A Network for Scene Processing in the Macaque Temporal Lobe

Spatial navigation is a complex process, but one that is essential for any mobile organism. We localized a region in the macaque occipitotemporal sulcus that responds preferentially to images of scenes. Single- unit recording revealed that this region, which we term the lateral place patch (LPP), contained a large concentration of scene-selective single units. These units were not modulated by spatial layout alone but were instead modulated by a combination of spatial and nonspatial factors, with individual units coding specific scene parts. We further demonstrate by microstimulation that LPP is connected with extrastriate visual areas V4V and DP and a sceneselective medial place patch in the parahippocampal gyrus, revealing a ventral network for visual scene processing in the macaque

Neutrophils as one of the major haptoglobin sources in mastitis affected milk

The antioxidant haptoglobin (Hp) is an acute-phase protein responsive to infectious and inflammatory diseases. Hp and somatic cell counts (SCC) are sharply elevated in bovine milk following intramammary administration of endotoxin or bacteria. However, the sources of milk Hp responsible for such increases are not fully understood. The purpose of this study was to define the source of milk Hp from dairy cows with naturally occurring mastitis. Quarter milk samples selected from 50 dairy cows were separated into four groups according to SCC as group A: < 100 (n = 19); B: 100–200 (n = 10); C: 201–500 (n = 10); and D: > 500 × 103 (n = 11) cells/mL. Our results reveal that milk Hp concentrations were correlated with SCC (r = 0.742; P < 0.01), and concentrations in group D were ~10-fold higher than in group A. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicates that the milk somatic cells from group D were not only capable of synthesizing Hp but could also markedly increase Hp mRNA expression. Western blot, immunocytochemistry, double confocal immunofluorescence, and Hp releasing experiments demonstrate that neutrophils were associated with the biosynthesis and release of Hp in milk. It further shows that Hp was significantly elevated in the epithelium of mammary gland tissue with mastitis and was also expressed in the cultured mammary epithelial cells. We propose that neutrophils and epithelial cells may play an essential role in elevating milk Hp in addition to previous suggestions that Hp may be derived from mammary tissues and circulation

Energy spread of ultracold electron bunches extracted from a laser cooled gas

Ultrashort and ultracold electron bunches created by near-threshold femtosecond photoionization of a laser-cooled gas hold great promise for single-shot ultrafast diffraction experiments. In previous publications the transverse beam quality and the bunch length have been determined. Here the longitudinal energy spread of the generated bunches is measured for the first time, using a specially developed Wien filter. The Wien filter has been calibrated by determining the average deflection of the electron bunch as a function of magnetic field. The measured relative energy spread $\frac{\sigma_{U}}{U} = 0.64 \pm 0.09\%$ agrees well with the theoretical model which states that it is governed by the width of the ionization laser and the acceleration length

Cytoplasmic Forkhead Box M1 (FoxM1) in Esophageal Squamous Cell Carcinoma Significantly Correlates with Pathological Disease Stage

Abstract: Esophageal cancer is a deadly cancer with esophageal squamous cell carcinoma (ESCC) as the major type. Until now there has been a lack of reliable prognostic markers for this malignancy. This study aims to investigate the clinical correlation between Forkhead box M1 (FoxM1) and patients' parameters in ESCC. Methods: Immunohistochemistry was performed to investigate the expression and localization of FoxM1 in 64 ESCC tissues and 10 nontumor esophageal tissues randomly selected from 64 patients before these data were used for clinical correlations. Results: Cytoplasmic and nuclear expressions of FoxM1 were found in 63 and 16 of the 64 ESCC tissues, respectively. Low cytoplasmic expression of FoxM1 was correlated with early pathological stage in ESCC (P = 0.018), while patients with nuclear FoxM1 were younger in age than those without nuclear expression (P < 0.001). Upregulation of FoxM1 mRNA was found in five ESCC cell lines (HKESC-1, HKESC-2, HKESC-3, HKESC-4, and SLMT-1) when compared to non-neoplastic esophageal squamous cell line NE-1 using quantitative polymerase chain reaction (qPCR). Except for HKESC-3, all studied ESCC cell lines demonstrated a high expression of FoxM1 protein using immunoblot. A high mRNA level of FoxM1 was observed in all of the ESCC tissues examined when compared to their adjacent nontumor tissues using qPCR. Conclusion: Cytoplasmic FoxM1 was correlated with pathological stage and might be a biomarker for advanced ESCC. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Addition of multiple rare SNPs to known common variants improves the association between disease and gene in the Genetic Analysis Workshop 17 data

The upcoming release of new whole-genome genotyping technologies will shed new light on whether there is an associative effect of previously immeasurable rare variants on incidence of disease. For Genetic Analysis Workshop 17, our team focused on a statistical method to detect associations between gene-based multiple rare variants and disease status. We added a combination of rare SNPs to a common variant shown to have an influence on disease status. This method provides us with an enhanced ability to detect the effect of these rare variants, which, modeled alone, would normally be undetectable. Adjusting for significant clinical parameters, several genes were found to have multiple rare variants that were significantly associated with disease outcome

On the knee in the energy spectrum of cosmic rays

The knee in the all-particle energy spectrum is scrutinized with a phenomenological model, named poly-gonato model, linking results from direct and indirect measurements. For this purpose, recent results from direct and indirect measurements of cosmic rays in the energy range from 10 GeV up to 1 EeV are examined. The energy spectra of individual elements, as obtained by direct observations, are extrapolated to high energies using power laws and compared to all-particle spectra from air shower measurements. A cut-off for each element proportional to its charge Z is assumed. The model describes the knee in the all-particle energy spectrum as a result of subsequent cut-offs for individual elements, starting with the proton component at 4.5 PeV, and the second change of the spectral index around 0.4 EeV as due to the end of stable elements (Z=92). The mass composition, extrapolated from direct measurements to high energies, using the poly-gonato model, is compatible with results from air shower experiments measuring the electromagnetic, muonic, and hadronic components. But it disagrees with the mass composition derived from X_max measurements using Cerenkov and fluorescence light detectors.Comment: 30 pages, 21 figures, 9 tables, accepted by Astroparticle Physic

Integrating complex genomic datasets and tumour cell sensitivity profiles to address a 'simple' question: which patients should get this drug?

It is becoming increasingly apparent that cancer drug therapies can only reach their full potential through appropriate patient selection. Matching drugs and cancer patients has proven to be a complex challenge, due in large part to the substantial molecular heterogeneity inherent to human cancers. This is not only a major hurdle to the improvement of the use of current treatments but also for the development of novel therapies and the ability to steer them to the relevant clinical indications. In this commentary we discuss recent studies from Kuo et al., published this month in BMC Medicine, in which they used a panel of cancer cell lines as a model for capturing patient heterogeneity at the genomic and proteomic level in order to identify potential biomarkers for predicting the clinical activity of a novel candidate chemotherapeutic across a patient population. The findings highlight the ability of a 'systems approach' to develop a better understanding of the properties of novel candidate therapeutics and to guide clinical testing and application

Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer

Detrusor muscle invasive transitional cell carcinoma is associated with poor prognosis and is responsible for the majority of bladder cancer related deaths. Amplifications of c-myc and CCND1 are associated with detrusor-muscle-invasive transitional cell carcinoma, however, their precise role in driving disease progression is unclear. Fluorescence in situ hybridisation on archival tissue from 16 patients with primary diagnosis of ⩾pT2 transitional cell carcinoma and 15 cases with primary pTa/pT1 disease subsequently progressing to detrusor-muscle-invasion was performed, in the latter group both pre and post muscle invasive events were studied. No patients presenting with ⩾pT2 had amplification of c-myc, two out of 16 (12.5%) had CCND1 amplification. Of patients who developed ⩾pT2, two out of 15 (13.3%) had amplification of c-myc, both in ⩾pT2, five out of 15 (33.3%) had CCND1 amplification, two in pTa/pT1 tumours, three in ⩾pT2 transitional cell carcinomas. In total, two out of 31 (6.5%) of patients' ⩾pT2 TCCs were amplified for c-myc and six out of 31 (19%) were amplified for CCND1. Eighty-seven per cent (40 out of 46) of tumours were polysomic for chromosome 8 and 80% (37 out of 46) were polysomic for chromosome 11 and this reflected the high copy numbers of c-myc and CCND1 observed. In almost all cases an increase in c-myc/CCND1 copy number occurred prior to invasion and persisted in advanced disease. Amplification of CCND1 or alterations in c-myc/CCND1 early in bladder cancer may have clinical relevance in promoting and predicting progression to detrusor-muscle-invasive transitional cell carcinoma

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN