Startle Responses in Motor Vehicle Accident Survivors: A Pilot Study

The aim of the present study was to investigate startle responses in motor vehicle accident (MVA) survivors to trauma-related, startle, and neutral sounds. Participants were 17 MVA survivors, 11 of whom participated in a controlled treatment study comparing cognitive-behavioral treatment (CBT) and supportive therapy (ST) versus a waitlist condition. Though participants differed significantly in their pretreatment clinical status and symptom severity, these differences were not reflected by group differences in EMG (at orbicularis oculi) to the stimuli at the initial assessment. Some cue-specificity was found, as all participants showed larger startle responses to trauma-related sounds, compared to startle and neutral sounds. At posttreatment, a significant reduction in EMG reactivity to all stimuli was observed in participants who received active treatment (either CBT or ST), compared to waitlist controls. The use of startle responses as a PTSD treatment outcome index is discussed.     

Prolonged Graft Survival in Older Recipient Mice Is Determined by Impaired Effector T-Cell but Intact Regulatory T-Cell Responses

Elderly organ transplant recipients represent a fast growing segment of patients on the waiting list. We examined age-dependent CD4⁺ T-cell functions in a wild-type (WT) and a transgenic mouse transplant model and analyzed the suppressive function of old regulatory T-cells. We found that splenocytes of naïve old B6 mice contained significantly higher frequencies of T-cells with an effector/memory phenotype (CD4⁺CD44^highCD62L^low). However, in-vitro proliferation (MLR) and IFNγ-production (ELISPOT) were markedly reduced with increasing age. Likewise, skin graft rejection was significantly delayed in older recipients and fewer graft infiltrating CD4⁺T-cells were observed. Old CD4⁺ T-cells demonstrated a significant impaired responsiveness as indicated by diminished proliferation and activation. In contrast, old alloantigen-specific CD4⁺CD25⁺FoxP3⁺ T-cells demonstrated a dose-dependent well-preserved suppressor function. Next, we examined characteristics of 18-month old alloreactive T-cells in a transgenic adoptive transfer model. Adoptively transferred old T-cells proliferated significantly less in response to antigen. Skin graft rejection was significantly delayed in older recipients, and graft infiltrating cells were reduced. In summary, advanced recipient age was associated with delayed acute rejection and impaired CD4⁺ T-cell function and proliferation while CD4⁺CD25⁺FoxP3⁺ T-cells (Tregs) showed a well-preserved function.     

Insulin-Like Growth Factor 1 Receptor Is a Prognostic Factor in Classical Hodgkin Lymphoma

The interaction between the tumor cells in classical Hodgkin lymphoma (cHL) and the microenvironment includes aberrant activity of receptor tyrosine kinases. In this study we evaluated the expression, functionality and prognostic significance of Insulin-like growth factor-1 receptor (IGF-1R) in cHL. IGF-1R was overexpressed in 55% (44/80) of cHL patients. Phosphorylated IGF-1R was detectable in a minority of the IGF-1R positive tumor cells. The overall survival (OS, 98%) and 5-year progression-free survival (PFS, 93%) was significantly higher in IGF-1R positive cHL patients compared to IGF-1R negative patients (OS 83%, p = .029 and PFS 77%, p = .047, respectively). Three cHL cell lines showed expression of IGF-1R, with strong staining especially in the mitotic cells and expression of IGF-1. IGF-1 treatment had a prominent effect on the cell growth of L428 and L1236 cells and resulted in an increased phosphorylation of IGF1R, Akt and ERK. Inhibition of IGF-1R with cyclolignan picropodophyllin (PPP) decreased cell growth and induced a G2/M cell cycle arrest in all three cell lines. Moreover, a decrease in pCcd2 and an increase in CyclinB1 levels were observed which is consistent with the G2/M cell cycle arrest. In conclusion, IGF-1R expression in HRS cells predicts a favorable outcome, despite the oncogenic effect of IGF-1R in cHL cell lines.     

Centennial-scale climate variability in the Timor Sea during Marine Isotope Stage 3

We present a high-resolution ( 60–110 yr) multi-proxy record spanning Marine Isotope Stage 3 from IMAGES Core MD01-2378 (13°04.95′ S and 121°47.27′ E, 1783 m water depth), located in the Timor Sea, off NW Australia. Today, this area is influenced by the Intertropical Convergence Zone, which drives monsoonal winds during austral summer and by the main outflow of the Indonesian Throughflow, which represents a key component of the global thermohaline circulation system. Thus, this core is ideally situated to monitor the linkages between tropical and high latitude climate variability. Benthic δ¹⁸O data (Planulina wuellerstorfi) clearly reflect Antarctic warm events (A1–A4) as recorded by the EPICA Byrd and Dronning Maud Land ice cores. This southern high latitude signal is transferred by deep and intermediate water masses flowing northward from the Southern Ocean into the Indian Ocean. Planktonic δ¹⁸O shows closer affinity to northern high latitudes planktonic and ice core records, although only the longer-lasting Dansgaard–Oeschger warm events, 8, 12, 14, and 16–17 are clearly expressed in our record. This northern high latitude signal in the surface water is probably transmitted through atmospheric teleconnections and coupling of the Asian–Australian monsoon systems. Benthic foraminiferal census counts suggest a coupling of Antarctic cooling with carbon flux patterns in the Timor Sea. We relate increasing abundances of carbon-flux sensitive species at 38–45 ka to the northeastward migration of the West Australian Current frontal area. This water mass reorganization is also supported by concurrent decreases in Mg/Ca and planktonic δ¹⁸O values (Globigerinoides ruber white).     

Gene Expression and Functional Annotation of the Human Ciliary Body Epithelia

Purpose

The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma.

Methods

We isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity.

Results

The gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (N)PE of 35 genes previously implicated in molecular mechanisms related to glaucoma.

Conclusion

Our gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma.     

Influence of a Probiotic Enterococcus Faecium Strain on Selected Bacterial Groups in the Small Intestine of Growing Turkey Poults

A feeding trial was carried out with turkey poults, which were fed a diet containing 10¹⁰ viable probiotic E. faecium NCIB 10415 cells/kg feed. Samples of the intestinal tract were analyzed for lactate, colony forming units of total anaerobic bacteria, lactic acid bacteria, enterobacteria and enterococci. Furthermore, metabolic activity of total eubacterial, lactobacilli and enterococci was recorded in selected RNA-extracts with specific ribosomal RNA oligonucleotide probes. Animals fed the probiotic diet showed continously increasing lactate concentrations throughout the sampling period up to day 42 of life. No correlation was found for colony forming units (cfu) of lactic acid bacteria, but metabolic activity of lactobacilli showed very close relation to continously increasing lactate concentrations. Throughout the feeding trial, enterococci in the control group continously increased to a maximum of 10⁴ cfu/g wet weight, but 10-fold higher enterococci cfu were generally found in the treated group. However, rRNA content as measure for metabolic activity showed a drastic decline in both groups after high metabolic activities on day 7. This study shows that E. faecium NCIB 10415 (E. faecium SF68) stimulates other lactic acid bacteria in the small intestine, especially lactobacilli.