The contribution of backbone hydrogen bonds in alpha-helices to the overall stability of a protein has been examined experimentally by replacing several backbone amide linkages in alpha-helix 39-50 of T4 lysozyme with ester linkages. T4 lysozyme variants wherein the backbone amide bonds between residues Ser38 and Leu39, Lys43 and Leu44, or Ala49 and Ile50 are replaced with ester bonds were generated by incorporating alpha-hydroxy acids at positions 39, 44, or 50, respectively, using unnatural amino acid mutagenesis. The stabilities of the proteins were determined from their thermal denaturation curves as monitored by circular dichroism. Comparison of the thermal stabilities of the amide- and ester-containing proteins shows that the ester substitution has a similar thermodynamic effect at all three positions. At the N- and C-terminal positions, where only one hydrogen-bonding interaction is perturbed, the ester substitution is destabilizing by 0.9 and 0.7 kcal/mol, respectively. Introduction of the ester linkage in the middle of the helix, which alters two hydrogen-bonding interactions, destabilizes the protein by 1.7 kcal/mol. The values obtained from these ester to amide mutations are compared to the values from similar mutations that have been made in other secondary structures and bimolecular complexes.

Background: In psychiatry, stigma is an attitude of disapproval towards people with mental illnesses. Psychiatric disorders are common in Asia but some Asians receive inadequate treatment. Previous review found that Asians with mental illness were perceived to be dangerous and aggressive. There is a need for renewed efforts to understand stigma and strategies which can effectively reduce stigma in specific Asian societies. The objective of this systematic review was to provide an up-to-date overview of existing research and status on stigma experienced by psychiatric patients and anti-stigma campaigns in China, Hong Kong, Japan, Singapore, Korea, and Thailand. Methods: A systematic literature search was conducted in the following databases, including PubMed, PsycINFO, Embase, Web of Science, and local databases. Studies published in English and the official language of included countries/territories were considered for inclusion in the systematic review. Any article on stigma related to any form of psychiatric illness in the six Asian societies was included. Results: One hundred and twenty-three articles were included for this systematic review. This review has six major findings. Firstly, Asians with mental illnesses were considered as dangerous and aggressive, especially patients suffering from schizophrenia and bipolar disorder; second, psychiatric illnesses in Asian societies were less socially-acceptable and were viewed as being personal weaknesses; third, stigma experienced by family members was pervasive and this is known as family stigma; fourth, this systemic review reported more initiatives to handle stigma in Asian societies than a decade ago; fifth, there have been initiatives to treat psychiatric patients in the community; and sixth, the role of supernatural and religious approaches to psychiatric illness was not prevailing. Conclusion: This systematic review provides an overview of the available scientific evidence that points to areas of needed intervention to reduce and ultimately eliminate inequities in mental health in Asia.

Many genes elicit their actions through their expression in precise spatial patterns in tissues. Photoregulated expression systems offer a means to remotely pattern gene expression in tissues. Using currently available photopatterning methods, gene expression is only transient. Herein is described a general method to permanently alter a cell's genome under the control of light. The photocaged estrogen receptor (ER) antagonists, nitroveratryl-hydroxytamoxifen (Nv-HTam) and nitroveratryl-hydroxytamoxifen aziridine (Nv-HTaz), mediate exposure-dependent recombination in cells expressing the Cre-ER, a fusion of the site-specific recombinase Cre and ER. Both Nv-HTam and Nv-HTaz only activate recombination by Cre-ER after exposure to light. When released only intracellularly, the covalent-modifying Taz can mediate significant amounts of recombination in an exposure-dependent manner. Nv-HTaz and Cre-ER represent perhaps the first compound that can be used to photopattern gene expression through recombination.

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