Characterizing tumor response to chemotherapy at various length scales using temporal diffusion spectroscopy

Measurements of apparent diffusion coefficient (ADC) using magnetic resonance imaging (MRI) have been suggested as potential imaging biomarkers for monitoring tumor response to treatment. However, conventional pulsed-gradient spin echo (PGSE) methods incorporate relatively long diffusion times, and are usually sensitive to changes in cell density and necrosis. Diffusion temporal spectroscopy using the oscillating gradient spin echo (OGSE) sequence is capable of probing short length scales, and may detect significant intracellular microstructural changes independent of gross cell density changes following anti-cancer treatment. To test this hypothesis, SW620 xenografts were treated by barasertib (AZD1152), a selective inhibitor of Aurora B kinase which causes SW620 cancer cells to develop polyploidy and increase in size following treatment, ultimately leading to cell death through apoptosis. Following treatment, the ADC values obtained by both the PGSE and low frequency OGSE methods increased. However, the ADC values at high gradient frequency (i.e. short diffusion times) were significantly lower in treated tumors, consistent with increased intracellular restrictions/hindrances. This suggests that ADC values at long diffusion times are dominated by tumor microstructure at long length scales, and may not convey unambiguous information of subcellular space. While the diffusion temporal spectroscopy provides more comprehensive means to probe tumor microstructure at various length scales. This work is the first study to probe intracellular microstructural variations due to polyploidy following treatment using diffusion MRI in vivo. It is also the first observation of post-treatment ADC changes occurring in opposite directions at short and long diffusion times. The current study suggests that temporal diffusion spectroscopy potentially provides pharmacodynamic biomarkers of tumor early response which distinguish microstructural variations following treatment at both the subcellular and supracellular length scales.     

Notes on the genus Trachyandra (Asphodelaceae: Asphodeloideae) 1: A review of the T. thyrsoidea group (Section Trachyandra), including three new species from the Northern Cape

Three new species of the genus Trachyandra are described, T. hantamensis Boatwr. & J.C.Manning, T. kamiesbergensis Boatwr. & J.C.Manning and T. sanguinorhiza Boatwr. & J.C.Manning. These species form part of a group of morphologically similar species referred to here as the T. thyrsoidea group and are distinguished by their generally small stature, filiform leaves (except for T. tortilis), and simple or shortly branched racemes of patent flowers with maculate tepals. Many of the species in the group have roots that contain abundant anthraquinones, visible as a red substance below the outer skin of the roots, and which is soluble in alcohol, thus often staining herbarium papers purple. A synopsis of the eight species that comprise the T. thyrsoidea group is presented, with maps of each species and illustrations of those described as new.     

Effect of chest wall vibration on breathlessness in normal subjects

This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessness was induced in normal subjects by a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end-tidal CO2 were kept constant. Cross-modality matching was used to rate breathlessness. Ratings during intercostal vibration were expressed as a percentage of ratings during the control condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changes in breathlessness, we assessed several aspects of ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory response to steady-state hypercapnia. Intercostal vibration reduced breathlessness ratings by 6.5 +/- 5.7% compared with deltoid vibration (P less than 0.05) and by 7.0 +/- 8.3% compared with no vibration (P less than 0.05). The reduction in breathlessness was accompanied by either no change or negligible change in minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response. We conclude that chest wall vibration reduces breathlessness and speculate that it may do so through stimulation of receptors in the chest wall.     

A cell culture model of the blood-brain barrier

Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.     

The value of scattered trees for wildlife: Contrasting effects of landscape context and tree size

Aim

The biodiversity value of scattered trees in modified landscapes is often overlooked in planning and conservation decisions. We conducted a multitaxa study to determine how wildlife abundance, species richness and community composition at individual trees are affected by (1) the landscape context in which trees are located; and (2) the size of trees.

Location

Canberra, south‐eastern Australia.

Methods

Trunk arthropod, bat and bird surveys were undertaken over 3 years (2012–2014) at 72 trees of three sizes (small (20–50 cm DBH), medium (51–80 cm), large (≥80 cm)) located in four landscape contexts (reserves, pasture, urban parklands, urban built‐up areas).

Results

Landscape context affected all taxa surveyed. Trunk arthropod communities differed between trees in urban built‐up areas and reserves. Bat activity and richness were significantly reduced at trees in urban built‐up areas suggesting that echolocating bats may be disturbed by high levels of urbanization. Bird abundance and richness were highest at trees located in modified landscapes, highlighting the value of scattered trees for birds. Bird communities also differed between non‐urban and urban trees. Tree size had a significant effect on birds but did not affect trunk arthropods and bats. Large trees supported higher bird abundance, richness and more unique species compared to medium and small trees.

Main conclusions

Scattered trees support a diversity of wildlife. However, landscape context and tree size affected wildlife in contrasting ways. Land management strategies are needed to collectively account for responses exhibited by multiple taxa at varying spatial scales. We recommend that the retention and perpetuation of scattered trees in modified landscapes should be prioritized, hereby providing crucial habitat benefits to a multitude of taxa.     

Differential requirement for NF-kappaB-inducing kinase in the induction of NF-kappaB by IL-1beta,TNF-alpha,and Fas

In this study, weexamined the role of the nuclear factor-B (NF-B)-inducing kinase(NIK) in distinct signaling pathways leading to NF-B activation. Weshow that a dominant-negative form of NIK (dnNIK) delivered byadenoviral (Ad5dnNIK) vector inhibits Fas-induced IBphosphorylation and NF-B-dependent gene expression in HT-29 and HeLacells. Interleukin (IL)-1- and tumor necrosis factor-(TNF-)-induced NF-B activation and B-dependent gene expressionare inhibited in HeLa cells but not in Ad5dnNIK-infected HT-29 cells.Moreover, Ad5dnNIK failed to sensitize HT-29 cells to TNF--inducedapoptosis at an early time point. However, cytokine- andFas-induced signals to NF-B are finally integrated by the IBkinase (IKK) complex, since IB phosphorylation, NF-B DNAbinding activity, and IL-8 gene expression were strongly inhibited inHT-29 and HeLa cells overexpressing dominant-negative IKK(Ad5dnIKK). Our findings support the concept that cytokine signalingto NF-B is redundant at the level of NIK. In addition, this studydemonstrates for the first time the critical role of NIK and IKK inFas-induced NF-B signaling cascade.

     

A global comparison of grassland biomass responses to CO2 and nitrogen enrichment

Grassland ecosystems cover vast areas of the Earth''s surface and provide many ecosystem services including carbon (C) storage, biodiversity preservation and the production of livestock forage. Predicting the future delivery of these services is difficult, because widespread changes in atmospheric CO₂ concentration, climate and nitrogen (N) inputs are expected. We compiled published data from global change driver manipulation experiments and combined these with climate data to assess grassland biomass responses to CO₂ and N enrichment across a range of climates. CO₂ and N enrichment generally increased aboveground biomass (AGB) but effects of CO₂ enrichment were weaker than those of N. The response to N was also dependent on the amount of N added and rainfall, with a greater response in high precipitation regions. No relationship between response to CO₂ and climate was detected within our dataset, thus suggesting that other site characteristics, e.g. soils and plant community composition, are more important regulators of grassland responses to CO₂. A statistical model of AGB response to N was used in conjunction with projected N deposition data to estimate changes to future biomass stocks. This highlighted several potential hotspots (e.g. in some regions of China and India) of grassland AGB gain. Possible benefits for C sequestration and forage production in these regions may be offset by declines in plant biodiversity caused by these biomass gains, thus necessitating careful management if ecosystem service delivery is to be maximized. An approach such as ours, in which meta-analysis is combined with global scale model outputs to make large-scale predictions, may complement the results of dynamic global vegetation models, thus allowing us to form better predictions of biosphere responses to environmental change.