Stress and the developing hippocampus: a double-edged sword?

The mechanisms that regulate neuronal function are a sum of genetically determined programs and experience. The effect of experience on neuronal function is particularly important during development, because early-life positive and adverse experience (stress) may influence the still “plastic” nervous system long-term. Specifically, for hippocampal-mediated learning and memory processes, acute stress may enhance synaptic efficacy and overall learning ability, and conversely, chronic or severe stress has been shown to be detrimental. The mechanisms that enable stress to act as this “double-edged sword” are unclear. Here, we discuss the molecular mediators of the stress response in the hippocampus with an emphasis on novel findings regarding the role of the neuropeptide known as corticotropin-releasing hormone (CRH). We highlight the physiological and pathological roles of this peptide in the developing hippocampus, and their relevance to the long-term effects of early-life experience on cognitive function during adulthood.     

Prion processing: a double-edged sword?

The events leading to the degradation of the endogenous PrP(C) (normal cellular prion protein) have been the subject of numerous studies. Two cleavage processes, α-cleavage and β-cleavage, are responsible for the main C- and N-terminal fragments produced from PrP(C). Both cleavage processes occur within the N-terminus of PrP(C), a region that is significant in terms of function. α-Cleavage, an enzymatic event that occurs at amino acid residues 110 and 111 on PrP(C), interferes with the conversion of PrP(C) into the prion disease-associated isoform, PrP(Sc) (abnormal disease-specific conformation of prion protein). This processing is seen as a positive event in terms of disease development. The study of β-cleavage has taken some surprising turns. β-Cleavage is brought about by ROS (reactive oxygen species). The C-terminal fragment produced, C2, may provide the seed for the abnormal conversion process, as it resembles in size the fragments isolated from prion-infected brains. There is, however, strong evidence that β-cleavage provides an essential process to reduce oxidative stress. β-Cleavage may act as a double-edged sword. By β-cleavage, PrP(C) may try to balance the ROS levels produced during prion infection, but the C2 produced may provide a PrP(Sc) seed that maintains the prion conversion process.     

The microscopic anatomy and ultrastructure of the nephridium of the sipunculan Themiste hexadactyla Satô 1930) (Sipuncula: Sipunculidea)

The microscopic anatomy and ultrastructure of the nephridia of the sipunculan Themiste hexadactyla (Satô, 1930) from the Sea of Japan were studied by the histological and electron microscopic methods. The fine structures of the ciliary funnel, muscular “tongue,” excretory sac, and excretory tube of the nephridium were described. The ultrastructural features of the excretory epithelium, cupola-shaped epithelial infoldings, excretory canals, and muscular layer in the extracellular matrix of the nephridial wall were examined and described in detail. The ultrastructure of the nephridial coelomic epithelium composed of podocytes with long processes and multiciliary cells was also examined and illustrated. Characteristic cell contacts between the processes of podocytes, viz., paired “double diaphragms,” were described and illustrated for the first time.     

FoxO1 as a double-edged sword in the pancreas: analysis of pancreas- and β-cell-specific FoxO1 knockout mice

Diabetes is characterized by an absolute or relative deficiency of pancreatic β-cells. New strategies to accelerate β-cell neogenesis or maintain existing β-cells are desired for future therapies against diabetes. We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. P-FoxO1-KO, but not β-FoxO1-KO, showed improved glucose tolerance with HFHSD. Immunohistochemical analysis revealed that P-FoxO1-KO had increased β-cell mass due to increased islet number rather than islet size, indicating accelerated β-cell neogenesis. Furthermore, insulin-positive pancreatic duct cells were increased in P-FoxO1-KO but not β-FoxO1-KO. In contrast, db/db mice crossed with P-FoxO1-KO or β-FoxO1-KO showed more severe glucose intolerance than control db/db mice due to decreased glucose-responsive insulin secretion. Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress.     

SARS-CoV-2 variants: A double-edged sword?

Since the worldwide emergence of the COVID-19 outbreak, there have been international concerns about the possible viral evolution into variants with underlying mutations that may contribute to their increased transmissibility, disease severity, risk of death, and their potential escape from the immune response or may even lead to its extinction. Rigorous surveillance has revealed the variants harboring mutations in the spike protein, the main target of neutralizing antibodies generated through vaccination or herd immunity. In this review, we have highlighted major SARS-CoV-2 variants as well as other local strains along with their specific mutations, suspected changes in their characteristics, and their impact on the current pandemic and vaccine efficacy. We have also emphasized the need to develop widely protective interventions to curb further transmission of variants.     

IFN-α and TRAIL: A double edge sword in HIV-1 disease?

IFN-α is rapidly upregulated in response to viral infections and it is an essential player in innate immunity against viruses. pDCs are the most potent IFN-α-producing cells and serve as an essential link between innate and adaptive immunity. The fate of pDCs in the course of HIV-1 infection is still a matter of debate, and the question of the detrimental role of chronic production of IFN-α remains open. In particular, IFN-α has been shown to induce the expression of the death ligand TRAIL on pDCs, transforming them into killer pDCs that may contribute to the destruction of CD4(+) T cells, the hallmark of HIV-1-induced disease. In this review, we discuss our current understanding of the protective and pathogenic roles of both IFN-α and TRAIL in HIV-1 disease.     

Systematic and functional anatomy of seedlings in mangrove Rhizophoraceae: vivipary explained?

The hypocotyl of viviparous seedlings of mangrove Rhizophoraceae (tribe Rhizophoreae) has a common suite of anatomical features but a range of anatomical structures that may be diagnostic at the generic or even specific level. This information is summarized in the form of a dichotomous key. A common and previously unreported anatomical feature is the presence of tension wood fibres developed eccentrically in secondary xylem at the distal pole of seedlings grown in both artificial and natural conditions. These fibres are apparently the source of the mechanism whereby an initially horizontal seedling becomes erected rapidly once it is rooted distally, even though this appears to be achieved at a considerable mechanical disadvantage. The morphological result is a distinct 'hook' at the distal end of the established seedling. This mechanism allows rapid erection of a horizontally stranded seedling, such that the plumule is raised, snorkel-like, above immediate tidal influence. This may be necessary, since gas exchange through the surface of the seedling is not possible via the thick, cutinized and stomata-free epidermis of the hypocotyl. We suggest that the need to produce an elongated propagule, with this self-erecting capability favours the evolution of vivipary in these plants because it permits the earliest development of the plumule in air rather than water. The suitability of mangrove seedlings for further experimental and anatomical study is emphasized. The study also exemplifies how anatomy can be placed in a dynamic context.     

Morphology and development of the cranium of Felis silvestris f. catus Linné 1758--a contribution to the comparative anatomy of the Carnivora. III: Ear region and occipital region

In Felis, the otic region of younger embryonic stages up to Felis 1 is characterized by extremely medial extended cochleae, compressing the basal plate to a slender trabeculum. As a result of a quite strong rostrad convergence of the long axis of the ear capsules, the Commissura praefacialis fuses with the Commissura orbitoparietalis laterally. Until now, this has been found in whales only. Continuing embryogenesis towards Felis 2, the cochlea moves laterally and slightly ventrally, so the angle of convergence between the whole Capsula otica and the skull base decreases. The problem of interpreting these positional changes of the Capsula otica during phylogenesis and ontogenesis is discussed in detail. Up to recent literature, there is a discussion about homology of the Foramen perilymphaticum and allied structures in reptiles referring to the openings in the Capsula otica in mammals. Configuration of these structures in fissiped carnivores and the appearance of a "limitating membrane" in Felis 2, gives reason for a new discussion of these problems. Composition of the Bulla tympani is a very important feature for investigation of phylogeny and systematics in fissiped carnivores. In Felis 2, there appears a caudal entotympanic, consisting of young cartilaginous tissue. The development of the caudal entotympanic has impact on 2 structures in the occipital region: The Lamina alaris and the Processus paracondyloideus. Felis 1 shows a distinct Lamina alaris and a short Processus paracondyloideus. With Felis 2, either element is reduced largely, probably to the extent as the caudal entotympanic develops.     

What drives interspecies graft union success? Exploring the role of phylogenetic relatedness and stem anatomy

The underlying mechanisms that determine whether two species can form a successful graft union (graft compatibility) remain obscure. Two prominent hypotheses are (1) the more closely related species are, the higher the graft success and (2) the vascular anatomy at the graft junction influences graft success. In this paper these two hypotheses are examined in a systematic way using graft combinations selected from a range of (a) phylogenetically close and more distant legume species, (b) species displaying different germination patterns and (c) scions and rootstocks possessing contrasting stem tissues and vascular patterns. Relatedness of species was not a good predictor of graft compatibility, as vascular reconnection can occur between distantly related species and can fail to occur in some more closely related species. Similarly, neither the stem tissues present at the graft junction nor the vascular anatomy correlated with the success of vascular reconnection. Relatedness and stem anatomy therefore do not appear to be the determining factors in successful vascular reconnection after grafting in legumes. These results are discussed in conjunction with other hypotheses such as the role of auxin.     

C3−C4 Intermediate species in the genus Flaveria: leaf anatomy,ultrastructure, and the effect of O2 on the CO2 compensation concentration

Leaf anatomical, ultrastructural, and CO₂-exchange analyses of three closely related species of Flaveria indicate that they are C₃–C₄ intermediate plants. The leaf mesophyll of F. floridana J.R. Johnston, F. linearis Lag., and F. chloraefolia A. Gray is typical of that in dicotyledonous C₃ plants, but the bundle sheath cells contain granal, starch-containing chloroplasts. In F. floridana and F. chloraefolia, the chloroplasts and numerous associated mitochondria are arranged largely centripetally, as in the closely related C₄ species, F. brownii A.M. Powell. In F. linearis, fewer mitochondria are present and the chloroplasts are more evenly distributed throughout the bundle sheath cytosol. There is no correlation between the bundle sheath ultrastructure and CO₂ compensation concentration. () values of these C₃–C₄ intermediate Flaveria species. At 21% O₂ and 25°C, for F. chloraefolia, F. linearis, and F. floridana is 23–26, 14–19, and 8–10 l CO₂ l^-1, respectively. The O₂ dependence of is the greatest for F. chloraefolia and F. linearis (similar to that for C₃–C₄ intermediate Panicum and Moricandia species) and the least for F. floridana, whose O₂ response is identical to that for F. brownii from 1.5 to 21% O₂, but greater at higher pO₂. The variation in leaf anatomy, bundle sheath ultrastructure, and O₂ dependence of among these Flaveria species may indicate an active evolution in the pathway of photosynthetic carbon metabolism within this genus.Abbreviations CO₂ compensation concentration - IRGA infrared gas analysis Published as Paper No. 7068, Journal Series, Nebraska Agricultural Experiment Station     

Comparative anatomy of the heart–glomerulus complex of Cephalodiscus gracilis (Pterobranchia): structure,function, and phylogenetic implications

Cephalodiscus gracilis Harmer, 1905 is a semi-sessile deuterostome that shares with fish-like chordates pharyngeal gill slits and a dorsally situated brain. In order to reveal structures potentially homologous among deuterostomes and to infer their functional roles, we investigated the axial complex, associated blood vessels and structures of C. gracilis using transmission electron microscopy, light microscopy, and digital 3D reconstructions. We describe the smooth, bipartite cephalic shield retractor muscles that originate as solid compact muscles and fan out to traverse the protocoel as individual muscle cells. The axial complex consists of a cap-shaped coelomic sac, the pericardium that surrounds the central heart. The pericardium is constituted of myoepithelial cells, with the cells facing the heart being thicker and richer in myofilaments. A prominent dorsal median blood vessel opens into the heart, which gives rise to a short median ventral vessel that opens into the paired glomeruli connected to the ventral side of the stomochord. The tip of the curved stomochord rests precisely above the connection of the dorsal median vessel with the heart, a position that would allow the stomochord to function as a valve facilitating unidirectional blood flow. Glomeruli are lined by podocytes of the spacious protocoel and are considered to be the site of ultrafiltration. Two pairs of blood vessels enter the median dorsal blood vessel from the tentacles. The median dorsal blood vessel is separated from the brain by a thin basement membrane. This arrangement is consistent with the hypothesis that blood vessels in the tentacles increase oxygen supply for the brain. Based on detailed similarities, the heart–glomerulus complex of C. gracilis is considered homologous with the heart–glomerulus complex in Rhabdopleura spp., and Enteropneusta, and the axial complex in Echinodermata. In addition, we hypothesize homology to the excretory complex including Hatschek’s nephridium in Cephalochordata. Thus, the heart–glomerulus complex does not support a sister-group relationship between Echinodermata and Hemichordata, whereas the organization of the cephalic shield retractor muscles is consistent with the evolution of pterobranchs within enteropneusts.     

Stomatal malfunctioning under low VPD conditions: induced by alterations in stomatal morphology and leaf anatomy or in the ABA signaling?

Exposing plants to low VPD reduces leaf capacity to maintain adequate water status thereafter. To find the impact of VPD on functioning of stomata, stomatal morphology and leaf anatomy, fava bean plants were grown at low (L, 0.23 kPa) or moderate (M, 1.17 kPa) VPDs and some plants that developed their leaves at moderate VPD were then transferred for 4 days to low VPD (M→L). Part of the M→L‐plants were sprayed with ABA (abscisic acid) during exposure to L. L‐plants showed bigger stomata, larger pore area, thinner leaves and less spongy cells compared with M‐plants. Stomatal morphology (except aperture) and leaf anatomy of the M→L‐plants were almost similar to the M‐plants, while their transpiration rate and stomatal conductance were identical to that of L‐plants. The stomatal response to ABA was lost in L‐plants, but also after 1‐day exposure of M‐plants to low VPD. The level of foliar ABA sharply decreased within 1‐day exposure to L, while the level of ABA‐GE (ABA‐glucose ester) was not affected. Spraying ABA during the exposure to L prevented loss of stomatal closing response thereafter. The effect of low VPD was largely depending on exposure time: the stomatal responsiveness to ABA was lost after 1‐day exposure to low VPD, while the responsiveness to desiccation was gradually lost during 4‐day exposure to low VPD. Leaf anatomical and stomatal morphological alterations due to low VPD were not the main cause of loss of stomatal closure response to closing stimuli.     

Autophagy: A double-edged sword in Alzheimer’s disease

Autophagy is a major protein degradation pathway that is essential for stress-induced and constitutive protein turnover. Accumulated evidence has demonstrated that amyloid-beta (A beta) protein can be generated in autophagic vacuoles, promoting its extracellular deposition in neuritic plaques as the pathological hallmark of Alzheimer's disease (AD). The molecular machinery for A beta generation, including APP, APP-C99 and beta-/gamma-secretases, are all enriched in autophagic vacuoles. The induction of autophagy can be vividly observed in the brain at early stages of sporadic AD and in an AD transgenic mouse model. Accumulated evidence has also demonstrated a neuroprotective role of autophagy in mediating the degradation of aggregated proteins that are causative of various neurodegenerative diseases. Autophagy is thus widely regarded as an intracellular hub for the removal of the detrimental A beta peptides and Tau aggregates. Nonetheless, compelling data also reveal an unfavorable function of autophagy in facilitating the production of intracellular A beta. The two faces of autophagy on the homeostasis of A beta place it in a very unique and intriguing position in AD pathogenesis. This article briefly summarizes seminal discoveries that are shedding new light on the critical and unique roles of autophagy in AD and potential therapeutic approaches against autophagy-elicited AD.     

Leaf anatomy,water relations and crassulacean acid metabolism in the chlorenchyma and colourless internal water-storage tissue of Carpobrotus edulis and Senecio ?mandraliscae

Both Carpobrotus edulis and Senecio ?mandraliscae possess leaves with a peripheral chlorenchyma and colourless internal water-storage tissue. Water stress in C. edulis growing under semi-natural conditions resulted in the induction of weak Crassulacean acid metabolism (CAM) whereas well-watered plants of S. ?mandraliscae exhibited a similar degree of CAM. Titratable acidity in the separated water-storage tissue was substantially lower than in the chlorenchyma in both species but, nevertheless, increased during the night and decreased during the day either when sampled from the intact plant or from incubated tissue slices. Indeed, the increase in nocturnal titratable acidity produced by the water-storage tissue in situ accounted for approx. 30% of total acidification on a per-leaf basis. It appears that during the night the water-storage tissue in these species is able to fix CO₂ which is subsequently released during the day to enter the photosynthetic carbon-reduction cycle of the chlorenchyma. Diurnal rhythms of water potential (Ψ) and osmotic potential (Ψs) were measured in separated chlorenchyma and water-storage tissue by thermocouple psychrometry. Both parameters increased during the latter part of the daytime and initial nocturnal period and decreased during the rest of the night and into the post-dawn period. The chlorenchyma of water-stressed plants of C. edulis appeared to possess a marked negative turgor pressure (as determined from Ψ-Ψs) but this was caused by a severe underestimation in the measurement of the chlorenchyma Ψ. It is suggested that this artefact arose from release of colloidal polysaccharide mucilage, or possibly tannins, from broken tannin cells producing a lowering of water activity when measured using thermocouple psychrometry.     

Phytochemicals: the good, the bad and the ugly?

Phytochemicals are constitutive metabolites that enable plants to overcome temporary or continuous threats integral to their environment, while also controlling essential functions of growth and reproduction. All of these roles are generally advantageous to the producing organisms but the inherent biological activity of such constituents often causes dramatic adverse consequences in other organisms that may be exposed to them. Nevertheless, such effects may be the essential indicator of desirable properties, such as therapeutic potential, especially when the mechanism of bioactivity can be delineated. Careful observation of cause and effect, followed by a coordinated approach to identify the responsible entities, has proved extremely fruitful in discovering roles for phytochemical constituents. The process is illustrated by selected examples of plants poisonous to animals and include the steroidal alkaloid toxin of Veratrum californicum (Western false hellebore), piperidine alkaloids of Lupinus species (lupines), and polyhydroxy indolizidine, pyrrolizidine and nortropane alkaloids of Astragalus and Oxytropis species (locoweeds), Castanospermum australe (Moreton Bay chestnut) and Ipomoea species (morning glories).     

Eosinophils and Trichinella infection: toxic for the parasite and the host?

Peripheral blood and tissue eosinophilia characterize trichinellosis in humans, and present in addition to the increased total IgE levels that occur in many helminth infections. Both processes are the consequence of T-helper 2 activation. Blood and tissue eosinophilia begins with eosinophilopoiesis in the bone marrow, which is followed by the migration of eosinophils through the circulatory system, the eosinophil infiltration of tissues at the inflammatory foci and, finally, degranulation and cell death. Recently, some aspects of eosinophilia caused by Trichinella spiralis infection have been elucidated; however, the protective role of this population of cells against Trichinella parasites remains controversial. Furthermore, when eosinophils are numerous, they can be toxic for host tissues. This review discusses these issues in both human and rodent infection models.     

A black-and-red stick insect from the Philippines – observations on the external anatomy and natural history of a new species of Orthomeria

A new stick insect of the genus Orthomeria Kirby, 1904 (Phasmatodea, Aschiphasmatidae) is described from the Philippines. Orthomeria (Orthomeria) kangi sp. n. is readily distinguished from all other congeners by the distinctive blood red colouration of the costal region of the hind wings. Major features of the external morphology of adults, eggs, and first-instar nymphs are illustrated. Locomotory attachment pads are of the smooth type with irregular microgrooves on the contact surface. An unusual condition of male terminalia is the absence of tergal thorn pads on segment 10. The male clasping organs are represented by an elongated vomer terminating in a prominent spine, and by incurved cerci featuring a bilobed apex equipped with a sharp blade-like ridge. Intraspecific variation in body colouration and hind wing length occurs in females. The new species lives at 400-650 m elevation in the surroundings of the Sablang and Tuba regions, in the Benguet Province of Luzon island. Host plants include Ficus spp. (Moraceae), and Pipturus spp. and Leucosyke spp. (Urticaceae). Observations on the mating and defensive behaviour are presented. Orthomeria (Orthomeria) catadromus (Westwood, 1859) is recognised as a junior synonym of Orthomeria (Orthomeria) pandora (Westwood, 1859), syn. n. A lectotype is designated for both species. Finally, an updated identification key to the species of the subgenus Orthomeria is provided.