Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possibl

Hidden Order Beyond Hyperuniformity in Critical Absorbing States

Disordered hyperuniformity is a description of hidden correlations in point distributions revealed by an anomalous suppression in fluctuations of local density at various coarse-graining length scales. In the absorbing phase of models exhibiting an active-absorbing state transition, this suppression extends up to a hyperuniform length scale that diverges at the critical point. Here, we demonstrate the existence of additional many-body correlations beyond hyperuniformity. These correlations are hidden in the higher moments of the probability distribution of the local density, and extend up to a longer length scale with a faster divergence than the hyperuniform length on approaching the critical point. Our results suggest that a hidden order beyond hyperuniformity may generically be present in complex disordered systems.Comment: 5 Pages, 4 figures (Main) + 5 pages 7 figures (SI), Physical Review Letters (in press

Macrofaunal communities in the Gioia Canyon (Southern Tyrrhenian Sea, Italy)

Submarine canyons play pivotal roles in the physical, biological and ecological processes of coastal areas, especially in closed or semi-closed basins as the Mediterranean Sea, influencing the biodiversity and the abundance of the benthic fauna. On February 2013, during the Tyrrhenian Gravity Flows (TyGraF) campaign, samples have been collected along the Gioia Canyon Basin (Italy) with the aim to describe the taxonomical composition and the abundances of the macrobenthic assemblages, filling the gap of knowledge in this area. A total of 93 taxa were identified, and the Annelida was the phylum with the highest number of specimens and most diversified (46 taxa). The polychaetes Sternaspis scutata, Prionospio cirrifera and Monticellina sp., the bivalves Thyasira sp.1 and Saccella commutata and the amphipods belonging to the genera Ampelisca and Harpinia showed the highest densities in the studied area; however, results suggest low values of the abundances of the macrobenthos if compared with those generally reported for other canyons, both inside and outside the Mediterranean Sea. The marine biotic index (AMBI) highlights that the canyon system and the surrounded area were slightly disturbed and characterized by a high percentage of tolerant taxa. This study is the first baseline for future analyses of the macrobenthic communities of this area

Light Asymmetric Dark Matter on the Lattice: SU(2) Technicolor with Two Fundamental Flavors

The SU(2) gauge theory with two massless Dirac flavors constitutes the building block of several models of Technicolor. Furthermore it has also been used as a template for the construction of a natural light asymmetric, or mixed type, dark matter candidate. We use explicit lattice simulations to confirm the pattern of chiral symmetry breaking by determining the Goldstone spectrum and therefore show that the dark matter candidate can, de facto, be constituted by a complex Goldstone boson. We also determine the phenomenologically relevant spin-one and spin-zero isovector spectrum and demonstrate that it is well separated from the Goldstone spectrum.Comment: 22 pages, 8 figures, published versio

Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Immunomodulatory agents as potential therapeutic or preventive strategies for COVID-19

Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory “cytokine storm”, leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammation in patients with severe COVID-19 disease, may increase the risk of opportunistic infections, increasing the hospitalization time and mortality rate of these patients. Hence, there is an unmet need to develop more effective therapeutic options. Here, we discuss the potential use of natural immunomodulators such as Thymosin α1 (Tα1), all-trans retinoic acid (ATRA), and lactoferrin (LF), as adjunctive or preventive treatment of severe COVID-19 disease. These agents are considered to be multifunctional molecules because of their ability to enhance antiviral host immunity and restore the immune balance, depending on the host immune status. Furthermore, they are able to exert a broad-spectrum antimicrobial activity by means of direct interactions with cellular or molecular targets of pathogens or indirectly by increasing the host immune response. Thus, due to the aforementioned properties, these agents might have a great potential in a clinical setting, not only to counteract SARS-CoV-2 infection, but also to prevent opportunistic infections in critically ill COVID-19 patients

Comparison between the sponge fauna living outside and inside the coralligenous bioconstruction. A quantitative approach

Coralligenous habitat results from a multi-stratified accumulation of crustose coralline algae and animal builders in a dynamic equilibrium with disruptive agents. The result is a complex architecture crossed by crevices and holes. Due to this three-dimensional structure, coralligenous may host a rich and diversified fauna, more abundant than any other Mediterranean habitat. Unfortunately, very few data are available about the cryptic fauna that lives inside the conglomerate. As already reported for coral reefs, the cryptic fauna plays an important role in the exchange of material and energy between water column and benthic assemblages. Here we compare the sponge community present inside and outside the coralligenous framework of Portofino Promontory (Ligurian Sea) at different depths (15 and 30 meters) not only in terms of taxonomic diversity but for the first time also in term of biomass. Sponges present on the surface of each block were collected, weighed and identified; after blocks dissolution in HCl, target cryptic sponges were separated from other organisms, weighed, and identified. We recorded a total of 62 sponge species. The average number of sponge taxa occurring outside the coralligenous accretions is lower than the number of taxa identified inside. This pattern is confirmed also regarding sponge biomass. These results underlines that studies focused on coralligenous functioning should take in account the important contribution of cryptic fauna, as recently evidenced also for tropical reef habitats