Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression.     

Fine-scale genetic structure among genetic individuals of the clone-forming monotypic genus Echinosophora koreensis (Fabaceae)

• Background and Aims For rare endemics or endangered plantspecies that reproduce both sexually and vegetatively it iscritical to understand the extent of clonality because assessmentof clonal extent and distribution has important ecological andevolutionary consequences with conservation implications. Asurvey was undertaken to understand clonal effects on fine-scalegenetic structure (FSGS) in two populations (one from a disturbedand the other from an undisturbed locality) of Echinosophorakoreensis, an endangered small shrub belonging to a monotypicgenus in central Korea that reproduces both sexually and vegetativelyvia rhizomes. • Methods Using inter-simple sequence repeats (ISSRs) asgenetic markers, the spatial distribution of individuals wasevaluated using Ripley's L(d)-statistics and quantified thespatial scale of clonal spread and spatial distribution of ISSRgenotypes using spatial autocorrelation analysis techniques(join-count statistics and kinship coefficient, F_ij) for totalsamples and samples excluding clones. • Key Results A high degree of differentiation betweenpopulations was observed (_ST(g) = 0·184, P < 0·001).Ripley's L(d)-statistics revealed a near random distributionof individuals in a disturbed population, whereas significantaggregation of individuals was found in an undisturbed site.The join-count statistics revealed that most clones significantlyaggregate at 6-m interplant distance. The Sp statistic reflectingpatterns of correlograms revealed a strong pattern of FSGS forall four data sets (Sp = 0·072–0·154), butthese patterns were not significantly different from each other.At small interplant distances (2 m), however, jackknifed 95% CIs revealed that the total samples exhibited significantlyhigher F_ij values than the same samples excluding clones. • Conclusion The strong FSGS from genets is consistentwith two biological and ecological traits of E. koreensis: bee-pollinationand limited seed dispersal. Furthermore, potential clone matesover repeated generations would contribute to the observed highF_ij values among genets at short distance. To ensure long-termex situ genetic variability of the endangered E. koreensis,individuals located at distances of 10–12 m should becollected across entire populations of E. koreensis.     

Positional Distribution of Fatty Acids in Glycerolipids of the Marine Red Alga, Porphyra yezoensis

The positional distribution of fatty acids in glycerolipidsfrom thalli of Porphyra yezoensis was studied by enzymatic hydrolysis.In monogalactosyl diacylglycerol, icosapentaenoic acid was amajor fatty acid at both the sn-1 and sn-2 positions of theglycerol moiety, whereas palmitic acid was a minor componentat both positions. In digalactosyl diacylglycerol and sulfoquinovosyldiacylglycerol, icosapentaenoic and palmitic acids were almostexclusively distributed at the sn-1 and sn-2 positions, respectively.In phosphatidylglycerol, palmitic and trans--13-hexadecenoicacid were exclusively located at the sn-2 position. In phosphatidylcholine,icosapentaenoic acid occurred in both the sn-l and sn-2 positions,whereas palmitic acid was confined to the sn-1 position. Itis suggested that monogalactosyl diacylglycerol in P. yezoensissynthesized in both the cytoplasmic and chloroplastic pathways,while the diacylglycerol moieties of the other chloroplast lipidsare virtually all derived from the chloroplastic pathway. (Received March 7, 1986; Accepted April 6, 1987)     

中华蜜蜂信息素结合蛋白ASP1 cDNA的克隆及时空表达

信息素结合蛋白（pheromone binding proteins, PBPs）在昆虫信息素的识别、传递和处理过程中具有重要作用。本研究首次克隆了中华蜜蜂Apis cerana cerana的一个PBP基因Ac-ASP1（GenBank序列号为DQ449670）,其预测蛋白具有典型的气味结合蛋白（OBPs）标志（即成熟肽含有6个保守的半胱氨酸）。利用real-time PCR技术对Ac-ASP1在中蜂不同组织和发育历期的时空表达谱进行了鉴定。绝对定量结果显示Ac-ASP1高丰度地表达于工蜂触角（2.07×10⁶ 拷贝数/μg）,而在其他组织（如头、胸、腹、翅及足）中呈低丰度表达（10²拷贝数/μg）; 相对定量结果显示Ac-ASP1在各发育历期如幼虫、蛹以及成虫发育早期（1～6日龄）均有大量表达,而在21日龄前后具有另外一个高丰度表达时期。这些结果可为明确Ac-ASP1在中蜂蜂王信息素信号识别传递过程中的作用提供参考。     

An investigation into the zooplankton composition of a prominent 38-kHz scattering layer in the North Sea

This study aims to determine the contribution made by zooplanktonto acoustic scattering layers, which are particularly strongat 38 kHz, in the northern North Sea in summer. It uses a combinationof net sampling and forward and inverse acoustic modelling ofdata collected at 38, 120 and 200 kHz in July 2003. Zooplanktonsamples were collected from regions of strong acoustic scatteringin depths to 50 m, using a undulating towed (U-tow) vehicle.Acoustic data recorded simultaneously were scrutinized to determineactual backscattering, expressed as mean volume backscatteringstrength (MVBS) (dB). This observed MVBS (MVBS_obs) was comparedwith backscattering predicted by application of appropriateacoustic models (MVBS_pred) to sampled densities of zooplankton.In all instances, MVBS_obs was greater than MVBS_pred, with thedifference considerably more pronounced at 38 kHz. There wasa weak correlation between MVBS_pred and MVBS_obs at all threefrequencies, with the greatest correlation (r = 0.450, P = 0.545)at 120 kHz. A number of candidate acoustic models were invertedin order to infer the most likely type of scatterer. In mostcases, scatterers with a gas inclusion were predicted by thismethod. Potential sources of inconsistencies between MVBS_predand MVBS_obs were identified which, when considered alongsidethe presented forward and inverse solutions, indicate that 38kHz scattering in particular must be due to sources other thansampled zooplankton.     

Seasonal abundance and distribution of Caridea larvae in Isafjord-deep, north-west Iceland

The abundance and distribution of Candea larvae was studiedin Ísafjord-deep, north-west Iceland, at approximatelymonthly intervals from February 1987 to February 1988 Zooplanktonsampling was made at nine stations along the length of the fjord,while temperature and chlorophyll a measurements from one ofthe stations are also presented Larvae of six species occurredin the samples, Eualus pusiolus and Pandalus borealis were mostnumerous, constituting 62 8 and 25 9% of the larvae respectively.The other species were, in declining order of abundance, Pandalusmontagui, Spirontocaris spp. (S spinus and s lilljeborgii) andSabinea septemcarinata. Eualus pusiolus was of highest abundancein the outer and middle parts of the fjord, while P.borealiswas most common in the middle and inner parts The onset of hatchingof all species in April–May appeared closely linked tothe phytoplankton spring bloom, while the temperature in thefjord was by then near the annual low (2–3°C). Exceptfor E pusiolus, of which a small part of the population produceda second brood during the summer, most of the larvae had disappearedfrom the plankton by the middle of August The monthly carapacegrowth of P.borealis larvae during the summer months was estimatedto be 1.0 mm.     

A comparison of net and gross rates of oxygen production as a function of light intensity in some natural plankton populations and in a Synechococcus culture

In vitrorates of gross and net oxygen production were measuredas a function of light intensity in some plankton communitiescollected from Bedford Basin, Nova Scotia, and in a monoclonalculture of Synechococcus. The rate of gross oxygen productionwas measured by a technique in which the stable oxygen isotope,¹⁸O, serves as a photosynthetic tracer Net oxygen productionwas measured by automated Winkler technique. The rate of communityrespiration in the light was then determined by the differencebetween gross and net rates of oxygen production. In the naturalpopulations examined, neither gross nor net oxygen productionrates were significantly inhibited at the highest light intensitymeasured (500–800 µE m^–2 s^–1) In a samplein which the dark respiration rate was small relative to themaximal rate of production [P_max;sensu Platt et al (1980) JMar. Res., 38, 687–701] the rates of ‘light’respiration were 3 times greater. In two other communities,with high rates of dark respiration relative to P_maxthe ratesof ‘light’ respiration were closer to rates of darkrespiration. In the Synechococcus clone, both gross and netoxygen production rates were inhibited at high light intensities.Rates of ‘light’ respiration were found to varyas a function of light intensity. The greatest rates of respirationwere measured in samples incubated at light intensities thatwere just saturating (100 µE m^–2 s^–1). Therates of ¹⁴C production were also measured as a function oflight intensity The photosynthetic quotients, based on ¹⁴C productionrates and gross oxygen production rates, average 1 9     

Transplantation Immunity in Annelids. III. Effects of Temperature on Xenograft Rejection in Earthworms

Earthworms are capable of destroying body wall xenografts. Xenograftstransplanted Eisenia foetidaLumbricus terrestris at varioustemperatures showed that graft survival time is inversely proportionalto temperature in both cases. Colder temperatures slow graftrejection, but higher temperatures, up to optimal limits, accelerategraft destruction. At 21 C, Eisenia grafts on Lumbricus hostsare rejected faster than at any other experimental temperature;the variability in individual times is lessened. Beginning at23 C sub-optimal conditions are approached. Thus, graft survivaltimes are more prolonged. Lumbricus grafts on Eisenia hostsare rejected most quickly at 23 C; at 27 C all Eisenia are dead.A review of the earthworm's general thermal dependence is presentedand a rationalization for prolonged second-set graft survival(negative memory) at low temperatures is given. Temperatureeffects probably account for the lack of positive memory at15 C from previous studies.     

Up‐regulated SAMD9L modulated by TLR2 and HIF‐1α as a promising biomarker in tuberculosis

The aim of this study was to identify potential biomarkers of TB in blood and determine their function in Mtb‐infected macrophages. First of all, WGCNA was used to analyse 9451 genes with significant changes in TB patients’ whole blood. The 220 interferon‐γ‐related genes were identified, and then 30 key genes were screened using Cytoscape. Then, the AUC values of key genes were calculated to further narrow the gene range. Finally, we identified 9 genes from {"type":"entrez-geo","attrs":{"text":"GSE19444","term_id":"19444"}}GSE19444. ROC analysis showed that SAMD9L, among 9 genes, had a high diagnostic value (AUC = 0.925) and a differential diagnostic value (AUC>0.865). To further narrow down the range of DEGs, the top 10 hub‐connecting genes were screened from monocytes ({"type":"entrez-geo","attrs":{"text":"GSE19443","term_id":"19443"}}GSE19443). Finally, we obtained 4 genes (SAMD9L, GBP1, GBP5 and STAT1) by intersections of genes from monocytes and whole blood. Among them, it was found that the function of SAMD9L was unknown after data review, so this paper studied this gene. Our results showed that SAMD9L is up‐regulated and suppresses cell necrosis, and might be regulated by TLR2 and HIF‐1α during Mtb infection. In addition, miR‐181b‐5p is significantly up‐regulated in the peripheral blood plasma of tuberculosis patients, which has a high diagnostic value (AUC = 0.969).     

Do the polyunsaturated aldehydes produced by Phaeocystis pouchetii (Hariot) Lagerheim influence diatom growth during the spring bloom in Northern Norway?

The marine bloom-forming phytoplankter Phaeocystis pouchetii(Prymnesiophyceae) is known to produce and release the cytotoxic,ß,,-unsaturated aldehyde 2-trans-4-trans-decadienal(DD), known to inhibit mitotic cell divisions in several differentcell types. The possible allelopathic effects of DD on monoculturesof three common diatoms from the coastal waters of northernNorway were assessed. The results showed that division ratesfor all three diatom species (Skeletonema costatum, Chaetocerossocialis and Thalassiosira antarctica) decreased as concentrationof DD increased. Furthermore field data from the spring bloomin Vestfjorden (2000 and 2001) were analysed to examine whetherthe presence of P. pouchetii influences other species adversely.Our data revealed no significant adverse effect of P. pouchetiion diatom presence since diatom diversity generally was positivelycorrelated to P. pouchetii biomass. The year with the lowestamounts of P. pouchetii had the lowest diversities, and thediatom species composition and abundance was comparable to situationswhere P. pouchetii was either absent or present in minute amounts.At some instances low diversity co-occurred with large fractionsof P. pouchetii, but since this were at the strongest verticalmixing we believe this to be a result of physical control. P.pouchetii and S. costatum were the most frequently co-occurringspecies, and since they are both known producers of polyunsaturatedaldehydes we cannot exclude the possibility that the presenceof DD released from P. pouchetii induced by heavy grazing mightinfluence the growth of other phytoplankton species.     

Phenotypic plasticity of larval retreat design in a net-spinning caddisfly

Larval Macrostemum carolina caddisflies construct silken catchnetswithin protective retreats, often on submerged trees and branches(i.e., snags). In the Savannah River, M. carolina larvae constructthree distinct retreats that differ in the configuration ofthe water entrance hole: (1) at the end of a silken tube, (2)flush with the top of the retreat, and (3) backed by a 180-degreesilken backstop. To identify the proximate mechanism mediatingthis retreat polymorphism, we removed larvae of known phenotypefrom their original retreats and brought them into the laboratory,allowing them to construct new retreats. We found that (1) larvaecan construct more than one type of retreat, so variation inthis behavior is not under strict genetic control; (2) larvaedo not preferentially reconstruct their original retreat design,so these alternative behaviors apparently exhibit little heritability;and (3) larvae primarily construct each phenotype in a particularmicrohabitat (i.e., "tube" and "backstop" retreats are principallyconstructed on the downstream half of the snag, and "flush"retreats on the upstream–bottom quadrant). Therefore,the retreat polymorphism in M. carolina is phenotypically plasticand is controlled by microhabitat location or a correlated environmentalvariable. Most net-spinning caddisflies construct their netsin fairly specific microhabitats. However, behavioral plasticityallows M. carolina larvae to construct retreats all around asnag, thereby reducing potentially intense competition for spacewith other net-spinning caddisflies. Consequently, this maybe the ultimate reason this polymorphism evolved.     

Application of Monoculture Yield/Density Relationships to Plant Competition in Binary Additive Series

Binary additive series experiments involving various pairedcombinations of barnyardgrass (BYG), redroot pigweed (RPW),green foxtail (GFT) and rape (RPS) were undertaken in fieldplots in 1980 and 1981. The experimental design used permittedinvestigation of the performance of a one species (the ‘competitor’) over a range of densities, in the presenceof different constant densities of a second species (the ‘indicator’),and as pure stands. Top growth (d.wt after approximately 95d) in monoculture was found to be well-described by de Wit'sspacing formula where M_s is yield, s is space per seed or plant, is maximum(asymptotic) yield at infinite density and ß is spaceper seed or plant at half the maximum yield (i.e. /2). The formulawas also found to fit the observed yields of a competing speciesover the entire range of densities of an indicator. Correlationcoefficients between observed yields and values calculated bymeans of the spacing formula ranged from 0.934 to 0.999, withmost greater than 0.990. The changes in the slopes of a competingspecies' yield curves as indicator density increases reflectthe competitive abilities of the pair of species present. Barnyardgrassand RPS were found to be strong competitors against RPW andGFT, and RPW strongly competed against GFT. The spacing formulacan thus be used to predict the performance of a competing speciesin additive series experiments, and thereby provides anothermeans of investigating crop-weed and other interactions. Echinochloa crusgalli (L.) Beauv., Setaria viridis (L.) Beauv., Amaranthus retroflexus L., Brassica napus L., barnyardgrass, green foxtail, redroot pigweed, rape, competition, binary additive series, yield/density relationships     

Photophosphorylation in intact algae: Effects of inhibitors, intensity of light, electron acceptor and donors

The luciferin-luciferase method was used to determine ATP extractedfrom darkmaintained and light-exposed samples of the green algaChlorella pyrenoidosa and of the blue-green alga Anacystis nidulans.A few measurements on Synechococcus lividus (a bluegreen thermophile,clone 65?C) are also reported.

1. The light-minus-dark ATP levels (ATP) from aerobic cells ofChlorella and Anacystis were negative; however, ATP from Synechococcuswas positive. Large positive ATP was obtained in regularly grown(RG: moderate light) Chlorella treated with oligomycin; darklevels were reduced, light levels remained essentially unaffected.In high-light exposed (HLE) Chlorella, oligomycin reduced bothlight and dark ATP levels, but positive ATP was still obtained.However, in Anacystis, which has a different organization ofthylakoid membrane, oligomycin severely reduced both the lightand the dark ATP levels and the ATP remained negative.
2. Theoligomycin (12 µM) treated Chlorella and the untreatedAnacystis and Synechococcus show the presence of cyclic photophosphorylationunder conditions in which the non-cyclic electron flow fromphotosystem II to photosystem I is blocked by 10 µM 3-(3,4-dichlorophenyl)-l,l-dimethylurea(DCMU), or not allowed to operate by the absence of CO₂. Cyclicphotophosphorylation ranged from 10–30% of the maximumATP in RG, to 40–50% in HLE Chlorella. In RG Chlorella,cyclic and non-cyclic (in the absence of DCMU) photophosphorylation(ATP) saturate at about 10³ ergs cm^–2 sec^–1 and10⁴ ergs cm^–2 sec^–1 and 10⁴ ergs cm^–2 sec^–1red (>640 nm) light, respectively; a lag was observed inthe light curve.
3. In Chlorella, the addition of the photosystemI electron acceptormethyl viologen (MV; 1 mM) increased ATPby twofold. Furtheraddition of DCMU (25 µm) reduced thisto the level observedwith DCMU alone. If 1 mM reduced dichlorophenolindophenol orphenazine methosulphate (DCPIPH₂ or PMSH₂, respectively)wasadded along with DCMU, the ATP level was 30–40% ofthecontrol. Further addition of MV increased the JATP to be70–80%of that of the control. These and other resultsconfirm thepresence of both non-cyclic and cyclic photophosphorylationin vivo, the former predominating in Chlorella, and the latterin Anacystis and Synechococcus.

(Received May 1, 1973; )     

Carbon Metabolism in Seagrasses: III. ACTIVITIES OF CARBON-FIXING ENZYMES IN RELATION TO INTERNAL SALT CONCENTRATIONS

The internal salt content and distribution in photosynthetictissues as well as the effect of NaCl on photosynthetic carbonfixation enzymes was investigated in two seagrass species fromthe Red Sea. Concentrations of both Na⁺ and Cl^– were lower in the chloroplast-richepidermis than in underlying cell layers in Halophila stipulacea.In Halodule uninervis, the concentration of Na⁺ was lower inthe epidermis than in the underlying cells, while K⁺ was evenlydistributed between cell layers. The epidermal concentrationsof Na+ were estimated to be 0.17 and 0.10 M for Halophila stipulaceaand Halodule uninervis, respectively, which were about to the average leaf concentrations. Epidermal Cl^– concentrationof Halophila stipulacea was estimated to be 0.08 M, a valueonly about of the overall leaf concentration. Phosphoenolpyruvate carboxylase (PEPcase) extracted from leavesof these seagrasses showed increased activity at 0.05–0.3M NaCl in vitro. Ribulose-l, 5-bisphosphate carboxylase (RuBPcase)activity, on the other hand, was inhibited by NaCl at all testedconcentrations. At epidermal NaCl concentrations, PEPcase activitywas thus stimulated while RuBPcase was inhibited. The reducedRuBPcase activity at such concentrations compared to salt-freeconditions was still sufficient to account for observed photosyntheticrates. We conclude that these seagrasses have adapted to a saline environmentboth by maintaining relatively low ion concentrations in theepidermis where photosynthesis occurs and by having carbon-fixingenzymes capable of functioning in the presence of salt.     

Denervation produces different single fiber phenotypes in fast- and slow-twitch hindlimb muscles of the rat

Using a single, mechanically skinned fiber approach, we tested the hypothesis that denervation (0 to 50 days) of skeletal muscles that do not overlap in fiber type composition [extensor digitorum longus (EDL) and soleus (SOL) muscles of Long-Evans hooded rats] leads to development of different fiber phenotypes. Denervation (50 day) was accompanied by 1) a marked increase in the proportion of hybrid IIB/D fibers (EDL) and I/IIA fibers (SOL) from 30% to >75% in both muscles, and a corresponding decrease in the proportion of pure fibers expressing only one myosin heavy chain (MHC) isoform; 2) complex muscle- and fiber-type specific changes in sarcoplasmic reticulum Ca²⁺-loading level at physiological pCa 7.1, with EDL fibers displaying more consistent changes than SOL fibers; 3) decrease by 50% in specific force of all fiber types; 4) decrease in sensitivity to Ca²⁺, particularly for SOL fibers (by 40%); 5) decrease in the maximum steepness of the force-pCa curves, particularly for the hybrid I/IIA SOL fibers (by 35%); and 6) increased occurrence of biphasic behavior with respect to Sr²⁺ activation in SOL fibers, indicating the presence of both slow and fast troponin C isoforms. No fiber types common to the two muscles were detected at any time points (day 7, 21, and 50) after denervation. The results provide strong evidence that not only neural factors, but also the intrinsic properties of a muscle fiber, influence the structural and functional properties of a particular muscle cell and explain important functional changes induced by denervation at both whole muscle and single cell levels. mechanically skinned fibers; myosin heavy chain isoforms; lineage; sarcoplasmic reticulum; Ca²⁺; Sr²⁺ sensitivity; Long-Evans hooded rat     

AN f-TYPE CYTOCHROME FROM CHLORELLA VULGARIS

A method for isolating an f-type cytochrome (Chlorella cytochrome554) from Chlorella vulgaris var. viridis (CHODAT) utilizingN, N-diethylaminoethylcellulose is described. The spectrum ofreduced Chlorella cyt. 554 has absorption maxima at 554 mµ(-band), 524 mµ (ß-band), 417 mµ (SORETband), 352 mµ, 319 mµ and 277 mµ (proteinband). The oxidized form has absorption maxima at 554mµ530 mµ, (ß-band), 412 mµ (SORET band),360mµ 322 mµ and 275 mµ (protein band). Thespectral characteristics resembled other f-type cytochromes,e. g. in the high SORET to -extinction ratio (6.8) and an asymmetric-absorption band (especially at liquid N₂ temperature) ; butcharacteristic differences were present. Mitochondria from whitelupine seedlings and sweet potato roots reduced Chlorella cyt.554. From the effects of antimycin A and 2-heptyl-4-hydroxyquinolineN-oxide it appears that Chlorella cyt. 554 was reduced sequentiallybefore cytochrome a+a₃ and near the level of the cytochromesof the b type. Oxidation was slow using lupine mitochondriaand nil with sweet potato mitochondria. The oxidation-reductionpotential at pH 7.2 and 30? was 0.35 V. Ascorbate, cysteine,glutathione and Na₂S₂O₄ readily reduced Chlorella cyt. 554.The cytochrome was not autoxidizable and was slowly oxidizedby excess potassium ferricyanide. The reduced form did not reactwith CO and was not adsorbed by IRC-50 or Cellex-P cation exchangers. ¹ Temporary address until September 1961: Department of HorticulturalScience, University of California, Los Angeles 24, California,U. S. A. ² Present address: Plant Industry Station, Pioneering ResearchLaboratory, Marketing Quality Research Division, AgriculturalMarketing Service, Beltsville, Maryland, U. S. A. (Received January 16, 1961; )     

Modeling developmental changes in strength and aerobic power in children

The present studyexamined two contrasting multilevel model structures to describe thedevelopmental (longitudinal) changes in strength and aerobic power inchildren: 1) an additive polynomial structure and 2) a multiplicativestructure with allometric body size components. On the basis of themaximum log-likelihood criterion, the multiplicative "allometric"model was shown to be superior to the additive polynomial model whenfitted to the data from two published longitudinal studies and toprovide more plausible solutions within and beyond the range ofobservations.The multilevel regression analysis ofstudy 1 confirmed that aerobic powerdevelops approximately in proportion to body mass,m^1/3. Theanalyses from study 2 identified asignificant increase in quadriceps and biceps strength, in proportionto body size, plus an additional contribution from age, centered atabout peak height velocity (PHV). The positive "age" term forboys suggested that at PHV the boys were becoming stronger in thequadriceps and biceps in relation to their body size. In contrast, thegirls' age term was either negligible (quadriceps) or negative(biceps), indicating that at PHV the girls' strength was developing inproportion to or, in the case of the biceps, was becoming weaker inrelation to their body size.