Identifying causal gateways and mediators in complex spatio-temporal systems

J.R. received support by the German National Academic Foundation (Studienstiftung), a Humboldt University Postdoctoral Fellowship, and the German Federal Ministry of Science and Education (Young Investigators Group CoSy-CC2, grant no. 01LN1306A). J.F.D. thanks the Stordalen Foundation and BMBF (project GLUES) for financial support. D.H. has been funded by grant ERC-CZ CORES LL-1201 of the Czech Ministry of Education. M.P. and N.J. received funding from the Czech Science Foundation project No. P303-14-02634S and from the Czech Ministry of Education, Youth and Sports, project No. DAAD-15-30. J.H. was supported by the Czech Science Foundation project GA13-23940S and Czech Health Research Council project NV15-29835A. We thank Mary Lindsey from the National Oceanic and Atmospheric Administration for her kind help with Fig. 4e. NCEP Reanalysis data provided by NOAA/OAR/ESRL PSD, Boulder, Colorado, USA, from their web site at http://www.esrl.noaa.gov/psd/.Peer reviewedPublisher PD

High-Frequency network activity, global increase in Neuronal Activity, and Synchrony Expansion Precede Epileptic Seizures In Vitro

How seizures start is a major question in epilepsy research. Preictal EEG changes occur in both human patients and animal models, but their underlying mechanisms and relationship with seizure initiation remain unknown. Here we demonstrate the existence, in the hippocampal CA1 region, of a preictal state characterized by the progressive and global increase in neuronal activity associated with a widespread buildup of low-amplitude high-frequency activity (HFA) (100 Hz) and reduction in system complexity.HFAis generated by the firing of neurons, mainly pyramidal cells, at much lower frequencies. Individual cycles ofHFAare generated by the near-synchronous (within 5 ms) firing of small numbers of pyramidal cells. The presence of HFA in the low-calcium model implicates nonsynaptic synchronization; the presence of very similar HFA in the high-potassium model shows that it does not depend on an absence of synaptic transmission. Immediately before seizure onset, CA1 is in a state of high sensitivity in which weak depolarizing or synchronizing perturbations can trigger seizures. Transition to seizure is haracterized by a rapid expansion and fusion of the neuronal populations responsible for HFA, associated with a progressive slowing of HFA, leading to a single, massive, hypersynchronous cluster generating the high-amplitude low-frequency activity of the seizure

Blood-feeding adaptations and virome assessment of the poultry red mite Dermanyssus gallinae guided by RNA-seq

Dermanyssus gallinae is a blood-feeding mite that parasitises wild birds and farmed poultry. Its remarkably swift processing of blood, together with the capacity to blood-feed during most developmental stages, makes this mite a highly debilitating pest. To identify specific adaptations to digestion of a haemoglobin-rich diet, we constructed and compared transcriptomes from starved and blood-fed stages of the parasite and identified midgut-enriched transcripts. We noted that midgut transcripts encoding cysteine proteases were upregulated with a blood meal. Mapping the full proteolytic apparatus, we noted a reduction in the suite of cysteine proteases, missing homologues for Cathepsin B and C.Instituto de Patología VegetalFil: Ribeiro, José M. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research; Estados UnidosFil: Hartmann, David. Czech Academy of Sciences. Biology Centre. Institute of Parasitology. Biology Centre; República ChecaFil: Bartošová-Sojková, Pavla. Czech Academy of Sciences. Biology Centre. Institute of Parasitology. Biology Centre; República ChecaFil: Debat, Humberto Julio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Debat, Humberto Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); ArgentinaFil: Moos, Martin. Czech Academy of Sciences. Biology Centre. Institute of Entomology; República ChecaFil: Šimek, Petr. Czech Academy of Sciences. Biology Centre. Institute of Entomology; República ChecaFil: Fara, Jiří.International Poultry Testing Station Ústrašice; República ChecaFil: Palus, Martin. Czech Academy of Sciences. Biology Centre. Institute of Parasitology; República ChecaFil: Kučera, Matěj. Czech Academy of Sciences. Biology Centre. Institute of Parasitology; República ChecaFil: Hajdušek, Ondřej. Czech Academy of Sciences. Biology Centre. Institute of Parasitology; República Chec

The Effect of Selenium Supplementation in the Prevention of DNA Damage in White Blood Cells of Hemodialyzed Patients: A Pilot Study

Patients with chronic kidney disease (CKD) have an increased incidence of cancer. It is well known that long periods of hemodialysis (HD) treatment are linked to DNA damage due to oxidative stress. In this study, we examined the effect of selenium (Se) supplementation to CKD patients on HD on the prevention of oxidative DNA damage in white blood cells. Blood samples were drawn from 42 CKD patients on HD (at the beginning of the study and after 1 and 3 months) and from 30 healthy controls. Twenty-two patients were supplemented with 200 μg Se (as Se-rich yeast) per day and 20 with placebo (baker's yeast) for 3 months. Se concentration in plasma and DNA damage in white blood cells expressed as the tail moment, including single-strand breaks (SSB) and oxidative bases lesion in DNA, using formamidopyrimidine glycosylase (FPG), were measured. Se concentration in patients was significantly lower than in healthy subjects (P < 0.0001) and increased significantly after 3 months of Se supplementation (P < 0.0001). Tail moment (SSB) in patients before the study was three times higher than in healthy subjects (P < 0.01). After 3 months of Se supplementation, it decreased significantly (P < 0.01) and was about 16% lower than in healthy subjects. The oxidative bases lesion in DNA (tail moment, FPG) of HD patients at the beginning of the study was significantly higher (P < 0.01) compared with controls, and 3 months after Se supplementation it was 2.6 times lower than in controls (P < 0.01). No changes in tail moment was observed in the placebo group. In conclusion, our study shows that in CKD patients on HD, DNA damage in white blood cells is higher than in healthy controls, and Se supplementation prevents the damage of DNA

Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein

Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2´ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice expressing human ACE2 against infection when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants

Study of the pathogenesis of tick-borne encephalitis in hosts with different genetic and immunological background

We examined the influence of host genetic and immunological background on pathogenesis of tick-borne encephalitis. We determined virus titer in organs and serum in different time intervals post-infection. In addition, we also stated mean survival times in different strains of mice with different genetic background following virus inoculation