Several shrimp diseases are new or newly emerged in Asia, including acute hepatopancreatic necrosis disease (AHPND), hepatopancreatic microsporidiosis (HPM), hepatopancreatic haplosporidiosis (HPH), ...aggregated transformed microvilli (ATM) and covert mortality disease (CMD). In addition to these, white spot disease (WSD), yellow head disease (YHD) and infectious myonecrosis (IMN) continue as the most serious viral threats to shrimp farmers in the region. Other diseases such as monodon slow growth syndrome (MSGS), white tail disease (WTD) and abdominal segment deformity disease (ASDD) are of less concern. In contrast, Taura syndrome virus (TSV) and infectious hypodermal and hematopoietic necrosis virus (IHHNV) have become innocuous due to the widespread use of highly tolerant specific pathogen free (SPF) stocks of Penaeus (Litopenaeus) vannamei that dominate production. Similarly, diseases caused by monodon baculovirus (MBV) and hepatopancreatic parvovirus (HPV) appear not to affect P.vannamei. Spread of diseases has been promoted by the use of live or fresh broodstock feeds such as polychaetes and clams. Also, shortages in the supply of imported SPF broodstock led some entrepreneurs to employ post larvae (PL) of imported SPF stocks to produce 2nd generation broodstock in open shrimp ponds where they became contaminated and were then used to produce PL for stocking ponds. These practices left the whole shrimp industry vulnerable to rapid spread of the new and newly emerging diseases and resulted in the current crisis in Asian shrimp culture. The situation has been exacerbated since 2009 by an almost exclusive focus on AHPND, which is only partially responsible for what has been widely called early mortality syndrome (EMS). The purpose of this review is to summarize progress of research on AHPND bacteria and also to encourage a wider focus on additional pathogens that are causing farm losses. The significance of these diseases and their implications for the future of shrimp aquaculture are discussed.
This review summarizes recent information about new and newly emerging diseases of cultured shrimp in Asia and discusses the biosecurity lapses that led to the current shrimp production crisis. All industry stakeholders must be aware of this situation and of the need for regional and global collaborative efforts to stem this crisis and prevent future development of another.
•Diseases have caused the current production crisis in Asian shrimp aquaculture.•Most important is new AHPND caused by unique isolates of Vibrio parahaemolyticus.•Next most important is newly emerging hepatopancreatic microsporidiosis (HM).•Threats from white spot, yellow head and infectious myonecrosis viruses remain.•The key to stemming current and future crises is renewed, stringent biosecurity.
Adaptation to environmental variability is a prerequisite for species’ persistence in their natural environments. With climate change predicted to increase the frequency and severity of temperature ...fluctuations, ectothermic organisms may increasingly depend on acclimation capacity to accommodate thermal variability. To elucidate the molecular basis of fluctuating temperature‐induced phenotypic plasticity, we investigated heat tolerance and the mechanisms induced by acclimation to thermal variability as compared to those seen at constant temperature. We ran genome‐wide transcriptomic analysis on Drosophila melanogaster subjected to acclimation at constant (19 ± 0°C) and fluctuating (19 ± 8°C) temperatures and contrasted the induction of molecular mechanisms in adult males, adult females and larvae. We found life stage‐ and sex‐specific dynamics of the acclimation responses to fluctuating temperatures. Adult flies exposed to temperature fluctuations showed a constitutive improvement in heat tolerance while heat tolerance of larvae tracked thermal fluctuations. A constitutive down‐regulation of gene expression was observed for several genes in the larvae exposed to fluctuations. Our results for adult females showed that, for several genes, fluctuating temperature acclimation resulted in canalization of gene expression. Both transcriptional and post‐transcriptional machinery were greatly affected by fluctuations in adult males. Gene ontology analysis showed enrichment of the heat stress response involving several major heat shock proteins in both larvae and adults exposed to fluctuating temperatures, even though fluctuations were in a benign range of temperatures. Finally, molecular mechanisms related to environmental sensing seem to be an important component of insect responses to thermal variability.
Means and variances of the environmental thermal regime play an important role in determining the fitness of terrestrial ectotherms. Adaptive phenotypic responses induced by heterogeneous ...temperatures have been shown to be mediated by molecular pathways independent of the classic heat shock responses; however, an in-depth understanding of plasticity induced by fluctuating temperatures is still lacking. We investigated high and low temperature acclimation induced by fluctuating thermal regimes at two different mean temperatures, at two different amplitudes of fluctuation and across the developmental and adult life stages of
For developmental acclimation, we found mildly detrimental effects of high-amplitude fluctuations for critical thermal minima, while the critical thermal maxima showed a beneficial response to higher amplitude fluctuations. For adult acclimation involving shifts between fluctuating and constant regimes, cold tolerance was shown to be dictated by developmental temperature conditions irrespective of the adult treatments, while the acquired heat tolerance was readily lost when flies developed at fluctuating temperature were shifted to a constant regime as adults. Interestingly, we also found that the effect of fluctuations at any life stage was gradually lost with prolonged adult maintenance, suggesting a more prominent effect of fluctuations during developmental compared with adult acclimation in
.
Abstract
Prostate cancer (PCa) is a highly heterogeneous disease in terms of its molecular makeup and clinical prognosis. The prostate tumor microenvironment (TME) is hypothesized to play an ...important role in driving disease aggressiveness, but precise mechanisms remain elusive. In our study, we used spatial transcriptomics to explore for the first time the spatial gene expression heterogeneity within primary prostate tumors from patients with metastatic disease. In total, we analyzed 5459 tissue spots from three PCa patients comprising castration‐resistant (CRPC) and neuroendocrine (NEPC) disease stages. Within CRPC, we identified a T cell cluster whose activity might be impaired by nearby regulatory T cells, potentially mediating the aggressive disease phenotype. Moreover, we identified Hallmark signatures of epithelial‐mesenchymal transition in a cancer‐associated fibroblast (CAF) cluster, indicating the aggressive characteristic of the primary TME leading to metastatic dissemination. Within NEPC, we identified active immune‐stroma cross‐talk exemplified by significant ligand‐receptor interactions between CAFs and M2 macrophages. Further, we identified a malignant cell population that was associated with the down‐regulation of an immune‐related gene signature. Lower expression of this signature was associated with higher levels of genomic instability in advanced PCa patients (SU2C cohort, n = 99) and poor recurrence free survival in early‐stage PCa patients (TCGA cohort, n = 395), suggesting prognostic biomarker potential. Taken together, our study reveals the importance of whole transcriptome profiling at spatial resolution for biomarker discovery and for advancing our understanding of tumor biology.
Enterocytozoon hepatopenaei (EHP) causes hepatopancreatic microsporidiosis (HPM) in shrimp. It is probably endemic in Australasia and was first characterized and named from the giant or black tiger ...shrimp Penaeus monodon from Thailand in 2009. Later, it was also found to infect exotic Penaeus vannamei imported for cultivation in Asia. HPM is not normally associated with shrimp mortality, but information from shrimp farmers indicates that it is associated with significant growth retardation that is not clearly noticeable until 2-3 months of cultivation. In order to study modes of HPM transmission and to test possible control measures, a laboratory challenge model was needed that would mimic the mode of infection in shrimp ponds.
We describe successful transmission in a cohabitation model with natural E. hepatopenaei (EHP)-infected shrimp in closed, perforated plastic containers placed in aquaria together with free-swimming, uninfected shrimp. After a period of 14 days all the free-swimming shrimp tested positive by PCR (approximately 60% with heavy infections evident by 1-step PCR positive test results) and gave positive histological and in situ hybridization results for E. hepatopenaei (EHP) in the hepatopancreas.
A laboratory cohabitation model for studying E. hepatopenaei (EHP) has been developed and used to confirm that E. hepatopenaei (EHP) can be directly transmitted horizontally among shrimp via water. The model will facilitate studies on methods to prevent the E. hepatopenaei (EHP) transmission.
Copy number alterations (CNAs) are frequently observed in early-stage prostate cancer and are associated with disease recurrence and tumor aggressiveness. Cost-effective assessment of CNAs could ...enhance clinical utility of CNAs. Here, we combined the cost-effectiveness of low-pass (low coverage) whole genome sequencing (LPWGS) and the routine availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue for assessing CNAs in a cohort of 187 men with early-stage localised prostate cancer. We detected well known CNAs in 8p, 8q, 13q and 16q and recurrent gains of the oncogene MYC and losses of the tumor suppressor genes NKX3-1, PTEN and RB1, indicating assay reliability. The estimated burden of CNAs was significantly associated with Gleason score, pathological T stage, surgical margin status and biochemical recurrence. Further, genomic losses or gains in specific chromosomal arms were significantly associated with worse BCR-free survival. Copy number signatures extracted from the LPWGS data showed potential for risk stratifying patients, where signatures S1 and S2 showed significant association to worse BCR-free survival compared to S3. Our study provides clinical validation of the associations between CNAs and tumor aggressiveness in an independent and representative RP cohort, while demonstrating the feasibility of performing LPWGS of FFPE tumor tissue for cost-effective assessment of CNAs.
The role of the microbiota in human health and disease is well established, including its effects on several cancer types. However, the role of microbial dysbiosis in prostate cancer development, ...progression, and response to treatment is less well understood. This knowledge gap could perhaps be implicated in the lack of better risk stratification and prognostic tools that incorporate risk factors such as bacterial infections and inflammatory signatures. With over a decade's research investigating associations between microbiome and prostate carcinogenesis, we are ever closer to finding the crucial biological link between the two. Yet, definitive answers remain elusive, calling for continued research into this field. In this review, we outline the three frequently used NGS based analysis methodologies that are used for microbiome profiling, thereby serving as a quick guide for future microbiome research. We next provide a detailed overview of the current knowledge of the role of the human microbiome in prostate cancer development, progression, and treatment response. Finally, we describe proposed mechanisms of host-microbe interactions that could lead to prostate cancer development, progression or treatment response.
With over 350,000 estimated deaths worldwide in 2018, prostate cancer (PCa) continues to be a major health concern and a significant cause of cancer-associated mortality among men. While cancer in ...general is considered a disease of the human genome, there is a growing body of evidence suggesting that changes to the healthy microbiota could play a vital role in cancer development, progression, and/or treatment outcome.
Using a metatranscriptomic approach, we annotated the microbial reads obtained from total RNA sequencing of 106 prostate tissue samples from 94 PCa patients (discovery cohort). We investigated microbial dysbiosis associated with PCa by systematically comparing the microbiomes between benign and malignant tissue samples, between less vs. more-aggressive PCa, and between patients who had biochemical recurrence as opposed to those who did not. We further performed differential gene expression and cell type enrichment analysis to explore the host transcriptomic and cellular responses to selected microbial genera. A public dataset (GSE115414) of total RNA sequencing reads from 24 prostate tissue samples (8 benign and 16 malignant) served as the validation cohort.
We observed decreased species diversity and significant under-representation of Staphylococcus saprophyticus and Vibrio parahaemolyticus, as well as significant over-abundance of Shewanella in malignant as compared to benign prostate tissue samples in both the discovery (p < 0.01) and validation (p < 0.05) cohorts. In addition, we identified Microbacterium species (p < 0.01) to be significantly over-abundant in pathologically advanced T3 tumors compared to T2 in the discovery cohort. Malignant samples having high vs. low Shewanella counts were associated with downregulated Toll-like receptor signaling pathways and decreased enrichment of dendritic cells. Malignant samples having low vs. high V. parahaemolyticus counts were enriched for olfactory transduction and drug metabolism pathways. Finally, malignant samples were enriched for M1 and M2 macrophages as compared to benign tissue samples.
The results from this exploratory study support the existence of an important biological link between the prostate microbiota and PCa development/progression. Our results highlight Shewanella, V. parahaemolyticus, and Microbacterium sp. as interesting candidates for further investigation of their association with PCa.
Current prognostic tools cannot clearly distinguish indolent and aggressive prostate cancer (PC). We hypothesized that analyzing individual contributions of epithelial and stromal components in ...localized PC (LPC) could improve risk stratification, as stromal subtypes may have been overlooked due to the emphasis on malignant epithelial cells. Hence, we derived molecular subtypes of PC using gene expression analysis of LPC samples from prostatectomy patients (cohort 1, n = 127) and validated these subtypes in two independent prostatectomy cohorts (cohort 2, n = 406, cohort 3, n = 126). Stroma and epithelium-specific signatures were established from laser-capture microdissection data and non-negative matrix factorization was used to identify subtypes based on these signatures. Subtypes were functionally characterized by gene set and cell type enrichment analyses, and survival analysis was conducted. Three epithelial (E1-E3) and three stromal (S1-S3) PC subtypes were identified. While subtyping based on epithelial signatures showed inconsistent associations to biochemical recurrence (BCR), subtyping by stromal signatures was significantly associated with BCR in all three cohorts, with subtype S3 indicating high BCR risk. Subtype S3 exhibited distinct features, including significantly decreased cell-polarity and myogenesis, significantly increased infiltration of M2-polarized macrophages and CD8 + T-cells compared to subtype S1. For patients clinically classified as CAPRA-S intermediate risk, S3 improved prediction of BCR. This study demonstrates the potential of stromal signatures in identification of clinically relevant PC subtypes, and further indicated that stromal characterization may enhance risk stratification in LPC and may be particularly promising in cases with high prognostic ambiguity based on clinical parameters.
Abstract
To date, behavioural responses and their role in thermal adaptation have largely been overlooked in small ectotherms. Here, we measure reproductive output using four adult acclimation ...temperatures in Drosophila melanogaster and quantify egg-laying at restricted temperatures (thermal capacity) and across a thermal gradient (thermal preference). We demonstrate that different conclusions about insect responses to changing environmental temperatures can be drawn based on whether individuals are temperature restricted or allowed a behavioural choice of temperature. When measuring physiological capacity at forced temperatures, we find an acclimation response to increasing temperatures. In contrast, when measuring behavioural choice, we find limited variation in thermal preference regardless of the acclimation temperature. Although flies are physiologically capable of increased performance at higher temperatures, these benefits might not be realized in heterogeneous environments. Our data serve as an example to illustrate why it is important to understand how behaviour and physiology contribute to thermal biology and, ultimately, the ecology of organisms. To do this, we should consider the behavioural avenues available to the organism when estimating ecologically relevant fitness consequences in varying thermal environments.
PDF
