ResearchPad - 14 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Importance of γ-secretase in the regulation of liver X receptor and cellular lipid metabolism]]> https://www.researchpad.co/article/elastic_article_12861 Presenilins (PS) are the catalytic components of γ-secretase complexes that mediate intramembrane proteolysis. Mutations in the PS genes are a major cause of familial early-onset Alzheimer disease and affect the cleavage of the amyloid precursor protein, thereby altering the production of the amyloid β-peptide. However, multiple additional protein substrates have been identified, suggesting pleiotropic functions of γ-secretase. Here, we demonstrate that inhibition of γ-secretase causes dysregulation of cellular lipid homeostasis, including up-regulation of liver X receptors, and complex changes in the cellular lipid composition. Genetic and pharmacological inhibition of γsecretase leads to strong accumulation of cytoplasmic lipid droplets, associated with increased levels of acylglycerols, but lowered cholesteryl esters. Furthermore, accumulation of lipid droplets was augmented by increasing levels of amyloid precursor protein C-terminal fragments, indicating a critical involvement of this γ-secretase substrate. Together, these data provide a mechanism that functionally connects γ-secretase activity to cellular lipid metabolism. These effects were also observed in human astrocytic cells, indicating an important function of γ-secretase in cells critical for lipid homeostasis in the brain.

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<![CDATA[Re-imaging the intentional stance]]> https://www.researchpad.co/article/elastic_article_9537 The commonly used paradigm to investigate Dennet's ‘intentional stance’ compares neural activation when participants compete with a human versus a computer. This paradigm confounds whether the opponent is natural or artificial and whether it is intentional or an automaton. This functional magnetic resonance imaging study is, to our knowledge, the first to investigate the intentional stance by orthogonally varying perceptions of the opponents' intentionality (responding actively or passively according to a script) and embodiment (human or a computer). The mere perception of the opponent (whether human or computer) as intentional activated the mentalizing network: the temporoparietal junction (TPJ) bilaterally, right temporal pole, anterior paracingulate cortex (aPCC) and the precuneus. Interacting with humans versus computers induced activations in a more circumscribed right lateralized subnetwork within the mentalizing network, consisting of the TPJ and the aPCC, possibly reflective of the tendency to spontaneously attribute intentionality to humans. The interaction between intentionality (active versus passive) and opponent (human versus computer) recruited the left frontal pole, possibly in response to violations of the default intentional stance towards humans and computers. Employing an orthogonal design is important to adequately capture Dennett's conception of the intentional stance as a mentalizing strategy that can apply equally well to humans and other intentional agents.

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<![CDATA[Initial Results from Mobile Low‐Dose Computerized Tomographic Lung Cancer Screening Unit: Improved Outcomes for Underserved Populations]]> https://www.researchpad.co/article/elastic_article_8331 The BodyTom CT is the first mobile screening unit in the U.S., designed to improve access to lung cancer screening for underserved patient groups. This article reports results of the initial pilot study using this first‐of‐its‐kind mobile low‐dose whole body CT screening unit. Twelve cases of lung cancer were found in 550 smokers (including 6 early stage).

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<![CDATA[A Prospective Study of Apatinib in Patients with Extensive‐Stage Small Cell Lung Cancer After Failure of Two or More Lines of Chemotherapy]]> https://www.researchpad.co/article/elastic_article_6603 Alternative treatment strategies are needed to improve prognosis for patients with small‐cell lung cancer. This article evaluates the feasibility of single‐agent apatinib as a treatment option for patients with extensive‐stage small‐cell lung cancer.

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<![CDATA[Underwater caustics disrupt prey detection by a reef fish]]> https://www.researchpad.co/article/Nedd18f8c-0807-4d5b-a2ae-88d3646a98e9 Natural habitats contain dynamic elements, such as varying local illumination. Can such features mitigate the salience of organism movement? Dynamic illumination is particularly prevalent in coral reefs, where patterns known as ‘water caustics’ play chaotically in the shallows. In behavioural experiments with a wild-caught reef fish, the Picasso triggerfish (Rhinecanthus aculeatus), we demonstrate that the presence of dynamic water caustics negatively affects the detection of moving prey items, as measured by attack latency, relative to static water caustic controls. Manipulating two further features of water caustics (sharpness and scale) implies that the masking effect should be most effective in shallow water: scenes with fine scale and sharp water caustics induce the longest attack latencies. Due to the direct impact upon foraging efficiency, we expect the presence of dynamic water caustics to influence decisions about habitat choice and foraging by wild prey and predators.

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<![CDATA[Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes]]> https://www.researchpad.co/article/N6964f0da-e6b4-4f5b-86a0-5e5ef8e23ad0 The major function of B lymphocytes is to sense antigens and to produce protective antibodies after activation. This function requires the expression of a B-cell antigen receptor (BCR), and evolutionary conserved mechanisms seem to exist that ensure that B cells without a BCR do not develop nor survive in the periphery. Here, we show that the loss of BCR expression on Burkitt lymphoma cells leads to decreased mitochondrial function and impaired metabolic flexibility. Strikingly, this phenotype does not result from the absence of a classical Syk-dependent BCR signal but rather from compromised ER expansion. We show that the reexpression of immunoglobulins (Ig) in the absence of the BCR signaling subunits Igα and Igβ rescues the observed metabolic defects. We demonstrate that immunoglobulin expression is needed to maintain ER homeostasis not only in lymphoma cells but also in resting B cells. Our study provides evidence that the expression of BCR components, which is sensed in the ER and shapes mitochondrial function, represents a novel mechanism of metabolic control in B cells.

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<![CDATA[Sexual frequency is associated with age of natural menopause: results from the Study of Women's Health Across the Nation]]> https://www.researchpad.co/article/N9ca572b3-18fc-4cfb-9e0f-7d2629bf6aa4

It is often observed that married women have a later age of natural menopause (ANM) than unmarried women; however, the reason for this association is unknown. We test an original hypothesis that sexual frequency acts as a bio-behavioural mediator between marital status and ANM. We hypothesize that there is a trade-off between continued ovulation and menopause based on the woman's chances of becoming pregnant. If a woman is sexually inactive, then pregnancy is impossible, and continued investment in ovulation would not be adaptive. In addition, we test an existing hypothesis that the observed relationship is because of the exposure to male pheromones. Data from 2936 women were drawn from 11 waves of the Study of Women's Health Across the Nation, which is a longitudinal study conducted in the United States. Using time-varying Cox regression, we found no evidence for the pheromone hypothesis. However, we did observe that women who reported to have sex weekly during the study period were 28% less likely to experience menopause than women who had sex less than monthly. This is an indication that ANM may be somewhat facultative in response to the likelihood of pregnancy.

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<![CDATA[What makes a pair bond in a Neotropical primate: female and male contributions]]> https://www.researchpad.co/article/N83ea953f-5c33-488f-a14d-34442f3aac35

Pair living and pair bonding are rare in mammals, and the mechanisms of their maintenance remain a puzzle. Titi monkeys, a ‘textbook example’ for ‘monogamous’ primates, have strong pair bonds and extensive male care. To investigate mechanisms of pair-bond maintenance, we studied seven wild groups of red titis (Plecturocebus cupreus) in Peruvian Amazonia over a period of 14 months. We analysed pair bonds by measuring proximity, grooming and approaches/leaves within pairs, and collected data on intergroup encounters. Females contributed to grooming more than males, especially during infant dependency, when most of the grooming within pairs was done by females. Females were also more active in controlling proximity between pair mates, making most of the approaches and leaves. Males, on the other hand, invested more in territorial defences. They participated in more intergroup encounters than females and were more active during these encounters. Our data is most consistent with the ‘male-services’ hypothesis for pair-bond maintenance, where a female contributes more to the proximity and affiliation maintenance while a male provides beneficial services.

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<![CDATA[An experimental approach to evaluate the potential of drones in terrestrial mammal research: a gregarious ungulate as a study model]]> https://www.researchpad.co/article/N5745988f-3513-4c72-b094-70620994866c

Research on the use of unmanned aircraft systems (UAS) in wildlife has made remarkable progress recently. Few studies to date have experimentally evaluated the effect of UAS on animals and have usually focused primarily on aquatic fauna. In terrestrial open arid ecosystems, with relatively good visibility to detect animals but little environmental noise, there should be a trade-off between flying the UAS at high height above ground level (AGL) to limit the disturbance of animals and flying low enough to maintain count precision. In addition, body size or social aggregation of species can also affect the ability to detect animals from the air and their response to the UAS approach. To address this gap, we used a gregarious ungulate, the guanaco (Lama guanicoe), as a study model. Based on three types of experimental flights, we demonstrated that (i) the likelihood of miscounting guanacos in images increases with UAS height, but only for offspring and (ii) higher height AGL and lower UAS speed reduce disturbance, except for large groups, which always reacted. Our results call into question mostly indirect and observational previous evidence that terrestrial mammals are more tolerant to UAS than other species and highlight the need for experimental and species-specific studies before using UAS methods.

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<![CDATA[An atypical mating system in a neotropical manakin]]> https://www.researchpad.co/article/N3f9e6cbc-e8a0-42c4-bf6d-f36b51f0c46c

Most of the diversity in the mating systems of birds and other animals comes at higher taxonomic levels, such as across orders. Although divergent selective pressures should lead to animal mating systems that diverge sharply from those of close relatives, opportunities to examine the importance of such processes are scarce. We addressed this issue using the Araripe manakin (Antilophia bokermanni), a species endemic to a forest enclave surrounded by xeric shrublands in Brazil. Most manakins exhibit polygynous lekking mating systems that lack territoriality but exhibit strong sexual selection. In sharp contrast, we found that male Araripe manakins defended exclusive territories, and females nested within male territories. However, territoriality and offspring paternity were dissociated: males sired only 7% of nestlings from the nests within their territories and non-territorial males sired numerous nestlings. Moreover, female polyandry was widespread, with most broods exhibiting mixed paternity. Apparently, territories in this species function differently from both lekking arenas and resource-based territories of socially monogamous species. The unexpected territoriality of Araripe manakins and its dissociation from paternity is a unique evolutionary development within the manakin clade. Collectively, our findings underscore how divergences in mating systems might evolve based on selective pressures from novel environmental contexts.

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<![CDATA[Automated detection of lameness in sheep using machine learning approaches: novel insights into behavioural differences among lame and non-lame sheep]]> https://www.researchpad.co/article/N183bc01e-c2df-4f63-911a-93bdee63f3a9

Lameness in sheep is the biggest cause of concern regarding poor health and welfare among sheep-producing countries. Best practice for lameness relies on rapid treatment, yet there are no objective measures of lameness detection. Accelerometers and gyroscopes have been widely used in human activity studies and their use is becoming increasingly common in livestock. In this study, we used 23 datasets (10 non-lame and 13 lame sheep) from an accelerometer- and gyroscope-based ear sensor with a sampling frequency of 16 Hz to develop and compare algorithms that can differentiate lameness within three different activities (walking, standing and lying). We show for the first time that features extracted from accelerometer and gyroscope signals can differentiate between lame and non-lame sheep while standing, walking and lying. The random forest algorithm performed best for classifying lameness with an accuracy of 84.91% within lying, 81.15% within standing and 76.83% within walking and overall correctly classified over 80% sheep within activities. Both accelerometer- and gyroscope-based features ranked among the top 10 features for classification. Our results suggest that novel behavioural differences between lame and non-lame sheep across all three activities could be used to develop an automated system for lameness detection.

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<![CDATA[Field assessment of behavioural responses of southern stingrays (Hypanus americanus) to acoustic stimuli]]> https://www.researchpad.co/article/Nae95d22c-f704-412e-9ad7-93e2cb0e14f4

The ability of elasmobranchs to detect and use sound cues has been heavily debated in previous research and has only recently received revived attention. To properly understand the importance of sound to elasmobranchs, assessing their responses to acoustic stimuli in a field setting is vital. Here, we establish a behavioural audiogram of free-swimming male and female southern stingrays (Hypanus americanus) exposed to low-frequency tones. We demonstrate that female stingrays exposed to tones (50–500 Hz) exhibit significant changes in swimming behaviours (increased time spent swimming, decreased rest time, increased surface breaches and increased side swimming with pectoral flapping) at 140 dB re 1 µPa (−2.08 to −2.40 dB re 1 m s−2) while males exposed to the same tones did not exhibit a change in these behaviours until 160 dB re 1 µPa (−1.13 to −1.21 dB re 1 m s−2). Our results are the first demonstration of field responses to sound in the Batoidea and show a distinct sensitivity to low-frequency acoustic inputs.

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<![CDATA[A perceptual bias for man-made objects in humans]]> https://www.researchpad.co/article/N6eb95d67-220e-4afa-bd41-bd51c41dbc56

Ambiguous images are widely recognized as a valuable tool for probing human perception. Perceptual biases that arise when people make judgements about ambiguous images reveal their expectations about the environment. While perceptual biases in early visual processing have been well established, their existence in higher-level vision has been explored only for faces, which may be processed differently from other objects. Here we developed a new, highly versatile method of creating ambiguous hybrid images comprising two component objects belonging to distinct categories. We used these hybrids to measure perceptual biases in object classification and found that images of man-made (manufactured) objects dominated those of naturally occurring (non-man-made) ones in hybrids. This dominance generalized to a broad range of object categories, persisted when the horizontal and vertical elements that dominate man-made objects were removed and increased with the real-world size of the manufactured object. Our findings show for the first time that people have perceptual biases to see man-made objects and suggest that extended exposure to manufactured environments in our urban-living participants has changed the way that they see the world.

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<![CDATA[Multimodality and the origin of a novel communication system in face-to-face interaction]]> https://www.researchpad.co/article/N33aabe53-c5ad-409f-a17a-550e3fa57da8

Face-to-face communication is multimodal at its core: it consists of a combination of vocal and visual signalling. However, current evidence suggests that, in the absence of an established communication system, visual signalling, especially in the form of visible gesture, is a more powerful form of communication than vocalization and therefore likely to have played a primary role in the emergence of human language. This argument is based on experimental evidence of how vocal and visual modalities (i.e. gesture) are employed to communicate about familiar concepts when participants cannot use their existing languages. To investigate this further, we introduce an experiment where pairs of participants performed a referential communication task in which they described unfamiliar stimuli in order to reduce reliance on conventional signals. Visual and auditory stimuli were described in three conditions: using visible gestures only, using non-linguistic vocalizations only and given the option to use both (multimodal communication). The results suggest that even in the absence of conventional signals, gesture is a more powerful mode of communication compared with vocalization, but that there are also advantages to multimodality compared to using gesture alone. Participants with an option to produce multimodal signals had comparable accuracy to those using only gesture, but gained an efficiency advantage. The analysis of the interactions between participants showed that interactants developed novel communication systems for unfamiliar stimuli by deploying different modalities flexibly to suit their needs and by taking advantage of multimodality when required.

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<![CDATA[Coronavirus-JHM-Induced Demyelinating Encephalomyelitis in Rats.]]> https://www.researchpad.co/article/N7844edae-42f6-4e86-9950-e5450f5c6271 ]]> <![CDATA[Physical Activity and Exercise in Lung Cancer Care: Will Promises Be Fulfilled?]]> https://www.researchpad.co/article/Nd9cae7a1-114b-44be-b297-677c2d14264d

Abstract

Lung cancer remains the leading cause of cancer‐related death worldwide. Affected patients frequently experience debilitating disease‐related symptoms, including dyspnea, cough, fatigue, anxiety, depression, insomnia, and pain, despite the progresses achieved in term of treatment efficacy.

Physical activity and exercise are nonpharmacological interventions that have been shown to improve fatigue, quality of life, cardiorespiratory fitness, pulmonary function, muscle mass and strength, and psychological status in patients with lung cancer. Moreover, physical fitness levels, especially cardiorespiratory endurance and muscular strength, are demonstrated to be independent predictors of survival. Nevertheless, patients with lung cancer frequently present insufficient levels of physical activity and exercise, and these may contribute to quality of life impairment, reduction in functional capacity with skeletal muscle atrophy or weakness, and worsening of symptoms, particularly dyspnea.

The molecular bases underlying the potential impact of exercise on the fitness and treatment outcome of patients with lung cancer are still elusive. Counteracting specific cancer cells’ acquired capabilities (hallmarks of cancer), together with preventing treatment‐induced adverse events, represent main candidate mechanisms.

To date, the potential impact of physical activity and exercise in lung cancer remains to be fully appreciated, and no specific exercise guidelines for patients with lung cancer are available. In this article, we perform an in‐depth review of the evidence supporting physical activity and exercise in lung cancer and suggest that integrating this kind of intervention within the framework of a global, multidimensional approach, taking into account also nutritional and psychological aspects, might be the most effective strategy.

Implications for Practice

Although growing evidence supports the safety and efficacy of exercise in lung cancer, both after surgery and during and after medical treatments, most patients are insufficiently active or sedentary. Engaging in exercise programs is particularly arduous for patients with lung cancer, mainly because of a series of physical and psychosocial disease‐related barriers (including the smoking stigma). A continuous collaboration among oncologists and cancer exercise specialists is urgently needed in order to develop tailored programs based on patients’ needs, preferences, and physical and psychological status. In this regard, benefit of exercise appears to be potentially enhanced when administered as a multidimensional, comprehensive approach to patients’ well‐being.

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<![CDATA[A method yielding comparable estimates of the fraternal birth order and female fecundity effects in male homosexuality]]> https://www.researchpad.co/article/N23d37b70-3e88-441d-b53c-b177edd61a25

The fraternal birth order effect (FBOE) is the finding that older brothers increase the probability of homosexuality in later-born males, and the female fecundity effect (FFE) is the finding that the mothers of homosexual males produce more offspring than the mothers of heterosexual males. In a recent paper, Khovanova proposed a novel method for computing independent estimates of these effects on the same samples and expressing the magnitude and direction of the effects in the same metric. In her procedure, only families with one or two sons are examined, and daughters are ignored. The present study investigated the performance of Khovanova's method using archived data from 10 studies, comprising 14 samples totalling 5390 homosexual and heterosexual subjects. The effect estimate for the FBOE showed that an increase from zero older brothers to one older brother is associated with a 38% increase in the odds of homosexuality. By contrast, the effect estimate for the FFE showed that the increase from zero younger brothers to one younger brother is not associated with any increase in the odds of homosexuality. The former result supports the maternal immune hypothesis of male homosexuality; the latter result does not support the balancing selection hypothesis.

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<![CDATA[Does kin discrimination promote cooperation?]]> https://www.researchpad.co/article/N01b835c1-9d43-4386-b6c3-65c57bb08a49

Genetic relatedness is a key driver of the evolution of cooperation. One mechanism that may ensure social partners are genetically related is kin discrimination, in which individuals are able to distinguish kin from non-kin and adjust their behaviour accordingly. However, the impact of kin discrimination upon the overall level of cooperation remains obscure. Specifically, while kin discrimination allows an individual to help more-related social partners over less-related social partners, it is unclear whether and how the population average level of cooperation that is evolutionarily favoured should differ under kin discrimination versus indiscriminate social behaviour. Here, we perform a general mathematical analysis in order to assess whether, when and in which direction kin discrimination changes the average level of cooperation in an evolving population. We find that kin discrimination may increase, decrease or leave unchanged the average level of cooperation, depending upon whether the optimal level of cooperation is a convex, concave or linear function of genetic relatedness. We develop an extension of the classic ‘tragedy of the commons' model of cooperation in order to provide an illustration of these results. Our analysis provides a method to guide future research on the evolutionary consequences of kin discrimination.

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<![CDATA[New application of strontium isotopes reveals evidence of limited migratory behaviour in Late Cretaceous hadrosaurs]]> https://www.researchpad.co/article/Nb9091ab0-5d82-4a73-8c59-6c096c056520

Dinosaur migration patterns are very difficult to determine, often relying solely on the geographical distribution of fossils. Unfortunately, it is generally not possible to determine if a fossil taxon's geographical distribution is the result of migration or simply a wide distribution. Whereas some attempts have been made to use isotopic systems to determine migratory patterns in dinosaurs, these methods have yet to achieve wider usage in the study of dinosaur ecology. Here, we have used strontium isotope ratios from fossil enamel to reconstruct the movements of an individual hadrosaur from Dinosaur Provincial Park in Alberta, Canada. Results from this study are consistent with a range or migratory pattern between Dinosaur Provincial Park and a contemporaneous locality in the South Saskatchewan River area, Alberta, Canada. This represents a minimum distance of approximately 80 km, which is consistent with migrations seen in modern elephants. These results suggest the continent-wide distribution of some hadrosaur species in the Late Cretaceous of North America is not the result of extremely long-range migratory behaviours.

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<![CDATA[An Impaired Breeding Phenotype in Mice with a Genetic Deletion of Beta-2 Microglobulin and Diminished MHC Class I Expression: Role in Reproductive Fitness1]]> https://www.researchpad.co/article/Nabf07e58-f61e-4aee-a04f-33bc6007c9fd

Abstract

Beta-2 microglobulin (B2M) plays a pivotal role in the biology of mammals, including its association with major histocompatibility complex (MHC) Class I gene products. The latter molecules have been shown to affect reproduction in both mice and humans, although the exact mechanism is still unknown. Here we report the results of a longitudinal study of the reproductive performance of a genetically modified B2m deficient mouse strain with low MHC Class I expression. Our data show that this mouse strain has an impaired reproductive performance. However, the mice superovulate well and show a normal estrous cycle. Breeding studies from crosses between the transgenic mice and the wild-type parental strain show that B2m deficient mice have a significantly lower frequency of mating than the control B2m+/+ mice. In addition, the litter size and weaning success of B2m deficient mice were lower than the control. Perinatal lethality of the B2m deficient offspring was also inflicted by cannibalism of the young pups by the B2m deficient female. The impaired breeding phenotype (IBP) can be reversed by reintroducing the B2m gene in F1 heterozygous B2m+/− animals; thus the presence of B2M confers a normal breeding pattern. The acquisition of an impaired breeding phenotype (IBP) as a result of the knockout of B2m directly implicates B2M in the reproductive cycle of mice and raises the possibility of an effect of B2M on the reproduction of other mammals.

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