Scaling in Athletic World Records

World records in athletics provide a measure of physical as well as physiological human performance. Here we analyse running records and show that the mean speed as a function of race time can be described by two scaling laws that have a breakpoint at about 150-170 seconds (corresponding to the ~1,000 m race). We interpret this as being the transition time between anaerobic and aerobic energy expenditure by athletes.Comment: published in the Brief Communication section of Natur

Survival processing in times of stress

Recent studies have found that processing information according to an evolutionary relevant (i.e., survival) scenario improves its subsequent memorability, potentially as a result of fitness advantages gained in the ancestral past. So far, research has not revealed much about any proximate mechanisms that might underlie this so-called survival processing advantage in memory. Intriguingly, research has shown that the memorability of stressful situations is enhanced via the release of stress hormones acting on brain regions involved in memory. Since survival situations habitually involve some degree of stress, in the present study, we investigated whether stress serves as a proximate mechanism to promote survival processing. Participants rated words for their relevance to either a survival or a neutral (moving) scenario after they had been exposed to a psychosocial stressor or a no-stress control condition. Surprise retention tests immediately following the rating task revealed that survival processing and acute stress independently boosted memory performance. These results therefore suggest that stress does not serve as a proximate mechanism of the survival processing advantage in memory

Monoclonal antibodies for copper-64 PET dosimetry and radioimmunotherapy

BACKGROUND: We previously described a two-antibody model of (64)Cu radioimmunotherapy to evaluate low-dose, solid-tumor response. This model was designed to test the hypothesis that cellular internalization is critical in causing tumor cell death by mechanisms in addition to radiation damage. The purpose of the present study was to estimate radiation dosimetry for both antibodies (mAbs) using positron emission tomography (PET) imaging and evaluate the effect of internalization on tumor growth. RESULTS: Dosimetry was similar between therapy groups. Median time to tumor progression to 1 g ranged from 7–12 days for control groups and was 32 days for both treatment groups (p < 0.0001). No statistically significant difference existed between any control group or between the treatment groups. MATERIAL AND METHODS: In female nude mice bearing LS174T colon carcinoma xenografts, tumor dosimetry was calculated using serial PET images of three mice in each group of either internalizing (64)Cu-labeled DOTA-cBR96 (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or non-internalizing (64)Cu-labeled DOTA-cT84.66 from 3 to 48 h. For the therapy study, controls (n = 10) received saline, DOTA-cBR96 or DOTA-cT84.66. Treatment animals (n = 9) received 0.890 mCi of (64)Cu-labeled DOTA-cBR96 or 0.710 mCi of (64)Cu-labeled DOTA-cT84.66. Tumors were measured daily. CONCLUSIONS: PET imaging allows the use of (64)Cu for pre-therapy calculation of tumor dosimetry. In spite of highly similar tumor dosimetry, an internalizing antibody did not improve the outcome of (64)Cu radioimmunotherapy. Radio-resistance of this tumor cell line and copper efflux may have confounded the study. Further investigations of the therapeutic efficacy of (64)Cu-labeled mAbs will focus on interaction between (64)Cu and tumor suppressor genes and copper chaperones

Adaptive memory: Stereotype activation is not enough

Studies have shown that survival processing leads to superior memorability. The aim of the present study was to examine whether this survival recall advantage might result from stereotype activation. To test this hypothesis, we conducted a pilot study and two experiments in which participants were primed with stereotypes (Experiment 1, professor and elderly person; Experiment 2, survival-stereotype). In Experiment 1, 120 undergraduates were randomly assigned to a survival, professor stereotype, elderly person stereotype, or moving scenario and rated words for their relevance to the imagined scenario. In Experiment 2, 75 undergraduates were given a survival, survival-stereotype (based on our pilot study), or moving scenario. Both experiments showed that survival processing leads to a greater recall advantage over the stereotype groups and control group. These data indicate that the mere activation of stereotypes cannot explain the survival recall advantage

Malaria prevention and treatment awareness and practice among patent medicine vendors (PMVs) in Gombe Metropolis, Nigeria

The ravaging consequences of Malaria in Sub-Saharan Africa (SSA) have been a subject of serious concern to every stakeholder. Literature and anecdotal evidence shows that around 60% of Nigerians seek fever treatment from Patent Medicine Vendors (PMVs) despite the limited formal dispensing knowledge most possess. This study attempts to establish a base line of knowledge, attitude and practices of Malaria control among PMVs in Gombe Metropolis, North Eastern Nigeria. The study was a descriptive cross sectional survey based on structured questionnaires used to collect relevant information from 109 PMVs selected by purposive sampling technique. The result show that 85.3% of the participants in this study correctly identified fever or high body temperature as the common sign of uncomplicated (UC) Malaria, while 70.6% recognized convulsion as one of the main symptoms of severe Malaria. Furthermore, 86.2% of the PMVs also knew that sleeping inside treated nets constitute one of the best ways to prevent Malaria. In the same vein, awareness of change in Malaria treatment policy from monotherapy to Artemisinin based combination therapy (ACT) was high (73.3%) among them. However, those PMVs that had ever undergone some degree of drug dispensing training exhibited a significantly higher level of awareness of change in malaria treatment policy (X2 =17.903, P = 0.000). Although 85.3% of PMVs frequently recommend Arthemeter Lumefantrine (AL) as treatment of uncomplicated Malaria, only 39.4% of the participants would refer severe malaria cases. Even though most Malaria control awareness and practice variables were found to be fairly good among the participants, it is clear from the study that there is the need for enhanced training, monitoring and supervision by the relevant authorities so as to fully harness the vast potential in PMVs

Self-organization in the olfactory system: one shot odor recognition in insects

We show in a model of spiking neurons that synaptic plasticity in the mushroom bodies in combination with the general fan-in, fan-out properties of the early processing layers of the olfactory system might be sufficient to account for its efficient recognition of odors. For a large variety of initial conditions the model system consistently finds a working solution without any fine-tuning, and is, therefore, inherently robust. We demonstrate that gain control through the known feedforward inhibition of lateral horn interneurons increases the capacity of the system but is not essential for its general function. We also predict an upper limit for the number of odor classes Drosophila can discriminate based on the number and connectivity of its olfactory neurons

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors