Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses

Copyright: © 2015 Sudhakar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNeurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.Peer reviewedFinal Published versio

Midlatitude shelf seas in the Cenomanian-Turonian greenhouse world: Temperature evolution and North Atlantic circulation

An 8 million year record of subtropical and midlatitude shelf-sea temperatures, derived from oxygen isotopes of well-preserved brachiopods from a variety of European sections, demonstrates a long-term Cenomanian temperature rise (16–20°C, midlatitudes) that reached its maximum early in the late Turonian (23°C, midlatitudes). Superimposed on the long-term trend, shelf-sea temperatures vary at shorter timescales in relation to global carbon cycle perturbations. In the mid-Cenomanian and the late Turonian, two minor shelf-sea cooling events (2–3°C) coincide with carbon cycle perturbations and times of high-amplitude sea level falls. Although this evidence supports the hypothesis of potential glacioeustatic effects on Cretaceous sea level, the occurrence of minimum shelf-sea temperatures within transgressive beds argues for regional changes in shelf-sea circulation as the most plausible mechanism. The major carbon cycle event in the latest Cenomanian (oceanic anoxic event 2) is accompanied by a substantial increase in shelf-sea temperatures (4–5°C) that occurred ∼150 kyr after the commencement of the δ13C excursion and is related to the spread of oceanic conditions in western European shelf-sea basins. Our oxygen isotope record and published δ18O data of pristinely preserved foraminifera allow the consideration of North Atlantic surface water properties in the Cenomanian along a transect from the tropics to the midlatitudes. On the basis of fossil-derived δ18O, estimated δw ranges, and modeled salinities, temperature-salinity-density ranges were estimated for tropical, subtropical, and midlatitude surface waters. Accordingly, the Cenomanian temperate shelf-seas waters have potentially the highest surface water density and could have contributed to North Atlantic intermediate to deep waters in the preopening stage of the equatorial Atlantic gateway

The effect of non-specific LTD on pattern recognition in cerebellar Purkinje cells

© 2010 Safaryan et al; licensee BioMed Central Ltd.Poster presented at CNS 2010Peer reviewe

Nonspecific synaptic plasticity improves the recognition of sparse patterns degraded by local noise

Safaryan, K. et al. Nonspecific synaptic plasticity improves the recognition of sparse patterns degraded by local noise. Sci. Rep. 7, 46550; doi: 10.1038/srep46550 (2017). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ © The Author(s) 2017.Many forms of synaptic plasticity require the local production of volatile or rapidly diffusing substances such as nitric oxide. The nonspecific plasticity these neuromodulators may induce at neighboring non-active synapses is thought to be detrimental for the specificity of memory storage. We show here that memory retrieval may benefit from this non-specific plasticity when the applied sparse binary input patterns are degraded by local noise. Simulations of a biophysically realistic model of a cerebellar Purkinje cell in a pattern recognition task show that, in the absence of noise, leakage of plasticity to adjacent synapses degrades the recognition of sparse static patterns. However, above a local noise level of 20 %, the model with nonspecific plasticity outperforms the standard, specific model. The gain in performance is greatest when the spatial distribution of noise in the input matches the range of diffusion-induced plasticity. Hence non-specific plasticity may offer a benefit in noisy environments or when the pressure to generalize is strong.Peer reviewe

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Identification of Tsetse (Glossina spp.) using matrix-assisted laser desorption/ionisation time of flight mass spectrometry

Glossina (G.) spp. (Diptera: Glossinidae), known as tsetse flies, are vectors of African trypanosomes that cause sleeping sickness in humans and nagana in domestic livestock. Knowledge on tsetse distribution and accurate species identification help identify potential vector intervention sites. Morphological species identification of tsetse is challenging and sometimes not accurate. The matrix-assisted laser desorption/ionisation time of flight mass spectrometry (MALDI TOF MS) technique, already standardised for microbial identification, could become a standard method for tsetse fly diagnostics. Therefore, a unique spectra reference database was created for five lab-reared species of riverine-, savannah- and forest- type tsetse flies and incorporated with the commercial Biotyper 3.0 database. The standard formic acid/acetonitrile extraction of male and female whole insects and their body parts (head, thorax, abdomen, wings and legs) was used to obtain the flies' proteins. The computed composite correlation index and cluster analysis revealed the suitability of any tsetse body part for a rapid taxonomical identification. Phyloproteomic analysis revealed that the peak patterns of G. brevipalpis differed greatly from the other tsetse. This outcome was comparable to previous theories that they might be considered as a sister group to other tsetse spp. Freshly extracted samples were found to be matched at the species level. However, sex differentiation proved to be less reliable. Similarly processed samples of the common house fly Musca domestica (Diptera: Muscidae; strain: Lei) did not yield any match with the tsetse reference database. The inclusion of additional strains of morphologically defined wild caught flies of known origin and the availability of large-scale mass spectrometry data could facilitate rapid tsetse species identification in the futur

The Role of Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Primary Staging of Newly Diagnosed Prostate Cancer: A Systematic Review of the Literature

Context Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT), in initial staging remains controversial. Objective To systematically review the studies of MRI and/or PET/CT in the staging of newly diagnosed PCa with respect to tumor (T), nodal (N), and metastatic (M) staging (TNM staging). Evidence acquisition We performed a systematic review of the literature using MEDLINE and Web of Science databases between 2012 and 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. Evidence synthesis A total of 139 studies (83 on T, 47 on N, and 24 on M status) were included. Ninety-nine (71%) were retrospective, 39 (28%) were prospective, and one was a randomized controlled trial (RCT). Most studies on T staging examined MRI, while PET/CT was used primarily for N and M staging. Sensitivity for the detection of extraprostatic extension, seminal vesicle invasion, or lymph node invasion ranged widely. When imaging was incorporated into existing risk tools, gain in accuracy was observed in some studies, although these findings have not been replicated. For M staging, most favorable results were reported for prostate-specific membrane antigen (PSMA) PET/CT, which demonstrated significantly better performance than conventional imaging. Conclusions A variety of studies on modern imaging techniques for TNM staging in newly diagnosed PCa exist. For T and N staging, reported sensitivity of imaging modalities such as MRI or PET/CT varied widely due to data heterogeneity, small sample size, and low event rates resulting in large confidence intervals and a high level of uncertainty. Therefore, uniformity in data presentation and standardization on this topic are needed. The most promising technique for M staging, which was evaluated recently in an RCT, is PSMA-PET/CT. Patient summary We performed a systematic review of currently available imaging modalities to stage newly diagnosed prostate cancer. With respect to local tumor and lymph node assessment, performance of imaging ranged widely. However, prostate-specific membrane antigen positron emission tomography/computed tomography showed favorable results for the detection of distant metastases

Conformational coupling of redox-driven Na⁺-translocation in Vibrio cholerae NADH:quinone oxidoreductase

In the respiratory chain, NADH oxidation is coupled to ion translocation across the membrane to build up an electrochemical gradient. In the human pathogen Vibrio cholerae, the sodium-pumping NADH:quinone oxidoreductase (Na+-NQR) generates a sodium gradient by a so far unknown mechanism. Here we show that ion pumping in Na+-NQR is driven by large conformational changes coupling electron transfer to ion translocation. We have determined a series of cryo-EM and X-ray structures of the Na+-NQR that represent snapshots of the catalytic cycle. The six subunits NqrA, B, C, D, E, and F of Na+-NQR harbor a unique set of cofactors that shuttle the electrons from NADH twice across the membrane to quinone. The redox state of a unique intramembranous [2Fe-2S] cluster orchestrates the movements of subunit NqrC, which acts as an electron transfer switch. We propose that this switching movement controls the release of Na+ from a binding site localized in subunit NqrB

Anthelmintic resistance against benzimidazoles and macrocyclic lactones in strongyle populations on cattle farms in northern Germany

Anthelmintic resistance (AR) in cattle gastrointestinal nematodes (GIN) is an increasing global concern, with low to moderate levels recently documented in Central Europe. This study reports on resistance against both macrocyclic lactones (MLs) and benzimidazoles (BZs) in northern Germany, highlighting that AR is spreading. The fecal egg count reduction test (FECRT) remains the primary tool for AR assessment, yet differing methodologies and recent guideline updates complicate resistance interpretation across studies. Statistical methods, such as Bayesian approaches used by eggCounts and bayescount, yield varying confidence intervals, further influencing results. Notably, the nemabiome analysis identified Ostertagia ostertagi and Cooperia oncophora as predominant species in the region, though unexpected diversity among farms with additional GIN species occurring sometimes even at high frequency, suggests morphological analysis of coprocultures may underestimate species prevalence. Detecting AR against both drug classes on some farms underscores the urgency of implementing sustainable strategies, such as targeted selective treatment and combinations of anthelmintics with different mode of action, to prevent scenarios of multi-drug resistance observed elsewhere. Effective resistance management requires immediate discussions with veterinarians and stakeholders to steer toward informed, preventive measures in cattle farming

Alternative PCR protocol using a single primer set for assessing DNA quality in several tissues from a large variety of mammalian species living in areas endemic for leishmaniasis

The aim of this work was to establish a modified pre-diagnostic polymerase chain reaction (PCR) protocol using a single primer set that enables successful amplification of a highly conserved mammalian sequence in order to determine overall sample DNA quality for multiple mammalian species that inhabit areas endemic for leishmaniasis. The gene encoding interphotoreceptor retinoid-binding protein (IRBP), but not other conserved genes, was efficiently amplified in DNA samples from tail skin, ear skin, bone marrow, liver and spleen from all of the species tested. In tissue samples that were PCR-positive for Leishmania, we found that DNA from 100%, 55% and 22% of the samples tested resulted in a positive PCR reaction for the IRBP, beta-actin and beta-globin genes, respectively. Nucleotide sequencing of an IRBP amplicon resolved any questions regarding the taxonomical classification of a rodent, which was previously based simply on the morphological features of the animal. Therefore, PCR amplification and analysis of the IRBP amplicon are suitable for pre-diagnostically assessing DNA quality and identifying mammalian species living in areas endemic to leishmaniasis and other diseases