Canonical antigen-binding loop structures in immunoglobulins: more structures, more canonical classes?

Grafting the antigen-binding loops onto a human antibody scaffold is a widely used technique to humanise murine antibodies. The success of this approach depends largely on the observation that the antigen-binding loops adopt only a limited number of canonical structures. Identification of the correct canonical structure is therefore essential. Algorithms that predict the main-chain conformation of the hypervariable loops using only the amino acid sequence often provide this information. Here, we describe new canonical loop conformations for the hypervariable regions H1 and H2 as found in single-domain antibody fragments of dromedaries or llama. Although the occurrence of these new loop conformations was not predicted by the algorithms used, it seems that they could occur in human or mouse antigen-binding loops. Their discovery indicates that the currently used set of canonical structures is incomplete and that the prediction algorithms should be extended to include these new structures.     

Are Chaoborus larvae more abundant in acidified than in non-acidified lakes in Central Canada?

Eriksson et al (1980) hypothesized that the abundance of certain macroinvertebrate predators, such as larvae of the phantom midge Chaoborus , should increase in acidified lakes because of the elimination of fish. To examine the influence of pH and presence of fish on Chaoborus abundance, we surveyed Chaoborus populations in 33 lakes in Ontario, Canada which ranged in pH from 4.5 to 7.4. Chaoborus larvae were not more abundant in the acidified lakes that were devoid of fish than in the remaining lakes. Therefore, we concluded that pH and presence of fish are not prime determinants of total Chaoborus abundance in Canadian Shield lakes. We hypothesized that significant increases in Chaoborus abundance should only be anticipated when fish populations are eliminated by acidification of relatively nutrient rich lakes.     

mTOR signaling in protein homeostasis: Less is more?

A proper balance between synthesis, maturation and degradation of cellular proteins is crucial for cells to maintain physiological functions. The costly process of protein synthesis is tightly coupled to energy status and nutrient levels by the mammalian target of rapamycin (mTOR), whereas the quality of newly synthesized polypeptides is largely maintained by molecular chaperones and the ubiquitin-proteasome system. There is a wealth of evidence indicating close ties between the nutrient signaling pathway and the intracellular stress response. Dysregulation of both systems has been implicated in aging and age-associated pathologies. In this review, we describe molecular mechanisms underlying the connection between mTOR and the chaperone network and discuss the importance of their functional interaction in growth and aging.Key words: target of rapamycin, stress response, ribosome, chaperone, translation, folding, degradation, aging     

Molecular domestication – more than a sporadic episode in evolution

Transposable elements are short but complex pieces of DNA or RNA containing a streamlined minimal-genome with the capacity for its selfish replication in a foreign genomic environment. Cis-regulatory sections within the elements orchestrate tempo and mode of TE expression. Proteins encoded by TEs mainly direct their own propagation within the genome by recruitment of host-encoded factors. On the other hand, TE-encoded proteins harbor a very attractive repertoire of functional abilities for a cell. These proteins mediate excision, replication and integration of defined DNA fragments. Furthermore, some of these proteins are able to manipulate important host factors by altering their original function. Thus, if the host genome succeeds in domesticating such TE-encoded proteins by taming their ‘anarchistic behavior,’ such an event can be considered as an important evolutionary innovation for its own benefit. In fact, the domestication of TE-derived cis-regulatory modules and protein coding sections took place repeatedly in the course of genome evolution. We will present prominent cases that impressively demonstrate the beneficial impact of TEs on host biology over evolutionary time. Furthermore, we will propose that molecular domestication might be considered as a resumption of the same evolutionary process that drove the transition from ‘primitive genomes’ to ‘modern’ ones at the early dawn of life, that is, the adaptive integration of a short piece of autonomous DNA into a complex regulatory network. This revised version was published online in July 2006 with corrections to the Cover Date.     

Patterns of fluctuating asymmetry in the limbs of freshwater turtles: Are more functionally important limbs more symmetrical?

Understanding how selective forces influence patterns of symmetry remains an active area of research in evolutionary biology. One hypothesis, which has received relatively little attention, suggests that the functional importance of morphological characters may influence patterns of symmetry. Specifically, it posits that for structures that display bilateral symmetry, those with greater functional importance should display lower levels of asymmetry. The aim of this study was to examine the patterns of fluctuating asymmetry (FA) present in the limb bones of freshwater turtles in the family Emydidae. Aquatic emydid turtles of the subfamily Deirochelyinae employ a hindlimb-dominant swimming style, suggesting that hindlimbs should display lower levels of FA. Consistent with the morpho-functional hypothesis of symmetry, we found a strong, clade-wise pattern of humeral-biased FA in aquatic Deirochelyinae. In contrast, some emydids of the subfamily Emydinae possess more terrestrial tendencies. As terrestrial locomotion places more equal importance on fore- and hindlimbs, we predicted that such behaviors may minimize differences in FA. No clade-wise pattern was detected in the subfamily Emydinae. We also detected a phylogenetic signal in FA within the femur and discovered that FA has evolved at vastly different rates between the fore- and hindlimbs.     

Test of an environmental flow release in a British Columbia river: does more water mean more fish?

1. Water managers must make difficult decisions about the allocation of streamflows between out‐of‐channel human uses and environmental flows for aquatic resources. However, the effects environmental flows on stream ecosystems are infrequently evaluated. 2. We used a 13‐year experiment in the regulated Bridge River, British Columbia, Canada, to determine whether an environmental flow release designed to increase salmonid productivity was successful. A hierarchical Bayesian model was used to compare juvenile Pacific salmon (Oncorhynchus spp.) abundance before and after the flow release. 3. We found that the total number of salmonids did increase after the release, but most of the gains could be attributed to the rewatering of a previously dry channel located immediately below the dam. In reaches that had flowing water during the baseline period, the response of individual salmon species to the increase in flow was variable, and there was little change in total abundance after the flow release. Our results were inconsistent with both habitat modelling, which predicted a decrease in habitat quality with increasing flow, and holistic instream flow approaches, which imply greater benefits with larger flows. 4. We question whether biotic responses to flow changes can be predicted reliably with currently available methods and suggest that adaptive management or the use of decision tools that account for the uncertainty in the biotic response is required for instream flow decisions when the competing demands for water are great.     

More plant biomass results in more offspring production in annuals,or does it?

Competitive ability in plants has been previously measured almost exclusively in terms of traits related to growth (biomass) or plant size. In this study, however, we used a multi‐species competition experiment with six annuals to measure relative competitive ability in terms of reproductive output, i.e. the number of offspring produced for the next generation. Under greenhouse conditions, plants of each species were started in pots from germinating seeds and were grown singly (free of competition) and at high density in both monocultures and in mixtures with all study species. Several traits traditionally regarded as determinants of competitive ability in plants were recorded for each species grown singly, including: seed mass, germination time, early growth rate and potential plant size (biomass and height). Under competition, several traits were recorded as indicators of relative performance in both monocultures and mixtures, including: biomass of survivors, total number of survivors, number of reproductive survivors, and reproductive output (total seed production) of the survivors. As expected, species that grew to a larger biomass in isolation had higher seed production in isolation. However, none of the traditional plant growth/size‐related traits, measured either in isolation or under competition, could predict between species variation in reproductive output under competition in either monocultures or mixtures. In mixtures, 97% of this variation in reproductive output could be explained by between‐species variation in the number of reproductive survivors. The results indicate that traits measured on plants grown singly may be poor predictors of reproductive output under competition, and that species’ rank order of competitive ability in terms of the biomass of survivors may bear no relationship to their rank order in terms of the number of offspring produced by these survivors. This has important implications for the interpretation of mechanisms of species coexistence and community assembly within vegetation.     

Hybrid speciation in birds: allopatry more important than ecology?

Hybrid speciation was once thought to be rare in animals, but over the past decade, improved molecular analysis techniques and increased research attention have allowed scientists to uncover many examples. In this issue, two papers ( Elgvin et al. 2011 ; Hermansen et al. 2011 ) present compelling evidence for the hybrid origin of the Italian sparrow based on nuclear and mitochondrial DNA sequences, microsatellites, and plumage coloration. These studies point to an important role for geographic isolation in the process of hybrid speciation, and provide a starting point for closer examination of the genetic and behavioural mechanisms involved.     

Suckling behavior in goitered gazelle: do females invest more in twins or singletons?

The mother–offspring social unit is a universal feature in the social life of all mammals and nursing is the most direct and vital component of maternal investment in young. Living in diverse environments, various ungulate species have different strategies for rearing offspring, from bearing a single, relatively large newborn and supplying only limited amounts of milk, to bearing several relatively small newborns with intensive post-partum lactation. In this paper, we consider the rearing strategy of goitered gazelle with a focus on suckling behavior, which, until now, has never been a subject of special investigation. Adult females of this species in their reproductive prime typically bear twins when environmental conditions are favorable, but the proportion of singletons increases when conditions are unfavorable. We expected that in goitered gazelles suckling intensity would be maximal during the first weeks after birth, and then decrease with the growth of the young; we also expected that twins would demand more energy, but receive significantly less maternal investment per young than singletons. We found that, indeed, suckling behavior had similar dynamics as typical of all bovid species, but our expectation for less maternal investment in twins vs. singletons was wrong. In reality, female goitered gazelles suckled twins significantly more intensively and terminated suckling less often compared to singletons. We concluded that in favorable situations females of high quality have the ability to show significantly more maternal investment in each twin, while singletons are typically born to weaker females. This ability of females to produce mostly twins allows goitered gazelles to take advantage of any favorable opportunity to quickly increase their population in an environment with unpredictable and abrupt yearly changes typical of the arid regions of Central Asia.     

ANGPTL8 in metabolic homeostasis: more friend than foe?

ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed.     

Scientific misconduct: more cops, more robbers?

Abandoning an earlier pretense that research misconduct is too rare to matter, the scientific community is trying to figure out how to minimize and police it. Could broadening the definition be the key?     

Do faculty in Southern Indian medical colleges support animal use in postgraduate education more than in undergraduate education?

In India, animal experiments play an integral role in both undergraduate medical education (UGME) and postgraduate medical education (PGME) in the discipline of Pharmacology. Therefore, we aimed to compare the perceptions of pharmacology faculty members in southern India with regard to the use of animal experiments and alternatives in UGME and in PGME. We also determined the association between these perceptions and the socio-demographic characteristics of the participants. Pharmacology faculty members in 15 medical colleges located in southern India answered a 27-statement, 5-domain questionnaire with a total score of 108. The means of the total, domain and statement scores were analysed by the Wilcoxon signed-rank test. The mean total score obtained for faculty members (n = 52) was significantly higher (p < 0.001) for PGME (61.2/108) than that for UGME (51.9/108). Significant differences were observed in the mean total and in the domain scores for PGME when compared to UGME in all of the socio-demographic groups, except for male faculty members and those without an MD or doctoral degree. The mean individual statement scores also indicated that there is more support for animal use in PGME. Overall, it was apparent that pharmacology faculty members in southern Indian medical colleges support animal use in PGME more than in UGME. Increased awareness is required among faculty members concerning alternatives to animal experiments in medical education, especially in PGME.     

Large seasonal fluctuations in whole-tree carbohydrate reserves: is storage more dynamic in boreal ecosystems?

Background and AimsCarbon reserves are a critical source of energy and substrates that allow trees to cope with periods of minimal carbon gain and/or high carbon demands, conditions which are prevalent in high-latitude forests. However, we have a poor understanding of carbon reserve dynamics at the whole-tree level in mature boreal trees. We therefore sought to quantify the seasonal changes in whole-tree and organ-level carbon reserve pools in mature boreal Betula papyrifera.MethodsNon-structural carbohydrate (NSC; soluble sugars and starch) tissue concentrations were measured at key phenological stages throughout a calendar year in the roots, stem (inner bark and xylem), branches and leaves, and scaled up to estimate changes in organ and whole-tree NSC pool sizes. Fine root and stem growth were also measured to compare the timing of growth processes with changes in NSC pools.Key ResultsThe whole-tree NSC pool increased from its spring minimum to its maximum at bud set, producing an average seasonal fluctuation of 0.96 kg per tree. This fluctuation represents a 72 % change in the whole-tree NSC pool, which greatly exceeds the relative change reported for more temperate conspecifics. At the organ level, branches accounted for roughly 48–60 % of the whole-tree NSC pool throughout the year, and their seasonal fluctuation was four to eight times greater than that observed in the stemwood, coarse roots and inner bark.ConclusionsBranches in boreal B. papyrifera were the largest and most dynamic storage pool, suggesting that storage changes at the branch level largely drive whole-tree storage dynamics in these trees. The greater whole-tree seasonal NSC fluctuation in boreal vs. temperate B. papyrifera may result from (1) higher soluble sugar concentration requirements in branches for frost protection, and/or (2) a larger reliance on reserves to fuel new leaf and shoot growth in the spring.