More dendritic spine synapses occur on mature neurons in hippocampal slices by 2 h of incubation in vitro, than in perfusion-fixed hippocampus. What conditions initiate this spinogenesis and how rapidly do the spines begin to proliferate on mature neurons? To address these questions, CA1 field of the hippocampus neurons expressing green fluorescent protein in living slices from mature mice were imaged with two-photon microscopy. Spines disappeared and dendrites were varicose immediately after slice preparation in ice-cold artificial cerebrospinal fluid (ACSF). Electron microscopy (EM) revealed disrupted dendritic cytoplasm, enlarged or free-floating postsynaptic densities, and excessive axonal endocytosis. Upon warming dendritic varicosities shrank and spines rapidly reappeared within a few minutes illustrating the remarkable resilience of mature hippocampal neurons in slices. When membrane impermeant sucrose was substituted for NaCl in ACSF dendrites remained spiny at ice-cold temperatures and EM revealed less disruption. Nevertheless, spine number and length increased within 30 min in warm ACSF even when the extracellular calcium concentration was zero and synaptic transmission was blocked. When slices were first recovered for several hours and then chilled in 6 degrees C ACSF many spines disappeared and the dendrites became varicose. Upon re-warming varicosities shrank and spines reemerged in the same position from which they disappeared. In addition, new spines formed and spines were longer suggesting that chilling, not the initial injury from slicing, caused the spines to disappear while re-warming triggered the spine proliferation on mature neurons. The new spines might be a substrate for neuronal recovery of function, when neurons have been chilled or exposed to other traumatic conditions that disrupt ionic homeostasis.

BACKGROUND

Single-center trials have shown that monocytic HLA-DR is a good marker for monitoring the severity of temporary immunodepression after trauma, major surgery, or sepsis. A new test for measuring monocytic HLA-DR is now available.

METHODS

We evaluated a new test reagent set for monocytic HLA-DR expression (BD Quantibritetrade mark HLA-DR/Monocyte reagent; Becton Dickinson) in single-laboratory and interlaboratory experiments, assessing preanalytical handling, lyse-no-wash (LNW) vs lyse-wash (LW) values, reference values, and the effect of use of different flow cytometers and different instrument settings on test variance.

RESULTS

For preanalytical handling, EDTA anticoagulation, storage on ice as soon as possible, and staining within 4 h after blood collection gave results comparable to values obtained for samples analyzed immediately after collection (mean increase of approximately 4% in monocytic HLA-DR). Comparison of LNW and LW revealed slightly higher results for LNW ( approximately 18% higher for LNW compared with LW; r = 0.982). Comparison of different flow cytometers and instrument settings gave CVs <4%, demonstrating the independence of the test from these variables and suggesting that this method qualifies as a standardized test. CV values from the interlaboratory comparison ranged from 15% (blood sample unprocessed before transport) to 25% (stained and fixed before transport).

CONCLUSIONS

For the BD Quantibrite HLA-DR/Monocyte test, preanalytical handling is standardized. Single-laboratory results demonstrated the independence of this test from flow cytometer and instrument settings. Interlaboratory results showed greater variance than single-laboratory values. This interlaboratory variance was partly attributable to the influence of transport and can be reduced by optimization of transport conditions.

The vaccinia virus (VV) strain Western Reserve B13R gene encodes a 38.5 kDa intracellular polypeptide that is non-essential for virus replication in vitro and does not affect virus virulence in a murine intranasal model. The protein has 92% amino acid identity with the cowpox virus cytokine response modifier A (crmA) protein which inhibits the interleukin (IL)-1beta converting enzyme (ICE). Here, we show that extracts from THP-1 cells infected with VV strains expressing B13R prevent the cleavage of in vitro transcribed and translated pro-IL-1beta into mature IL-1beta. Similarly, THP-1 cells infected with VVs expressing B13R process pro-IL-1beta into mature IL-1beta inefficiently in situ. Despite its inhibition of ICE, B13R does not prevent fever in infected mice, a systemic effect mediated by IL-1beta. Instead, fever is controlled by the VV IL-1beta receptor, encoded by gene B15R, and deletion of both the B13R and B15R genes did not increase the febrile response compared to deletion of B15R alone. The B13R protein does, however, block apoptosis mediated by anti-Fas antibodies or by tumour necrosis factor (TNF) and cycloheximide. Using DNA fragmentation, chromium release and microscopic analyses it was shown that cells infected with wild-type VV strain WR, or a revertant virus in which the B13R gene had been re-inserted into the B13R deletion mutant, are more resistant than uninfected cells or deletion mutant-infected cells to apoptosis mediated by anti-Fas and TNF.

The major mechanism of cytotoxic lymphocyte killing involves the directed release of granules containing perforin and a number of proteases onto the target cell membrane. One of these proteases, granzyme B, has an unusual substrate site preference for Asp residues, a property that it shares with members of the emerging interleukin-1beta-converting enzyme (ICE)/CED-3 family of proteases. Here we show that granzyme B is sufficient to reproduce rapidly all of the key features of apoptosis, including the degradation of several protein substrates, when introduced into Jurkat cell-free extracts. Granzyme B-induced apoptosis was neutralized by a tetrapeptide inhibitor of the ICE/CED-3 family protease, CPP32, whereas a similar inhibitor of ICE had no effect. Granzyme B was found to convert CPP32, but not ICE, to its active form by cleaving between the large and small subunits of the CPP32 proenzyme, resulting in removal of the prodomain via an autocatalytic step. The cowpox virus protein CrmA, a known inhibitor of ICE family proteases as well as granzyme B, inhibited granzyme B-mediated CPP32 processing and apoptosis. These data demonstrate that CPP32 activation is a key event during apoptosis initiated by granzyme B.

More than 1.4 billion people depend on water from the Indus, Ganges, Brahmaputra, Yangtze, and Yellow rivers. Upstream snow and ice reserves of these basins, important in sustaining seasonal water availability, are likely to be affected substantially by climate change, but to what extent is yet unclear. Here, we show that meltwater is extremely important in the Indus basin and important for the Brahmaputra basin, but plays only a modest role for the Ganges, Yangtze, and Yellow rivers. A huge difference also exists between basins in the extent to which climate change is predicted to affect water availability and food security. The Brahmaputra and Indus basins are most susceptible to reductions of flow, threatening the food security of an estimated 60 million people.

The molecular pathway of p53-dependent apoptosis (programmed cell death) is poorly understood. Because p53 binds to the basal transcription-repair complex TFIIH and modulates its DNA helicase activities, we hypothesized that TFIIH DNA helicases XPB and XPD are members of the p53-mediated apoptotic pathway. Whereas transfer of a wild-type p53 expression vector by microinjection or retroviral infection into primary normal human fibroblasts resulted in apoptosis, primary fibroblasts from individuals with xeroderma pigmentosum (XP), who are deficient in DNA repair and have germ-line mutations in the XPB or XPD gene, but not in the XPA or XPC gene, have a deficiency in the apoptotic response. This deficiency can be rescued by transferring the wild-type XPB or XPD gene into the corresponding mutant cells. XP-D lymphocytes also have a decreased apoptotic response to DNA damage by adriamycin, indicating a physiologically relevant deficiency. The XP-B or XP-D mutant cells undergo a normal apoptotic response when microinjected with the Ich-L, and ICE genes. Analyses of p53 mutants and the effects of microinjected anti-p53 antibody, Pab421, indicate that the carboxyl terminus of p53 may be required for apoptosis. Direct microinjection of the p53 carboxy-terminal-derived peptide (amino acid residues 319-393) resulted in apoptosis of primary normal human fibroblasts. These results disclose a novel pathway of p53-induced apoptosis.

Fas/APO-1(CD95) ligation activates programmed cell death, a cellular process that plays an important role in the maturation of the host immune response. We show that activation of a specific MAP kinase kinase (MKK), MKK6b, is necessary and sufficient for Fas-induced apoptosis of Jurkat T cells. MKK6b activation occurs downstream of an interleukin-1 converting enzyme-like (ICE-like) protease(s), while execution of the apoptotic pathway by MKK6b requires both ICE- and CPP32-like proteases. Surprisingly, the p38 MAP kinase protein, a known substrate of MKK6b, does not participate in Fas/MKK6b-mediated apoptosis. These findings indicate a divergence of the MKK6b signaling pathways, one of which activates p38 and leads to regulation of gene expression, and one of which activates the ICE/Ced-3 family of proteases and leads to cell death. These studies represent a demonstration of an apoptotic pathway that is comprised of both the ICE/Ced-3 family of proteases and MAP kinase kinase 6.

Phosphatidylserine (PS), a lipid normally confined to the inner leaflet of the plasma membrane, is exported to the outer plasma membrane leaflet during apoptosis to serve as a trigger for recognition of apoptotic cells by phagocytes. The mechanism of PS export during apoptosis is not known nor is it clear whether the nuclear changes that typify apoptosis contribute in any way to this event. Here, we demonstrate that ligation of the CD95 (Fas/APO-1) molecule on Jurkat cytoplasts induces dramatic PS externalization similar to that observed during apoptosis of intact cells. Apoptosis of both cells and cytoplasts was associated with proteolytic processing of CPP32, a member of the interleukin-1beta converting enzyme (ICE)/CED-3 protease family, to its active form. Fodrin, a component of the cortical cytoskeleton, also underwent proteolytic cleavage during apoptosis of both cytoplasts and intact cells. Strikingly, CPP32 activation, fodrin proteolysis, and PS externalization were all inhibited in the presence of peptide inhibitors of ICE/CED-3 family proteases. These data provide strong support for the notion that the cell death machinery is extranuclear and is likely to be comprised of one or more members of the ICE/CED-3 family and that activation of this machinery does not require nuclear participation.

Mountain ranges, deserts, ice fields and oceans generally act as barriers to the movement of land-dependent animals, often profoundly shaping migration routes. We used satellite telemetry to track the southward flights of bar-tailed godwits (Limosa lapponica baueri), shorebirds whose breeding and non-breeding areas are separated by the vast central Pacific Ocean. Seven females with surgically implanted transmitters flew non-stop 8,117-11,680 km (10153+/-1043 s.d.) directly across the Pacific Ocean; two males with external transmitters flew non-stop along the same corridor for 7,008-7,390 km. Flight duration ranged from 6.0 to 9.4 days (7.8+/-1.3 s.d.) for birds with implants and 5.0 to 6.6 days for birds with externally attached transmitters. These extraordinary non-stop flights establish new extremes for avian flight performance, have profound implications for understanding the physiological capabilities of vertebrates and how birds navigate, and challenge current physiological paradigms on topics such as sleep, dehydration and phenotypic flexibility. Predicted changes in climatic systems may affect survival rates if weather conditions at their departure hub or along the migration corridor should change. We propose that this transoceanic route may function as an ecological corridor rather than a barrier, providing a wind-assisted passage relatively free of pathogens and predators.

A record of atmospheric carbon dioxide (CO2) concentration during the transition from the Last Glacial Maximum to the Holocene, obtained from the Dome Concordia, Antarctica, ice core, reveals that an increase of 76 parts per million by volume occurred over a period of 6000 years in four clearly distinguishable intervals. The close correlation between CO2 concentration and Antarctic temperature indicates that the Southern Ocean played an important role in causing the CO2 increase. However, the similarity of changes in CO2 concentration and variations of atmospheric methane concentration suggests that processes in the tropics and in the Northern Hemisphere, where the main sources for methane are located, also had substantial effects on atmospheric CO2 concentrations.

Insects are highly successful animals inhabiting marine, freshwater and terrestrial habitats from the equator to the poles. As a group, insects have limited ability to regulate their body temperature and have thus required a range of strategies to support life in thermally stressful environments, including behavioural avoidance through migration and seasonal changes in cold tolerance. With respect to overwintering strategies, insects have traditionally been divided into two main groups: freeze tolerant and freeze avoiding, although this simple classification is underpinned by a complex of interacting processes, i.e. synthesis of ice nucleating agents, cryoprotectants, antifreeze proteins and changes in membrane lipid composition. Also, in temperate and colder climates, the overwintering ability of many species is closely linked to the diapause state, which often increases cold tolerance ahead of temperature-induced seasonal acclimatisation. Importantly, even though most species can invoke one or both of these responses, the majority of insects die from the effects of cold rather than freezing. Most studies on the effects of a changing climate on insects have focused on processes that occur predominantly in summer (development, reproduction) and on changes in distributions rather than winter survival per se. For species that routinely experience cold stress, a general hypothesis would be that predicted temperature increases of 1 degree C to 5 degrees C over the next 50-100 years would increase winter survival in some climatic zones. However, this is unlikely to be a universal effect. Negative impacts may occur if climate warming leads to a reduction or loss of winter snow cover in polar and sub-polar areas, resulting in exposure to more severe air temperatures, increasing frequency of freeze-thaw cycles and risks of ice encasement. Likewise, whilst the dominant diapause-inducing cue (photoperiod) will be unaffected by global climate change, higher temperatures may modify normal rates of development, leading to a decoupling of synchrony between diapause-sensitive life-cycle stages and critical photoperiods for diapause induction. In terms of climate warming and potential heat stress, the most recent predictions of summer temperatures in Europe of 40 degrees C or higher in 50-75 years, are close to the current upper lethal limit of some insects. Long-term data sets on insect distributions and the timing of annual migrations provide strong evidence for 'positive' responses to higher winter temperatures over timescales of the past 20-50 years in North America, Europe and Asia.

We have identified a novel cDNA encoding a protein (named TX) with>> 50% overall sequence identity with the interleukin-1 beta converting enzyme (ICE) and approximately 30% sequence identity with the ICE homologs NEDD-2/ICH-1L and CED-3. A computer homology model of TX was constructed based on the X-ray coordinates of the ICE crystal recently published. This model suggests that TX is a cysteine protease, with the P1 aspartic acid substrate specificity retained. Transfection experiments demonstrate that TX is a protease which is able to cleave itself and the p30 ICE precursor, but not to generate mature IL-1 beta from pro-IL-1 beta. In addition, this protein induces apoptosis in transfected COS cells. TX therefore delineates a new member of the growing Ice/ced-3 gene family coding for proteases with cytokine processing activity or involved in programmed cell death.

Mechanisms of molecular self-replication have the potential to shed light on the origins of life. In particular, self-replication through RNA-catalysed templated RNA synthesis is thought to have supported a primordial 'RNA world'. However, existing polymerase ribozymes lack the capacity to synthesize RNAs approaching their own size. Here, we report the in vitro evolution of such catalysts directly in the RNA-stabilizing medium of water ice, which yielded RNA polymerase ribozymes specifically adapted to sub-zero temperatures and able to synthesize RNA in ices at temperatures as low as -19 °C. The combination of cold-adaptive mutations with a previously described 5' extension operating at ambient temperatures enabled the design of a first polymerase ribozyme capable of catalysing the accurate synthesis of an RNA sequence longer than itself (adding up to 206 nucleotides), an important stepping stone towards RNA self-replication.

The covariation of carbon dioxide (CO(2)) concentration and temperature in Antarctic ice-core records suggests a close link between CO(2) and climate during the Pleistocene ice ages. The role and relative importance of CO(2) in producing these climate changes remains unclear, however, in part because the ice-core deuterium record reflects local rather than global temperature. Here we construct a record of global surface temperature from 80 proxy records and show that temperature is correlated with and generally lags CO(2) during the last (that is, the most recent) deglaciation. Differences between the respective temperature changes of the Northern Hemisphere and Southern Hemisphere parallel variations in the strength of the Atlantic meridional overturning circulation recorded in marine sediments. These observations, together with transient global climate model simulations, support the conclusion that an antiphased hemispheric temperature response to ocean circulation changes superimposed on globally in-phase warming driven by increasing CO(2) concentrations is an explanation for much of the temperature change at the end of the most recent ice age.

OBJECTIVE

To determine if there is a gender difference in the incidence and outcomes of sport concussion.

METHODS

Critical literature review of sport concussion by gender.

METHODS

PubMed and major sports medicine journals were reviewed using the keywords concussion and gender. Articles included in this paper were English prospective surveillance that included concussion as an injury option conducted over the past 10 years, involved data collected by qualified medical personnel (athletic trainers/therapists or medical doctors) and used injury rates as opposed to raw counts. Only data from sports (soccer, basketball and ice hockey) where actions, equipment and most rules were similar between genders were reviewed.

RESULTS

For the PubMed search, using "concussion" and "gender" as keywords, there were 51 articles. Ten studies (four in football (soccer), four in basketball and two in ice hockey, including high school, college and professional athletes) were included in the incidence portion of the paper. Nine of the studies showed higher absolute injury rates for female concussion compared to their male counterparts with four of them reaching statistical significance. Five of the studies (two football (soccer), two basketball and one ice hockey) examined concussion mechanism and in all cases, males had a higher absolute percent of player contact concussions while females had a higher absolute percentage of surface or ball contact concussion episodes. Two brain injury and four sport concussion outcome papers were reviewed. Traumatic brain injury outcome was shown to be worse in females than in males for a majority of measured variables; females also are shown to have different baseline and post-concussion outcomes on neuropsychological testing.

CONCLUSIONS

After evaluating multiple years of concussion data in comparable sports, the evidence indicates that female athletes may be at greater risk for concussion than their male counterparts. There also is some evidence that gender differences exist in outcomes of traumatic brain injury and concussions. Because concussion is a clinical diagnosis often depending on self reporting and with no established biological marker or consistent symptoms/definitions, and because there is evidence that females are more honest in reporting general injuries than males, it is unclear whether the concussion incidence data, while generally consistent in showing a higher risk in females as compared to males in similar sports, is a true difference or is influenced by a reporting bias.

Interleukin-1beta (IL-1beta), a proinflammatory cytokine, is elevated in cigarette smokers. To determine whether IL-1beta plays a role in the pathogenesis of cigarette smoke-induced emphysema and small airway remodeling, IL-1 receptor knockout (IL1RKO), TNF-alpha receptor knockout (TNFRKO), or C57Bl/6 (control) mice were exposed to cigarette smoke acutely or for up to 6 months. With a single acute exposure, smoke elevated IL-1beta in C57Bl/6 mice. IL1RKO mice were protected against acute smoke-mediated increases in lavage inflammatory cells and matrix breakdown. In C57Bl/6 mice, acute smoke-mediated increases in inflammatory cells, serum IL-1beta, and serum TNF-alpha were blocked by z-VAD-fmk, a pan-caspase inhibitor, or z-WEHD-fmk, a caspase-1 (IL-1-converting enzyme, [ICE]) inhibitor. With 6 months of exposure, IL-1beta was no longer increased, but IL-18 was elevated. After 6 months of exposure, IL1RKO mice were 65% protected against emphysema, whereas TNFRKO mice were 83% protected. Both strains were completely protected against small airway remodeling. Lavage desmosine, hydroxyproline, and hyaluronan, matrix breakdown markers, were elevated in C57 but not IL1RKO mice. We conclude that IL-1beta plays a significant role in induction of murine emphysema and small airway remodeling, and is comparable to TNF-alpha in its effects. The protective effects of caspase inhibitors appear to be related to inhibition of ICE and raise the question of whether models that ameliorate emphysema with caspase inhibitors are really blocking IL-1beta (and IL-18) activation rather than blocking apoptosis.

Cryogenic electron tomography (cryo- ET) enables the 3D visualization of biological material at a previously unseeable scale. Carefully controlled cryogenic specimen preparation avoids the artefacts that are notorious to conventional electron microscopy specimen preparation. To date, studies employing cryo- ET have mostly been restricted to isolated macromolecular assemblies, small prokaryotic cells or thin regions of eukaryotic cells owing to the limited penetration depth of electrons through ice-embedded preparations. Recent progress in cryosectioning makes it possible to acquire tomograms from many kinds of vitrified cells and tissues. The systematic and comprehensive interpretation of such tomograms will provide unprecedented insight into the molecular organization of cellular landscapes.

The Wet Chemistry Laboratory on the Phoenix Mars Lander performed aqueous chemical analyses of martian soil from the polygon-patterned northern plains of the Vastitas Borealis. The solutions contained approximately 10 mM of dissolved salts with 0.4 to 0.6% perchlorate (ClO4) by mass leached from each sample. The remaining anions included small concentrations of chloride, bicarbonate, and possibly sulfate. Cations were dominated by Mg2+ and Na+, with small contributions from K+ and Ca2+. A moderately alkaline pH of 7.7 +/- 0.5 was measured, consistent with a carbonate-buffered solution. Samples analyzed from the surface and the excavated boundary of the approximately 5-centimeter-deep ice table showed no significant difference in soluble chemistry.

Although the majority of factor VII (FVII) circulates in the zymogen form, low levels of activated factor VII (FVIIa) have been postulated to exist in plasma and to serve a priming function for triggering of the clotting cascade. However, direct measurement of plasma FVIIa has not previously been possible. We have quantified plasma FVIIa levels using a novel, highly sensitive assay that is free from interference by FVII. Specificity of this clot-based assay results from the use of a mutant tissue factor that is selectively deficient in promoting FVII activation, but retains FVIIa cofactor function. In normal adults, FVIIa was found to be present in plasma (mean: 3.6 ng/mL) with considerable variation between individuals (range: 0.5 to 8.4 ng/mL). FVIIa levels were only loosely correlated with FVII coagulant activity, but were elevated in pregnancy and reduced with oral anticoagulant therapy. Incubation of plasma on ice in glass containers (cold activation) resulted in substantial FVIIa generation. Measurement of plasma forms of factor VII is of potential clinical importance because elevated FVII coagulant activity has been implicated as a significant risk predictor for ischemic heart disease. Clinically, this new assay will now permit direct assessment of the role of plasma FVIIa in thrombotic disorders.

OBJECTIVE

Overactive bladder symptoms due to various etiologies have been successfully treated with capsaicin by desensitization of the temperature sensitive vanilloid receptor TRPV1. Recently another temperature sensitive receptor, TRPM8, activated by menthol and cool temperatures (8C to 28C) was described that may be the proposed cool receptor, at least in part mediating the bladder response in the diagnostic ice water test. We defined the sites of mRNA and protein expression of TRPM8 and TRPV1 in the rat and human genitourinary tract.

METHODS

Prostate, testis, penis, bladder and dorsal root ganglion tissue was obtained from rats. Prostate, testicle, seminiferous tubules, corpus cavernosum, glans, overlying glans skin, scrotal skin and bladder were obtained from human patients. Reverse transcription-polymerase chain reaction was done using species specific primers for TRPM8 and TRPV1. Immunofluorescence staining for TRPM8 was performed in rat tissues as well as in cultured human urothelial cells.

RESULTS

TRPM8 and TRPV1 mRNA were detected in all rat tissues. Human samples demonstrated TRPM8 mRNA in prostate, testicle, seminiferous tubules, scrotal skin and bladder. No TRPM8 mRNA was identified in human corpus cavernosum, glans or overlying glans skin. Separation of layers in human bladder demonstrated mRNA for TRPM8 only in the urothelium and not in the detrusor. Immunofluorescence location of TRPM8 was found in rat prostate, DRG and bladder, and in human urothelial cells in culture. TRPV1 mRNA was detected in all human genitourinary tract tissues.

CONCLUSIONS

These results demonstrate that mRNA and protein for TRPM8 exist in multiple genitourinary organs in the rat and human, and it may be considered a possible new target, as is TRPV1, for the pharmacological treatment of detrusor overactivity or other urological disorders.

We have developed a system to automatically acquire cryo-electron micrographs. The system is designed to emulate all of the decisions and actions of a highly trained microscopist in collecting data from a vitreous ice specimen. These include identifying suitable areas of vitreous ice at low magnification, determining the presence and location of specimen on the grid, automatically adjusting imaging parameters (focus, astigmatism) under low-dose conditions, and acquiring images at high magnification to either film or a digital camera. This system is responsible for every aspect of image acquisition and can run unattended, other than requiring periodic refilling of the cryogens, for over 24 h. The system has been tested out on a variety of specimens that represent typical challenges in the field of cryo-electron microscopy. The results show that the overall performance of the system is equivalent to that of an experienced microscopist.

The blood serums of Antarctic fishes freeze at -2 degrees C, which is approximately 1 degrees C below the melting points of their serums. This thermal hysteresis is due to the influence of serum glycoproteins. The temperatures of freezing and melting of aqueous solutions of the purified glycoproteins suggest that this thermal hysteresis results from the adsorption of the glycoprotein molecule onto the surface of ice crystals.

OBJECTIVE

The longitudinal relationship between the consumption of energy-dense snack (EDS) foods and relative weight change during adolescence is uncertain. Using data from the Massachusetts Institute of Technology Growth and Development Study, the current analysis was undertaken to examine the longitudinal relationship of EDS food intake with relative weight status and percentage body fat and to examine how EDS food consumption is related to television viewing.

METHODS

One hundred ninety-six nonobese premenarcheal girls 8 to 12 years old were enrolled between 1990 and 1993 and followed until 4 years after menarche. At each annual follow-up visit, data were collected on percentage body fat (%BF), BMI z score, and dietary intake. Categories of EDS foods considered were baked goods, ice cream, chips, sugar-sweetened soda, and candy.

RESULTS

At study entry, girls had a mean +/- SD BMI z score of -0.27 +/- 0.89, consumed 2.3 +/- 1.7 servings of EDS foods per day, and consumed 15.7 +/- 8.1% of daily calories from EDS foods. Linear mixed effects modeling indicated no relationship between BMI z score or %BF and total EDS food consumption. Soda was the only EDS food that was significantly related to BMI z score over the 10-year study period, but it was not related to %BF. In addition, a significant, positive relationship was observed between EDS food consumption and television viewing.

CONCLUSIONS

In this cohort of initially nonobese girls, overall EDS food consumption does not seem to influence weight status or fatness change over the adolescent period.

Genetic studies indicated that the Drosophila melanogaster protein REAPER (RPR) controls apoptosis during embryo development. Induction of RPR expression in Drosophila Schneider cells rapidly stimulated apoptosis. RPR-mediated apoptosis was blocked by N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk), which suggests that an interleukin-1 beta converting enzyme (ICE)-like protease is required for RPR function. RPR-induced apoptosis was associated with increased ceramide production that was also blocked by Z-VAD-fmk, which suggests that ceramide generation requires an ICE-like protease as well. Thus, the intracellular RPR protein uses cell death signaling pathways similar to those used by the vertebrate transmembrane receptors Fas (CD95) and tumor necrosis factor receptor type 1.