Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

Background  

The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour.     

Chronic and acute stress as predictors of relapse in primary breast cancer patients

In this paper we present data on predictors of early relapse (at three and a half years post-surgery) in 44 patients with primary breast carcinoma. We expected that the degree to which receiving the diagnosis of malignancy would act as an acute stressor would allow a prediction of early relapse. Acute stress is measured by means of changes in psychological, neurochemical and immunological indicators of stress before and after the communication of the diagnosis. The results indicate that the assumption does not hold. Chronic stress, however, appears to be a strong predictor of early relapse. The measure of chronic stress is based on a self-report questionnaire of health complaints in the year before the diagnosis of breast cancer.     

Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

Purpose

Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB₁ and CB₂) have been suggested. The purpose of this study was to evaluate CB₁ and CB₂ receptor binding over time in vivo in a rat photothrombotic stroke model using PET.

Methods

CB₁ and CB₂ microPET imaging was performed at regular time-points up to 2?weeks after stroke using [¹⁸F]MK-9470 and [¹¹C]NE40. Stroke size was measured using MRI at 9.4?T. Ex vivo validation was performed via immunostaining for CB₁ and CB₂. Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68).

Results

[¹⁸F]MK-9470 PET showed a strong increase in CB₁ binding 24?h and 72?h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24?h after surgery. These alterations were consistently confirmed by CB₁ immunohistochemical staining. [¹¹C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB₂ revealed minor immunoreactivity at 1 and 2?weeks after stroke in this model. Both CB ₁ ⁺ and CB ₂ ⁺ cells showed minor immunoreactivity for CD68.

Conclusion

Time-dependent and regionally strongly increased CB₁, but not CB₂, binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB₁ signalling as the role of CB₂ seems minor in the acute and subacute phases of stroke.     

Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm Formation In Vivo

We here report on the in vitro activity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, including Candida albicans, Candida glabrata, Candida dubliniensis, Candida krusei, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. We validated the in vivo efficacy of orally administered toremifene against C. albicans and S. aureus biofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.     

Evidence for cross-modal plasticity in adult mouse visual cortex following monocular enucleation

The goal of this study was to assess cortical reorganization in the visual system of adult mice in detail. A combination of deprivation of one eye and stimulation of the remaining eye previously led to the identification of input-specific subdivisions in mouse visual cortex. Using this information as a reference map, we established to what extent each of these functional subdivisions take part in cortical reactivation and reorganization upon unilateral enucleation. A recovery experiment revealed a differential laminar and temporal reactivation profile. Initiation of infragranular recovery of molecular activity near the border with nonvisual cortex and simultaneous hyperactivation of this adjacent cortex implied a partial nonvisual contribution to this plasticity. The strong effect of somatosensory deprivation as well as stimulation on infragranular visual cortex activation in long-term enucleated animals support this view. Furthermore, targeted tracer injections in visual cortex of control and enucleated animals revealed preexisting connections between the visual and somatosensory cortices of adult mice as possible mediators. In conclusion, this study supports an important cross-modal component in reorganization of adult mouse visual cortex upon monocular enucleation.     

Vulnerabilities and Caregiving in an Ethnically Diverse HIV-Infected Population

The current study aimed to identify the primary informal caregivers of a group of urban HIV+ adults (n = 250) and to determine relationships between demographic, medical, and substance use characteristics and caregivers types. Reported caregiver types included 36.8% familial, 22.4% significant other, and 22.8% institutional or other caregiver relationships. The remaining 18% of the sample reported having no individual that rendered informal care. Factors associated with the absence of an informal caregiver included African American race and low education. Hispanic participants reported the highest frequency of family caregivers while participants with a history of substance disorder were less likely to identify a significant other as a caregiver. This study demonstrates the evolving nature of informal caregiving in HIV, race- and education-related disparities in the absence of primary caregivers, and the importance of sociocultural and demographic factors in the study of HIV caregiving. Research supported by R24MH59724 from the National Institutes of Health.     

Analytical and clinical performance of two cardiac troponin I immunoassays.

Cardiac troponin I assays for Axsym (Abbott Diagnostics, Abbott Park, IL, USA) and Immuno 1 (Bayer Corporation, Tarrytown, NY, USA) analysers were evaluated. Heparin plasma or serum could be used for both assays. Samples were stable for 24 h at ambient temperature, 3 days at 4-8 degrees C and 3 months at -20 degrees C. After 10 months' storage at -80 degrees C, the recoveries were well above 100% by both assays. Total coefficients of variation for Axsym assay were 9.0%, 5.8% and 5.3% at concentrations of 2.6 microg/l, 9.83 microg/l and 34.3 microg/l respectively; for Immuno 1 these were 4.4 %, 1.6% and 1.8% at 2.3 microg/l, 6.27 microg/l and 44.35 microg/l respectively. It was > or =20% at concentration of < or =0.5 microg/l for Axysm assay and < or =0.15 microg/l for Immuno 1 assay. Recoveries were < or =90% at < or =0.22 microg/l on Axsym and at < or =1.47 microg/l on Immuno 1. Neither method showed significant interference with haemoglobin, bilirubin, triglycerides or rheumatoid factor. Correlation between the two methods was excellent (r = 0.997, Y (Axsym) = 4.2X (Immuno 1) +3.2). The highest concentrations detected in 50 healthy subjects were 0.3 microg/l and 0.1 microg/l by Axsym and Immuno 1 methods, respectively. Twelve out of 43 renal failure patients had troponin I 0.13-0.9 microg/l using Axsym method and 4 had levels of 0.07-0.13 microg/l using Immuno 1. In muscle trauma patients, troponin I was undetectable.