internal and external factors operated on geneticists, the lesson of this study is that external factors were more important in influencing their attitudes toward the movement than internal factors. At the turn of the century, geneticists inherited from Social Darwinism a general interest in applying biological principles to the analysis of social problems; discoveries within genetics mainly provided a convenient and persuasive terminology with which to express their interest. Later, both internal and external factors caused their enthusiasm for the movement to wane, but their public renunciation of it was caused primarily by external factors alone.The importance of external factors is seen to be even greater by considering the model I suggested to explain the development of social responsibility in modern form among scientists. According to this model, social responsibility results after a crisis in the social uses of a given science—as a response to external factors. This model appears to account satisfactorily for the emergence of geneticists' sense of social responsibility: alarmed by eugenicists' frequent endorsement of Nazi eugenic programs, many geneticists claimed it was their duty to explain the facts of their science to the public so that the layman could see for himself the scientific errors of racism. Geneticists were now presenting the layman the facts, though not necessarily interpreting the facts for him. This same pattern—the emergence of modern social responsibility after an externally induced crisis-appears to be present in the other examples that I gave.The ironies revealed by this study are many. First, it is ironic that principles of genetics created feelings of both pessimism and optimism among many geneticists. Early developments in genetics-Mendel's laws, the concept of unit inheritance, and Weismann's theory-supplemented Social Darwinism in creating an atmosphere of pessimism among many geneticists by posing the grim assumption that human defects are hereditarily determined and incapable of medical cure. In recognizing the importance of heredity in development, many geneticists for a while were overly pessimistic in their forecasts of the evolutionary future of the human race. These same three genetic developments, however, by suggesting the feasibility of a eugenics program, of controlling reproduction to eliminate defective genes from the population, provided a remedy to the problem they had helped create.It is also ironic that even though the classical eugenics movement has been discredited in America for over thirty years, many individuals today are speaking of certain dangers to society in terms remarkably similar to those used by the classical eugenicists. The explosion of the atomic bomb created a sudden awareness among the public of the dangers of gene mutation from radiation and other sources⁴¹. Today, as topics such as the genetic load are increasingly discussed, many individuals are experiencing a growing alarm over the future genetic condition of the American people, a marked concern over the rising genetic and financial costs to society of modern medicine for preserving defectives and allowing them to reproduce.Although geneticists in the 1930's generally abandoned the ideal of using science to prescribe policy, to construct ends for social action, it was this ideal which initially attracted many of them to the eugenics movement in the first place. In the early years of the century, geneticists viewed science in a new light: as a restraint upon conduct. Hitherto, science had been valued for its products, for releasing man from old burdens, for supplying him new opportunities to enjoy and to explore life. In supporting the eugenics movement, geneticists departed from this mode. They now appealed to science, not for a particular product, but to determine who should and who should not reproduce. They let science act as a constraint upon their actions; they let science tell them that individual desires are less important than the biological and moral imperative of improving the human race⁴². Thus, it becomes understandable why many geneticists for a time regarded eugenics as a religion, for they had permitted biology to assume religion's traditional function of defining permissible conduct. The history of geneticists' involvement with the eugenics movement reminds us that science can play many roles and be put to many purposes.