Plasmodium berghei MAPK1 displays differential and dynamic subcellular localizations during liver stage development

Mitogen-activated protein kinases (MAPKs) regulate key signaling events in eukaryotic cells. In the genomes of protozoan Plasmodium parasites, the causative agents of malaria, two genes encoding kinases with significant homology to other eukaryotic MAPKs have been identified (mapk1, mapk2). In this work, we show that both genes are transcribed during Plasmodium berghei liver stage development, and analyze expression and subcellular localization of the PbMAPK1 protein in liver stage parasites. Live cell imaging of transgenic parasites expressing GFP-tagged PbMAPK1 revealed a nuclear localization of PbMAPK1 in the early schizont stage mediated by nuclear localization signals in the C-terminal domain. In contrast, a distinct localization of PbMAPK1 in comma/ring-shaped structures in proximity to the parasite's nuclei and the invaginating parasite membrane was observed during the cytomere stage of parasite development as well as in immature blood stage schizonts. The PbMAPK1 localization was found to be independent of integrity of a motif putatively involved in ATP binding, integrity of the putative activation motif and the presence of a predicted coiled-coil domain in the C-terminal domain. Although PbMAPK1 knock out parasites showed normal liver stage development, the kinase may still fulfill a dual function in both schizogony and merogony of liver stage parasites regulated by its dynamic and stage-dependent subcellular localization.

Optimizing stereo-to-multiview conversion for autostereoscopic displays

We present a novel stereo-to-multiview video conversion method for glasses-free multiview displays. Different from previous stereo-to-multiview approaches, our mapping algorithm utilizes the limited depth range of autostereoscopic displays optimally and strives to preserve the scene's artistic composition and perceived depth even under strong depth compression. We first present an investigation of how perceived image quality relates to spatial frequency and disparity. The outcome of this study is utilized in a two-step mapping algorithm, where we (i) compress the scene depth using a non-linear global function to the depth range of an autostereoscopic display and (ii) enhance the depth gradients of salient objects to restore the perceived depth and salient scene structure. Finally, an adapted image domain warping algorithm is proposed to generate the multiview output, which enables overall disparity range extension.

Association between Head Injury and Helmet Use in Alpine Skiers: Cohort Study from a Swiss Level I Trauma Center.

The association between helmet use during alpine skiing and incidence and severity of head injuries was analyzed. All patients admitted to a level 1 trauma center for traumatic brain injuries (TBIs) sustained from skiing accidents during the seasons 2000-2001 and 2010-2011 were eligible. Primary outcome was the association between helmet use and severity of TBI measured by Glasgow Coma Scale (GCS), computed tomography (CT) results, and necessity of neurosurgical intervention. Of 1362 patients injured during alpine skiing, 245 (18%) sustained TBI and were included. TBI was fatal in 3%. Head injury was in 76% minor (Glasgow Coma Scale, 13-15), 6% moderate, and 14% severe. Number and percentage of TBI patients showed no significant trend over the investigated seasons. Forty-five percent of the 245 patients had pathological CT findings and 26% of these required neurosurgical intervention. Helmet use increased from 0% in 2000-2001 to 71% in 2010-2011 (p<0.001). The main analysis, comparing TBI in patients with or without a helmet, showed an adjusted odds ratio (OR) of 1.44 (p=0.430) for suffering moderate-to-severe head injury in helmet users. Analyses comparing off-piste to on-slope skiers revealed a significantly increased OR among off-piste skiers of 7.62 (p=0.004) for sustaining a TBI requiring surgical intervention. Despite increases in helmet use, we found no decrease in severe TBI among alpine skiers. Logistic regression analysis showed no significant difference in TBI with regard to helmet use, but increased risk for off-piste skiers. The limited protection of helmets and dangers of skiing off-piste should be targeted by prevention programs.

CXCL14 Displays Antimicrobial Activity against Respiratory Tract Bacteria and Contributes to Clearance of Streptococcus pneumoniae Pulmonary Infection

CXCL14 is a chemokine with an atypical, yet highly conserved, primary structure characterized by a short N terminus and high sequence identity between human and mouse. Although it induces chemotaxis of monocytic cells at high concentrations, its physiological role in leukocyte trafficking remains elusive. In contrast, several studies have demonstrated that CXCL14 is a broad-spectrum antimicrobial peptide that is expressed abundantly and constitutively in epithelial tissues. In this study, we further explored the antimicrobial properties of CXCL14 against respiratory pathogens in vitro and in vivo. We found that CXCL14 potently killed Pseudomonas aeruginosa, Streptococcus mitis, and Streptococcus pneumoniae in a dose-dependent manner in part through membrane depolarization and rupture. By performing structure-activity studies, we found that the activity against Gram-negative bacteria was largely associated with the N-terminal peptide CXCL141-13. Interestingly, the central part of the molecule representing the β-sheet also maintained ∼62% killing activity and was sufficient to induce chemotaxis of THP-1 cells. The C-terminal α-helix of CXCL14 had neither antimicrobial nor chemotactic effect. To investigate a physiological function for CXCL14 in innate immunity in vivo, we infected CXCL14-deficient mice with lung pathogens and we found that CXCL14 contributed to enhanced clearance of Streptococcus pneumoniae, but not Pseudomonas aeruginosa. Our comprehensive studies reflect the complex bactericidal mechanisms of CXCL14, and we propose that different structural features are relevant for the killing of Gram-negative and Gram-positive bacteria. Taken together, our studies show that evolutionary-conserved features of CXCL14 are important for constitutive antimicrobial defenses against pneumonia.

Cohort Study on the Association Between Helmet Use and Traumatic Brain Injury in Snowboarders From a Swiss Tertiary Trauma Center.

BACKGROUND Since the introduction of helmets in winter sports there is on-going debate on whether they decrease traumatic brain injuries (TBI). METHODS This cohort study included 117 adult (≥ 16 years) snowboarders with TBI admitted to a level I alpine trauma center in Switzerland between 2000/2001 and 2010/2011. The primary objective was to examine the association between helmet use and moderate-to-severe TBI. Secondary objectives were to describe the epidemiology of TBI during the past decade in relation to increased helmet use. RESULTS Of 691 injured snowboarders evaluated, 117 (17%) suffered TBI. Sixty-six percent were men (median age, 23 years). Two percent of accidents were fatal. Ninety-two percent of patients sustained minor, 1% moderate, and 7% severe TBI according to the Glasgow coma scale. Pathologic computed tomography findings were present in 16% of patients, 26% of which required surgery. Eighty-three percent of TBIs occurred while riding on-slope. There was no trend in the TBI rate during the studied period, although helmet use increased from 10% to 69%. Comparing patients with and without a helmet showed no significant difference in odds ratios for the severity of TBI. However, of the 5 patients requiring surgery only 1 was wearing a helmet. Off-piste compared with on-slope snowboarders showed an odds ratio of 26.5 (P = 0.003) for sustaining a moderate-to-severe TBI. CONCLUSIONS Despite increased helmet use we found no decrease in TBI among snowboarders. The possibility of TBI despite helmet use and the dangers of riding off-piste should be a focus of future prevention programs.

Comparing reading processes on e-ink displays and print

E-book reading devices open new possibilities in the field of reading. More activities than just reading a book can be performed with a single electronic device. For a long time, electronic reading devices have not been favored because their active LCD displays used to have a relatively low contrast. The new generation of electronic reading devices differs from earlier ones in the nature of the display: active LCD displays have been replaced with displays based on e-ink technology, which has display properties closer to that of printed paper. Moreover, e-ink technology has higher power efficiency, thereby increasing battery life and reducing weight. At first sight, the display looks similar to paper print, but the question remains whether the reading behavior also is equal to that of reading a printed book. In the present study, we analyzed and compared reading behavior on e-reader displays and on printed paper. The results suggest that the reading behavior on e-readers is indeed very similar to the reading behavior on print. Participants shared similar proportions of regressive saccades while reading on e-readers and print. Significant differences in fixation duration suggest that e-readers, in some situations, may even provide better legibility.