Failure to Maintain Glycolysis in Anoxic Nerve Terminals

Synaptosomal glycolysis is stimulated eight- to 10-fold when the respiratory chain is inhibited by cyanide or by anoxia. However, the stimulation is transient and after 15 min declines toward the preanoxic rate. The decline is not seen when Ca2+ is absent or when the respiratory chain is inhibited by rotenone. The decline in glycolysis is reversible, is not due to substrate exhaustion, and is the cause, rather than the effect, of lowered synaptosomal ATP/ADP ratios. The failure to maintain glycolysis when the terminal oxidase of the respiratory chain is inhibited may have relevance to the sensitivity of the brain to anoxic damage.     

Equipoise, knowledge and ethics in clinical research and practice

It is widely maintained that a clinical trial is ethical only if some form of equipoise between the treatments being compared obtains. To be in equipoise between two treatments A and B is to be cognitively indifferent between the statement 'A is strictly more effective than B' and its negation. It is natural to claim that equipoise regarding A and B is necessary for randomised assignment to treatments A and B to be beneficent and non-maleficent and is sufficient for such an assignment to be fair. Cashing this out precisely is difficult, and various forms of equipoise have been discussed which consider whose equipoise is relevant to the decision. This is to make judgement of equipoise something to be managed socially, while its prima facie significance is supposedly cognitive. Recent reconstructions of equipoise-like concepts in epistemology give clues about how to understand equipoise cognitively. In this paper I examine some of this work and discuss how successful it has been. I suggest that while this work is promising, it still has far to go, and that while equipoise remains the best theory we have of the cognitive justification for clinical trials, it is nonetheless incoherent.     

Site of graviperception in roots: a re-examination

Two lines of evidence have been cited to support the assertion that the root cap is the sole site of graviperception in the root. The first evidence is based on surgical removal of the cap, which abolishes the response to gravity. This is sufficient to conclude that the cap is involved in gravitropism, but not to conclude that the cap is the site of graviperception. The second is based on the results of centrifugation experiments, in which different parts of the plant are subjected to different centrifugal forces. The data from such experiments have been cited to support the conclusion that the perception of gravity is limited to the rootcap. However, these data actually support the conclusion that gravity is perceived throughout the root tip, and not only in the root cap. We believe that the data support the conclusion that the root cap is involved in root gravitropism, but that there is inadequate evidence to conclude that the cap is the sole site of graviperception.     

Gynecomastia: suction lipectomy as a contemporary solution

Suction lipectomy is adapted for the correction of gynecomastia. Previous attempts using suction lipectomy for gynecomastia still required the use of sharp dissection for removal of the glandular breast tissue as well as excision of redundant skin. With this new technique, gynecomastia is corrected solely with the use of suction lipectomy. The technique is successful if the gynecomastia is due to excess fat or parenchymal hypertrophy. A 7-mm cannula is inserted first, to remove the adipose tissue. Then a 2.4-mm cannula is used to remove the glandular and ductal tissue. The 7-mm cannula is then reinserted to remove subareolar parenchyma and to make final contour adjustments. The surrounding subcutaneous tissue is easily undermined to avoid a saucer deformity and to allow for skin contraction. Patients return to full activities in 48 hours. A compressive garment is worn for 4 to 6 weeks. The results of 10 patients are discussed.     

Sequential allocation in clinical trials comparing two exponential survival curves.

The problem of comparing two medical treatments with respect to survival is considered. Treatment outcome is assumed to follow an exponential distribution. The ratio of expected survivals associated with the two treatments is the clinical parameter of interest. A nuisance parameter is present, but it is removed by an invariance reduction and a sequential probability ratio test is applied to the invariant likelihood ratio. A class of data-dependent treatment assignment rules is identified over which the probability of correct treatment selection at the termination of the trial is approximately constant. A cost function, the weighted sum of total patients in the trial and the number assigned to the inferior treatment is introduced, and a treatment allocation rule conjectured to minimize the expected cost is constructed. Both analytic and simulation results show that it is an improvement over rules previously proposed. The methodology contained herein can be used to construct near-optimal rules in other testing contexts.     

Coalescent-based DNA barcoding: multilocus analysis and robustness

DNA barcoding is the assignment of individuals to species using standardized mitochondrial sequences. Nuclear data are sometimes added to the mitochondrial data to increase power. A barcoding method for analysing mitochondrial and nuclear data is developed. It is a Bayesian method based on the coalescent model. Then this method is assessed using simulated and real data. It is found that adding nuclear data can reduce the number of ambiguous assignments. Finally, the robustness of coalescent-based barcoding to departures from model assumptions is studied using simulations. This method is found to be robust to past population size variations, to within-species population structures, and to designs that poorly sample populations within species. Supplementary Material is available online at www.liebertonline.com/cmb.     

Characterisation of PduS, the pdu metabolosome corrin reductase, and evidence of substructural organisation within the bacterial microcompartment

PduS is a corrin reductase and is required for the reactivation of the cobalamin-dependent diol dehydratase. It is one component encoded within the large propanediol utilisation (pdu) operon, which is responsible for the catabolism of 1,2-propanediol within a self-assembled proteinaceous bacterial microcompartment. The enzyme is responsible for the reactivation of the cobalamin coenzyme required by the diol dehydratase. The gene for the cobalamin reductase from Citrobacter freundii (pduS) has been cloned to allow the protein to be overproduced recombinantly in E. coli with an N-terminal His-tag. Purified recombinant PduS is shown to be a flavoprotein with a non-covalently bound FMN that also contains two coupled [4Fe-4S] centres. It is an NADH-dependent flavin reductase that is able to mediate the one-electron reductions of cob(III)alamin to cob(II)alamin and cob(II)alamin to cob(I)alamin. The [4Fe-4S] centres are labile to oxygen and their presence affects the midpoint redox potential of flavin. Evidence is presented that PduS is able to bind cobalamin, which is inconsistent with the view that PduS is merely a flavin reductase. PduS is also shown to interact with one of the shell proteins of the metabolosome, PduT, which is also thought to contain an [Fe-S] cluster. PduS is shown to act as a corrin reductase and its interaction with a shell protein could allow for electron passage out of the bacterial microcompartment.     

Oxidation of glycine by Phaseolus leghaemoglobin with associated catabolic reactions at the haem.

Leghaemoglobin from the root nodules of kidney bean (Phaseolus vulgaris) reacts in alkaline glycine solutions as a glycine oxidase in a reaction that may also be regarded as a coupled oxidation. Leghaemoglobin is reduced to the ferrous form by glycinate, the oxygen complex is formed, and finally the haem is attacked to yield a green reaction product. Glycine is simultaneously oxidized to glyoxylate, and hydrogen peroxide is generated. The initial velocity of the formation of the green product is proportional to the concentrations of leghaemoglobin and glycine, and the optimum pH for the reaction is 10.2. The green product is not formed if carbon monoxide, azide of imidazole is bound to the haem, whereas oxidation of glycine to glyoxylate is not inhibited by azide and not essentially by carbon monoxide. Haem breakdown is activated by digestion of leghaemoglobin by carboxypeptidase, and partly inhibited by catalase and superoxide dismutase.     

Children as means and ends in large-scale medical research

This paper considers the often-expressed fear that medical research may use children merely as means, and not respect them as ends in themselves - especially insofar as they are deemed less able to consent than adults. The main focus is on large-scale genetic, socio-medical and epidemiological research. The theoretical starting point of the paper is that to be treated as an end in oneself is to be regarded as - and to act as - a participant in cooperative endeavours. This participatory status is certainly connected with individual authority to consent and dissent; and there is no doubt that consent plays an important role when adults participate in many research projects. However, insofar as consent is located within structures of human cooperation, the authority to consent is not a straightforward privilege. Rather, consent is bound up with responsibility for one's choices and commitment to shared terms of cooperation. Given this understanding, it is argued that consent should not be our principal concern when we involve children in research. This is not because of children's (possible) incompetence to consent as such, but rather because children are still learning how to respect and assess the cooperative terms involved in our institutional lives. Instead, our leading concern should be with the terms regulating their involvement in research. Given suitable safeguards, research is one way in which children may learn what it is to bear responsibilities and to act as an end in oneself - that is, to cooperate with others on reasonable terms and for worthy ends.     

长豇豆荚色、籽粒色及生长习性的遗传研究

以性状多样的长豇豆为材料,对其荚色、籽粒色和生长习性进行遗传分析。结果表明：籽粒色的相对性状间均表现1对等位基因差异的遗传,黑籽对红籽为显性,黑籽对白籽、红籽对白籽均为显性,花斑籽对红籽为显性。生长习性由2对等位基因控制,其中蔓生对矮生为显性上位性。荚角因材料不同有的表现为质量性状,且紫荚对浅绿荚为显性、浅绿荚对绿荚为显性、白荚对浅绿荚为显性;有的表现为数量性状,即由多基因控制。     

Determination of the maximum velocity and Michaelis constant of enzymes by a fixed-point method which avoids the necessity to measure initial rates

Measuring the initial velocity is difficult in some enzyme assays where a significant fraction of the substrate is consumed. Here a solution to this problem is proposed; the time to produce a fixed amount of reaction product is measured. This time is inversely proportional to the initial velocity, and is related to the maximum velocity and Michaelis constant by a simple equation and linear plot. The method is illustrated using the reaction catalysed by pyruvate kinase.     

Analytical studies of injury criteria for the thorax

The viscous criterion is a recently developed criterion to assess injury severity of the human thorax. In the viscous criterion, the peak viscous response, which is defined as the maximum product of deformation velocity and compression of an object, is proposed as a predictor of injury risk. However, the physical meaning of the criterion is not very clear. In this paper, the mathematical properties of the viscous criterion are analyzed. A mechanical thorax model is then used to relate the criterion to the physical quantities of the model using energy concepts. It is found that the so-called peak viscous response is strongly related to the peak energy storing rate of the thorax which is not related to the viscosity of the thorax. It is also shown that the viscous response of the thorax is given by the integral of the velocity squared with respect to time. The analysis is further expanded to a more general case to result in four criteria based upon the energy concepts. A hypothesis for injury assessment is proposed by using the four criteria.     

WHAT IS THE GOOD OF HEALTH CARE?

This paper sets out to discuss what precisely is meant by 'benefit" when we talk of the requirement that the health care system concern itself with health gain or with maximizing beneficial health care. In particular I argue that in discharging the duty to do what is most beneficial we need to choose between rival conceptions of what is meant by beneficial. One is the patient's conception of benefit and the second is the provider's or funder's conception of benefit. I argue that it is the patient's conception of benefit which is paramount and that if this is followed it commits us to a conception of patient care which must be blind to prognosis in so far as prognosis is thought to bear upon issues of prioritisation or resource allocation.     

Phosphorylation by protein kinase CK2: a signaling switch for the caspase-inhibiting protein ARC

Caspases play a central role in apoptosis, but their activity is under the control of caspase-inhibiting proteins. A characteristic of caspase-inhibiting proteins is direct caspase binding. It is yet unknown how the localization of caspase-inhibiting proteins is regulated and whether there are upstream signals controlling their function. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm. Our results reveal a molecular mechanism by which a caspase-inhibiting protein requires phosphorylation in order to prevent apoptosis.     

Biotin deficiency in Nigrospora oryzae

Nigrospora oryzae is reported to be partially deficient for biotin. The external requirement for the vitamin is shown to be conditioned by the nitrogen source. The deficiency for biotin is apparent when urea or nitrate is used to supply the nitrogen. The organism is found to be more dependent on an external supply of biotin in media where autoclaved urea is the source of nitrogen than where nitrate or sterilefiltered urea is that source. Aspartic acid is found to induce a complete sparing action for biotin requirement should the nitrogen source be nitrate. Malt and yeast extracts are reported to supply probable unidentified growth promoting substances other than biotin.     

Role of physical activity in preventing and treating obesity.

There is an inverse relationship between physical activity and weight gain. However, additional research is needed to quantify the amount of physical activity required to prevent weight gain in different populations, improve the way we convey physical activity recommendations to the public, and help the individuals increase their physical activity. Although physical activity does not appear to contribute significantly to weight loss, it is critical for maintenance of weight loss. Available data are consistent in that 60-90 min/day of moderate-intensity physical activity is required to maintain a significant weight loss. Although there is agreement about the need for high levels of physical activity to maintain weight loss, there is a need for more research to understand why physical activity is critical for weight loss maintenance. Finally, additional research is needed to determine whether there is an optimal level of physical activity below which it is difficult for most people to achieve a balance between energy intake and expenditure at a healthy body weight. The increasing prevalence of obesity may reflect the fact that the majority of the population has fallen below such a level of physical activity.     

Mitochondrial metabolism of hydroxocobalamin: synthesis of adenosylcobalamin by intact rat liver mitochondria.

When free hydroxocobalamin (vitamin B₁₂) is added in vitro to a suspension of intact rat liver mitochondria in the presence of a source of both reducing equivalents and ATP, adenosylcobalamin synthesis is observed. This synthetic process is not dependent on electron transport or oxidative phosphorylation and is not detected when cyanocobalamin is substituted for hydroxocobalamin. Adenosylcobalamin synthesis is linear with time for at least 10 min and with hydroxocobalamin concentration up to 37 nm. At the latter concentration of hydroxocobalamin, the rate of synthesis at 37 °C is 0.26 pmol/min/mg of protein. Only part (<30%) of the newly synthesized adenosylcobalamin is bound to the mitochondrial cobalamin binding protein, whereas most (90%) of the concurrently accumulated hydroxocobalamin is bound. On the other hand, when adenosylcobalamin is added to a suspension of intact mitochondria, it is accumulated at a rate similar to that for hydroxocobalamin, and is bound to the mitochondrial binding protein to a similar extent. These findings indicate that rat liver mitochondria contain all of the enzymatic components necessary to convert hydroxocobalamin to adenosylcobalamin, the coenzyme for the mitochondrial enzyme methylmalonyl CoA mutase.     

Risk avoidance and nesting strategies

Gillespie (1974,1975) has shown that selection will tend to minimize variance in offspring number. It is shown that this effect is due to selection maximizing the average number of surviving offspring when there is density-dependent survival, and that it is unnecessary to invoke principles such as minimizing the variability of fitness (Real, 1980). The effect of this principle of selecting for laying several small clutches rather than one large clutch when there is predation on whole clutches is investigated. It is found that the selection pressure is weak, contrary to the conclusion of Rubenstein (1982), and is unlikely to be of evolutionary importance.     

The kinetics of hemolytic plaque formation. III. Inhibition of plaques by antigen.

Equations are presented which can be used to describe the inhibition of plaques by multifunctional antigen which binds γG antibody bivalently. The interaction is treated as a bimolecular reaction which is irreversible within the time of the experiment. It is shown that under these conditions the characteristics of the inhibition curve, and their relationship to kinetic and thermodynamic parameters are strongly dependent upon how antibody interacts with RBCs. When the epitope coating is dense, multivalent attachment of antibody is likely and the interaction is considered irreversible. When the epitope coating is sparse, only rapid, reversible univalent attachment is considered and local equilibrium is assumed to hold.The first case leads to an abrupt inhibition curve whose position is determined by the forward rate constant and RBC density. The second case leads to broad asymmetric curves. For this situation the relation between the extent of inhibition and the affinity of the population is generally complicated and reliable affinity information is difficult to obtain. This is contrasted to results obtained previously for unifunctional inhibitors from which reliable affinity information can, in principle, be obtained. The results emphasize the need for carefully designed experiments if affinity information is to be obtained from inhibition studies.