Mutations in blind cavefish target the light-regulated circadian clock gene, period 2

Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors

Antiviral activity of fecal water samples from HIV-1 infected subjects treated with a specific probiotic formulation

Objectives: The aim of the study was to investigate if the supplementation with multistrain probiotics may be able to modulate T cell response in HIV-1 infected patients and to evaluate the anti-HIV activity of probiotic by studying fecal water (FW) samples. Methods: Three HIV-1-positive patients (Pt1, Pt2 and Pt3) on long-term suppressive combined antiretroviral therapy (cART) received a specific multi-strain probiotic supplementation (Vivomixx ®), for six months (T6). Levels of T cell subsets were evaluated by flow cytometry. Anti- HIV activity of FW samples was evaluated in vitro. Results: CD4+ T cells levels increased in all HIV-1 infected patients whereas activation markers (CD38 and HLA-DR) were decreased both on CD4+ and CD8+ T cells. FW samples presented an increased inhibitory activity against HIV-1 compared to T0 (FW-Pt1: T0 =40%, T6 = 65% of reduction; FW Pt2: T0 = 26%, T6 = 46% of reduction; FW Pt3: T0 = 47%, T6 = 94% of reduction). Discussion: Our data suggest that the administration of the specific probiotic formulation improves the antiviral status of people living with HIV-1 under cART, also modulating T cell response. Conclusion: Anti-HIV activity of FW may have several public health and social implications for sexually transmitted diseases that need to be further explored

Infected chronic ischemic wound topically treated with a multi-strain probiotic formulation: A novel tailored treatment strategy

Background A wide debate is ongoing regarding the role of cutaneous dysbiosis in the pathogenesis and evolution of difficult-to-treat chronic wounds. Nowadays, probiotic treatment considered as an useful tool to counteract dysbiosis but the evidence in regard to their therapeutic use in the setting of difficult-to-treat cutaneous ulcers is still poor. Aim: clinical report An 83-year-old woman suffering a critical limb ischemia and an infected difficult-to-treat ulcerated cutaneous lesion of the right leg, was complementary treated with local application of a mixture of probiotic bacteria. Methods Microbiological and metabolomic analysis were conducted on wound swabs obtained before and after bacteriotherapy. Results During the treatment course, a progressive healing of the lesion was observed with microbiological resolution of the polymicrobial infection of the wound. Metabolomic analysis showed a significant difference in the local concentration of propionate, 2-hydroxyisovalerate, 2-oxoisocaproate, 2,3-butanediol, putrescine, thymine, and trimethylamine before and after bacteriotherapy. Conclusion The microbiological and metabolomic results seem to confirm the usefulness of complementary probiotic treatment in difficult-to-treat infected wounds. Further investigations are needed to confirm these preliminary findings

Oral bacteriotherapy in patients with COVID-19: a retrospective cohort study

Background: Mounting evidence suggests SARS-CoV-2 may impact on host microbiota and gut inflammation, infecting intestinal epithelial cells. This possible link and its implications can be investigated by observing the effects of modulation of the microbial flora in patients with COVID-19. The aim of this study was to compare the rate of mortality, the need of ICU hospitalization and the length of hospitalization in patients with severe COVID-19 pneumonia who received the best available therapy (BAT) vs. patients treated with BAT and supplemented with oral bacteriotherapy. Methods: This retrospective, observational cohort study included 200 adults with severe COVID-19 pneumonia. All patients received therapeutic regimens including low molecular weight heparin plus one or more between hydroxychloroquine, azithromycin, antivirals, and Tocilizumab. Oral bacteriotherapy was used as complementary treatment. Results: Out of the 200 patients, 112 received BAT without oral bacteriotherapy, and 88 BAT with oral bacteriotherapy. Crude mortality was 22%. Eleven percent died in the group of patients treated with BAT plus oral bacteriotherapy vs. 30% subjects in the group of patients managed only with BAT (p < 0.001). By multivariate analysis, the age >65 years, CRP >41.8 mg/L, Platelets <150.000 mmc, and cardiovascular events were associated with the increased risk of mortality. Oral bacteriotherapy was an independent variable associated with a reduced risk for death. Despite large prospective trials are needed, this study highlights a possible role for oral bacteriotherapy in the management of patients hospitalized for COVID-19 pneumonia

Altered Rest-Activity Patterns Evolve via Circadian Independent Mechanisms in Cave Adapted Balitorid Loaches

Circadian rhythms and rest homeostasis are independent processes, each regulating important components of rest-activity patterns. Evolutionarily, the two are distinct from one another; total rest time is maintained unaffected even when circadian pacemaker cells are ablated. Throughout the animal kingdom, there exists a huge variation in rest-activity patterns, yet it is unclear how these behaviors have evolved. Here we show that four species of balitorid cavefish have greatly reduced rest times in comparison to rest times of their surface relatives. All four cave species retained biological rhythmicity, and in three of the four there is a pronounced 24-hour rhythm; in the fourth there is an altered rhythmicity of 38–40 hours. Thus, consistent changes in total rest have evolved in these species independent of circadian rhythmicity. Taken together, our data suggest that consistent reduction in total rest times were accomplished evolutionarily through alterations in rest homeostasis

Estrutura e composicao floristica da reserva genetica florestal Tamandua-DF.

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IGEC2: A 17-month search for gravitational wave bursts in 2005-2007

We present here the results of a 515 days long run of the IGEC2 observatory, consisting of the four resonant mass detectors ALLEGRO, AURIGA, EXPLORER and NAUTILUS. The reported results are related to the fourfold observation time from Nov. 6 2005 until Apr. 14 2007, when Allegro ceased its operation. This period overlapped with the first long term observations performed by the LIGO interferometric detectors. The IGEC observations aim at the identification of gravitational wave candidates with high confidence, keeping the false alarm rate at the level of 1 per century, and high duty cycle, namely 57% with all four sites and 94% with at least three sites in simultaneous observation. The network data analysis is based on time coincidence searches over at least three detectors: the four 3-fold searches and the 4-fold one are combined in a logical OR. We exchanged data with the usual blind procedure, by applying a unique confidential time offset to the events in each set of data. The accidental background was investigated by performing sets of 10^8 coincidence analyses per each detector configuration on off-source data, obtained by shifting the time series of each detector. The thresholds of the five searches were tuned so as to control the overall false alarm rate to 1/century. When the confidential time shifts was disclosed, no gravitational wave candidate was found in the on-source data. As an additional output of this search, we make available to other observatories the list of triple coincidence found below search thresholds, corresponding to a false alarm rate of 1/month.Comment: 10 pages, 8 figures Accepted for publication on Phys. Rev.

Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered

Results of the IGEC-2 search for gravitational wave bursts during 2005

The network of resonant bar detectors of gravitational waves resumed coordinated observations within the International Gravitational Event Collaboration (IGEC-2). Four detectors are taking part in this collaboration: ALLEGRO, AURIGA, EXPLORER and NAUTILUS. We present here the results of the search for gravitational wave bursts over 6 months during 2005, when IGEC-2 was the only gravitational wave observatory in operation. The network data analysis implemented is based on a time coincidence search among AURIGA, EXPLORER and NAUTILUS, keeping the data from ALLEGRO for follow-up studies. With respect to the previous IGEC 1997-2000 observations, the amplitude sensitivity of the detectors to bursts improved by a factor about 3 and the sensitivity bandwidths are wider, so that the data analysis was tuned considering a larger class of detectable waveforms. Thanks to the higher duty cycles of the single detectors, we decided to focus the analysis on three-fold observation, so to ensure the identification of any single candidate of gravitational waves (gw) with high statistical confidence. The achieved false detection rate is as low as 1 per century. No candidates were found.Comment: 10 pages, to be submitted to Phys. Rev.