Diagnosis of toxic shock syndrome by two different systems; clinical criteria and monitoring of TSST‐1‐reactive T cells

Two methods of TSS diagnosis were evaluated: comparison of symptoms with clinical criteria and monitoring for evidence of selective activation of Vβ2⁺ T cells by the causative toxin, TSS toxin‐1 (TSST‐1). Ten patients with acute and systemic febrile infections caused by Staphylococcus aureus were monitored for increase in TSST‐1‐reactive Vβ2⁺ T cells during their clinical courses. Nine of the ten patients were diagnosed with TSS based on evidence of selective activation of Vβ2⁺ T cells by TSST‐1; however, clinical symptoms met the clinical criteria for TSS in only six of these nine patients. In the remaining patient, clinical symptoms met the clinical criteria, but selective activation of Vβ2⁺ T cells was not observed. Time taken to reach the diagnosis of TSS could be significantly shortened by utilizing the findings from tracing Vβ2⁺ T cells. In vitro studies showed that TSST‐1‐ reactive T cells from TSS patients were anergic in the early phase of their illness. Examining selective activation of Vβ2⁺ T cells could be a useful tool to supplement clinical criteria for early diagnosis of TSS.     

Isocyanides Derived from α,α‐Disubstituted Amino Acids: Synthesis and Antifouling Activity Assessment

Herein, we contribute to the development of environmentally friendly antifoulants by synthesizing eighteen isocyanides derived from α,α‐disubstituted amino acids and evaluating their antifouling activity/toxicity against the cypris larvae of the Balanus amphitrite barnacle. Almost all isocyanides showed good antifouling activity without significant toxicity and exhibited EC₅₀ values of 0.07 – 7.30 μg/mL after 120‐h exposure. The lowest EC₅₀ values were observed for valine‐, methionine‐, and phenylalanine‐derived isocyanides, which achieved > 95% cypris larvae settlement inhibition at concentrations of less than 30 μg/mL without exhibiting significant toxicity. Thus, the prepared isocyanides should be useful for further research focused on the development of environmentally friendly antifouling agents.     

DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells

In addition to their well-known function in apoptosis, caspases are also important in several nonapoptotic processes. How caspase activity is restrained and shut down under such nonapoptotic conditions remains unknown. Here, we show that Drosophila melanogaster inhibitor of apoptosis protein 2 (DIAP2) controls the level of caspase activity in living cells. Animals that lack DIAP2 have higher levels of drICE activity. Although diap2-deficient cells remain viable, they are sensitized to apoptosis following treatment with sublethal doses of x-ray irradiation. We find that DIAP2 regulates the effector caspase drICE through a mechanism that resembles the one of the caspase inhibitor p35. As for p35, cleavage of DIAP2 is required for caspase inhibition. Our data suggest that DIAP2 forms a covalent adduct with the catalytic machinery of drICE. In addition, DIAP2 also requires a functional RING finger domain to block cell death and target drICE for ubiquitylation. Because DIAP2 efficiently interacts with drICE, our data suggest that DIAP2 controls drICE in its apoptotic and nonapoptotic roles.     

Differential Effects of the Proteasome Inhibitor NPI-0052 against Glioma Cells

Proteasome inhibitors are emerging as a new class of cancer therapeutics, and bortezomib has shown promise in the treatment of multiple myeloma and mantle cell lymphoma. However, bortezomib has failed to have an effect in preclinical models of glioma. NPI-0052 is a new generation of proteasome inhibitors with increased potency and strong inhibition of all three catalytic activities of the 26S proteasome. In this article, we test the antitumor efficacy of NPI-0052 against glioma, as a single agent and in combination with temozolomide and radiation using five different glioma lines. The intrinsic radiation sensitivities differed for all the lines and correlated with their PTEN expression status. In vitro, NPI-0052 showed a dose-dependent toxicity, and its combination with temozolomide resulted in radiosensitization of only the cell lines with a mutated p53. The effect of NPI-0052 as a single agent on glioma xenografts in vivo was only modest in controlling tumor growth, and it failed to radiosensitize the glioma xenografts to fractionated radiation. We conclude that NPI-0052 is not a suitable drug for the treatment of malignant gliomas despite its efficacy in other cancer types.     

Oral health‐related quality of life and nutritional status of institutionalized elderly population aged 60 years and above in Mysore City,India

doi: 10.1111/j.1741‐2358.2012.00651.x Oral health‐related quality of life and nutritional status of institutionalized elderly population aged 60 years and above in Mysore City, India Objective: To assess whether oral health–related quality of life (OHRQoL) is associated with nutritional status in the institutionalised elderly population of Mysore. Background: Malnutrition in the elderly has an evident impact on their general health and quality of life. Analysis of data of the Geriatric Oral Health Assessment Index (GOHAI) and their association with the Mini Nutritional Assessment (MNA) results improves our understanding of the complex relationship between oral health and malnutrition. Materials and methods: The study was conducted among the institutionalised elderly population in Mysore city, Karnataka. Data on socio‐demographic, oral health status were gathered. OHRQoL was evaluated using GOHAI, and malnutrition risk using MNA. Results: Out of 141 elderly, 41.1% were men and 58.9% were women with mean age of 72.2 ± 7.5 years. Mean GOHAI score was 47.03 ± 9.2, with 69.5% had low perception of oral health. Mean MNA score was 9.91 ± 2.4, 15.6% were malnourished, 52.5% were at risk of malnutrition and 31.9% were adequately nourished. A strong association was found between the mean GOHAI and MNA scores. Conclusion: Oral health–related quality of life was associated with nutritional deficit, and it requires a greater integration between dentistry and nutrition in the health promotion of older adults.     

Nonapoptotic functions of caspases: caspases as regulatory molecules for immunity and cell-fate determination

Caspases are a family of cysteine proteases that are highly conserved in multicellular organisms and function as central regulators of apoptosis. Recent investigations in Caenorhabditis elegans, Drosophila and mice suggest that caspases also function as regulatory molecules for immunity and cell-fate determination. Here, we review genetic studies of nonapoptotic functions of caspases and discuss the regulatory mechanisms of caspases for executing nonapoptotic functions.     

Molecular mapping of movement-associated areas in the avian brain: a motor theory for vocal learning origin

Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor pathway that controls movement.