The Multipurpose Tool of Social Media: Applications for Scientists, Science Communicators, and Educators.

Social media has become the fastest way to disseminate new information, share personal experiences, and discuss scientific reports in an open-access setting. It acts as an aggregator of news and reports, a platform for education, a means of public outreach, and a tool for scientific research. Each social media service offers unique communication benefits. This review discusses how scientists are using social media to inform and learn from social media communities, concentrating on microbiology and infectious disease.

Virulence-Associated Enzymes of Cryptococcus neoformans.

Enzymes play key roles in fungal pathogenesis. Manipulation of enzyme expression or activity can significantly alter the infection process, and enzyme expression profiles can be a hallmark of disease. Hence, enzymes are worthy targets for better understanding pathogenesis and identifying new options for combatting fungal infections. Advances in genomics, proteomics, transcriptomics, and mass spectrometry have enabled the identification and characterization of new fungal enzymes. This review focuses on recent developments in the virulence-associated enzymes from Cryptococcus neoformans. The enzymatic suite of C. neoformans has evolved for environmental survival, but several of these enzymes play a dual role in colonizing the mammalian host. We also discuss new therapeutic and diagnostic strategies that could be based on the underlying enzymology.

Lipid Biosynthetic Genes Affect Candida albicans Extracellular Vesicle Morphology, Cargo, and Immunostimulatory Properties.

Microbial secretion is integral for regulating cell homeostasis as well as releasing virulence factors during infection. The genes encoding phosphatidylserine synthase (CHO1) and phosphatidylserine decarboxylase (PSD1 and PSD2) are Candida albicans genes involved in phospholipid biosynthesis, and mutations in these genes affect mitochondrial function, cell wall thickness, and virulence in mice. We tested the roles of these genes in several agar-based secretion assays and observed that the cho1Δ/Δ and psd1Δ/Δ psd2Δ/Δ strains manifested less protease and phospholipase activity. Since extracellular vesicles (EVs) are surrounded by a lipid membrane, we investigated the effects of these mutations on EV structure, composition, and biological activity. The cho1Δ/Δ mutant releases EVs comparable in size to wild-type EVs, but EVs from the psd1Δ/Δ psd2Δ/Δ strain are much larger than those from the wild type, including a population of >100-nm EVs not observed in the EVs from the wild type. Proteomic analysis revealed that EVs from both mutants had a significantly different protein cargo than that of EVs from the wild type. EVs were tested for their ability to activate NF-κB in bone marrow-derived macrophage cells. While wild-type and psd1Δ/Δ psd2Δ/Δ mutant-derived EVs activated NF-κB, the cho1Δ/Δ mutant-derived EV did not. These studies indicate that the presence and absence of these C. albicans genes have qualitative and quantitative effects on EV size, composition, and immunostimulatory phenotypes that highlight a complex interplay between lipid metabolism and vesicle production.

Interaction of Cryptococcus neoformans extracellular vesicles with the cell wall.

Cryptococcus neoformans produces extracellular vesicles containing a variety of cargo, including virulence factors. To become extracellular, these vesicles not only must be released from the plasma membrane but also must pass through the dense matrix of the cell wall. The greatest unknown in the area of fungal vesicles is the mechanism by which these vesicles are released to the extracellular space given the presence of the fungal cell wall. Here we used electron microscopy techniques to image the interactions of vesicles with the cell wall. Our goal was to define the ultrastructural morphology of the process to gain insights into the mechanisms involved. We describe single and multiple vesicle-leaving events, which we hypothesized were due to plasma membrane and multivesicular body vesicle origins, respectively. We further utilized melanized cells to "trap" vesicles and visualize those passing through the cell wall. Vesicle size differed depending on whether vesicles left the cytoplasm in single versus multiple release events. Furthermore, we analyzed different vesicle populations for vesicle dimensions and protein composition. Proteomic analysis tripled the number of proteins known to be associated with vesicles. Despite separation of vesicles into batches differing in size, we did not identify major differences in protein composition. In summary, our results indicate that vesicles are generated by more than one mechanism, that vesicles exit the cell by traversing the cell wall, and that vesicle populations exist as a continuum with regard to size and protein composition.

Characterization of Alternaria infectoria extracellular vesicles.

Many fungi use membrane vesicles to transport complex molecules across their cell walls. Like mammalian exosomes, fungal vesicles contain lipids, proteins, and polysaccharides, many of which are associated with virulence. Here we identify and characterize extracellular vesicles (EVs) in Alternaria infectoria, a ubiquitous, environmental filamentous fungus that is also an opportunistic human pathogen. Examination of the A. infectoria EVs revealed a morphology similar to that of vesicles described in other fungal species. Of note, proteomic analysis detected a reduced number of vesicle-associated proteins. There were two prevalent categories among the 20 identified proteins, including the polysaccharide metabolism group, probably related to plant host invasion or biosynthesis/degradation of cell wall components, and the nuclear proteins, especially DNA repair enzymes. We also found enzymes related to pigment synthesis, adhesion to the host cell, and trafficking of vesicles/organelles/molecules. This is the first time EV secretions have been identified in a filamentous fungus. We believe that these vesicles might have a role in virulence.

Serum albumin disrupts Cryptococcus neoformans and Bacillus anthracis extracellular vesicles.

For both pathogenic fungi and bacteria, extracellular vesicles have been shown to contain many microbial components associated with virulence, suggesting a role in pathogenesis. However, there are many unresolved issues regarding vesicle synthesis and stability, including the fact that vesicular packaging for extracellular factors involved in virulence must also have a mechanism for vesicle unloading. Consequently, we studied the kinetics of vesicle production and stability using [1-(14) C] palmitic acid metabolic labelling and dynamic light scattering techniques. Cryptococcus neoformans vesicles were produced throughout all stages of fungal culture growth and they were stable once isolated. Density gradient analysis revealed that only a portion of the vesicle population carried cryptococcal polysaccharide, implying heterogeneity in vesicular cargo. Vesicle incubation with macrophages resulted in rapid vesicle instability, a phenomenon that was ultimately associated with serum albumin. Additionally, albumin, along with mouse serum and murine immunoglobulin destabilized Bacillus anthracis vesicles, but the effect was not observed with ovalbumin or keyhole limpet haemocyanin, demonstrating that this phenomenon is neither host-, microbe- nor protein-specific. Our findings strongly suggest that cryptococcal vesicles are short-lived in vivo and vesicle destabilization is mediated by albumin. The ability of albumin to promote vesicular offload through destabilization indicates a new activity for this abundant serum protein.

Neural signatures of autism.

Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system-level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.

Development of peak alpha frequency reflects a distinct trajectory of neural maturation in autistic children.

Electroencephalographic peak alpha frequency (PAF) is a marker of neural maturation that increases with age throughout childhood. Distinct maturation of PAF is observed in children with autism spectrum disorder such that PAF does not increase with age and is instead positively associated with cognitive ability. The current study clarifies and extends previous findings by characterizing the effects of age and cognitive ability on PAF between diagnostic groups in a sample of children and adolescents with and without autism spectrum disorder. Resting EEG data and behavioral measures were collected from 45 autistic children and 34 neurotypical controls aged 8 to 18 years. Utilizing generalized additive models to account for nonlinear relations, we examined differences in the joint effect of age and nonverbal IQ by diagnosis as well as bivariate relations between age, nonverbal IQ, and PAF across diagnostic groups. Age was positively associated with PAF among neurotypical children but not among autistic children. In contrast, nonverbal IQ but not age was positively associated with PAF among autistic children. Models accounting for nonlinear relations revealed different developmental trajectories as a function of age and cognitive ability based on diagnostic status. Results align with prior evidence indicating that typical age-related increases in PAF are absent in autistic children and that PAF instead increases with cognitive ability in these children. Findings suggest the potential of PAF to index distinct trajectories of neural maturation in autistic children.

EDTA inhibits biofilm formation, extracellular vesicular secretion, and shedding of the capsular polysaccharide glucuronoxylomannan by Cryptococcus neoformans.

The fungal pathogen Cryptococcus neoformans can grow as a biofilm on a range of synthetic and prosthetic materials. Cryptococcal biofilm formation can complicate the placement of shunts used to relieve increased intracranial pressure in cryptococcal meningitis and can serve as a nidus for chronic infection. Biofilms are generally advantageous to pathogens in vivo, as they can confer resistance to antimicrobial compounds, including fluconazole and voriconazole in the case of C. neoformans. EDTA can inhibit biofilm formation by several microbes and enhances the susceptibility of biofilms to antifungal drugs. In this study, we evaluated the effect of sublethal concentrations of EDTA on the growth of cryptococcal biofilms. EDTA inhibited biofilm growth by C. neoformans, and the inhibition could be reversed by the addition of magnesium or calcium, implying that the inhibitory effect was by divalent cation starvation. EDTA also reduced the amount of the capsular polysaccharide glucuronoxylomannan shed into the biofilm matrix and decreased vesicular secretion from the cell, thus providing a potential mechanism for the inhibitory effect of this cation-chelating compound. Our data imply that the growth of C. neoformans biofilms requires the presence of divalent metals in the growth medium and suggest that cations are required for the export of materials needed for biofilm formation, possibly including extracellular vesicles.

The perception and identification of facial emotions in individuals with autism spectrum disorders using the Let's Face It! Emotion Skills Battery.

BACKGROUND: Although impaired social-emotional ability is a hallmark of autism spectrum disorder (ASD), the perceptual skills and mediating strategies contributing to the social deficits of autism are not well understood. A perceptual skill that is fundamental to effective social communication is the ability to accurately perceive and interpret facial emotions. To evaluate the expression processing of participants with ASD, we designed the Let's Face It! Emotion Skills Battery (LFI! Battery), a computer-based assessment composed of three subscales measuring verbal and perceptual skills implicated in the recognition of facial emotions. METHODS: We administered the LFI! Battery to groups of participants with ASD and typically developing control (TDC) participants that were matched for age and IQ. RESULTS: On the Name Game labeling task, participants with ASD (N = 68) performed on par with TDC individuals (N = 66) in their ability to name the facial emotions of happy, sad, disgust and surprise and were only impaired in their ability to identify the angry expression. On the Matchmaker Expression task that measures the recognition of facial emotions across different facial identities, the ASD participants (N = 66) performed reliably worse than TDC participants (N = 67) on the emotions of happy, sad, disgust, frighten and angry. In the Parts-Wholes test of perceptual strategies of expression, the TDC participants (N = 67) displayed more holistic encoding for the eyes than the mouths in expressive faces whereas ASD participants (N = 66) exhibited the reverse pattern of holistic recognition for the mouth and analytic recognition of the eyes. CONCLUSION: In summary, findings from the LFI! Battery show that participants with ASD were able to label the basic facial emotions (with the exception of angry expression) on par with age- and IQ-matched TDC participants. However, participants with ASD were impaired in their ability to generalize facial emotions across different identities and showed a tendency to recognize the mouth feature holistically and the eyes as isolated parts.

Predictability modulates neural response to eye contact in ASD.

BACKGROUND: Deficits in establishing and maintaining eye-contact are early and persistent vulnerabilities of autism spectrum disorder (ASD), and the neural bases of these deficits remain elusive. A promising hypothesis is that social features of autism may reflect difficulties in making predictions about the social world under conditions of uncertainty. However, no research in ASD has examined how predictability impacts the neural processing of eye-contact in naturalistic interpersonal interactions. METHOD: We used eye tracking to facilitate an interactive social simulation wherein onscreen faces would establish eye-contact when the participant looked at them. In Experiment One, receipt of eye-contact was unpredictable; in Experiment Two, receipt of eye-contact was predictable. Neural response to eye-contact was measured via the N170 and P300 event-related potentials (ERPs). Experiment One included 23 ASD and 46 typically developing (TD) adult participants. Experiment Two included 25 ASD and 43 TD adult participants. RESULTS: When receipt of eye-contact was unpredictable, individuals with ASD showed increased N170 and increased, but non-specific, P300 responses. The magnitude of the N170 responses correlated with measures of sensory and anxiety symptomology, such that increased response to eye-contact was associated with increased symptomology. However, when receipt of eye-contact was predictable, individuals with ASD, relative to controls, exhibited slower N170s and no differences in the amplitude of N170 or P300. LIMITATIONS: Our ASD sample was composed of adults with IQ > 70 and included only four autistic women. Thus, further research is needed to evaluate how these results generalize across the spectrum of age, sex, and cognitive ability. Additionally, as analyses were exploratory, some findings failed to survive false-discovery rate adjustment. CONCLUSIONS: Neural response to eye-contact in ASD ranged from attenuated to hypersensitive depending on the predictability of the social context. These findings suggest that the vulnerabilities in eye-contact during social interactions in ASD may arise from differences in anticipation and expectation of eye-contact in addition to the perception of gaze alone.

Neural correlates of eye contact and social function in autism spectrum disorder.

Reluctance to make eye contact during natural interactions is a central diagnostic criterion for autism spectrum disorder (ASD). However, the underlying neural correlates for eye contacts in ASD are unknown, and diagnostic biomarkers are active areas of investigation. Here, neuroimaging, eye-tracking, and pupillometry data were acquired simultaneously using two-person functional near-infrared spectroscopy (fNIRS) during live "in-person" eye-to-eye contact and eye-gaze at a video face for typically-developed (TD) and participants with ASD to identify the neural correlates of live eye-to-eye contact in both groups. Comparisons between ASD and TD showed decreased right dorsal-parietal activity and increased right ventral temporal-parietal activity for ASD during live eye-to-eye contact (p≤0.05, FDR-corrected) and reduced cross-brain coherence consistent with atypical neural systems for live eye contact. Hypoactivity of right dorsal-parietal regions during eye contact in ASD was further associated with gold standard measures of social performance by the correlation of neural responses and individual measures of: ADOS-2, Autism Diagnostic Observation Schedule, 2nd Edition (r = -0.76, -0.92 and -0.77); and SRS-2, Social Responsiveness Scale, Second Edition (r = -0.58). The findings indicate that as categorized social ability decreases, neural responses to real eye-contact in the right dorsal parietal region also decrease consistent with a neural correlate for social characteristics in ASD.

The Candida albicans ESCRT pathway makes Rim101-dependent and -independent contributions to pathogenesis.

Candida albicans is an opportunistic pathogen that colonizes diverse mucosal niches with distinct environmental characteristics. To adapt to these different sites, C. albicans must activate and attenuate a variety of signal transduction pathways. A mechanism of signal attenuation is through receptor endocytosis and subsequent vacuolar degradation, which requires the endosomal sorting complex required for transport (ESCRT) pathway. This pathway comprises several polyprotein complexes (ESCRT-0, -I, -II, -III, and -DS) that are sequentially recruited to the endosomal membrane. The ESCRT pathway also activates the Rim101 transcription factor, which governs expression of genes required for virulence. Here, we tested the hypothesis that the ESCRT pathway plays a Rim101-independent role(s) in pathogenesis. We generated deletion mutants in each ESCRT complex and determined that ESCRT-I, -II, and -III are required for Rim101 activation but that ESCRT-0 and ESCRT-DS are not. We found that the ESCRT-0 member Vps27 and ESCRT-DS components are required to promote epithelial cell damage and, using a murine model of oral candidiasis, found that the vps27Delta/Delta mutant had a decreased fungal burden compared to that of the wild type. We found that a high-dose inoculum can compensate for fungal burden defects but that mice colonized with the vps27Delta/Delta strain exhibit less morbidity than do mice infected with the wild-type strain. These results demonstrate that the ESCRT pathway has Rim101-independent functions for C. albicans virulence.

Face perception predicts affective theory of mind in autism spectrum disorder but not schizophrenia or typical development.

Autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SCZ) have overlapping symptomatology related to difficulties with social cognition. Yet, few studies have directly compared social cognition in ASD, SCZ, and typical development (TD). The current study examined individual differences in face recognition and its relation to affective theory of mind (ToM) in each diagnostic group. Adults with ASD (n = 31), SCZ (n = 43), and TD (n = 47) between the ages of 18 and 48 years-old with full scale IQ above 80 participated in this study. The Reading the Mind in the Eyes Test (RMET) measured affective ToM, and the Benton Facial Recognition Test (BFRT) measured face perception. Adults with ASD and SCZ did not differ in their affective ToM abilities, and both groups showed affective ToM difficulties compared with TD. However, better face recognition ability uniquely predicted better affective ToM ability in ASD. Results suggest that affective ToM difficulties may relate to face processing in ASD but not SCZ. By clarifying the complex nature of individual differences in affective ToM and face recognition difficulties in these disorders, the present study suggests there may be divergent mechanisms underlying pathways to social dysfunction in ASD compared with SCZ. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Using computerized games to teach face recognition skills to children with autism spectrum disorder: the Let's Face It! program.

BACKGROUND: An emerging body of evidence indicates that relative to typically developing children, children with autism are selectively impaired in their ability to recognize facial identity. A critical question is whether face recognition skills can be enhanced through a direct training intervention. METHODS: In a randomized clinical trial, children diagnosed with autism spectrum disorder were pre-screened with a battery of subtests (the Let's Face It! Skills battery) examining face and object processing abilities. Participants who were significantly impaired in their face processing abilities were assigned to either a treatment or a waitlist group. Children in the treatment group (N = 42) received 20 hours of face training with the Let's Face It! (LFI!) computer-based intervention. The LFI! program is comprised of seven interactive computer games that target the specific face impairments associated with autism, including the recognition of identity across image changes in expression, viewpoint and features, analytic and holistic face processing strategies and attention to information in the eye region. Time 1 and Time 2 performance for the treatment and waitlist groups was assessed with the Let's Face It! Skills battery. RESULTS: The main finding was that relative to the control group (N = 37), children in the face training group demonstrated reliable improvements in their analytic recognition of mouth features and holistic recognition of a face based on its eyes features. CONCLUSION: These results indicate that a relatively short-term intervention program can produce measurable improvements in the face recognition skills of children with autism. As a treatment for face processing deficits, the Let's Face It! program has advantages of being cost-free, adaptable to the specific learning needs of the individual child and suitable for home and school applications.

Sibling Relationships: Parent-Child Agreement and Contributions of Siblings With and Without ASD.

Research on the experiences of siblings of individuals with ASD and the quality of their sibling relationships has yielded mixed results. The present study examined the significance of parent- versus child-report of both positive and negative behaviors exhibited by siblings and their brothers and sisters with ASD within sibling dyads. Findings indicated that siblings were more positive in their assessment of the sibling relationship than were their parents. Siblings exhibited more positive behaviors within the sibling relationship than did their brothers and sisters with ASD, and were recipients of aggression. These findings are consistent with prior research suggesting that siblings tend to take on a caretaking role, and point to important targets for intervention.

Analysis of multiple components involved in the interaction between Cryptococcus neoformans and Acanthamoeba castellanii.

Cryptococcus neoformans is an environmental fungus that can cause lethal meningoencephalitis in immunocompromised individuals. The mechanisms by which environmental microbes become pathogenic to mammals are still obscure, but different studies suggest that fungal virulence evolved from selection imposed by environmental predators. The soil-living Acanthamoeba castellanii is a well-known predator of C. neoformans. In this work, we evaluated the participation of C. neoformans virulence-associated structures in the interaction of fungal cells with A. castellanii. Fungal extracellular vesicles (EVs) and the polysaccharide glucuronoxylomannan (GXM) were internalized by A. castellanii with no impact on the viability of amoebal cells. EVs, but not free GXM, modulated antifungal properties of A. castellanii by inducing enhanced yeast survival. Phagocytosis of C. neoformans by amoebal cells and the pathogenic potential in a Galleria mellonella model were not affected by EVs, but previous interactions with A. castellanii rendered fungal cells more efficient in killing this invertebrate host. This observation was apparently associated with marked amoeba-induced changes in surface architecture and increased resistance to both oxygen- and nitrogen-derived molecular species. Our results indicate that multiple components with the potential to impact pathogenesis are involved in C. neoformans environmental interactions.

Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects.

Cryptococcus neoformans is an encapsulated fungal pathogen that causes cryptococcosis, which is a major opportunistic infection in immunosuppressed individuals. Mammalian ß-galactoside-binding protein Galectin-3 (Gal-3) modulates the host innate and adaptive immunity, and plays significant roles during microbial infections including some fungal diseases. Here we show that this protein plays a role also in C. neoformans infection. We find augmented Gal-3 serum levels in human and experimental infections, as well as in spleen, lung, and brain tissues of infected mice. Gal-3-deficient mice are more susceptible to cryptococcosis than WT animals, as demonstrated by the higher fungal burden and lower animal survival. In vitro experiments show that Gal-3 inhibits fungal growth and exerts a direct lytic effect on C. neoformans extracellular vesicles (EVs). Our results indicate a direct role for Gal-3 in antifungal immunity whereby this molecule affects the outcome of C. neoformans infection by inhibiting fungal growth and reducing EV stability, which in turn could benefit the host.

IFNgamma sensitization to TRAIL-induced apoptosis in human thyroid carcinoma cells by upregulating Bak expression.

TRAIL preferentially induces apoptosis in tumor cells and virus-infected cells. Unlike other tumor necrosis factor family members, TRAIL does not kill cells from most normal tissues and has thus been proposed as a promising new cancer treatment. Our study demonstrated that IFNgamma combined with TRAIL can trigger apoptosis in vitro in several resistant thyroid tumor cell lines, such as thyroid anaplastic carcinoma cells (ARO cells), while either agent alone exerts only a minimal effect. We further tested this effect on a mouse thyroid tumor model, when in vivo tumor growth was also significantly inhibited by this combination. The mechanism of how IFNgamma sensitized thyroid carcinoma cells to TRAIL-induced apoptosis was investigated by screening global gene alterations in ARO cells treated with IFNgamma. Microarray data revealed that a proapoptotic gene, Bak, is markedly upregulated by IFNgamma, and this was confirmed by RNase protection assay. Western blot analysis also showed a significant increase in Bak at the protein level. Upregulation of Bak and sensitization for apoptosis by IFNgamma was blocked by overexpression of antisense Bak in ARO cells. Furthermore, overexpression of Bak sensitized ARO cell to TRAIL-induced apoptosis without the need for IFNgamma pretreatment. This suggests that Bak is a regulatory molecule involved in IFNgamma-facilitated TRAIL-mediated apoptosis in thyroid cancer cells.

Death ligand tumor necrosis factor-related apoptosis-inducing ligand inhibits experimental autoimmune thyroiditis.

The role of TNF-related apoptosis-inducing ligand (TRAIL) in autoimmune thyroiditis is unclear. We used experimental autoimmune thyroiditis to clarify the contribution of TRAIL to the development of autoimmune thyroiditis. CBA/J mice were immunized with murine thyroglobulin, and spleen cells from these mice were subsequently injected into irradiated recipient CBA/J mice. One week later, the recipient mice were treated with recombinant TRAIL or a control protein. Compared with control animals, TRAIL-treated mice developed a milder form of the disease with a significant decrease in mononuclear cell infiltration in the thyroid and less thyroid follicular destruction. Furthermore, the number of apoptotic thyrocytes and also thyroglobulin-specific T helper-1 cell responses in TRAIL-treated mice was lower than that in the control animals. This study suggests that exogenous TRAIL suppresses the development of autoimmune thyroiditis via altering the function of cells involved in the immune response. These findings may contribute toward a novel treatment autoimmune thyroiditis.