Lasting effects of early life stress in mice: interaction of maternal environment and infant genes

In the mouse, a powerful paradigm of early life stress, infant maternal separation (IMS), can trigger emotional and cognitive dysfunctions in adulthood similar to those found in humans with a history of childhood adversity. The magnitude of IMS effects differs among diverse inbred strains suggesting an interaction between the genetic background of pups and the maternal care they received. Here, we investigated this interaction with studies on reciprocal F1 hybrid mice of the stress‐susceptible Balb/c and the resilient C57Bl/6 strains that were either raised by Balb/c mothers (low maternal care) or by C57Bl/6 mothers (higher maternal care) with or without IMS exposure. The ultrasonic vocalization response to isolation was recorded from infant F1 pups, and their emotional, executive cognitive and epigenetic phenotypes were assessed in adulthood. These studies showed that, regardless of the maternal care received, the emotional phenotype of F1 hybrids was not significantly affected by IMS exposure. However, F1 pups raised by Balb/c (but not C57Bl/6) mothers during IMS exposure exhibit deficits in working memory and attention‐set‐shifting in adulthood. They also exhibit reduced histone deacetylase 1 levels at promotors of brain‐derived neurotrophic factor and early growth response 2 genes, and abnormally high induction of expression of these genes during cognitive testing. As one of affected genes was previously shown to associate with the Balb/c and the other with the C57Bl/6 genetic background, these findings indicate that both parental alleles interact with the maternal environment to modulate the cognitive and epigenetic phenotypes of F1 mice exposed to the IMS.     

Drosophila Sgs genes: Stage and tissue specificity of hormone responsiveness

The up- and down-regulation of the salivary gland secretion protein (Sgs) genes during the third larval instar of Drosophila melanogaster are controlled by fluctuations of the titre of the steroid hormone 20-hydroxyecdysone (20E). Induction of these genes by a low hormone titre is a secondary response to 20E mediated by products of 20E-induced ‘early’ genes. Surprisingly, in the case of the Sgs-4 gene this response also requires a direct contribution of the 20E-receptor complex. A model is presented which proposes that the Sgs genes, and other 20E-regulated genes with similar temporal expression profiles, are regulated by complex hormone response units. The hormonal signal is effectively transmitted by these response units only after binding of additional factors, e.g. secretion enhancer binding proteins, which act together in a synergistic manner with the 20E receptor and early gene products to establish a stage- and tissuespecific expression pattern.     

Vasopressin analgesia: specificity of action and non-opioid effects

Recent neuroanatomical and behavioral evidence has indicated that vasopressin (VP) increases pain thresholds. In the present study intracerebroventricular (ICV) administration of both arginine VP (AVP: 75-500 ng) and 1-deamino-8-D-arginine vasopressin (DDAVP: 150-500 ng) elevated tail flick latencies. Oxytocin (OXY, ICV), also elevated tail-flick latencies (150-1000 ng); however this increase was accompanied by "barrel-roll" seizure activity. VP analgesia was eliminated by pretreatment with 1-deamino-penicillamine-2(O-methyl)tyrosine-AVP (dPTyr(me)AVP: 500 ng, ICV), a VP antagonist, but not naloxone (1 or 10 micrograms, ICV), suggesting that VP modulates nonciceptive thresholds through its own binding sites. Conversely, pretreatment with naloxone (1 micrograms, ICV) but not dPTyr(me)AVP (1 microgram, ICV) attenuated the analgesic efficacy of systemic morphine (10 mg/kg), further dissociating VP and central opiate analgesic processes. Finally, systemic pretreatment with dexamethasone potentiated VP analgesia. These data support the notion that VP is a specific non-opioid pain inhibitor.     

Pattern and process in the afterlife: legacy effects of canopy tree distribution on post‐disturbance regeneration

Wild et al. (2014, Journal of Vegetation Science 25: 1327–1340) document persistent effects of the spatial distribution of canopy trees on the distribution of regeneration following stand‐replacing disturbance in montane Norway spruce forests. The authors suggest a simple physical process for these legacy effects – the accumulation of winter‐dispersed seeds in ‘tree‐wells’ with lower snow depth around the trunks of living and recently dead trees.     

Cardiovascular protection of magnolol: cell-type specificity and dose-related effects

Magnolia officinalis has been widely used in traditional Chinese medicine. Magnolol, an active component isolated from Magnolia officinalis, is known to be a cardiovascular protector since 1994. The multiplex mechanisms of magnolol on cardiovascular protection depends on cell types and dosages, and will be reviewed and discussed in this article. Magnolol under low and moderate dosage possesses the ability to protect heart from ischemic/reperfusion injury, reduces atherosclerotic change, protects endothelial cell against apoptosis and inhibits neutrophil-endothelial adhesion. The moderate to high concentration of magnolol mainly acts on smooth muscle cells and platelets. Magnolol induces apoptosis in vascular smooth muscle cells at moderate concentration and inhibits proliferation at moderate and high concentration. High concentration of magnolol also abrogates platelet activation, aggregation and thrombus formation. Magnolol also serves as an smooth muscle relaxant only upon the high concentration. Oral intake of magnolol to reach the therapeutic level for cardiovascular protection is applicable, thus makes magnolol an agent of great potential for preventing cardiovascular diseases in high-risk patients.     

Suicide and the afterlife: popular religion and the standardisation of 'culture' in Japan

For an overwhelming majority of commentators, including many anthropologists, 'Japanese culture' is still associated with a positive view of suicide. Western-language writings have contributed by feedback loop to perpetuate this stereotype. Besides the local 'samurai ethic', Japanese Buddhism is also said not to prohibit taking one's life. However, the most popular examples of heroic self-sacrifice, from the Edo period to WWII, are fraught with covert contradictions. From ancient times to the present religious practitioners of all sorts have maintained that suicide creates unhappy, resentful spirits who harm the living. This article discusses many examples of a diverse series of narratives, from spirit medium's séances to drama to contemporary films, in which the anguished spirits of suicides are allowed to express themselves directly. After the figures rose alarmingly in the late 1990s various religious organisations have attempted to fight the stigma suffered by bereaved family members and have introduced new interpretations and new rituals.     

Essence of life: essential genes of minimal genomes

Essential genes are absolutely required for cell survival. Determination of the universal minimal set of genes needed to sustain life is, therefore, expected to contribute greatly to our understanding of life at its simplest level, with applications in medicine and synthetic biology. The search for the minimal genome has led to the identification of often variable gene sets. We argue here that, based on the outcome of these analyses, it is becoming increasingly evident that some genes, and the functions encoded by them, are absolutely necessary for the survival of any living entity, whereas others can be omitted. We also examine ways of determining the minimal genome and discuss possible practical applications of a minimal cell.     

Substrate specificity of phosphorylase kinase: effects of heparin and calcium

Phosphorylase b and two peptides with sequences homologous to phosphorylation site 2 (syntide 2) and site 3 (syntide 3) of glycogen synthase were compared as substrates for purified muscle phosphorylase kinase. The substrate specificity of phosphorylase kinase varied according to whether heparin (at pH 6.5) or Ca2+ (at pH 8.2) was used as a stimulator of its activity. Phosphorylase b was preferentially phosphorylated in the presence of Ca2+; the rate of syntide 2 phosphorylation was the same for both stimulators; and the phosphorylation of syntide 3 was completely dependent on the presence of heparin. A kinetic analysis confirmed this stimulator-dependent substrate specificity since both the Vmax and Km for these substrates were affected diversely by heparin and Ca2+. Heparin stimulated phosphorylase kinase maximally at pH 6.5, whereas the effect of Ca2+ was optimal at a pH above 8. However, the stimulator-related substrate specificity could not be explained by the different pH values at which the effects of the stimulators were assessed. Nor did substrate-directed effects by heparin or Ca2+ apparently play a role. No indications were found for a stimulator-dependent specificity in the phosphorylation of sites in protein substrates of phosphorylase kinase (phosphorylase b, the alpha- and beta-subunits of phosphorylase kinase, or glycogen synthase). The diverse substrate specificity of the calcium- and heparin-dependent activities of phosphorylase kinase could be explained in two ways: either by the existence of separate calcium- and heparin-stimulated catalytic sites, or by just one catalytic site with two active conformations. The second possibility is favored by the observation that both calcium and heparin stimulated the isolated gamma-subunit (gamma X calmodulin complex) of phosphorylase kinase.     

Measuring and analyzing tissue specificity of human genes and protein complexes

Proteins and their interactions are essential for the survival of each human cell. Knowledge of their tissue occurrence is important for understanding biological processes. Therefore, we analyzed microarray and high-throughput RNA-sequencing data to identify tissue-specific and universally expressed genes. Gene expression data were used to investigate the presence of proteins, protein interactions and protein complexes in different tissues. Our comparison shows that the detection of tissue-specific genes and proteins strongly depends on the applied measurement technique. We found that microarrays are less sensitive for low expressed genes than high-throughput sequencing. Functional analyses based on microarray data are thus biased towards high expressed genes. This also means that previous biological findings based on microarrays might have to be re-examined using high-throughput sequencing results.     

Isochore specificity of AUG initiator context of human genes

The efficiency of AUG start codon recognition in translation initiation is modulated by its sequence context. Here we investigated a non-redundant set of 5914 human genes and show that this context is different in genes located in different isochores. In particular, of the two main consensus start sequences, RCCaugR is five-fold more represented than AARaugR in genes from the GC-rich H3 isochores compared to genes from the GC-poor L isochores. Furthermore, genes located in GC-rich isochores have shorter 5' UTRs and stronger avoidance of upstream AUG than genes located in GC-poor isochores. This suggests that genes requiring highly efficient translation are located in GC-rich isochores and genes requiring fine modulation of expression are located in GC-poor isochores. This is in agreement with independent data from the literature concerning the location of housekeeping and tissue-specific genes, respectively.     

On the specificity of caffeine effects

Summary Caffeine in 0.1% or higher concentration reversibly inhibits E. coli and yeast growth. It inhibits RNA and protein synthesis (Tables 1+3) within a few minutes after being added to the incubation medium (Fig. 2). The suggestion is made that these effects of caffeine, as well as its synergism with some mutagens, are due to its ability to costack with free purines and to form complexes with single-stranded nucleic acids.     

Substrate specificity of human kallikrein 6: salt and glycosaminoglycan activation effects

Human kallikrein 6 (hK6) is abundantly expressed in the central nervous system and is implicated in demyelinating disease. This study provided biochemical data about the substrate specificity and activation of hK6 by glycosaminoglycans and by kosmotropic salts, which followed the Hofmeister series. The screening of fluorescence resonance energy transfer (FRET) peptide families derived from Abz-KLRSSKQ-EDDnp resulted in the finding that Abz-AFRFSQ-EDDnp (where Abz is ortho-aminobenzoic acid and EDDnp is N-[2,4-dinitrophenyl]ethylenediamine)) is the best synthetic substrate described so far for hK6 (kcat/Km 38,667 s(-1) mm(-1)). It is noteworthy that the AFRFS sequence was found as a motif in the amino-terminal domain of seven human ionotropic glutamate receptor subunits. We also examined the hK6 hydrolytic activity on FRET peptides derived from human myelin basic protein, precursor of the Abeta amyloid peptide, reactive center loop of alpha1-antichymotrypsin, plasminogen, and maturation and inactivation cleavage sites of hK6, which were described earlier as natural substrates for hK6. The best substrates were derived from myelin basic protein. The hK6 maturation cleavage site was poorly hydrolyzed, and no evidence was found to support a two-step self-activation process reported previously. Finally, we assayed FRET peptides derived from sequences that span the cleavage sites for activation of protease-activated receptors (PAR) 1-4, and only the substrate with the PAR 2 sequence was hydrolyzed. These results further supported the hypothesis that hK6 expressed in the central nervous system is involved in normal myelin turnover/demyelination processes, but it is unlikely to self-activate. This report also suggested the possible modulation of ionotropic glutamate receptors and activation of PAR 2 by hK6.     

Sugar-mediated induction of Agrobacterium tumefaciens virulence genes: structural specificity and activities of monosaccharides.

The virulence genes of Agrobacterium tumefaciens are induced by specific plant phenolic metabolites and sugars (G. A. Cangelosi, R. G. Ankenbauer, and E. W. Nester, Proc. Natl. Acad. Sci. USA, in press). In this report, monosaccharides, derivatives, and analogs which induce the vir regulon have been identified and the structural requirements for monosaccharide-mediated induction have been determined. Pyranose sugars with equatorial hydroxyls at C-1, C-2, and C-3 displayed strong vir gene-inducing activity; the C-4 hydroxyl could be epimeric and a wide variety of substitutions at C-5 were permissible. The acidic monosaccharide derivatives D-galacturonic acid and D-glucuronic acid were the strongest inducers among the monosaccharides tested. Eight of the 11 inducing compounds are known plant metabolites, and 7 are monomers of major plant cell wall polysaccharides. A role for monosaccharides and plant phenolic compounds as wound-specific plant metabolites which signal the ChvE/VirA/VirG regulatory system is proposed.     

Anti-abortion strategizing and the afterlife of the Geneva Consensus Declaration

The Geneva Consensus Declaration, introduced by the Trump-Pence administration in 2020 and signed by thirty-two countries, claims that there is no international right to abortion. Although the Declaration was subsequently repudiated by the Biden administration, it did not die. This paper traces the afterlife of the Geneva Consensus Declaration as part of an ongoing antiabortion strategy to form a global coalition. Its supporters hope to mobilize signing nations to remove sexual and reproductive rights from the agendas of multilateral agencies including the United Nations and Organization of American States. The Geneva Consensus Declaration puts antiabortion politics above all other considerations, creating common cause among governments that oppose reproductive and sexual rights by undermining multilateral governance.     

Virulence genes and the evolution of host specificity in plant-pathogenic fungi

In the fungal kingdom, the ability to cause disease in plants appears to have arisen multiple times during evolution. In many cases, the ability to infect particular plant species depends on specific genes that distinguish virulent fungi from their sometimes closely related nonvirulent relatives. These genes encode host-determining "virulence factors," including small, secreted proteins and enzymes involved in the synthesis of toxins. These virulence factors typically are involved in evolutionary arms races between plants and pathogens. We briefly summarize current knowledge of these virulence factors from several fungal species in terms of function, phylogenetic distribution, sequence variation, and genomic location. Second, we address some issues that are relevant to the evolution of virulence in fungi toward plants; in particular, horizontal gene transfer and the genomic organization of virulence genes.     

The role of genes in life

Summary In this paper two widely held ideas are criticized: (1) that chromosomal genes are the fundamental units of biological machinery and (2) that organisms have arisen from assemblies of free genes.Instead it is suggested that (3) the information encoded in the chromosomes may better be compared with the instructions contained in a textbook or leaflet, an that (4) basic cell activities may have preceded the instructions dealing with them in the same way in which human skills have preceded any texts dealing with them.This analogy is elaborated in certain details and some of its limitations are shown.

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Zusammenfassung Die Arbeit ist eine Kritik zweier weitverbreiteter Ideen, nämlich dass (1) die Gene in den Chromosomen die fundamentalen Bestandteile der biologischen Maschinerie sind und (2) dass die Organismen von Aggregaten freier Gene abstammen.Statt dessen wird vorgeschlagen, dass (3) die in den Chromosomen kodifizierte Information eher mit den Instruktionen eines Lehrbuchs oder einer Gebrauchsanweisung vergleichbar ist und dass (4) die grundlegenden Zellaktivitäten früheren Ursprungs sein dürften, als die Instruktionen zu ihrer Ausführung, etwa in der Weise in der menschliche Fertigkeiten gedruckten Anweisungen zu ihrer Ausführung vorausgegangen sind.Verschiedene Einzelheiten dieser Analogie werden verfolgt und einige ihrer Grenzen aufgezeigt.

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Résumé Cette étude critique deux notions très répandues: 1° que les genes chromosomes forment les unités fondamentales du mécanisme biologique: 2° que les organismes sont des conséquences d'ensembles de genes libres.Il est suggéré que 3° l'information codée dans les chromosomes est plutôt comparable aux indications données par un livret d'instructions et que 4° des actions fondamentales des cellules ont pu précéder les instructions qui les concernent de même façon que les techniques humaines ont précédé des textes qui les analysent.Cette analogie est élaborée en certains détails et quelquesunes de ses limitations sont demonstrées.