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Background The Copper Metabolism MURR1 (COMM) domain family has been reported to play important roles in tumorigenesis. As a prototype for the COMMD family, the expression pattern and biological function of COMMD6 in human tumours remain unknown. Methods COMMD6 expression in BALB/c mice and human tissues was examined using real-time PCR and immunohistochemistry. Kaplan–Meier analysis was applied to evaluate the prognosis of COMMD6 in tumours. Competing endogenous RNA (ceRNA) and transcriptional regulation network were constructed based on differentially expressed mRNAs, microRNAs and long non-coding RNAs from the cancer genome atlas database. GO and KEGG enrichment analysis were used to explore the bioinformatics implication. Results COMMD6 expression was widely observed in BALB/c mice and human tissues, which predicted prognosis of cancer patients. Furthermore, we shed light on the underlying tumour promoting role and mechanism of COMMD6 by constructing a TEX41-miR-340-COMMD6 ceRNA network in head and neck squamous cell carcinoma and miR-218-CDX1-COMMD6 transcriptional network in cholangiocarcinoma. In addition, COMMD6 may modulate the ubiquitination and degradation of NF-κB subunits and regulate ribonucleoprotein and spliceosome complex biogenesis in tumours. Conclusions This study may help to elucidate the functions and mechanisms of COMMD6 in human tumours, providing a potential biomarker for tumour prevention and therapy.

SummaryBackgroundIt has been reported that several cases recovered from COVID-19 tested positive for SARS-CoV-2 after discharge (re-detectable positive, RP), however the clinical characteristics, significance and potential cause of RP patients remained elusive.MethodsA total of 262 COVID-19 patients were discharged from January 23 to February 25, 2020, and were enrolled for analysis of their clinical parameters. The RP and non-RP (NRP) patients were grouped according to the disease severity during their hospitalization period. The clinical characterization at re-admission to the hospital was analyzed. SARS-CoV-2 RNA and plasma antibody levels were detected using high-sensitive detection methods.FindingsUp to March 10, 2020, all of patients were followed up for at least 14 days, and 38/262 of RP patients (14.5%) were present. The RP patients were characterized by being less than 14-years old and having mild and moderate conditions as compared to NRP patients, while no severe patients became RP. Retrospectively, the RP patients displayed fewer symptoms, more sustained remission of CT imaging and earlier RNA negative-conversion but similar plasma antibody levels during their hospitalization period as compared to those NRP patients. When re-admitted to the hospital, these RP patients showed no obvious clinical symptoms or disease progression indicated by normal or improving CT imaging and inflammatory cytokine levels. All 21 close contacts of RP patients were tested negative for SARS-CoV-2 RNA, and no suspicious clinical symptoms were reported. However, 18/24 of RNA-negative samples detected by the commercial kit were tested to be positive for virus RNA using a hyper-sensitive method, suggesting the carrier status of virus possibly existed in patients recovered from COVID-19.InterpretationOur results showed that young and mild COVID-19 patients seem to be RP patients after discharge, who show no obviously clinical symptoms and disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients during follow-up. Our findings provide empirical information and evidence for the effective management of COVID-19 patients during their convalescent phase.

Anaplasmosis, the most prevalent tick-transmitted disease of cattle, is caused by the rickettsial intracellular parasite Anaplasma marginale. The pathogen replicates within a parasitophorous vacuole formed from the invagination of the erythrocyte membrane. Several strains of A. marginale form “tails” or “appendages” which are attached to, and extend out from, the cytoplasmic side of the parasitophorous vacuole. Genomic analysis of the parasite antigen distributed along the appendage led to the discovery of the aaap (Anaplasma appendage associated protein) gene family located within a highly plastic region in the genome. The aaap gene family consists of aaap and several alps (for aaap-like proteins), depending on the strain. These genes/proteins are characterized by repeat sequences. To investigate locus plasticity, different versions of the locus were cloned from the same strain as well as from different strains, sequenced and aligned to identify changes. Our findings show that repeat sequences both within and between genes facilitated rearrangement events within the locus. Structural variation of the locus in the St. Maries strain was further investigated during infection of different cellular environments, i.e., bovine erythrocytes and tick cells, with a reduction in subpopulations of the aaap locus within the tick as compared to erythrocytes. Interestingly, subpopulations bearing alternative locus structures began to arise again when the pathogen was transferred from the tick environment into a naïve calf. Additionally, the Aaap protein expression profile between blood and tick samples showed a regulatory shift, indicating a host-specific response. Alignment of the protein sequences from different species of Anaplasma reveals six similar repeating motifs that appear to be unique to a few species of Anaplasma. The role the aaap locus may play in the pathogenesis of the bovine host or in tick infection/transmission remains unknown; however, the changes in aaap locus subpopulations, locus structure, and protein expression indicate that these genes have a role in strain diversification.

Background: This study was designed initially to explore the effect of chemoradiotherapy on patients diagnosed with head and neck cancer (HNC) with respect to the alteration of systematic immunity. Methods: We did a retrospective study enrolling patients received concurrent chemoradiotherapy (CCRT), with or without induction chemotherapy (IC). Blood tests were performed before IC, before and after CCRT. Flow cytometric analysis and turbidimetric inhibition immunoassay were used for detection. Results: A total number of 58 patients were included from April 1, 2018, to March 31, 2019. Levels of immunoglobulins (Ig), including IgA, IgG, and IgM, declined after 2 to 3 cycles of IC and CCRT, respectively. Serum level of total hemolytic complement (CH50) increased ( P < .001) after IC, but kept stably post-CCRT. Natural killer (NK) cells decreased ( P < .01) after IC and enhanced ( P < .001) post-CCRT. The number of CD3+CD4+ T cells got increased ( P < .01) after IC and decreased ( P < .001) post-CCRT. Consistently, both IC and CCRT induced the increase in CD3+CD8+ T cells significantly ( P < .001 vs P < .01). Conclusion: Both radiotherapy (RT) and chemotherapy (CT) induced dual effect of immune response. Concurrent chemoradiotherapy created an active immune response based on the effect induced by IC, suggesting that RT exerted a potential function on mobilizing immune system.

Background: The characteristics, significance and potential cause of positive SARS-CoV-2 diagnoses in recovered coronavirus disease 2019 (COVID-19) patients post discharge (re-detectable positive, RP) remained elusive. Methods: A total of 262 COVID-19 patients discharged from January 23 to February 25, 2020 were enrolled into this study. RP and non-RP (NRP) patients were grouped according to disease severity, and the characterization at re-admission was analyzed. SARS-CoV-2 RNA and plasma antibody levels were measured, and all patients were followed up for at least 14 days, with a cutoff date of March 10, 2020. Results: A total of 14.5% of RP patients were detected. These patients were characterized as young and displayed mild and moderate conditions compared to NRP patients while no severe patients were RP. RP patients displayed fewer symptoms but similar plasma antibody levels during their hospitalization compared to NRP patients. Upon hospital readmission, these patients showed no obvious symptoms or disease progression. All 21 close contacts of RP patients were tested negative for viral RNA and showed no suspicious symptoms. Eighteen out of 24 of RNA-negative samples detected by the commercial kit were tested positive for viral RNA using a hyper-sensitive method, suggesting that these patients were potential carriers of the virus after recovery from COVID-19. Conclusions: Our results indicated that young patients, with a mild diagnosis of COVID-19 are more likely to display RP status after discharge. These patients show no obvious symptoms or disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients. Our findings provide information and evidence for the management of convalescent COVID-19 patients.

The Interagency Monitoring of Protected Visual Environments (IMPROVE) network measures the chemical composition of atmospheric particulate matter at over 160 locations throughout the United States. As part of the routine quality control process, we noted decreases in the network-wide vanadium (V) and nickel (Ni) concentrations in 2015 relative to the previous years. Enriched V and Ni with respect to soil are indicative of heavy fuel oil burning and are often used as tracers for emissions from marine vessels. Multiple regulations on the fuel used by marine vessels were implemented in North America since 2010, and the most sweeping regulation was implemented at the start of 2015. The 2015 regulations reduced the allowable fuel oil sulfur concentrations within the North America Emissions Control Area from 1.0% to 0.1% to reduce the environmental and human health impacts of sulfates. As a side effect, these requirements economically favored fuels with lower V and Ni concentrations. The atmospheric concentrations of V and Ni decreased markedly at many IMPROVE monitoring sites, particularly sites near major ports. Between 2011 and 2015, annual mean V concentrations measured on IMPROVE samples collected near the ports of Seattle, Washington and New Orleans, Louisiana decreased by 35% and 85%, respectively. These decreases have brought the coastal V and Ni concentrations much closer to those measured far inland.

Anaplasmosis, the most prevalent tick-transmitted disease of cattle, is caused by the rickettsial intracellular parasite Anaplasma marginale. The pathogen replicates within a parasitophorous vacuole formed from the invagination of the erythrocyte membrane. Several strains of A. marginale form "tails" or "appendages" which are attached to, and extend out from, the cytoplasmic side of the parasitophorous vacuole. Genomic analysis of the parasite antigen distributed along the appendage led to the discovery of the aaap (Anaplasma appendage associated protein) gene family located within a highly plastic region in the genome. The aaap gene family consists of aaap and several alps (for aaap-like proteins), depending on the strain. These genes/proteins are characterized by repeat sequences. To investigate locus plasticity, different versions of the locus were cloned from the same strain as well as from different strains, sequenced and aligned to identify changes. Our findings show that repeat sequences both within and between genes facilitated rearrangement events within the locus. Structural variation of the locus in the St. Maries strain was further investigated during infection of different cellular environments, i.e., bovine erythrocytes and tick cells, with a reduction in subpopulations of the aaap locus within the tick as compared to erythrocytes. Interestingly, subpopulations bearing alternative locus structures began to arise again when the pathogen was transferred from the tick environment into a naïve calf. Additionally, the Aaap protein expression profile between blood and tick samples showed a regulatory shift, indicating a host-specific response. Alignment of the protein sequences from different species of Anaplasma reveals six similar repeating motifs that appear to be unique to a few species of Anaplasma. The role the aaap locus may play in the pathogenesis of the bovine host or in tick infection/transmission remains unknown; however, the changes in aaap locus subpopulations, locus structure, and protein expression indicate that these genes have a role in strain diversification.

Background Pathogens dependent upon vectors for transmission to new hosts undergo environment specific changes in gene transcription dependent on whether they are replicating in the vector or the mammalian host. Differential gene transcription, especially of potential vaccine candidates, is of interest in Anaplasma marginale, the tick-borne causative agent of bovine anaplasmosis. Methods RNA-seq technology allowed a comprehensive analysis of the transcriptional status of A. marginale genes in two conditions: bovine host blood and tick derived cell culture, a model for the tick vector. Quantitative PCR was used to assess transcription of a set of genes in A. marginale infected tick midguts and salivary glands at two time points during the transmission cycle. Results Genes belonging to fourteen pathways or component groups were found to be differentially transcribed in A. marginale in the bovine host versus the tick vector. One of the most significantly altered groups was composed of surface proteins. Of the 56 genes included in the surface protein group, eight were up regulated and 26 were down regulated. The down regulated surface protein encoding genes include several that are well studied due to their immunogenicity and function. Quantitative PCR of a set of genes demonstrated that transcription in tick cell culture most closely approximates transcription in salivary glands of recently infected ticks. Conclusions The ISE6 tick cell culture line is an acceptable model for early infection in tick salivary glands, and reveals disproportionate down regulation of surface protein genes in the tick. Transcriptional profiling in other cell lines may help us simulate additional microenvironments. Understanding vector-specific alteration of gene transcription, especially of surface protein encoding genes, may aid in the development of vaccines or transmission blocking therapies.

Predicting runoff producing areas and their corresponding risks of generating storm runoff is important for developing watershed management strategies to mitigate non-point source pollution. However, few methods for making these predictions have been proposed, especially operational approaches that would be useful in areas where variable source area (VSA) hydrology dominates storm runoff. The objective of this study is to develop a simple approach to estimate spatially-distributed risks of runoff production. By considering the development of overland flow as a bivariate process, we incorporated both rainfall and antecedent soil moisture conditions into a method for predicting VSAs based on the Natural Resource Conservation Service-Curve Number equation. We used base-flow immediately preceding storm events as an index of antecedent soil wetness status. Using nine sub-basins of the Upper Susquehanna River Basin, we demonstrated that our estimated runoff volumes and extent of VSAs agreed with observations. We further demonstrated a method for mapping these areas in a Geographic Information System using a Soil Topographic Index. The proposed methodology provides a new tool for watershed planners for quantifying runoff risks across watersheds, which can be used to target water quality protection strategies.