Real-time nanoscale organization of amyloid precursor protein.

Despite an intuitive understanding of the role of APP in health and disease, there exist few attempts to dissect its molecular localization at excitatory synapses. Though the biochemistry involved in the enzymatic processing of APP is well understood, there is a void in understanding the nonuniformity of the product formation in vivo. Here, we employed multiple paradigms of single molecules and ensemble based nanoscopic imaging to reveal that APP molecules are organized into regulatory nanodomains that are differentially compartmentalized in the functional zones of an excitatory synapse. Furthermore, with the aid of high density single particle tracking, we show that the lateral diffusion of APP in live cells dictates an equilibrium between these nanodomains and their nano-environment, which is affected in a detrimental variant of APP. Additionally, we incorporate this spatio-temporal detail 'in silico' to generate a realistic nanoscale topography of APP in dendrites and synapses. This approach uncovers a nanoscale heterogeneity in the molecular organization of APP, depicting a locus for differential APP processing. This holistic paradigm, to decipher the real-time heterogeneity of the substrate molecules on the nanoscale, could enable us to better evaluate the molecular constraints overcoming the ensemble approaches used traditionally to understand the kinetics of product formation.

Cultural, ethical, and spiritual competencies of health care providers responding to a catastrophic event.

Compassion is a language that is understood across cultures, religions, and nations. Being compassionate and empathetic is a basic responsibility of health care providers responding to disasters. Compassion and empathy cannot be operationalized unless providers show culturally competent, ethically right, and spiritually caring behavior. In addition to being accepting of cultures other than their own, providers must read literature and familiarize themselves with the predominant cultures of the affected population. Ethically right decision making is essentially an act of balancing the risks and benefits to the entire society. Spiritual care is an important dimension of total health, and therefore recognition and resolution of the spiritual needs of disaster victims is an essential role of health care providers. Disaster management is teamwork and therefore requires that health care providers draw on the expertise and support of other team members; coordinating efforts with local religious, social governmental organizations, and NGOs to deal with the intangible effects of the cultural and spiritual impact of a disaster and to prevent further demoralization of the affected community is imperative. Disasters occur, and the only thing that can ameliorate their devastating effects is to improve disaster preparedness and respond collectively and courageously to every catastrophic event.