Small genome of the fungus Escovopsis weberi,a specialized disease agent of ant agriculture

Many microorganisms with specialized lifestyles have reduced genomes. This is best understood in beneficial bacterial symbioses, where partner fidelity facilitates loss of genes necessary for living independently. Specialized microbial pathogens may also exhibit gene loss relative to generalists. Here, we demonstrate that Escovopsis weberi, a fungal parasite of the crops of fungus-growing ants, has a reduced genome in terms of both size and gene content relative to closely related but less specialized fungi. Although primary metabolism genes have been retained, the E. weberi genome is depleted in carbohydrate active enzymes, which is consistent with reliance on a host with these functions. E. weberi has also lost genes considered necessary for sexual reproduction. Contrasting these losses, the genome encodes unique secondary metabolite biosynthesis clusters, some of which include genes that exhibit up-regulated expression during host attack. Thus, the specialized nature of the interaction between Escovopsis and ant agriculture is reflected in the parasite’s genome.The highly evolved agricultural lifestyle of leaf-cutting ants has attracted particular attention because these ants cultivate a symbiotic fungus that serves as their major food source. These ants cut leaves, preprocess them into small pieces, and feed them to the cultivated fungus (1). The capacity of the cultivated fungus to break down plant material gives ant agriculturalists access to the vast nutrient stores locked within neotropical plants (Fig. 1A) (2–5). The symbiosis between fungus-growing ants and their cultivated fungi has persisted for at least 50 million years (6).Open in a separate windowFig. 1.Escovopsis weberi, a specialized mycoparasite of the fungus-growing ant symbiosis, has a small genome compared with other Pezizomycotina fungi. (A) Both fungus-growing ants and the mycoparasite E. weberi use the ants’ cultivated fungi as their primary food source. The ability of the cultivated fungi to efficiently break down plant material gives both consumers access to the biomass of neotropical plants. (B) Size and protein-coding gene content of genomes of diverse fungi in the Pezizomycotina. Bayesian phylogeny estimated using partial amino acid alignments of three genes (Rpb1, Rpb2, ef1-α). All posterior probabilities are greater than 0.95. Phylogeny is rooted with Sacchormyces cervesiae (not shown). (C) Relationship between genome size and gene content. A list of genomes included in this panel is in SI Appendix, Table S1.Like human agriculture, ant agriculture is hampered by disease. The ants’ fungal crops are attacked and consumed by fungal parasites of the genus Escovopsis (Ascomycota, Pezizomycotina: anamorphic Hypocreales) (Fig. 1A) (7), which have evolved in association with the ants and their cultivated fungi (8). Escovopsis infection can have detrimental impacts on garden health and, consequently, on the survival of ant colonies (9, 10). Such mycoparasitism, the phenomenon whereby one fungus is parasitic on another fungus, is rare. It is most well-known for species from the genus Trichoderma, some of which are used as biocontrol agents for fungal diseases and others of which attack human-cultivated fungi (11–13). In contrast to Trichoderma species, however, Escovopsis species grow poorly in their hosts’ absence (SI Appendix, Figs. S1 and S2).Escovopsis species have never been isolated outside of fungus-growing ant colonies, and different strains of Escovopsis are capable of attacking the fungi grown by different fungus-growing ant species (8, 14, 15). The long-term, specialized evolutionary history of the association between Escovopsis and their hosts provides a unique venue to explore the consequences of host specialization on pathogen genome evolution. Here, we assemble and annotate the genome of a strain of Escovopsis weberi. Consistent with expectations under an evolutionary transition toward using a narrow host range, and similar to many other specialized, host-associated microbes (16, 17), E. weberi exhibits gene loss. Contrasting other fungal pathogens, the large genomes of which are expanded with genetic elements that influence host adaptation (18), the genome size of Escovopsis is small compared with those of its closest sequenced relatives.     

St. Louis encephalitis virus: first isolation from a human in São Paulo State, Brazil

This paper reports the isolation of St. Louis encephalitis virus (SLEV) from a febrile human case suspected to be dengue, in S?o Pedro, S?o Paulo State. A MAC-ELISA done on the patient's acute and convalescent sera was inconclusive and hemagglutination inhibition test detected IgG antibody for flaviviruses. An indirect immunofluorescent assay done on the C6/36 cell culture inoculated with the acute serum was positive for flaviviruses but negative when tested with dengue monoclonal antibodies. RNA extracted from the infected cell culture supernatant was amplified by RT-PCR in the presence of NS5 universal flavivirus primers and directly sequenced. Results of BLAST search indicated that this sequence shares 93% nucleotide similarity with the sequence of SLEV (strain-MSI.7), confirmed by RT-PCR performed with SLEV specific primers. Since SLEV was identified as the cause of human disease, it is necessary to improve surveillance in order to achieve early detection of this agent in the state of S?o Paulo and in Brazil. This finding is also an alert to health professionals about the need for more complete clinical and epidemiological investigations of febrile illnesses as in the reported case. SLEV infections can be unrecognized or confused with other ones caused by an arbovirus, such as dengue.     

From the Cover: Functional changes of the reward system underlie blunted response to social gaze in cocaine users

Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants’ gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction.Cocaine dependence is a chronically relapsing disorder defined by uncontrolled and compulsive drug use (1). Despite severe negative consequences including disrupted social relationships, loss of employment, and somatic and psychiatric illnesses, an addicted person’s life is often centered around the drug of choice and activities related to it (2). Therefore, drug use is classified as a major social, legal, and public health problem (3). After cannabis, cocaine is the second most prevalent illegal drug in the United States and Europe (4, 5), with a lifetime prevalence among young adults of 6.3% in Europe (15- to 34-y-olds) (4) and 13.3% in the United States (18- to 25-y-olds) (5).Social cognition and social support for drug users are of great clinical relevance, as they have been reported to influence onset of drug use and development of substance use disorders, and treatment success in patients with substance use disorders (6, 7). Impairments in social cognition may augment the risk of social isolation, aggression, and depression, likely supporting the vicious circle of drug use (8). Additionally, impaired social cognition may contribute to the decay of social relationships in addicted patients (9) with negative consequences for treatment success given that higher social support predicted longer abstinence duration (10). Furthermore, no efficient pharmacological treatment for cocaine addiction is currently available (11), and treatment approaches such as cognitive behavioral therapy rely, at least in part, on the emotional responsiveness and social abilities of drug users (12). Previous results suggest that cocaine users (CUs) show impairments in different facets of social cognition, particularly in emotional empathy, mental perspective taking, and emotion recognition in prosody, which are related to deficits in real-life social behavior such as fewer social contacts and more criminal offenses (13, 14). Furthermore, in money distribution games, CUs act more self-servingly and less altruistically than stimulant-naïve controls (15). Volkow et al. (9) postulated that neuroadaptations in the reward systems of drug users (e.g., ventral striatum and orbitofrontal cortex) alter reward processing such that the value of the abused drug is enhanced and concurrently the value of nondrug rewards, including social interaction, is reduced. Consequently, general social competence might become impaired and promote antisocial and criminal behavior. This may explain why social consequences of drug use (e.g., imprisonment or familial problems) do not prompt drug-addicted people to quit using the drug as well as how they contribute to increased drug use and transition from recreational drug use to addiction (9). However, whereas altered processing of monetary rewards has been reported in CUs (16), social reward processing has not been studied yet, neither on the psychological nor the neural level. Therefore, it remains elusive whether CUs (i) show behavioral differences to reward stemming from social interactions and, if so, (ii) which neural adaptations within reward circuitry underlie these potential changes in social interaction behavior.An essential part of social interaction is the phenomenon of “social gaze,” which has two aspects: Gaze can be used by the gazing person as a deictic cue to manipulate the attention of others, and can be read out by observers as a hint toward attentional focus of the gazing person (17). Both aspects can converge in joint attention (JA), which is a central element of social interaction (18) and is established when a person follows the direction of another person’s gaze so that both attend to the same object (19). Engagement in JA is considered to reflect our understanding of another person’s point of view (20). The capacity of JA emerges at 8–12 mo of age (21) and is predictive for later language learning (22) and the development of more advanced social skills such as mental perspective taking (e.g., the attribution of intentions and goals to others, also known as theory of mind) (23). Impaired JA is a core symptom of autism spectrum disorders (24).To test for social gaze differences between CUs and healthy controls (HCs), we applied a paradigm designed to capture the reciprocal and interactive nature of JA (25) (Fig. S1), where participants engage in an online interaction with an anthropomorphic virtual character in real time. Compared with self-initiated nonjoint attention (NJA; i.e., if the counterpart does not follow one’s gaze but rather pays attention to another object), self-initiated JA (i.e., if the counterpart follows one’s own gaze) is perceived as more pleasurable and associated with stronger activation of reward-related brain areas in healthy controls (25). This rewarding nature of JA might underlie the human motivation to engage in the sharing of experiences that emerges in early childhood (22, 25).It has been suggested that changes in social reward processing might underlie alterations in social behavior and cognition in CUs (9). Here we conducted two studies assessing JA processing, which constitutes an elegant approach to investigate basic social interaction patterns related to social reward processing (25), in CUs and stimulant-naïve HCs by means of behavioral, psychophysiological, and functional brain-imaging methods. In study I, a large sample of relatively pure CUs with few psychiatric comorbidities (n = 80) and stimulant-naïve HCs (n = 63) completed an interactive JA task (25) while valence and arousal ratings, error scores, reaction time, and pupil size were obtained. Pupil dilation provides an objective index of affective processing (26, 27). Based on the observations obtained in study I, we further investigated the neural correlates of the blunted emotional response to social gaze in subsamples of 16 CUs and 16 HCs using functional magnetic resonance imaging (fMRI) during an abridged version of the paradigm (study II). We hypothesized that altered emotional responses to JA are accompanied by less pronounced activation in reward-related brain areas of CUs.     

The endogenous nociceptin/orphanin FQ‐NOP receptor system as a potential therapeutic target for intestinal disorders

In 1995, by reverse pharmacology approach, used here for the first time in the history of pharmacology, nociceptin/orphanin FQ (N/OFQ) has been discovered as the endogenous ligand of a preidentified receptor named opioid receptor like 1. Subsequent studies showed that N/OFQ and its receptor (N/OFQergic system) are widely distributed in central and peripheral nervous systems as well as in peripheral organs of human and animals, and represent a system that is involved in a very large range of biological functions such as pain perception, intestinal motility and secretion, immune modulation, stress. From the time of its discovery to now, a high number of NOP agonists and antagonists have been synthesized and tested in various pathologies. Nevertheless, none of the molecules targeting N/OFQergic system have currently succeeded in going through clinical trials concerning gut pathologies, indicating that further studies are required. The work from Dr. Fichna et al., published in the present issue of Neurogastroenterology and Motility, adds another brick in the wall of understanding the role of N/OFQergic system in IBS‐D pathology by the pharmacological evaluation of a new NOP receptor agonist, SCH 221510, in animal models of intestinal alterations (diarrhea and visceral hyperalgesia). Interestingly, authors report clinical data confirming the involvement of N/OFQergic system in IBS‐D patients and, consequently, suggest this system as a valuable therapeutic target for IBS‐D pathology. This minireview aims to give a brief summary of experimental and clinical studies focusing on the N/OFQergic system as pharmacological target for the therapeutic treatment of intestinal pathologies such as IBS and IBD.     

The Lepidopteran endoribonuclease-U domain protein P102 displays dramatically reduced enzymatic activity and forms functional amyloids

Hemocytes of Heliothis virescens (F.) (Lepidoptera, Noctuidae) larvae produce a protein, P102, with a putative endoribonuclease-U domain. In previous works we have shown that P102 is involved in Lepidopteran immune response by forming amyloid fibrils, which catalyze and localize melanin deposition around non-self intruders during encapsulation, preventing harmful systemic spreading. Here we demonstrate that P102 belongs to a new class of proteins that, at least in Lepidoptera, has a diminished endoribonuclease-U activity probably due to the lack of two out of five catalytically essential residues. We show that the P102 homolog from Trichoplusia ni (Lepidoptera, Noctuidae) displays catalytic site residues identical to P102, a residual endoribonuclease-U activity and the ability to form functional amyloids. On the basis of these results as well as sequence and structural analyses, we hypothesize that all the Lepidoptera endoribonuclease-U orthologs with catalytic site residues identical to P102 form a subfamily with similar function.