Therapeutic antibodies: their mechanisms of action and the pathological findings they induce in toxicity studies

Antibodies can swiftly provide therapeutics to target disease-related molecules discovered in genomic research. Antibody engineering techniques have been actively developed and these technological innovations have intensified the development of therapeutic antibodies. From the mid-1990’s, a series of therapeutic antibodies were launched that are now being used in clinic. The disease areas that therapeutic antibodies can target have subsequently expanded, and antibodies are currently utilized as pharmaceuticals for cancer, inflammatory disease, organ transplantation, cardiovascular disease, infection, respiratory disease, ophthalmologic disease, and so on. This paper briefly describes the modes of action of therapeutic antibodies. Several non-clinical study results of the pathological changes induced by therapeutic antibodies are also presented to aid the future assessment of the toxic potential of an antibody developed as a therapeutic.     

Dual effects of reversed winter–spring temperatures on year‐to‐year variation in the recruitment of chub mackerel (Scomber japonicus)

To clarify the effects of temperature on the recruitment of chub mackerel (Scomber japonicus) in the North Pacific, we investigated the influence of winter surface temperature (WST) on spawners at the time of maturity around the spawning grounds and the influence of ambient spring temperature on larvae using estimated temperature (ET) obtained from particle tracking experiments. We found a significant positive correlation between ET approximately 10 days following hatching and the recruitment per spawning stock biomass (RPS) after 2000. The closer (more meandering) the Kuroshio Current (KC) axis was in relation to the spawning ground, the higher (lower) the spring surface temperature and the higher (lower) RPS was in the spawning ground. In contrast, WST inside KC near the maturity/spawning ground was significantly negatively correlated with RPS. A significant negative correlation between the temperatures in winter and spring was detected in the area after 2000, when the conditions of the Pacific decadal oscillation index and the stability of the Kuroshio Extension were synchronous, indicating that KC shifted northward during this time. The reversed temperature pattern was consistent with the winter–spring movement of KC axis in the offshore direction and was correlated with the winter–spring difference in the intensity of the Aleutian low. These results suggest that the annual variation in chub mackerel recruitment after 2000 was strongly affected by the combined effects of ambient temperature because of the reversal of conditions that occurred between winter and spring around the maturity/spawning ground, which was related to the KC path.     

α-Melanocyte-stimulating hormone directly increases the plasma calcitonin level and involves calcium metabolism in goldfish

International Aquatic Research - The effects of α-melanocyte-stimulating hormone (α-MSH) on calcium metabolism were examined with goldfish. The scales on the left side of goldfish bodies...     

The locus for resistance to Asian soybean rust in PI 587855

Asian soybean rust (ASR) caused by Phakopsora pachyrhizi is one of the most serious soybean (Glycine max) diseases in tropical and subtropical areas. A soybean line, PI 587855, showed a resistance phenotype against ASR pathogens in Japan and South America at high frequency; however, little is known of the genetic control of this resistance and chromosomal location of the corresponding locus. Therefore, the aim of this study was to study the inheritance of PI 587855 resistance and map the corresponding locus with SSR markers aiming to use the linked markers in marker‐assisted selection. In the segregating population, resistance to ASR appeared to be controlled by a single dominant gene. The ASR resistance locus was mapped near to the chromosomal region where the resistant loci, Rpp1 and Rpp1‐b, were previously mapped. Comparative genetic mapping and disease reaction profiles of other seven lines carrying Rpp1 or Rpp1‐b to four Brazilian ASR isolates revealed that the resistance reaction exhibited by PI 587855 was similar to that of Rpp1‐b‐carrying varieties which have useful resistance to South American ASR strains.     

Comparisons among MRI signs,apparent diffusion coefficient,and fractional anisotropy in dogs with a solitary intracranial meningioma or histiocytic sarcoma

Although MRI has become widely used in small animal practice, little is known about the validity of advanced MRI techniques such as diffusion‐weighted imaging and diffusion tensor imaging. The aim of this retrospective analytical observational study was to investigate the characteristics of diffusion parameters, that is the apparent diffusion coefficient and fractional anisotropy, in dogs with a solitary intracranial meningioma or histiocytic sarcoma. Dogs were included based on the performance of diffusion MRI and histological confirmation. Statistical analyses were performed to compare apparent diffusion coefficient and fractional anisotropy for the two types of tumor in the intra‐ and peritumoral regions. Eleven cases with meningioma and six with histiocytic sarcoma satisfied the inclusion criteria. Significant differences in apparent diffusion coefficient value (× 10^?3 mm²/s) between meningioma vs. histiocytic sarcoma were recognized in intratumoral small (1.07 vs. 0.76) and large (1.04 vs. 0.77) regions of interest, in the peritumoral margin (0.93 vs. 1.08), and in the T2 high region (1.21 vs. 1.41). Significant differences in fractional anisotropy values were found in the peritumoral margin (0.29 vs. 0.24) and the T2 high region (0.24 vs. 0.17). The current study identified differences in measurements of apparent diffusion coefficient and fractional anisotropy for meningioma and histiocytic sarcoma in a small sample of dogs. In addition, we observed that all cases of intracranial histiocytic sarcoma showed leptomeningeal enhancement and/or mass formation invading into the sulci in the contrast study. Future studies are needed to determine the sensitivity of these imaging characteristics for differentiating between these tumor types.     

Census and effective population sizes of white‐spotted charr (Salvelinus leucomaenis) in a fragmented landscape

Several habitat models have been proposed to predict population size for stream fishes and to guide habitat assessment and monitoring techniques. However, most models do not incorporate the potential advantage of molecular genetic markers. We conducted a field survey and microsatellite DNA analyses to quantify the relationships among genetic diversity, census/effective population size and habitat variables in fragmented populations of white‐spotted charr (Salvelinus leucomaenis). The census population size significantly increased with the stream length, the number of pools and a pool‐riffle sequence index, a proxy for channel‐unit habitat type complexity within reaches. Population density was correlated with the pool‐riffle sequence index only. Genetic diversity and effective population size were not correlated with the habitat variables or census population size. There was a lack of isolation‐by‐distance population structure in the studied populations. Our results suggest that stream length and the number of pools within reaches associated with habitat complexity are the habitat variables that explain the majority of variation in population size of white‐spotted charr. Our findings provide further evidence that census population size per se is a poor indicator of the inclusive genetic diversity within populations in a fragmented landscape.     

Spectrophotometrical characteristics in the near infrared region in beech (<Emphasis Type="Italic">Fagus crenata</Emphasis>) and pine (<Emphasis Type="Italic">Pinus densiflora</Emphasis>) litters at the various decomposing stages

We examined the relationships between the absorptional characteristics in the near infrared region and the chemical changes of decomposing beech (Fagus crenata) and pine (Pinus densiflora) litters. Spectra as well as the concentrations of chemical substances approached each other and converged with decomposition, although both initial characteristics differed markedly between beech and pine. This indicated that the fundamental chemical structures were almost the same, although their organochemical composition differed. Specific absorption bands for lignin, polysaccharide, and protein were identified at 2,140 and 1,670 nm, 2,270, 1,720, 1,590, and 1,216 nm, and 2,350 nm, respectively. Absorbance at 1,670 nm, peculiar band of aromatics, showed a positive correlation with lignin concentration, which suggested the relative increment of aromatics due to condensed lignin in decomposing litters. Absorbance at 2,140 nm, characterized as the C–H bond in HRC = CHR, showed a negative correlation with lignin concentration, which suggested the decrements of some structures such as side-chains in lignin polymers unrelated to aromatics. Absorbance at 2,270, 1,720, and 1,216 nm, specified to O–H/C–O/C–H bonds in saccharide, might reflect the change of polysaccharide during decomposition because they showed a positive correlation to polysaccharide concentration. In the same way, absorbance at 2,350 nm, identified to the C–H/CH₂ bonds in protein, showed a negative correlation to nitrogen concentration in decomposing litters, which might indicate that the C–H/CH₂ bonds in protein decreased with decomposition due to microbial consumption of carbon in protein. Our findings suggested the possibility that the spectral changes indicate the litter digestibility during decomposition and that also explain the compositional change in decomposing litters.     

Effects of polyline simplification of dynamic GPS data under forest canopy on area and perimeter estimations

The objectives of this study were to determine Global Positioning System (GPS) positional errors while moving under the forest canopy and to clarify the effects of polyline simplification on area and perimeter estimations. We used the Pathfinder Pro XR and GPSMAP 76S, which are categorized as “high-end mapping” and “general navigation” GPS receivers, respectively. The field tests were conducted in both natural and plantation forests. The results showed that the Pathfinder Pro XR, which has better multipath rejection technology, worked well, especially in the plantation forest under unfavorable conditions of higher stand density. We used analysis of variance to clarify the effects of the receiver type, positioning mode, stand type, and polyline simplification method on area and perimeter estimations. The receiver type and positioning mode were found to be significant factors that affected area estimation. The Pathfinder Pro XR estimated the area more accurately than the GPSMAP 76S, and differential GPS estimated the area more accurately than autonomous GPS. With respect to the perimeter, the receiver type, positioning mode, and polyline simplification method were found to be significant factors. The results showed that perimeter estimation was improved by using the velocity filter, and further improved by using the velocity filter and Douglas-Peucker algorithm, especially when the Pathfinder Pro XR was used. The GPSMAP 76S estimated the perimeter accurately without any filtering because its default speed filter worked well, even though the GPSMAP 76S is a general navigation GPS receiver.     

Ecology of Armillaria species on conifers in Japan

Distribution, host preference and pathogenicity of Japanese Armillaria species on conifers were investigated on the basis of field collections of 65 isolates. We identified seven Armillaria species from 19 conifer species including six major Japanese plantation conifers using mating tests and sequences of the translation elongation‐1 α gene. Armillaria mellea, Armillaria ostoyae, Armillaria cepistipes and Armillaria sinapina were frequently collected, whereas Armillaria nabsnona, Armillaria tabescens and a biological species Nagasawa’s E were rare. On the basis of host condition when the isolates were collected, A. mellea, A. ostoyae, A. cepistipes and A. tabescens are considered as moderate to aggressive pathogens of conifers in Japan.     

Identification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysates

In the present study, we identified several food-derived collagen peptides in human blood after oral ingestion of some gelatin hydrolysates. Healthy human volunteers ingested the gelatin hydrolysates (9.4-23 g) from porcine skin, chicken feet, and cartilage after 12 h of fasting. Negligible amounts of the peptide form of hydroxyproline (Hyp) were observed in human blood before the ingestion. After the oral ingestion, the peptide form of Hyp significantly increased and reached a maximum level (20-60 nmol/mL of plasma) after 1-2 h and then decreased to half of the maximum level at 4 h after the ingestion. Major constituents of food-derived collagen peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amounts of Ala-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, and Phe-Hyp were contained.