Effect of vaccinations with recombinant fusion proteins on Ancylostoma caninum habitat selection in the canine intestine

Laboratory dogs were vaccinated subcutaneously with 3 different recombinant fusion proteins, each precipitated with alum or calcium phosphate. The vaccinated dogs were then challenged orally with 400 third-stage infective larvae (L3) of the canine hookworm, Ancylostoma caninum. The 3 A. caninum antigens selected were Ac-TMP, an adult-specific secreted tissue inhibitor of metalloproteases; Ac-AP, an adult-specific secreted factor Xa serine protease inhibitor anticoagulant; and Ac-ARR-1, a cathepsin D-like aspartic protease. Each of the 3 groups comprised 6 male beagles (8 +/- 1 wk of age). A fourth group comprised control dogs injected with alum. All of the dogs vaccinated with Ac-TMP or Ac-APR-1 exhibited a vigorous antigen-specific antibody response, whereas only a single dog vaccinated with Ac-AP developed an antibody response. Dogs with circulating antibody responses exhibited 4.5-18% reduction in the numbers of adult hookworms recovered from the small intestines at necropsy, relative to alum-injected dogs. In contrast, there was a concomitant increase in the number of adult hookworms recovered from the colon. The increase in colonic hookworms was as high as 500%, relative to alum-injected dogs. Female adult hookworms were more likely to migrate into the colon than were males. Anti-enzyme and anti-enzyme inhibitor antibodies correlated with an alteration in adult hookworm habitat selection in the canine gastroinntestinal tract.     

Modelling the protective efficacy of alternative delivery schedules for intermittent preventive treatment of malaria in infants and children

Background

Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is recommended by WHO where malaria incidence in infancy is high and SP resistance is low. The current delivery strategy is via routine Expanded Program on Immunisation contacts during infancy (EPI-IPTi). However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy.

Methods and Findings

A mathematical model was developed to estimate the protective efficacy (PE) of IPT against clinical malaria in children aged 2-24 months, using entomological and epidemiological data from an EPI-IPTi trial in Navrongo, Ghana to parameterise the model. The protection achieved by seasonally-targeted IPT in infants (sIPTi), seasonal IPT in children (sIPTc), and by case-management with long-acting artemisinin combination therapies (LA-ACTs) was predicted for Navrongo and for sites with different transmission intensity and seasonality. In Navrongo, the predicted PE of sIPTi was 26% by 24 months of age, compared to 16% with EPI-IPTi. sIPTc given to all children under 2 years would provide PE of 52% by 24 months of age. Seasonally-targeted IPT retained its advantages in a range of transmission patterns. Under certain circumstances, LA-ACTs for case-management may provide similar protection to EPI-IPTi. However, EPI-IPTi or sIPT combined with LA-ACTs would be substantially more protective than either strategy used alone.

Conclusion

Delivery of IPT to infants via the EPI is sub-optimal because individuals are not protected by IPT at the time of highest malaria risk, and because older children are not protected. Alternative delivery strategies to the EPI are needed where transmission varies seasonally or the malaria burden extends beyond infancy. Long-acting ACTs may also make important reductions in malaria incidence. However, delivery systems must be developed to ensure that both forms of chemoprevention reach the individuals who are most exposed to malaria.     

Microbial communities colonising nutrient-enriched marine sediment

Sediment cores were set up to study microbial colonisation and interactions on marine sand grains under enrichment conditions. Cores were enriched with photosynthetic media in the light and dark (PL, PD) and heterotrophic media in the light and dark (HL, HD), and were incubated for 25 days. Sediment chlorophylls were then measured by acetone extraction, viable heterotrophic bacteria by plate counts, and numbers of cells mm^–2 sand grain surface by s.e.m. Chlorophyll a occurred in all sediments but was highest in the PL sediment. Bacteriochlorophyll a was only observed in the HL sediment. Heterotrophic viable counts were high in the HL and HD sediments. Dense growth of diatoms and blue-green algae, and a marine fungal Thraustochytrid sp. occurred on PL grains. The blue-green alga Schizothrix was often associated with the diatom Amphora on PL grains. Many different bacteria grew on HL and HD grains and some unusual colony and cell morphologies were recorded (Caulobacter, Flexibacter, polymer strands). Characteristic flakey material sometimes occurred in hollows on grains. The results are discussed in relation to microbial communities in low energy sedimentary environments.     

Anopheles culicifacies giles: Adult ecological parameters measured in rural punjab province,pakistan using capture-mark-release-recapture and dissection methods,with comparative observations onAn. stephensi liston andAn. subpictus grassi

Dispersal, immigration and emigration rates, horizontal and vertical survivorship and absolute population size were estimated for micropopulations of An. culicifacies, An. stephensi and An. subpictus at a series of cattle sheds in rural Punjab Province, Pakistan, during November 1979 and May 1980 using capture-mark-release-recapture and dissection methods. Dispersal was temperature-related, with populations more vagile during May. Mean dispersal distance per individual was low for all species. More than 70% of all recaptures were taken at the point of release and the longest detected flight was 1250 meters. Horizontal survivorship was greater during November and was always less than vertical survivorship calculated from dissection agegrading data. Survivorship during the nulliparous period was greater than survivorship throughout total life, indicating the survivorship curve may be slightly sigmoid. Daily population sizes of endemic and immigrating females and males were calculated usingBailey 's (1952) modification of the Lincoln Index, with the daily captures adjusted for immigration which was highest in May. Daily additions to the indoor resting population exclusive of immigrants were estimated using the method ofManly andParr (1968). The relationship of the present findings to malaria transmission and genetic control were discussed.     

Area 5 influences excitability within the primary motor cortex in humans

In non-human primates, Brodmann's area 5 (BA 5) has direct connectivity with primary motor cortex (M1), is largely dedicated to the representation of the hand and may have evolved with the ability to perform skilled hand movement. Less is known about human BA 5 and its interaction with M1 neural circuits related to hand control. The present study examines the influence of BA 5 on excitatory and inhibitory neural circuitry within M1 bilaterally before and after continuous (cTBS), intermittent (iTBS), and sham theta-burst stimulation (sham TBS) over left hemisphere BA 5. Using single and paired-pulse TMS, measurements of motor evoked potentials (MEPs), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were quantified for the representation of the first dorsal interosseous muscle. Results indicate that cTBS over BA 5 influences M1 excitability such that MEP amplitudes are increased bilaterally for up to one hour. ITBS over BA 5 results in an increase in MEP amplitude contralateral to stimulation with a delayed onset that persists up to one hour. SICI and ICF were unaltered following TBS over BA 5. Similarly, F-wave amplitude and latency were unaltered following cTBS over BA 5. The data suggest that BA 5 alters M1 output directed to the hand by influencing corticospinal neurons and not interneurons that mediate SICI or ICF circuitry. Targeting BA 5 via cTBS and iTBS is a novel mechanism to powerfully modulate activity within M1 and may provide an avenue for investigating hand control in healthy populations and modifying impaired hand function in clinical populations.     

Vibrational characteristics of bone fracture and fracture repair: application to excised rat femur

BACKGROUND: The vibrational characteristics of any object are directly dependent on the physical properties of that object. Therefore, changing the physical properties of an object will cause the object to adopt changed natural frequencies. A fracture in a bone results in the loss of mechanical stability of the bone. This change in mechanical properties of a bone should result in a change of the resonant frequencies of that bone. A vibrational method for bone evaluation has been introduced. METHOD OF APPROACH: This method uses the radiation force of focused amplitude-modulated ultrasound to exert a vibrating force directly, and remotely, on a bone. The vibration frequency is varied in the range of interest to induce resonances in the bone. The resulting bone motion is recorded and the resonance frequencies are determined. Experiments are conducted on excised rat femurs and resonance frequencies of intact, fractured, and bonded (simulating healed) bones are measured. RESULTS: The experiments demonstrate that changes in the resonance frequency are indicative of bone fracture and healing, i.e., the fractured bone exhibits a lower resonance frequency than the intact bone, and the resonance frequency of the bonded bone approaches that of the intact bone. CONCLUSION: It is concluded that the proposed radiation force method may be used as a remote and noninvasive tool for monitoring bone fracture and healing process, and the use of focused ultrasound enables one to selectively evaluate individual bones.     

Binding of antitumor antibiotic daunomycin to histones in chromatin and in solution

Daunomycin is an anticancer drug that is well-known to interact with DNA in chromatin. Using a compositionally defined chicken erythrocyte chromatin fraction, we have obtained conclusive evidence that the drug is also able to interact with chromatin-bound linker histones without any noticeable binding to core histones. The drug can interact in an equal fashion with both histone H1 and H5 and to a greater extent with core histones H3/H4 and H2A/H2B as free proteins in solution. Thus, the binding of daunomycin to linker histones in the chromatin fiber is most likely due to the well-known higher accessibility of these histones to the surrounding environment of the fiber. Binding of daunomycin to linker histones appears to primarily involve the trypsin-resistant (winged-helix) domain of these proteins. The studies described here reveal the occurrence of a previously undisclosed mechanism for the antitumor activity of anthracycline drugs at the chromatin level.