Role of Cerebellar Interpositus Nucleus in the Genesis and Control of Reflex and Conditioned Eyelid Responses

The role of cerebellar circuits in the acquisition of new motor abilities is still a matter of intensive debate. To establish the contribution of posterior interpositus nucleus (PIN) to the performance and/or acquisition of reflex and classically conditioned responses (CRs) of the eyelid, the effects of microstimulation and/or pharmacological inhibition by muscimol of the nucleus were investigated in conscious cats. Microstimulation of the PIN in naive animals evoked ramp-like eyelid responses with a wavy appearance, without producing any noticeable plastic functional change in the cerebellar and brainstem circuits involved. Muscimol microinjections decreased the amplitude of reflex eyeblinks evoked by air puffs, both when presented alone or when paired with a tone as conditioned stimulus (CS). In half-conditioned animals, muscimol injections also decreased the amplitude and damped the typical wavy profile of CRs, whereas microstimulation of the same sites increased both parameters. However, neither muscimol injections nor microstimulation modified the expected percentage of CRs, suggesting a major role of the PIN in the performance of eyelid responses rather than in the learning process. Moreover, the simultaneous presentation of CS and microstimulation in well trained animals evoked CRs similar in amplitude to the added value of those evoked by the two stimuli presented separately. In contrast, muscimol-injected animals developed CRs to paired CS and microstimulation presentations, larger than those evoked by the two stimuli when presented alone. It is concluded that the PIN contributes to the enhancement of both reflex and conditioned eyelid responses and to the damping of resonant properties of neuromuscular elements controlling eyelid kinematics

EEG findings of reduced neural synchronization during visual integration in schizophrenia

Schizophrenia patients exhibit well-documented visual processing deficits. One area of disruption is visual integration, the ability to form global objects from local elements. However, most studies of visual integration in schizophrenia have been conducted in the context of an active attention task, which may influence the findings. In this study we examined visual integration using electroencephalography (EEG) in a passive task to elucidate neural mechanisms associated with poor visual integration. Forty-six schizophrenia patients and 30 healthy controls had EEG recorded while passively viewing figures comprised of real, illusory, or no contours. We examined visual P100, N100, and P200 event-related potential (ERP) components, as well as neural synchronization in the gamma (30-60 Hz) band assessed by the EEG phase locking factor (PLF). The N100 was significantly larger to illusory vs. no contour, and illusory vs. real contour stimuli while the P200 was larger only to real vs. illusory stimuli; there were no significant interactions with group. Compared to controls, patients failed to show increased phase locking to illusory versus no contours between 40-60 Hz. Also, controls, but not patients, had larger PLF between 30-40 Hz when viewing real vs. illusory contours. Finally, the positive symptom factor of the BPRS was negatively correlated with PLF values between 40-60 Hz to illusory stimuli, and with PLF between 30-40 Hz to real contour stimuli. These results suggest that the pattern of results across visual processing conditions is similar in patients and controls. However, patients have deficits in neural synchronization in the gamma range during basic processing of illusory contours when attentional demand is limited

Presence of Adult Companion Goats Favors the Rumen Microbial and Functional Development in Artificially Reared Kids

Newborn dairy ruminants are usually separated from their dams after birth and fed on milk replacer. This lack of contact with adult animals may hinder the rumen microbiological and physiological development. This study evaluates the effects of rearing newborn goat kids in contact with adult companions on the rumen development. Thirty-two newborn goat kids were randomly allocated to two experimental groups which were reared either in the absence (CTL) or in the presence of non-lactating adult goats (CMP) and weaned at 7 weeks of age. Blood and rumen samples were taken at 5, 7, and 9 weeks of age to evaluate blood metabolites and rumen microbial fermentation. Next-generation sequencing was carried out on rumen samples collected at 7 weeks of age. Results showed that CTL kids lacked rumen protozoa, whereas CMP kids had an abundant and complex protozoal community as well as higher methanogen abundance which positively correlated with the body weight and blood beta-hydroxybutyrate as indicators of the physiological development. CMP kids also had a more diverse bacterial community (+132 ASVs) and a different structure of the bacterial and methanogen communities than CTL kids. The core rumen bacterial community in CMP animals had 53 more ASVs than that of CTL animals. Furthermore, the number of ASVs shared with the adult companions was over 4-fold higher in CMP kids than in CTL kids. Greater levels of early rumen colonizers Proteobacteria and Spirochaetes were found in CTL kids, while CMP kids had higher levels of Bacteroidetes and other less abundant taxa (Veillonellaceae, Cyanobacteria, and Selenomonas). These findings suggest that the presence of adult companions facilitated the rumen microbial development prior to weaning. This accelerated microbial development had no effect on the animal growth, but CMP animals presented higher rumen pH and butyrate (+45%) and ammonia concentrations than CTL kids, suggesting higher fibrolytic and proteolytic activities. CMP kids also had higher blood beta-hydroxybutyrate (+79%) and lower blood glucose concentrations (-23%) at weaning, indicating an earlier metabolic development which could favor the transition from pre-ruminant to ruminant after the weaning process. Further research is needed to determine the effects of this intervention in more challenging farm conditions

b-Initiated processes at the LHC: a reappraisal

Several key processes at the LHC in the standard model and beyond that involve $b$ quarks, such as single-top, Higgs, and weak vector boson associated production, can be described in QCD either in a 4-flavor or 5-flavor scheme. In the former, $b$ quarks appear only in the final state and are typically considered massive. In 5-flavor schemes, calculations include $b$ quarks in the initial state, are simpler and allow the resummation of possibly large initial state logarithms of the type $\log \frac{{\cal Q}^2}{m_b^2}$ into the $b$ parton distribution function (PDF), ${\cal Q}$ being the typical scale of the hard process. In this work we critically reconsider the rationale for using 5-flavor improved schemes at the LHC. Our motivation stems from the observation that the effects of initial state logs are rarely very large in hadron collisions: 4-flavor computations are pertubatively well behaved and a substantial agreement between predictions in the two schemes is found. We identify two distinct reasons that explain this behaviour, i.e., the resummation of the initial state logarithms into the $b$-PDF is relevant only at large Bjorken $x$ and the possibly large ratios ${\cal Q}^2/m_b^2$'s are always accompanied by universal phase space suppression factors. Our study paves the way to using both schemes for the same process so to exploit their complementary advantages for different observables, such as employing a 5-flavor scheme to accurately predict the total cross section at NNLO and the corresponding 4-flavor computation at NLO for fully exclusive studies.Comment: Fixed typo in Eq. (A.10) and few typos in Eq. (C.2) and (C.3

Heterogeneity in multistage carcinogenesis and mixture modeling

Carcinogenesis is commonly described as a multistage process, in which stem cells are transformed into cancer cells via a series of mutations. In this article, we consider extensions of the multistage carcinogenesis model by mixture modeling. This approach allows us to describe population heterogeneity in a biologically meaningful way. We focus on finite mixture models, for which we prove identifiability. These models are applied to human lung cancer data from several birth cohorts. Maximum likelihood estimation does not perform well in this application due to the heavy censoring in our data. We thus use analytic graduation instead. Very good fits are achieved for models that combine a small high risk group with a large group that is quasi immune

Study of radiactivity on Arctic marine seaweed from Kongsfjorden (Svalbard)

Levels of natural and anthropogenic radionuclides have been determined in six brown and red seaweed species from Arctic coasts (Kongsfjorden, Spitsbergen, Svalbard Islands) in order to characterize the radioactivity in this ecosystem. Samples were collected in September 2014, August 2017 and July 2019. Levels of 7Be, 40K, 208Tl, 210Pb, 226Ra and 228Ra were measured by high-resolution gamma spectrometry. While anthropogenic radionuclides (1 4 C and 1 2 9 I) were determined by low-energy accelerator mass spectrometry (LEAMS). The activities of 129I are two orders of magnitude higher than those found in algae collected on the Spanish Atlantic Coast and presents more variability than the 14C results, indicating their different affinity to this element depending on the species. Radionuclide tracers discharged from Sellafield and La Hague are transported into the Arctic Ocean where they circulate at different depth levels, marking water of Atlantic origin (Karcher et al., 2012).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Proyecto CGL2015/67014

Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain terminating nucleosides

PrimPol is a DNA damage tolerance enzyme possessing both translesion synthesis (TLS) and primase activities. To uncover its potential role in TLS-mediated IgVλ hypermutation and define its interplay with other TLS polymerases, PrimPol-/- and PrimPol-/-/Polη-/-/Polζ -/- gene knockouts were generated in avian cells. Loss of PrimPol had no significant impact on the rate of hypermutation or the mutation spectrum of IgVλ. However, PrimPol-/- cells were sensitive to methylmethane sulfonate, suggesting that it may bypass abasic sites at the IgVλ segment by repriming DNA synthesis downstream of these sites. PrimPol-/- cells were also sensitive to cisplatin and hydroxyurea, indicating that it assists in maintaining / restarting replication at a variety of lesions. To accurately measure the relative contribution of the TLS and primase activities, we examined DNA damage sensitivity in PrimPol-/- cells complemented with polymerase or primase-deficient PrimPol. Polymerase-deficient, but not primase-deficient, PrimPol suppresses the hypersensitivity of PrimPol-/- cells. This indicates that its primase, rather than TLS activity, is pivotal for DNA damage tolerance. Loss of TLS polymerases, Polη and Polζ has an additive effect on the sensitivity of PrimPol-/- cells. Moreover, we found that PrimPol and Polη-Polζ redundantly prevented cell death and facilitated unperturbed cell cycle progression. PrimPol-/- cells also exhibited increased sensitivity to a wide variety of chain-terminating nucleoside analogs (CTNAs). PrimPol could perform close-coupled repriming downstream of CTNAs and oxidative damage in vitro. Together, these results indicate that PrimPol’s repriming activity plays a central role in reinitiating replication downstream from CTNAs and other specific DNA lesions. downstream from CTNAs and other specific DNA lesions