scholarly journals Multilocus Sequence Typing Reveals A Unique Co-Dominant Population Structure of Cryptococcus Neoformans Var. Grubii in Vietnam

2017 ◽  
Author(s):  
Thanh Lam Tuan ◽  
Trieu Phan Hai ◽  
Sayaphet Rattanavong ◽  
Trinh Mai Nguyen ◽  
Anh Duong Van ◽  
...  
Keyword(s):  
Population Structure ◽  
Southeast Asia ◽  
East Asia ◽  
Cryptococcus Neoformans ◽  
Cryptococcal Meningitis ◽  
Multilocus Sequence Typing ◽  
Fungal Infections ◽  
Total N ◽  
Global Context ◽  
The Relationship

AbstractCryptococcosis is amongst the most important invasive fungal infections globally, with cryptococcal meningitis causing an estimated 180,000 deaths each year in HIV infected patients alone. Patients with other forms of immunosuppression are also at risk, and disease is increasingly recognized in apparently immunocompetent individuals. Cryptococcus neoformans var. grubii (serotype A, molecular type VNI) has a global distribution and is responsible for the majority of cases. Here, we used the consensus ISHAM Multilocus Sequence Typing (MLST) for C. neoformans to define the population structure of clinical isolates of Cryptococcus neoformans var. grubii from Vietnam (n=136) and Laos (n=81). We placed these isolates into the global context using published MLST data from 8 other countries (total N = 669). We observed a phylo-geographical relationship in which Laos was similar to its Southeast Asian neighbor Thailand in being dominated (83%) by Sequence Type (ST) 4 and its Single Locus Variant ST6. On the other hand, Vietnam was uniquely intermediate between Southeast Asia and East Asia having both ST4/ST6 (35%) and ST5 (48%) which causes the majority of cases in East Asia. Analysis of genetic distance (Fst) between different populations of Cryptococcus neoformans var. grubii supported the intermediate nature of the population from Vietnam. A strong association between ST5 and infection in apparently immunocompetent, HIV-uninfected patients was observed in Vietnam (OR: 7.97, [95%CI: 3.18-19.97], p < 0.0001). Our study emphasizes that Vietnam, with its intermediate Cryptococcus neoformans var. grubii population structure, provides the strongest epidemiological evidence of the relationship between ST5 and infection of HIV-uninfected patients. Human population genetic distances within the region suggest these differences in CNVG population across Southeast Asia are driven by ecological factors rather than host factors.Author summaryCryptococcus neoformans is a yeast that causes meningitis in people, usually with damaged immune systems. There are >180,000 deaths in HIV-infected patients each year, most occurring where there are the highest HIV/AIDS disease burdens. Vietnam and Laos have contributed significantly to clinical trials aiming to improve the treatment of cryptococcal meningitis, but the relationship of isolates from these countries to the global population is not yet described. Here, we address this knowledge gap by using Multilocus Sequence Typing to study the population of Cryptococcus neoformans var. grubii (CNVG) in Laos and Vietnam, with the specific aim of incorporating these populations into the wider global context. We found that, in most countries, a single lineage (family) of strains was responsible for most disease. The Vietnamese CNVG population was unusual in that 2 main lineages circulated at the same time. The Vietnamese CNVG population occupies a middle ground between Thailand/Laos in the west and China in the east. The differences in population structure moving from West to East are probably due to ecological differences. Disease in HIV uninfected patients was almost always due to members of a single family of strains (ST5).

scholarly journals Multilocus sequence typing of Cryptococcus neoformans var. grubii from Laos in a regional and global context

2018 ◽  
Vol 57 (5) ◽  
pp. 557-565 ◽  
Author(s):  
Lam Tuan Thanh ◽  
Trieu Hai Phan ◽  
Sayaphet Rattanavong ◽  
Trinh Mai Nguyen ◽  
Anh Van Duong ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Multilocus Sequence Typing ◽  
Global Context

scholarly journals MiR-4792 regulates inflammatory responses in Cryptococcus neoformans infected microglia

2020 ◽  
Author(s):  
Jianghan Chen ◽  
Guotai Yao ◽  
Xiaoli Wang ◽  
Qing Hou ◽  
Rui Gao ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Inflammatory Cytokines ◽  
Cryptococcal Meningitis ◽  
Target Gene ◽  
Inflammatory Responses ◽  
Fungal Infections ◽  
Mapk Signaling ◽  
Microbial Infection ◽  
Bv2 Cells ◽  
Infected Cells

Abstract Background: Investigating the factors that influence inflammatory response of microglial cells is important to understand the pathogenesis of cryptococcal meningitis (CM). MicroRNA (miRNA) have been shown to play an important role in inducing host defenses and activating immune response in the process of microbial infection; however, the regulatory mechanisms of miRNAs in cryptococcal meningitis are poorly defined. In our previous analysis, we assessed the miRNA profiles of BV2 cells following Cryptococcus neoformans (C. neoformans) infection. In this study, we characterized the expression of miR-4792 in CM patients to further our understanding of the host response to pathogen infections. Results: miR-4792 was downregulated in BV2 cells infected with C. neoformans while its target gene EGFR was upregulated. Infected cells with up-regulated miR-4792 exhibited a trend towards decreased EGFR transcript expression, reduced MAPK signaling and a decreased secretion of inflammatory cytokines. Afterantifungal treatment in cryptococcal meningitis patients, the levels of miR-4792 in the CSF significantly increased, while the expression of EGFR significantly decreased. Conclusion: This study identified that miR-4792 and its target gene EGFR regulate the secretion of inflammatory cytokines in BV2 cells infected with C. neoformans. This furthers our knowledge of the inflammatoryresponses to fungal infections in the CNS.

scholarly journals An Antivirulence Approach for Preventing Cryptococcus neoformans from Crossing the Blood-Brain Barrier via Novel Natural Product Inhibitors of a Fungal Metalloprotease

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Phylicia A. Aaron ◽  
Kiem Vu ◽  
Angie Gelli
Keyword(s):  
Cryptococcus Neoformans ◽  
Blood Brain Barrier ◽  
Cryptococcal Meningitis ◽  
Mammalian Cells ◽  
Large Scale ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Brain Barrier ◽  
Content Type ◽  
Blood Brain

ABSTRACT Cryptococcus neoformans (Cn) is the leading cause of fungal meningitis, a deadly disease with limited therapeutic options. Dissemination to the central nervous system hinges on the ability of Cn to breach the blood-brain barrier (BBB) and is considered an attribute of Cn virulence. Targeting virulence instead of growth for antifungal drug development has not been fully exploited despite the benefits of this approach. Mpr1 is a secreted fungal metalloprotease not required for fungal growth, but rather, it functions as a virulence factor by facilitating Cn migration across the BBB. This central role for Mpr1, its extracellular location, and lack of expression in mammalian cells make Mpr1 a high-value target for an antivirulence approach aimed at developing therapeutics for cryptococcal meningitis. To test this notion, we devised a large-scale screen to identify compounds that prohibited Cn from crossing the BBB by selectively blocking Mpr1 proteolytic activity, without inhibiting the growth of Cn. A phytochemical natural product-derived library was screened to identify new molecular scaffolds of prototypes unique to a Cn microecosystem. Of the 240 pure natural products examined, 3 lead compounds, abietic acid, diosgenin, and lupinine inhibited Mpr1 proteolytic activity with 50% inhibitory concentration (IC50) values of <10 μM, displayed little to no mammalian cell toxicity, and did not affect Cn growth. Notably, the lead compounds blocked Cn from crossing the BBB, without damaging the barrier integrity, suggesting the bioactive molecules had no off-target effects. We propose that these new drug scaffolds are promising candidates for the development of antivirulence therapy against cryptococcal meningitis. IMPORTANCE Fungal infections like cryptococcal meningitis are difficult to resolve because of the limited therapies available. The small arsenal of antifungal drugs reflect the difficulty in finding available targets in fungi because like mammalian cells, fungi are eukaryotes. The limited efficacy, toxicity, and rising resistance of antifungals contribute to the high morbidity and mortality of fungal infections and further underscore the dire but unmet need for new antifungal drugs. The traditional approach in antifungal drug development has been to target fungal growth, but an attractive alternative is to target mechanisms of pathogenesis. An important attribute of Cryptococcus neoformans (Cn) pathogenesis is its ability to enter the central nervous system. Here, we describe a large-scale screen that identified three natural products that prevented Cn from crossing the blood-brain barrier by inhibiting the virulence factor Mpr1 without affecting the growth of Cn. We propose that compounds identified here could be further developed as antivirulence therapy that would be administered preemptively or serve as a prophylactic in patients at high risk for developing cryptococcal meningitis.

scholarly journals MiR-4792 regulates inflammatory responses in Cryptococcus neoformans infected microglia

2020 ◽  
Author(s):  
Jianghan Chen ◽  
Guotai Yao ◽  
Xiaoli Wang ◽  
Qing Hou ◽  
Rui Gao ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Inflammatory Cytokines ◽  
Cryptococcal Meningitis ◽  
Inflammatory Responses ◽  
Fungal Infections ◽  
Mapk Signaling ◽  
Microbial Infection ◽  
Host Immune Responses ◽  
Egfr Expression ◽  
Bv2 Cells

Abstract Background: Investigating the factors that influence inflammatory response of microglial cells is important to understand the pathogenesis of cryptococcal meningitis (CM). MicroRNA (miRNA) have been shown to play an important role in inducing host defenses and activating immune response in the process of microbial infection; however, the regulatory mechanisms of miRNAs in cryptococcal meningitis are poorly defined. In our previous analysis, we assessed the miRNA profiles of BV2 cells following Cryptococcus neoformans (C. neoformans) infection. In this study, we characterized the expression of miR-4792 in CM patients to further our understanding of the host response to pathogen infections.Results: miR-4792 was downregulated in BV2 cells infected with C. neoformans while its target gene EGFR was upregulated. Infected cells with up-regulated miR-4792 exhibited decreased EGFR expression, reduced MAPK signaling and a decreased secretion of inflammatory cytokines. Following antifungal treatment in cryptococcal meningitis patients, the levels of miR-4792 in the CSF significantly increased, while the expression of EGFR significantly decreased.Conclusion: This study identified that miR-4792 and its target EGFR regulate the secretion of inflammatory cytokines in C. neoformans infected BV2 cells. This furthers our knowledge of the host immune responses to fungal infections in the CNS.

Anthropological communities of interpretation for Burma: An overview

2008 ◽  
Vol 39 (2) ◽  
pp. 239-254 ◽  
Author(s):  
U Chit Hlaing
Keyword(s):  
Southeast Asia ◽  
Ethnic Groups ◽  
Field Of Study ◽  
Anthropological Theory ◽  
History Of ◽  
Relationship Of ◽  
The Relationship ◽  
The Way

AbstractThis paper surveys the history of anthropological work on Burma, dealing both with Burman and other ethnic groups. It focuses upon the relations between anthropology and other disciplines, and upon the relationship of such work to the development of anthropological theory. It tries to show how anthropology has contributed to an overall understanding of Burma as a field of study and, conversely, how work on Burma has influenced the development of anthropology as a subject. It also tries to relate the way in which anthropology helps place Burma in the broader context of Southeast Asia.

A new species of the montane lacewing genus Rapisma McLachlan (Neuroptera, Ithonidae) from northwestern Yunnan, China

Zootaxa ◽  
2020 ◽  
Vol 4763 (3) ◽  
pp. 439-443
Author(s):  
XINGYUE LIU
Keyword(s):  
New Species ◽  
Southeast Asia ◽  
East Asia ◽  
South Asia ◽  
The Family ◽  
A New Species ◽  
Northwestern Yunnan

The genus Rapisma McLachlan, 1866 (montane lacewings) is a rare and little known group of the family Ithonidae (Insecta: Neuroptera). There have been 21 described species of Rapisma, and all of them are distributed from East Asia, South Asia and Southeast Asia. Here I report a new species of Rapisma from northwestern Yunnan, China, namely Rapisma weixiense sp. nov. The new species belongs to a group of Rapisma species with very short antennae. 

scholarly journals Pain, Culture and Pedagogy: A Preliminary Investigation of Attitudes Towards “Reasonable” Pain Tolerance in the Grassroots Reproduction of a Culture of Risk

2021 ◽  
pp. 003329412098809
Author(s):  
Paul K. Miller ◽  
Sophie Van Der Zee ◽  
David Elliott
Keyword(s):  
Undergraduate Students ◽  
Pain Perception ◽  
Tertiary Education ◽  
Preliminary Investigation ◽  
Psychological Research ◽  
Pain Tolerance ◽  
Total N ◽  
Sporting Culture ◽  
Significant Difference ◽  
The Relationship

In recent years a considerable body of psychological research has explored the relationship between membership of socio-cultural groups and personal pain perception. Rather less systematic attention has, however, been accorded to how such group membership(s) might influence individual attitudes towards the pain of others. In this paper, immersion in the culture of competitive sport, widely regarded as being exaggeratedly tolerant of risky behaviours around pain, is taken as a case-in-point with students of Physical Education (PE) in tertiary education as the key focus. PE students are highly-immersed in competitive sporting culture both academically and (typically) practically, and also represent a key nexus of cross-generational transmission regarding the norms of sport itself. Their attitudes towards the pain that others should reasonably tolerate during a range of activities, sporting and otherwise, were evaluated through a direct comparison with those of peers much less immersed in competitive sporting culture. In total, N=301 (144 PE, 157 non-PE) undergraduate students in the UK responded to a vignette-based survey. Therein, all participants were required to rate the pain (on a standard 0-10 scale) at which a standardised “other” should desist engagement with a set of five defined sporting and non-sporting tasks, each with weak and strong task severities. Results indicated that PE students were significantly more likely to expect others to persevere through higher levels of pain than their non-PE peers, but only during the sport-related tasks – an effect further magnified when task severity was high. In other tasks, there was no significant difference between groups, or valence of the effect was actually reversed. It is argued that the findings underscore some extant knowledge about the relationship between acculturated attitudes to pain, while also having practical implications for understanding sport-based pedagogy, and its potentially problematic role in the ongoing reproduction of a “culture of risk.”

scholarly journals Trends in Antifungal Drug Susceptibility of Cryptococcus neoformans Isolates Obtained through Population-Based Surveillance in South Africa in 2002-2003 and 2007-2008

2011 ◽  
Vol 55 (6) ◽  
pp. 2606-2611 ◽  
Author(s):  
Nelesh P. Govender ◽  
Jaymati Patel ◽  
Marelize van Wyk ◽  
Tom M. Chiller ◽  
Shawn R. Lockhart ◽  
...  
Keyword(s):  
South Africa ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Drug Susceptibility ◽  
Population Based ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method

ABSTRACTCryptococcus neoformansis the most common cause of meningitis among adult South Africans with HIV infection/AIDS. Widespread use of fluconazole for treatment of cryptococcal meningitis and other HIV-associated opportunistic fungal infections in South Africa may lead to the emergence of isolates with reduced fluconazole susceptibility. MIC testing using a reference broth microdilution method was used to determine if isolates with reduced susceptibility to fluconazole or amphotericin B had emerged among cases of incident disease. Incident isolates were tested from two surveillance periods (2002-2003 and 2007-2008) when population-based surveillance was conducted in Gauteng Province, South Africa. These isolates were also tested for susceptibility to flucytosine, itraconazole, voriconazole, and posaconazole. Serially collected isolate pairs from cases at several large South African hospitals were also tested for susceptibility to fluconazole. Of the 487 incident isolates tested, only 3 (0.6%) demonstrated a fluconazole MIC of ≥16 μg/ml; all of these isolates were from 2002-2003. All incident isolates were inhibited by very low concentrations of amphotericin B and exhibited very low MICs to voriconazole and posaconazole. Of 67 cases with serially collected isolate pairs, only 1 case was detected where the isolate collected more than 30 days later had a fluconazole MIC value significantly higher than the MIC of the corresponding incident isolate. Although routine antifungal susceptibility testing of incident isolates is not currently recommended in clinical settings, it is still clearly important for public health to periodically monitor for the emergence of resistance.

CLT using CEFR and EIL in Southeast Asia and East Asia in the English language classroom

RELC Journal ◽  
2021 ◽  
pp. 003368822199807
Author(s):  
Joseph Foley
Keyword(s):  
Southeast Asia ◽  
East Asia ◽  
Language Proficiency ◽  
English Language ◽  
Language Teaching ◽  
Communicative Language Teaching ◽  
World Language ◽  
International Language ◽  
Language Classroom ◽  
English Proficiency Index

This article discusses language teaching and the move from a predominantly psycholinguistic to a more sociolinguistic approach through Communicative Language Teaching (CLT), the Common European Framework of Reference Languages (CEFR) and English as an International Language (EIL). The context is four plurilingual and pluricultural societies in Southeast Asia and East Asia, (Thailand, Japan, Vietnam and China). These countries were chosen as they had similarities in the development of CEFR and consequently there were common factors that needed to be addressed in implementing CEFR. According to the English Proficiency Index (2020) a number of countries in the region have been described as being in the category of low or very low with regard to proficiency. To help improve such a situation, given the need for economic development, CEFR was introduced by various Ministries of Education in addition to the already existing official CLT syllabuses. English as an international language has also been widely proposed by a number of researchers, in terms of making teachers, students and educators aware of English as a world language as well as developing an attitudinal change with regard to ‘standard’ English. This article suggests that the basic principles of Communicative Language Teaching (CLT) can be best applied through scaffolding using CEFR and EIL given the reality of teaching in relatively low English language proficiency contexts.

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