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How should consumers sequence the different stimuli they consume: cluster each stimulus together, or intermix them to break things up? Surprisingly, prior literature has provided little insight into this question, even though consumers face it on a regular basis. We propose that clustering each stimulus type together can prolong enjoyment (vs. intermixing the types). Six studies confirm that clustering slows hedonic decline, and process evidence shows this happens because clustering leads people to attend more to the different details offered by a stimulus during repeated exposures. We also establish two boundary conditions for this effect: clustering does not slow hedonic decline in the presence of regular intervening distractions, or for impoverished stimuli lacking rich details. The present work is among the first to examine the interplay of consumption sequence and hedonic decline, and the findings provide consumers and firms with practical guidance on how to consider sequencing experiences to enjoy them longer. [ABSTRACT FROM AUTHOR]

Key points Physiologists often express the change in the value of a measurement made on two occasions as a ratio of the initial value. This is usually motivated by an assumption that the absolute change fails to capture the true extent of the alteration that has occurred in attaining the final value – if there is initial variation among individual cases. While it may appear reasonable to use ratios to standardize the magnitude of change in this way, the perils of doing so have been widely documented. Ratios frequently have intractable statistical properties, both when taken in isolation and when analysed using techniques such as regression. A new method of computing a standardized metric of change, based on principal components analysis (PCA), is described. It exploits the collinearity within sets of initial, absolute change and final values. When these sets define variables subjected to PCA, the standardized measure of change is obtained as the product of the loading of absolute change onto the first principal component (PC1) and the eigenvalue of PC1. It is demonstrated that a sample drawn from a population of these standardized measures: approximates a normal distribution (unlike the corresponding ratios); lies within the same range; and preserves the rank order of the ratios. It is also shown that this method can be used to express the magnitude of a physiological response in an experimental condition relative to that obtained in a control condition. The intractable statistical properties of ratios and the perils of using ratios to standardize the magnitude of change are well known. A new method of computing a standardized metric, based on principal components analysis (PCA), is described, which exploits the collinearity within sets of initial, absolute change and final values. A sample drawn from a population of these PCA‐derived measures: approximates a normal distribution (unlike the corresponding ratios); lies within the same range as the ratios; and preserves the rank order of the ratios. The method can also be applied to express the magnitude of a physiological response in an experimental condition relative to a control condition. [ABSTRACT FROM AUTHOR]

The delicate balance between discrimination and generalization of responses is crucial for survival in our ever-changing environment. In particular, it is important to understand how stimulus discrimination affects the level of stimulus generalization. For example, when we use non-differential training for Pavlovian eyeblink conditioning to investigate generalization of cerebellarrelated eyelid motor responses, we find generalization effects on amount, amplitude and timing of the conditioned responses. However, it is unknown what the generalization effects are following differential training. We trained mice to close their eyelids to a 10 kHz tone with an air-puff as the reinforcing stimulus (CS+), while alternatingly exposing them to a tone frequency of either 4 kHz, 9 kHz or 9.5 kHz without the air-puff (CS-) during the training blocks. We tested the generalization effects during the expression of the responses after the training period with tones ranging from 2 kHz to 20 kHz. Our results show that the level of generalization tended to positively correlate with the difference between the CS+ and the CS- training stimuli. These effects of generalization were found for the probability, amplitude but not for the timing of the conditioned eyelid responses. These data indicate the specificity of the generalization effects following differential versus non-differential training, highlighting the relevance of discrimination learning for stimulus generalization. [ABSTRACT FROM AUTHOR]

Extending lactation length reduces the frequency of critical calving events for the cow and herewith reduces the frequency of periods with increased risk for health problems. Moreover, breeding is postponed until a moment later in lactation, which is associated with better conception rates and less days open after start of the breeding period in most studies. Potential risks of an extended lactation are that milk yield of cows at the end of the lactation may be too low which may lead to cows being overconditioned at the end of the extended lactation. Therefore, extending lactation length might not fit every cow. Individual cow characteristics like parity, milk yield level, or body condition determine the response of the cow to an extended lactation. These individual cow characteristics can be used in customized management strategies to optimize lactation length for individual cows. Customized lactation length for individual cows could limit the impact at herd level of disadvantages concerning milk losses and overconditioning and maintain benefits for improved cow health and fertility, reduced number of surplus calves and increased work satisfaction for the farmer. In conclusion, extending lactation length has interesting perspectives for health and fertility of high‐producing dairy cows, although questions remain concerning management approaches to support lactation persistency of cows with an extended lactation, and consequences for calf health and development. Moreover, ongoing studies aim to develop decision support tools to select individual cows for a specific lactation length. [ABSTRACT FROM AUTHOR]

Fear‐related psychopathologies, such as post‐traumatic stress disorder, are linked to dysfunction in neural circuits that govern fear memory and arousal. The lateral hypothalamus (LH) and zona incerta (ZI) regulate fear, but our understanding of the precise neural circuits and cell types involved remains limited. Here, we examined the role of relaxin family peptide receptor 3 (RXFP3) expressing cells in the LH/ZI in conditioned fear expression and general arousal in male RXFP3‐Cre mice. We found that LH/ZI RXFP3+ (LH/ZIRXFP3) cells projected strongly to fear learning, stress, and arousal centres, notably, the periaqueductal grey, lateral habenula, and nucleus reuniens. These cells do not express hypocretin/orexin or melanin‐concentrating hormone but display putative efferent connectivity with LH hypocretin/orexin+ neurons and dopaminergic A13 cells. Following Pavlovian fear conditioning, chemogenetically activating LH/ZIRXFP3 cells reduced fear expression (freezing) overall but also induced jumping behaviour and increased locomotor activity. Therefore, the decreased freezing was more likely to reflect enhanced arousal rather than reduced fear. Indeed, stimulating these cells produced distinct patterns of coactivation between several motor, stress, and arousal regions, as measured by Fos expression. These results suggest that activating LH/ZIRXFP3 cells generates brain‐wide activation patterns that augment behavioural arousal. [ABSTRACT FROM AUTHOR]

During the first half of the twentieth century, ethnic Mexican beet workers in Colorado endured a daunting array of challenges that included dismal housing, meager wages, and a family labor system that forced children as well as adults to labor relentless hours in the sugar-beet fields. In response to these conditions, Catholic reformer Thomas Mahony promoted a vision of the American economy in which marginalized populations like the beet laborers would take their rightful place as healthy consumers and effective family providers. His vision was shaped by the Catholic social justice movement of the Progressive Era, as well as by a career in agricultural consumerism. From 1910 to 1913, for example, he served as director of exhibits for the Chicago Land Show, a position that immersed him in a world that marketed farm lands as idealized consumer commodities while rendering invisible the struggles of propertyless farm workers. When Mahony began his reform career a decade later, he strove to do exactly the opposite: make beet field workers as visible as possible in his blueprint for a vigorous consumerist democracy. At the same time, however, Mahony's intense fears of radicalism overshadowed his reform impulses, reflecting profound tensions within the Catholic reform ethos that shaped him: a yearning for spiritual and social regeneration in constant battle with a dread of social upheaval. Mahony's story therefore helps to illuminate the considerable potential of twentieth-century religious reform, even as his obsessive fears highlight the perils of antiradicalism in the U.S. West. [ABSTRACT FROM AUTHOR]

Extensive antibiotic use in the poultry industry has given rise to concerns of the proliferation and potential zoonotic transmission of antimicrobial-resistant pathogens. To mitigate the extent of antibiotic dosing, probiotics have been proposed as an alternate means of enhancing chick immune function by boosting host defense peptide (HDP) production. This study measured chick immune response to in ovo supplementation of a commercial poultry probiotic when subsequently exposed to a mimicked viral threat using polyinosinic-polycytidylic acid (poly(I:C)). To assess systemic immune responses to these conditions, real-time PCR was conducted to measure changes in expression of five immune-related genes in the spleen: TLR-3, AvBD-2, IFN-a, IFN-b, and IL-6. The chicks that received only the probiotic treatment saw a downregulation of TLR-3 (p50.0013) and an upregulation of AvBD-2 (p50.0105). The expression of IL-6 tended towards downregulation (p50.06) with a potential interaction between the probiotic and poly(I:C) treatments (p50.0794). Upregulation of AvBD-2 indicates a higher basal output of the chick's innate immune system upon early exposure to probiotics. These results suggest that enhanced systemic immune response in chicks can be achieved through early application of probiotics and is occurring through immunomodulation pathways that have not been fully elucidated. [ABSTRACT FROM AUTHOR]

Home appliances such as residential air conditioners are based on the variable speed drives for AC motors such as IPMSM and IM. These variable speed drives always require the simple and low‐cost system configurations without the large electrolytic capacitors, reactors, and power devices that consist of PFC converters. This paper surveys and analyzes the proposed and advanced control techniques to achieve high input power factor and sinusoidal source current control in electrolytic capacitor‐less inverters. The investigated control methods consist of control algorithms based on the energy flow between input and output of the electrolytic capacitor‐less inverter, and all of them are useful as high‐power factor control methods for compressor drive motors such as air conditioners. Moreover, these techniques realize the variable speed drives for AC motors to meet power supply harmonics regulations (IEC61000‐3‐2). © 2024 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

This paper provides a discourse analysis of 12 Swedish sexuality education texts intended for preschool practitioners and published between 1969 and 2021. Using Fairclough's framework, we identify three discourses about children's sexual play in relation to children's sexual agency in the texts: child sexuality as encouraged and entangled with adult sexuality; child sexuality as conditioned by what is perceived as normal or abnormal in children; and child sexuality as repressed. These three discourses mainly appear chronologically, but also overlap and connect with one another. When analysis begins from children's position and a theoretical understanding of children's and adults' agency as interdependent, it becomes possible to see how the child is construed as agentic, and how the adult role changes from encouraging sexual play to regulating and monitoring behaviour so that it does not occur. Over time, discourse on young children's sexual play has changed our understanding of both adults and children. Adults are increasingly construed as less knowledgeable in relation to young children's sexuality, and young children have become understood as more dangerous and in need of having their sexuality constrained and civilised. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to develop a green, economical and efficient ultrasonic-/microwave assisted extraction (UMAE) process for the extraction of anthocyanins. Design/methodology/approach: After optimizing the extraction conditions by response surface methodology, three assays including DPPH, ABTS·+, FRAP were applied to analyze the antioxidant activity of the extracted anthocyanins. The stability under different temperatures, reductant concentrations and pHs was also discussed. The components of anthocyanins in blueberry were analyzed by HPLC-QTOF-MS2. Findings: The optimal extraction parameters were ultrasonic power of 300 W, microwave power of 365.28 W and solid–liquid ratio of 30 (g/mL). The possible structures can be speculated as Delphinidin-3-O-galactoside, Delphinidin, Petunidin, Delphinidin-3-O-glucoside, Petunidin-3-O-glucoside, Cyanidin-3-O-glucoside. The results demonstrated that the UMAE can improve the yield of anthocyanins in shorter extraction time with higher activity. Originality/value: The present study may provide a promising and feasible route for extracting anthocyanins from blueberries and studying their physicochemical properties, ultimately promoting the utilization of blueberry anthocyanins. [ABSTRACT FROM AUTHOR]

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• The estrous cycle does not affect the innate startle but influences fear learning. • In high-anxious females, hormonal increase during proestrus reduces learned fear. • In BLA, 5-HT reduces potentiated startle by combining with estrous cycle hormones. • In BLA, 5-HT interacts with female hormones likely through 5-HT1A receptors. • DPAG stimulation of high-anxious females increases the response to stressful stimuli. Despite significant advances in the study of fear and fear memory formation, little is known about fear learning and expression in females. This omission has been proven surprising, as normal and pathological behaviors are highly influenced by ovarian hormones, particularly estradiol and progesterone. In the current study, we investigated the joint influence of serotonin (5-HT) neurotransmission and estrous cycle phases (low or high levels of estradiol and progesterone) on the expression of conditioned fear in a group of female rats that were previously divided according to their response to stressful stimuli into low or high anxiety-like subjects. The baseline amplitude of the unconditioned acoustic startle responses was high in high-anxiety female rats, with no effect on the estrous cycle observed. Data collected during the proestrus-estrus phase revealed that low-anxiety rats had startle amplitudes similar to those of high-anxiety rats. It is supposed that high-anxiety female rats benefit from increased estradiol and progesterone levels to achieve comparable potentiated startle amplitudes. In contrast, female rats experienced a significant decrease in hormone levels during the Diestrus phase. This decrease is believed to play a role in preventing them from displaying a heightened startle response when faced with strongly aversive stimuli. Data collected after 5-HT and 8-OH-DPAT were administered into the basolateral nuclei and dorsal periaqueductal gray suggest that 5-HT neurotransmission works with progesterone and estrogen to reduce startle potentiation, most likely by activating the serotonin-1A receptor subtype. [ABSTRACT FROM AUTHOR]

Technologies capable of noninvasively sampling different locations in the gut upstream of the colon will enable new insights into the role of organ‐specific microbiomes on human health. Herein, an ingestible pill for the sampling of gut lumen based on one of the earliest hydraulic machines known as an Archimedes screw is reported. The design contains twisted wires as Archimedes screw driven by a motor, wirelessly activated using a magnet. The sampling performance of the screw‐pump pill is characterized using realistic in vitro models and validated in vitro using E. coli expressing different fluorescent proteins. The use of the Archimedes screw enables the pill to sample the dense GI environment. The pill is also tested ex vivo in the pig intestine and in vivo in pigs. Herein, the results show that the bacterial populations recovered from the pill's chamber closely resemble the targeted bacterial population of the microenvironment to which the pill is exposed. Such ingestible devices have the potential to revolutionize the understanding of the spatial diversity of the gut microbiome and its response to medical conditions and treatments. [ABSTRACT FROM AUTHOR]

AbstractThe elbow is presented in pressurized tubular structures as a connecting element, generally subjected to bending moments either out-of-plane or in-plane, in closure or opening. Another mode of bending moment that can also occur in these tubular structures is the combined bending moment between out-of-plane and in-plane in closure, or out-of-plane and in-plane in opening. In this work, to better present the potential severity caused by this loading mode, an elbow structure attached by straight tubular sections made of X60 steel is analyzed and its damage under this combined bending moment with orientations between the plane and out-of-plane of the structure is discussed. A reinforcement proposal will be made in the second part of this work. Indeed, the structure is pretreated thermally at the elbow, resulting in a graded structure along the thickness with two different material constituents: the base metal and the thermally affected zone (HAZ). Based on the concept of Functionally Graded Materials (FGM), the gradation is by volume fraction between the base metal and the HAZ, following a power law function of a volume fraction index (n). This graded property is introduced along the thickness by finite element layers. The elastic-plastic behavior of the HAZ-base metal mixture is modeled using the Voce model and the Von Mises equivalent stress flow theory. Using the XFEM technique(extended finite element method), the damage of the pressurized and thermally treated structure under a combined out-of-plane bending moment shows that these parameters condition the response and the level of damage. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsResultsConclusionsULK4 is an established candidate gene for mental disorders and antipsychotic treatment response. We investigated the association of functional genetic variation at the ULK4 locus with the human extended dopaminergic reward system using fMRI during the performance of a well-established reward paradigm.Two hundred and thirty-four patients were included in this study. Association of genetic variation in the ULK4 gene with reward system functioning were determined using the Desire-Reason-Dilemma (DRD) paradigm which allows to assess brain activation in response to conditioned reward stimuli.Variant prioritisation revealed the strongest functional signatures for the ULK4 variant rs17215589, coding for amino acid exchange Ala715Thr. For rs17215589 minor allele carriers, we detected increased activation responses to conditioned reward stimuli in the ventral tegmental area, nucleus accumbens and several cortical brain regions of the extended reward system.Our findings provide further evidence in humans that genetic variation in ULK4 may increase the vulnerability to mental disorders, by modulating the extended reward system function. Future studies are needed to confirm the modulation of the extended reward system by ULK4 and to specify the role of this mechanism in the pathogenesis of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Resurgence can be defined as increases in previously reinforced and subsequently extinguished target responding when conditions for an alternative response worsen. Worsening of alternative conditions, such as extinction, has been linked to relapse of clinically relevant behavior. Preclinical researchers have evaluated whether punishing target responses while differentially reinforcing an alternative response could reduce resurgence when conditions are worsened with extinction, with mixed results. In the present investigation, we systematically replicated this line of research with human participants recruited via crowdsourcing, using response cost as punishment. During Phase 1, we reinforced target responses with 100 points per delivery, exchangeable for money. During Phase 2, we reinforced alternative responses, discontinued point reinforcement for target responses, and parametrically manipulated across groups the magnitude of point loss (1, 100, 320, or 1,000 points) contingent on target responses. During Phase 3, we tested for resurgence by extinguishing target and alternative responses. Added punishment systematically decreased target responding during Phase 2 but did not influence resurgence during Phase 3. With a meta‐analysis, we compared our findings with existing research examining a range of punishers and species. The results of the meta‐analysis comport with the present findings, suggesting that the inclusion of punishment reduces target responding during DRA but, overall, has no systematic effects on resurgence. [ABSTRACT FROM AUTHOR]

In a number of species, including humans, perceived outgroup threat can promote ingroup cohesion. However, the distribution and selection history of this association across species with varied intergroup relations remains unclear. Using a sample of 8 captive groups (N = 43 individuals), we here tested whether bonobos, like chimpanzees, show more affiliative ingroup behaviour following perception of outgroup cues (unfamiliar male long-distance vocalisations). We used comparable methods to our previous study of captive chimpanzees, and found that, although weaker, there was an association for more frequent social grooming in response to the outgroup condition than the control condition, alongside more alert posture and increased self-directed behaviour. This provides preliminary evidence for an ancestral origin to the proximate association between outgroup cues and ingroup cohesion, at least prior to the Pan-Homo split, and suggests the presence of intergroup competition in our last common ancestor. [ABSTRACT FROM AUTHOR]

AbstractInteraction screening for high-dimensional data is a challenging issue, especially for the strongly correlated predictors. A new two-stage interaction screening procedure based on the projected distance correlation is proposed when the predictors are highly correlated. To remove the confounding effect from the target variable that is induced by its correlated variables, we project the predictors and responses onto a conditional set. Our method can successfully identify important variables when the variables are highly correlated, and it can also identify variables that make a contribution to the response conditionally but not marginally. Moreover, our method is computationally efficient and simple, generally applicable without the requirement of the heredity assumption. Theoretical results show that the proposed method can yield the sure screening property. Simulation studies and real data analysis demonstrate the utility and validity of our method. [ABSTRACT FROM AUTHOR]

AbstractSteel tubular structures in pipelines, or those connections such as concentric reductions, reduced tees, and elbows, all differ in their response to loading, they are sometimes solicited to complex and combined loads, which accumulate with the internal pressure to their solicitation cause in certain situation their damage, the objective in this analysis is to numerically predict the mechanical behavior until damage of a complete tubular structure, which contains the connecting elements of an elbow and a reduced tee attached to each other by straight tubular parts, this structure, by its standardized dimensions presents a real design of a main pipeline spigot for a possible supply line, this tubular structure is analyzed in this work under these real pressure conditions, and combined loads probably coming from the weight of a valve, or a pipe flanged to this spigot element or other, in X60 steel This structure is solicited under different combined modes of loading. The elastic-plastic behavior is under Voce’s model and Von Mises’ equivalent stress flow theory, the damage of the structure by crack initiation and propagation is ensured by using the XFEM technique, the response up to damage of the structure is evaluated under the effect of the parameters of the combined loading mode, we present by angular bendingrotation moment curves that these parameters clearly condition the response and the level of damage. [ABSTRACT FROM AUTHOR]

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency Aβ-mediated response, considered tactile, and a longer-latency Aδ-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to Aβ tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of Aβ fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50–150 ms). The current required to elicit the NWR was higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the Aβ-mediated tuning fork sensation was lost while Aδ-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current, the reflex could not be evoked despite a two-fold increase in the pre-block current and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of Aβ-fiber inputs in pain and reflex signaling. [ABSTRACT FROM AUTHOR]

Understanding how sensory processing demands affect the ability to ignore task‐irrelevant, loud auditory stimuli (LAS) during a task is key to performance in dynamic environments. For example, tennis players must ignore crowd noise to perform optimally. We investigated how practice affects this ability by examining the effects of delivering LASs during preparatory phase of an anticipatory timing (AT) task on the voluntary and reflexive responses in two conditions: lower and higher visual processing loads. Twenty‐four participants (mean age = 23.1, 11 females) completed the experiment. The AT task involved synchronizing a finger abduction response with the last visual stimulus item in a sequence of four Gabor grating patches briefly flashed on screen. The lower demand condition involved only this task, and the higher demand condition required processing the orientations of the patches to report changes in the final stimulus item. Our results showed that higher visual processing demands affected the release of voluntary actions, particularly in the first block of trials. When the perceptual load was lower, responses were released earlier by the LAS compared to the high‐load condition. Practice reduced these effects largely, but high perceptual load still led to earlier action release in the second block. In contrast, practice led to more apparent facilitation of eyeblink latency in the second block. These findings indicate that a simple perceptual load manipulation can impact the execution of voluntary motor actions, particularly for inexperienced participants. They also suggest distinct movement preparation influences on voluntary and involuntary actions triggered by acoustic stimuli. [ABSTRACT FROM AUTHOR]

Simple Summary: A better understanding of cattle behavioural responses during high environmental temperatures could be beneficial for the diagnosis of heat loads. In the current study, 24 Black Angus steers fed a finisher diet based on cereal grain or a substituted diet (8% of the grain replaced by an isoenergetic amount of lucerne hay) were exposed to hot conditions, and changes in their behavioural and physiological dynamics were assessed. Compared to the recovery period, hot conditions increased respiration rate and were associated with increased stepping behaviour, especially by left limbs. Cattle also increased the orientation of their heads downward, their ears backward, and their tail vertically or raised, and they reduced eating, grooming, and scratching during the heat load period. Changes in head, ear and tail position, breathing changes persisted during the heat load period, suggesting that these behaviours have diagnostic value. Cattle that were fed a diet based on the cereal grain stood for longer and were more likely to hold their ears backward and tail vertically, whereas those on the substituted diet were more likely to display axial ears and hold their head in a neutral position. We conclude that cattle have subtle changes in behaviour in response to hot conditions, which may be of value for diagnostic purposes. Cattle are increasingly exposed to hot temperatures as a result of climate change, and a better understanding of behavioural responses could be beneficial for the diagnosis of heat loads. The changes in the positioning of key body parts, feeding behaviour, body maintenance, and respiratory dynamics were assessed in 24 Black Angus steers individually exposed to hot conditions and fed a finisher diet based on cereal grain or a substituted diet (8% of the grain replaced by an isoenergetic amount of lucerne hay). Increased respiration rate during the heat load period, compared to the recovery period, was associated with increased stepping, especially by left limbs. Cattle also reduced eating, grooming, and scratching during the heat load period. The lowered head, backward ear, vertical or raised tail, and increased respiration rate and panting persisted in cattle during the heat load period. Cattle on the cereal grain diet stood for longer and were more likely to hold their ears backward and tail vertical than those on the substituted diet. We conclude that these behaviours could be used to detect animals that are most affected and that changing from a cereal-based diet to a substituted diet containing a higher amount of fibre, such as lucerne hay, can reduce hyperthermic behavioural responses to a heat load. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin condition characterized by a multifaceted pathophysiology that gives rise to diverse clinical manifestations. The management of AD remains challenging due to the suboptimal efficacy of existing treatment options. Nonetheless, recent progress in elucidating the underlying mechanisms of the disease has facilitated the identification of new potential therapeutic targets and promising drug candidates. In this review, we summarize the newest data, considering multiple connections between IL-22 and AD. The presence of circulating IL-22 has been found to correlate with the severity of AD and is identified as a critical factor driving the inflammatory response associated with the condition. Elevated levels of IL-22 in patients with AD are correlated with increased proliferation of keratinocytes, alterations in the skin microbiota, and impaired epidermal barrier function. Collectively, these factors contribute to the manifestation of the characteristic symptoms observed in AD. [ABSTRACT FROM AUTHOR]

To adapt to threats in the environment, animals must predict them and engage in defensive behavior. While the representation of a prediction error signal for reward has been linked to dopamine, a neuromodulatory prediction error for aversive learning has not been identified. We measured and manipulated norepinephrine release during threat learning using optogenetics and a novel fluorescent norepinephrine sensor. We found that norepinephrine response to conditioned stimuli reflects aversive memory strength. When delays between auditory stimuli and footshock are introduced, norepinephrine acts as a prediction error signal. However, temporal difference prediction errors do not fully explain norepinephrine dynamics. To explain noradrenergic signaling, we used an updated reinforcement learning model with uncertainty about time and found that it explained norepinephrine dynamics across learning and variations in temporal and auditory task structure. Norepinephrine thus combines cognitive and affective information into a predictive signal and links time with the anticipation of danger. [ABSTRACT FROM AUTHOR]

Human standing balance relies on the continuous monitoring and integration of sensory signals to infer our body's motion and orientation within the environment. However, when sensory information is no longer contextually relevant to balancing the body (e.g., when sensory and motor signals are incongruent), sensory-evoked balance responses are rapidly suppressed, much earlier than any conscious perception of changes in balance control. Here, we used a robotic balance simulator to assess whether associatively learned postural responses are similarly modulated by sensorimotor incongruence and contextual relevance to postural control. Twenty-nine participants in three groups were classically conditioned to generate postural responses to whole-body perturbations when presented with an initially neutral sound cue. During catch and extinction trials, participants received only the auditory stimulus but in different sensorimotor states corresponding to their group: 1) during normal active balance, 2) while immobilized, and 3) throughout periods where the computer subtly removed active control over balance. In the balancing and immobilized states, conditioned responses were either evoked or suppressed, respectively, according to the (in)ability to control movement. Following the immobilized state, conditioned responses were renewed when balance was restored, indicating that conditioning was retained but only expressed when contextually relevant. In contrast, conditioned responses persisted in the computer-controlled state even though there was no causal relationship between motor and sensory signals. These findings suggest that mechanisms responsible for sensory-evoked and conditioned postural responses do not share a single, central contextual inference and assessment of their relevance to postural control, and may instead operate in parallel. [ABSTRACT FROM AUTHOR]

In this article, we reflect on experiences of gender euphoria and do-it-yourself (DIY) queer joy during a collage-making workshop with an intergenerational group of 2SLGBTQIA+ participants and researchers. The workshop is part of a larger participatory visual research project called Pride/Swell±an initiative that has been bringing together queer and trans people from across Atlantic Canada to make art since 2020. During an in-person workshop with 40 participants in 2023, we made collages in response to the conditions which gave rise to pleasure, euphoria, and joy. Through our artmaking, participants and the project’s research team shared that joy often emerged through queer self-expression, chosen families and communities, and by having an affirming experience. We also found collage-making acted as a resistive practice and that too became an expression of joy. As scholarship begins to respond to the joy deficit in sociological research, our aim is to add to these conversations by exploring how participatory visual research production creates conditions for queer joy and euphoria to emerge. At the same time, we also highlight the moments during our workshop where queer joy failed – reminding us that queer joy, as praxis, needs to be further complicated and theorized. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study demonstrated neural encoding of incidental sensory regularities leading to modulation of cortical responses to both predictive and predicted sensory stimuli. As in the case of goal-directed behavior, such task-irrelevant predictive mechanisms might result from the brain's intrinsic drive of reducing uncertainty about state transition dynamics of the environment. Statistical learning of sensory patterns can lead to predictive neural processes enhancing stimulus perception and enabling fast deviancy detection. Predictive processes have been extensively demonstrated when environmental statistical regularities are relevant to task execution. Preliminary evidence indicates that statistical learning can even occur independently of task relevance and top-down attention, although the temporal profile and neural mechanisms underlying sensory predictions and error signals induced by statistical learning of incidental sensory regularities remain unclear. In our study, we adopted an implicit sensory conditioning paradigm that elicited the generation of specific perceptual priors in relation to task-irrelevant audio–visual associations, while recording Electroencephalography (EEG). Our results showed that learning task-irrelevant associations between audio–visual stimuli resulted in anticipatory neural responses to predictive auditory stimuli conveying anticipatory signals of expected visual stimulus presence or absence. Moreover, we observed specific modulation of cortical responses to probabilistic visual stimulus presentation or omission. Pattern similarity analysis indicated that predictive auditory stimuli tended to resemble the response to expected visual stimulus presence or absence. Remarkably, Hierarchical Gaussian filter modeling estimating dynamic changes of prediction error signals in relation to differential probabilistic occurrences of audio–visual stimuli further demonstrated instantiation of predictive neural signals by showing distinct neural processing of prediction error in relation to violation of expected visual stimulus presence or absence. Overall, our findings indicated that statistical learning of non-salient and task-irrelevant perceptual regularities could induce the generation of neural priors at the time of predictive stimulus presentation, possibly conveying sensory-specific information about the predicted consecutive stimulus. [ABSTRACT FROM AUTHOR]

A host of metabolic enzymes reversibly self‐assemble to form membrane‐less, intracellular filaments under normal physiological conditions and in response to stress. Often, these enzymes reside at metabolic control points, suggesting that filament formation affords an additional regulatory mechanism. Examples include cytidine‐5′‐triphosphate (CTP) synthase (CTPS), which catalyzes the rate‐limiting step for the de novo biosynthesis of CTP; inosine‐5′‐monophosphate dehydrogenase (IMPDH), which controls biosynthetic access to guanosine‐5′‐triphosphate (GTP); and ∆1‐pyrroline‐5‐carboxylate (P5C) synthase (P5CS) that catalyzes the formation of P5C, which links the Krebs cycle, urea cycle, and proline metabolism. Intriguingly, CTPS can exist in co‐assemblies with IMPDH or P5CS. Since GTP is an allosteric activator of CTPS, the association of CTPS and IMPDH filaments accords with the need to coordinate pyrimidine and purine biosynthesis. Herein, a hypothesis is presented furnishing a biochemical connection underlying co‐assembly of CTPS and P5CS filaments – potent inhibition of CTPS by glutamate γ‐semialdehyde, the open‐chain form of P5C. [ABSTRACT FROM AUTHOR]

In this paper, minimization of delamination effect on laminated composite plates using smart (piezoelectric and magnetostrictive) materials has been investigated. The static and dynamic responses of the smart composite plates with/without delamination have been obtained using the finite element method. The validation and comparison studies of the laminated composite plate have also been performed to show the level of accuracy of the presently adopted model by solving a few examples related to static and frequency cases. For control and minimization of delamination effect, smart materials have been introduced at the various layers of the laminated panel. Further, the influence of delamination size, location, orientation scheme, aspect ratio, modular ratio and different boundary conditions on the dynamic response of the smart delaminated composite plate has been analyzed. Finally, optimization study has been carried out to find the optimal value of these parameters by minimizing the difference between the frequency responses. Here, two optimization algorithms TLBO and PSO have been considered to carry out the optimization study and results obtained from both techniques are validated and compared. [ABSTRACT FROM AUTHOR]

[Objective] The aims of this study are to understand the vegetation ecological status and dissect the factors affecting vegetation change. [Methods] Based on the MOD13A3 NDVI data and meteorological data, the spatiotemporal variation of NDVI and its response to hydrothermal conditions were analyzed by using the Theil-Sen median trend analysis. Mann-Kendall test. Hurst index and correlation analysis in order to provide a scientific basis for ecological conservation and rational resource allocation in this region. [Results] During the study period. NDVI in Inner Mongolia increased significantly (p<0.01), and its spatial distribution was higher in the east and lower in the west. In most regions, NDVI showed an increasing trend. The growth rate of cultivated land was the largest and the proportion of cultivated land area with increasing trend was also the largest. The change of NDVI was relatively stable with low average coefficient variation, and the stability of forestland was the best. In the future, the change trend of NDVI in Inner Mongolia will be dominated by reverse sustainability, and the proportion of reverse sustainability and sustainability area will be 76.51% and 23.49%. The areas with negative correlation between NDVI and temperature accounted for 78.25% of the regions, and the areas with extremely significant and significant negative correlation between NDVI and temperature accounted for 19.92% of the regions. The areas with positive correlation between NDVI and precipitation and soil moisture accounted for 93.16% and 93.53%, and the areas with extremely significant and significant positive correlation between NDVI and precipitation and soil moisture accounted for 51.37% and 55.85%, respectively. [Conclusion] The overall vegetation ecology in Inner Mongolia showed a tendency towards improvement during the study period, and the vegetation ecology may deteriorate in the future. Soil moisture was the major effective factor on vegetation growth in Inner Mongolia. [ABSTRACT FROM AUTHOR]

The McMurdo Dry Valleys in Southern Victoria Land, Antarctica, are known for their extreme aridity, cold, and nutrient‐poor conditions. These valleys provide a valuable comparison to environments on Mars. The survival of microorganisms in these areas hinges on their ability to withstand dehydration due to the limited availability of liquid water. Some microorganisms have adapted to survive extended periods of metabolic inactivity and dehydration, a physiological response to the harsh conditions in which they exist. This adaptation is significant for astrobiology studies as it allows for testing the resilience of microorganisms under extraterrestrial conditions, exploring the boundaries and potential for life beyond Earth. In this study, we examined the survivability, metabolic activity, cellular membrane integrity, and ultrastructural damage of Cryomyces antarcticus, a eukaryotic organism used for astrobiological studies, following two dehydration processes. We conducted a fast dehydration process, simulating what happens on the surface of Antarctic rocks under typical environmental conditions, and a slow dehydration process, which is commonly used in astrobiological experiments. Our findings revealed a higher percentage of damaged cells following slow dehydration treatments, confirming that rapid dehydration reflects the adaptability of microorganisms to respond to sudden and drastic changes in the Antarctic environment. [ABSTRACT FROM AUTHOR]

The present design guidelines for rigid-faced (RF) geosynthetic reinforced soil (GRS) walls recommend a minimum toe embedment depth as a geometric requirement. The toe condition effect is ignored in these designs. Development of tools for serviceability design and refinement of present design methods require a complete understanding of the toe condition's role. Finite element analysis of RF-GRS walls is carried out in this study for different toe conditions, such as fixed, rotating and frictional toe, representing different construction methods. The analysis of fixed toe conditions shows 3–5 times lesser deformations and 10–20 times lesser loads in bottom reinforcements compared to other toe conditions. Reduced reinforcement stiffness at the bottom of the wall for a fixed toe condition has a negligible effect on deformations. The fascia experiences high bending moments at the bottom of the wall with fixed toe conditions. Frictional toe condition mobilizes both sliding and rotation modes of wall deformations. It also shows toe force increasing by 5–20% for embedment depth increase by 6 times. The results for rotating toe with restrained sliding show higher top displacements than other toe conditions. The use of stiffer reinforcements at the wall top reduces such rotations. Possible design concepts to impart toe fixity in the field are also discussed. [ABSTRACT FROM AUTHOR]

Objective: This study proposed a model to predict passenger motion sickness under the presence of a visual-vestibular conflict and assessed its performance with respect to previously recorded experimental data. Background: While several models have been shown useful to predict motion sickness under repetitive motion, improvements are still desired in terms of predicting motion sickness in realistic driving conditions. There remains a need for a model that considers angular and linear visual-vestibular motion inputs in three dimensions to improve prediction of passenger motion sickness. Method: The model combined the subjective vertical conflict theory and human motion perception models. The proposed model integrates visual and vestibular sensed 6 DoF motion signals in a novel architecture. Results: Model prediction results were compared to motion sickness data obtained from studies conducted in motion simulators as well as on-road vehicle testing, yielding trends that are congruent with observed results in both cases. Conclusion: The model demonstrated the ability to predict trends in motion sickness response for conditions in which a passenger performs a task on a handheld device versus facing forward looking ahead under realistic driving conditions. However, further analysis across a larger population is necessary to better assess the model's performance. Application: The proposed model can be used as a tool to predict motion sickness under different levels of visual-vestibular conflict. This can be leveraged to design interventions capable of mitigating passenger motion sickness. Further, this model can provide insights that aid in the development of passenger experiences inside autonomous vehicles. [ABSTRACT FROM AUTHOR]

Among several hydrological processes, river flow is an essential parameter that is vital for different water resources engineering activities. Although several methodologies have been adopted over the literature for modeling river flow, the limitation still exists in modeling the river flow time series curve. In this research, a functional quantile autoregressive of order one model was developed to characterize the entire conditional distribution of the river flow time series curve. Based on the functional principal component analysis, the regression parameter function was estimated using a multivariate quantile regression framework. For this purpose, hourly scale river flow collected from three rivers in Australia (Mary River, Lockyer Valley, and Albert River) were used to evaluate the finite‐sample performance of the proposed methodology. A series of Monte‐Carlo experiments and historical data sets were examined at three stations. Further, uncertainty analysis was adopted for the methodology evaluation. Compared with the existing methods, the proposed model provides more robust forecasts for outlying observations, non‐Gaussian and heavy‐tailed error distribution, and heteroskedasticity. Also, the proposed model has the merit of predicting the intervals of future realizations of river flow time series at the central and non‐central locations. The results confirmed the potential for predicting the river flow time series curve with a high level of accuracy in comparison with the benchmark existing functional time series methods. Plain Language Summary: This paper proposes a functional quantile autoregressive model of order one, which is used to predict the entire distribution of the realizations of river flow time series curve. The proposed model allows modeling the conditional quantiles of the response variable as a function of its past values of it. The proposed method for historical river flow curves is an excellent alternative to existing mean regression methods at the 0.5 quantile level (median regression). Also, as an advantage over existing methods, it offers a more thorough explanation of the connection among previous and future realizations of river flow curves at various quantile levels, providing a more extensive understanding of the relationship. Moreover, this feature of the proposed method allows for the effortless generation of pointwise prediction intervals for future realizations of river flow curves. The numerical results obtained by Monte Carlo experiments and empirical data analyses exhibit that, compared with existing methods, the proposed method produces competitive or even better forecasting results. The results also indicate that the future realizations of the river flow measurements are well covered by the prediction intervals constructed by the proposed method. Key Points: Predicting the mean and extreme values of the river flow curve is important for various applications in water resources managementThe FQAR(1) allows predicting the entire distribution of future realizations of the river flow curve as a function of its past values of itNumerical results based on river flow measurements collected from the Australia Continent confirmed the potential of the FQAR(1) [ABSTRACT FROM AUTHOR]

The parietal P300 wave of event‐related potentials (ERPs) has been associated with various psychological operations in numerous laboratory tasks. This study aims to decompose the P3 wave of ERPs into subcomponents and link them with behavioral parameters, such as the strength of stimulus–response (S‐R) links and GO/NOGO responses. EEGs (31 channels), referenced to linked ears, were recorded from 172 healthy adults (107 women) who participated in two cued GO/NOGO tasks, where the strength of S‐R links was manipulated through instructions. P300 waves were observed in active conditions in response to cues, GO/NOGO stimuli, and in passive conditions when no manual response was required. Utilizing a combination of current source density transformation and blind source separation methods, we decomposed the P300 wave into two distinct components, purportedly originating from different parts of the parietal lobules. The amplitude of the parietal midline component (with current sources around Pz) closely mirrored the strength of the S‐R link across proactive, reactive, and passive conditions. The amplitude of the lateral parietal component (with current sources around P3 and P4) resembled the push–pull activity of the output nuclei of the basal ganglia in action selection‐inhibition operations. These findings provide insights into the neural mechanisms underlying action selection processes and the reactivation of S‐R links. We aimed to associate subcomponents of P3 waves in event‐related potentials with behavioral parameters in cued GO/NOGO tasks. The parietal midline component was shown to reflect the strength of stimulus–response (S‐R) links across proactive, reactive, and passive conditions. The lateral parietal component mirrored basal ganglia activity in action selection. These results illuminate neural mechanisms for S‐R links and action selection operations. [ABSTRACT FROM AUTHOR]

Vacuolar processing enzymes (VPEs) are important proteases for the processing and maturation of vacuolar proteins. The VPEs in model plant Arabidopsis have been well researched. However, less is known about this gene family in the crop plant soybean (Glycine max). This study performed genome-wide identification of soybean VPE genes and 7 members were isolated. Their sequence information was firstly collected, and then phylogenetic relationship, chromosome distribution, gene duplication, conserved motifs as well as gene structure were analyzed for further insight into this gene family. The 7 GmVPEs were located on 6 chromosomes, and their encoding proteins were classified into three groups. Collinearity analysis indicated that 5 GmVPEs were involved in gene duplication events and they have undergone purifying selection during evolution. Conserved motif and gene structure analysis revealed the similarity and diversity among the sequences of different GmVPEs. To uncover the possible functions of soybean VPEs, cis-acting elements and TF binding sites on their promoters were identified, the results implied soybean VPE genes might participate in various biological processes and transcriptional regulation pathways. Through analyzing the RNA-Seq data, expression of the soybean VPE genes were found to exhibit spatiotemporal differences, with some being expressed almost ubiquitously, while others being expressed uniquely in seed. Finally, the expression profile analysis indicated that two VPE members, namely GmVPE4 and GmVPE7, likely play key roles in plant response to both biotic and abiotic stresses. [ABSTRACT FROM AUTHOR]

Flash drought (FD) has attracted much attention due to its severe stress on vegetation ecosystems. Yet to date, the impacts of FD on vegetation ecosystems in different regions have not been fully evaluated and explored, especially for ecologically fragile areas. In this study, we identified the FD events in the Loess Plateau from 2000 to 2023 based on the attenuation rate in soil moisture percentile over time. The evolution process of FD, the driving roles of meteorological conditions and the responses of different vegetation types to FD were explored by vegetation indicators such as solar-induced chlorophyll fluorescence (SIF), SIFyield, SIF-RCI, etc. The results showed that FD events were predominantly concentrated in wetter areas with dense vegetation, with the highest frequency being 29. Meteorological factors contributed differently to the occurrence and development of FD. The responses of vegetation to FD were not only related to vegetation types (cropland was more sensitive to FD than forest and grassland) but were also significantly influenced by background climate. The SIFyield anomaly of vegetation was more sensitive than SIF anomaly and SIF-RCI. The results advance our understanding of the formation mechanisms of FD and facilitate the exploration of vegetative photosynthetic responses to FD. [ABSTRACT FROM AUTHOR]

Maurice Blanchot’s itinerary as a critic and writer is marked by a transformation occurring around the beginning of WW2, when Blanchot abandoned right-wing political journalism to focus on literature. His criticism and narrative fictions from the 1940s elaborate the notion of a ‘pure novel’, inspired partly by Mallarmé, in response to historical conditions of the Occupation, in an assertion of literary sovereignty after bitter political defeat. Blanchot casts this pure form of writing through figures of light and luminosity that would transcend, even destroy, empirical experience – moving toward the disaster he will later invoke – thus affording a certain evasion from historical realities, while also betraying an intimate relation to their specific concrete historical conjuncture. The argument is not that Blanchot sublimates / allegorises political disappointment through literary narrative (see Jeffrey Mehlman in the 1980s), but that his literary texts enact a relation to factual political and historical responsibility that ‘pure’ literature fails to liquidate, but rather continually evokes. Tracing out constitutive evasions in Thomas the Obscure, Aminadab, The Madness of the Day, and The Instant of my Death, reveals how Blanchot’s fiction betrays a necessary accounting of the author’s factual history, a historical responsibility called up in the strange vacuous light of literature itself. [ABSTRACT FROM AUTHOR]

Understanding the ecological and evolutionary aspects of mutualistic interactions is essential for predicting species responses to environmental changes. This study aimed to investigate the phenological patterns and reproductive strategies in two closely related fig tree species, Ficus citrifolia and Ficus eximia. We monitored 99 F. citrifolia and 21 F. eximia trees weekly from January 2006 to April 2011 in an area close to the southern edge of the tropical region in Brazil. Our results revealed contrasting phenological patterns between the two species, with F. citrifolia displaying an annual flowering pattern (1.4 episodes per tree per year) and F. eximia a supra-annual pattern (0.5 episodes per tree per year). We also found significant differences in reproductive strategies, with F. eximia producing more pistillate flowers and, consequently, more seeds and pollinating wasps per fig than F. citrifolia, likely as an adaptation to overcome limitations of low population density by maximizing the gene flow. As the shorter-lived organism, the fig wasp was found to influence critical processes associated with the success and stability of mutualism, such as fig development and ripening. Our findings emphasize the importance of understanding the intricate interactions between mutualistic partners and their adaptive responses to environmental conditions in shaping fig tree populations' reproductive strategies and genetic structure. [ABSTRACT FROM AUTHOR]

While it is important to learn what is good and bad, can people learn what is neither? The answer to this question is not readily apparent, but it has important implications for how people learn affective responses. Six experiments examined whether evaluative conditioning (EC) can instill neutral affect. They tested four hypotheses: EC, in which novel conditioned stimuli (CSs) are paired with neutral unconditioned stimuli (USs) (1) creates neutral affect, (2) forms stronger experiences of neutrality when the number of contingent CS-US pairings is high rather than low, (3) creates positive affect, due to mere exposure, and (4) forms responses that are distinct from no US pairings. Respondents rated how positive, negative, and neutral they felt about a CS before and after an EC task in which CSs were paired with USs (positive, negative, neutral, or no stimuli). The positive/negative US conditions increased/decreased positivity, decreased/increased negativity, and decreased neutrality ratings, respectively. Supporting hypotheses 1, 2, and 4, the neutral US, but not the no US, condition increased neutral evaluations when respondents experienced a high (vs. low) number of CS-US pairings. Hypothesis 3 was not supported. The results reveal that people learn not only valenced, but also neutral, preferences. [ABSTRACT FROM AUTHOR]

High-altitude illnesses, encompassing a spectrumof health threats including Acute Mountain Sickness (AMS), pose significant challenges to individuals exposed to high altitude environments, necessitating effective prophylaxis and immediate management. Given the variability in individual responses to these conditions, accurate prediction of high-altitude illnesses onset is of paramount importance. This review systematically consolidates recent advancements in research on predicting AMS by evaluating existing cohort data, predictive models, and methodologies, while also delving into the application of emerging technologies. Through a thorough analysis of scholarly literature, we discuss traditional prediction methods anchored in physiological parameters (e.g., heart rate, respiratory frequency, blood pressure) and biochemicalmarkers, aswell as the integration and utility of novel technologies such as biosensors, genetic testing, and artificial intelligence within high-altitude prediction research. While conventional pre-diction techniques have been extensively used, they are often constrained by limitations in accuracy, reliability, andmultifactorial influences. The advent of these innovative technologies holds promise formore precise individual risk assessments and personalized preventive and therapeutic strategies across various forms of AMS. Future research endeavors must pivot decisively towards the meticulous identification and stringent validation of innovative predictive biomarkers and models. This strategic re-direction should catalyze intensified interdisciplinary cooperation to significantly deepen our mechanistic insights into the pathogenesis of AMS while refining existing prediction methodologies. These groundbreaking advancements harbor the potential to fundamentally transform preventive and therapeutic frameworks for high-altitude illnesses, ultimately securing augmented safety standards and wellbeing for individuals operating at elevated altitudes with far-reaching global implications. [ABSTRACT FROM AUTHOR]

Cellular starvation occurs when a cell is deprived of nutrition and oxygen availability. The genesis of this state of deprivation is exclusively contingent upon the inadequacy in the supply of essential components, namely amino acids, glucose, and oxygen. Consequently, the impact of this altered condition manifests in the regulation of cellular respiratory, metabolic, and stress responses. Subsequently, as a reactive outcome, cell death may transpire through mechanisms such as autophagy or apoptosis, particularly under prolonged circumstances. However, the cell combats such situations by evolving altered activity in their metabolic and protein level. Modulated signaling cascades help them to conquer starvation. But as in a prolonged condition, the battle that a cell has to evolve will come into and result in the form of cellular death. Therefore, in cancer therapy, cellular starvation may also act as a possible way out so that the cancer cell can undergo its death pathway in an induced starved condition. This review has collectively depicted the mechanism of cellular starvation. Besides this, the cellular response in this starved condition has also been summarized. Gaining such knowledge of the causation of cell starvation and cellular response during starvation not only generates new insight into the mechanism of cell survivability but also may act as a beneficial role in combating cellular diseases like cancer. Significance statement: Cellular survivability in diverse microenvironmental states remains a mystery of evolution. Under starvation, cellular adaptability manifests mainly through the modulation in mTORC, fatty acid trafficking, and hypoxic growth responses. In a starved condition, cells block the death pathways to survive until nutrients become available again. This adaptive response underscores cellular resilience in hostile environments. However, while this ability to evade cell death pathways aids in cell survival, it also poses significant challenges for therapeutic interventions aimed at inducing apoptosis in cancer cells. Therefore, understanding the cellular behavior in starvation holds immense potential for advancing cancer therapeutics. By analyzing the cellular response researchers can pave the way for more effective treatment strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved. Objective: The overall objective of this study was to investigate the direct impact of corticosterone challenge on a tractable epididymal epithelial cell line (i.e., mECap18 cells), in terms of driving adaptation of the cellular proteome and phosphoproteome signaling networks. Materials and methods: The newly developed phosphoproteomic platform EasyPhos coupled with sequencing via an Orbitrap Exploris 480 mass spectrometer, was applied to survey global changes in the mECap18 cell (phospho)proteome resulting from sub‐chronic (10‐day) corticosterone challenge. Results: The imposed corticosterone exposure regimen elicited relatively subtle modifications of the global mECap18 proteome (i.e., only 73 out of 4171 [∼1.8%] proteins displayed altered abundance). By contrast, ∼15% of the mECap18 phosphoproteome was substantially altered following corticosterone challenge. In silico analysis of the corresponding parent proteins revealed an activation of pathways linked to DNA damage repair and oxidative stress responses as well as a reciprocal inhibition of pathways associated with organismal death. Corticosterone challenge also induced the phosphorylation of several proteins linked to the biogenesis of microRNAs. Accordingly, orthogonal validation strategies confirmed an increase in DNA damage, which was ameliorated upon selective kinase inhibition, and an altered abundance profile of a subset of microRNAs in corticosterone‐treated cells. Conclusions: Together, these data confirm that epididymal epithelial cells are reactive to corticosterone challenge, and that their response is tightly coupled to the opposing action of cellular kinases and phosphatases. [ABSTRACT FROM AUTHOR]

In this study we apply electron tomography to characterize 3D dislocation microstructures in two quartz mylonite specimens from the Moine and Main Central Thrusts, both of which accommodated displacements by dislocation creep in the presence of water. Both specimens show dislocation activity with dislocation densities of the order of 3–4 × 1012 m−2 and evidence of recovery from the presence of subgrain boundaries. 〈a〉 slip occurs predominantly on pyramidal and prismatic planes (〈a〉 basal glide is not active). [c] Glide is not significant. On the other hand, we observe a very high level of activation of 〈c + a〉 glide on the 101‾0 $\left\{10\overline{1}0\right\}$, 101‾1 $\left\{10\overline{1}1\right\}$, 112‾n $\left\{11\overline{2}n\right\}$ (n = 1,2) and even 213‾1 $\left\{21\overline{3}1\right\}$ planes. Approximately 60% of all dislocations show evidence of climb with a predominance of mixed climb, a deformation mechanism characterized by dislocations moving in a plane intermediate between the glide and the climb planes. This atypical mode of deformation demonstrates comparable glide and climb efficiency under natural deformation conditions. It promotes dislocation glide in planes not expected for the quartz structure, probably by inhibiting lattice friction. Our quantitative characterization of the microstructure enables us to assess the strain that dislocations can generate. We show that glide systems indicated by the observed dislocations are sufficient to accommodate any arbitrary 3D strain by themselves. Although historically dislocation glide has been regarded as being primarily responsible for producing strain, activation of climb can also directly contribute to the finite strain. On the basis of this characterization, we propose a numerical modeling approach for attempting to characterize the local stress state that gave rise to the observed microstructure. Plain Language Summary: In this study, we characterize dislocation microstructures generated in quartz deformed in natural shear zones by advanced transmission electron microscopy to better understand the geological deformation conditions and the response of quartz to applied stresses. We characterize the crystal defects responsible for deformation of the mineral and their three‐dimensional geometries. We highlight an original deformation mechanism activated at very low natural strain rates that involves simultaneous dislocation glide and climb outside of their crystallographic glide planes. Key Points: Deformation involves mostly 〈a〉 and 〈c + a〉 slip on pyramidal and prismatic planes; [c] glide is marginal, 〈a〉 basal is not activatedApproximately 60% of the dislocations move by mixed climb, that is, a combination of glide and climbUnder natural strain‐rates glide and climb velocities are comparable [ABSTRACT FROM AUTHOR]

Overgeneralization of conditioned fear is associated with anxiety disorders (AD). Most results stem from studies done in adult patients, but studies with children are rare, although the median onset of anxiety disorders lies already in childhood. Thus, the goal of the present study was to examine fear learning and generalization in youth participants, aged 10–17 years, with AD (n = 39) compared to healthy controls (HC) (n = 40). A discriminative fear conditioning and generalization paradigm was used. Ratings of arousal, valence, and US expectancy (the probability of an aversive noise following each stimulus) were measured, hypothesizing that children with AD compared to HC would show heightened ratings of arousal and US expectancy, and decreased positive valence ratings, respectively, as well as overgeneralization of fear. The results indicated that children with AD rated all stimuli as more arousing and less pleasant, and demonstrated higher US expectancy ratings to all stimuli when compared to HC. Thus, rather than displaying qualitatively different generalization patterns (e.g., a linear vs. quadratic slope of the gradient), differences between groups were more quantitative (similar, but parallel shifted gradient). Therefore, overgeneralization of conditioned fear does not seem to be a general marker of anxiety disorders in children and adolescents. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa (AN) is a pernicious psychiatric disorder which is principally characterized by a fear of weight gain. Notwithstanding the centrality of fear in the psychopathology of AN, controlled assessments of negative valence systems are lacking. Herein we assess fear conditioning in adolescent females with AN. Method: Adolescent girls (Mage = 14.6 years, ±1.57) with DSM‐5 diagnoses of AN (N = 25) and age‐matched control girls (Mage = 14.8 years, ±1.46) with no DSM‐5 diagnoses (N = 25) completed structured clinical interviews and participated in a classical three‐phase Pavlovian fear conditioning paradigm. Participants with comorbid anxiety disorders were excluded. Skin conductance response (SCR) was measured, alongside self‐reported fear, valence, and fear expectancy ratings. Results: Both groups demonstrated significant differential acquisition across all four measures. Regarding group comparisons, no differences emerged for self‐reported fear, valence, and fear expectancy ratings during acquisition, although for SCR, those with AN demonstrated reduced physiological arousal relative to controls. Both groups demonstrated significant differential extinction for unconditioned stimuli (US) expectancy, self‐report fear, and self‐report valence. No statistically significant group differences were evident during extinction to the conditioned stimuli (CS)+, on any outcome measure. However, controls reported more positive valence to the CS− than those with AN. Conclusions: Contrary to our hypotheses, our preliminary assessment did not find support for elevated fear responding among adolescent girls with AN with regards to fear acquisition or extinction. These data suggest that AN in adolescent girls may not be associated with a heightened propensity to acquire fear, but conversely, may suggest that exposure treatments for AN may be helpful, since extinction learning is intact in AN. Public significance: AN is characterized by fear‐related symptoms, including food and weight‐related fear, and behavioral avoidance, yet controlled studies assessing fear learning are limited. Our preliminary assessment of adolescent AN indicates no abnormalities in fear learning among adolescents with AN. These findings may inform existing mechanistic models of AN psychopathology, and the development of exposure‐based treatments for AN. [ABSTRACT FROM AUTHOR]

Determining how internal and external stimuli interact to determine developmental trajectories of traits is a challenge that requires the integration of different subfields of biology. Internal stimuli, such as hormones, control developmental patterns of phenotypic changes, which might be modified by external environmental cues (e.g. plasticity). Thyroid hormone (TH) modulates the timing of opsin gene expression in developing Midas cichlid fish (Amphilophus citrinellus). Moreover, fish reared in red light accelerate this developmental timing compared to fish reared in white light. Hence, we hypothesized that plasticity caused by variation in light conditions has coopted the TH signaling pathway to induce changes in opsin gene expression. We treated Midas cichlids with TH and crossed this treatment with two light conditions, white and red. We observed that not only opsin expression responded similarly to TH and red light but also that, at high TH levels, there is limited capacity for light-induced plasticity. Transcriptomic analysis of the eye showed that genes in the TH pathway were affected by TH, but not by light treatments. Coexpression network analyses further suggested that response to light was independent of the response to TH manipulations. Taken together, our results suggest independent mechanisms mediating development and plasticity during development of opsin gene expression, and that responses to environmental stimuli may vary depending on internal stimuli. This conditional developmental response to external factors depending on internal ones (e.g. hormones) might play a fundamental role in the patterns of phenotypic divergence observed in Midas cichlids and potentially other organisms. [ABSTRACT FROM AUTHOR]

Infectious challenge can trigger alterations in sleep–wake behavior. Accumulating evidence has shown that the serine/threonine kinases Akt1 and Akt2 are important targets in both physiological and infectious signaling processes. However, the involvement of Akt1 and Akt2 in sleep–wake activity under basal conditions and in response to inflammatory stimulation has not been established. In the present study, we assessed the precise role of Akt1 and Akt2 in sleep–wake behavior using electroencephalography (EEG)/electromyography (EMG) data from Akt1- and Akt2-deficient mice and wild-type (WT) mice. The results showed that both Akt1 and Akt2 deficiency affect sleep–wake activity, as indicated by reduced nonrapid eye movement (NREM) sleep and increased wakefulness in mutant mice compared to WT mice. Sleep amount and intensity (delta, theta and alpha activity) at night were also drastically attenuated in Akt1- and Akt2-deficient mice. Moreover, since Akt1 and Akt2 are involved in immune responses, we assessed their roles in the sleep response to the inflammatory stimulus lipopolysaccharide (LPS) throughout the following 24 h. We observed that the decrease in wakefulness and increase in NREM sleep induced by LPS were restored in Akt1 knockout mice but not in Akt2 knockout mice. Correspondingly, the decrease in the number of positive orexin-A neurons induced by LPS was abrogated in Akt1 knockout mice but not in Akt2 knockout mice. Our results revealed that both Akt1 and Akt2 deficiency affect the sleep response under basal conditions, but only Akt1 deficiency protects against the aberrant changes in sleep behavior induced by peripheral immune challenge. [ABSTRACT FROM AUTHOR]

Pavlovian conditioning is widely used to study the substrates of learning and memory in the mammalian brain. In a standard protocol, subjects are exposed to pairings of a conditioned stimulus (CS; e.g., a tone) with an unconditioned stimulus (US; e.g., an electric shock). Subsequent presentations of the CS elicit a range of behaviors that relate to the US (e.g., freezing) showing that animals learned the CS–US relation. However, it is still unclear how neuronal activity pertaining to the CS comes to excite a representation of the US, and thereby, conditioned responses. The current analysis of this problem, based on neurophysiological evidence, views Pavlovian conditioning as a process of facilitating the disinhibition, rather than the excitation, of neuronal responses representing the US. Conversely, Pavlovian extinction is viewed as a process of relearning to inhibit neuronal responses representing the US. We propose a mathematical equation that confirms the predictions made by this novel perspective on Pavlovian conditioning when applied to conditioning phenomena that fall beyond classic associative learning theories. [ABSTRACT FROM AUTHOR]

Airway mucus is a hydrogel with unique biophysical properties due to its primary water composition and a small proportion of large anionic glycoproteins or mucins. The predominant mucins in human mucus, MUC5AC and MUC5B, are secreted by specialized cells within the airway epithelium both in normal conditions and in response to various stimuli. Their relative proportions are correlated with specific inflammatory responses and disease mechanisms. The dysregulation of mucin expression is implicated in numerous respiratory diseases, including asthma, COPD, and cystic fibrosis, where the pathogenic role of mucus has been extensively described yet often overlooked. In airway diseases, excessive mucus production or impaired mucus clearance leads to mucus plugging, with secondary airway occlusion that contribute to airflow obstruction, asthma severity and poor control. Eosinophils and Charcot Leyden crystals in sputum contribute to the mucus burden and tenacity. Mucin may also contribute to eosinophil survival. Other mechanisms, including eosinophil-independent IL-13 release, mast-cell activation and non-type-2 (T2) cytokines, are also likely to participate in mucus pathobiology. An accurate assessment of mucus and its clinical and functional consequences require a thorough approach that includes evaluation of cellular predominance in sputum, airway cytokines and other inflammatory markers, mucus characteristics and composition and structural and functional impact measured by advanced lung imaging. This review, illustrated with clinical scenarios, provides an overview of current methods to assess mucus and its relevance to the choice of biologics to treat patients with severe asthma. [ABSTRACT FROM AUTHOR]