Cortical radial glial cells in human fetuses: Depth‐correlated transformation into astrocytes

In the human brain, the transformation of radial glial cells (RGC) into astrocytes has been studied only rarely. In this work, we were interested in studying the morphologic aspects underlying this transformation during the fetal/perinatal period, particularly emphasizing the region‐specific glial fiber anatomy in the medial cortex. We have used carbocyanine dyes (DiI/DiA) to identify the RGC transitional forms and glial fiber morphology. Immunocytochemical markers such as vimentin and glial fibrillary acidic protein (GFAP) were also employed to label the radial cells of glial lineage and to reveal the early pattern of astrocyte distribution. Neuronal markers such as neuronal‐specific nuclear protein (NeuN) and microtubule‐associated protein (MAP‐2) were employed to discern whether or not these radial cells could, in fact, be neurons or neuronal precursors. The main findings concern the beginning of RGC transformation showing loss of the ventricular fixation in most cases, followed by transitional figures and the appearance of mature astrocytes. In addition, diverse fiber morphology related to depth within the cortical mantle was clearly demonstrated. We concluded that during the fetal/perinatal period the cerebral cortex is undergoing the final stages of radial neuronal migration, followed by involution of RGC ventricular processes and transformation into astrocytes. None of the transitional or other radial glia were positive for neuronal markers. Furthermore, the differential morphology of RGC fibers according to depth suggests that factors may act locally in the subplate and could have a role in the process of cortical RGC transformation and astrocyte localization. The early pattern of astrocyte distribution is bilaminar, sparing the cortical plate. Few astrocytes (GFAP+) in the upper band could be found with radial processes at anytime. This suggests that astrocytes in the marginal zone could be derived from different precursors than those that differentiate from RGCs during this period. © 2003 Wiley Periodicals, Inc. J Neurobiol 55: 288–298, 2003     

Dissociation of rugose‐dependent short‐term memory component from memory consolidation in Drosophila

Extensive investigations show several molecular and neuroanatomical mechanisms underlying short‐lived and long‐lasting memory in Drosophila. At the molecular level, the genetic pathway of memory formation, which was obtained through mutant research, seems to occur sequentially. So far, studies of Drosophila mutants appear to support the idea that mutants defective in short‐term memory (STM) are always associated with long‐term memory (LTM) impairment. At the neuroanatomical level, distinct memory traces are partially independently distributed. However, whether memory phase dissociation also exists at the molecular level remains unclear. Here, we report on molecular separation of STM and consolidated memory through genetic dissection of rugose mutants. Mutants in the rugose gene, which encodes an evolutionarily conserved A‐kinase anchor protein, show immediate memory defects as assayed through aversive olfactory conditioning. Intriguingly, two well‐defined consolidated memory components, anesthesia‐resistant memory and protein synthesis‐dependent LTM, are both normal in spite of the defective immediate memory after 10‐session massed and spaced training. Moreover, rugose genetically interacts with cyclic AMP‐protein kinase A signaling during STM formation. Considering our previous study that AKAP Yu specifically participates in LTM formation, these results suggest that there exists a molecular level of memory phase dissociation with distinct AKAPs in Drosophila.     

A meta‐analysis of bird and mammal response to short‐rotation woody crops

Short‐rotation woody cropping (SRWC) refers to silvicultural systems designed to produce woody biomass using short harvest cycles (1–15 years), intensive silvicultural techniques, high‐yielding varieties, and often coppice regeneration. Recent emphasis on alternatives to fossil fuels has spurred interest in producing SRWC on privately owned and intensively managed forests of North America. We examined potential bird and small mammal response at the stand level to conversion of existing, intensively managed forests to SRWCs using meta‐analysis of existing studies. We found 257 effect sizes for birds (243 effect sizes) and mammals (14 effect sizes) from 8 studies involving Populus spp. plantations. Diversity and abundance of bird guilds were lower on short‐rotation plantations compared with reference woodlands, while abundance of individual bird species was more variable and not consistently higher or lower on SRWC plantations. Shrub‐associated birds were more abundant on SRWC plantations, but forest‐associated and cavity‐nesting birds were less abundant. Effects on birds appeared to decrease with age of the SRWC plantation, but plantation age was also confounded with variation in the type of reference forest used for comparison. Both guilds and species of mammals were less abundant on SRWC plantations. These conclusions are tentative because none of these studies directly compared SRWC plantations to intensively managed forests. Plantations of SRWCs could contribute to overall landscape diversity in forest‐dominated landscapes by providing shrubby habitat structure for nonforest species. However, extensive conversion of mature or intensively managed forests to SRWC would likely decrease overall diversity, especially if they replace habitat types of high conservation value.     

Changes in short‐chain acyl‐coA dehydrogenase during rat cardiac development and stress

This study was designed to investigate the expression of short‐chain acyl‐CoA dehydrogenase (SCAD), a key enzyme of fatty acid β‐oxidation, during rat heart development and the difference of SCAD between pathological and physiological cardiac hypertrophy. The expression of SCAD was lowest in the foetal and neonatal heart, which had time‐dependent increase during normal heart development. In contrast, a significant decrease in SCAD expression was observed in different ages of spontaneously hypertensive rats (SHR). On the other hand, swim‐trained rats developed physiological cardiac hypertrophy, whereas SHR developed pathological cardiac hypertrophy. The two kinds of cardiac hypertrophy exhibited divergent SCAD changes in myocardial fatty acids utilization. In addition, the expression of SCAD was significantly decreased in pathological cardiomyocyte hypertrophy, however, increased in physiological cardiomyocyte hypertrophy. SCAD siRNA treatment triggered the pathological cardiomyocyte hypertrophy, which showed that the down‐regulation of SCAD expression may play an important role in pathological cardiac hypertrophy. The changes in peroxisome proliferator‐activated receptor α (PPARα) was accordant with that of SCAD. Moreover, the specific PPARα ligand fenofibrate treatment increased the expression of SCAD and inhibited pathological cardiac hypertrophy. Therefore, we speculate that the down‐regulated expression of SCAD in pathological cardiac hypertrophy may be responsible for ‘the recapitulation of foetal energy metabolism’. The deactivation of PPARα may result in the decrease in SCAD expression in pathological cardiac hypertrophy. Changes in SCAD are different in pathological and physiological cardiac hypertrophy, which may be used as the molecular markers of pathological and physiological cardiac hypertrophy.     

Comparative proteomic analysis in children with idiopathic short stature (ISS) before and after short‐term recombinant human growth hormone (rhGH) therapy

This study was undertaken to identify growth hormone (GH) responsive proteins and protein expression patterns by short‐term recombinant human growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS) using proteomic analysis. Seventeen children (14 males and three females) with ISS were included. They were treated with rhGH at a dose of 0.31 ± 0.078 mg/kg/week for 3 months. Immunodepletion of six highly‐abundant serum proteins followed by 2D DIGE analysis, and subsequent MALDI TOF MS, were employed to generate a panel of proteins differentially expressed after short‐term rhGH therapy and verify the differences in serum levels of specific proteins by rhGH therapy. Fourteen spots were differentially expressed after rhGH treatment. Among them, apo E and apo L‐1 expression were consistently enhanced, whereas serum amyloid A was reduced after rhGH therapy. The differential expressions of these proteins were subsequently verified by Western blot analysis using sera of the before and after rhGH treatment. This study suggests that rhGH therapy influences lipoprotein metabolism and enhances apo L‐1 protein expression in ISS patients.     

Late Devonian dimpled phosphatic microspherules associated with conodonts are possible otoliths of short‐lived and opportunistic organisms

Dimpled phosphatic microspherules, contradictorily associated with conodonts, are widely distributed in strata ranging in age from the Cambrian to Carboniferous. These microspherules have attracted much attention from palaeobiologists and were suggested to be ‘conodont pearls’, ‘conodont otoliths’ or ‘fish otoliths’ due to their similar chemical composition and co‐occurrence with conodonts or fish teeth. However, these hypotheses are still highly controversial. Here, we report ‘checks’, ‘rhythmic growth patterns’ and ‘sub‐diurnal increments’ from growth annuli of the Late Devonian phosphatic microspherules from South China, on the basis of quantitative microstructure analysis. The annulus width of phosphatic microspherules becomes narrower with increasing radius. These microstructural characteristics of growth annuli are most typical indicators of modern animal otoliths. In addition, a maximum value of about 90 annuli is encountered from all the specimens. We propose that these microspherules are essentially phosphatic otoliths, which might have been secreted by a specific kind of marine organisms with very short lifespans (less than 90 days). Furthermore, the sudden enrichment of phosphatic microspherules in the late Frasnian may represent a biological response of short‐lived animals to ecological crisis such as ocean eutrophication.     

Aversive phototaxic suppression: evaluation of a short‐term memory assay in Drosophila melanogaster

Drosophila melanogaster is increasingly being used to model human conditions that are associated with cognitive deficits including fragile‐X syndrome, Alzheimer’s disease, Parkinson’s disease, sleep loss, etc. With few exceptions, cognitive abilities that are known to be modified in these conditions in humans have not been evaluated in fly models. One reason is the absence of a simple, inexpensive and reliable behavioral assay that can be used by laboratories that are not expert in learning and memory. Aversive phototaxic suppression (APS) is a simple assay in which flies learn to avoid light that is paired with an aversive stimulus (quinine/humidity). However, questions remain about whether the change in the fly’s behavior reflects learning an association between light and quinine/humidity or whether the change in behavior is because of nonassociative effects of habituation and/or sensitization. We evaluated potential effects of sensitization and habituation on behavior in the T‐maze and conducted a series of yoked control experiments to further exclude nonassociative effects and determine whether this task evaluates operant learning. Together these experiments indicate that a fly must associate the light with quinine/humidity to successfully complete the task. Next, we show that five classic memory mutants are deficient in this assay. Finally, we evaluate performance in a fly model of neurodegenerative disorders associated with the accumulation of Tau. These data indicate that APS is a simple and effective assay that can be used to evaluate fly models of human conditions associated with cognitive deficits.     

HIF‐2α regulates non‐canonical glutamine metabolism via activation of PI3K/mTORC2 pathway in human pancreatic ductal adenocarcinoma

Hypoxia‐inducible factor‐2α (HIF‐2α) plays an important role in increasing cancer progression and distant metastasis in a variety of tumour types. We aimed to investigate its biological function and clinical significance in human pancreatic ductal adenocarcinoma (PDAC). A total of 283 paired PDAC tissues and adjacent normal tissues were collected from patients who underwent surgery or biopsy at Sun Yat‐sen Memorial Hospital between February 2004 and October 2016. In this study, we noted that HIF‐2α expression was significantly up‐regulated in PDAC, positively associated with disease stage, lymph‐node metastasis and patient survival, and identified as an independent prognostic factor of PDAC patients. We demonstrated that HIF‐2α silencing could reduce proliferation, migration and invasion of PDAC cells in vitro. The similar effect on growth was demonstrated in vivo. Furthermore, we noted that knock‐down of HIF‐2α significantly decreased the expression of glutamate oxaloacetate transaminase 1 (GOT1). Importantly, we confirmed that the PI3K/mTORC2 pathway promoted GOT1 expression by targeting HIF‐2α. Our study validated HIF‐2α was an important factor in PDAC progression and poor prognosis and may promote non‐canonical glutamine metabolism via activation of PI3K/mTORC2 pathway. Targeting HIF‐2α represents a novel prognostic biomarker and therapeutic target for patients with PDAC.     

Contrasting mechanisms underlie short‐ and longer‐term soil respiration responses to experimental warming in a dryland ecosystem

Soil carbon losses to the atmosphere through soil respiration are expected to rise with ongoing temperature increases, but available evidence from mesic biomes suggests that such response disappears after a few years of experimental warming. However, there is lack of empirical basis for these temporal dynamics in soil respiration responses, and for the mechanisms underlying them, in drylands, which collectively form the largest biome on Earth and store 32% of the global soil organic carbon pool. We coupled data from a 10 year warming experiment in a biocrust‐dominated dryland ecosystem with laboratory incubations to confront 0–2 years (short‐term hereafter) versus 8–10 years (longer‐term hereafter) soil respiration responses to warming. Our results showed that increased soil respiration rates with short‐term warming observed in areas with high biocrust cover returned to control levels in the longer‐term. Warming‐induced increases in soil temperature were the main drivers of the short‐term soil respiration responses, whereas longer‐term soil respiration responses to warming were primarily driven by thermal acclimation and warming‐induced reductions in biocrust cover. Our results highlight the importance of evaluating short‐ and longer‐term soil respiration responses to warming as a mean to reduce the uncertainty in predicting the soil carbon–climate feedback in drylands.     

Diadinoxanthin de‐epoxidation as important factor in the short‐term stabilization of diatom photosynthetic membranes exposed to different temperatures

The importance of diadinoxanthin (Ddx) de‐epoxidation in the short‐term modulation of the temperature effect on photosynthetic membranes of the diatom Phaeodactylum tricornutum was demonstrated by electron paramagnetic resonance (EPR), Laurdan fluorescence spectroscopy, and high‐performance liquid chromatography. The 5‐SASL spin probe employed for the EPR measurements and Laurdan provided information about the membrane area close to the polar head groups of the membrane lipids, whereas with the 16‐SASL spin probe, the hydrophobic core, where the fatty acid residues are located, was probed. The obtained results indicate that Ddx de‐epoxidation induces a two component mechanism in the short‐term regulation of the membrane fluidity of diatom thylakoids during changing temperatures. One component has been termed the “dynamic effect” and the second the “stable effect” of Ddx de‐epoxidation. The “dynamic effect” includes changes of the membrane during the time course of de‐epoxidation whereas the “stable effect” is based on the rigidifying properties of Dtx. The combination of both effects results in a temporary increase of the rigidity of both peripheral and internal parts of the membrane whereas the persistent increase of the rigidity of the hydrophobic core of the membrane is solely based on the “stable effect.”     

Spectroscopic and in silico study of binding mechanism of cynidine‐3‐O‐glucoside with human serum albumin and glycated human serum albumin

The drug–serum albumin interaction plays a dominant role in drug efficacy and disposition. The glycation of serum albumin that occurs during diabetes may affect its drug‐binding properties in vivo. In order to evaluate the interactivity characteristics of cyanidin‐3‐O‐glucoside (C3G) with human serum albumin (HSA) and glycated human serum albumin (gHSA), this study was undertaken using multiple spectroscopic techniques and molecular modeling analysis. Time‐resolved fluorescence and the thermodynamic parameters indicated that the quenching mechanism was static quenching, and hydrogen bonding and Van der Waals force were the main forces. The protein fluorescence could be quenched by C3G, whereas the polarity of the fluorophore was not obviously changed. C3G significantly altered the secondary structure of the proteins. Furthermore, the interaction force that existed in the HSA–C3G system was greater than that in the gHSA–C3G system. Fluorescence excitation emission matrix spectra, red edge excitation shift, Fourier transform infrared spectroscopy and circular dichroism spectra provided further evidence that glycation could inhibit the binding between C3G and proteins. In addition, molecular modeling analysis supported the experimental results. The results provided more details for the application of C3G in the treatment of diabetes.     

Biomass production and energy balance of a 12‐year‐old short‐rotation coppice poplar stand under different cutting cycles

Given today's political targets, energy production from agricultural areas is likely to increase and therefore needs to be more sustainable. The aim of this study was thus to carry out a long‐term field trial based on the poplar short‐rotation coppice (SRC), in order to compare dry matter, energy‐use efficiency and the net energy yield obtainable from this crop in relation to different harvest frequencies (1‐, 2‐ and 3‐year cutting cycles). The results showed that poplar SRC performed very well under temperate climates as it can survive up to 12 years, providing a considerable annual biomass yield (9.9, 13.8, 16.4 t ha^?1 yr^?1 for annual T1, biannual T2 and triennial T3 cutting cycles, respectively). The system tested in southern Europe showed a positive energy balance characterized by a high energy efficiency. We found that the choice of harvest interval had huge consequences in terms of energy yields. In fact, the energy efficiency improved from T1 to T2 and T3, while the net energy yield increased from 172 to 299 GJ ha^?1 yr^?1. This study suggests that, with 3‐year harvest cycles, poplar SRC can contribute to agronomic and environmental sustainability not only in terms of its high yield and energy efficiency but also in terms of its positive influence on limiting soil tillage and on the environment, given its low pesticide and nutrient requirements.     

The carbon implications of large‐scale afforestation of agriculturally marginal land with short‐rotation willow in Saskatchewan

Afforestation with short‐rotation coppice (SRC) willow plantations for the purpose of producing bioenergy feedstock was contemplated as one potential climate change mitigation option. The objectives of this study were to assess the magnitude of this mitigation potential by addressing: (i) the land area potentially available for SRC systems in the province of Saskatchewan, Canada; (ii) the potential biomass yields of SRC plantations; and (iii) the carbon implications from such a large‐scale afforestation program. Digital soils and land‐use data were used to identify, map, and group into clusters of similar polygons 2.12 million hectares (Mha) of agriculturally marginal land that was potentially suitable for willow in the Boreal Plains and Prairies ecozones in Saskatchewan. The Physiological Principles in Predicting Growth (3PG) model was calibrated with data from SRC experiments in Saskatchewan, to quantify potential willow biomass yields, and the Carbon Budget Model of the Canadian Forest Sector (CBM‐CFS3), was used to simulate stand and landscape‐level C fluxes and stocks. Short‐rotation willow plantations managed in 3 year rotations for seven consecutive harvests (21 years) after coppicing at Year 1 produced about 12 Mg ha^?1 yr^?1 biomass. The more significant contribution to the C cycle was the cumulative harvest. After 44 years, the potential average cumulative harvested biomass C in the Prairies was 244 Mg C ha^?1 (5.5 Mg C ha^?1 yr^?1) about 20% higher than the average for the Boreal Plains, 203 Mg C ha^?1 (4.6 Mg C ha^?1 yr^?1). This analysis did not consider afforestation costs, rate of establishment of willow plantations, and other constraints, such as drought and disease effects on biomass yield. The results must therefore be interpreted as a biophysical mitigation potential with the technical and economic potential being both lower than our estimates. Nevertheless, short‐rotation bioenergy plantations offer one potential mitigation option to reduce the rate of CO₂ accumulation in the earth's atmosphere and further research is needed to operationalise such a mitigation effort.     

Accumulation of soil organic carbon after cropland conversion to short‐rotation willow and poplar

The demand for bioenergy has increased the interest in short‐rotation woody crops (SRWCs) in temperate zones. With increased litter input and ceased annual soil cultivation, SRWC plantations may become soil carbon sinks for climate change mitigation. A chronosequence of 26 paired plots was used to study the potential for increasing soil organic carbon (SOC) under SRWC willow and poplar after conversion from cropland (CR) on well‐drained soils. We estimated SOC stocks in SRWC stands and adjacent CR and related the difference to time since conversion, energy crop species, SOC stock of the adjacent CR (proxy for initial SOC of SRWC) and the fine soil percentage (<63 μm) (FS). Soil cores to 40 cm depth were sampled and separated by layers of fixed depths (0–5, 5–10, 10–15, 15–25 and 25–40 cm). Additionally, soils were sampled from soil pits by genetic horizons to 100 cm depth. Comparisons of SOC stocks by equivalent soil masses showed that mean SOC stocks in SRWC were 1.7 times higher than those of CR in the top 5 cm of the soil (P < 0.001). The differences between SRWC and CR remained significant for the plough layer (0–25 cm) by a factor of 1.2 (P = 0.003), while no changes were detectable for the 0–40 cm (P = 0.32), or for the entire 0–100 cm soil layer (P = 0.29). The SOC stock ratio, that is the ratio of SOC stock in SRWC relative to CR, did not change significantly with time since conversion, although there was a tendency to an increase over time for the top 40 cm (P = 0.09). The SOC stock ratio was negatively correlated to SOC in CR and FS percentage, but there was no significant difference between willow and poplar at any depth. Our results suggest that SOC stocks in the plough layer increase after conversion to SRWC.     

Cytokine and cellular responses to human herpesvirus‐6B in patients with B‐acute lymphoblastic leukemia

Primary infection with human herpesvirus‐6 (HHV‐6), is followed by its lifelong persistence in the host. Most T‐cell responses to HHV‐6 have been characterized using peripheral blood from healthy adults; however, the role of HHV‐6 infection in immune modulation has not been elucidated for some diseases. Therefore, in this study the immune response to HHV‐6 infection in patients with B‐acute lymphoblastic leukemia (B‐ALL) was analyzed. HHV‐6 load was quantified in blood samples taken at the time of diagnosis of leukemia and on remission. The same concentrations of anti‐ and pro‐inflammatory cytokines (IL‐4, IL‐1, IL‐6, IL‐8, IL‐12p70, IL‐17a, TNF‐α and IFN‐γ) were detected in plasma samples from 20 patients with and 20 without detectable HHV‐6 virus loads in blood. Characterization of T‐cell responses to HHV‐6 showed low specific T‐cells frequencies of 2.08% and 1.46% in patients with and without detectable viral loads, respectively. IFN‐γ‐producing T cells were detected in 0.03%–0.23% and in 0%–0.2% of CD4+T cells, respectively. Strong production of IL‐6 was detected in medium supernatants of challenged T‐cells whatever the HHV‐6 status of the patients (973.51 ± 210.06 versus 825.70 ± 210.81 pg/mL). However, concentrations of TNF‐α and IFN‐γ were low. Thus, no association between plasma concentrations of cytokines and detection of HHV‐6 in blood was identified, suggesting that HHV‐6 is not strongly associated with development of B‐ALL. The low viral loads detected may correspond with latently infected cells. Alternatively, HHV‐6B specific immune responses may be below the detection threshold of the assays used.