A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

The Faces in Infant-Perspective Scenes Change over the First Year of Life

Mature face perception has its origins in the face experiences of infants. However, little is known about the basic statistics of faces in early visual environments. We used head cameras to capture and analyze over 72,000 infant-perspective scenes from 22 infants aged 1-11 months as they engaged in daily activities. The frequency of faces in these scenes declined markedly with age: for the youngest infants, faces were present 15 minutes in every waking hour but only 5 minutes for the oldest infants. In general, the available faces were well characterized by three properties: (1) they belonged to relatively few individuals; (2) they were close and visually large; and (3) they presented views showing both eyes. These three properties most strongly characterized the face corpora of our youngest infants and constitute environmental constraints on the early development of the visual system

The burden of co-existing dermatological disorders and their tendency of being overlooked among patients admitted to muhimbili national hospital in Dar es Salaam, Tanzania

\ud Skin diseases are underestimated and overlooked by most clinicians despite being common in clinical practice. Many patients are hospitalized with co-existing dermatological conditions which may not be detected and managed by the attending physicians. The objective of this study was to determine the burden of co-existing and overlooked dermatological disorders among patients admitted to medical wards of Muhimbili National hospital in Dar es Salaam. A hospital-based descriptive cross-sectional study conducted at Muhimbili National hospital in Dar es Salaam, Tanzania. Patients were consecutively recruited from the medical wards. Detailed interview to obtain clinico-demographic characteristics was followed by a complete physical examination. Dermatological diagnoses were made mainly clinically. Appropriate confirmatory laboratory investigations were performed where necessary. Data was analyzed using the 'Statistical Package for Social Sciences' (SPSS) program version 10.0. A p-value of < 0.5 was statistically significant. Three hundred and ninety patients admitted to medical wards were enrolled into the study of whom, 221(56.7%) were females. The mean age was 36.7 ± 17.9 (range 7-84 years). Overall, 232/390 patients (59.5%) had co-existing dermatological disorders with 49% (191/390) having one, 9% (36/390) two and 5 patients (1%) three. A wide range of co-existing skin diseases was encountered, the most diverse being non-infectious conditions which together accounted for 36.4% (142/390) while infectious dermatoses accounted for 31.5% (123/390). The leading infectious skin diseases were superficial fungal infections accounting for 18%. Pruritic papular eruption of HIV/AIDS (PPE) and seborrheic eczema were the most common non-infectious conditions, each accounting for 4.3%. Of the 232/390 patients with dermatological disorders, 191/232 (82.3%) and 154/232 (66.3%) had been overlooked by their referring and admitting doctors respectively. Dermatological disorders are common among patients admitted to medical wards and many are not detected by their referring or admitting physicians. Basic dermatological education should be emphasized to improve knowledge and awareness among clinicians.\u

The Nature of Abstract Orthographic Codes: Evidence from Masked Priming and Magnetoencephalography

What kind of mental objects are letters? Research on letter perception has mainly focussed on the visual properties of letters, showing that orthographic representations are abstract and size/shape invariant. But given that letters are, by definition, mappings between symbols and sounds, what is the role of sound in orthographic representation? We present two experiments suggesting that letters are fundamentally sound-based representations. To examine the role of sound in orthographic representation, we took advantage of the multiple scripts of Japanese. We show two types of evidence that if a Japanese word is presented in a script it never appears in, this presentation immediately activates the (“actual”) visual word form of that lexical item. First, equal amounts of masked repetition priming are observed for full repetition and when the prime appears in an atypical script. Second, visual word form frequency affects neuromagnetic measures already at 100–130 ms whether the word is presented in its conventional script or in a script it never otherwise appears in. This suggests that Japanese orthographic codes are not only shape-invariant, but also script invariant. The finding that two characters belonging to different writing systems can activate the same form representation suggests that sound identity is what determines orthographic identity: as long as two symbols express the same sound, our minds represent them as part of the same character/letter

Identification of a Novel Class of Farnesylation Targets by Structure-Based Modeling of Binding Specificity

Farnesylation is an important post-translational modification catalyzed by farnesyltransferase (FTase). Until recently it was believed that a C-terminal CaaX motif is required for farnesylation, but recent experiments have revealed larger substrate diversity. In this study, we propose a general structural modeling scheme to account for peptide binding specificity and recapitulate the experimentally derived selectivity profile of FTase in vitro. In addition to highly accurate recovery of known FTase targets, we also identify a range of novel potential targets in the human genome, including a new substrate class with an acidic C-terminal residue (CxxD/E). In vitro experiments verified farnesylation of 26/29 tested peptides, including both novel human targets, as well as peptides predicted to tightly bind FTase. This study extends the putative range of biological farnesylation substrates. Moreover, it suggests that the ability of a peptide to bind FTase is a main determinant for the farnesylation reaction. Finally, simple adaptation of our approach can contribute to more accurate and complete elucidation of peptide-mediated interactions and modifications in the cell

Reductions in co-contraction following neuromuscular re-education in people with knee osteoarthritis

Background Both increased knee muscle co-contraction and alterations in central pain processing have been suggested to play a role in knee osteoarthritis pain. However, current interventions do not target either of these mechanisms. The Alexander Technique provides neuromuscular re-education and may also influence anticipation of pain. This study therefore sought to investigate the potential clinical effectiveness of the AT intervention in the management of knee osteoarthritis and also to identify a possible mechanism of action. Methods A cohort of 21 participants with confirmed knee osteoarthritis were given 20 lessons of instruction in the Alexander Technique. In addition to clinical outcomes EMG data, quantifying knee muscle co-contraction and EEG data, characterising brain activity during anticipation of pain, were collected. All data were compared between baseline and post-intervention time points with a further 15-month clinical follow up. In addition, biomechanical data were collected from a healthy control group and compared with the data from the osteoarthritis subjects. Results: Following AT instruction the mean WOMAC pain score reduced by 56% from 9.6 to 4.2 (P<0.01) and this reduction was maintained at 15 month follow up. There was a clear decrease in medial co-contraction at the end of the intervention, towards the levels observed in the healthy control group, both during a pre-contact phase of gait (p<0.05) and during early stance (p<0.01). However, no changes in pain-anticipatory brain activity were observed. Interestingly, decreases in WOMAC pain were associated with reductions in medial co-contraction during the pre-contact phase of gait. Conclusions: This is the first study to investigate the potential effectiveness of an intervention aimed at increasing awareness of muscle behaviour in the clinical management of knee osteoarthritis. These data suggest a complex relationship between muscle contraction, joint loading and pain and support the idea that excessive muscle co-contraction may be a maladaptive response in this patient group. Furthermore, these data provide evidence that, if the activation of certain muscles can be reduced during gait, this may lead to positive long-term clinical outcomes. This finding challenges clinical management models of knee osteoarthritis which focus primarily on muscle strengthening

Essential function for ErbB3 in breast cancer proliferation

The overexpression of the ErbB family of tyrosine kinase receptors is thought to be important in the development of many breast tumours. To date, most attention has focused on the ErbB2 receptor. Now, in a recent report, it has been shown that ErbB3 is a critical partner for the transforming activity of ErbB2 in breast cancer cells. Importantly, the proliferative signals from this transforming complex appear to act via the PI-3 kinase pathway