bluuebunny/crossref_metadata_2025 huggingface dataset:
Depth-targeted intracortical microstroke by two-photon photothrombosis in rodent brain
Authors: Fukuda Masahiro , Matsumura Takayoshi , Suda Toshio , Hirase Hajime
Published: November 2021

Significance

Photothrombosis is a widely used model of ischemic stroke in rodent experiments. In the photothromboris model, the photosensitizer Rose Bengal is systemically introduced to the blood stream and activated by green light to induce aggregation of platelets that eventually cause vessel occlusion. Since the activation of Rose Bengal is a one-photon phenomenon and the molecules in the illuminated area (light path) are subject to excitation, targeting of thrombosis is unspecific especially in the depth dimension. We have developed a photothrombosis protocol that can target a single vessel in the cortical parenchyma by two-photon excitation.

Aim

We aim to induce a thrombotic stroke in the cortical parenchyma by two-photon activation of Rose Bengal so that we confine photothrombosis within a vessel of a target depth.

Approach

FITC-dextran is injected into the blood stream to visualize the cerebral blood flow in anesthetized adult mice with a cranial window. After a target vessel is chosen by two-photon imaging (950 nm), Rose Bengal is injected into the blood stream. The scanning wavelength is changed to 720 nm and photothrombosis was induced by scanning the target vessel.

Results

Two-photon depth-targeted single vessel photothrombosis was achieved with a success rate of 84.9±1.7% within 80 s. Attempts without Rose Bengal (i.e., only with FITC) did not result in photothrombosis at the excitation wavelength of 720 nm.

Conclusions

We described a protocol that achieves depth-targeted single vessel photothrombosis by two-photon excitation. Simultaneous imaging of blood flow in the targeted vessel using FITC dextran enabled the confirmation of vessel occlusion and prevention of excess irradiation that possibly induces unintended photodamage.
Increased frequency of CD4+ and CD8+ follicular helper T cells in human lymph node biopsies during the earliest stages of rheumatoid arthritis
Authors: Anang Dornatien C. , Ramwadhdoebe Tamara H. , Hahnlein Janine , van Kuijk Bo , Smits N. , van Lienden Krijn P. , Maas Mario , Gerlag Danielle M. , Tak Paul P. , de Vries Niek , van Baarsen Lisa G.
Published: November 2021

Objectives

Follicular helper T cells (Tfh cells) provide key B cell help, and are essential in germinal center (GC) formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA) we analyzed their frequencies, phenotype and cytokine profile in peripheral blood and lymphoid tissues.

Methods

Using flow cytometry, we studied the frequency of Tfh and B cells in peripheral blood and lymph node (LN) needle biopsies. Three donor groups were included and compared: healthy controls (HCs), autoantibody positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Ex vivo stimulation of lymphocytes with PMA/ionomycin was performed to assess cytokine secretion by Tfh cells.

Results

In blood, the frequency of circular Tfh cells (cTfh) did not differ between study groups. In lymphoid tissue, the frequency of Tfh cells correlated strongly with the frequency of CD19+ B cells. Compared to healthy controls, LN samples of RA patients and RA-risk individuals showed more CD19+ B cells and more CD4+CXCR5+ and CD8+CXCR5+ Tfh cells. These Tfh cells from LNs expressed less IL-21 upon ex vivo stimulation.

Conclusion

LN tissue of early RA patients as well as part of RA-risk individuals exhibit increased frequencies of Tfh cells correlating with increased numbers of B cells. Interestingly, IL-21 production is already aberrant in the very early at risk phase of the disease. This suggests that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of the disease to prevent further disease progression.
Deep assessment of human disease-associated ribosomal RNA modifications using Nanopore direct RNA sequencing
Authors: Naarmann-de Vries Isabel S. , Zorbas Christiane , Lemsara Amina , Bencun Maja , Schudy Sarah , Meder Benjamin , Eschenbach Jessica , Lafontaine Denis L.J. , Dieterich Christoph
Published: November 2021

The catalytically active component of ribosomes, rRNA, is long studied and heavily modified. However, little is known about functional and pathological consequences of changes in human rRNA modification status. Direct RNA sequencing on the Nanopore platform enables the direct assessment of rRNA modifications. We established a targeted Nanopore direct rRNA sequencing approach and applied it to CRISPR-Cas9 engineered HCT116 cells, lacking specific enzymatic activities required to establish defined rRNA base modifications. We analyzed these sequencing data along with wild type samples andin vitrotranscribed reference sequences to specifically detect changes in modification status. We show for the first time that direct RNA-sequencing is feasible on smaller, i.e. Flongle, flow cells. Our targeted approach reduces RNA input requirements, making it accessible to the analysis of limited samples such as patient derived material. The analysis of rRNA modifications during cardiomyocyte differentiation of human induced pluripotent stem cells, and of heart biopsies from cardiomyopathy patients revealed altered modifications of specific sites, among them pseudouridines, 2’-O-methylation of riboses and acetylation of cytidines. Targeted direct rRNA-seq analysis with JACUSA2 opens up the possibility to analyze dynamic changes in rRNA modifications in a wide range of biological and clinical samples.
Intrasexual cuticular hydrocarbon dimorphism in a wasp sheds light on hydrocarbon biosynthesis genes in Hymenoptera
Authors: Moris Victoria C. , Podsiadlowski Lars , Martin Sebastian , Oeyen Jan Philip , Donath Alexander , Petersen Malte , Wilbrandt Jeanne , Misof Bernhard , Liedtke Daniel , Thamm Markus , Scheiner Ricarda , Schmitt Thomas , Niehuis Oliver
Published: November 2021

Cuticular hydrocarbons (CHCs) cover the cuticle of insects and serve as desiccation barrier and for chemical communication. While the main enzymatic steps of CHC biosynthesis are well understood, few of the underlying genes have been identified. Here we show how exploitation of intrasexual CHC dimorphism in a mason wasp, Odynerus spinipes, in combination with whole-genome sequencing and comparative transcriptomics facilitated identification of such genes. RNAi-mediated knockdown of twelve candidate gene orthologs in honey bees, Apis mellifera, confirmed nine genes impacting CHC profile composition. Most of them have predicted functions consistent with current knowledge of CHC metabolism. However, we found first-time evidence for a fatty acid amide hydrolase also influencing CHC profile composition. In situ hybridization experiments furthermore suggest trophocytes participating in CHC biosynthesis. Our results set the base for experimental CHC profile manipulation in Hymenoptera and imply that the evolutionary origin of CHC biosynthesis predates the arthropods’ colonization of land.
Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing
Authors: Ly Michael , Burgess Hannah M. , Mohr Ian , Glaunsinger Britt A.
Published: November 2021

The mRNA 5’ cap structure serves both to protect transcripts from degradation and promote their translation. Cap removal is thus an integral component of mRNA turnover that is carried out by cellular decapping enzymes, whose activity is tightly regulated and coupled to other stages of the mRNA decay pathway. The poxvirus vaccinia virus (VACV) encodes its own decapping enzymes, D9 and D10, that act on cellular and viral mRNA, but may be regulated differently than their cellular counterparts. Here, we evaluated the targeting potential of these viral enzymes using RNA sequencing from cells infected with wild-type and decapping mutant versions of VACV as well as in uninfected cells expressing D10. We found that D9 and D10 target an overlapping subset of viral transcripts but that D10 plays a dominant role in depleting the vast majority of human transcripts, although not in an indiscriminate manner. Unexpectedly, the splicing architecture of a gene influences how robustly its corresponding transcript is targeted by D10, as transcripts derived from intronless genes are less susceptible to enzymatic decapping by D10. As all VACV genes are intronless, preferential decapping of transcripts from intron-encoding genes provides an unanticipated mechanism for the virus to disproportionately deplete host transcripts and remodel the infected cell transcriptome.
Pluripotency-Independent Induction of Human Trophoblast Stem Cells from Fibroblasts
Authors: Naama Moriyah , Radwan Ahmed , Zayat Valery , Sebban Shulamit , Rahamim Moran , Lasry Rachel , Jaber Mohammad , Sabag Ofra , Yassen Hazar , Orzech Dana , Khatib Areej , Epsztejn-Litman Silvina , Novoselsky-Persky Michal , Makedonski Kirill , Deri Noy , Goldman-Wohl Debra , Cedar Howard , Yagel Simcha , Eiges Rachel , Buganim Yosef
Published: November 2021

Recent studies demonstrated that human trophoblast stem-like cells (hTS-like cells) can be derived from naïve embryonic stem cells or be induced from somatic cells by the pluripotency factors, OSKM. This raises two main questions; (i) whether human induced TSCs (hiTSCs) can be generated independently to pluripotent state or factors and (ii) what are the mechanisms by which hTSC state is established during reprogramming. Here, we identify GATA3, OCT4, KLF4 and MYC (GOKM) as a pluripotency-independent combination of factors that can generate stable and functional hiTSCs, from both male and female fibroblasts. By using single and double knockout (KO) fibroblasts for major pluripotency genes (i.e. SOX2 or NANOG/PRDM14) we show that GOKM not only is capable of generating hiTSCs from the KO cells, but rather that the efficiency of the process is increased. Through H3K4me2 and chromatin accessibility profiling we demonstrate that GOKM target different loci and genes than OSKM, and that a significant fraction of them is related to placenta and trophoblast function. Moreover, we show that GOKM exert a greater pioneer activity compared to OSKM. While GOKM target many specific hTSC loci, OSKM mainly target hTSC loci that are shared with hESCs. Finally, we reveal a gene signature of trophoblast-related genes, consisting of 172 genes which are highly expressed in blastocyst-derived TSCs and GOKM-hiTSCs but absent or mildly expressed in OSKM-hiTSCs.

Taken together, these results imply that not only is the pluripotent state, and SOX2 specifically, not required to produce functional hiTSCs, but that pluripotency-specific factors actually interfere with the acquisition of the hTSC state during reprogramming.
YAP1 Activation by Human Papillomavirus E7 Promotes Basal Cell Identity in Squamous Epithelia
Authors: Hatterschide Joshua , Castagnino Paola , Kim Hee Won , Sperry Steven M. , Montone Kathleen T. , Basu Devraj , White Elizabeth A.
Published: November 2021

Persistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly five percent of cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative cancers at the same anatomical site, prompting the hypothesis that an HPV-encoded protein inactivates the Hippo pathway and activates the Hippo effector YAP1. The HPV E7 oncoprotein is required for HPV infection and for HPV-mediated oncogenic transformation. We investigated the effects of HPV oncoproteins on YAP1 and found that E7 activates YAP1, promoting YAP1 nuclear localization in basal epithelial cells. YAP1 activation by HPV E7 required that E7 bind and degrade the tumor suppressor PTPN14. E7 required YAP1 transcriptional activity to extend the lifespan of primary keratinocytes, indicating that YAP1 activation contributes to E7 carcinogenic activity. Maintaining infection in basal cells is critical for HPV persistence, and here we demonstrate that YAP1 activation causes HPV E7 expressing cells to be retained in the basal compartment of stratified epithelia. We propose that YAP1 activation resulting from PTPN14 inactivation is an essential, targetable activity of the HPV E7 oncoprotein relevant to HPV infection and carcinogenesis.
Calcium current modulation by the γ1 subunit depends on alternative splicing of CaV1.1
Authors: El Ghaleb Yousra , Ortner Nadine J. , Posch Wilfried , Fernández-Quintero Monica L. , Tuinte Wietske E. , Monteleone Stefania , Draheim Henning J. , Liedl Klaus R. , Wilflingseder Doris , Striessnig Jörg , Tuluc Petronel , Flucher Bernhard E. , Campiglio Marta
Published: November 2021

The skeletal muscle voltage-gated calcium channel (CaV1.1) primarily functions as voltage sensor for excitation-contraction coupling. Conversely, its ion-conducting function is modulated by multiple mechanisms within the pore-forming α1S subunit and the auxiliary α2δ-1 and γ1 subunits. Particularly, developmentally regulated alternative splicing of exon 29, which inserts 19 amino acids in the extracellular IVS3-S4 loop of CaV1.1a, greatly reduces the current density and shifts the voltage-dependence of activation to positive potentials outside the physiological range. We generated a new HEK293-cell line stably expressing α2δ-1, β3, and STAC3. When the adult (CaV1.1a) and the embryonic (CaV1.1e) splice variants were expressed in these cells, the difference in the voltage-dependence of activation observed in muscle cells was reproduced, but not the reduced current density of CaV1.1a. Only when we further co-expressed the γ1 subunit, the current density of CaV1.1a, but not of CaV1.1e, was reduced by >50 %. In addition, γ1 caused a shift of the voltage-dependence of inactivation to negative voltages in both variants. Thus, the current-reducing effect of γ1, but not its effect on inactivation, is specifically dependent on the inclusion of exon 29 in CaV1.1a. Molecular structure modeling revealed several direct ionic interactions between oppositely charged residues in the IVS3-S4 loop and the γ1 subunit. However, substitution of these residues by alanine, individually or in combination, did not abolish the γ1-dependent reduction of current density, suggesting that structural rearrangements of CaV1.1a induced by inclusion of exon 29 allosterically empower the γ1 subunit to exert its inhibitory action on CaV1.1 calcium currents.

El Ghaleb et al. analyzed the effects of the γ1 subunit on current properties and expression of the adult (CaV1.1a) and embryonic (CaV1.1e) calcium channel splice variants, demonstrating that γ1 reduces the current amplitude in a splicing-dependent manner.
A theory of the dynamics of DNA loop initiation in condensin/cohesin complexes
Authors: Khatri Bhavin S.
Published: November 2021

The structural maintenance of chromosome complexes exhibit the remarkable ability to actively extrude DNA, which has led to the appealing and popular “loop extrusion” model to explain one of the most important processes in biology: the compaction of chromatin during the cell cycle. A potential mechanism for the action of extrusion is the classic Brownian ratchet, which requires short DNA loops to overcome an initial enthalpic barrier to bending, before favoured entropic growth of longer loops. We present a simple model of the constrained dynamics of DNA loop formation based on a frictional worm like chain, where for circular loops of order, or smaller than the persistence length, internal friction to bending dominates solvent dynamics. Using Rayleigh’s dissipation function, we show how bending friction can be translated to simple one dimensional diffusion of the angle of the loop resulting in a Smoluchowski equation with a coordinate dependent diffusion constant. This interplay between Brownian motion, bending dissipation and geometry of loops leads to a qualitatively new phenomenon, where the friction vanishes for bends with an angle of exactly 180 degrees, due to a decoupling between changes in loop curvature and angle. Using this theory and given current parameter uncertainties, we tentatively predict mean first passage times of between 1 and 10 seconds, which is of order the cycle time of ATP, suggesting spontaneous looping could be sufficient to achieve efficient initiation of looping.
Three year experience of Upper Gastrointestinal Endoscopic procedures at a tertiary care hospital of South Punjab
Authors: Din Chaudhary Farooq Mohyud , Gul Muhammad Asif , Hameed Rizwan , Ilyas Muhammad , Zubair Muhammad , Umar Qasim , Altaf Syeda Manal , Tameez-ud-din Ahsan
Published: November 2021

Introduction

Endoscopy has become a necessity in diagnosing gastrointestinal (GI) disorders. The objective of our study was to evaluate the different indications and findings of upper GI endoscopy.

Methods

This retrospective analysis was undertaken at department of Gastroenterology, Nishtar Hospital Multan. Records of all upper GI endoscopic procedures from 1st January 2018 till 31st December 2020 were evaluated.

Results

A total 3299 upper GI endoscopic procedures were perfumed during the three-year time period. Mean age was 47 years. Majority of patients were males. Almost 48% of patients belonged to the middle-aged group. The most common indication was upper GI bleeding (57%), followed by dyspepsia (15%). The most common finding was esophageal varices (43%), followed by portal gastropathy (26%) and gastritis (16%).

Conclusion

This study concludes that the majority of endoscopies are being undertaken as a result of complications of cirrhosis and portal hypertension.
Effectiveness of non-pharmaceutical measures (NPIs) on COVID-19 in Europe: A systematic literature review
Authors: Vardavas Constantine I. , Nikitara Katerina , Aslanoglou Katerina , Hilton-Boon Michele , Phalkey Revati , Leonardi-Bee Jo , Magiorkinis Gkikas , Katsaounou Paraskevi , Pharris Anastasia , Severi Ettore , Suk Jonathan E.
Published: November 2021

Background

The study objective was to conduct a systematic review to assess the effectiveness of non-pharmaceutical interventions (NPIs) to reduce the transmission of SARS-CoV-2 in Europe during the first wave of the pandemic.

Methods

We searched OVID Medline, EMBASE, and the Cochrane and Campbell Databases for Systematic Reviews published up to April 15th 2021. Focusing on community (meso-level) and society (macro-level) level NPIs, we included all study designs, while a geographic restriction was limited to the EU, UK and European Economic Area (EEA) countries. Using the PICO framework, two reviewers independently extracted data and assessed quality using appropriate quality appraisal tools. A qualitative synthesis was performed, with NPIs grouped initially by a) Physical Distancing measures, b) Case detection and management measures, and c) hygiene measures and subsequently by country.

Results

Of 17,692 studies initially assessed, 45 met all inclusion criteria. Most studies (n=30) had a modelling study design, while 13 were observational, one quasi-experimental and one experimental. Evidence from across the European continent, presented by country, indicates that the implementations of physical distancing measures (i.e., lockdowns/quarantines), preferably earlier in the pandemic, reduce the number of cases and hospitalisation across settings and for which the timing and duration are essential parameters. Case detection and management measures were also identified as effective measures at certain levels of testing and incidence, while hygiene and safety measures complemented the implementation of physical distancing measures.

Conclusions

This literature review represents a comprehensive assessment of the effectiveness of NPIs in Europe up to April 2021. Despite heterogeneity across studies, NPIs, as assessed within the context of this systematic review at the macro and meso level, are effective in reducing SARS-CoV-2 transmission rates and COVID-19 hospitalisation rates and deaths in the European Region and may be applied as response strategies to reduce the burden of COVID-19 in forthcoming waves.
The β-NGF/TrkA signalling pathway is associated with the production of anti- nucleoprotein IgG in convalescent COVID-19
Authors: Usai Carla , Gibbons Joseph M. , Pade Corinna , Li Wenhao , Jacobs Sabina R.M. , McKnight Áine , Kennedy Patrick T. F. , Gill Upkar S.
Published: November 2021

Background

The presentation of SARS-CoV-2 infection varies from asymptomatic to severe COVID. Similarly, high variability in the presence, titre and duration of specific antibodies has been reported. While some host factors determining these differences, such as age and ethnicity have been identified, the underlying molecular mechanisms underpinning these differences remain poorly defined.

Methods

We analysed serum and PBMC from 17 subjects with a previous PCR confirmed SARS-CoV-2 infection and 10 unexposed volunteers following the first wave of the pandemic, in the UK. Anti-NP IgG and neutralising antibodies were measured, as well as a panel of infection and inflammation related cytokines. The virus-specific T cell response was determined by IFN-γ ELISPOT and flow cytometry after over-night incubation of PBMCs with pools of selected SARS-CoV-2 specific peptides.

Results

Seven of 17 convalescent subjects had undetectable levels of anti-NP IgG, and a positive correlation was shown between anti-NP IgG levels and the titre of neutralising antibodies (IC50). In contrast, a discrepancy was noted between antibody levels and T cell IFN-γ production by ELISpot following stimulation with specific peptides. Among the analysed cytokines, β-NGF and IL-1α levels were significantly different between anti-NP positive and negative subjects, and only β-NGF significantly correlated with anti-NP positivity. Interestingly, CD4+ T cells of anti-NP negative subjects expressed lower amounts of the β-NGF-specific receptor TrkA.

Conclusions

Our results suggest that the β-NGF/TrkA signalling pathway is associated with the production of anti-NP specific antibody in mild SARS-CoV-2 infection and the mechanistic regulation of this pathway in COVID-19 requires further investigation.
Flexibility in a Single Behavioral Variable of Drosophila
Authors: Heisenberg Martin , Wolf Reinhard , Brembs Björn
Published: November 2021

The flexibility of behavior is so rich, and its components are so exquisitely interwoven, that one may be well advised to turn to an isolated behavioral module for study. Gill withdrawal inAplysia, the proboscis extension reflex in the honeybee, and lid closure in mammals are such examples. We have chosen yawing, a single component of flight orientation in Drosophila melanogaster, for this approach. A specialty of this preparation is that the behavioral output can be reduced beyond the single module by one further step. It can be studied in tethered animals in which all turns are blocked while the differentially beating wings still provide the momentum. These intended yaw turns are measured by a torque meter to which the fly is hooked. The fly is held horizontally as if cruising at high speed. The head is glued to the thorax. It can bend its abdomen, extend its proboscis, and move its legs but cannot shift its direction of gaze or its orientation in space. Evidently, a fly hardly ever encounters this bizarre situation in the wild. We describe here the flexibility in this single behavioral variable. It provides insights into the relation between classical and operant conditioning, the processing of and interactions between the conditioned visual stimuli, early visual memory, visual pattern recognition, selective attention, and several other experience-dependent properties of visual orientation behavior. We start with a brief summary of visual flight control at the torque meter.
Tripartite Mushroom Body Architecture Revealed by Antigenic Markers
Authors: Crittenden Jill R. , Skoulakis Efthimios M.C. , Han Kyung-An , Kalderon Daniel , Davis Ronald L.
Published: November 2021

We have explored the organization of the axonal lobes in Drosophila mushroom bodies by using a panel of immunohistochemical markers. These markers consist of antibodies to eight proteins expressed preferentially in the mushroom bodies: DAMB, DCO, DRK, FASII, LEO, OAMB, PKA RII, and RUT. Previous to this work, four axonal lobes, two projecting dorsally (α and α′) and two medially (β and γ), had been described inDrosophila mushroom bodies. However, our analysis of immunohistochemically stained frontal and sagittal sections of the brain revealed three medially projecting lobes. The newly distinguished lobe, which we term β′, lies along the dorsal surface of β, just posterior to γ. In addition to resolving a fifth lobe, our studies revealed that there are specific lobe sets defined by equivalent marker expression levels. These sets are (1) the α and β lobes, (2) the α′ and β′ lobes, and (3) the γ lobe and heel (a lateral projection formed by a hairpin turn of some of the peduncle fibers). All of the markers we have examined are consistent with these three sets. Previous Golgi studies demonstrate that each mushroom body cell projects one axon that branches into a dorsal lobe and a medial lobe, or one unbranched axon that projects medially. Taken together with the lobe sets listed above, we propose that there are three major projection configurations of mushroom body cell axons: (1) one branch in the α and one in the β lobe, (2) one branch in the α′ and one in the β′ lobe, and (3) one unbranched axon projecting to the heel and the γ lobe. The fact that these neuron types exhibit differential expression levels of a number of mushroom body genes suggests that they may have corresponding functional differences. These functions may be conserved in the larvae, as several of these genes were expressed in larval and embryonic mushroom bodies as well. The basic mushroom body structure, including the denritic calyx, peduncle, and lobes, was already visible by the late stages of embryogenesis. With new insights into mushroom body organization, and the characterization of markers for developing mushroom bodies, we are beginning to understand how these structures form and function.
Reduced K+ Channel Inactivation, Spike Broadening, and After-Hyperpolarization in Kvβ1.1-Deficient Mice with Impaired Learning
Authors: Giese Karl Peter , Storm Johan F. , Reuter Dirk , Fedorov Nikolai B. , Shao Li-Rong , Leicher Thorsten , Pongs Olaf , Silva Alcino J.
Published: November 2021

A-type K+ channels are known to regulate neuronal firing, but their role in repetitive firing and learning in mammals is not well characterized. To determine the contribution of the auxiliary K+ channel subunit Kvβ1.1 to A-type K+ currents and to study the physiological role of A-type K+ channels in repetitive firing and learning, we deleted the Kvβ1.1 gene in mice. The loss of Kvβ1.1 resulted in a reduced K+ current inactivation in hippocampal CA1 pyramidal neurons. Furthermore, in the mutant neurons, frequency-dependent spike broadening and the slow afterhyperpolarization (sAHP) were reduced. This suggests that Kvβ1.1-dependent A-type K+ channels contribute to frequency-dependent spike broadening and may regulate the sAHP by controlling Ca2+ influx during action potentials. The Kvβ1.1-deficient mice showed normal synaptic plasticity but were impaired in the learning of a water maze test and in the social transmission of food preference task, indicating that the Kvβ1.1 subunit contributes to certain types of learning and memory.
Contrasting Cortical Activity Associated with Category Memory and Recognition Memory
Authors: Reber Paul J. , Stark Craig E.L. , Squire Larry R.
Published: November 2021

We collected functional neuroimaging data while volunteers performed similar categorization and recognition memory tasks. In the categorization task, volunteers first studied a series of 40 dot patterns that were distortions of a nonstudied prototype dot pattern. After a delay, while fMRI data were collected, they categorized 72 novel dot patterns according to whether or not they belonged to the previously studied category. In the recognition task, volunteers first studied five dot patterns eight times each. After a delay, while fMRI data were collected, they judged whether each of 72 dot patterns had been studied earlier. We found strikingly different patterns of brain activity in visual processing areas for the two tasks. During the categorization task, the familiar stimuli were associated with decreased activity in posterior occipital cortex, whereas during the recognition task, the familiar stimuli were associated with increased activity in this area. The findings indicate that these two types of memory have contrasting effects on early visual processing and reinforce the view that declarative and nondeclarative memory operate independently.
Rapid, Labile, and Protein Synthesis– Independent Short-Term Memory in Conditioned Taste Aversion
Authors: Houpt Thomas A. , Berlin RoseAnn
Published: November 2021

Short-term memory is a rapid, labile, and protein-synthesis-independent phase of memory. The existence of short-term memory in conditioned taste aversion (CTA) learning has not been demonstrated formally. To determine the earliest time at which a CTA is expressed, we measured intraoral intake of sucrose at 15 min, 1 hr, 6 hr, or 48 h after contingent pairing of an intraoral infusion of 5% sucrose (6.6 ml over 6 min) and toxic lithium chloride injection (76 mg/kg). Rats were implanted with intraoral catheters to allow presentation of taste solutions at arbitrary times. Intraoral intake was measured under conditions of long-delay, single-trial learning typical of CTA. Rats decreased intraoral intake of sucrose at 15 min after contingent pairing of sucrose and LiCl, but not after noncontingent LiCl or sucrose. Thus CTA learning can be expressed rapidly. To determine if short-term CTA memory is labile and decays in the absence of long-term memory, we measured intraoral intake of sucrose after pairing sucrose with low doses of LiCl. Rats received an intraoral infusion of 5% sucrose (6 ml/6 min); 30 min later LiCl was injected at three different doses (19, 38, or 76 mg/kg). A second intraoral infusion of sucrose was administered 15 min, 1 hr, 3 hr, 4.5 hr, 6 hr, or 48 hr later. The formation of long-term CTA memory was dependent on the dose of LiCl paired with sucrose during acquisition. Low doses of LiCl induced a CTA that decayed within 6 hr after pairing. Central administration of the protein synthesis inhibitor cycloheximide prior to LiCl injection blocked long-term CTA expression at 6 and 48 hr, but not short-term CTA expression at 1 hr. Thus, short-term memory for CTA learning exists that is acquired rapidly and independent of protein synthesis, but labile in the absence of long-term memory formation.
Two Modulatory Inputs Exert Reciprocal Reinforcing Effects on Synaptic Input of Premotor Interneurons for Withdrawal in Terrestrial Snails
Authors: Maksimova Olga A. , Bravarenko Natalia I. , Balaban Pavel M.
Published: November 2021

A cluster of serotonergic cells in the rostral part of pedal ganglia of the terrestrial snail Helix lucorum was shown previously to participate in modulation of withdrawal behavior, and to be necessary for elaboration of aversive withdrawal conditioning in intact snails. In the present experiments local extracellular stimulation of the serotonergic cells elicited a pairing-specific increase (difference between paired and explicitly unpaired sessions was significant, P < 0.01) of synaptic responses in the premotor interneurons involved in withdrawal to paired nerve stimulation. Intracellular stimulation of only one Pd4 cell from the pedal group of serotonergic neurons increased (P < 0.05) synaptic responses to contingent test nerve stimulation significantly in the same premotor interneurons for 2–3 hr.

Mesocerebral cells are known to participate in male sexual behavior, and their extracellular stimulation was shown previously to suppress the amplitude of synaptic responses in withdrawal interneurons. Local extracellular stimulation of the mesocerebral cells elicited a pairing-specific decrease (P < 0.01) of synaptic responses to contingent test nerve stimulation in the premotor interneurons involved in withdrawal for 2–3 hr. Paired application of met-enkephaline (10−6m, some mesocerebral cells are enkephaline-like immunoreactive) also selectively decreased synaptic responses to contingent nerve stimulation in the premotor interneurons for hours. Thus, two modulatory inputs exert pairing-specific effects that influence the same synaptic connection in opposite directions, which may underlie the long-term up- and down-regulation of behavioral responses.
Consolidation of Memory for Odor–Reward Association: β-Adrenergic Receptor Involvement in the Late Phase
Authors: Sara Susan J. , Roullet Pascal , Przybyslawski Jean
Published: November 2021

Experimentally naive rats can learn rapidly to discriminate among three odors to obtain food reinforcement. After three massed trials, they show almost errorless performance. This task has proved to be useful in studying time-dependent postacquisition intracellular processes necessary for long-term memory. The present experiments evaluated the temporal dynamics of the role of β-noradrenergic receptors in long-term consolidation. Rats were implanted with intracerebroventricular cannulae and trained in a single session to find reinforcement in a hole in a sponge impregnated with a particular odor. Injections of the β-receptor antagonist timolol were made at 5 min, 1, 2, or 5 hr after training. Memory and relearning ability were evaluated 48 hr later. Rats treated with timolol 2 hr after training showed a memory deficit at the retention test, but were able to relearn the task normally. Injections at the earlier or later time points were ineffective. The results reinforce previous observations with systemic injections that β-noradrenergic receptors are involved in the late phase of memory consolidation and suggest a critical time window during which they are necessary. The time window is compatible with the current view that long-term memory depends on late involvement of the cAMP cascade leading to new protein synthesis necessary for synaptic reorganization.
Sites of Plasticity in the Neural Circuit Mediating Tentacle Withdrawal in the Snail Helix aspersa: Implications for Behavioral Change and Learning Kinetics
Authors: Prescott Steven A. , Chase Ronald
Published: November 2021

The tentacle withdrawal reflex of the snail Helix aspersa exhibits a complex combination of habituation and sensitization consistent with the dual-process theory of plasticity. Habituation, sensitization, or a combination of both were elicited by varying stimulation parameters and lesion condition. Analysis of response plasticity shows that the late phase of the response is selectively enhanced by sensitization, whereas all phases are decreased by habituation. Previous data have shown that tentacle withdrawal is mediated conjointly by parallel monosynaptic and polysynaptic pathways. The former mediates the early phase, whereas the latter mediates the late phase of the response. Plastic loci were identified by stimulating and recording at different points within the neural circuit, in combination with selective lesions. Results indicate that depression occurs at an upstream locus, before circuit divergence, and is therefore expressed in all pathways, whereas facilitation requires downstream facilitatory neurons and is selectively expressed in polysynaptic pathways. Differential expression of plasticity between pathways helps explain the behavioral manifestation of depression and facilitation. A simple mathematical model is used to show how serial positioning of depression and facilitation can explain the kinetics of dual-process learning. These results illustrate how the position of cellular plasticity in the network affects behavioral change and how forms of plasticity can interact to determine the kinetics of the net changes.
Perception and Recognition Memory in Monkeys Following Lesions of Area TE and Perirhinal Cortex
Authors: Buffalo Elizabeth A. , Ramus Seth J. , Squire Larry R. , Zola Stuart M.
Published: November 2021

Monkeys with lesions of perirhinal cortex (PR group) and monkeys with lesions of inferotemporal cortical area TE (TE group) were tested on a modified version of the delayed nonmatching to sample (DNMS) task that included very short delay intervals (0.5 sec) as well as longer delay intervals (1 min and 10 min). Lesions of the perirhinal cortex and lesions of area TE produced different patterns of impairment. The PR group learned the DNMS task as quickly as normal monkeys (N) when the delay between sample and choice was very short (0.5 sec). However, performance of the PR group, unlike that of the N group, fell to chance levels when the delay between sample and choice was lengthened to 10 min. In contrast to the PR group, the TE group was markedly impaired on the DNMS task even at the 0.5-sec delay, and three of four monkeys with TE lesions failed to acquire the task. The results provide support for the idea that perirhinal cortex is important not for perceptual processing, but for the formation and maintenance of long-term memory. Area TE is important for the perceptual processing of visual stimuli.
Thermal elastohydrodynamic lubrication characteristics and optimisation of the ball-type tripod universal joint
Authors: Yang Fuqin , Han Xiaojie , Si Mingqing
Published: November 2021

Purpose

This paper aims to study the influence of three-column groove shell radius, ball radius, lubricating oil viscosity and elastic modulus on the thermal elastohydrodynamic lubrication (TEHL) characteristics and optimisation of the ball-type tripod universal joint.

Design/methodology/approach

The point contact TEHL model of the joint was developed, and the multi-grid method was used to solve it. The influence of three-column groove shell radius, ball radius, lubricating oil viscosity and elastic modulus on the lubrication characteristics was analysed. Further, the optimisation of the joint TEHL performance was carried out by the Kriging approximation model combined with the multi-objective particle swarm optimisation (MOPSO) algorithm.

Findings

The research results show that increasing groove shell radius and ball radius can effectively increase the oil film thickness, and decrease the oil film pressure, as well as the temperature rise. Decreasing elastic modulus can reduce the oil film temperature rise and pressure, and increasing viscosity can effectively increase the oil film thickness. The optimised minimum oil film thickness increases by 33.23% and the optimised maximum oil film pressure and maximum temperature rise decrease by 11.92% and 28.87%, respectively. Furthermore, the relative error of each response output is less than 10%.

Originality/value

This study applies TEHL theory to the tribological research of the ball-type tripod universal joint, and the joint’s lubrication performance is improved greatly by the Kriging model and MOPSO algorithm, which provides an effective measure to raise the joint’s working efficiency.
When workers matter most: a study of worker cooperatives and the prioritization of workers through COVID-19
Authors: Prushinskaya Olga , Pockrandt Jamie , McKinley Julian , Hoover Melissa
Published: November 2021

Purpose

As a part of the authors’ continued efforts to understand the experience and trends related to small business cooperatives, the US Federation of Worker Cooperatives (USFWC) and the Democracy at Work Institute (DAWI) explored themes around the impact of the COVID-19 pandemic on worker cooperatives and democratic workplaces.

Design/methodology/approach

The USFWC and DAWI conduct a biannual Economic Census of worker cooperatives and democratic workplaces. Survey themes this year included questions around the impact of the COVID-19 pandemic on individual firms.

Findings

General findings indicate that worker cooperatives experienced financial losses similar to conventional small businesses, but that this varied widely by industry. Although it has been found that BIPOC-owned conventional small businesses have been some of the hardest hit during the pandemic, the authors find that there may be some mitigating protective effects of the worker cooperative form when the authors explore the impacts on worker cooperatives with a majority BIPOC workforce. Additionally, the authors find that worker cooperatives and democratic workplaces strive to ensure the safety and wellbeing of their workers even when facing significant financial challenges throughout the pandemic.

Research limitations/implications

This research utilizes non-random convenience sampling in data collection. The outreach for our biannual Economic Census is concentrated on a highly connected worker cooperative and democratic workplace network, the experiences of which may not generalize to the larger worker cooperative and democratic workplace landscape. Additionally, outreach efforts were hindered by challenges presented by the pandemic that were not present in prior census years, as was firm bandwidth to respond, which likely affected the sample composition in comparison to prior years.

Originality/value

Worker cooperatives have been proven to be a resilient crisis response form of business, but little is known about how the worker cooperative ecosystem in the United States is faring in the face of the continuing COVID-19 crisis.
Forgoing plans for alcohol and cannabis use in daily life: Examining reasons for nonuse when use was planned in a predominantly white college student sample
Authors: Stevens Angela K. , Blanchard Brittany E. , Sokolovsky Alexander W. , Gunn Rachel L. , White Helene R. , Jackson Kristina M.
Published: November 2021

Background

The reasons for college students to abstain from alcohol and cannabis use on a given day can inform efforts to prevent or intervene in those behaviors. Research on reasons for alcohol nonuse remains in its nascent stages and no study to date has examined reasons for cannabis nonuse on a given day. Here we examine reasons for nonuse among college students after they planned to use alcohol and/or cannabis.

Methods

College students (N = 341; Mage = 19.79; 53% women; 74% White) from 3 universities completed 54 days of data collection across which approximately 50% were nonuse days. Each morning, participants indicated whether they planned to use that day; nonuse reasons were assessed the next morning, if applicable. Generalized linear mixed‐effects models were used to disentangle within‐ and between‐person effects.

Results

On a given nonuse day (at the within‐person level), “work” and “school” were reasons associated with having no plan to use alcohol and “to feel in control” was linked to having no plan to use cannabis. “Did not want to get high” was related to forgoing plans (did not use when originally planned) for alcohol use at the within‐person level. At the between‐person level, “no desire” was associated with no plans for alcohol or cannabis use and “did not want to get high” was related to no plans for cannabis use. “School” and “could not get” were related to forgoing plans for alcohol and cannabis use, respectively, at the between‐person level.

Conclusion

An examination of earlier intentions for alcohol and/or cannabis use on nonuse days yielded novel findings on the intention–behavior gap. Reasons for nonuse can inform intervention and prevention strategies (e.g., those involving social norms or just‐in‐time adaptive efforts) for alcohol and cannabis use on college campuses.
The seasonally dry tropical forest species Cavanillesia chicamochae has a middle Quaternary origin
Authors: Bacon Christine D. , Gutiérrez‐Pinto Natalia , Flantua Suzette , Castellanos Suárez Diego , Jaramillo Carlos , Pennington R. Toby , Antonelli Alexandre
Published: November 2021

We use DNA sequence data to understand the evolutionary history of the genus Cavanillesia (Malvaceae), with particular emphasis on C. chicamochae, an emblematic succulent‐trunked tree endemic to seasonally dry tropical forests (SDTFs) of the Chicamocha Canyon of Colombia, South America. Based on field sampling of multiple individuals from different populations, we inferred a phylogeny calibrated into absolute time using robust macrofossil information. We show strong support for a monophyletic Cavanillesia chicamochae, with a mean stem age of 1.46 Ma. Two different mechanisms could explain its origin, either a late uplift age of the eastern cordillera or increased dryness of the Chicamocha Canyon during the Middle Pleistocene Transition. We also find marked genetic differentiation of its populations within the Chicamocha Canyon, likely driven by a combination of climate change and local landscape processes. Our results suggest that within northern inter‐Andean SDTFs, as has been demonstrated in the central Andes, dispersal limitation leads to species and even population monophyly within individual valleys. The genetic differentiation of populations of C. chicamochae, together with the presence of other endemic and threatened species in the Chicamocha Canyon, calls for urgent management to conserve the unique biodiversity in the region.

Abstract in Spanish is available with online material.
Alluvial fan development during the Holocene in the Qu'Appelle Valley, Saskatchewan
Authors: Hardenbicker Ulrike Maria , Kelly Christina L. , Watanabe Makiko , Kotowich Roberta
Published: November 2021

Alluvial fan sediments contain valuable information on environmental change and anthropogenic influences, and function as an archive of landscape development. The purpose of this paper is to describe the analysis of the sedimentary information from core samples taken from two alluvial fans in the Saskatchewan prairies. The analysis assessed grain size, organic matter content, and microfossil presence to identify periods of accumulation and stabilization. Parker, Beavers, and Product weathering indices were used to analyze the modern source soil samples and the borehole cores to determine weathering/leaching conditions. The bed‐load transport sediments showed a higher leaching intensity whereas lower leaching was revealed for periods of stability, silt sheet flows, and sand sheet flows. The Beavers Index was not only a strong indicator of a bed‐load transport layer, but also of calcium accumulation zones marking alluvial fan surface stability. The large Dolomite/Calcite ratio marking the calcium accumulation zones was used for correlation between the two alluvial fan sites on a regional scale. A comparison of the stratigraphy of the two alluvial fans documents that a relationship exists between agriculture and an increase in erosion.
Empirical Evidence for Extended Cognitive Systems
Authors: Favela Luis H. , Amon Mary Jean , Lobo Lorena , Chemero Anthony
Published: November 2021

We present an empirically supported theoretical and methodological framework for quantifying the system‐level properties of person‐plus‐tool interactions in order to answer the question: “Are person‐plus‐tool‐systems extended cognitive systems?” Nineteen participants provided perceptual judgments regarding their ability to pass through apertures of various widths while using visual information, blindfolded wielding a rod, or blindfolded wielding an Enactive Torch—a vibrotactile sensory‐substitution device for detecting distance. Monofractal, multifractal, and recurrence quantification analyses were conducted to assess features of person‐plus‐tool movement dynamics. Trials where people utilized the rod or Enactive Torch demonstrated stable “self‐similarity,” or indices of healthy and adaptive single systems, regardless of aperture width, trial order, features of the participants’ judgments, and participant characteristics. Enactive Torch trials exhibited a somewhat greater range of dynamic fluctuations than the rod trials, as well as less movement recurrence, suggesting that the Enactive Torch allowed for more exploratory movements. Findings provide support for the notion that person‐plus‐tool systems can be classified as extended cognitive systems and a framework for quantifying system‐level properties of these systems. Implications concerning future research on extended cognition are discussed.