Multiple conformational states of a new hematopoietic cytokine (megakaryocyte growth and development factor): pH- and urea-induced denaturation

The effect of pH and urea on the conformation of recombinant human megakaryocyte growth and development factor (rHuMGDF) was determined by circular dichroism, intrinsic fluorescence spectroscopy, and equilibrium ultracentrifugation. The conformation of rHuMGDF was dependent on pH and urea concentration. Multiple folding forms were evidenced by multiple pH-induced transitions and urea-induced equilibrium transitions that deviated from a simple two-state process. In neutral to alkaline pH, rHuMGDF exists as a monomer, but an acid-induced conformational state self-associates to form a soluble aggregate. A folding intermediate(s) was observed with a more stable secondary structure than tertiary structure and was dependent on the pH of the urea-induced denaturation. The differences in the stabilities of the folding states were most distinct in the pH range of 4.5 to 6.5. The presence of intermediates in the folding pathway of rHuMGDF are similar to findings of previous studies of related growth factors that share a common three-dimensional structure. Proteins 32:495–503, 1998. © 1998 Wiley-Liss, Inc.     

Bioturbation enhances the aerobic respiration of lake sediments in warming lakes

While lakes occupy less than 2% of the total surface of the Earth, they play a substantial role in global biogeochemical cycles. For instance, shallow lakes are important sites of carbon metabolism. Aerobic respiration is one of the important drivers of the carbon metabolism in lakes. In this context, bioturbation impacts of benthic animals (biological reworking of sediment matrix and ventilation of the sediment) on sediment aerobic respiration have previously been underestimated. Biological activity is likely to change over the course of a year due to seasonal changes of water temperatures. This study uses microcosm experiments to investigate how the impact of bioturbation (by Diptera, Chironomidae larvae) on lake sediment respiration changes when temperatures increase. While at 5°C, respiration in sediments with and without chironomids did not differ, at 30°C sediment respiration in microcosms with 2000 chironomids per m² was 4.9 times higher than in uninhabited sediments. Our results indicate that lake water temperature increases could significantly enhance lake sediment respiration, which allows us to better understand seasonal changes in lake respiration and carbon metabolism as well as the potential impacts of global warming.     

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Evidence for spreading seizure as a cause of theta-alpha activity electrographic pattern in stereo-EEG seizure recordings

Intracranial electroencephalography is a standard tool in clinical evaluation of patients with focal epilepsy. Various early electrographic seizure patterns differing in frequency, amplitude, and waveform of the oscillations are observed. The pattern most common in the areas of seizure propagation is the so-called theta-alpha activity (TAA), whose defining features are oscillations in the θ − α range and gradually increasing amplitude. A deeper understanding of the mechanism underlying the generation of the TAA pattern is however lacking. In this work we evaluate the hypothesis that the TAA patterns are caused by seizures spreading across the cortex. To do so, we perform simulations of seizure dynamics on detailed patient-derived cortical surfaces using the spreading seizure model as well as reference models with one or two homogeneous sources. We then detect the occurrences of the TAA patterns both in the simulated stereo-electroencephalographic signals and in the signals of recorded epileptic seizures from a cohort of fifty patients, and we compare the features of the groups of detected TAA patterns to assess the plausibility of the different models. Our results show that spreading seizure hypothesis is qualitatively consistent with the evidence available in the seizure recordings, and it can explain the features of the detected TAA groups best among the examined models.     

Long-term treatment of acromegaly with bromocryptine: postprandial HGH levels and response to TRH and glucose administration.

Fourteen patients with acromegaly were treated with bromocryptine (CB 154, Sandoz), 4 X 2.5 mg, for periods of up to eleven months. One patient did not tolerate the drug, ten of the remaining thirteen experienced considerable clinical improvement. There was a dose-dependent suppression of plasma growth hormone levels, but growth hormone response to TRH injection and to glucose administration was still present during therapy although reduced. TSH response to TRH was not significantly altered. The suppressive power of bromocryptine on growth hormone appears to be related to the mechanism by which TRH stimulates growth hormone secretion in acromegaly, but long-term administration of this drug may be successful in spite of an absent response to TRH in some cases. Bromocryptine appears to be a safe and effective drug for the treatment of acromegaly.     

The effect of tissue culture agar on chromosome breakage, sister-chromatid exchanges and clonogenicity in human cells

To investigate the cytogenetic effects of electromagnetic fields, a system containing an agar gel was developed to support the growth of various human cell types (peripheral lymphocytes, lymphoblasts, and fibroblasts). When compared to alioquots of identical cells, grown in plastic culture vessels, statistically significant increases in the frequencies of chromosome breakage, sister-chromatid exchange and decreased cloning efficiency were observed in those cells cultured in the agar. These results suggest a possible clastogenic and/or cytotoxic component in the agar gel.     

Density‐dependent offspring interactions do not explain macroevolutionary scaling of adult size and offspring size

Most life forms exhibit a correlated evolution of adult size (AS) and size at independence (SI), giving rise to AS–SI scaling relationships. Theory suggests that scaling arises because relatively large adults have relatively high reproductive output, resulting in strong density‐dependent competition in early life, where large size at independence provides a competitive advantage to juveniles. The primary goal of our study is to test this density hypothesis, using large datasets that span the vertebrate tree of life (fishes, amphibians, reptiles, birds, and mammals). Our secondary goal is to motivate new hypotheses for AS–SI scaling by exploring how subtle variation in life‐histories among closely related species is associated with variation in scaling. Our phylogenetically informed comparisons do not support the density hypothesis. Instead, exploration of AS–SI scaling among life‐history variants suggests that steeper AS–SI scaling slopes are associated with evolutionary increases in size at independence. We suggest that a positive association between size at independence and juvenile growth rate may represent an important mechanism underlying AS–SI scaling, a mechanism that has been underappreciated by theorists. If faster juvenile growth is a consequence of evolutionary increases in size at independence, this may help offset the cost of delayed maturation, leading to steeper AS–SI scaling slopes.     

Behavioral responses of unrelated rhesus monkey females paired for the purpose of environmental enrichment

An attempt was made to socialize unrelated and unfamiliar adult rhesus monkey females that had lived in single cages for more than one year. Partners first were given the opportunity for noncontact familiarization in partitioned double cages. They were then transferred into an ordinary double cage. Clear-cut rank relationships were evident within the first 90 minutes of pair formation in 94% (17/18) of dyads tested. Only 28% (5/18) of pairs resorted to fighting (in no case with infliction of serious injury), while 50% (9/18) engaged in social grooming or hugging during this initial phase of pair formation. Eighty-three percent (15/18) of pairs were compatible, with none of the partners showing signs of depression and none inflicting serious injury on the other. Seventeen percent (3/18) of pairs were incompatible (two cases of depression, one serious tail injury) and were separated. It was concluded that the barren environment of singly caged rhesus monkey females can be enriched with little risk by carefully making them compatible companions.