Circulating tumor cells: Isolation, expansion, characterization and translation to clinic

Circulating tumor cells (CTCs) are the seeds for cancer metastases development, which is responsible for >90% of cancer-related deaths. Accurate quantification of CTCs in human fluids could be an invaluable tool for understanding cancer prognosis, delivering personalized medicine to prevent metastasis and finding cancer therapy effectiveness. Although CTCs were first discovered more than 200 years ago, until now it has been a nightmare for clinical practitioners to capture and diagnose CTCs in clinical settings. Our society needs rapid, sensitive, and reliable assays to identify the CTCs from blood in order to help save millions of lives. Due to the phenotypic EMT transition, CTCs are undetected for more than one-third of metastatic breast cancer patients in clinics. To tackle the above challenges, the first volume in “Circulating Tumor Cells (CTCs): Detection Methods, Health Impact and Emerging Clinical Challenges discusses recent developments of different technologies, which have the capability to target and elucidate the phenotype heterogenity of CTCS. It contains seven chapters written by world leaders in this area, covering basic science to possible device design which can have beneficial applications in society. This book is unique in its design and content, providing an in-depth analysis to elucidate biological mechanisms of cancer disease progression, CTC detection challenges, possible health effects and the latest research on evolving technologies which have the capability to tackle the above challenges. It describes the broad range of coverage on understanding CTCs biology from early predictors of the metastatic spread of cancer, new promising technology for CTC separation and detection in clinical environment and monitoring therapy efficacy via finding the heterogeneous nature of CTCs. (Imprint: Nova Biomedical)

Biology and Management of Psocids Infesting Stored Products

Previously regarded as minor nuisance pests, psocids belonging to the genus Liposcelis now pose a major problem for the effective protection of stored products worldwide. Here we examine the apparent biological and operational reasons behind this phenomenon and why conventional pest management seems to be failing. We investigate what is known about the biology, behavior, and population dynamics of major pest species to ascertain their strengths, and perhaps find weaknesses, as a basis for a rational pest management strategy. We outline the contribution of molecular techniques to clarifying species identification and understanding genetic diversity. We discuss progress in sampling and trapping and our comprehension of spatial distribution of these pests as a foundation for developing management strategies. The effectiveness of various chemical treatments and the availability and potential of nonchemical control methods are critically examined. Finally, we identify research gaps and suggest future directions for research.

Low temperature exposure of root system and inflorescence affected flowering and fruit set in 'Chardonnay' grapevines (Vitis vinifera)

The mechanisms by which low temperature affects flowering and fruit set of grapevines are poorly understood, as is the specific response of the grapevine root system and inflorescence to low temperature effects that reduce fruit set. This study aimed to determine the responses of the root system and inflorescence of the grapevine 'Chardonnay' to low temperature (10 degrees C) during flowering, and considered the possible mechanisms of low temperature effects on those parts. Temperature treatments of 10 degrees C or 20 degrees C were imposed to potted 'Chardonnay' grapevines in a glasshouse for up to two weeks during the early stages of flowering. When the root system alone was exposed to 10 degrees C (with the rest of the plant at 20 degrees C) during flowering, the number of attached berries and percentage fruit set were significantly reduced by 50 % than when the root system alone was exposed to 20 degrees C. Whereas, exposure of the inflorescence alone to 10 degrees C (with the rest of the plant at 20 degrees C) delayed flowering, allowed rachis to grow longer, and increased both the number of attached berries (from 22 to 62 per vine) and fruit set (from 8 % to, 20 %), than when the inflorescence alone was exposed to 20 degrees C. This study will enhance our understanding of the possible mechanisms of low temperature effects on grapevine fruit set and productivity.

Robust features of future climate change impacts on sorghum yields in West Africa

West Africa is highly vulnerable to climate hazards and better quantification and understanding of the impact of climate change on crop yields are urgently needed. Here we provide an assessment of near-term climate change impacts on sorghum yields in West Africa and account for uncertainties both in future climate scenarios and in crop models. Towards this goal, we use simulations of nine bias-corrected CMIP5 climate models and two crop models (SARRA-H and APSIM) to evaluate the robustness of projected crop yield impacts in this area. In broad agreement with the full CMIP5 ensemble, our subset of bias-corrected climate models projects a mean warming of +2.8 °C in the decades of 2031–2060 compared to a baseline of 1961–1990 and a robust change in rainfall in West Africa with less rain in the Western part of the Sahel (Senegal, South-West Mali) and more rain in Central Sahel (Burkina Faso, South-West Niger). Projected rainfall deficits are concentrated in early monsoon season in the Western part of the Sahel while positive rainfall changes are found in late monsoon season all over the Sahel, suggesting a shift in the seasonality of the monsoon. In response to such climate change, but without accounting for direct crop responses to CO2, mean crop yield decreases by about 16–20% and year-to-year variability increases in the Western part of the Sahel, while the eastern domain sees much milder impacts. Such differences in climate and impacts projections between the Western and Eastern parts of the Sahel are highly consistent across the climate and crop models used in this study. We investigate the robustness of impacts for different choices of cultivars, nutrient treatments, and crop responses to CO2. Adverse impacts on mean yield and yield variability are lowest for modern cultivars, as their short and nearly fixed growth cycle appears to be more resilient to the seasonality shift of the monsoon, thus suggesting shorter season varieties could be considered a potential adaptation to ongoing climate changes. Easing nitrogen stress via increasing fertilizer inputs would increase absolute yields, but also make the crops more responsive to climate stresses, thus enhancing the negative impacts of climate change in a relative sense. Finally, CO2 fertilization would significantly offset the negative climate

Interference and management of parthenium: The world's most important invasive weed

Parthenium (Parthenium hysterophorus L.) is one of the most aggressive herbaceous weeds of the Asteraceae family. It is widely distributed, almost across the world and has become the most important invasive weed. Comprehensive information on interference and control of this devastating species is required to facilitate better management decisions. A broad review on the interference and management of this weed is presented here. Inspite of its non-tropical origin, parthenium grows quite successfully under a wide range of environmental conditions. It is spreading rapidly in Australia, Western Africa, Asia, and Caribbean countries, and has become a serious weed of pastures, wastelands, roadsides, railwaysides, water courses, and agricultural crops. The infestations of parthenium have been reported to reduce grain and forage yields by 40–90%. The spread of parthenium has been attributed to its allelopathic activity, strong competitiveness for soil moisture and nutrients, and its capability to exploit natural biodiversity. Allelochemicals released from parthenium has been reported to decrease germination and growth of agronomic crops, vegetables, trees, and many other weed species. Growth promoting effects of parthenium extracts at low concentrations have also been reported in certain crops. Many pre- and post-emergence herbicides have been evaluated for the control of parthenium in cropped and non-cropped areas. The most effective herbicides are clomazone, metribuzin, atrazine, glyphosate, metsulfuron methyl, butachlor, bentazone, dicamba, and metsulfuron methyl. Extracts, residues, and essential oils of many allelopathic herbs (Cassia, Amaranthus, and Xanthium species), grasses (Imperata and Desmostachya species), and trees (Eucalyptus, Azadirachta, Mangifera species, etc.) have demonstrated inhibitory activities on seed germination and seedling growth of parthenium. Metabolites of several fungi, e.g., Fusarium oxysporun and Fusarium monilifonne, exhibit bioherbicidal activity against seeds and seedlings of this weed. Intercropping, displacement by competitive plant species like Cassia species, bisset bluegrass, florgen blugress, buffelgrass, along with the use of biological control agents like Mexican beetle, seed-feeding and stem-boring weevils, stem-galling and leaf-mining moth, and sap-feeding plant hopper, have been reported as possible strategies for the management of parthenium. An appropriate integration of these approaches could help minimize spread of parthenium and provide sustainable weed management with reduced environmental concerns.

The Miocene of Western Asia; Fossil mammals at the crossroads of faunal provinces and climate regimes

Being at the crossroads of the Old World continents, Western Asia has a unique position through which the dispersal and migration of mammals and the interaction of faunal bioprovinces occurred. Despite its critical position, the record of Miocene mammals in Western Asia is sporadic and there are large spatial and temporal gaps between the known fossil localities. Although the development of the mammalian faunas in the Miocene of the Old World is well known and there is ample evidence for environmental shifts in this epoch, efforts toward quantification of habitat changes and development of chronofaunas based on faunal compositions were mostly neglected. Advancement of chronological, paleoclimatological, and paleogeographical reconstruction tools and techniques and increased numbers of new discoveries in recent decades have brought the need for updating and modification of our level of understanding. We under took fieldwork and systematic study of mammalian trace and body fossils from the northwestern parts of Iran along with analysis of large mammal data from the NOW database. The data analysis was used to study the provinciality, relative abundance, and distribution history of the closed- and open-adapted taxa and chronofaunas in the Miocene of the Old World and Western Asia. The provinciality analysis was carried out, using locality clustering, and the relative abundance of the closed- and open-adapted taxa was surveyed at the family level. The distribution history of the chronofaunas was studied, using faunal resemblance indices and new mapping techniques, together with humidity analysis based on mean ordinated hypsodonty. Paleoichnological studies revealed the abundance of mammalian footprints in several parts of the basins studied, which are normally not fossiliferous in terms of body fossils. The systematic study and biochronology of the newly discovered mammalian fossils in northwestern Iran indicates their close affinities with middle Turolian faunas. Large cranial remains of hipparionine horses, previously unknown in Iran and Western Asia, are among the material studied. The initiation of a new field project in the famous Maragheh locality also brings new opportunities to address questions regarding the chronology and paleoenvironment of this classical site. Provinciality analysis modified our previous level of understandings, indicating the interaction of four provinces in Western Asia. The development of these provinces was apparently due to the presence of high mountain ranges in the area, which affected the dispersal of mammals and also climatic patterns. Higher temperatures and possibly higher co2 levels in the Middle Miocene Climatic Optimum apparently favored the development of the closed forested environments that supported the dominance of the closed-adapted taxa. The increased seasonality and the progressive cooling and drying of the midlatitudes toward the Late Miocene maintained the dominance of open-adapted faunas. It appears that the late Middle Miocene was the time of transition from a more forested to a less forested world. The distribution history of the closed- and open-adapted chronofaunas shows the presence of cosmopolitan and endemic faunas in Western Asia. The closed-adapted faunas, such as the Arabian chronofauna of the late Early‒early Middle Miocene, demonstrated a rapid buildup and gradual decline. The open-adapted chronofaunas, such as the Late Miocene Maraghean fauna, climaxed gradually by filling the opening environments and moving in response to changes in humidity patterns. They abruptly declined due to demise of their favored environments. The Siwalikan chronofauna of the early Late Miocene remained endemic and restricted through all its history. This study highlights the importance of field investigations and indicates that new surveys in the vast areas of Western Asia, which are poorly sampled in terms of fossil mammal localities, can still be promising. Clustering of the localities supports the consistency of formerly known patterns and augments them. Although the quantitative approach to relative abundance history of the closed- and open-adapted mammals harks back to more than half a century ago, it is a novel technique providing robust results. Tracking the history of the chronofaunas in space and time by means of new computational and illustration methods is also a new practice that can be expanded to new areas and time spans.

Electrophysiological activity of the Sirex noctilio ovipositor: You know the drill?

Sirex woodwasp (Sirex noctilio F: Hymenoptera: Siricidae) is a major worldwide pest of pine (Pinus) species. The female woodwasp undertakes exploratory drills with the ovipositor prior to egg-laying to assess tree suitability. Previous work has shown that this behaviour is associated with assessing the osmotic pressure of the tree. Here we show that, in addition, the ovipositor is electrophysiologically active and capable of detecting ethanol and chemical components of solvent extracts of pine needles and bark. Scanning electron micrographs of the ovipositor show the presence of structures which may have a chemoreceptive function. Our research expands our knowledge of the role that the Sirex ovipositor plays in egg-laying site selection.

Development of a Rapid Multiplex PCR Assay To Genotype Pasteurella multocida Strains by Use of the Lipopolysaccharide Outer Core Biosynthesis Locus

Pasteurella multocida is a Gram-negative bacterial pathogen that is the causative agent of a wide range of diseases in many animal species, including humans. A widely used method for differentiation of P. multocida strains involves the Heddleston serotyping scheme. This scheme was developed in the early 1970s and classifies P. multocida strains into 16 somatic or lipopolysaccharide (LPS) serovars using an agar gel diffusion precipitin test. However, this gel diffusion assay is problematic, with difficulties reported in accuracy, reproducibility, and the sourcing of quality serovar-specific antisera. Using our knowledge of the genetics of LPS biosynthesis in P. multocida, we have developed a multiplex PCR (mPCR) that is able to differentiate strains based on the genetic organization of the LPS outer core biosynthesis loci. The accuracy of the LPS-mPCR was compared with classical Heddleston serotyping using LPS compositional data as the "gold standard." The LPS-mPCR correctly typed 57 of 58 isolates; Heddleston serotyping was able to correctly and unambiguously type only 20 of the 58 isolates. We conclude that our LPS-mPCR is a highly accurate LPS genotyping method that should replace the Heddleston serotyping scheme for the classification of P. multocida strains.

Vertical Distribution of Soil Denitrifying Communities in a Wet Sclerophyll Forest under Long-Term Repeated Burning

Soil biogeochemical cycles are largely mediated by microorganisms, while fire significantly modifies biogeochemical cycles mainly via altering microbial community and substrate availability. Majority of studies on fire effects have focused on the surface soil; therefore, our understanding of the vertical distribution of microbial communities and the impacts of fire on nitrogen (N) dynamics in the soil profile is limited. Here, we examined the changes of soil denitrification capacity (DNC) and denitrifying communities with depth under different burning regimes, and their interaction with environmental gradients along the soil profile. Results showed that soil depth had a more pronounced impact than the burning treatment on the bacterial community size. The abundance of 16S rRNA and denitrification genes (narG, nirK, and nirS) declined exponentially with soil depth. Surprisingly, the nosZ-harboring denitrifiers were enriched in the deeper soil layers, which was likely to indicate that the nosZ-harboring denitrifiers could better adapt to the stress conditions (i.e., oxygen deficiency, nutrient limitation, etc.) than other denitrifiers. Soil nutrients, including dissolved organic carbon (DOC), total soluble N (TSN), ammonium (NH4 +), and nitrate (NO3 −), declined significantly with soil depth, which probably contributed to the vertical distribution of denitrifying communities. Soil DNC decreased significantly with soil depth, which was negligible in the depths below 20 cm. These findings have provided new insights into niche separation of the N-cycling functional guilds along the soil profile, under a varied fire disturbance regime.

Fine mapping of qGW1, a major QTL for grain weight in sorghum

Key message We detected seven QTLs for 100-grain weight in sorghum using an F 2 population, and delimited qGW1 to a 101-kb region on the short arm of chromosome 1, which contained 13 putative genes. Abstract Sorghum is one of the most important cereal crops. Breeding high-yielding sorghum varieties will have a profound impact on global food security. Grain weight is an important component of grain yield. It is a quantitative trait controlled by multiple quantitative trait loci (QTLs); however, the genetic basis of grain weight in sorghum is not well understood. In the present study, using an F2 population derived from a cross between the grain sorghum variety SA2313 (Sorghum bicolor) and the Sudan-grass variety Hiro-1 (S. bicolor), we detected seven QTLs for 100-grain weight. One of them, qGW1, was detected consistently over 2 years and contributed between 20 and 40 % of the phenotypic variation across multiple genetic backgrounds. Using extreme recombinants from a fine-mapping F3 population, we delimited qGW1 to a 101-kb region on the short arm of chromosome 1, containing 13 predicted gene models, one of which was found to be under purifying selection during domestication. However, none of the grain size candidate genes shared sequence similarity with previously cloned grain weight-related genes from rice. This study will facilitate isolation of the gene underlying qGW1 and advance our understanding of the regulatory mechanisms of grain weight. SSR markers linked to the qGW1 locus can be used for improving sorghum grain yield through marker-assisted selection.

Making the most of spatial information in health: A tutorial in Bayesian disease mapping for areal data

Disease maps are effective tools for explaining and predicting patterns of disease outcomes across geographical space, identifying areas of potentially elevated risk, and formulating and validating aetiological hypotheses for a disease. Bayesian models have become a standard approach to disease mapping in recent decades. This article aims to provide a basic understanding of the key concepts involved in Bayesian disease mapping methods for areal data. It is anticipated that this will help in interpretation of published maps, and provide a useful starting point for anyone interested in running disease mapping methods for areal data. The article provides detailed motivation and descriptions on disease mapping methods by explaining the concepts, defining the technical terms, and illustrating the utility of disease mapping for epidemiological research by demonstrating various ways of visualising model outputs using a case study. The target audience includes spatial scientists in health and other fields, policy or decision makers, health geographers, spatial analysts, public health professionals, and epidemiologists.

Isotope shifts and hyperfine structure in the 555.8-nm S-1(0) -> P-3(1) line of Yb

We apply our technique of using a Rb-stabilized ring-cavity resonator to measure the frequencies of various spectral components in the 555.8-nm 1S0-->3P1 line of Yb. We determine the isotope shifts with 60 kHz precision, which is an order-of-magnitude improvement over the best previous measurement on this line. There are two overlapping transitions, 171Yb(1/2-->3/2) and 173Yb(5/2-->3/2), which we resolve by applying a magnetic field. We thus obtain the hyperfine constants in the 3P1 state of the odd isotopes with a significantly improved precision. Knowledge of isotope shifts and hyperfine structure should prove useful for high-precision calculations in Yb necessary to interpret ongoing experiments testing parity and time-reversal symmetry violation in the laws of physics.

Estimation and evaluation of multi-decadal fire severity patterns using Landsat sensors

Retrospective identification of fire severity can improve our understanding of fire behaviour and ecological responses. However, burnt area records for many ecosystems are non-existent or incomplete, and those that are documented rarely include fire severity data. Retrospective analysis using satellite remote sensing data captured over extended periods can provide better estimates of fire history. This study aimed to assess the relationship between the Landsat differenced normalised burn ratio (dNBR) and field measured geometrically structured composite burn index (GeoCBI) for retrospective analysis of fire severity over a 23 year period in sclerophyll woodland and heath ecosystems. Further, we assessed for reduced dNBR fire severity classification accuracies associated with vegetation regrowth at increasing time between ignition and image capture. This was achieved by assessing four Landsat images captured at increasing time since ignition of the most recent burnt area. We found significant linear GeoCBI–dNBR relationships (R2 = 0.81 and 0.71) for data collected across ecosystems and for Eucalyptus racemosa ecosystems, respectively. Non-significant and weak linear relationships were observed for heath and Melaleuca quinquenervia ecosystems, suggesting that GeoCBI–dNBR was not appropriate for fire severity classification in specific ecosystems. Therefore, retrospective fire severity was classified across ecosystems. Landsat images captured within ~ 30 days after fire events were minimally affected by post burn vegetation regrowth.

Shifting centres: Pedagogical relations in the Era of Big Data

This paper presents a cautious argument for re-thinking both the nature and the centrality of the one-to-one teacher/student relationship in contemporary pedagogy. A case is made that learning in and for our times requires us to broaden our understanding of pedagogical relations beyond the singularity of the teacher/student binary and to promote the connected teacher as better placed to lead learning for these times. The argument proceeds in three parts: first, a characterization of our times as defined increasingly by the digital knowledge explosion of Big Data; second, a re-thinking of the nature of pedagogical relationships in the context of Big Data; and third, an account of the ways in which leaders can support their teachers to become more effective in leading learning by being more closely connected to their professional colleagues.

Molecular structure of nicotinamide adenine dinucleotide

NICOTINAMIDE adenine dinucleotide (NAD) has a fundamental role in metabolic processes as an electron transport molecule. Although its chemical structure was elucidated1 in 1934, its detailed conformation remains still to be established in spite of numerous physicochemical applications2. NAD analogues with a variety of substitutions on the bases are known to retain considerable activity of the natural coenzyme as long as the pyrophosphate diester group has been retained3,4. The geometry of this backbone moiety is therefore indispensable to our understanding of the conformation and function of the coenzyme. We have so far no experimental evidence on this in NAD or any other nucleotide coenzyme molecule. X-ray studies have been possible only on those analogues5,6 where the nicotinamide and adenine rings are linked by a trimethylene bridge. The results are conflicting and it is difficult to use them to provide a structural basis for the NAD molecule itself, particularly as the phosphate backbone is absent from these analogues.