cDNAs encoding 2 Ancylostoma-secreted proteins (ASPs), Ancylostoma ceylanicum (Ay)-ASP-1 and Ay-ASP-2, were cloned from infective third-stage larvae (L3) of the hookworm A. ceylanicum and were ...expressed as soluble recombinant fusion proteins secreted by the yeast Pichia pastoris. The recombinant fusion proteins were purified, adjuvant formulated, and injected intramuscularly into hamsters. Hamsters vaccinated either by oral vaccination with irradiated L3 (irL3) or by injections of the adjuvants alone served as positive and negative controls, respectively. Anti-ASP-1 and anti-ASP-2 antibody titers exceeded 1:100,000. Each vaccinated hamster was challenged orally with 100 L3. Two groups of vaccinated hamsters (i.e., those vaccinated with either irL3 or ASP-2 formulated with Quil A) exhibited significant reductions in adult hookworm burdens, compared with control hamsters. The hookworms recovered from the hamsters vaccinated with ASP-2 plus Quil A were reduced in length. Splenomegaly, which was observed in control hamsters, was not seen in hamsters vaccinated with either irL3 or ASP-2 formulated with Quil A. These results indicate that ASP-2 is a promising molecule for the development of a hookworm vaccine.
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The idea that memory is encoded by means of synaptic growth is not new. However, this idea has been difficult to demonstrate in the mammalian brain because of both the complexity of mammalian ...behavior and the neural circuitry by which it is supported. Here we examine how eyeblink classical conditioning affects synapse number within the cerebellum; the brain region essential for long-term retention of the conditioned response. Results showed eyeblink-conditioned rats to have significantly more synapses per neuron within the cerebellar interpositus nucleus than both explicitly unpaired and untrained controls. Further analysis showed that the increase was caused by the addition of excitatory rather than inhibitory synapses. Thus, development of the conditioned eyeblink response is associated with a strengthening of inputs from precerebellar nuclei rather than from cerebellar cortex. These results demonstrate that the modifications of specific neural pathways by means of synaptogenesis contributes to formation of a specific memory within the mammalian brain.
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Zook, B. C. and Simmens, S. J. The Effects of 860 MHz Radiofrequency Radiation on the Induction or Promotion of Brain Tumors and Other Neoplasms in Rats. Sprague-Dawley rats were irradiated with a ...continuous- wave (CW) or a pulsed-wave (P) radiofrequency (RF) for 6 h/day, 5 days/week from 2 up to 24 months of age. The RFs emanated from dipole antennas (1 W average output) 2.0 ± 0.5 cm from the tip of each rat's nose. The RFs had an 860 MHz frequency, and the specific absorption rate was 1.0 W/ kg averaged over the brain. Fifteen groups of 60 rats (900 total) were formed from offspring of females injected i.v. with 0 (groups 1, 2, 9, 10, 13), 2.5 (groups 5, 6, 7, 8, 11, 12, 14) or 10 mg/kg (groups 3, 4, 15) ethylnitrosourea (ENU) to induce brain tumors. Groups 1, 3, 5 and 7 received the PRF, and groups 9 and 11 the CWRF; groups 2, 4, 6, 8, 10 and 12 were sham-irradiated, and groups 13–15 were cage controls. All rats but 2, totaling 898, were necropsied, and major tissues were studied histopathologically. There was no statistically significant evidence that the PRF or CWRF induced neoplasia in any tissues. Additionally, there was no significant evidence of promotion of cranial or spinal nerve or spinal cord tumors. The PRF or CWRF had no statistically significant effect on the number, volume, location, multiplicity, histological type, malignancy or fatality of brain tumors. There was a trend for the group that received a high dose of ENU and was exposed to the PRF to develop fatal brain tumors at a higher rate than its sham group; however, the result was not significant using the log-rank test (P = 0.14, 2-tailed). No statistically significant differences were related to the PRF or CWRF compared to controls in the low- or zero-dose groups regarding tumors of any kind.
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Zook, B. C. and Simmens, S. J. The Effects of Pulsed 860 MHz Radiofrequency Radiation on the Promotion of Neurogenic Tumors in Rats. Radiat. Res. 165, 608–615 (2006). In a previous study, this ...laboratory reported a statistically nonsignificant trend for shortened latency of ethylnitrosourea (ENU)-induced brain tumors in Sprague-Dawley rats exposed to an 860 MHz pulsed radiofrequency (RF) signal. The present study was designed to investigate further any promoting effect of the pulsed RF signal on latency and other characteristics of neurogenic tumors in the progeny of pregnant rats treated with 6.25 or 10 mg/kg ENU. The resulting 1080 offspring were randomized equally by number, sex and ENU dose into pulsed RF, sham and cage control groups. The rats were exposed to the pulsed RF signal 6 h per day 5 days per week; the sham-exposed group was similarly confined for the same periods, and the cage controls were housed in standard cages. An essentially equal number of rats from each group were killed humanely every 30 days between the ages of 171 and 325 days; 32 rats died and 225 rats were killed when they were moribund. Postmortem examinations on the 1080 rats revealed 38 spinal cord tumors, 191 spinal nerve tumors, 232 cranial nerve tumors, and 823 brain tumors. A methodical study of the tumor characteristics disclosed no evidence that exposure to the pulsed RF signal affected the incidence, malignancy, volume, multiplicity, latency or fatality associated with any kind of neurogenic tumor.
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The virulence of the CDC1551 strain of Mycobacterium tuberculosis was compared to that of H37Rv in a rabbit inhalation model. While rabbits that inhaled the two strains produced equal numbers of ...grossly visible primary tubercles, CDC1551 tubercles were smaller and contained fewer bacilli than H37Rv tubercles. These findings suggest that a miniepidemic near the Kentucky-Tennessee border caused by CDC1551 was due not to increased virulence but to increased transmissibility.
Rats developed mixed gliomas, oligodendrogliomas, and a few astrocytomas in response to transplacental ethylnitrosourea. The neoplastic cell composition of mixed gliomas must be defined; this study ...required a 20-80% admixture of neoplastic astrocytes and oligodendroglia for the diagnosis of mixed glioma. A battery of immunoantibodies, including Leu-7, S-100, and vimentin, were helpful in classifying rat gliomas, and the histologic features of each tumor type are described. Other brain tumor characteristics that may decide the outcome of carcinogenicity studies include incidence, multiplicity, latency, fatality, size, and malignancy. The size of tumors was determined by measuring their 3-dimensional volumes. Brain tumor volume was found to be highly correlated with malignancy and fatality. Systematic evaluation of the malignancy of brain tumors is an important but often overlooked adjunct method of measuring the effectiveness of a carcinogen. A system to estimate malignancy, one that grades 9 tumor characteristics and weights, each according to clinical outcome, was developed. It was found that mixed gliomas grew larger, had a shorter latency, and were significantly more malignant than were other gliomas.
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An efficient synthesis of nelfinavir
1 was developed. The synthesis features an unusual rearrangement of a 3-amidotetrahydrofuran into a functionalized oxazoline.
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Understanding ice sheet evolution through the geologic past can help constrain ice sheet models that predict future ice dynamics. Existing geological records of grounding line retreat in the Ross ...Sea, Antarctica, have been confined to ice‐free and terrestrial archives, which reflect dynamics from periods of more extensive ice cover. Therefore, our perspective of grounding line retreat since the Last Glacial Maximum remains incomplete. Sediments beneath Ross Ice Shelf and grounded ice offer complementary insight into the southernmost extent of grounding line retreat, yielding a more complete view of ice dynamics during deglaciation. Here we thermochemically separate the youngest organic carbon to estimate ages from sediments extracted near the Whillans Ice Stream grounding line to provide direct evidence of mid‐Holocene (7.5–4.8 kyr B.P.) grounding line retreat in that region. Our study demonstrates the utility of accurately dated, grounding‐line‐proximal sediment deposits for reconstructing past interactions between marine and subglacial environments.
Plain Language Summary
Ice sheet grounding lines, where ice loses contact with the underlying bed and transitions to an ice shelf floating on the ocean, are critical areas that govern the stability of marine‐based ice sheets. However, the short period (years to decades) that we have been able to map grounding lines from ground, airborne, and satellite observations compared to the long periods over which ice sheets change (centuries to millenia) limits our knowledge of grounding line stability. We focus our geologic perspective of grounding line retreat in the Ross Sea, a region that has experienced a high degree of change throughout the last glacial‐interglacial cycle. Prior work reconstructing the timeline of ice sheet change in this region is based heavily on ice‐free marine sedimentary records, where dates of the first open marine sedimentation after ice retreat can be estimated. Dating sediments from beneath floating ice shelves and near grounding lines has proven difficult for both logistical and methodological reasons, limiting our understanding of grounding line evolution. We used novel radiocarbon dating methods on sediments collected from beneath the floating Ross Ice Shelf to find that the grounding line retreated inland of the current position during the mid‐Holocene and subsequently readvanced.
Key Points
Direct evidence is found for mid‐Holocene grounding line retreat on the Siple Coast, West Antarctica
Chronological constraints at Whillans Ice Stream imply western Ross Sea forcing on the southern Siple Coast, in contrast to other Siple Coast ice streams
Ramped PyrOx allows for accurate 14C dating of low carbon, grounding‐line‐proximal sediments
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