Miracle-dz/UniFAR-FTUs huggingface dataset:
Histochemical method for demonstrating quail mast cell types simultaneously

Abstract The development and application of selective staining methods for routine detection of mast cells are of considerable interest, because these cells play an important role in health and disease. The composition of cytoplasmic mast cell granules depends on the species and type of mast cell. The study reported here was conducted to investigate the combined use of aldehyde fuchsin (AF) and the Alcian blue-critical electrolyte concentration (AB-CEC) (pH 5.8, 0.3 M MgCl2) techniques for differentiating avian mast cell subtypes. Tissue samples from skin, intestines, and lungs of six healthy adult quail and two control rats were fixed in Carnoy's solution and 10% formolin for routine histological processing. To determine the staining properties of sulfated glycosaminoglycans (GAGs), a three-step staining technique was applied using berberine sulfate, AF, and AB-CEC. In quail, AF positivity following application of the AB-CEC technique was found only in the lungs, mostly in cells that gave a berberine sulfate-positive reaction, and this positivity was determined to be localized particularly in the nucleus and perinuclear cytoplasm. In other regions, the pale AF staining of cells that did not emit fluorescence when stained with berberine sulfate was determined to be replaced by a blue color after application of AB-CEC. The AF/AB-CEC (pH 5.8, 0.3 M MgCl2) technique demonstrated that rat and quail mast cells varied in both GAG types and their distribution within the cell. Especially in avian species, this technique can be applied to distinguish mast cells according to their GAG content. It can be used as an alternative to the AB/safranin O staining procedure for differentiating mast cells that contain and lack heparin.
Exfoliative cytology for diagnosing oral cancer

Abstract Exfoliative cytology is a minimally invasive technique for obtaining oral cell specimens from patients for diagnostic purposes. Classical applications of oral cytology studies, such as oral candidiasis, have been extended to include oral precancerous and cancerous lesions. A number of analytical methods are available for studying cytology specimens. The development of molecular analysis techniques, the oral cancer etiopathogenic process, and improvements in liquid-based exfoliative cytology are leading to renewed interest in exfoliative cytology. Results sometimes are disputed, so the aim of our review was to clarify the applicability of exfoliative cytology to the diagnosis of oral precancerous and cancerous lesions.
Cerebellar Roles in Self-Timing for Sub- and Supra-Second Intervals

Previous studies suggest that the cerebellum and basal ganglia are involved in sub-second and supra-second timing, respectively. To test this hypothesis at the cellular level, we examined the activity of single neurons in the cerebellar dentate nucleus in monkeys performing the oculomotor version of the self-timing task. Animals were trained to report the passage of time of 400, 600, 1200, or 2400 ms following a visual cue by making self-initiated memory-guided saccades. We found a sizeable preparatory neuronal activity before self-timed saccades across delay intervals, while the time course of activity correlated with the trial-by-trial variation of saccade latency in different ways depending on the length of the delay intervals. For the shorter delay intervals, the ramping up of neuronal firing rate started just after the visual cue and the rate of rise of neuronal activity correlated with saccade timing. In contrast, for the longest delay (2400 ms), the preparatory activity started late during the delay period, and its onset time correlated with self-timed saccade latency. Because electrical microstimulation applied to the recording sites during saccade preparation advanced self-timed but not reactive saccades, regardless of their directions, the signals in the cerebellum may have a causal role in self-timing. We suggest that the cerebellum may regulate timing in both sub-second and supra-second ranges, although its relative contribution might be greater for sub-second than for supra-second time intervals. SIGNIFICANCE STATEMENT How we decide the timing of self-initiated movement is a fundamental question. According to the prevailing hypothesis, the cerebellum plays a role in monitoring sub-second timing, whereas the basal ganglia are important for supra-second timing. To verify this, we explored neuronal signals in the monkey cerebellum while animals reported the passage of time in the range 400–2400 ms by making eye movements. Contrary to our expectations, we found that neurons in the cerebellar dentate nucleus exhibited a similar preparatory activity for both sub-second and supra-second intervals, and that electrical simulation advanced self-timed saccades in both conditions. We suggest that the cerebellum plays a causal role in the fine adjustment of self-timing in a larger time range than previously thought.
Possible neoplastic effects of acrylamide on rat exocrine pancreas

Abstract We investigated whether the acrylamide formed during cooking carbohydrate-rich foods at high temperatures causes neoplastic changes in rat pancreas. Azaserine, which is an amino acid derivative that has the ability to initiate neoplastic changes in rat pancreas, was injected into 14-day-old male rats once a week for three weeks. Acrylamide was given to both azaserine-injected and non-injected rats at doses of 5 and 10 mg/kg/day in drinking water for 16 weeks after which tissue slides were prepared from the pancreata. Pancreas weights and body weights of rats treated with azaserine and acrylamide together increased significantly compared to the other groups. Moreover, the size, average diameter and volume of atypical acinar cell foci that developed in the pancreata of rats treated with azaserine and acrylamide together increased significantly compared to rats treated with either azaserine or acrylamide alone and control groups. Atypical acinar cell adenoma or adenocarcinoma was not observed in the pancreata of rats in any group.
Distinctive Features of Adult Ocular Dominance Plasticity

Sensory experience profoundly shapes neural circuitry of juvenile brain. Although the visual cortex of adult rodents retains a capacity for plasticity in response to monocular visual deprivation, the nature of this plasticity and the neural circuit changes that accompany it remain enigmatic. Here, we investigate differences between adult and juvenile ocular dominance plasticity using Fourier optical imaging of intrinsic signals in mouse visual cortex. This comparison reveals that adult plasticity takes longer than in the juvenile mouse, is of smaller magnitude, has a greater contribution from the increase in response to the open eye, and has less effect on the hemisphere ipsilateral to the deprived eye. Binocular deprivation also causes different changes in the adult. Adult plasticity is similar to juvenile plasticity in its dependence on signaling through NMDA receptors. We propose that adult ocular dominance plasticity arises from compensatory mechanisms that counterbalance the loss of afferent activity caused by visual deprivation.
Protein Tyrosine Phosphatase δ Mediates the Sema3A-Induced Cortical Basal Dendritic Arborization through the Activation of Fyn Tyrosine Kinase

Leukocyte common antigen-related (LAR) class protein tyrosine phosphatases (PTPs) are critical for axonal guidance; however, their relation to specific guidance cues is poorly defined. We here show that PTP-3, a LAR homolog in Caenorhabditis elegans, is involved in axon guidance regulated by Semaphorin-2A-signaling. PTPδ, one of the vertebrate LAR class PTPs, participates in the Semaphorin-3A (Sema3A)-induced growth cone collapse response of primary cultured dorsal root ganglion neurons from Mus musculus embryos. In vivo, however, the contribution of PTPδ in Sema3A-regualted axon guidance was minimal. Instead, PTPδ played a major role in Sema3A-dependent cortical dendritic growth. Ptpδ−/− and Sema3a−/− mutant mice exhibited poor arborization of basal dendrites of cortical layer V neurons. This phenotype was observed in both male and female mutants. The double-heterozygous mutants, Ptpδ+/−; Sema3a+/−, also showed a similar phenotype, indicating the genetic interaction. In Ptpδ−/− brains, Fyn and Src kinases were hyperphosphorylated at their C-terminal Tyr527 residues. Sema3A-stimulation induced dephosphorylation of Tyr527 in the dendrites of wild-type cortical neurons but not of Ptpδ−/−. Arborization of cortical basal dendrites was reduced in Fyn−/− as well as in Ptpδ+/−; Fyn+/− double-heterozygous mutants. Collectively, PTPδ mediates Sema3A-signaling through the activation of Fyn by C-terminal dephosphorylation. SIGNIFICANCE STATEMENT The relation of leukocyte common antigen-related (LAR) class protein tyrosine phosphatases (PTPs) and specific axon guidance cues is poorly defined. We show that PTP-3, a LAR homolog in Caenorhabditis elegans, participates in Sema2A-regulated axon guidance. PTPδ, a member of vertebrate LAR class PTPs, is involved in Sema3A-regulated cortical dendritic growth. In Sema3A signaling, PTPδ activates Fyn and Src kinases by dephosphorylating their C-terminal Tyr residues. This is the first evidence showing that LAR class PTPs participate in Semaphorin signaling in vivo.
Acid-Sensing Ion Channels Activated by Evoked Released Protons Modulate Synaptic Transmission at the Mouse Calyx of Held Synapse

Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. A drop in extracellular pH induces transient inward ASIC currents (IASICs) in postsynaptic MNTB neurons from wild-type mice. The inhibition of IASICs by psalmotoxin-1 (PcTx1) and the absence of these currents in knock-out mice for ASIC-1a subunit (ASIC1a−/−) suggest that homomeric ASIC-1as are mediating these currents in MNTB neurons. Furthermore, we detect ASIC1a-dependent currents during synaptic transmission, suggesting an acidification of the synaptic cleft due to the corelease of neurotransmitter and H+ from synaptic vesicles. These currents are capable of eliciting action potentials in the absence of glutamatergic currents. A significant characteristic of these homomeric ASIC-1as is their permeability to Ca2+. Activation of ASIC-1a in MNTB neurons by exogenous H+ induces an increase in intracellular Ca2+. Furthermore, the activation of postsynaptic ASIC-1as during high-frequency stimulation (HFS) of the presynaptic nerve terminal leads to a PcTx1-sensitive increase in intracellular Ca2+ in MNTB neurons, which is independent of glutamate receptors and is absent in neurons from ASIC1a−/− mice. During HFS, the lack of functional ASICs in synaptic transmission results in an enhanced short-term depression of glutamatergic EPSCs. These results strongly support the hypothesis of protons as neurotransmitters and demonstrate that presynaptic released protons modulate synaptic transmission by activating ASIC-1as at the calyx of Held–MNTB synapse. SIGNIFICANCE STATEMENT The manuscript demonstrates that postsynaptic neurons of the medial nucleus of the trapezoid body at the mouse calyx of Held synapse express functional homomeric Acid-sensing ion channel-1a (ASIC-1as) that can be activated by protons (coreleased with neurotransmitter from acidified synaptic vesicles). These ASIC-1as contribute to the generation of postsynaptic currents and, more relevant, to calcium influx, which could be involved in the modulation of presynaptic transmitter release. Inhibition or deletion of ASIC-1a leads to enhanced short-term depression, demonstrating that they are concerned with short-term plasticity of the synapse. ASICs represent a widespread communication system with unique properties. We expect that our experiments will have an impact in the neurobiology field and will spread in areas related to neuronal plasticity.
How Does the Brain Implement Adaptive Decision Making to Eat?

Adaptive decision making to eat is crucial for survival, but in anorexia nervosa, the brain persistently supports reduced food intake despite a growing need for energy. How the brain persists in reducing food intake, sometimes even to the point of death and despite the evolution of multiple mechanisms to ensure survival by governing adaptive eating behaviors, remains mysterious. Neural substrates belong to the reward-habit system, which could differ among the eating disorders. The present review provides an overview of neural circuitry of restrictive food choice, binge eating, and the contribution of specific serotonin receptors. One possibility is that restrictive food intake critically engages goal-directed (decision making) systems and “habit,” supporting the view that persistent caloric restriction mimics some aspects of addiction to drugs of abuse. SIGNIFICANCE STATEMENT An improved understanding of the neural basis of eating disorders is a timely challenge because these disorders can be deadly. Up to 70 million of people in the world suffer from eating disorders. Anorexia nervosa affects 1–4% of women in United States and is the first cause of death among adolescents in Europe. Studies relying on animal models suggest that decision making to eat (or not) can prevail over actual energy requirements due to emotional disturbances resulting in abnormal habitual behavior, mimicking dependence. These recent studies provide a foundation for developing more specific and effective interventions for these disorders.
Genetic Factors and Orofacial Motor Learning Selectively Influence Variability in Central Sulcus Morphology in Chimpanzees (Pan troglodytes)

Captive chimpanzees (Pan troglodytes) have been shown to learn the use of novel attention-getting (AG) sounds to capture the attention of humans as a means of requesting or drawing their attention to a desired object or food. There are significant individual differences in the use of AG sounds by chimpanzees and, here, we examined whether changes in cortical organization of the central sulcus (CS) were associated with AG sound production. MRI scans were collected from 240 chimpanzees, including 122 that reliably produced AG sounds and 118 that did not. For each subject, the depth of CS was quantified along the superior–inferior plane with specific interest in the inferior portion corresponding to the region of the motor cortex where the mouth and orofacial movements are controlled. Results indicated that CS depth in the inferior, but not superior, portion was significantly greater in chimpanzees that reliably produced AG sounds compared with those who did not. Quantitative genetic analyses indicated that overall CS surface area and depth were significantly heritable, particularly in the superior regions, but less so in the inferior and central portions. Further, heritability in CS depth was altered as a function of acquisition of AG sounds. The collective results suggest that learning to produce AG sounds resulted in region-specific cortical reorganization within the inferior portion of the CS, a finding previously undocumented in chimpanzees or any nonhuman primate. SIGNIFICANCE STATEMENT Recent studies in chimpanzees (Pan troglodytes) have shown that some can learn to produce novel sounds by configuring different orofacial movement patterns and these sounds are used in communicatively relevant contexts. Here, we examined the neuromorphological correlates in the production of these sounds in chimpanzees. We show that chimpanzees that have learned to produce these sounds show significant differences in central sulcus (CS) morphology, particularly in the inferior region. We further show that overall CS morphology and regions within the superior portion are significantly heritable, whereas central and inferior portions of the CS are not. The collective findings suggest chimpanzees exhibit cortical plasticity in regions of the brain that were central to the emergence of speech functions in humans.
P194Serum uric acid as independent predictor of decreased number of circulating proangiogenic progenitor cells in asymptomatic coronary artery disease patients

Background: Serum uric acid (SUA) plays a pivotal role in the pathogenesis of cardiovascular diseases affecting xanthine oxidase pathway that contributes to the production of active oxygen species generation. Vascular oxidative stress and endothelial dysfunction contribute an injury of both cardiomyocytes and vascular endothelium that requires an activation of reparation processing. However, several types of circulating progenitor cells (CPCs) mediate an angiogenesis and tissue repair following injuries. Few studies have investigated the association of hyperuricemia with subclinical heart failure and atherosclerosis The aim of this study was to determine whether serum uric acid (SUA) is an independent predictor of the decreased number of CPC of in asymptomatic CAD patients. Design and Methods: 126 subjects (54 male), aged 48 to 62 years, and with asymptomatic CAD documented previously with angiography, and 25 healthy volunteers were enrolled in the study. Concentration of SUA was measured with enzymatic methods. The flow cytometric technique was used for predictably distinguishing cell subsets that depend on the expression of CD14, CD34, Tie-2, CD45, and CD309 (VEGFR2). Results: The analysis of the outcome obtained shows a trend of decrease of circulating CD45-CD34+ CMCs and a reduction of number of CMCs defined as CD14+CD309+ and CD14+CD309+Tie2+ in known asymptomatic CAD patients in comparison with healthy volunteers. Substantial correlations between number of both CD14+CD309+ and CD14+CD309+Tie2+ and conventional cardiovascular risk factors (hs-CRP, T2DM, SUA and hypertension) were found in the patient cohort. Univariate regression analysis showed that T2DM (RR = 1.21; 95% CI = 1.10–1.40; P = 0.008), hs-CRP > 2.54 mg/L (RR = 1.29; 95% CI = 1.12–1.58; P = 0.006), Agatston score index (RR = 1.2095% CI = 1.15–1.27; P = 0.034), SUA > 459 mmol / L (RR = 1.31; 95% CI = 1.12–1.49; P = 0.008) were factors that associated with decreased both CD14+CD309+ and CD14+CD309+Tie2+ CPCs. In multivariate model SUA> 459 mmol / L had independent predicted value (RR = 1.18; 95% CI = 1.04–1.27; P = 0.001) for decreased CPCs defined as CD14+CD309+ and CD14+CD309+Tie2+. Conclusion: Serum uric acid is independently associated with lowed circulating CD14+ CD309+ and CD14+CD309+Tei2+ cells in asymptomatic patients with known CAD.
Mapping of Functionally Characterized Cell Classes onto Canonical Circuit Operations in Primate Prefrontal Cortex

Microcircuits are composed of multiple cell classes that likely serve unique circuit operations. But how cell classes map onto circuit functions is largely unknown, particularly for primate prefrontal cortex during actual goal-directed behavior. One difficulty in this quest is to reliably distinguish cell classes in extracellular recordings of action potentials. Here we surmount this issue and report that spike shape and neural firing variability provide reliable markers to segregate seven functional classes of prefrontal cells in macaques engaged in an attention task. We delineate an unbiased clustering protocol that identifies four broad spiking (BS) putative pyramidal cell classes and three narrow spiking (NS) putative inhibitory cell classes dissociated by how sparse, bursty, or regular they fire. We speculate that these functional classes map onto canonical circuit functions. First, two BS classes show sparse, bursty firing, and phase synchronize their spiking to 3–7 Hz (theta) and 12–20 Hz (beta) frequency bands of the local field potential (LFP). These properties make cells flexibly responsive to network activation at varying frequencies. Second, one NS and two BS cell classes show regular firing and higher rate with only marginal synchronization preference. These properties are akin to setting tonically the excitation and inhibition balance. Finally, two NS classes fired irregularly and synchronized to either theta or beta LFP fluctuations, tuning them potentially to frequency-specific subnetworks. These results suggest that a limited set of functional cell classes emerges in macaque prefrontal cortex (PFC) during attentional engagement to not only represent information, but to subserve basic circuit operations.
Eliminating Direction Specificity in Visuomotor Learning

The generalization of learning offers a unique window for investigating the nature of motor learning. Error-based motor learning reportedly cannot generalize to distant directions because the aftereffects are direction specific. This direction specificity is often regarded as evidence that motor adaptation is model-based learning, and is constrained by neuronal tuning characteristics in the primary motor cortices and the cerebellum. However, recent evidence indicates that motor adaptation also involves model-free learning and explicit strategy learning. Using rotation paradigms, here we demonstrate that savings (faster relearning), which is closely related to model-free learning and explicit strategy learning, is also direction specific. However, this new direction specificity can be abolished when the participants receive exposure to the generalization directions via an irrelevant visuomotor gain-learning task. Control evidence indicates that this exposure effect is weakened when direction error signals are absent during gain learning. Therefore, the direction specificity in visuomotor learning is not solely related to model-based learning; it may also result from the impeded expression of model-free learning and explicit strategy learning with untrained directions. Our findings provide new insights into the mechanisms underlying motor learning, and may have important implications for practical applications such as motor rehabilitation. SIGNIFICANCE STATEMENT Motor learning is more useful if it generalizes to untrained scenarios when needed, especially for sports training and motor rehabilitation. However, as a form of motor learning, motor adaptation is typically direction specific. Here we first show that savings with motor adaptation, an index for model-free learning and explicit strategy learning in motor learning, is also direction specific. However, the participants' additional exposure to untrained directions via an irrelevant gain-learning task can enable the complete generalization of learning. Our findings challenge existing models of motor generalization and may have important implications for practical applications.
Phenotypic variability and therapeutic implications of Candida species in patients with oral lichen planus

We investigated the prevalence and phenotypic variation of Candida species in oral lichen planus (OLP) and the therapeutic implications of our findings. Eighty patients with clinically and histopathologically confirmed cases of OLP (64 non-erosive, 16 erosive) and a control group of 80 healthy individuals with no predisposing factors for oral candidiasis were examined for evidence of Candida infection. Oral swabs and smears were obtained for cytology and culture. Identification, speciation and antifungal susceptibility tests of Candida isolates were performed using an automated microbial identification system. Fifty percent of erosive OLP cases, 28% of non-erosive cases and none of the controls showed evidence of Candida. Candida albicans was found predominantly in non-erosive OLP, while other Candida species were predominate in erosive OLP. Non-Candida albicans isolates (C. glabrata, C. krusei) were resistant to the commonly used antifungals, clotrimazole and fluconazole. Candida infection is common in cases of OLP. We recommend antifungal sensitivity testing prior to antifungal therapy for the erosive form of OLP.