Gastric haemolymphangioma is a very rare benign tumour. Pathologically, it is composed of lymphatic vessels and blood vessels. Only a few cases of haemolymphangioma have been reported in the literature so far, all of which developed at sites other than the stomach. The authors believe that a haemolymphangioma occurring in the stomach has not been previously reported. The patient was a healthy 68-year-old male who had felt light epigastric discomfort for 3 months. A CT scan and a gastrofiberscope examination revealed a well-demarcated mass on the posterior wall of the stomach near the lesser curvature. The mass was successfully removed by surgery. During the 18-month follow-up period, the patient was asymptomatic with no recurrence. In this case report, we discuss the imaging findings as well as the pathological features of this unusual case, with a review of the related literature.

The complex structural transformation in crystals under static pressure or shock loading has been a subject of long-standing interest to materials scientists and physicists. The polymorphic transformation is of particular importance for iron (Fe), due to its technological and sociological significance in the development of human civilization, as well as its prominent presence in the earth's core. The martensitic transformation α→ε (bcc→hcp) in iron under shock-loading, due to its reversible and transient nature, requires non-trivial detective work to uncover its occurrence. Here we reveal refined microstructural fingerprints, needle-like colonies and three sets of {112}<111> twins with a threefold symmetry, with tell-tale features that are indicative of two sequential martensitic transformations in the reversible α→ε phase transition, even though no ε is retained in the post-shock samples. The signature orientation relationships are consistent with previously-proposed transformation mechanisms, and the unique microstructural fingerprints enable a quantitative assessment of the volume fraction transformed.

Ancient DNA methodologies can be applied in the investigation of the genetics of extinct populations. A search for beta thalassemia mutations was performed on 49 Minoan individuals from the Bronze Age who were living in the island of Crete approximately 4,000 Years Before Present (YBP). Standard precautionary measures were employed in the laboratory to ensure authenticity of the DNA extracted from the ancient bones, resulting in the successful analysis of DNA of 24 Minoans. DNA sequencing focused on the Intervening Sequence 1 (IVS-1) of the beta globin gene and its splicing junctions. 63% of the thalassemia mutations observed among modern Cretans reside in beta IVS -1. None of the Minoan individuals carried one of the IVS-1 mutations known to cause beta thalassemia; however, only one was expected to be observed if the average frequency of beta thalassemia heterozygotes in the Minoan population was the same with that of modern day Cretans (7.6 %). One individual contained a C to G substitution in position 91 of the IVS-1, located 40 bp 5′ to the intron 1/exon 2 junction. Functional studies indicated that the mutation did not affect mRNA splicing or stability, and most likely represented an innocent single nucleotide polymorphism.

Aims/hypothesis

Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes.

Methods

The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m2 and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case–control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans.

Results

Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10−14), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10−11) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10−10).

Conclusions/interpretation

We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

Electronic supplementary material

The online version of this article (doi:10.1007/s00125-012-2756-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Background:

Interferon-λs (IFN-λs) are novel cytokines with multiple functions, like IFN-α and -β. We examined possible anti-tumour effects produced by adenoviruses bearing the IFN-λ1 or -λ2 gene (Ad/IFN-λ) with the type-35 fibre-knob structure.

Methods:

Proliferation of oesophageal carcinoma cells transduced with Ad/IFN-λ and mechanisms of the inhibited growth were investigated.

Results:

Transduction with Ad/IFN-λ upregulated the expression of the class I antigens of the major histocompatibility complexes and induced the growth suppression. Increased sub-G1 populations and the cleavage of caspase-3 and poly (ADP-ribose) polymerase were detected in IFN-λ-sensitive YES-2 and T.Tn cells. The cell death was accompanied by cytoplasmic cytochrome C and increased cleaved caspase-9 and Bax expression, suggesting mitochondria-mediated apoptosis. Adenovirus/IFN-λ-infected YES-2 cells subsequently reduced the tumourigenicity. Adenovirus/IFN-λ-infected fibroblasts, negative for the IFN-λ receptors, induced death of YES-2 or T.Tn cells that were co-cultured. Inoculation of YES-2 cells in nude mice, when mixed with the Ad/IFN-λ-infected fibroblasts, resulted in retardation of the tumour growth. The growth suppression was not linked with upregulated CD69 expression on natural killer cells or increased numbers of CD31-positive cells.

Conclusion:

Adenovirus/IFN-λ induced apoptosis, and fibroblast-mediated delivery of IFN-λs is a potential cancer treatment by inducing direct cell death of the target carcinoma.

Background

The varying nature of chronic pain (CP) is difficult to correlate to neural activity using typical functional magnetic resonance imaging methods. Arterial spin labeling is a perfusion-based imaging technique allowing the absolute quantification of regional cerebral blood flow, which is a surrogate measure of neuronal activity.

Methods

Subjects with chronic low back and radicular pain and matched healthy normals, undergoing identical procedures, participated in three sessions—a characterization and training session and two arterial spin labeling sessions. In the first imaging session CP (if any) was exacerbated using clinical maneuvers and in the second session noxious heat was applied to the affected leg dermatome, the intensity of which was matched to the pain intensity level of the CP exacerbations for each back pain subject.

Results

The clinically significant worsening of ongoing CP (≥30%, n=16) was associated with significant regional blood flow increases (6–10 mm/100gr of tissue/min, p<0.01) within brain regions known to activate with experimental pain (somatosensory, prefrontal, and insular cortices) and in other structures observed less frequently in experimental pain studies, such as the superior parietal lobule (part of the dorsal attention network). This effect is specific to changes in ongoing CP as it is observed during worsening CP, but it is not observed after thermal pain application, or in matched, pain-free healthy controls.

Conclusions

Our findings demonstrate the use of arterial spin labeling to investigate the neural processing of CP, and they are a step forward in the quest for objective biomarkers of the chronic pain experience.

Although there are a number of different allopolyploids in the plant kingdom, the exact ancestral parents of some allopolyploids have not been well characterized. We propose a strategy in which virtual allopolyploid lines derived from different types of parental species are used to investigate the progenitors of an allopolyploid. The genotypes of the parental lines and the natural allopolyploid were established using a set of DNA molecular markers. The genotypes of the virtual lines were then derived from those of the parental lines, and compared extensively with that of the natural allopolyploid. We applied this strategy to investigate the progenitors of the C subgenome of Brassica napus (rapeseed, AACC). A total of 39 accessions from 10 wild and 7 cultivated types of the B. oleracea cytodeme (CC), and 4 accessions of B. rapa (AA) were used to construct 156 virtual rapeseed lines. Genetic structure was compared among natural rapeseed, virtual rapeseed lines, and their parental lines by principal component analysis and analysis of ancestry. Our data showed that the C subgenome of natural rapeseed was related closely to the genome of cultivated B. oleracea and its related wild types, such as B. incana, B. bourgeaui, B. montana, B. oleracea ssp. oleracea and B. cretica. This finding indicated that these types or their progeny might be ancestral donors of the C subgenome of rapeseed. The successful application of the strategy of virtual allopolyploidy in rapeseed demonstrates that it can possibly be used to identify the progenitors of an allopolyploid species.

The epithelial–mesenchymal transition (EMT) induced by chemotherapeutic agents promotes malignant tumor progression; however, the mechanism underlying the drug-induced EMT remains unclear. In this study, we reported that miR-448 is the most downregulated microRNA following chemotherapy. Suppression of miR-448 correlated with EMT induction in breast cancer in vitro and in vivo. With the use of chromatin immunoprecipitation-seq analysis, we demonstrated that miR-448 suppression induces EMT by directly targeting special AT-rich sequence-binding protein-1 (SATB1) mRNA, leading to elevated levels of amphiregulin and thereby, increasing epidermal growth factor receptor (EGFR)-mediated Twist1 expression, as well as nuclear factor κB (NF-κB) activation. On the other hand, we also found that the adriamycin-activated NF-κB directly binds the promoter of miR-448 suppressing its transcription, suggesting a positive feedback loop between NF-κB and miR-448. Furthermore, all patients who received cyclophosphamide (CP), epirubicin plus taxotere/CP, epirubicin plus 5-fluorouracil chemotherapy showed miR-448 suppression, an increased SATB1, Twist1 expression and acquisition of mesenchymal phenotypes. These findings reveal an underlying regulatory pathway, in which the autoregulation between NF-κB and miR-448 is important for restrain miR-448 suppression upon chemotherapy and may have a role in the regulation of chemotherapy-induced EMT. Disruption of the NF-κB-miR-448 feedback loop during clinical treatment may improve the chemotherapy response of human breast cancers in which EMT is a critical component.

Sorafenib, a multi-tyrosine kinase inhibitor, kills more effectively the non-metastatic prostate cancer cell line 22Rv1 than the highly metastatic prostate cancer cell line PC3. In 22Rv1 cells, constitutively active STAT3 and ERK are targeted by sorafenib, contrasting with PC3 cells, in which these kinases are not active. Notably, overexpression of a constitutively active MEK construct in 22Rv1 cells stimulates the sustained phosphorylation of Bad and protects from sorafenib-induced cell death. In PC3 cells, Src and AKT are constitutively activated and targeted by sorafenib, leading to an increase in Bim protein levels. Overexpression of constitutively active AKT or knockdown of Bim protects PC3 cells from sorafenib-induced killing. In both PC3 and 22Rv1 cells, Mcl-1 depletion is required for the induction of cell death by sorafenib as transient overexpression of Mcl-1 is protective. Interestingly, co-culturing of primary cancer-associated fibroblasts (CAFs) with 22Rv1 or PC3 cells protected the cancer cells from sorafenib-induced cell death, and this protection was largely overcome by co-administration of the Bcl-2 antagonist, ABT737. In summary, the differential tyrosine kinase profile of prostate cancer cells defines the cytotoxic efficacy of sorafenib and this profile is modulated by CAFs to promote resistance. The combination of sorafenib with Bcl-2 antagonists, such as ABT737, may constitute a promising therapeutic strategy against prostate cancer.

Porous silicon (pSi) is being extensively studied as an emerging material for use in biomedical applications, including drug delivery, based on the biodegradability and versatile chemical and biophysical properties. We have recently introduced multistage nanoporous silicon microparticles (S1MP) designed as a cargo for nanocarrier drug delivery to enable the loaded therapeutics and diagnostics to sequential overcoming of the biological barriers to reach their target. In this first report on biocompatibility of intravenously administered pSi structures, we examined biocompatibility of negatively (−32.5±3.1mV) and positively (8.7±2.5mV) charged S1MP in acute single dose (107, 108, 5×108 S1MP/animal) and subchronic multiple dose (108 S1MP/animal/week for 4 weeks) administration schedules. Our data demonstrate that S1MP did not change plasma levels of renal (BUN and creatinine) and hepatic (LDH) biomarkers as well as23 plasma cytokines. LDH plasma levels of 145.2±23.6, 115.4±29.1 vs. 127.0±10.4; and 155.8±38.4, 135.5±52.3 vs. 178.4±74.6 were detected in mice treated with 108 negatively charged S1MP, 108 positively charged S1MP vs. saline control in single and multiple dose schedules, respectively. The S1MPs did not alter LDH levels in liver and spleen, nor lead to infiltration of leukocytes into the liver, spleen, kidney, lung, brain, heart, and thyroid. Collectively, these data provide evidence of a safe intravenous administration of S1MPs as a drug delivery carrier.

In order to elucidate the relationship between androgens and the function of the muskrat (Ondatra zibethicus) scented glands during the breeding season, we investigated immunolocalization of steroidogenic enzymes P450scc, 3βHSD and P450c17 in the muskrat testes and scented glands. Nine adult muskrats were obtained in March (n=3), May (n=3) and July (n=3) 2010. Steroidogenic enzymes were immunolocalized using polyclonal antisera raised against bovine adrenal P450scc, human placental 3βHSD and porcine testicular P450c17. Histologically, all types of spermatogenic cells including mature-phase spermatozoa in seminiferous tubules were observed in all testes. Glandular cells, interstitial cells, epithelial cells and excretory tubules were identified in scented glands during the breeding season. P450scc, 3βHSD and P450c17 were only identified in Leydig cells during the breeding season; P450scc and P450c17 were observed in glandular cells of scented glands, however, 3βHSD was not found in scented glands during the breeding season. These novel findings provide the first evidence showing that scented glands of the muskrats are capable of locally synthesizing androgens and androgens acting via an endocrine, autocrine or paracrine manner may play an important role in scented gland function during the breeding season.

Estrogen plays an important role in bone metabolism and only high dose can stimulate osteoblast bone formation. However, the underlying mechanisms have not been elucidated. The epithelial sodium channel (ENaC) is a key pathway for sodium transport in epithelia, vascular endothelium, and other tissues; although the expressions of α and γ ENaC mRNA were found in osteoblasts, the regulation of ENaC by estrogen in osteoblasts has not been studied. Our recent data confirmed the ENaC expression in mouse primary osteoblasts by immunocytofluorescence, RT-PCR, western blot, and patch clamp. Furthermore, we found estrogen (10−5M) increased the expression of α and γ ENaC subunits at both the mRNA and protein levels in osteoblasts. On the other hand, 17βestradiol (20nM) increased inward Na+ currents which were inhibited by amiloride. The estrogen dose used in patch clamp is much lower than those of mRNA and protein analysis, which means single cell ENaC electrophoretic mobility is much more sensitive to estrogen than the mRNA and protein production by estrogen stimulation. Our results suggest that estrogen regulates expression and function of ENaC in osteoblasts may provide a new clue that the mechanism of high dose of estrogen influence osteoblast bone formation via ENaC activity.

Chronic pain patients who show aberrant drug-related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain. The purpose of this study was to conduct a randomized trial in patients prescribed opioids for noncancer back pain who showed risk potential for or demonstration of opioid misuse to see if close monitoring and cognitive behavioral substance misuse counseling could increase overall compliance with opioids. Forty two patients meeting criteria for high risk for opioid misuse were randomized to either standard control (High-Risk Control; N=21) or experimental compliance treatment consisting of monthly urine screens, compliance checklists, and individual and group motivational counseling (High-Risk Experimental; N=21). Twenty patients who met criteria indicating low potential for misuse were recruited to a low-risk control group (Low-Risk Control). Patients were followed for 6 months and completed pre- and post-study questionnaires and monthly electronic diaries. Outcomes consisted of the percent with a positive Drug Misuse Index (DMI), which was a composite score of self-reported drug misuse (Prescription Drug Use Questionnaire), physician-reported abuse behavior (Addiction Behavior Checklist), and abnormal urine toxicology results. Significant differences were found between groups with 73.7 % of the High-Risk Control patients demonstrating positive scores on the DMI compared with 26.3% from the High-Risk Experimental group and 25.0% from the Low-Risk Controls (p<0.05). The results of this study demonstrate support for the benefits of a brief behavioral intervention in the management of opioid compliance among chronic back pain patient at high-risk for prescription opioid misuse.

Background:

Biliary tract cancers are rare but fatal malignancies. Diabetes has been related to biliary stones, but its association with biliary tract cancers is less conclusive.

Methods:

In a population-based case–control study of 627 cancers, 1037 stones, and 959 controls in Shanghai, China, we examined the association between diabetes and the risks of biliary tract cancer and stones, as well as the effect of potential mediating factors, including serum lipids and biliary stones (for cancer), contributing to the causal pathway from diabetes to biliary diseases.

Results:

Independent of body mass index (BMI), diabetes was significantly associated with gallbladder cancer and biliary stones ((odds ratio (OR) (95% confidence interval)=2.6 (1.5–4.7) and 2.0 (1.2–3.3), respectively). Biliary stones and low serum levels of high-density lipoprotein (HDL) were significant mediators of the diabetes effect on gallbladder cancer risk, accounting for 60 and 17% of the diabetes effect, respectively. High-density lipoprotein was also a significant mediator of the diabetes effect on biliary stones, accounting for 18% of the diabetes effect.

Conclusions:

Independent of BMI, diabetes is a risk factor for gallbladder cancer, but its effect is mediated in part by biliary stones and serum HDL levels, suggesting that gallbladder cancer risk may be reduced by controlling diabetes, stones, and HDL levels.

BACKGROUND

In the PEPI-Malawi trial, most women received single dose nevirapine (sdNVP) at delivery, and infants in the extended study arms received sdNVP plus 1 week of daily zidovudine (ZDV), followed by either extended daily NVP or extended daily NVP+ZDV up to 14 weeks of age. While extended NVP prophylaxis reduces the risk of postnatal HIV transmission, it may increase the risk of NVP resistance among infants who are HIV-infected despite prophylaxis.

METHODS

We analyzed 88 infants in the PEPI- Malawi trial with in utero HIV infection who received prophylaxis for a median of 6 weeks prior to HIV diagnosis. HIV genotyping was performed using the ViroSeq HIV Genotyping System.

RESULTS

At 14 weeks of age, the proportion of infants with NVP resistance was lower in the extended NVP+ZDV arm than in the extended NVP arm (28/45=62.2% vs. 37/43=86.0%, p=0.015). None of the infants had ZDV resistance. Addition of extended ZDV to extended NVP was associated with reduced risk of NVP resistance at 14 weeks if prophylaxis was stopped by 6 weeks (54.5% vs. 85.7%, p=0.007), but not if prophylaxis was continued beyond 6 weeks (83.3% vs. 87.5%, p=1.00).

CONCLUSIONS

Addition of extended ZDV to extended NVP prophylaxis significantly reduced the risk of NVP resistance at 14 weeks in infants with in utero HIV infection, provided that HIV infection was diagnosed and the prophylaxis was stopped by 6 weeks of age.

Background

Basaloid squamous cell carcinoma of the lung is a rare and highly malignant tumor mostly observed in the proximal bronchi. Basaloid squamous cell carcinoma of the lung cases typically show rapid clinical progression, very poor prognosis and special pathological morphology. This project aimed to examine the clinical features of basaloid squamous cell carcinoma of the lung and the factors related to its prognosis; and to compare survival outcomes between basaloid squamous cell carcinoma and poorly differentiated squamous cell carcinomas (PDSC).

Methods

Between January 2004 and December 2008, pathological sections from basaloid squamous cell carcinoma and PDSC of the lung were collected and retrospectively analyzed at Tianjin Medical University Cancer Institute and Hospital. Data analysis was performed using Statistical Package for the Social Sciences (SPSS11.0). The Kaplan-Meier method was used to calculate the survival rate. Log-rank test was used to compare the differences in survival rate between the two groups. The factors influencing prognosis were analyzed using the Cox proportional hazard model.

Results

A total of 120 pathological sections were used in the analysis of this study-22 from basaloid squamous cell carcinoma cases and 98 from PDSC cases. Compared to the PDSC group, the basaloid squamous cell carcinoma group had a larger proportion of female patients (p = 0.001); however it had higher proportion of male smokers (p = 0.003). There were no statistically significant differences in survival rate between the two groups (χ2 = 1.200, p = 0.273). Additionally, prognosis of basaloid squamous cell carcinoma is significantly influenced by treatment mode and clinical stages of the tumor. The post-operation mortality hazard of patients treated with a combination chemotherapy and radiotherapy was 1.296 times higher than other treatment modes (p = 0.025). Increases in post-operation mortality hazard ratio were also associated with more advanced clinical stage of tumors (χ2 trend = 11.907, p = 0.000).

Conclusions

This study demonstrated that basaloid squamous cell carcinoma and PDSC have very similar clinical features, and there are no significant differences in survival rates between the two groups. Hence, we conclude that in the short term, the same clinical treatments and therapeutic modes can be administered to patients with basaloid squamous cell carcinoma and PDSC of the lung.

Background:

Uncertainty surrounds the effects of cerebral edema on outcomes in intracerebral hemorrhage (ICH).

Methods:

We used data from the INTERACT trial to determine the predictors and prognostic significance of “perihematomal” edema over 72 hours after ICH. INTERACT included 404 patients with CT-confirmed ICH and elevated systolic blood pressure (BP) (150–220 mm Hg) who had the capacity to commence BP lowering treatment within 6 hours of ICH. Baseline and repeat CT (24 and 72 hours) were performed using standardized techniques, with digital images analyzed centrally. Predictors of growth in edema were determined using generalized estimating equations, and its effects on clinical outcomes were estimated using a logistic regression model.

Results:

Overall, 270 patients had 3 sequential CT scans available for analyses. At baseline, there was a highly significant correlation between hematoma and perihematomal edema volumes (r2 = 0.45). Lower systolic BP and baseline hematoma volume were independently associated with absolute increase in perihematomal edema volume. History of hypertension, baseline hematoma volume, and earlier time from onset to CT were independently associated with relative increase in edema volume. Both absolute and relative increases in perihematomal edema growth were significantly associated with death or dependency at 90 days after adjustment for age, gender, and randomized treatment, but not when additionally adjusted for baseline hematoma volume.

Conclusions:

The degree of, and growth in, perihematomal edema are strongly related to the size of the underlying hematoma of acute intracerebral hemorrhage, and do not appear to have a major independent effect in determining the outcome from this condition.

GLOSSARY

= American Heart Association;

= blood pressure;

= confidence interval;

= Digital Imaging and Communications in Medicine;

= Glasgow Coma Scale;

= intracerebral hemorrhage;

= Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial;

= interquartile range;

= modified Rankin scale;

= National Institutes of Health Stroke Scale;

= standard deviation;

= standard error.

Background

Many smokers in Western countries perceive “light” or “low tar” cigarettes as less harmful and less addictive than “regular” or “full flavoured” cigarettes. However, there is little research on whether similar perceptions exist among smokers in low and middle incomes, including China.

Objective

To characterise beliefs about “light” and “low tar” cigarettes among adult urban smokers in China.

Methods

We analysed data from Wave 1 of the ITC China Survey, a face-to-face household survey of 4732 adult Chinese smokers randomly selected from six cities in China in 2006. Households were sampled using a stratified multistage design.

Findings

Half (50.0%) of smokers in our sample reported having ever tried a cigarette described as “light,” “mild” or “low tar”. The majority of smokers in our sample (71%) believed that “light” and/or “low tar” cigarettes are less harmful compared to “full flavoured” cigarettes. By far the strongest predictor of the belief that “light” and/or “low tar” cigarettes are less harmful was the belief that “light” and/or “low tar” cigarettes feel smoother on the respiratory system (p<0.001, OR=53.87, 95% CI 41.28 to 70.31).

Conclusion

Misperceptions about “light” and/or “low tar” cigarettes were strongly related to the belief that these cigarettes are smoother on the respiratory system. Future tobacco control policies should go beyond eliminating labelling and marketing that promotes “light” and “low tar” cigarettes by regulation of product characteristics (for example, additives, filter vents) that reinforce perceptions that “light” and “low tar” cigarettes are smoother on the respiratory system and therefore less harmful.

Background:

The type I insulin-like growth factor receptor (IGF1R) is a transmembrane tyrosine kinase involved in cancer proliferation, survival, and metastasis.

Methods:

In this study, we used two different fluorescent technologies (small-molecule fluorophores and quantum dot (QD) nanoparticles) to detect receptor expression and its downregulation by antibodies in vivo.

Results:

After conjugation with AVE-1642, a humanised anti-IGF1R monoclonal antibody, both QDs (705 nm) or Alexa 680 (small-molecule fluorophore) detected expression and downregulation of IGF1R in vitro. To examine their utility in vivo, either AVE-1642 conjugates were intravenously delivered to mice bearing xenograft tumours of mouse embryo fibroblasts expressing human IGF1R or MCF-7 human breast cancer cells. Quantum dot fluorescence was mainly localised to the reticuloendothelial system in several organs and engulfed by macrophages, with only very small amount of QDs detected in the xenograft tumours. Depletion of macrophages by clodronate liposomes did not alter the nonspecific uptake of QDs. In contrast, AVE-1642-conjugated Alexa 680 solely targeted to xenograft tumour and was able to detect IGF1R downregulation, with little nonspecific targeting to other tissues or organs in mice.

Conclusion:

Taken together, our data suggest that small-molecule fluorophores, not QDs, are suitable to detect the expression and downregulation of IGF1R in vivo.

Lithium is used in the treatment of bipolar mood disorder. Reportedly, lithium can be neuroprotective in models of adult brain ischemia. The purpose of this study was to evaluate the effects of lithium in a model of neonatal hypoxic–ischemic brain injury. Nine-day-old male rats were subjected to unilateral hypoxia–ischemia (HI) and 2 mmol/kg lithium chloride was injected i.p. immediately after the insult. Additional lithium injections, 1 mmol/kg, were administered at 24-h intervals. Pups were killed 6, 24 or 72 h after HI. Lithium reduced the infarct volume from 24.7±2.9 to 13.8±3.3 mm3 (44.1%) and total tissue loss (degeneration + lack of growth) from 67.4±4.4 to 38.4±5.9 mm3 (43.1%) compared with vehicle at 72 h after HI. Injury was reduced in the cortex, hippocampus, thalamus and striatum. Lithium reduced the ischemia-induced dephosphorylation of glycogen synthase kinase-3β and extracellular signal-regulated kinase, the activation of calpain and caspase-3, the mitochondrial release of cytochrome c and apoptosis-inducing factor, as well as autophagy. We conclude that lithium could mitigate the brain injury after HI by inhibiting neuronal apoptosis. The lithium doses used were in the same range as those used in bipolar patients, suggesting that lithium might be safely used for the avoidance of neonatal brain injury.

Background

Pollen development from the microspore involves a series of coordinated cellular events, and the resulting mature pollen has a specialized function to quickly germinate, produce a polar-growth pollen tube derived from the vegetative cell, and deliver two sperm cells into the embryo sac for double fertilization. The gene expression profiles of developing and germinated pollen have been characterised by use of the eudicot model plant Arabidopsis. Rice, one of the most important cereal crops, has been used as an excellent monocot model. A comprehensive analysis of transcriptome profiles of developing and germinated pollen in rice is important to understand the conserved and diverse mechanism underlying pollen development and germination in eudicots and monocots.

Results

We used Affymetrix GeneChip® Rice Genome Array to comprehensively analyzed the dynamic changes in the transcriptomes of rice pollen at five sequential developmental stages from microspores to germinated pollen. Among the 51,279 transcripts on the array, we found 25,062 pollen-preferential transcripts, among which 2,203 were development stage-enriched. The diversity of transcripts decreased greatly from microspores to mature and germinated pollen, whereas the number of stage-enriched transcripts displayed a "U-type" change, with the lowest at the bicellular pollen stage; and a transition of overrepresented stage-enriched transcript groups associated with different functional categories, which indicates a shift in gene expression program at the bicellular pollen stage. About 54% of the now-annotated rice F-box protein genes were expressed preferentially in pollen. The transcriptome profile of germinated pollen was significantly and positively correlated with that of mature pollen. Analysis of expression profiles and coexpressed features of the pollen-preferential transcripts related to cell cycle, transcription, the ubiquitin/26S proteasome system, phytohormone signalling, the kinase system and defense/stress response revealed five expression patterns, which are compatible with changes in major cellular events during pollen development and germination. A comparison of pollen transcriptomes between rice and Arabidopsis revealed that 56.6% of the rice pollen preferential genes had homologs in Arabidopsis genome, but 63.4% of these homologs were expressed, with a small proportion being expressed preferentially, in Arabidopsis pollen. Rice and Arabidopsis pollen had non-conservative transcription factors each.

Conclusions

Our results demonstrated that rice pollen expressed a set of reduced but specific transcripts in comparison with vegetative tissues, and the number of stage-enriched transcripts displayed a "U-type" change during pollen development, with the lowest at the bicellular pollen stage. These features are conserved in rice and Arabidopsis. The shift in gene expression program at the bicellular pollen stage may be important to the transition from earlier cell division to later pollen maturity. Pollen at maturity pre-synthesized transcripts needed for germination and early pollen tube growth. The transcription regulation associated with pollen development would have divergence between the two species. Our results also provide novel insights into the molecular program and key components of the regulatory network regulating pollen development and germination.

Monodisperse FePt nanoparticles with size of 4.5 and 6.0 nm were prepared by simultaneous reduction of platinum acetylacetonate and thermal decomposition of iron pentacarbonyl in benzylether. The crystallography structure, size, and composition of the FePt nanoparticles were examined by X-ray diffraction and transmission electron microscopy. Energy dispersive X-ray spectrometry measurements of individual particles indicate a broad compositional distribution in both the 4.5 and 6 nm FePt nanoparticles. The effects of compositional distribution on the phase-transition and magnetic properties of the FePt nanoparticles were investigated.