•Individual behavior is integral to the organization of ecological systems.•Automated image-based tracking offers novel opportunities to study behavior.•Tracking data allows linking individual to ...higher-level ecological processes.•A diverse range of taxa have now been tracked in a variety of habitats.•Automated image-based tracking has an important role in ecology.
The behavior of individuals determines the strength and outcome of ecological interactions, which drive population, community, and ecosystem organization. Bio-logging, such as telemetry and animal-borne imaging, provides essential individual viewpoints, tracks, and life histories, but requires capture of individuals and is often impractical to scale. Recent developments in automated image-based tracking offers opportunities to remotely quantify and understand individual behavior at scales and resolutions not previously possible, providing an essential supplement to other tracking methodologies in ecology. Automated image-based tracking should continue to advance the field of ecology by enabling better understanding of the linkages between individual and higher-level ecological processes, via high-throughput quantitative analysis of complex ecological patterns and processes across scales, including analysis of environmental drivers.
•Biomass is pretreated by torrefaction and carbonization for the use in blast furnace.•Biomass is pretreated in a rotary furnace to uniformly upgrade solid fuel.•Fuel ratio, ignition temperature, and ...burnout of torrefied biomass and biochar are analyzed.•Carbonization is feasible to improve the energy densities of bamboo and Madagascar almond.•Biomass torrefied at 300°C or carbonized below 500°C can be blended with coal for PCI.
To evaluate the utility potential of pretreated biomass in blast furnaces, the fuel properties, including fuel ratio, ignition temperature, and burnout, of bamboo, oil palm, rice husk, sugarcane bagasse, and Madagascar almond undergoing torrefaction and carbonization in a rotary furnace are analyzed and compared to those of a high-volatile coal and a low-volatile one used in pulverized coal injection (PCI). The energy densities of bamboo and Madagascar almond are improved drastically from carbonization, whereas the increase in the calorific value of rice husk from the pretreatment is not obvious. Intensifying pretreatment extent significantly increases the fuel ratio and ignition temperature of biomass, but decreases burnout. The fuel properties of pretreated biomass materials are superior to those of the low-volatile coal. For biomass torrefied at 300°C or carbonized at temperatures below 500°C, the pretreated biomass can be blended with coals for PCI.
Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ...ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up to 34% editing (on average, 26%) in macaques. Plasma PCSK9 and LDL levels were stably reduced by 95% and 58% in mice and by 32% and 14% in macaques, respectively. ABE mRNA was cleared rapidly, and no off-target mutations in genomic DNA were found. Re-dosing in macaques did not increase editing, possibly owing to the detected humoral immune response to ABE upon treatment. These findings support further investigation of ABEs to treat patients with monogenic liver diseases.
Ovarian adenocarcinoma is not generally discovered in patients until there has been widespread intraperitoneal dissemination, which is why ovarian cancer is the deadliest gynecologic malignancy. ...Though incompletely understood, the mechanism of peritoneal metastasis relies on primary tumor cells being able to detach themselves from the tumor, escape normal apoptotic pathways while free floating, and adhere to, and eventually invade through, the peritoneal surface. Our laboratory has previously shown that the Golgi glycosyltransferase, ST6Gal-I, mediates the hypersialylation of beta1 integrins in colon adenocarcinoma, which leads to a more metastatic tumor cell phenotype. Interestingly, ST6Gal-I mRNA is known to be upregulated in metastatic ovarian cancer, therefore the goal of the present study was to determine whether ST6Gal-I confers a similarly aggressive phenotype to ovarian tumor cells.
Three ovarian carcinoma cell lines were screened for ST6Gal-I expression, and two of these, PA-1 and SKOV3, were found to produce ST6Gal-I protein. The third cell line, OV4, lacked endogenous ST6Gal-I. In order to understand the effects of ST6Gal-I on cell behavior, OV4 cells were stably-transduced with ST6Gal-I using a lentiviral vector, and integrin-mediated responses were compared in parental and ST6Gal-I-expressing cells.
Forced expression of ST6Gal-I in OV4 cells, resulting in sialylation of beta1 integrins, induced greater cell adhesion to, and migration toward, collagen I. Similarly, ST6Gal-I expressing cells were more invasive through Matrigel.
ST6Gal-I mediated sialylation of beta1 integrins in ovarian cancer cells may contribute to peritoneal metastasis by altering tumor cell adhesion and migration through extracellular matrix.
The evolution of fungicide resistance Lucas, John A; Hawkins, Nichola J; Fraaije, Bart A
Advances in applied microbiology,
01/2015, Volume:
90
Journal Article
Peer reviewed
Fungicides are widely used in developed agricultural systems to control disease and safeguard crop yield and quality. Over time, however, resistance to many of the most effective fungicides has ...emerged and spread in pathogen populations, compromising disease control. This review describes the development of resistance using case histories based on four important diseases of temperate cereal crops: eyespot (Oculimacula yallundae and Oculimacula acuformis), Septoria tritici blotch (Zymoseptoria tritici), powdery mildew (Blumeria graminis), and Fusarium ear blight (a complex of Fusarium and Microdochium spp). The sequential emergence of variant genotypes of these pathogens with reduced sensitivity to the most active single-site fungicides, methyl benzimidazole carbamates, demethylation inhibitors, quinone outside inhibitors, and succinate dehydrogenase inhibitors illustrates an ongoing evolutionary process in response to the introduction and use of different chemical classes. Analysis of the molecular mechanisms and genetic basis of resistance has provided more rapid and precise methods for detecting and monitoring the incidence of resistance in field populations, but when or where resistance will occur remains difficult to predict. The extent to which the predictability of resistance evolution can be improved by laboratory mutagenesis studies and fitness measurements, comparison between pathogens, and reconstruction of evolutionary pathways is discussed. Risk models based on fungal life cycles, fungicide properties, and exposure to the fungicide are now being refined to take account of additional traits associated with the rate of pathogen evolution. Experimental data on the selection of specific mutations or resistant genotypes in pathogen populations in response to fungicide treatments can be used in models evaluating the most effective strategies for reducing or preventing resistance. Resistance management based on robust scientific evidence is vital to prolong the effective life of fungicides and safeguard their future use in crop protection.
Aims/hypothesis
The aim of this study was to investigate whether small doses of intense exercise before each main meal (‘exercise snacks’) would result in better blood glucose control than a single ...bout of prolonged, continuous, moderate-intensity exercise in individuals with insulin resistance.
Methods
Nine individuals completed three exercise interventions in randomised order. Measures were recorded across 3 days with exercise performed on the middle day, as either: (1) traditional continuous exercise (CONT), comprising 30 min moderate-intensity (60% of maximal heart rate HR
max
) incline walking before dinner; (2) exercise snacking (ES), consisting of 6 × 1 min intense (90% HR
max
) incline walking intervals 30 min before each meal; or (3) composite exercise snacking (CES), encompassing 6 × 1 min intervals alternating between walking and resistance-based exercise, 30 min before meals. Meal timing and composition were controlled within participants for exercise interventions.
Results
ES attenuated mean 3 h postprandial glucose concentration following breakfast (by 1.4 ± 1.5 mmol/l,
p
= 0.02) but not lunch (0.4 ± 1.0 mmol/l,
p
= 0.22), and was more effective than CONT following dinner (0.7 ± 1.5 mmol/l below CONT;
p
= 0.04). ES also reduced 24 h mean glucose concentration by 0.7 ± 0.6 mmol/l (
p
= 0.01) and this reduction persisted for the subsequent 24 h (lower by 0.6 ± 0.4 mmol/l vs CONT, relative to their baselines;
p
= 0.01). CES was just as effective as ES (
p
> 0.05 for all glycaemic variables) at improving glycaemic control.
Conclusions/interpretation
Dosing exercise as brief, intense ‘exercise snacks’ before main meals is a time-efficient and effective approach to improve glycaemic control in individuals with insulin resistance.
Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active ...in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept phase Ib study of ibrutinib monotherapy followed by ibrutinib plus chemotherapy (DA-TEDDi-R). In 18 PCNSL patients, 94% showed tumor reductions with ibrutinib alone, including patients having PCNSL with CD79B and/or MYD88 mutations, and 86% of evaluable patients achieved complete remission with DA-TEDDi-R. Increased aspergillosis was observed with ibrutinib monotherapy and DA-TEDDi-R. Aspergillosis was linked to BTK-dependent fungal immunity in a murine model. PCNSL is highly dependent on BCR signaling, and ibrutinib appears to enhance the efficacy of chemotherapy.
•Ibrutinib reduced tumor masses in 94% of patients with primary brain lymphoma•Chronic active B cell receptor signaling is a feature of primary brain lymphoma•Ibrutinib promotes fungal infections with Aspergillus fumigatus•TEDDi-R treatment produced durable remissions in refractory primary brain lymphoma
Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor signaling. In a phase 1b study, Lionakis et al. observe promising therapeutic effects of the BTK inhibitor ibrutinib in PCNSL but also increased aspergillosis, which they show is linked to BTK-dependent fungal immunity in a mouse model.
Defining functional DNA elements in the human genome Kellis, Manolis; Wold, Barbara; Snyderd, Michael P. ...
Proceedings of the National Academy of Sciences - PNAS,
04/2014, Volume:
111, Issue:
17
Journal Article
Peer reviewed
Open access
With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the ...Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease.
Natural killer (NK)-cell-based immunotherapy may overcome obstacles to effective T-cell-based immunotherapy such as the presence of genomic alterations in IFN response genes and antigen presentation ...machinery. All immunotherapy approaches may be abrogated by the presence of an immunosuppressive tumor microenvironment present in many solid tumor types, including head and neck squamous cell carcinoma (HNSCC). Here, we studied the role of myeloid-derived suppressor cells (MDSC) in suppressing NK-cell function in HNSCC.
The ability of peripheral and tumor-infiltrating MDSC from mice bearing murine oral cancer 2 (MOC2) non-T-cell-inflamed tumors and from patients with HNSCC to suppress NK-cell function was studied with real-time impedance and ELISpot assays. The therapeutic efficacy of SX-682, a small-molecule inhibitor of CXCR1 and CXCR2, was assessed in combination with adoptively transferred NK cells.
Mice bearing MOC2 tumors pathologically accumulate peripheral CXCR2
neutrophilic-MDSC (PMN-MDSC) that traffic into tumors and suppress NK-cell function through TGFβ and production of H
O
. Inhibition of MDSC trafficking with orally bioavailable SX-682 significantly abrogated tumor MDSC accumulation and enhanced the tumor infiltration, activation, and therapeutic efficacy of adoptively transferred murine NK cells. Patients with HNSCC harbor significant levels of circulating and tumor-infiltrating CXCR1/2
CD15
PMN-MDSC and CD14
monocytic-MDSC. Tumor MDSC exhibited greater immunosuppression than those in circulation. HNSCC tumor MDSC immunosuppression was mediated by multiple, independent, cell-specific mechanisms including TGFβ and nitric oxide.
The clinical study of CXCR1/2 inhibitors in combination with adoptively transferred NK cells is warranted.
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