Why is Listeria monocytogenes such a potent inducer of CD8+ T‐cells?

Listeria monocytogenes is a rapidly growing, Gram‐positive, facultative intracellular pathogen that has been used for over 5 decades as a model to study basic aspects of infection and immunity. In a murine intravenous infection model, immunisation with a sublethal infection of L. monocytogenes initially leads to rapid intracellular multiplication followed by clearance of the bacteria and ultimately culminates in the development of long‐lived cell‐mediated immunity (CMI) mediated by antigen‐specific CD8+ cytotoxic T‐cells. Importantly, effective immunisation requires live, replicating bacteria. In this review, we summarise the cell and immunobiology of L. monocytogenes infection and discuss aspects of its pathogenesis that we suspect lead to robust CMI. We suggest five specific features of L. monocytogenes infection that positively impact the development of CMI: (a) the bacteria have a predilection for professional antigen‐presenting cells; (b) the bacteria escape from phagosomes, grow, and secrete antigens into the host cell cytosol; (c) bacterial‐secreted proteins enter the major histocompatibility complex (MHC) class I pathway of antigen processing and presentation; (d) the bacteria do not induce rapid host cell death; and (e) cytosolic bacteria induce a cytokine response that favours CMI. Collectively, these features make L. monocytogenes an attractive vaccine vector for both infectious disease applications and cancer immunotherapy.     

Why is <Emphasis Type="Italic">Aedes aegypti</Emphasis> Linnaeus so Successful as a Species?

Diseases transmitted by mosquitoes impose enormous burden towards human morbidity and mortality. Over the last three decades, Brazil has suffered from severe Dengue epidemics. In September 2014, this situation is further complicated by the introduction of two other viruses, Zika and Chikungunya, placing Brazil in a triple epidemic. In this article, we discuss the biology of Aedes aegypti Linnaeus, and the principal initiatives currently used to control mosquito populations and the diseases they transmit. Aedes aegypti has broad global distribution and is involved in the transmission of various arboviral diseases such as Dengue, Zika, and Chikungunya. Several factors contribute to the success of the species, particularly behavioral plasticity, rapid development, desiccation-resistant eggs, resistance to the principle insecticide classes currently available on the market, preference for the urban environment, and proximity to humans. Vector control programs are the best way to reduce the burden of mosquito-borne diseases. Chemical control is most commonly used in recent times, and unfortunately, the results have not been satisfactory but instead, there is increased vector dispersal and, subsequently, the spread of disease epidemics. Investigations of alternative control methods such as release of Wolbachia-infected mosquitoes for blocking vector-borne pathogens, release of transgenic mosquitoes carrying a lethal gene for offspring, and the use of insecticide-dispersing mosquitoes are under way in Brazil, and some have shown promising results. Special emphasis should be placed on integrated management of all available tactics, so as to maximize efforts towards mosquito control. Finally, we emphasize that continuous actions and community participation control initiatives are critically important for success.     

Why species composition is not a good indicator to assess restoration success? Counter‐response to Reid (2015)

The absence of species composition among the indicators of restoration success, recommended for the Brazilian Atlantic Forest by Suganuma and Durigan, was criticized by Reid. In his critic, Reid argues that species composition can be (1) predictable from site history and restoration technique and (2) a surrogate for poor ecosystem functioning and lack of resilience. We disagree on the deterministic view behind the first argument, and the latter is still controversial. Even though, we recommended richness as a good indicator of ecosystem functioning instead of composition—which depends on the exhaustive labor of botanical identification.     

Why is Coccidoxenoides perminutus, a mealybug parasitoid, ineffective as a biocontrol agent—Inaccurate measures of parasitism or low adult survival?

Coccidoxenoides perminutus achieves only low levels of parasitism of its host Planococcus citri in southeast Queensland citrus. Two possible causes were investigated. Adult survival under natural conditions was assessed to determine whether providing adult food sources could enhance survival. Behavioural changes of hosts, induced by C. perminutus parasitism, was also investigated to establish if parasitised P. citri move from their feeding site to seek protected shelters some distance away and are thus not accounted for in field assessments of parasitism rates. Unparasitised mealybugs placed in the field for two periods were retrieved before the effects of parasitism were manifested and parasitism rates were still low (0.3% at 5 days and 1.2% at 10 days). Levels of locomotion of P. citri exposed to C. perminutus were compared with those of “unexposed” ones. Parasitised mealybugs, regardless of instar, undergo behavioural changes. In comparison to unparasitised controls, the mealybugs become highly active 7–14 days after exposure to wasps. All parasitised mealybugs undergo physical changes, their body becomes cylindrical, their legs go so rigid that the mealybugs become immobile, and this signifies the typical mummy appearance. All mealybugs that became mummies eventually fell from the host lemon fruit because of impaired locomotion and were caught on sticky traps that had been placed beneath the lemons. Consequently, their final site of mummification was not established. C. perminutus adults provided with nectar or honey survived longer (about 5 days) in the field than those without food (about a day). Nectar from two plant species, Alpinia zerumbet and Datura candida, proved to be good sources of food for the adult wasps, and were comparable in quality to honey. The low level of parasitism achieved by C. perminutus in southeast Queensland citrus thus appears to be a consequence of the short adult life and the negative effects of a harsh environment. Provision of a suitable food source (e.g., nectar) may well enhance levels of parasitism in the field.     

Review of the genotoxicity and carcinogenicity of antischistosomal drugs; is there a case for a study of mutation epidemiology? Report of a task group on mutagenic antischistosomals

One of the interests of ICPEMC is to identify situations in which the possible induction of inherited defects in man by mutagen exposure could actually be studied. The large-scale use of mutagenic drugs in field programmes against schistosomiasis, mainly during the 1970's, was considered a possible case. An ICPEMC task group approached the problem by (1) updating the genetic toxicology data base for antischistosomal drugs, and (2) reviewing possible study areas. Expertise was combined from genetic toxicology, mutation epidemiology and tropical medicine.It was considered that: (a) if any, hycanthone would be the most appropriate candidate drug for study; (b) it would be virtually impossible to meet the basic requirements of an appropriate mutation epidemiology study, in endemic countries; (c) as more defined genetic endpoints would be selected (e.g. sentinel phenotypes) the required large sample sizes would seem prohibitive, since documentation on past programmes is limited and local demography would render the reliable tracking of substantial numbers of offspring of treated persons an almost impossible task; (d) in most endemic countries proper diagnosis and registration of inherited defects is largely lacking; (e) the problems encountered in demonstrating inherited effects in humans after heavy or chronic exposure to established animal mutagens such as ionizing radiation and cancer chemotherapy, in combination with the ambiguous nature of the animal germ cell data with hycanthone, do not particularly warrant large expectations; (f) since non-mutagenic antischistosomal drugs are now in use, the problem is academic and of low priority in the endemic countries whose medical and research resources are often limited. Thus, studying offspring of hycanthone-treated people to demonstrate the mutagenic potential of the drug in man is not a viable enterprise. (See, however, note added in proof, p. 75.)     

Lipopolysaccharide‐induced increase in signalling in hippocampus is abrogated by IL‐10 – a role for IL‐1β?

Parenterally administered lipopolysaccharide (LPS) increases the concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the rat hippocampus and evidence suggests that this effect plays a significant role in inhibiting long-term potentiation (LTP). The anti-inflammatory cytokine IL-10, antagonizes certain effects of IL-1beta, so if the effects of LPS are mediated through an increase in IL-1beta, it might be predicted that IL-10 would also abrogate the effect of LPS. Here, we report that IL-10 reversed the inhibitory effect of LPS on LTP and the data couple this with an inhibitory effect on the LPS-induced increase in IL-1beta. LPS treatment increased hippocampal expression of IL-1 receptor Type I protein. Consistent with the LPS-induced increases in IL-1beta concentration and receptor expression, were downstream changes which included enhanced phosphorylation of IRAK and the stress-activated kinases, JNK and p38; these LPS-induced changes were reversed by IL-10, which concurs with the idea that these events are triggered by increased activation of IL-1RI by IL-1beta. We provide evidence which indicates that LPS treatment leads to evidence of cell death and this was reversed in hippocampus prepared from LPS-treated rats which received IL-10. The evidence is therefore consistent with the idea that IL-10 acts to protect neuronal tissue from the detrimental effects induced by LPS.     

From the Wuhan-Hu-1 strain to the XD and XE variants: is targeting the SARS-CoV-2 spike protein still a pharmaceutically relevant option against COVID-19?

Since the outbreak of the COVID-19 pandemic in December 2019, the SARS-CoV-2 genome has undergone several mutations. The emergence of such variants has resulted in multiple pandemic waves, contributing to sustaining to date the number of infections, hospitalisations, and deaths despite the swift development of vaccines, since most of these mutations are concentrated on the Spike protein, a viral surface glycoprotein that is the main target for most vaccines. A milestone in the fight against the COVID-19 pandemic has been represented by the development of Paxlovid, the first orally available drug against COVID-19, which acts on the Main Protease (Mpro). In this article, we analyse the structural features of both the Spike protein and the Mpro of the recently reported SARS-CoV-2 variant XE, as well the closely related XD and XF ones, discussing their impact on the efficacy of existing treatments against COVID-19 and on the development of future ones.     

Effects of ferric soils on arthropod abundance and herbivory on <Emphasis Type="Italic">Tibouchina heteromalla</Emphasis> (Melastomataceae): is fluctuating asymmetry a good indicator of environmental stress?

High concentration of heavy metals in the soils represents an important factor of physiological stress that influences the normal functioning of plants through oxidation processes, and negatively affects insect performance and leaf consumption by herbivorous insects. One useful indicator to evaluate environmental stress in plants by heavy metals and herbivory is the fluctuating asymmetry, which describes the random differences in size or shape between the two sides of a bilateral character in organisms and it is a widely used measure of developmental instability in plants. We evaluated under natural conditions, the effects of variation of heavy metals in the soils on herbivore patterns, fluctuating asymmetry and arthropod abundance in Tibouchina heteromalla in rupestrian grasslands along the Espinhaço chain in Brazil. We selected two study areas, the first characterized by the presence of soils with low concentration of heavy metals (quartzite soils). In the second area, the soils are characterized by the presence of high concentration of heavy metals such as iron (ferric soils). We found that leaf thickness was higher in ferric soils than in quartzite soils. Conversely, total leaf area was greater in quartzite soils in comparison to ferric soils. Plants in soils with heavy metals had both lower herbivory levels and arthropod abundance than plants in soils with low concentrations of heavy metals. Fluctuating asymmetry levels were significantly greater in individuals from quartzite soils compared to individuals from ferric soils. Herbivory was positively related with individual fluctuating asymmetry in quartzite soils. Our results suggest that T. heteromalla presents tolerance to soils with heavy metals suggesting an acclimatization to these environmental conditions, and therefore, ferric soils may not represent a factor of environmental stress.     

Borderline nuclear change; can a subgroup be identified which is suspicious of high‐grade cervical intraepithelial neoplasia,i.e. CIN 2 or worse?

Borderline nuclear change; can a subgroup be identified which is suspicious of high‐grade cervical intraepithelial neoplasia, i.e. CIN 2 or worse? Only 10% of first borderline smears are associated with a histological high‐grade (HG) abnormality, i.e. CIN 2,3, invasive malignancy or glandular neoplasia on subsequent investigation. The advantages of highlighting this subgroup are obvious but is this possible? From 1996 and 1997, 242 borderline smears with histological follow‐up were examined by two independent experienced observers (observer 1 and 2) without prior knowledge of further investigation results. For each smear a profile of nuclear details was produced, also noting the type of cell mainly affected by the process; then the observers were asked to assess the degree of worry of HG disease for each smear i.e. whether the smear fell into group 1 borderline changes indicative of low‐grade (normal, inflammatory, CIN1/HPV) disease (BL/LG) or group 2 difficult borderline smear, HG disease (CIN 2,3, invasive neoplasia or glandular neoplasia) cannot be excluded (BL/HG). Observer 1 selected a group of BL/HG with a PPV for HG disease of 38%, with observer 2 having a PPV of 50%; this compared with the overall laboratory HG disease PPV for borderline smears of 14%. Both observers found the most useful criterion to be the increase in nuclear:cytoplasmic ratio. Our results show that it is possible to separate a small group of borderline smears which should be classified as ‘borderline/high grade lesion difficult to exclude’ (BL/HG). Both observers had some success in arriving at this classification although their method of selecting out this group was quite different.     

Critical‐weight‐range marsupials in northern Australia are declining: a commentary on Fisher et al. (2014) ‘The current decline of tropical marsupials in Australia: is history repeating?’

Many mammal species are declining in parts of Australia's tropical savannas, for reasons that are not yet well defined. A recent paper (Fisher et al., 2014, Global Ecology and Biogeography, 23 , 181–190) suggested that the primary cause is predation by feral cats, with the main evidence presented being a purported over‐representation of small species amongst the marsupials that have contracted in range (‘small body size signifies high current extinction risk’). However, a review here of the information presented in that paper shows that no marsupial species smaller than 100 g has shown range contraction in northern Australia, and that most (15 of 17) declines are of species in the ‘critical weight range’ (35 g to 5.5 kg).     

Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-alpha 2 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease?

Fukuyama-type congenital muscular dystrophy (FCMD) and laminin-alpha2 deficient congenital muscular dystrophy (MDC1A) are congenital muscular dystrophies (CMDs) and they both are categorized into the same clinical entity of muscular dystrophy as Duchenne muscular dystrophy (DMD). All three disorders share a common etiologic defect in the dystrophin-glycoprotein complex, which connects muscle structural proteins with the extracellular basement membrane. To investigate the pathophysiology of these CMDs, we generated microarray gene expression profiles of skeletal muscle from patients in various clinical stages. Despite diverse pathological changes, the correlation coefficient of overall gene expression among these samples was considerably high. We performed a multi-dimensional statistical analysis, the Distillation, to extract determinant genes that distinguish CMD muscle from normal controls. Up-regulated genes were primarily extracellular matrix (ECM) components, whereas down-regulated genes included structural components of mature muscle. These observations reflect active interstitial fibrosis with less active regeneration of muscle cell components in the CMDs, characteristics that are clearly distinct from those of DMD. Although the severity of fibrosis varied among the specimens tested, ECM gene expression was consistently high without substantial changes through the clinical course. Further, in situ hybridization showed more prominent ECM gene expression on muscle cells than on interstitial tissue cells, suggesting that ECM components are induced by regeneration process rather than by 'dystrophy.' These data imply that the etiology of FCMD and MDC1A differs from that of the chronic phase of classical muscular dystrophy, and the major pathophysiologic change in CMDs might instead result from primary active fibrosis.     

Animal evolution and atmospheric pO<Subscript>2</Subscript>: is there a link between gradual animal adaptation to terrain elevation due to Ural orogeny and survival of subsequent hypoxic periods?

Considering evolution of terrestrial animals as something happening only on flat continental plains seems wrong. Many mountains have arisen and disappeared over the geologic time scale, so in all periods some areas of high altitude existed, with reduced oxygen pressure (pO₂) and increased aridity. During orogeny, animal species of the raising terrain can slowly adapt to reduced oxygen levels.This review proposes that animal evolution was often driven by atmospheric oxygen availability. Transitions of insect ancestors and amphibians out of water are here interpreted as events forced by the lack of oxygen in shallow and warm water during Devonian. Hyperoxia during early Carboniferous allowed giant insects to be predators of lowlands, forcing small amphibians to move to higher terrains, unsuitable to large insects due to reduced pO₂. In arid mountainous habitats, ascended animals evolved in early reptiles with more efficient lungs and improved circulation. Animals with alveolar lungs became the mammalian ancestors, while those with respiratory duct lungs developed in archosaurs. In this interpretation, limb precursors of wings and pneumatised bones might have been adaptations for moving on steep slopes.Ural mountains have risen to an estimated height of 3000 m between 318 and 251 Mya. The earliest archosaurs have been found on the European Ural side, estimated 275 Myr old. It is proposed that Ural orogeny slowly elevated several highland habitats within the modern Ural region to heights above 2500 m. Since this process took near 60 Myr, animals in these habitats fully to adapted to hypoxia.The protracted P-Tr hypoxic extinction event killed many aquatic and terrestrial animals. Devastated lowland areas were repopulated by mammaliaformes that came down from mountainous areas. Archosaurs were better adapted to very low pO₂, so they were forced to descend to the sea level later when the lack of oxygen became severe. During the Triassic period, when the relative content of O₂ reduced to near 12%, archosaurs prevailed as only animals that could cope with profound hypoxia at the sea level. Their diverse descendants has become dominant terrestrial animals, until the K-Pg extinction due to meteor impact.     

Response to commentary by Woinarski (Critical‐weight‐range marsupials in northern Australia are declining: a commentary on Fisher et al. (2014) ‘The current decline of tropical marsupials in Australia: is history repeating?’)

The recent commentary by Woinarski (2014, Global Ecology and Biogeography, doi: 10.1111/geb.12165) disagreed with our conclusions on the correlates of decline in the marsupials of tropical Australia (Fisher et al., 2014, Global Ecology and Biogeography, 23 , 181–190). We compared traits of species that were associated with range decline in southern and northern Australia. We found that habitat structure, climate and body size were correlated with range decline. In the north, declines of marsupials were most severe in savanna with moderate rainfall. In the south, the ranges of species in open habitat with very low rainfall have declined most. Also, the association between range decline and body mass differed between north and south: this is the main concern of Woinarski, who further disagreed with our choice of the Tropic of Capricorn as a boundary between north and south, our omission of rodents, how to treat timing of extinctions, and our inference that cats are major drivers of decline. We address these concerns in this response.