Experimental confirmation of calculated phases and electron density profile for wet native collagen.

An experimental procedure is developed to phase the reflections obtained in x-ray diffraction investigations of collagen in native wet tendons. Phosphotungstic acid was used for isomorphous addition in phase determination and was located by electron microscopy. Structure factors (with phases) were obtained from the electron microscopy data for the heavy metal. Structure-factor magnitudes for collagen with and without the heavy metal were obtained from the x-ray diffraction data. The first 10 orders were investigated. Standard Argand diagrams provided two solutions for each of these, except the weak sixth order. In each case, one of the two possible solutions agrees well with the phases proposed on theoretical grounds by Hulmes et al. The present results suggest that their other proposed phases are probably correct. An electron density profile along the unit cell of the fibril is presented that shows a distinct step, as expected on the basis of the hole-overlap model. The overlap region is 48% of the length of the unit cell.     

Differential responsiveness to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in sub-regions of the primate substantia nigra and striatum

After treatment with the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), there was a severe loss of dopamine (DA) at all examined sites in the striatum, both in those monkeys which remained asymptomatic (77-99%) and in one monkey which developed severe parkinsonian disability (94-99%). However, the asymptomatic animals had normal DA concentration in the substantia nigra (SN); yet in the symptomatic animal DA was largely depleted in the central (86%) and medial (94%), but not lateral (8%) regions of the SN. The HVA/DA ratio was raised in the striatum of all MPTP-treated animals. In the SN though, this ratio was elevated only in the symptomatic animal, in the central and medial, but not lateral regions. The contralateral half of these brains were examined for DA histofluorescence. The SN of asymptomatic animals had a slight increase in lipofuscin fluorescence within dopaminergic neurons and a small reduction in the number of dopaminergic cells, while fluorescent intensity of individual neurons was unchanged. The SN of the symptomatic animal displayed a sharp decline in the number of DA neurons along with an increase in autofluorescent pigment granules; these changes were most pronounced in the central and medial regions of the SN. These data suggest that after MPTP the terminals of the nigrostriatal pathway are affected before the cell bodies. In the one symptomatic animal emergence of parkinsonian disability corresponded with a marked loss of DA neurons and DA concentration in the central and medial regions of the SN. In the control monkeys a gradient in the concentration of amines and metabolites was observed within the SN; the lateral region contained the highest and the medial region the lowest concentration.     

Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism

Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent.     

Plasma amine oxidase activity in 136 normal rhesus monkeys: relationships between enzyme activity and age, sex and genetic factors.

Normative data on plasma amine oxidase activity were obtained for four primate species, M. mulatta, M. arctoides, C. aethiops and H. sapiens. Significant between-species differences in activity were observed. In a large sample of M. mulatta, no significant relationship between age and plasma amine oxidase activity was observed, but adult males had significantly higher enzyme activities than adult females.     

Dredge and fill regulatory constraints in meeting the ecological goals of restoration projects

Regulators face the problem of ensuring that wetland functions that are lost due to permitting actions are restored via mitigation of those impacts. While there has been considerable study of wetland function, little of it has been directed toward the practical assessment of mitigation success. Development of quantitatively based rapid assessment methods would provide valuable assistance to the regulatory community. Regional and local goal setting, including a determination of whether strict in-kind restoration or restoration of habitat balance is preferable, is needed to ensure that the ecological health of the area is restored to the greatest extent possible.     

Some sampling considerations in the quantitation of monkey behavior under field and captive conditions

Observations of monkey behavior were made on free-ranging and corral-enclosedMacaca mulatta. Two sampling techniques were used: focal animal and group observations. Group observations measured frequencies of social behavior whereas focal observations used time samples which estimated durations of social and nonsocial activities as well as frequencies of social behavior. Analysis of concordance within and between sampling techniques revealed that short duration focal time samples provide a reliable estimate of total frequencies of social behaviors derived using group observations and furthermore, allows the recording of important nonsocial activities not easily recorded in terms of frequencies. Focal time sampling is advantageous for certain types of studies where the equal distribution of observation time between individuals is important, particularly in the field where visibility is often limited and individuals can only be observed continuously for short periods of time. This work was supported by grants from the H. F. Guggenheim Foundation, Dr.H. C. Robinson, Jr., and USPHS grants MH 24607 and MH 25642.     

Supplemented nutrition decreases helminth burden and increases drug efficacy in a natural host–helminth system

Gastrointestinal (GI) helminths are common parasites of humans, wildlife, and livestock, causing chronic infections. In humans and wildlife, poor nutrition or limited resources can compromise an individual''s immune response, predisposing them to higher helminth burdens. This relationship has been tested in laboratory models by investigating infection outcomes following reductions of specific nutrients. However, much less is known about how diet supplementation can impact susceptibility to infection, acquisition of immunity, and drug efficacy in natural host–helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) with high-quality nutrition and measured resistance to the common GI nematode Heligmosomoides polygyrus. To test whether diet can enhance immunity to reinfection, we also administered anthelmintic treatment in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, avoided a post-treatment infection rebound, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, when applied in conjunction with anthelmintic treatment, supplemented nutrition significantly reduced H. polygyrus transmission potential. These results show the rapid and extensive benefits of a well-balanced diet and have important implications for both disease control and wildlife health under changing environmental conditions.