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Background Chronic obstructive pulmonary disease (COPD) patients exhibit skeletal muscle atrophy, denervation, and reduced mitochondrial oxidative capacity. Whilst chronic tobacco smoke exposure is implicated in COPD muscle impairment, the mechanisms involved are ambiguous. The aryl hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that activates detoxifying pathways with numerous exogenous ligands, including tobacco smoke. Whereas transient AHR activation is adaptive, chronic activation can be toxic. On this basis, we tested the hypothesis that chronic smoke‐induced AHR activation causes adverse muscle impact. Methods We used clinical patient muscle samples, and in vitro (C2C12 myotubes) and in vivo models (mouse), to perform gene expression, mitochondrial function, muscle and neuromuscular junction morphology, and genetic manipulations (adeno‐associated virus‐mediated gene transfer). Results Sixteen weeks of tobacco smoke exposure in mice caused muscle atrophy, neuromuscular junction degeneration, and reduced oxidative capacity. Similarly, smoke exposure reprogrammed the muscle transcriptome, with down‐regulation of mitochondrial and neuromuscular junction genes. In mouse and human patient specimens, smoke exposure increased muscle AHR signalling. Mechanistically, experiments in cultured myotubes demonstrated that smoke condensate activated the AHR, caused mitochondrial impairments, and induced an AHR‐dependent myotube atrophy. Finally, to isolate the role of AHR activity, expression of a constitutively active AHR mutant without smoke exposure caused atrophy and mitochondrial impairments in cultured myotubes, and muscle atrophy and neuromuscular junction degeneration in mice. Conclusions These results establish that chronic AHR activity, as occurs in smokers, phenocopies the atrophy, mitochondrial impairment, and neuromuscular junction degeneration caused by chronic tobacco smoke exposure.

Crested wheatgrass (CWG) [Agropyron cristatum (L.) Gaertn.] is a commonly introduced grass in the Canadian prairies, but concerns remain about its possible long-term effects on soil quality, and its influence on soil water repellency (SWR) has not been determined. The long-term (24 yr) effects of CWG on SWR in comparison to seeded native grasses and annual cropping were determined for a clay loam soil in southern Alberta, Canada by measuring SOC concentration and SWR using soil hydrophobicity (SH) and soil water repellency index (RI) methods. The cropping treatments were CWG, seeded native grass mix (NGM), continuous wheat, and wheat–fallow rotation, each with fertilized (nitrogen) and non-fertilized subplots, replicated four times. Mean SOC concentration, SH, and RI in samples of surface soil were similar (P > 0.05) for CWG and seeded NGM, and they did not support our hypothesis (seeded NGM > CWG). Mean SOC was significantly greater for seeded perennial grasses than annual crops by 1.7–2 times and SH by 2.1–2.5 times, which supported our hypothesis, but RI was similar among treatments. As expected, nitrogen fertilization significantly increased SOC concentrations, but the effects on SH and RI were undetectable. A strong positive correlation occurred between SOC concentration and SH (r = 0.92) but not for RI (r = 0.10). Our findings suggested that SWR was similar for CWG and seeded NGM. The SWR as measured using SH was greater for seeded perennial grasses than annual cropping but was similar using RI.

The iconic Tasmanian devil (Sarcophilus harrisii) is endangered due to the transmissible cancer Devil Facial Tumour Disease (DFTD), of which there are two genetically independent subtypes (DFT1 and DFT2). While DFT1 and DFT2 can be differentially diagnosed using tumour biopsies, there is an urgent need to develop less-invasive biomarkers that can detect DFTD and distinguish between subtypes. Extracellular vesicles (EVs), the nano-sized membrane-enclosed vesicles present in most biofluids, represent a valuable resource for biomarker discovery. Here, we characterized the proteome of EVs from cultured DFTD cells using data-independent acquisition–mass spectrometry and an in-house spectral library of > 1500 proteins. EVs from both DFT1 and DFT2 cell lines expressed higher levels of proteins associated with focal adhesion functions. Furthermore, hallmark proteins of epithelial–mesenchymal transition were enriched in DFT2 EVs relative to DFT1 EVs. These findings were validated in EVs derived from serum samples, revealing that the mesenchymal marker tenascin-C was also enriched in EVs derived from the serum of devils infected with DFT2 relative to those infected with DFT1 and healthy controls. This first EV-based investigation of DFTD increases our understanding of the cancers’ EVs and their possible involvement in DFTD progression, such as metastasis. Finally, we demonstrated the potential of EVs to differentiate between DFT1 and DFT2, highlighting their potential use as less-invasive liquid biopsies for the Tasmanian devil.

Members of the verrucomicrobial clade 'Candidatus Udaeobacter' rank among the most dominant bacterial phylotypes in soil. Nevertheless, despite this global prevalence, in-depth analyses with respect to pH preferences of 'Ca. Udaeobacter' representatives are still lacking. Here, we utilized a recently designed primer pair, specifically targeting 'Ca. Udaeobacter', to investigate links between soil pH and the abundance as well as phylotype composition of this largely unexplored verrucomicrobial clade. Based on 150 forest and 150 grassland soils, comprising a broad pH range, we determined the highest total abundance of 'Ca. Udaeobacter' in strongly acidic soil (pH, ~5.1) and, noteworthy, in ultra-acidic soil (pH

Purpose HMGA2 has frequently been found in benign as well as malignant tumors and a significant association between HMGA2 overexpression and poor survival in different malignancies was described. In pancreatic ductal adenocarcinoma (PDAC), nuclear HMGA2 expression is associated with tumor dedifferentiation and presence of lymph node metastasis. Nevertheless, the impact of HMGA2 occurrence in other cell compartments is unknown. Methods Intracellular distribution of HMGA2 was analyzed in PDAC (n = 106) and peritumoral, non-malignant ducts (n = 28) by immunohistochemistry. Findings were correlated with clinico-pathological data. Additionally, intracellular HMGA2 presence was studied by Western blotting of cytoplasmic and nuclear fractions of cultured cells. Results HMGA2 was found in the cytoplasm and in the nucleus of cultured cells. In human tumor tissue, HMGA2 was also frequently found in the cytoplasm and the nucleus of tumor cells, however, nuclear staining was generally stronger. Direct comparison from tumor tissue with corresponding non-neoplastic peritumoral tissue revealed significantly stronger expression in tumors (p = 0.003). Of note, the nuclear staining was significantly stronger in lymph node metastatic cell nuclei compared to primary tumor cell nuclei (p = 0.049). Interestingly, cytoplasmic staining positively correlated with lymph vessel (p = 0.004) and venous invasion (p = 0.046). Conclusion HMGA2 is a prognostic marker in PDAC. Firstly, we found a positive correlation for cytoplasmic HMGA2 expression with lympho-vascular invasion and, secondly, we found a significantly stronger nuclear expression of HMGA2 in cancer-positive lymph node nuclei compared to primary tumor cell nuclei. So far, the role of cytoplasmic HMGA2 is nearly unknown, however, our data lend support to the hypothesis that cytoplasmic HMGA2 expression is involved in nodal spread.

TNF-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2) can induce apoptosis in cancer cells upon crosslinking by TRAIL. However, TRAIL-R2 is highly expressed by many cancers suggesting pro-tumor functions. Indeed, TRAIL/TRAIL-R2 also activate pro-inflammatory pathways enhancing tumor cell invasion, migration, and proliferation. In addition, nuclear TRAIL-R2 (nTRAIL-R2) promotes malignancy by inhibiting miRNA let-7-maturation. Here, we show that TRAIL-R2 interacts with the tumor suppressor protein p53 in the nucleus, assigning a novel pro-tumor function to TRAIL-R2. Knockdown of TRAIL-R2 in p53 wild-type cells increases the half-life of p53 and the expression of its target genes, whereas its re-expression decreases p53 protein levels. Interestingly, TRAIL-R2 also interacts with promyelocytic leukemia protein (PML), a major regulator of p53 stability. PML-nuclear bodies are also the main sites of TRAIL-R2/p53 co-localization. Notably, knockdown or destruction of PML abolishes the TRAIL-R2-mediated regulation of p53 levels. In summary, our finding that nTRAIL-R2 facilitates p53 degradation and thereby negatively regulates p53 target gene expression provides insight into an oncogenic role of TRAIL-R2 in tumorigenesis that particularly manifests in p53 wild-type tumors.

Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) is a significant contributor to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. Prior experimental evidence has suggested cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) as a pathophysiological driver of SAH-SBI. The aim of this study was to investigate the clinical and pathophysiological association between CSF-Hb and SAH-SBI. We prospectively enrolled 47 consecutive patients and collected daily CSF samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between CSF-Hb and SAH-SBI. The diagnostic accuracy of CSF-Hb for SAH-SBI markedly exceeded that of established methods (area under the curve: 0.89 [0.85-0.92]). Temporal LC-MS/MS CSF proteomics demonstrated that erythrolysis accompanied by an adaptive macrophage response are the two dominant biological processes occurring in the CSF space after aneurysm rupture. To further investigate the pathophysiology between CSF-Hb and SAH-SBI, we explored the vasoconstrictive and lipid peroxidation activities of Hb ex-vivo. These experiments revealed critical inflection points overlapping CSF-Hb concentration thresholds in patients with SAH-SBI. Selective Hb depletion and in-solution neutralization by the Hb-scavenger haptoglobin or the heme-scavenger hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb in patient CSF. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.

Vaccines against Staphylococcus aureus have eluded researchers for >3 decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More recently, leukocidin AB (LukAB) has gained interest as a vaccine antigen. We developed a minipig deep surgical wound infection model offering 3 independent efficacy readouts: bacterial load at the superficial and at the deep-seated surgical site, and dissemination of bacteria. Due to similarities with humans, minipigs are an attractive option to study novel vaccine candidates. With this model, we characterized the efficacy of a LukAB toxoid as vaccine candidate. Compared to control animals, a 3-log reduction of bacteria at the deep-seated surgical site was observed in LukAB-treated minipigs and dissemination of bacteria was dramatically reduced. Therefore, LukAB toxoids may be a useful addition to S. aureus vaccines and warrant further study.

Cell plasticity is a crucial hallmark leading to cancer metastasis. Upregulation of Rho/ROCK pathway drives actomyosin contractility, protrusive forces, and contributes to the occurrence of highly invasive amoeboid cells in tumors. Cancer stem cells are similarly associated with metastasis, but how these populations arise in tumors is not fully understood. Here, we show that the novel oncogene RASSF1C drives mesenchymal‐to‐amoeboid transition and stem cell attributes in breast cancer cells. Mechanistically, RASSF1C activates Rho/ROCK via SRC‐mediated RhoGDI inhibition, resulting in generation of actomyosin contractility. Moreover, we demonstrate that RASSF1C‐induced amoeboid cells display increased expression of cancer stem‐like markers such as CD133, ALDH1, and Nanog, and are accompanied by higher invasive potential in vitro and in vivo. Further, RASSF1C‐induced amoeboid cells employ extracellular vesicles to transfer the invasive phenotype to target cells and tissue. Importantly, the underlying RASSF1C‐driven biological processes concur to explain clinical data: namely, methylation of the RASSF1C promoter correlates with better survival in early‐stage breast cancer patients. Therefore, we propose the use of RASSF1 gene promoter methylation status as a biomarker for patient stratification., Tumour‐suppressor RASSF1A encodes an alternative transcript, RASSF1C, that acts as oncogene in human breast cancer, triggering pro‐invasive cellular features and aggressiveness.

BackgroundCOPD patients exhibit skeletal muscle atrophy, denervation, and reduced mitochondrial oxidative capacity. Whilst chronic tobacco smoke exposure is implicated in COPD muscle impairment, the mechanisms involved are ambiguous. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that activates detoxifying pathways with numerous exogenous ligands, including tobacco smoke. Whereas transient AHR activation is adaptive, chronic activation can be toxic. On this basis, we tested the hypothesis that chronic smoke-induced AHR activation causes adverse muscle impact.MethodsWe used clinical patient muscle samples, and in vitro (C2C12 myotubes) and in vivo models (mouse), to perform gene expression, mitochondrial function, muscle and neuromuscular junction morphology, and genetic manipulations (adeno-associated virus-mediated gene transfer).Results16 weeks tobacco smoke exposure in mice caused: muscle atrophy, neuromuscular junction degeneration, and reduced oxidative capacity. Similarly, smoke exposure reprogrammed the muscle transcriptome, with down-regulation of mitochondrial and neuromuscular junction genes. In mouse and human patient specimens, smoke exposure increased muscle AHR signaling. Mechanistically, experiments in cultured myotubes demonstrated that smoke condensate activated the AHR, caused mitochondrial impairments, and induced an AHR-dependent myotube atrophy. Finally, to isolate the role of AHR activity, expression of a constitutively active AHR mutant without smoke exposure caused atrophy and mitochondrial impairments in cultured myotubes, and muscle atrophy and neuromuscular junction degeneration in mice.ConclusionsThese results establish that chronic AHR activity, as occurs in smokers, phenocopies the atrophy, mitochondrial impairment and neuromuscular junction degeneration caused by chronic tobacco smoke exposure.

Management intensive grazing (MIG) may not maximize plant productivity on rangelands because of morphophysiological traits of grassland vegetation. We examined defoliation and moisture effects on the biomass yield of rhizomatous and caespitose grass pairs that were either phylogenetically similar or of similar agroclimatic adaptation, including two agronomic grasses. From relatively low to high moisture regime adaptation, species pairs included western wheatgrass (Pascopyrum smithii [Rydb.] A. Love) and needle-and-thread (Hesperostipa comata [Trin. & Rupr.] Barkw.), northern wheatgrass (Elymus lanceolatus [Scribn. & J.G. Sm.]) and western porcupine grass (H. curtiseta [Hitchc.] Barkw.), plains and foothills rough fescue (Festuca hallii [Vasey] and F. campestris Rydb.), and smooth and meadow brome (Bromus inermis Leyss. and B. riparius Rehm). Response variables were shoot yield, root-shoot ratio, and water-use efficiency. We hypothesized that caespitose grasses, regardless of their origin or adaptation to agroclimate regime, would respond more determinately in biomass accumulation. Defoliation effects on shoot biomass were more pronounced under high moisture. Low intensity − high frequency defoliation yielded similarly to deferred controls in all grasses, and the same was true for high-intensity − low-frequency (HILF) defoliation in 1 rhizomatous grass. Three of the 4 rhizomatous grasses and 1 caespitose grass yielded greater under HILF defoliation compared with high-intensity − high-frequency defoliation. Caespitose grasses allocated more biomass to roots under low moisture conditions. Water-use efficiency decreased under high moisture conditions and more intense and/or frequent defoliation and peaked in agronomic grasses. Overall, our results suggested that growth patterns corresponded more with phylogenetic similarity as opposed to growth form. A conceptual model from these results showed that across all species, only the introduced bromes generated greater biomass under HILF defoliation, and this may explain why past research consistently concludes that MIG does not enhance plant productivity on rangelands.

Cultivating native rangeland can have detrimental effects on soil carbon and nitrogen storage. Understanding how vegetation and soil recover after returning marginal cultivated land to its native state is important since soil plays a key role not only in food production but also in regulating global climate change. Soil samples were taken from two sites, a mixedgrass and a dry mixedgrass prairie, which have different climates and plant species composition. Each study site included one undisturbed native plot (CK) and two cultivated treatments that were abandoned in 2008 after being cultivated for more than ten years prior to this study, one with continuous wheat (Triticum aestivum L.) and the other with wheat-fallow rotations. Soil organic carbon (SOC), total nitrogen (TN), and labile organic fraction content were measured in 2016, while plant coverage and species diversity were investigated in 2017. In both study sites, grass and sedge coverage in the previously cultivated treatments were lower than, with shrub and forb coverage similar to, the CK. The highest invasive species coverage appeared in the previously cultivated treatments. Species richness was higher with CK in the mixedgrass prairie but no differences were found in the more arid dry mixedgrass prairie. No differences were found among all treatments for species evenness, Simpson's index and Shannon–Wiener index. On average, in the 0–15 cm depth, SOC and TN contents with the previous cultivated treatments were still 20% and 16% lower than CK, respectively, whereas in the 15–30 cm depth, SOC and TN contents did not differ among all treatments except for SOC content in the mixedgrass prairie. Relative to CK, previously cultivated treatments had similar active carbon (AC), microbial respiration-carbon and NH4+-N contents but the mixedgrass prairie had lower water extractable-organic carbon and water extractable-nitrogen. In contrast, in the dry mixedgrass prairie all labile organic fraction contents, except for AC, were the same among all treatments. Negative relationships were found between plant diversity and surface soil carbon and nitrogen storage. Our results indicate that for short-term disturbed rangeland, 9 years is likely sufficient for the recovery of soil labile organic fractions and plant diversity but a longer time will be needed for the recovery of SOC and TN.

Antibiotic resistance genes (ARGs) in soil are considered to represent one of the largest environmental resistomes on our planet. As these genes can potentially be disseminated among microorganisms via horizontal gene transfer (HGT) and in some cases are acquired by clinical pathogens, knowledge about their diversity, mobility and encoded resistance spectra gained increasing public attention. This knowledge offers opportunities with respect to improved risk prediction and development of strategies to tackle antibiotic resistance, and might help to direct the design of novel antibiotics, before further resistances reach hospital settings or the animal sector. Here, metagenomic libraries, which comprise genes of cultivated microorganisms, but, importantly, also those carried by the uncultured microbial majority, were screened for novel ARGs from forest and grassland soils. We detected three new beta-lactam, a so far unknown chloramphenicol, a novel fosfomycin, as well as three previously undiscovered trimethoprim resistance genes. These ARGs were derived from phylogenetically diverse soil bacteria and predicted to encode antibiotic inactivation, antibiotic efflux, or alternative variants of target enzymes. Moreover, deduced gene products show a minimum identity of ~21% to reference database entries and confer high-level resistance. This highlights the vast potential of functional metagenomics for the discovery of novel ARGs from soil ecosystems.

Extracellular vesicles (EVs) are nano-sized membrane enclosed vesicles that are released by cells. While initially thought to be cellular detritus or particles involved in eliminating waste from cells, EVs have been recognised as important mediators of intercellular communication by transferring their bioactive cargoes. Notably, over the last two decades, a substantial research effort has been undertaken to understand the role of EVs in cancer. It is now understood that tumour derived EVs can transfer their contents to influence metastatic behaviour, as well as establish favourable microenvironments and pre-metastatic niches that support cancer development and progression. EV-mediated intercellular communication in cancer will be of importance to understanding the emerging paradigm which views cancer as the establishment of a new species within the host organism. Here, we provide a concise overview of EVs and the current understanding of their role and application in cancer. In addition, we explore the potential wider role of EVs in the transfer of inherited characteristics and evolutionary biology.

Cell plasticity is a crucial hallmark leading to cancer metastasis. Upregulation of Rho/ROCK pathway drives actomyosin contractility, protrusive forces and contributes to the occurrence of highly invasive amoeboid cells in tumors. Cancer stem cells are similarly associated with metastasis, but how these populations arise in tumors is not fully understood. Here we show that the novel oncogene RASSF1C drives mesenchymal to amoeboid transition and stem cell attributes in breast cancer cells. Mechanistically, RASSF1C activates Rho/ROCK via SRC mediated RhoGDI inhibition, resulting in generation of actomyosin contractility. Moreover, we demonstrate that amoeboid cells display the cancer stem cell markers CD133, ALDH1 and the pluripotent marker Nanog; are accompanied by higher invasive potential in vitro and in vivo; and employ extracellular vesicles to transfer the invasive phenotype to target cells and tissue. Importantly, the underlying RASSF1C driven biological processes concur to explain clinical data: namely, methylation of the RASSF1C promoter correlates with better survival in early stage breast cancer patients. Therefore, we propose the use of RASSF1 gene promoter methylation status as a biomarker for patient stratification.

Gut microbial products direct growth, differentiation, and development in the animal host. Disruptions to host-microbe interactions have profound health consequences, that include onset of chronic inflammatory illnesses. However, we lack system-wide understanding of cell-specific responses to the microbiome. We profiled transcriptional activity in individual cells from the intestine, and associated tissue, of zebrafish larvae that we raised in the presence or absence of a microbiome. We uncovered extensive cellular heterogeneity in the conventional zebrafish intestinal epithelium, including previously undescribed cell types with known mammalian homologs. By comparing conventional to germ-free profiles, we mapped microbial impacts on transcriptional activity in each cell population. We revealed intricate degrees of cellular specificity in host responses to the microbiome that included regulatory effects on patterning, metabolic and immune activity. For example, we showed that removal of microbes hindered pro-angiogenic signals in the developing vasculature, resulting in impaired intestinal vascularization. Our work provides a high-resolution atlas of intestinal cellular composition in the developing fish gut and details the effects of the microbiome on each cell type. Furthermore, we provide a web-based resource for single-cell gene expression visualization under conventional and germ-free conditions to facilitate exploration of this dataset.

Extracellular vesicles (EVs) are important modulators of physiological functions in the central nervous system (CNS). These cell-derived lipid-bilayer encapsulated nanovesicles contain a wide array of cargoes such as proteins, RNA and bioactive lipids—all of which can take part in different functional roles in cell to cell communication. Furthermore, emerging evidence highlights that secreted EVs are highly heterogeneous, differing in their hydrodynamic size as well as EV surface composition. In neurodegenerative disorders EV secretion is dysfunctional in a sense that EVs secreted from diseased cells in the CNS take on additional roles in spreading the disease pathology. This alters the balance of the entire cell communication network. Understanding these pathological mechanisms helps not only to shed light to novel aspects of biological mechanisms of neurodegenerative diseases, it also helps to devise innovative therapeutic strategies, and to develop biomarkers for monitoring disease progression and response to treatments. In this chapter we discuss the role of EVs in normal CNS physiology and in neurodegenerative diseases, by focusing on Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and prion diseases as examples.

Little is known about the specific role of exotic species on measures of grassland plant diversity, including how this may vary with climatic conditions or large mammal herbivory. This study examined vegetation responses to long-term livestock grazing, including plant richness and diversity, as well as the contribution of exotic species to these metrics, across a network of 107 northern temperate grasslands in Alberta, Canada, spanning a broad aridity gradient. Exposure to grazing modestly increased plant richness, but did not alter Shannon’s diversity, Simpson’s diversity, or evenness, suggesting stability in floral diversity relative to grazing. However, grazing did increase grass cover while reducing shrub cover, the latter of which was only apparent in mesic grasslands. Unlike total plant diversity, exotic species richness and cover, together with exotic plant contributions to diversity, varied jointly with grazing and aridity. While long-term grazing increased exotic species, this response was most apparent in wetter areas, and non-grazed grasslands remained more resistant to the presence of exotics. Several exotic species were positive indicators of grazing in wetter grasslands, and coincided with lower native species cover, indicating grazing may be facilitating a shift from native to exotic vegetation under these conditions. Overall, our results indicate that while long-term grazing has altered the composition and cover of certain functional groups, including favoring exotics and minimizing woody vegetation in mesic areas, overall changes to plant diversity were limited. Additionally, these findings suggest that semi-arid northern temperate grasslands remain relatively resistant to grazing effects, including their susceptibility to exotic plant encroachment. These results improve our understanding of how ongoing grazing exposure may impact grassland diversity, including efforts to conserve native vegetation, as well as the important role of climate in altering fundamental grassland responses to grazing.

Rotational stocking theoretically enables regrazing of regrowth, but regrowth may be limited in xerophytic vegetation. We tested the hypothesis that regrowth would be slow and fixed in Hesperostipa comata (a caespitose, drought-tolerant grass), while growth would be flexible in Pascopyrum smithii (a rhizomatous, less drought-tolerant grass) under increasing defoliation and moisture, by assessing tiller growth rates, population dynamics and plant yield on marked plants in a Dry Mixed Grass prairie. Plots were clipped in late summer to simulate a deferred control, or intermittently during the growing season (May–August) at high intensity–low frequency (HILF), low intensity–high frequency (LIHF) or high intensity–high frequency and crossed with two water treatments (ambient and addition) in both a xeric upland and a mesic lowland. Growing season defoliation increased tiller growth rates of P. smithii in the upland, whereas HILF and LIHF reduced growth in the lowland. All defoliation regimes increased tiller growth for H. comata. Tiller populations of H. comata increased with frequent defoliation, while tiller populations of P. smithii decreased regardless of defoliation regime. Frequent defoliation, regardless of intensity, reduced yield relative to the deferred control for both grasses. While water addition consistently increased growth rates and reduced differences in tiller number among defoliation treatments, the regrowth of both grasses remained similar under varied defoliation with ambient moisture. High moisture conditions also promoted regrowth more in P. smithii compared to H. comata. In summary, neither grass species displayed an inherently fixed or flexible tiller or plant yield response in response to defoliation or moisture.

Intestinal parasites have a high prevalence in many developing countries. In particular, Hymenolepis nana affects primarily children and available treatments are not 100% effective. In Mexico, Psidium sartorianum fruit has been used in traditional medicine to cure intestinal worms. In this paper, the in vitro antiparasitic activity of the methanol extract from P. sartorianum fruit was analyzed by a bioguided strategy and through light and electronic microscopy. Chloroform fraction (CF) of the methanol extract and its sub-fraction (F4-sCF) showed the highest activities; the results for the times of paralysis (5 min) and death (20 min) and the ultrastructural damage were better with F4-sCF than those found using the commercially pure compound Praziquantel. The compound identified in the F4-sCF by nuclear magnetic resonance (1H and 13C nuclear magnetic resonance) and gas-chromatography mass-spectrometry was the 2′,6′-dihidroxy-4′-methoxychalcone (pinostrobin chalcone). Accordingly to the literature, this chalcone may be acting by inhibition of tubulin polymerization and apoptosis induction, but future studies must identify what the molecular targets in H. nana are behind the effect of this chalcone.

To evaluate mechanisms by which defoliation alters grassland productivity, we examined mixed grass prairie herbage yields under recurring treatments that included hand-clipping of plots over five growing seasons at high intensity and low frequency (HILF), low intensity and high frequency (LIHF), high intensity and high frequency (HIHF), or the end of the growing season (deferred control), combined with water treatments of ambient rainfall or water addition. The study was repeated in a drier upland and mesic lowland range site. Yield was assessed as annual accumulated herbage production and, for HILF and control treatments in 2012 (year 3), evaluated separately for forbs and major graminoids. Temporal changes in the proportional yield during the growing season were also examined for the HILF and HIHF treatments. Moisture addition increased accumulated herbage, especially in the upland, and exacerbated differences among defoliation effects in select years. Productivity was greatest in the deferred controls, suggesting no treatment led to overcompensation, even with moisture addition. Among growing season treatments, yields under HILF exceeded that of the HIHF in 6 of 10 different combinations of site and year, particularly early in the study and under high moisture. Observed herbage yields suggest deferred patches of grassland may boost productivity and limit the ability of HILF defoliation to increase production, a pattern magnified by a reduction in Pascopyrum smithii in lowlands before mid-July. Accumulated herbage yield did respond favorably to HILF defoliation in uplands due to increased yields of Bouteloua gracilis (Willd. ex Kunth) Lag. ex Griffiths. Overall, these results suggest that any growing season defoliation reduces yields, although where defoliation is necessary at that time, production may be more likely to be maintained under HILF defoliation. More studies examining long-term growth responses to defoliation that include variation in vegetation types, environmental conditions, and defoliation regime are warranted.

Summary: The Drosophila midgut is an excellent system for characterizing cell cycle regulation in the context of tissue homeostasis. Two major progenitor cell types populate the midgut: mitotic intestinal stem cells and their post-mitotic daughters, enteroblasts. Although regulatory networks that control stem cell proliferation are well characterized, how enteroblast mitotic-cell-cycle exit is coordinated with endocycle entry and enterocyte specification remains poorly defined. Myt1 is a conserved Cdk1 inhibitory kinase that regulates mitotic timing during animal development. Here, we use myt1-null mutants and cell-specific RNA interference to investigate Myt1 function in stem cells and enteroblast progenitors. Myt1 depletion alters cell cycle kinetics and promotes ectopic stem cell and enteroblast mitoses at the expense of enteroblast-enterocyte differentiation. These aberrant enteroblast mitoses rely upon cyclin A, implicating Myt1 inhibition of cyclin A/Cdk1 as a mechanism for the coupling mitotic exit with differentiation in enteroblasts.

SUMMARYInhibitory phosphorylation of Cdk1 is a well-established mechanism for gating mitotic entry during development. However, failure to inhibit Cdk1 in adult organs causes ectopic cell division and tissue dysplasia, indicating that Cdk1 inhibition is also required for cell cycle exit. Two types of progenitor cells populate the adultDrosophilamidgut: intestinal stem cells (ISCs) and post-mitotic enteroblasts (EBs). ISCs are the only mitotic cells under homeostatic conditions, dividing asymmetrically to produce quiescent EB daughter cells. We show here that Myt1, the membrane associated Cdk1 inhibitory kinase, is required for EB quiescence and subsequent differentiation. Loss of Myt1 disrupts EB cell cycle dynamics, promoting Cyclin A-dependent mitosis and accumulation of smaller progenitor-like cells that fail to differentiate. Thus, Myt1 inhibition of Cyclin A/Cdk1 functions as a mechanism for coupling cell cycle arrest with terminal cell differentiation in this developmental context.

Intestinal progenitor cells integrate signals from their niche, and from the gut lumen, to divide and differentiate at a rate that maintains an epithelial barrier to microbial invasion of the host interior. Despite the importance of evolutionarily conserved innate immune defenses to maintain stable host-microbiota relationships, we know little about specific contributions of stem cell immunity to gut homeostasis. We used the Drosophila model to determine the consequences of compromised intestinal stem cell immune activity for epithelial homeostasis. We showed that loss of stem cell immunity greatly impacted growth and renewal in the adult gut. In particular, we noticed that inhibition of stem cell immunity impeded key growth and differentiation events in the progenitor cell compartment leading to a gradual loss of stem cell numbers with age, and an impaired differentiation of mature enteroendocrine cells. Our results highlight the importance of immune signaling in the stem cell population for epithelial function in the adult gut.HIGHLIGHTSThe TNFR-like Immune Deficiency (IMD) pathway is active in Drosophila intestinal progenitor cells.Inhibition of IMD in progenitors impairs progenitor cell proliferation.Blocking progenitor cell IMD negatively affects generation of mature epithelial cells.

Little is known about how defoliation intensity and frequency alter plant community composition and diversity in northern Great Plains mixedgrass communities. We evaluated defoliation effects in combination with watering on vascular plant composition and diversity in two contrasting ecological sites, a drier upland and more mesic lowland, in the Dry Mixedgrass natural subregion of Alberta, Canada. Treatments were applied for three growing seasons (2010 through 2012, inclusive) and included defoliation regimes of high intensity at high frequency, high intensity at low frequency, low intensity at high frequency, and defoliation deferred until the end of the growing season. Moisture regimes were ambient and elevated. Defoliation rather than moisture was the primary determinant of plant composition after 3 yr, particularly in the lowland site. Watering effects on composition were more apparent in the drier upland. All growing season defoliation regimes markedly altered composition relative to the deferred control, with relatively minor differences in composition among growing season defoliation treatments, particularly in the mesic lowland site. We conclude that growing season defoliation alters mixedgrass composition by reducing canopy dominant grasses (Pascopyrum smithii and Hesperostipa comata) and releasing shorter-statured grasses and forbs, which can either increase or decrease diversity depending on site (edaphic) conditions and the relative dominance of midgrasses and shortgrasses (Koeleria macrantha and Bouteloua gracilis). Finally, increased moisture did not ameliorate defoliation effects during the growing season, suggesting compositional responses were predictable and independent of growing season defoliation regime.

Resprouting is a key functional trait for species in disturbance prone environments. In many semi-arid environments, woody plants face both fire and drought as recurring disturbances. Past work has demonstrated that oaks inhabiting sky-island forests of the northern Sierra Madre Oriental have differing microhabitat preferences and heavy stem dieback occured during the historic 2011 drought indicating potential xylem failure. These oak species, representing two sections within the genus, are all post-fire resprouters: they can resprout from underground storage organs when fire kills above ground tissue. Resprouts provide an opportunity to examine how functional traits may change as plastic responses to changing environmental conditions. Post-fire resprouts have increased root:shoot ratios relative to adults and therefore have access to more water relative to leaf demand. We expected that if resprouts exhibit plasticity in xylem function, they should favor water transport efficiency over safety: they should have higher maximum xylem conductivity, but greater susceptibility to drought-induced cavitation. We examined four oak species common in the Davis Mountains in west Texas and compared adult physiology with that of resprouts following wildfire. We found that species differed in degree of desiccation avoidance (isohydry) consistent with microhabitat preferences and that the species that were most desiccation tolerant as adults had resprouts significantly more susceptible to xylem cavitation. We found no evidence for a trade-off between efficiency and safety, however.

OBJECTIVES Patients with Hashimoto thyroiditis show structural changes of the thyroid that can be identified by a variety of sonographic criteria. We conducted this study to investigate whether there is a correlation between sonography and antibody activity and to assess the role of sonography in the diagnosis and follow-up of Hashimoto thyroiditis. In addition, we present a new classification system (termed the VESINC system [volume, echogenicity, sonographic texture, pseudonodular hypoechoic infiltration, nodules, and cysts]), which helps improve the clarity of sonographic findings. METHODS The study included 223 consecutive patients with previously diagnosed Hashimoto autoimmune thyroiditis who attended the thyroid clinic of the German Armed Forces Central Hospital in Koblenz for follow-up examinations between 2006 and 2008. Laboratory tests were performed to measure the levels of free triiodothyronine, free thyroxine, thyrotropin, anti-thyroglobulin antibodies (TgAbs), and antithyroid peroxidase antibodies (TPOAbs). Sonography was performed according to a strict protocol. We then assessed whether a correlation existed between antibody activity and the 6 sonographic variables of the VESINC system. RESULTS Hypoechogenicity, heterogeneity, and pseudonodular hypoechoic infiltration were associated with significantly higher TPOAb activity (P < .001). There were no significant correlations between the other sonographic variables examined (cysts, nodules, and volume) or the biometric data with the TPOAb and TgAb levels. In addition, an assessment of TgAb levels did not show significant differences in correlations with any of the sonographic variables. CONCLUSIONS Sonography is a noninvasive diagnostic imaging modality that provides information about the level of inflammatory activity. Markedly decreased echogenicity, heterogeneity, and multifocal pseudoinodular hypoechoic infiltration are indicative of a high level of inflammatory activity. The sonographic classification system presented here (VESINC system) can be a useful tool for comparing sonographic findings in a rapid and objective manner during follow-up of Hashimoto thyroiditis.

Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and disease., Ministerio Español de Economía y Competitividad (MINECO). IM is supported by European Union’s Horizon 2020 research and innovation programme under grant agreement No. 721058 (the B-SMART Consortium) and by Estonian Research Council Personal Research Grant PUT618. PV is supported by a VENI Fellowship from the Netherlands Organisation for Scientific Research (NWO)

Author(s): Rering, CC; Beck, JJ; Vannette, RL; Willms, SD | Abstract: Nectar microbe-produced volatiles can contribute to floral blends and modify pollinator preference for flowers. Identifying and describing the compounds that may underlie this effect is a key goal. Semi-quantitative or quantitative data is often critical for chemical ecology investigations, given that biotic responses (i.e., insects or plants) can fluctuate with concentration, relative ratios, or composition of the emitted volatile profiles. However, field-based, in situ microbial volatile detection and quantification is difficult due to the small scale of the nectar microhabitat. Laboratory-based inoculations of bulk synthetic nectars are useful for screening weakly-abundant and difficult to analyze volatiles, which may be crucial in eliciting responses. Despite the limitations of this approach, it allows rapid identification of target molecules for further validation with bioassays. Targeted analytical methods to identify or quantify semiochemicals may then be developed and validated for field tests. Here, we report the first quantitative assessment of microbe volatile emission in laboratory-based tests with synthetic nectar. We also review briefly solid-phase microextraction collection and gas-chromatography data interpretation. Nectar microbe interactions with plants and insects offer opportunities for agricultural improvement, and a selection of potential uses are highlighted.

Influenza A virus (IAV) in swine is a pathogen that causes a threat to the health as well as to the production of swine. Moreover, swine can spread this virus to other species including humans. The virus persists in different types of swine farms as evident in a number of studies. The core objectives of this study are (i) to analyze the dynamics of influenza infection of a farrow-to-finish swine farm, (ii) to explore the reinfection at the farm level, and finally (iii) to examine the effectiveness of two control strategies: vaccination and reduction of indirect contact. The analyses are conducted using a deterministic Susceptible-Exposed-Infectious-Recovered (SEIR) model. Simulation results show that the disease is maintained in gilts and piglets because of new susceptible pigs entering the population on a weekly basis. A sensitivity analysis shows that the results are not sensitive to variation in the parameters. The results of the reinfection simulation indicate that the virus persists in the entire farm. The control strategies studied in this work are not successful in eliminating the virus within the farm.

Among patients newly infected with hepatitis C virus (HCV), only 20-30% clear the infection spontaneously. In the remaining 70% the infection persists, causing chronic liver inflammation and disease. It is well established that polymorphisms in host genes, especially in components of the innate immune response, contribute to the phenomenon of spontaneous HCV clearance. Retinoic acid inducible gene-I (RIG-I)-like helicases such as melanoma differentiation-associated gene 5 (MDA-5) are cytoplasmic sensors of viral RNA that are critical for triggering innate immune responses after infection with RNA viruses. We analyzed 14 nonsynonymous single-nucleotide polymorphisms in RIG-I-like helicase-pathway-genes comparing European patients who spontaneously cleared HCV (n = 285) or had persistent infection (n = 509). We found that polymorphic haplotypes in the MDA-5 gene IFIH1 encoding histidine at position 843 and threonine at position 946 strongly correlate with the resolution of HCV infection (odds ratio [OR]: 16.23; 95% confidence interval [CI]: 3.67-71.87; P = 1.1 × 10−6). Overexpression of MDA-5 genetic variants in HEK 293 cells and in a tissue culture model of HCV infection revealed that the histidine 843/threonine 946 variant leads to increased baseline and ligand-induced expression of interferon-induced genes and confers an increased ability to suppress HCV replication. Conclusion: These data suggest that MDA-5 plays a significant role in the defense against HCV and that polymorphisms in MDA-5 can influence the outcome of HCV infection. (Hepatology 2015;61:460-470)

Cysticercosis is a disease caused by the larval stage of Taenia solium cestodes that belongs to the family Taeniidae that affects a number of hosts including humans. Taeniids tapeworms are hermaphroditic organisms that have reproductive units called proglottids that gradually mature to develop testis and ovaries. Cysticerci, the larval stage of these parasites synthesize steroids. To our knowledge there is no information about the capacity of T. solium tapeworms to metabolize progesterone or other precursors to steroid hormones. Therefore, the aim of this paper was to investigate if T. solium tapeworms were able to transform steroid precursors to corticosteroids and sex steroids. T. solium tapeworms were recovered from the intestine of golden hamsters that had been orally infected with cysticerci. The worms were cultured in the presence of tritiated progesterone or androstenedione. At the end of the experiments the culture media were analyzed by thin layer chromatography. The experiments described here showed that small amounts of testosterone were synthesized from 3 H-progesterone by complete or segmented tapeworms whereas the incubation of segmented tapeworms with 3 H-androstenedione, instead of 3 H-progesterone, improved their capacity to synthesize testosterone. In addition, the incubation of the parasites with 3 H-progesterone yielded corticosteroids, mainly deoxicorticosterone (DOC) and 11-deoxicortisol. In summary, the results described here, demonstrate that T. solium tapeworms synthesize corticosteroid and sex steroid like metabolites. The capacity of T. solium tapeworms to synthesize steroid hormones may contribute to the physiological functions of the parasite and also to their interaction with the host.

Fosmidomycin has been reported to have many biological activities as an antibacterial and antimalarial, along with being a herbicidal agent. Its unique mode of action involves the inhibition of a key step of the non mevalonate pathway by blockade of a crucial enzyme, the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), whose expression is present in bacteria, plasmodium parasites and higher plants, but not in mammals. Herein we report the development of fosmidomycin and of FR-900098 constrained analogues belonging to an unusual heterocyclic based complexing subunit involving N-hydroxyimidazoles and cyclic N-hydroxyureas.

A previous physiologically-structured model for a fish population based on individual-level characteristics is studied. The foraging rate is generalized to include a size-dependent functional response and the energy distribution of adults is generalized to permit both reproduction and growth. Equilibria are determined and their stability studied along with a discussion of harvesting strategies. The model with these generalizations is shown to give different predictions than the original model regarding age distribution of fish and harvesting strategies.

Gnathostomiasis is now recognized as a zoonosis with a worldwide distribution. In the Americas, it is caused by the third-stage larvae of Gnathostoma binucleatum and in Asia mainly by G. spinigerum. The availability and preparation of specific antigens are among the main obstacles for developing reliable immunodiagnostic tests. In this study, six immunodominant peptides were identified and characterized from G. binucleatum, somatic antigens (AgS: 24, 32, and 40 kDa) and excretory-secretory antigens (AgES: 42, 44, and 56 kDa) by two-dimensional immunoblot analysis. Among those immunodominant peptides, two AgS spots were characterized by mass spectrometric analysis (32 kDa; pI 6.3 and 6.5) and identified as type 1 galectins. In accordance with this finding, a fraction of AgS exhibited affinity to lactose and displayed a 100% specificity and sensitivity for the diagnosis of human gnathostomiasis.

Currently, interest in phage science is on the rise again as this subject remains largely unexplored, and its potential diversity mainly untapped. Here, we present phage vB\_BsuP-Goe1, a new isolate that infects Bacillus subtilis . The phage forms round plaques with a matt outline on agar plates containing a B. subtilis Δ6 lawn. Transmission electron microscopy and genomic analyses revealed that phage vB\_BsuP-Goe1 belongs to the Podoviridae family as a new member of the Phi29likevirus genus. The phage genome comprises 18 379 bp that encode for one RNA gene and for 24 open reading frames. Phage vB_BsuP-Goe1 clusters with phage B103 and Nf within the Phi29likevirus genus and is currently the smallest member of this genus. Genome comparison with members of the Phi29likevirus genus reveals a conserved gene set coding for essential replication and morphogenesis functions while the genome extremities are more prone to gene and genome organisation variability.

Mitochondria play a central role in the maturation of proteins with iron-sulfur (Fe/S) clusters. During their biogenesis, the apoforms of Fe/S proteins expose unprotected Fe/S cluster-coordinating cysteine side chains, rendering them vulnerable to oxidative modifications that interfere with subsequent Fe/S cluster insertion. Whether and how cells protect these delicate cysteine residues are unknown.In this study, we show that sulfhydryl groups of Fe/S cluster-coordinating cysteine residues of mitochondrial Fe/S apoproteins acquire cyclic S-polythiol modifications. These adducts are the result of persulfide addition, followed by a subsequent oxidation step. These modifications not only accumulate upon defects in the early stages of the mitochondrial Fe/S cluster assembly system but are also found in wild-type cells under normal growth conditions. They are, however, not found on Fe/S apoproteins in the cytosol.Our work describes a novel in vivo chemical modification of cysteine side chains in mitochondrial Fe/S apoproteins. These cyclic S-polythiolation adducts are resistant to oxidation, yet can be removed by reductive cleavage, suggesting that they serve as a reversible protection device for cysteine ligands sensitive to oxidative modification. Antioxid. Redox Signal. 25, 28-40.

Cytokine storms are a potentially fatal exaggerated immune response consisting of an uncontrolled positive feedback loop between immune cells and cytokines. The dynamics of cytokines are highly complex and little is known about specific interactions. Researchers at the Ontario Veterinary College have encountered cytokine storms during virotherapy. Multiple mouse trials were conducted where a virus was injected into mice whose leukocytes lacked expression of the type I interferon receptor. In each case a rapid, fatal cytokine storm occurred. A nonlinear differential equation model of the recorded cytokine amounts was produced to obtain some information on their mutual interactions. Results provide insight into the complex mechanism that drives the storm and possible ways to prevent such immune responses.

The purpose of this study was to investigate the response of δ15N in herbage and cattle tail switch hair to long-term grazing pressure on a rough fescue grassland (Festuca campestris Rydb.) near Stavely, Alberta, Canada. Cattle have grazed the paddocks from 15 May to 15 November annually since 1949. Stocking rates were 0, 2.4 and 4.8 animal unit months ha−1 for non-grazing (Control), moderate grazing (MG) and heavy grazing (HG), respectively. Green standing crop (GSC) was sampled monthly throughout the grazing season in 2007. The GSC was fractioned into neutral detergent fiber (NDF), acid detergent fiber (ADF), and their total nitrogen (TN) concentration and δ15N values in NDF, ADF and GSC were determined. Tail switch hair samples from cows (>2 years old) and calves (

The small hive beetle (Aethina tumida Murray) is a scavenger and facultative predator in honey bee colonies, where it feeds on pollen, honey, and bee brood. Although a minor problem in its native Africa, it is an invasive pest of honey bees in the United States and Australia. Adult beetles enter bee hives to oviposit and feed. Larval development occurs within the hive, but mature larvae leave the hive to pupate in soil. The numbers leaving, which can be estimated by trapping, measure the reproductive success of adult beetles in the hive over any given period of time. We describe a trap designed to intercept mature larvae as they reach the end of the bottom board on their way to the ground. Trap efficiency was estimated by releasing groups of 100 larvae into empty brood boxes and counting the numbers trapped. Some larvae escaped, but mean efficiency ranged from 87.2 to 94.2%. We envision the trap as a research tool for study of beetle population dynamics, and we used it to track numbers of larvae leaving active hives for pupation in the soil. The traps detected large increases and then decreases in numbers of larvae leaving colonies that weakened and died. They also detected small numbers of larvae leaving strong European and African colonies, even when no larvae were observed in the hives.

Grazing by large herbivores has been shown to condition vegetation in a manner that improves grassland quality for subsequent herbivory. Fescue grasslands evolved with disturbance from fire and winter grazing by bison but are now grazed primarily by cattle during summer. We examined the effect of long-term summer grazing on the seasonal forage production and quality of fescue grasslands in an examination of the hypothesis that long-term grazing had conditioned fescue grasslands to benefit livestock. This hypothesis was examined by comparing, between grazed and ungrazed plots, the biomass and composition of herbage components, concentrations of nitrogen (N) and acid detergent fiber (ADF) therein, and the ability of major plant types to maintain their biomass and quality throughout the growing season. The study was conducted in southern Alberta at five sites that had long-term exclosures (20+ yr) on grasslands that had been moderately grazed. Grazing had no effect on the N concentration of associated grasses, but grasses had lower N concentration than forbs. Concentrations of ADF followed a reciprocal trend to N. Grazing increased the mass of forbs from about 10% to 20% as a proportion of total biomass, which in turn, was not affected by grazing history. However, this grazing-induced shift to a higher quality vegetation type was not sufficient to affect total mass of N or total digestible nutrients at the community level. Rather than changes in current growth and quality, the predominant effect of summer grazing was in reducing litter mass, which also had the potential for affecting forage production and selection by herbivores. Finally, grazing reduced the relative contribution of rough fescue to total biomass by about 30%, and despite no significant effect on the potential to support summer grazing, this change could reduce the quality of these grasslands for winter grazing.

Livestock performance is a critical indicator of grassland production systems and is influenced strongly by precipitation and stocking rates. However, these relationships require further investigation in the arid Desert Steppe region of northeastern China. We employed a randomized complete block design with three replications and four grazing treatments (nongrazed exclosure [Control]), lightly grazed [LG], moderately grazed [MG], and heavily grazed [HG]) by sheep in a continuously grazed system (June to November), to test the effect of stocking rate on sheep performance. The planned stocking rates were 0, 0.15, 0.30, and 0.45 sheep?ha 21 ?mo 21 ,f or the control, LG, MG, and HG treatments, respectively. However, actual stocking rates were calculated for each paddock in each year based on a 50-kg sheep equivalent (SE). Annual net primary production (ANP P) was determined at peak standing crop in August 2004 to 2008. Live weight gain was determined for the summer and fall periods, as well as the total grazing period, in each year. ANPP decreased with increasing stocking rate, and daily live weight gain per head decreased linearly with increasing stocking rates over the total grazing period but in a quadratic manner over the summer period with a plateau at the lower rates. Maximum sheep production per unit area over the total grazing season occurred at about 2 SE ha 21 for about a 5-mo grazing period, but individual gains per sheep were predicted to decline after about 1 SE ha 21 presumably because of forage limitations. However, in order to achieve stable annual production, we recommend that the Desert Steppe be grazed at about 0.77 SE ha 21 for a 5-mo period (0.15 SE ha 21 ?mo 21 ). This estimate is based on published grazing strategies that consider an averag eA NPP with a recommended utilization rate of 30%.

Studies of the relative sizes of brain components in mammals suggest that areas responsible for sensory processing, including visual processing, are correlated with aspects of ecology, especially activity pattern. Some studies suggest that primate orbit convergence and binocular vision are correlated with the overall size of the brain as well as components of the visual pathway, such as the lateral geniculate nucleus. However, the question remains whether components of the visual pathway are correlated with orbit convergence and binocular visual field overlap in nonprimate mammals. Here, we examine the relationship between orbit convergence and the volumes of components of the visual pathway (optic tract, dorsal lateral geniculate nucleus and primary visual cortex). Data on orbit orientation are combined with those on overall brain volume as well as brain component volumes in a taxonomically diverse sample of mammals. Our results demonstrate that nonprimate mammals scale isometrically for component volumes along the visual pathway, whereas primates display negatively allometric relationships. However, only among primates is higher orbit convergence correlated with volumetrically larger lateral geniculate nuclei and visual cortices. Diurnal primates exhibit statistically larger visual pathway components when compared to nocturnal primates. Nonprimate mammals do not display activity pattern differences with the single exception of optic tract sizes. We conclude that binocular vision was a much stronger factor in the evolution of the visual system in primates than in other mammals.

Numerous studies have examined the nutritive quality of fodder plants in different seasons but few have related this seasonal response to long-term grazing intensity. Our objective was to examine the effect of long-term grazing on the concentrations of total nitrogen, δ15N, and total phosphorus in selected forage species from the fescue grassland near Stavely, Alberta. Plants were selected from paddocks that had been stocked at 0 (control), 2.4 (moderate grazing), and 4.8 (heavy grazing) animal unit months ha–1 for 58 years. Plant material from ten species was sampled and analyzed at monthly intervals from May to September in 2007. Total N and P concentrations were not (p > 0.05) affected by grazing for most species, but total N and P concentrations in Poa. pratensis L. were higher (p < 0.05) in grazed treatments than in the control. These results reflect an altered plant phenology through defoliation and illustrate delayed phenology in P. pratensis when grazed. The higher δ15N concentration for most species in the grazed treatments than the control is an indication of accelerated nitrogen cycling through dung and urine deposition.

SUMMARYTaenia crassicepsis a cestode parasite of wild and domestic animals that rarely affects humans; it has been widely used as an experimental model. The asexual proliferation by budding is a useful attribute ofT. crassicepscysticerci, which allows the various strains to be maintained indefinitely in the peritoneal cavity of inbred mice. Over the last 50 years, experimental results using larval and adult stages ofT. crassicepshave yielded much information on the morphology, infectivity, proliferation dynamics, host immune response, endrocrinological responses and vaccine research, all of which have contributed to our knowledge of cestode biology.

This study investigated the effect of long-term cattle grazing on herbage production and its nutrient and mineral concentrations over the grazing season. The grazing experiment was conducted on a Rough Fescue (Festuca campestris Rydb.) grassland established in 1949. The three grazing treatments were moderate grazing (MG), heavy grazing (HG), and a non-grazed exclosure (CK) with corresponding stocking rates of 2.4, 4.8, and 0 animal unit months (AUM) ha−1, respectively. Within each of these three treatments four sampling locations were selected as four replications. Herbage biomass (green standing crop [current years’ production] and litter biomass [previous years’ production]) and its nutrient and mineral concentrations were determined monthly from May to September 2007. The green standing crop increased but litter biomass decreased with grazing and peak green standing crop for MG and HG occurred one month earlier than in the CK. For the green standing crop, total nitrogen (TN) concentration increased with grazing from 28.2 g kg−1 in the CK to 39.9 g kg−1 in the HG treatment in May while increases (12.4–15.7%) in other months were not significant. Total phosphorus (TP) (16.4%) and δ15N were higher in the HG than in the CK. For the litter, TN and Ca concentrations decreased with grazing, but TP, δ15N, K and Mg concentrations increased. The herbage feed quality also varied over the grazing season with TN, TP, K, and Mg concentrations decreasing over the grazing season while Ca concentration was lowest in spring (3.07 g kg−1) and late fall (4.08 g kg−1). Grazing appeared to accelerate nutrient cycling and improved herbage quality. These grasslands require disturbance for optimal performance but heavy grazing pressure could severely reduce their health.