An evaluation of metal removal during wastewater treatment: The potential to achieve more stringent final effluent standards

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 Taylor & Francis.Metals are of particular importance in relation to water quality, and concern regarding the impact of these contaminants on biodiversity is being encapsulated within the latest water-related legislation such as the Water Framework Directive in Europe and criteria revisions to the Clean Water Act in the United States. This review undertakes an evaluation of the potential of 2-stage wastewater treatment consisting of primary sedimentation and biological treatment in the form of activated sludge processes, to meet more stringent discharge consents that are likely to be introduced as a consequence. The legislation, sources of metals, and mechanisms responsible for their removal are discussed, to elucidate possible pathways by which the performance of conventional processes may be optimized or enhanced. Improvements in effluent quality, achievable by reducing concentrations of suspended solids or biochemical oxygen demand, may also reduce metal concentrations although meeting possible requirements for the removal of copper my be challenging

Deficiency of Leishmania phosphoglycans influences the magnitude but does not affect the quality of secondary (memory) anti-Leishmania immunity

Despite inducing very low IFN-γ response and highly attenuated in vivo, infection of mice with phosphoglycan (PG) deficient Leishmania major (lpg2-) induces protection against virulent L. major challenge. Here, we show that mice infected with lpg2- L. major generate Leishmania-specific memory T cells. However, in vitro and in vivo proliferation, IL-10 and IFN-γ production by lpg2- induced memory cells were impaired in comparison to those induced by wild type (WT) parasites. Interestingly, TNF recall response was comparable to WT infected mice. Despite the impaired proliferation and IFN-γ response, lpg2- infected mice were protected against virulent L. major challenge and their T cells mediated efficient infection-induced immunity. In vivo depletion and neutralization studies with mAbs demonstrated that lpg2- L. major-induced resistance was strongly dependent on IFN-γ, but independent of TNF and CD8(+) T cells. Collectively, these data show that the effectiveness of secondary anti-Leishmania immunity depends on the quality (and not the magnitude) of IFN-γ response. These observations provide further support for consideration of lpg2- L. major as a live-attenuated candidate for leishmanization in humans since it protects strongly against virulent challenge, without inducing pathology in infected animals

Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer

Colorectal cancer (CRC) is a heterogeneous disease that is associated with a gradual accumulation of genetic and epigenetic alterations. Among all CRC stages, stage II tumors are highly heterogeneous with a high relapse rate in about 20-25 % of stage II CRC patients following surgery. Thus, a comprehensive analysis of gene signatures to identify aggressive and metastatic phenotypes in stage II CRC is desired for a more accurate disease classification and outcome prediction. By utilizing a Cancer Array, containing 440 oncogenes and tumor suppressors to profile mRNA expression, we identified a larger number of differentially expressed genes in poorly differentiated stage II colorectal adenocarcinoma tissues, compared to their matched normal tissues. Ontology and Ingenuity Pathway Analysis (IPA) indicated that these genes are involved in functional mechanisms associated with several transcription factors. Genomic alterations of these genes were also investigated through The Cancer Genome Atlas (TCGA) database, utilizing 195 published CRC specimens. The percentage of genomic alterations in these genes was ranked based on their mRNA expression, copy number variations and mutations. This data was further combined with published microarray studies from a large set of CRC tumors classified based on prognostic features. This led to the identification of eight candidate genes including RPN2, HMGB1, AARS, IGFBP3, STAT1, HYOU1, NQO1 and PEA15 that were associated with the progressive phenotype. In particular, RPN2 and HMGB1 displayed a higher genomic alteration frequency in CRC, compared to eight other major solid cancers. Immunohistochemistry was performed on additional 78 stage I-IV CRC samples, where RPN2 protein immunostaining exhibited a significant association with stage III/IV tumors, distant metastasis, and poor differentiation, indicating that RPN2 expression is associated with poor prognosis. Further, our study revealed significant transcriptional regulatory mechanisms, networks and gene signatures, underlying CRC malignant progression and phenotype warranting future clinical investigations.published_or_final_versio

Prospects for the development of odour baits to control the tsetse flies Glossina tachinoides and G. palpalis s.l.

Field studies were done of the responses of Glossina palpalis palpalis in Côte d'Ivoire, and G. p. gambiensis and G. tachinoides in Burkina Faso, to odours from humans, cattle and pigs. Responses were measured either by baiting (1.) biconical traps or (2.) electrocuting black targets with natural host odours. The catch of G. tachinoides from traps was significantly enhanced (~5×) by odour from cattle but not humans. In contrast, catches from electric targets showed inconsistent results. For G. p. gambiensis both human and cattle odour increased (>2×) the trap catch significantly but not the catch from electric targets. For G. p. palpalis, odours from pigs and humans increased (~5×) the numbers of tsetse attracted to the vicinity of the odour source but had little effect on landing or trap-entry. For G. tachinoides a blend of POCA (P = 3-n-propylphenol; O = 1-octen-3-ol; C = 4-methylphenol; A = acetone) alone or synthetic cattle odour (acetone, 1-octen-3-ol, 4-methylphenol and 3-n-propylphenol with carbon dioxide) consistently caught more tsetse than natural cattle odour. For G. p. gambiensis, POCA consistently increased catches from both traps and targets. For G. p. palpalis, doses of carbon dioxide similar to those produced by a host resulted in similar increases in attraction. Baiting traps with super-normal (~500 mg/h) doses of acetone also consistently produced significant but slight (~1.6×) increases in catches of male flies. The results suggest that odour-baited traps and insecticide-treated targets could assist the AU-Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) in its current efforts to monitor and control Palpalis group tsetse in West Africa. For all three species, only ~50% of the flies attracted to the vicinity of the trap were actually caught by it, suggesting that better traps might be developed by an analysis of the visual responses and identification of any semiochemicals involved in short-range interaction

Differential impact of LPG-and PG-deficient Leishmania major mutants on the immune response of human dendritic cells

<div><p>Background</p><p><i>Leishmania major</i> infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of <i>Leishmania</i> parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction.</p><p>Methodology/Principal Findings</p><p>Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating <i>L</i>. <i>major</i> Friedlin V1 mutants defective in LPG alone, (FV1 <i>lpg1-</i>), or generally deficient for all PGs, (FV1 <i>lpg2-</i>). Infection with metacyclic, infective stage, <i>L</i>. <i>major</i> or purified LPG induced high levels of <i>IL12B</i> subunit gene transcripts in hDCs, which was abrogated with FV1 <i>lpg1-</i> infections. In contrast, hDC infections with FV1 <i>lpg2-</i> displayed increased <i>IL12B</i> expression, suggesting other PG-related/<i>LPG2</i> dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 <i>lpg1-</i>, FV1 <i>lpg2-</i> infections revealed that FV1 <i>lpg1-</i> mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB) and Interferon Regulatory Factor (IRF) mediated transcription.</p><p>Conclusions/Significance</p><p>These data suggest that <i>L</i>. <i>major</i> LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring <i>Leishmania</i> surface glycoconjugates that result in modulation of host cellular IL12.</p></div

Clinical application of a protocol based on universal next-generation sequencing for the diagnosis of beta-thalassaemia and sickle cell anaemia in preimplantation embryos

Research question Mutations of the beta-globin gene (HBB) cause beta-thalassaemia and sickle cell anaemia and are the most common cause of severe inherited disease in humans. Traditional PGD protocols for the detection of HBB mutations frequently involve labour intensive, patient-specific test design due to the wide diversity of disease associated HBB mutations. For this reason, we aimed to develop and clinically apply a universal PGD method to test for mutations in the HBB gene. Design A multiplex PCR protocol was designed, allowing simultaneous amplification of multiple overlapping DNA fragments encompassing the entire HBB gene sequence in addition to 17 characterized, closely linked single nucleotide polymorphisms (SNPs). Amplicons were then analyzed using a next generation sequencing (NGS) method, revealing mutations and SNP genotypes. The protocol was extensively validated, optimized and eventually clinically applied on whole-genome amplified (WGA) DNA derived from embryos of three couples carrying different combinations of β-thalassemia mutations. Results The HBB mutation status and associated SNP haplotypes were successfully determined in all 21 embryos. Interestingly, analysis of 141 heterozygous sites showed no instances of allele dropout (ADO) and the test displayed 100% concordance when compared to the results obtained from karyomapping. This suggests that the combination of trophectoderm biopsy and highly sensitive NGS may provide superior accuracy than typically achieved using traditional PGD methods. Importantly, no patient-specific test design or optimization was needed. Conclusions It is hoped that protocols that deliver almost universally-applicable low-cost tests, without compromising diagnostic accuracy, will improve patient access to PGD, especially in less affluent parts of the world

Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages

Promastigote form of Leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. But till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict Leishmania growth. Attenuated Leishmania strain exposed RAW 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. The augmentation of pro-inflammatory activity is mostly attributed to p38 MAPK and p44/42 MAPK. In our study, these activated macrophages are found to induce phagosome maturation when infected with pathogenic Leishmania donovani. Increased co-localization of carboxyfluorescein succinimidyl ester labeled pathogenic L. donovani with Lysosome was found. Moreover, increased co-localization was observed between pathogenic L. donovani and late phagosomal markers viz. Rab7, Lysosomal Associated Membrane Protein 1, Cathepsin D, Rab9, and V-ATPase which indicate phagosome maturation. It was also observed that inhibition of V-type ATPase caused significant hindrance in attenuated Leishmania induced phagosome maturation. Finally, it was confirmed that p38 MAPK is the key player in acidification and maturation of phagosome in attenuated Leishmania strain preexposed macrophages. To our knowledge, this study for the first time reported an approach to induce phagosome maturation in L. donovani infected macrophages which could potentiate short-term prophylactic response in futur

Salamander Abundance along Road Edges and within Abandoned Logging Roads in Appalachian Forests

Roads may be one of the most common disturbances in otherwise continuous forested habitat in the southern Appalachian Mountains. Despite their obvious presence on the landscape, there is limited data on the ecological effects along a road edge or the size of the “road-effect zone.” We sampled salamanders at current and abandoned road sites within the Nantahala National Forest, North Carolina (U.S.A.) to determine the road-effect zone for an assemblage of woodland salamanders. Salamander abundance near the road was reduced significantly, and salamanders along the edges were predominantly large individuals. These results indicate that the road-effect zone for these salamanders extended 35 m on either side of the relatively narrow, low-use forest roads along which we sampled. Furthermore, salamander abundance was significantly lower on old, abandoned logging roads compared with the adjacent upslope sites. These results indicate that forest roads and abandoned logging roads have negative effects on forest-dependent species such as plethodontid salamanders. Our results may apply to other protected forests in the southern Appalachians and may exemplify a problem created by current and past land use activities in all forested regions, especially those related to road building for natural-resource extraction. Our results show that the effect of roads reached well beyond their boundary and that abandonment or the decommissioning of roads did not reverse detrimental ecological effects; rather, our results indicate that management decisions have significant repercussions for generations to come. Furthermore, the quantity of suitable forested habitat in the protected areas we studied was significantly reduced: between 28.6% and 36.9% of the area was affected by roads. Management and policy decisions must use current and historical data on land use to understand cumulative impacts on forest-dependent species and to fully protect biodiversity on national landsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73456/1/j.1523-1739.2006.00571.x.pd

First record of Rhabdoceras suessi (Ammonoidea, Late Triassic) from the Transylvanian Triassic Series of the Eastern Carpathians (Romania) and a review of its biochronology, paleobiogeography and paleoecology

Abstract The occurrence of the heteromorphic ammonoid Rhabdoceras suessi Hauer, 1860, is recorded for the first time in the Upper Triassic limestone of the Timon-Ciungi olistolith in the Rarău Syncline, Eastern Carpathians. A single specimen of Rhabdoceras suessi co-occurs with Monotis (Monotis) salinaria that constrains its occurrence here to the Upper Norian (Sevatian 1). It is the only known heteromorphic ammonoid in the Upper Triassic of the Romanian Carpathians. Rhabdoceras suessi is a cosmopolitan species widely recorded in low and mid-paleolatitude faunas. It ranges from the Late Norian to the Rhaetian and is suitable for high-resolution worldwide correlations only when it co-occurs with shorter-ranging choristoceratids, monotid bivalves, or the hydrozoan Heterastridium. Formerly considered as the index fossil for the Upper Norian (Sevatian) Suessi Zone, by the latest 1970s this species lost its key biochronologic status among Late Triassic ammonoids, and it generated a controversy in the 1980s concerning the status of the Rhaetian stage. New stratigraphic data from North America and Europe in the subsequent decades resulted in a revised ammonoid biostratigraphy for the uppermost Triassic, the Rhaetian being reinstalled as the topmost stage in the current standard timescale of the Triassic. The geographic distribution of Rhabdoceras is compiled from published worldwide records, and its paleobiogeography and paleoecology are discussed

Penumbra indigo percutaneous aspiration thrombectomy system in the treatment of aortic endograft iliac limb occlusion: results from an Italian Multicentre Registry

Objective: This study aimed to evaluate the safety and effectiveness of the Penumbra Indigo percutaneous aspiration thrombectomy (PAT) system in the clinical presentation of iliac limb occlusion (ILO) after endovascular aortic repair (EVAR).Methods: A retrospective, observational, multicentre study conducted in eight Italian vascular centres. Consecutive patients presenting with ILO after EVAR were eligible. To assess vessel revascularisation, Thrombo-aspiration In Peripheral Ischaemia (TIPI) classification (score 0-3) was used at presentation (t1), after PAT (t2), and after adjunctive procedures (t3). Successful revascularisation was considered TIPI 2-3 (near complete or complete). Primary intra-operative outcomes were technical success (TS) of Indigo PAT and combined TS of PAT associated with adjunctive procedures when needed. Primary follow up outcomes were safety and effectiveness at one, six, and 12 months.Results: From September 2019 to December 2021, there were 48 ILO and 17 patients (35%) [median age 75 years, IQR 71, 83 years; male, 14 (82%); urgent, 8 (47%)] were treated and enrolled. The median time after primary EVAR was 24 months (IQR 0, 42 months). The median clot age from ILO diagnosis to PAT was three days (IQR 1, 12 days). Ten patients (59%) presented with limb threatening ischaemia. At t1, TIPI 0 and 1 was present in 13 (76%) and four (24%) cases, respectively. At t2, primary TS (TIPI 2-3) was achieved in 14 cases (82%) after Indigo PAT (p &lt; .001). Fifteen patients (88%) required adjunctive procedures (14 re-linings, one surgical patch angioplasty). At t3, combined TS was achieved in 16 cases (94%). Intra-operative complication included one (6%) distal embolisation, treated successfully. The 30 day mortality was one case (6%) due to pneumonia. At one, six, and 12 months, clinical success was 100% without ILO recurrence. The median follow up was 23 months (IQR 11, 41 months): at 18 months, survival and freedom from re-intervention were 91 + 8% and 90 + 9%, respectively.Conclusion: This study reports for the first time the efficacy and safety of Penumbra Indigo PAT for ILO after EVAR, with promising technical and clinical success up to one year