bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of past infection with SARS-CoV-2 on the response to the BioTech/Pfizer BNT162b2 mRNA vaccine in health care workers: kinetics and durability of the humoral response
Authors: Ontañón Jesús , Blas Joaquín , de Cabo Carlos , Santos Celia , Ruiz-Escribano Elena , García Antonio , Marín Luis , Sáez Lourdes , Beato José Luis , Rada Ramón , Navarro Laura , de Baranda Caridad Sainz , Solera Javier 
Published: May 2021

AbstractBackgroundVaccines against SARS-CoV-2 have provided an invaluable resource in the fight against this infection. Given the current vaccine shortage, vaccination programs must prioritize their distribution to the most appropriate segments of the population.MethodsWe carried out a prospective cohort study with 63 health care workers (HCWs) from a public General Hospital. We compared antibody responses to two doses of BNT162b2 mRNA Covid-19 vaccine between HCWs with laboratory-confirmed SARS-CoV-2 infection before vaccination (experienced HCWs) and HCWs who were not previously infected (naïve HCWs).ResultsSeven days after the first vaccine dose HCWs with previous infection experienced a 126 fold increase in antibody levels (GMC 26955 AU; 95% CI 18785-35125). However, in the HCW naïve group the response was much lower and only 5 of them showed positive antibody levels (>50 AU). The HCWs with previous infection did not significantly increased their antibody levels after the second dose while there was a significant increase in the naive HCW group (16 fold; GMC 20227 AU; 95% CI: 15179-25275). Approximately two months after completing vaccination, the level of antibodies was much lower in naive HCWs (GMC 6595 AU vs. 25003 AU; p<0.001)ConclusionThe study shows that 10 months after the disease has passed, the immune system is capable of producing a rapid and powerful secondary antibody response after one single dose of the vaccine. This response reflects the persistence of immunological memory and it is independent of whether or not anti-SARS-CoV-2 antibodies are detected in blood. Besides, we found that the second dose does not improve the antibody response in individuals with previous Covid-19 infection. Nonetheless, two months later, the persistence of antibody levels is still higher in the experienced HCWs. These data suggest that immune memory remains for a long time in recovered individuals, and therefore, vaccination in this group could be postponed until immunization of the rest of the population is complete.
Bacterial CRISPR-Cas Abundance Increases Precipitously at Around 45°C: Linking Antivirus Immunity to Grazing Risk
Authors: Lan Xin-Ran , Liu Zhi-Ling , Niu Deng-Ke 
Published: May 2021

AbstractAlthough performing adaptive immunity, CRISPR-Cas systems are present in only 40% of bacterial genomes. Here, we observed an abrupt transition of bacterial CRISPR-Cas abundance at around 45°C. Phylogenetic comparative analyses confirmed that the abundance correlates with growth temperature only at the temperature range around 45°C. Meanwhile, we noticed that the diversities of cellular predators have a precipitous decline at this temperature range. The grazing risk faced by bacteria reduces substantially at around 45°C and almost disappears above 60°C. So viral lysis would become the dominating factor of bacterial mortality, and antivirus immunity has a higher priority. In temperature ranges where the abundance of cellular predators does not change with temperature, temperatures would have negligible effects on CRISPR-Cas abundance. The hypothesis predicts that bacteria should also be rich in CRISPR-Cas systems if they live in other extreme conditions inaccessible to grazing predators.
ThePlasmodiumNOT1-G Paralogue Acts as an Essential Nexus for Sexual Stage Maturation and Parasite Transmission
Authors: Hart Kevin J. , Power B. Joanne , Rios Kelly T. , Sebastian Aswathy , Lindner Scott E. 
Published: May 2021

AbstractProductive transmission of malaria parasites hinges upon the execution of key transcriptional and post-transcriptional regulatory events. While much is now known about how specific transcription factors activate or repress sexual commitment programs, far less is known about the production of a preferred mRNA homeostasis following commitment and through the host-to-vector transmission event. Here we show thatPlasmodiumparasites have taken the unique approach to duplicate the NOT1 scaffold protein of the CAF1/CCR4/Not complex in order to dedicate one paralogue for essential transmission functions. Moreover, this NOT1-G paralogue is central to the sex-specific functions previously associated with its interacting partners, as deletion ofnot1-ginPlasmodium yoeliileads to a comparable or complete arrest phenotype for both male and female parasites. We show that, consistent with its role in other eukaryotes, PyNOT1-G localizes to cytosolic puncta throughout much of thePlasmodiumlife cycle. PyNOT1-G is essential to both the complete maturation of male gametes and to the continued development of the fertilized zygote originating from female parasites. Comparative transcriptomics of wild-type andpynot1-g-parasites shows that loss of PyNOT1-G leads to transcript dysregulation preceding and during gametocytogenesis, and shows that PyNOT1-G acts to preserve mRNAs that are critical to sexual and early mosquito stage development. Finally, we demonstrate that the tristetraprolin-binding domain, which acts as the typical organization platform for RNA decay (TTP) and RNA preservation (ELAV/HuR) factors is dispensable for PyNOT1-G’s essential blood stage functions but impacts host-to-vector transmission. Together, we conclude thatPlasmodiumhas created and adapted a NOT1-G paralogue to fulfill the complex transmission requirements of both male and female parasites.
Interneuron subtypes enable independent modulation of excitatory and inhibitory firing rates after sensory deprivation
Authors: Richter Leonidas M. A. , Gjorgjieva Julijana 
Published: May 2021

AbstractDiverse interneuron subtypes determine how cortical circuits process sensory information depending on their connectivity. Sensory deprivation experiments are ideally suited to unravel the plasticity mechanisms which shape circuit connectivity, but have yet to consider the role of different inhibitory subtypes. We investigate how synaptic changes due to monocular deprivation affect the firing rate dynamics in a microcircuit network model of the visual cortex. We demonstrate that, in highly recurrent networks, deprivation-induced plasticity generates fundamentally different activity changes depending on interneuron composition. Considering parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneuron subtypes can capture the experimentally observed independent modulation of excitatory and inhibitory activity during sensory deprivation when SST+ feedback is sufficiently strong. Our model also applies to whisker deprivation in the somatosensory cortex revealing that these mechanisms are general across sensory cortices. Therefore, we provide a mechanistic explanation for the differential role of interneuron subtypes in regulating cortical dynamics during deprivation-induced plasticity.
Double face of cytochrome c in cancers. New look into human breast ducts with Raman imaging
Authors: Abramczyk H. , Brozek-Pluska B. , Kopeć M. 
Published: May 2021

SUMMARYCytochrome c (Cyt c) is a key protein that is needed to maintain life (respiration) and cell death (apoptosis). The dual-function of Cyt c comes from its capability to act as mitochondrial redox carrier that transfers electrons between the membrane-embedded complexes III and IV and to serve as a cytoplasmic apoptosis-triggering agent, activating the caspase cascade.1–6 However, the precise roles of Cyt c in mitochondria, cytoplasm and extracellular matrix under normal and pathological conditions are not completely understood.7–9To date, no pathway of Cyt c release that results in caspase activation has been compellingly demon-strated in any invertebrate.10 The significance of mitochondrial dysfunctionality has not been studied in ductal carcinoma to the best of our knowledge.1Here we show that proper concentration of monounsaturated fatty acids, saturated fatty acids, cardi-olipin and Cyt c is critical in the correct breast ductal functioning and constitutes an important parameter to assess breast epithelial cells integrity and homeostasis. We look inside human breast ducts answering fundamental questions about location and distribution of various biochemical components inside the lumen, epithelial cells of the duct and the extracellular matrix around the cancer duct during cancer development in situ. We found in histopathologically controlled breast cancer duct that Cyt c, cardi-olipin, and palmitic acid are the main components inside the lumen of cancerous duct in situ. The pre-sented results show direct evidence that Cyt c is released to the lumen from the epithelial cells in can-cerous duct. In contrast the lumen in normal duct is empty and free of Cyt c. Our results demonstrate how Cyt c is likely to function in cancer development. We anticipate our results to be a starting point for more sophisticated in vitro and in vivo animal models. For example, the correlation between concentration of Cyt c and cancer grade could be tested in various types of cancer. Furthermore, Cyt c is a target of anti-cancer drug development 11,12 and a well-defined and quantitative Raman based assay for oxidative phosphorylation and apoptosis will be relevant for such developments.
A neural network account of memory replay and knowledge consolidation
Authors: Barry Daniel N. , Love Bradley C. 
Published: May 2021

AbstractReplay can consolidate memories through offline neural reactivation related to past experiences. Category knowledge is learned across multiple experiences, and its subsequent generalisation is promoted by consolidation and replay during rest and sleep. However, aspects of replay are difficult to determine from neuroimaging studies. We provided insights into category knowledge replay by simulating these processes in a neural network which approximated the roles of the human ventral visual stream and hippocampus. Generative replay, akin to imagining new category instances, facilitated generalisation to new experiences. Consolidation-related replay may therefore help to prepare us for the future as much as remember the past. Generative replay was more effective in later network layers functionally similar to the lateral occipital cortex than layers corresponding to early visual cortex, drawing a distinction between neural replay and its relevance to consolidation. Category replay was most beneficial for newly acquired knowledge, suggesting replay helps us adapt to changes in our environment. Finally, we present a novel mechanism for the observation that the brain selectively consolidates weaker information; a reinforcement learning process in which categories were replayed according to their contribution to network performance. This reinforces the idea of consolidation-related replay as an active rather than passive process.
Hippocampal reconfiguration of events in mnemonic networks
Authors: Collin Silvy H.P. , Milivojevic Branka , Doeller Christian F. 
Published: May 2021

ABSTRACTIt is widely assumed that episodic memories are not stored in isolation but rather in dynamic event networks. However, the mechanisms of the underlying dynamic of these representations, in particular how such networks are updated, remain elusive. In this study, we investigated the reconfiguration of events into event networks in the hippocampus by presenting new events that could update either one of two competing narratives. During the first session, participants viewed four animated movies, each representing a distinct narrative; two distinct narratives from the Jones family and two distinct narratives from the Smith family. During the second session, we re-exposed participants to snapshots of these narratives along with snapshots of new events from one of the two families, allowing updating of the acquired event networks of that family. Our findings show that the hippocampus integrated new events that relate to the old family, and then integrated these new events with the corresponding old events. Furthermore, hippocampal representations of the events within a narrative became better integrated after updating. Our results shed new light on the neural mechanisms underlying flexible mnemonic updating with realistic events and further advance our understanding of the structured reconfiguration of event networks in memory.
Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through cAMP/PKA pathway
Authors: Wang Shan , van Rhijn Jon-Ruben , Akkouh Ibrahim , Kogo Naoki , Maas Nadine , Bleeck Anna , Ortiz Irene Santisteban , Lewerissa Elly , Wu Ka Man , Schoenmaker Chantal , Djurovic Srdjan , van Bokhoven Hans , Kleefstra Tjitske , Kasri Nael Nadif , Schubert Dirk 
Published: May 2021

SummaryHeterozygous loss-of-function (LoF) mutations in SETD1A, which encodes a subunit of histone H3 lysine 4 methyltransferase, were shown to cause a novel neurodevelopmental syndrome and increase the risk for schizophrenia. We generated excitatory/inhibitory neuronal networks from human induced pluripotent stem cells with a SETD1A heterozygous LoF mutation (SETD1A+/-) using CRISPR/Cas9. Our data show that SETD1A haploinsufficiency resulted in morphologically increased dendritic complexity and functionally increased bursting activity. This network phenotype was primarily driven by SETD1A haploinsufficiency in glutamatergic neurons. In accordance with the functional changes, transcriptomic profiling revealed perturbations in gene sets associated with glutamatergic synaptic function. At the molecular level, we identified specific changes in the cAMP/PKA pathway pointing toward a hyperactive cAMP pathway in SETD1A+/- neurons. Finally, by pharmacologically targeting the cAMP pathway we were able to rescue the network deficits in SETD1A+/- cultures. Our results demonstrate a link between SETD1A and the cAMP-dependent pathway in human neurons.
Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate Retriever-mediated recycling on endosomes
Authors: Giridharan Sai Srinivas Panapakkam , Luo Guangming , Rivero-Ríos Pilar , Steinfeld Noah , Tronchere Helene , Singla Amika , Burstein Ezra , Billadeau Daniel D. , Sutton Michael A. , Weisman Lois 
Published: May 2021

AbstractCell-surface receptors control how cells respond to their environment. Many cell-surface receptors recycle from endosomes to the plasma membrane via a recently discovered pathway, which includes sorting-nexin SNX17, Retriever, WASH and CCC complexes. Here we discover that PIKfyve and its upstream PI3-kinase VPS34 positively regulate this pathway. VPS34 produces PI3P, which is the substrate for PIKfyve to generate PI3,5P2. We show that PIKfyve controls recycling of cargoes including integrins, receptors that control cell migration. Furthermore, endogenous PIKfyve colocalizes with SNX17, Retriever, WASH and CCC complexes on endosomes. Importantly, PIKfyve inhibition causes a loss of Retriever and CCC from endosomes, and mutation of the lipid binding site on a CCC subunit impairs its endosomal localization and delays integrin recycling. In addition, we show that recruitment of SNX17 is an early step and requires VPS34. These discoveries suggest that VPS34 and PIKfyve coordinate an ordered pathway to regulate recycling from endosomes and suggest how PIKfyve functions in cell migration.
AAV-BR1 targets endothelial cells in the retina to reveal their morphological diversity and to deliver Cx43
Authors: Ivanova Elena , Corona Carlo , Eleftheriou Cyril G. , Stout Randy F. , Körbelin Jakob , Sagdullaev Botir T. 
Published: May 2021

AbstractEndothelial cells (ECs) are key players in the development and maintenance of the vascular tree, the establishment of the blood brain barrier and control of blood flow. Disruption in ECs is an early and active component of vascular pathogenesis. However, our ability to selectively target ECs in the CNS for identification and manipulation is limited. Here, in the mouse retina, a tractable model of the CNS, we utilized a recently developed AAV-BR1 system to identify distinct classes of ECs along the vascular tree using a GFP reporter. We then developed an inducible EC-specific ectopic Connexin 43 (Cx43) expression system using AAV-BR1-CAG-DIO-Cx43-P2A-DsRed2 in combination with a mouse line carrying inducible CreERT2 in ECs. We targeted Cx43 because its loss has been implicated in microvascular impariment in numerous diseases such as diabetic retinopathy and vascular edema. GFP-labeled ECs were numerous, evenly distributed along the vascular tree and their morphology was polarized with respect to the direction of blood flow. After tamoxifen induction, ectopic Cx43 was specifically expressed in ECs. Similarly to endogenous Cx43, ectopic Cx43 was localized at the membrane contacts of ECs and it did not affect tight junction proteins. The ability to enhance gap junctions in ECs provides a precise and potentially powerful tool to treat microcirculation deficits, an early pathology in numerous diseases.
An infection-activated redox switch promotes tumor growth
Authors: Kovalyova Yekaterina , Bak Daniel W. , Gordon Elizabeth M. , Fung Connie , Shuman Jennifer H. B. , Cover Timothy L. , Amieva Manuel R. , Weerapana Eranthie , Hatzios Stavroula K. 
Published: May 2021

AbstractOxidative stress is a defining feature of most cancers, including those that stem from carcinogenic infections1. Reactive oxygen species (ROS) can drive tumor formation2–4, yet the molecular oxidation events that contribute to tumorigenesis are largely unknown. Here we show that inactivation of a single, redox-sensitive cysteine in the host protease legumain, which is oxidized during infection with the gastric cancer-causing bacterium Helicobacter pylori, accelerates tumor growth. By using chemical proteomics to map cysteine reactivity in human gastric cells, we determined that H. pylori infection induces oxidation of legumain at Cys219. Legumain oxidation, which is enhanced by the ROS-promoting bacterial oncoprotein CagA, dysregulates intracellular legumain processing and localization and decreases legumain activity in H. pylori-infected cells. We further show that the site-specific loss of Cys219 reactivity increases tumor growth and mortality in a xenograft model. Our findings establish a link between the precise oxidation of a host protein and tumorigenic signaling during bacterial infection and demonstrate the importance of oxidative post-translational modifications in tumor growth.
Cognitive impairment and treatment outcomes amongst people attending an alcohol intervention service for those aged 50+
Authors: Seddon Jennifer , Wadd Sarah , Elliott Lawrie , Madoc-Jones Iolo 
Published: May 2021

PurposeNo studies have evaluated the relationship between cognitive impairment and alcohol treatment outcomes amongst older drinkers. This study aims to explore the extent of cognitive impairment amongst older adults seeking alcohol treatment and examine the relationship between cognitive impairment, treatment retention and alcohol use following treatment.Design/methodology/approachThe study used data from the Drink Wise Age Well programme; an alcohol intervention service for older adults (aged 50+). The Montreal Cognitive Assessment was used to screen for cognitive impairment; alcohol use was assessed using the alcohol use disorders identification test.FindingsIn total, 531 participants completed the assessment at treatment entry. Over half the sample were male (57%), with a mean age of 60 years (Standard deviation: 7.09). Almost half (48.4%) had cognitive impairment at the entry to treatment: 51.6% had a normal cognitive function, 41.4% had mild cognitive impairment, 5.8% had moderate cognitive impairment and 1.1% had severe cognitive impairment. Cognitive impairment was not associated with increased treatment drop-out and was not predictive of alcohol use following treatment. Alcohol treatment was associated with a significant improvement in cognitive functioning.Originality/valueThis study suggests there may be a significant amount of unidentified cognitive impairment amongst older adults attending alcohol treatment. Assessment and routine screening for cognitive impairment in drug and alcohol services may help in care planning and setting treatment goals; in the absence of routine screening opportunities for treatment planning and intervention may be missed.
The influence of sexual objectification on guilt assessment on a sample of Italian graduates
Authors: Cabras Cristina , Tumatis Roberta , Mondo Marina , Sechi Cristina 
Published: May 2021

PurposeThe purpose of this study was to investigate the influence of sexual objectification on the attribution processes of the guilt of a defendant – and also on the level of guilt. It was also hypothesized that legal expertise could be a protective factor in countering the influence of sexual objectification.Design/methodology/approachSexual objectification can be defined as the perspective in which a person is evaluated solely in terms of his or her body parts or sexual function. As yet, no studies have assessed the influence of sexual objectification on guilt assessment in the legal system; this paper aims to explore whether sexual objectification has an influence on the attribution processes of a defendant's guilt.FindingsThe statistical analysis revealed that the sexually objectified defendant received a guilty verdict more often than a non-sexually objectified defendant; additionally, legal experts were more likely to identify the defendant as not guilty than non-legal experts. The findings support the hypothesis that sexual objectification is indeed one of the common stereotypes that lead to discrimination.Originality/valueThe present study provides novel findings regarding sexual objectification in the forensic context in which the defendant is viewed and evaluated.
Professionals’ views on children’s service user involvement
Authors: Kiili Johanna , Itäpuisto Maritta , Moilanen Johanna , Svenlin Anu-Riina , Malinen Kaisa Eveliina 
Published: May 2021

Purpose
Children are gradually attaining recognition as service users and their involvement in service development has been advanced in recent years. This study draws on empirical research in social and health-care services designed for children and families. The purpose of this paper is to analyse how professionals understand children’s involvement as experts by experience. The focus is on professionals’ views and intergenerational relations.

Design/methodology/approach
The research data comprise 25 individual and 10 group interviews with managers and professionals working in social and health-care services in one Finnish province. The data were analysed using qualitative thematic analysis.

Findings
The professionals recognised the value of children’s service user involvement. However, they concentrated more on the challenges than the possibilities it presents. Health-care professionals emphasised parental needs and children’s vulnerability. In turn, the professionals from social services and child welfare non-governmental organisations perceived children as partners, although with reservations, as they discussed ethical issues widely and foregrounded the responsibilities of adults in protecting children. In general, the professionals in both domains saw themselves as having ethical responsibility to support children’s service user involvement while at the same time setting limits to it.

Originality/value
This study confirmed the importance of taking intergenerational relations into account when developing children’s service user involvement. The results indicate that professionals also need to reflect on the ethical challenges with children themselves as, largely owing to the generational position of children as minors, they rarely perceive them as partners in ethical reflection.