Cytoskeletal Signaling: Is Memory Encoded in Microtubule Lattices by CaMKII Phosphorylation?

Memory is attributed to strengthened synaptic connections among particular brain neurons, yet synaptic membrane components are transient, whereas memories can endure. This suggests synaptic information is encoded and ‘hard-wired’ elsewhere, e.g. at molecular levels within the post-synaptic neuron. In long-term potentiation (LTP), a cellular and molecular model for memory, post-synaptic calcium ion (Ca2+) flux activates the hexagonal Ca2+-calmodulin dependent kinase II (CaMKII), a dodacameric holoenzyme containing 2 hexagonal sets of 6 kinase domains. Each kinase domain can either phosphorylate substrate proteins, or not (i.e. encoding one bit). Thus each set of extended CaMKII kinases can potentially encode synaptic Ca2+ information via phosphorylation as ordered arrays of binary ‘bits’. Candidate sites for CaMKII phosphorylation-encoded molecular memory include microtubules (MTs), cylindrical organelles whose surfaces represent a regular lattice with a pattern of hexagonal polymers of the protein tubulin. Using molecular mechanics modeling and electrostatic profiling, we find that spatial dimensions and geometry of the extended CaMKII kinase domains precisely match those of MT hexagonal lattices. This suggests sets of six CaMKII kinase domains phosphorylate hexagonal MT lattice neighborhoods collectively, e.g. conveying synaptic information as ordered arrays of six “bits”, and thus “bytes”, with 64 to 5,281 possible bit states per CaMKII-MT byte. Signaling and encoding in MTs and other cytoskeletal structures offer rapid, robust solid-state information processing which may reflect a general code for MT-based memory and information processing within neurons and other eukaryotic cells

Can antibiotic prescriptions in respiratory tract infections be improved? A cluster-randomized educational intervention in general practice – The Prescription Peer Academic Detailing (Rx-PAD) Study [NCT00272155]

BACKGROUND: More than half of all antibiotic prescriptions in general practice are issued for respiratory tract infections (RTIs), despite convincing evidence that many of these infections are caused by viruses. Frequent misuse of antimicrobial agents is of great global health concern, as we face an emerging worldwide threat of bacterial antibiotic resistance. There is an increasing need to identify determinants and patterns of antibiotic prescribing, in order to identify where clinical practice can be improved. METHODS/DESIGN: Approximately 80 peer continuing medical education (CME) groups in southern Norway will be recruited to a cluster randomized trial. Participating groups will be randomized either to an intervention- or a control group. A multifaceted intervention has been tailored, where key components are educational outreach visits to the CME-groups, work-shops, audit and feedback. Prescription Peer Academic Detailers (Rx-PADs), who are trained GPs, will conduct the educational outreach visits. During these visits, evidence-based recommendations of antibiotic prescriptions for RTIs will be presented and software will be handed out for installation in participants PCs, enabling collection of prescription data. These data will subsequently be linked to corresponding data from the Norwegian Prescription Database (NorPD). Individual feedback reports will be sent all participating GPs during and one year after the intervention. Main outcomes are baseline proportion of inappropriate antibiotic prescriptions for RTIs and change in prescription patterns compared to baseline one year after the initiation of the tailored pedagogic intervention. DISCUSSION: Improvement of prescription patterns in medical practice is a challenging task. A thorough evaluation of guidelines for antibiotic treatment in RTIs may impose important benefits, whereas inappropriate prescribing entails substantial costs, as well as undesirable consequences like development of antibiotic resistance. Our hypothesis is that an educational intervention program will be effective in improving prescription patterns by reducing the total number of antibiotic prescriptions, as well as reducing the amount of broad-spectrum antibiotics, with special emphasis on macrolides

Rancher Use of Compound 1080 Toxic Collars in New Mexico

Twenty-three ranchers were trained and certified to use Compound 1080 in toxic collars to control coyote ( Ca nts l a tran s predation on sheep during a 2-year experimental program conducted by the New Mexico Department of Agriculture. Fifteen ranchers employed a total of 330 collars in field use. Two used collars in preventive control schemes and success was unknown. Thirteen used collars in corrective control (i.e. predation was in progress); 6 had collared lambs attacked and killed by coyotes; 4 had 1 or more collars punctured by coyotes and in 1 case a bobcat; 3 solved specific coyote problems that they were unable to solve by other means. Although punctured collars were not recovered for verification, 2 other ranchers were believed to have stopped killer coyotes based on circumstantial evidence. Two ranchers were found to be in violation of use restrictions during the 2-year program. One was dropped from the program and the other was reprimanded and found in compliance upon subsequent inspection. One nontarget animal, a skunk (M ephitis m e phitis), was discovered that my have died from scavenging on a collared lamb carcass. Problems encountered by ranchers in using collars included restrictions against using collars on federal land and lack of suitable areas to keep main flocks of sheep while collared target flocks were in use. Conclusions drawn from the experimental program were: (1) ranchers can be expected to safely use 1080 in toxic collars; (2) some ranchers will not be successful in using collars; however, others will be able to solve certain coyote predation problems they are unable to solve by other means; (3) some violations of use restrictions may occur; however, they likely will be infrequent

Cougar Predation on Livestock in New Mexico, January 1983 Through June 1984

A telephone survey was conducted in which the objective was to obtain information from the entire population of livestock producers in New Mexico who had losses to cougars (Felis concolor) in 1983 and the first six months of 1984. A total of 103 ranchers reported losses in 1983 and 60 reported losses in the first six months of 1984. Verified (by examination of kills) losses of sheep and lambs to cougars totaled 1,202 in 1983 and 525 in the first half of 1984. Verified losses of cattle and calves totaled 230 in 1983 and 102 in the first half of 1984. Suspected losses (not verified) of sheep and cattle were similar in number to verified losses. Other verified livestock losses reported were 3 goats and 4 colts in 1983, and 25 goats and 2 colts in the first half of 1984. The value of reported losses to cougars in 1983 was at least $125,000 (producer-verified losses) and may have been as much as$220,000 (when suspected losses are included. The data suggested statewide cougar predation losses are substantially underrepresented by the passive reporting system used by the New Mexico Department of Game and Fish (NMDGF). Respondents reported a total of 217 cougars that were taken to control predation on livestock in the 18 months covered by the survey; 49% were reportedly taken on sport hunting tags suggesting that sport hunting has been a major method used by ranchers to address cougar predation problems

AN EVALUATION OF ROOST DISPERSAL FOR REDUCING CORMORANT ACTIVITY ON CATFISH PONDS

Pyrotechnics and helicopter fly overs were used to harass double-crested cormorants (Phalacrocorax auritus) at 4 roost sites in the Delta region of Mississippi. Roosting cormorants were easily dispersed from 3 of the 4 sites. Average numbers of cormorants observed at selected catfish (Ictaluridae) ponds and day roosts near foraging areas also declined after harassment began

PRIVATE COSTS OF PREDATOR CONTROL IN NEW MEXICO IN 1983

A survey was conducted by the New Mexico Department of Agriculture in early 1984 to determine costs incurred by livestock producers to control predation on livestock during 1983. Out of a sample of 1,848 producers who were sent questionnaires, 706 (38%) usable responses were returned. The respondents reported having about 30% of the peak number of sheep and lambs and 19% of the peak number of range beef cattle and calves, respectively, estimated to have been in New Mexico in 1983. Total cost reported by 306 respondents who had costs, not including donations to the New Mexico cooperative Animal Damage Control program, was about $450,000. Trapping (including the use of traps, snares, and M-44 devices) accounted for 38$1.8 million. Adding this estimate to the total estimated value of sheep and cattle lost to predation brought the total economic impact of predation on the livestock industry in New Mexico in 1983 to $5.3 million. The data suggested private predator control costs are approximately one-third of the economic impact of predation on livestock producers