Cholecystokinin, a satiety signal in newborn infants?

This study was undertaken in order to describe circulating glucose and cholecystokinin (CCK) concentrations in relation to the spontaneous feeding behavior of the human newborn infant. Eighty-three, healthy, 3-days-old infants were studied in connection with breast feeding. Blood samples from the infants were cross-sectionally collected before feeding, 5 and 10 min after the start of sucking, and after the infants had sucked ad libitum. Before feeding, the infants presented a typical "hunger behavior", which changed in connection with breast feeding into a pattern associated with satiety. A significant increase in the plasma CCK concentration was found, 5 min (P = 0.004) and 10 min (P = 0.02) after the start of sucking, as well as after feeding (P = 0.04). Furthermore, a positive correlation between the CCK concentration and the volume of ingested milk was found 10 min after the start of sucking, when 91% of of the volume of milk had been ingested; Rs = 0.51, n = 19, P < 0.02. However, no change was found in the glucose concentration in connection with breast feeding. It is concluded that CCK may be important as a satiety factor in the regulation of food intake in the newborn infant.     

Endoreduplication and development: rule without dividing?

Endoreduplication, a strategy to amplify nuclear DNA without cell division, is very common but poorly understood in plants. Recent findings in Drosophila provide a first picture of the molecular mechanism, which appears to be conserved between plants and animals. In Arabidopsis, the study of trichomes, leaf epidermis and hypocotyl cells sheds new light on the developmental regulation of this process, and its relation to cell expansion.     

Seed development: With or without sex?

In Arabidopsis, mutations in the genes FIE, FIS2 or MEDEA disrupt the normal dependence of seed development on fertilization. The products of these genes are similar to Polycomb group proteins, suggesting possible mechanisms for determining whether seeds can be produced sexually or asexually.     

New analogs of physostigmine: Alternative drugs for Alzheimer's disease?

The synthesis of a series of physostigmine analogs, in which the methylcarbamyl group has been substituted with monoalkylcarbamyl, dimethyl- and diethylcarbamyl groups, is reported. These compounds were prepared with the aim of investigating their possible therapeutic effects in the treatment of Alzheimer's type dementia. The new analogs of physostigmine are inhibitors of acetylcholinesterase from Electroforus electricus, with a value of the reactivation constant, k3 smaller than the one of physostigmine. The percentage of anticholinesterase activity in vitro and in vivo, the acute toxicity and some behavioural effects were also evaluated for selected derivatives. The reactivation constant, in vitro, supports the view that the derivatives described would be more suitable for therapeutic use than physostigmine.     

NMCP/LINC proteins: Putative lamin analogs in plants?

Lamins are the main components of the metazoan lamina, and while the organization of the nuclear lamina of metazoans and plants is similar, there are apparently no genes encoding lamins or most lamin-binding proteins in plants. Thus, the plant lamina is not lamin-based and the proteins that form this structure are still to be characterized. Members of the plant NMCP/LINC/CRWN protein family share the typical tripartite structure of lamins, although the 2 exhibit no sequence similarity. However, given the many similarities between NMCP/LINC/CRWN proteins and lamins (structural organization, position of conserved regions, sub-nuclear distribution, solubility, and pattern of expression), these proteins are good candidates to carry out the functions of lamins in plants. Moreover, functional analysis of NMCP/LINC mutants has revealed their involvement in maintaining nuclear size and shape, another activity fulfilled by lamins. This review summarizes the current understanding of NMCP/LINC proteins and discusses future studies that will be required to demonstrate definitively that these proteins are plant analogs of lamins.     

Genes without frontiers?

For bacteria, the primary genetic barrier against the genetic exchange of DNA that is not self-transmissible is dissimilarity in the bacterial DNA sequences concerned. Genetic exchange by homologous recombination is frequent among close bacterial relatives and recent experiments have shown that it can enable the uptake of closely linked nonhomologous foreign DNA. Artificial vectors are mosaics of mobile DNA elements from free-living bacterial isolates and so bear a residual similarity to their ubiquitous natural progenitors. This homology is tightly linked to the multitude of different DNA sequences that are inserted into synthetic vectors. Can homology between vector and bacterial DNA enable the uptake of these foreign DNA inserts? In this review we investigate pUC18 as an example of an artificial vector and consider whether its homology to broad host-range antibiotic resistance transposons and plasmid origins of replication could enable the uptake of insert DNA in the light of studies of homology-facilitated foreign DNA uptake. We also discuss the disposal of recombinant DNA, its persistence in the environment and whether homologies to pUC18 may exist in naturally competent bacteria. Most DNA that is inserted into the cloning site of artificial vectors would be of little use to a bacterium, but perhaps not all.     

Assimilation without groups?

In “Origins and Destinations”, Luthra, Soehl and Waldinger aim at “extending the canon” in research on immigrant integration. They do so by studying group and individual level characteristics across a large number of origin groups, thereby replacing group labels with theoretically relevant variables at the group level. In this review, three challenges in this endeavour are discussed: First of all, the analyses do not allow to disentangle the impact of group and individual level characteristics for all variables alike. Secondly, a primary data collection more tailored to the specifics of their conceptual framework is needed. This would many conclusions about how contexts of emigration and immigration truly matter above and beyond individual characteristic on a more solid ground. And third, the authors’ aim to abandon the use of origin group categories in empirical research on immigrant integration may come at a price.     

The physiological role of GLP-1 in human: incretin, ileal brake or more?

The proglucagon-derived peptide glucagon-like peptide-1 (GLP-1) is an intestinal signal peptide postprandially released from the L cells of the lower gut. Exogenously administered the synthetic hormone exerts a glucose-dependent insulinotropic effect at the pancreatic beta-cells and lowers plasma glucagon by an inhibitory effect against the alpha-cells. It delays gastric emptying by relaxation of the gastric fundus, inhibition of antral contractility, and stimulation of both the tonic and phasic motility of the pyloric sphincter. Enhancement of insulin, suppression of glucagon, and inhibition of gastric emptying are the main determinants controlling glucose homeostasis with GLP-1. Human studies employing the specific GLP-1 receptor antagonist exendin(9-39) show that endogenously released GLP-1 likewise controls fasting plasma glucagon, stimulates insulin, and influences all the motoric mechanisms known to control gastric emptying. Therefore, GLP-1 is discussed as an incretin hormone and as an enterogastrone in man. Synthetic GLP-1 also suppresses gastric acid and pancreatic enzyme secretion. The inhibitory effects on upper gastrointestinal functions are at least partly mediated by vagal-cholinergic inhibition and may involve interactions with vagal afferent pathways and/or circumventricular regions within the CNS. GLP-1 is a candidate humoral mediator of the 'ileal brake' exerting inhibition of upper gastrointestinal function preventing malabsorption and postprandial metabolic disturbances. As human studies indicate a central action of GLP-1 in reduction of food intake, it is uncertain if this is a consequence of induction of satiety or of transduction of visceral aversive stress signals.     

Allosteric Modulation of the Activity of the Glucagon-like Peptide-1 (GLP-1) Metabolite GLP-1 9–36 Amide at the GLP-1 Receptor

Glucagon-like peptide-1 (GLP-1) released from intestinal L cells in response to nutrients has many physiological effects but particularly enhances glucose-dependent insulin release through the GLP-1 receptor (GLP-1R). GLP-1 7–36 amide, the predominant circulating active form of GLP-1, is rapidly truncated by dipeptidyl peptidase-4 to GLP-1 9–36 amide, which is generally considered inactive. Given its physiological roles, the GLP-1R is targeted for treatment of type 2 diabetes. Recently ‘compound 2’ has been described as both an agonist and positive allosteric modulator of GLP-1 7–36 amide affinity, but not potency, at the GLP-1R. Importantly, we demonstrated previously that exendin 9–39, generally considered a GLP-1R antagonist, enhances compound 2 efficacy (or vice versa) at the GLP-1R. Given that GLP-1 9–36 amide is the major circulating form of GLP-1 post-prandially and is a low affinity weak partial agonist or antagonist at the GLP-1R, we investigated interaction between this metabolite and compound 2 in a cell line with recombinant expression of the human GLP-1R and the rat insulinoma cell line, INS-1E, with native expression of the GLP-1R. We show compound 2 markedly enhances efficacy and potency of GLP-1 9–36 amide for key cellular responses including AMP generation, Ca²⁺ signaling and extracellular signal-regulated kinase. Thus, metabolites of peptide hormones including GLP-1 that are often considered inactive may provide a means of manipulating key aspects of receptor function and a novel therapeutic strategy.     

下丘脑室旁核注射GLP-1 对糖尿病大鼠中枢GLP-1 受体表达

目的:探讨下丘脑室旁核(hypothalamic paraventricular nucleus,PVN)注射GLP-1(胰高血糖素样肽-1)对糖尿病大鼠胃排空的影响及机制。方法:30只Wistar大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)和GLP-1干预组(GLP-1组),每组各10只。DM组和GLP-1组腹腔注射链脲佐菌素,三组大鼠均PVN区埋置套管,恢复7d,GLP-1组微量注射0.5μg/0.5μl的GLP-1,NC组和DM组大鼠PVN区微量注射等体积生理盐水。甲基纤维素-酚红灌胃法检测胃排空;半定量RT-PCR检测大鼠下丘脑GLP-1RmRNA的表达。结果:DM组胃排空率较NC组明显升高(P<0.05),GLP-1组胃排空明显低于DM组(P<0.05),GLP-1组和NC组差异无统计学意义(P>0.05)。GLP-1组下丘脑GLP-1RmRNA的表达明显高于DM组和NC组(P<0.05),并与胃排空率成负相关(P<0.05)。DM组和NC组差异无统计学意义(P>0.05)。结论:PVN区注射GLP-1可以抑制糖尿病大鼠早期胃排空加速,作用机制可能和促进下丘脑GLP-1受体表达有关。     

Gene transfer in bacteria: speciation without species?

Although Bacteria and Archaea reproduce by binary fission, exchange of genes among lineages has shaped the diversity of their populations and the diversification of their lineages. Gene exchange can occur by two distinct routes, each differentially impacting the recipient genome. First, homologous recombination mediates the exchange of DNA between closely related individuals (those whose sequences are sufficient similarly to allow efficient integration). As a result, homologous recombination mediates the dispersal of advantageous alleles that may rise to high frequency among genetically related individuals via periodic selection events. Second, lateral gene transfer can introduce novel DNA into a genome from completely unrelated lineages via illegitimate recombination. Gene exchange by this route serves to distribute genes throughout distantly related clades and therefore may confer complex abilities--not otherwise found among closely related lineages--onto the recipient organisms. These two mechanisms of gene exchange play complementary roles in the diversification of microbial populations into independent, ecologically distinct lineages. Although the delineation of microbial "species" then becomes difficult--if not impossible--to achieve, a cogent process of speciation can be predicted.     

Apoptosis without caspases: an inefficient molecular guillotine?

Since the discovery that the cysteine protease CED-3 was essential for developmental death in the nematode C. elegans, the search has been on to identify homologous proteases governing mammalian apoptosis. Fourteen of these proteases, now called caspases, have been found to date, and studies with natural or chemical inhibitors, and more recently knock-out mice, confirmed the involvement of at least a subset of these proteases in various forms of mammalian apoptosis. However, there has been recent evidence that some apoptotic morphologies, such as cell shrinkage, membrane blebbing and nuclear condensation, are not blocked by caspase inhibitors and that the cells continue to die in a protracted and inefficient manner. This has led to the notion that caspases are not required for all aspects of apoptosis in mammals. Here we review the current knowledge about caspase-independent apoptosis, discuss the strengths and weaknesses of the reasoning that led to its proposition and provide insights into its possible regulation and physiological significance.     

Asexual Evolution: Can Species Exist without Sex?

Most explanations for the existence of species involve a role for sex. A new study of a group of asexual rotifers supports the idea that selection for a common ecological niche can produce a pattern that mimics sexual species, even in the absence of sex.     

Oxytocinergic and serotonergic systems involvement in sodium intake regulation: satiety or hypertonicity markers?

Previous studies demonstrated the inhibitory participation of serotonergic (5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD-induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD-induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5-HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and non-depleted animals. The OT plasma levels significantly increased only in the PD-induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.     

Sympatric speciation without borders?

The biogeography of speciation remains a controversial issue and the process of allopatric speciation reigns. Sympatric speciation differs from allopatric speciation in terms of geographic setting and the role of selection in bringing about reproductive isolating mechanisms, making it a particularly fascinating and controversial subject for evolutionary biologists. Mayr (1947) explained the difference eloquently: for allopatric speciation, populations spatially diverge and then become reproductively isolated; for sympatric speciation, populations first become reproductively isolated and then diverge. Because of this, sympatric speciation is difficult to show empirically and most evolutionary biologists agree that strict ecological, evolutionary, and geographic criteria must be met ( Coyne & Orr 2004 ). In this issue, Crow et al. (2010) challenge us to expand the definition of sympatric speciation by studying species of marine fishes that they propose have arisen by sympatric speciation in a setting that does not appear to conform to the usual geographical criteria.