Incomplete protein packing as a selectivity filter in drug design

The conservation of structure across paralog proteins promotes alternative protein-ligand associations often leading to side effects in drug-based inhibition. However, sticky packing defects are typically not conserved across paralogs, making them suitable targets to reduce drug toxicity. This observation enables a strategy for the design of highly specific inhibitors involving ligands that wrap nonconserved packing defects. The selectivity of these inhibitors is evidenced in affinity assays on a cancer-related pharmacokinome: a powerful inhibitor is redesigned by using the wrapping technology to enhance its selectivity and affinity for a target kinase. In this way, the packing defects of a soluble protein may be used as selectivity filters for drug design.     

Artemisinin(Qinghaosu): a mesmerizing drug that still puzzles

<正>The awarding of the 2015 Nobel Prize to Chinese scientist You You Tu created quite a stir in the media and scientific community.This award is the first Nobel Prize in natural     

CpG still rocks! Update on an accidental drug

The discovery of the CpG motif in 1995 led to a change in the perception of the immune stimulatory effects of oligodeoxynucleotides (ODN) from an unwanted nonspecific effect to a highly evolved immune defense that can be selectively triggered for a wide range of therapeutic applications. Over the last decade dozens of human clinical trials have been conducted with different CpG ODN in thousands of humans for applications ranging from vaccine adjuvant to immunotherapies for allergy, cancer, and infectious diseases. Along with many positive results have come some failures showing the limitations of several therapeutic approaches. This review summarizes these results to provide an overview of the clinical development of CpG ODN.     

Interfacing a flow cytometer computer with a PC-based patient information system

We have established an interface between our flow cytometer's computer and the personal computer (PC) which supports our patient database system. The PC has been equipped with a commercially available IEEE-488 bus interface board which is connected to the interface bus of the cytometer's Hewlett-Packard 9000/300 computer (HP). The PC is set as a bus device with the same address as that of the HP's printer. It is programmed to examine the stream of data sent to the printer and extract from it and store in an MS-DOS text file selected information which subsequently may be transferred to the database system.     

Doctors and drug companies: still cozy after all these years

Geoff Spurling and colleagues report findings of a systematic review looking at the relationship between exposure to promotional material from pharmaceutical companies and the quality, quantity, and cost of prescribing. They fail to find evidence of improvements in prescribing after exposure, and find some evidence of an association with higher prescribing frequency, higher costs, or lower prescribing quality.     

Saskatchewan dial-access drug information service.

In September 1974 the colleges of pharmacy and medicine of the University of Saskatchewan began offering a drug information service to the pharmacists and physicians of Saskatchewan without charge. With the help of a radio-page system, calls are taken immediately by experienced pharmacists and pharmacologists. The cost of long-distance phone calls is borne by grants from the Saskatchewan medical and pharmaceutical associations. During the 1st year of operation 415 requests for information were received. Of 93 persons who called up to Feb. 28, 1975, 76% responded to an evaluation questionnaire; virtually all described the service as very valuable. The information received resulted in the alteration of drug therapy in one third of calls requesting information to assist in current treatment of a patient.     

More taxa,more characters: the hoatzin problem is still unresolved

The apparently rapid and ancient diversification of many avian orders complicates the resolution of their relationships using molecular data. Recent studies based on complete mitochondrial DNA (mtDNA) sequences or shorter lengths of nuclear sequence have helped corroborate the basic structure of the avian tree (e.g., a basal split between Paleognathae and Neognathae) but have made relatively little progress in resolving relationships among the many orders within Neoaves. We explored the potential of a moderately sized mtDNA data set ( approximately 5000 bp for each of 41 taxa), supplemented with data from a nuclear intron ( approximately 700 bp per taxon), to resolve relationships among avian orders. Our sampling of taxa addresses two issues: (1). the sister relationship and monophyly, respectively, of Anseriformes and Galliformes and (2). relationships of the enigmatic hoatzin Opisthocomus hoazin. Our analyses support a basal split between Galloanserae and Neoaves within Neognathae and monophyly of both Galliformes and Anseriformes. Within Galliformes, megapodes and then cracids branch basally. Within Anseriformes, mitochondrial data support a screamer (Anhimidae) plus magpie goose (Anseranatidae) clade. This result, however, may be an artifact of divergent base composition in one of the two anatids we sampled. With deletion of the latter taxon, Anseranas is sister to anatids as in traditional arrangements and recent morphological studies. Although our data provide limited resolution of relationships within Neoaves, we find no support for a sister relationship between either cuckoos (Cuculiformes) or turacos (Musophagiformes) and hoatzin. Both mitochondrial and nuclear data are consistent with a relationship between hoatzin and doves (Columbiformes), although this result is weakly supported. We also show that mtDNA sequences reported in another recent study included pervasive errors that biased the analysis towards finding a sister relationship between hoatzin and turacos.     

Neural information and the problem of objectivity

A fascinating research program in neurophysiology attempts to quantify the amount of information transmitted by single neurons. The claims that emerge from this research raise new philosophical questions about the nature of information. What kind of information is being quantified? Do the resulting quantities describe empirical magnitudes like those found elsewhere in the natural sciences? In this article, it is argued that neural information quantities have a relativisitic character that makes them distinct from the kinds of information typically discussed in the philosophical literature. It is also argued that despite this relativistic character, there are cases in which neural information quantities can be viewed as robustly objective empirical properties.