Non-linear cardiac output dynamics during ramp-incremental cycle ergometry

Published literature asserts that cardiac output (=O₂×1/C_(a-v)O₂) increases as a linear function of oxygen uptake with a slope of approximately 5–6 during constant work rate exercise. However, we have previously demonstrated that C_(a-v)O₂ has a linear relationship as a function of O₂ during progressively increasing work rate incremental exercise. Therefore, we hypothesized that may indeed have a non-linear relationship with respect to O₂ during incremental, non-steady state exercise. To investigate this hypothesis, we performed five maximal progressive work rate exercise studies in healthy human subjects. was determined every minute during exercise using measured breath-by-breath O₂, and arterial and pulmonary artery measurements of PO₂, hemoglobin saturation, and content. was plotted as a function of O₂ and the linear and non-linear (first order exponential and hyperbolic) fits determined for each subject. Tests for linearity were performed by assessing the significance of the quadratic terms added to the linear relation using least squares estimation in linear regression. Linearity was inadequate in all cases (group P<0.0001). We conclude that cardiac output is a non-linear function of O₂ during ramp-incremental exercise; the pattern of non-linearity suggests that while the kinetics of are faster than those of O₂ they progressively slow as work rate (and O₂) increases.     

Does feeding regime affect physiologic and thermal responses during exposure to 8, 20, and 27° C?

Summary When the loss of body heat is accelerated by exposure to low environmental temperatures, additional substrates must be oxidized to provide energy to sustain temperature homeostasis. Therefore, the present investigation examined the relation between feeding regime [pre-experimental carbohydrate feeding (FED) vs a fast (FAST)], during 120 min of exposure to 8, 20, and 27° C in well-nourished men. The following were examined: tissue insulation (I; °C · m² · W^–1), rectal temperature (T _re; °C), and oxygen consumption ( O₂; ml · kg^–1 · min^–1). O₂, T _re, and I revealed no significant differences between treatments (FED vs FAST) at any temperature. At 27° C, I was less (P < 0.05) than at 20 and 8° C, and decreased (P < 0.05) as exposure time increased. At 8° C, O₂was higher (P < 0.5) than at 20 or 27°C, and O₂increased as time increased (P < 0.05). T _re decreased (P < 0.05) as time increased for all conditions. Respiratory exchange ratio (R) differed (P < 0.05) between treatments (FED vs FAST), temperature (8 vs 20° C), and across time. Values for R suggests that carbohydrate accounted for 56% and 33% of caloric utilization during the FED vs FAST conditions, respectively. At 8 vs 20° C, R represented 54% vs 30% of cabohydrate utilization. Across time, R demonstrated that in both conditions (FED vs FAST) there was a decreased reliance on carbohydrate utilization for energy provision. From these data it appears that while substrate utilization differed between dietary treatment and across time this did not differentially affect O₂or T _re during protracted exposure to 8, 20, and 27° C. The higher R in the 8° C condition for both dietary treatments demonstrates that carbohydrate utilization is increased in shivering cold-exposed humans. However, the reduction in R across time suggests that fat oxidation is also involved in metabolic heat production and core temperature maintenance during shivering in the cold.     

Identification of a Putative Precursor to the Major Surface Glycoprotein of Pneumocystis carinii

The major surface glycoprotein (MSG) of Pneumocystis carinii f. sp. carinii is a family of proteins encoded by a family of heterogeneous genes. Messenger RNAs encoding different MSGs each begin with the same 365-bp sequence, called the Upstream Conserved Sequence (UCS), which is in frame with the contiguous MSG sequence. The UCS contains several potential start sites for translation. To determine if translation of MSG mRNAs begins in the UCS, polyclonal antiserum was raised against the 123-amino-acid peptide encoded by the UCS. The anti-UCS serum reacted with a P. carinii protein that migrated at 170 kDa; however, it did not react with the mature MSG protein, which migrates at 116 kDa. A 170-kDa protein was immunoprecipitated with anti-UCS serum and shown to react with a monoclonal antibody against a conserved MSG epitope. To explore the functional role of the UCS in the trafficking of MSG, the nucleotide sequence encoding the UCS peptide was ligated to the 5′ end of an MSG gene and incorporated into a recombinant baculovirus. Insect cells infected with the UCS-MSG hybrid gene expressed a 160-kDa protein which was N-glycosylated. By contrast, insect cells infected with a baculovirus carrying an MSG gene lacking the UCS expressed a nonglycosylated 130-kDa protein. These data suggest that in P. carinii, translation begins in the UCS to produce a pre-MSG protein, which is subsequently directed to the endoplasmic reticulum and processed to the mature form by proteolytic cleavage.     

A geometric morphometric study of regional differences in the ontogeny of the modern human facial skeleton

This study examines interpopulation variations in the facial skeleton of 10 modern human populations and places these in an ontogenetic perspective. It aims to establish the extent to which the distinctive features of adult representatives of these populations are present in the early post natal period and to what extent population differences in ontogenetic scaling and allometric trajectories contribute to distinct facial forms. The analyses utilize configurations of facial landmarks and are carried out using geometric morphometric methods. The results of this study show that modern human populations can be distinguished based on facial shape alone, irrespective of age or sex, indicating the early presence of differences. Additionally, some populations have statistically distinct facial ontogenetic trajectories that lead to the development of further differences later in ontogeny. We conclude that population-specific facial morphologies develop principally through distinctions in facial shape probably already present at birth and further accentuated and modified to variable degrees during growth. These findings raise interesting questions regarding the plasticity of facial growth patterns in modern humans. Further, they have important implications in relation to the study of growth in the face of fossil hominins and in relation to the possibility of developing effective discriminant functions for the identification of population affinities of immature facial skeletal material. Such tools would be of value in archaeological, forensic and anthropological applications. The findings of this study underline the need to examine more deeply, and in more detail, the ontogenetic basis of other causes of craniometric variation, such as sexual dimorphism and hominin species differentiation.     

Defects in neurofibromatosis 2 protein function can arise at multiple levels

Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has revealed some general genotype-phenotype correlations. Severe disease has been associated with mutations that produce a premature termination while more mild disease has been associated with missense mutations. Here, we provide experimental proof for these genotype-phenotype correlations by demonstrating that nonsense mutations fail to produce stable merlin protein while missense mutations result in the generation of merlin proteins defective in negative growth regulation. This inability to suppress cell growth may result from defects in the function of merlin at several levels, including failure to form an intramolecular complex. Based on these findings, we propose a model for merlin growth suppression that provides a framework for analyzing NF2 patient mutations and merlin function.      

Cystic duct and Heister's "valves"

The anatomy and physiology of the cystic duct have been relatively neglected by anatomists and the function of the spiral mucosal folds or "valves" of Heister, first described in 1732, remains obscure. The gross and microscopic anatomy of the cystic duct is reviewed together with results from laboratory investigations into the function of the cystic duct and its spirally arranged folds. The duct and spiral folds contain muscle fibers responsive to pharmacologic, hormonal, and neural stimuli. There is, however, no convincing evidence of a discrete muscular sphincter within the duct. Although the cystic duct is unlikely to play a major role in gallbladder filling and emptying, it appears to function as more than a passive conduit. Coordinated, graded muscular activity in the cystic duct in response to hormonal and neural stimuli may facilitate gallbladder emptying. The principal function of the internal spiral folds that are found in man and other animals may be to preserve patency of this narrow, tortuous tube rather than to regulate bile flow.