Project description:In contrast with autosomes, lineages of sex chromosomes reside for different amounts of time in males and females, and this transmission asymmetry makes them hotspots for sexual conflict. Similarly, the maternal inheritance of the mitochondrial genome (mtDNA) means that mutations that are beneficial in females can spread in a population even if they are deleterious in males, a form of sexual conflict known as Mother's Curse. While both Mother's Curse and sex chromosome induced sexual conflict have been well studied on their own, the interaction between mitochondrial genes and genes on sex chromosomes is poorly understood. Here, we use analytical models and computer simulations to perform a comprehensive examination of how transmission asymmetries of nuclear, mitochondrial, and sex chromosome-linked genes may both cause and resolve sexual conflicts. For example, the accumulation of male-biased Mother's Curse mtDNA mutations will lead to selection in males for compensatory nuclear modifier loci that alleviate the effect. We show how the Y chromosome, being strictly paternally transmitted provides a particularly safe harbor for such modifiers. This analytical framework also allows us to discover a novel kind of sexual conflict, by which Y chromosome-autosome epistasis may result in the spread of male beneficial but female deleterious mutations in a population. We christen this phenomenon Father's Curse. Extending this analytical framework to ZW sex chromosome systems, where males are the heterogametic sex, we also show how W-autosome epistasis can lead to a novel kind of nuclear Mother's Curse. Overall, this study provides a comprehensive framework to understand how genetic transmission asymmetries may both cause and resolve sexual conflicts.
Project description:The ability to adopt others' perspectives-our "Theory of Mind"-underpins social interaction. Nevertheless, adults are imperfect perspective takers, demonstrating egocentric biases. Here, a series of experiments assessed whether (1) embodying an agent's physical perspective (working out whether he held something in his left or right hand) or (2) being bilingual, would benefit perspective taking. Participants were shown a scenario in which an agent puts a ball in one of four boxes. When he returns later, the boxes have been rearranged. Participants, who additionally know that the ball is now in a different box, then judge how likely the agent is to look for the ball in each of the four boxes first. In Experiments 1-3 participants were not more likely to judge the agent would look where he last saw it as a function of either factor. In Experiments 4 and 5, one group of participants were told where the ball had been moved to, the other only that the ball had been moved to a different box. In Experiment 4, participants in the latter condition assigned higher probability to the boxes that were never mentioned. In Experiment 5 this was replicated and was driven by monolinguals and those who had received the embodiment condition. These results suggest that egocentric biases may be more likely to arise when participants are more deliberative, such as when making a judgement under uncertainty, and that extrinsic factors such as bilingualism and embodiment may influence perspective attributions under such conditions.
Project description:The world is currently face to face with a pandemic which is spreading rapidly across the globe caused by SARS-CoV-2, a strain of Coronaviruses (CoVs) belonging to subgenus Sarbecovirus of genus Betacoronavirus. World Health Organisation (WHO) on 11 Feb 20 named this disease caused by SARS-CoV-2 as Covid-19. This pandemic is spreading rapidly and more than 20,00,000 cases have occurred globally. The human Coronaviruses discovered in 1960s were considered potentially harmless endemic viruses with seasonal distribution before late 2002. The CoVs are found in a large number of domestic and wild animals and birds. The first pandemic caused by Coronavirus caused by SARS-CoV was recognized in the late 2002 in Guangdong Province and resulted in widespread morbidity and mortality. This was followed by MERS-CoV which began in 2012 in the Arabian peninsula with multiple outbreaks related to it in various parts of the globe. Various studies have suggested how these viruses made their entry from their natural reservoir bats via intermediate host like civets and camels in case of SARS-CoV and MERS-CoV respectively. The intermediate host of the SARS-CoV-2 still needs to be established. The SARS-CoV-2 has 96.2% similarity to the bat Severe Acute Respiratory Syndrome related-Coronavirus (SARSr-CoV RaTG13). SARS-CoV-2 has been found to be more distant in relation to SARS-CoV (79%) and MERS-CoV (50%). At the whole genome sequence level pangolin CoV and SARSr-CoV RaTG13 show 91.02% and 96.2% similarity with SARS-CoV-2 but the S1 subunit of spike protein of pangolin CoV is more closely related to SARS-CoV-2 than SARSr-CoV RaTG13. The genetic analysis of the currently circulating strains of the pandemic have shown 99.98-100% similarity in their genomes implying a recent shift to humans. The animal source of SARS-CoV-2 needs to be identified to implement control measures in the present pandemic. Also, how the virus moves interspecies will help predict and prevent future pandemics.
Project description:Ondine's curse is one of the most enchanting mythical tales in the field of Medicine. The nymph Ondine was an immortal water spirit who became human after falling in love for a man, marrying him, and having a baby. In one of the versions of the tale, when she caught her husband sleeping with another woman, she cursed him to remain awake in order to control his own breathing. During the 19th century, the rare syndrome characterized by loss of autonomic breath control, while voluntary respiration remains intact, was cleverly named "Ondine's curse". Nowadays, the term Ondine's curse is usually associated with congenital central hypoventilation syndrome; however, in medical literature, it also designates several respiratory disorders. Here, we present a review of the myth focused on history, arts and medicine.
Project description:PurposeCould the curse of knowledge influence how antagonized we are towards political outgroups? Do we assume others know what we know but still disagree with us? This research investigates how the curse of knowledge may affect us politically, i.e., be a cause of political polarization.BackgroundResearch on the curse of knowledge has shown that even when people are incentivized to act as if others do not know what they know, they are still influenced by the knowledge they have.MethodsThis study consists of five studies consisting of both experimental and non-experimental and within- and between-subjects survey designs. Each study collected samples of 152-1,048.ResultsPartisans on both sides overestimate the extent to which stories from their news sources were familiar to contrapartisans. Introducing novel, unknown facts to support their political opinion made participants rate political outgroup members more negatively. In an experimental design, there was no difference in judging an opponent who did not know the same issue-relevant facts and someone who did know the same facts. However, when asked to compare those who know to those who do not, participants judged those who do not know more favorably, and their ratings of all issue-opponents were closer to those issue-opponents who shared the same knowledge. In a debiasing experiment, those who received an epistemological treatment judged someone who disagreed more favorably.ConclusionThis research provides evidence that the curse of knowledge may be a contributing cause of affective political polarization.
Project description:Human sterile α motif and HD domain-containing protein 1 (SAMHD1), originally described as the major cellular deoxyribonucleoside triphosphate triphosphohydrolase (dNTPase) balancing the intracellular deoxynucleotide (dNTP) pool, has come recently into focus of cancer research. As outlined in this review, SAMHD1 has been reported to be mutated in a variety of cancer types and the expression of SAMHD1 is dysregulated in many cancers. Therefore, SAMHD1 is regarded as a tumor suppressor in certain tumors. Moreover, it has been proposed that SAMHD1 might fulfill the requirements of a driver gene in tumor development or might promote a so-called mutator phenotype. Besides its role as a dNTPase, several novel cellular functions of SAMHD1 have come to light only recently, including a role as negative regulator of innate immune responses and as facilitator of DNA end resection during DNA replication and repair. Therefore, SAMHD1 can be placed at the crossroads of various cellular processes. The present review summarizes the negative role of SAMHD1 in chemotherapy sensitivity, highlights reported SAMHD1 mutations found in various cancer types, and aims to discuss functional consequences as well as underlying mechanisms of SAMHD1 dysregulation potentially involved in cancer development.
Project description:The international DNA sequence databases abound in fungal sequences not annotated beyond the kingdom level, typically bearing names such as "uncultured fungus". These sequences beget low-resolution mycological results and invite further deposition of similarly poorly annotated entries. What do these sequences represent? This study uses a 767,918-sequence corpus of public full-length fungal ITS sequences to estimate what proportion of the 95,055 "uncultured fungus" sequences that represent truly unidentifiable fungal taxa - and what proportion of them that would have been straightforward to annotate to some more meaningful taxonomic level at the time of sequence deposition. Our results suggest that more than 70% of these sequences would have been trivial to identify to at least the order/family level at the time of sequence deposition, hinting that factors other than poor availability of relevant reference sequences explain the low-resolution names. We speculate that researchers' perceived lack of time and lack of insight into the ramifications of this problem are the main explanations for the low-resolution names. We were surprised to find that more than a fifth of these sequences seem to have been deposited by mycologists rather than researchers unfamiliar with the consequences of poorly annotated fungal sequences in molecular repositories. The proportion of these needlessly poorly annotated sequences does not decline over time, suggesting that this problem must not be left unchecked.
Project description:Digital health data are multimodal and high-dimensional. A patient's health state can be characterized by a multitude of signals including medical imaging, clinical variables, genome sequencing, conversations between clinicians and patients, and continuous signals from wearables, among others. This high volume, personalized data stream aggregated over patients' lives has spurred interest in developing new artificial intelligence (AI) models for higher-precision diagnosis, prognosis, and tracking. While the promise of these algorithms is undeniable, their dissemination and adoption have been slow, owing partially to unpredictable AI model performance once deployed in the real world. We posit that one of the rate-limiting factors in developing algorithms that generalize to real-world scenarios is the very attribute that makes the data exciting-their high-dimensional nature. This paper considers how the large number of features in vast digital health data can challenge the development of robust AI models-a phenomenon known as "the curse of dimensionality" in statistical learning theory. We provide an overview of the curse of dimensionality in the context of digital health, demonstrate how it can negatively impact out-of-sample performance, and highlight important considerations for researchers and algorithm designers.
Project description:The imaging of neuronal activity using calcium indicators has become a staple of modern neuroscience. However, without ground truths, there is a real risk of missing a significant portion of the real responses. Here, we show that a common assumption, the non-negativity of the neuronal responses as detected by calcium indicators, biases all levels of the frequently used analytical methods for these data. From the extraction of meaningful fluorescence changes to spike inference and the analysis of inferred spikes, each step risks missing real responses because of the assumption of non-negativity. We first show that negative deviations from baseline can exist in calcium imaging of neuronal activity. Then, we use simulated data to test three popular algorithms for image analysis, CaImAn, suite2p, and CellSort, finding that suite2p may be the best suited to large datasets. We also tested the spike inference algorithms included in CaImAn, suite2p, and Cellsort, as well as the dedicated inference algorithms MLspike and CASCADE, and found each to have limitations in dealing with inhibited neurons. Among these spike inference algorithms, FOOPSI, from CaImAn, performed the best on inhibited neurons, but even this algorithm inferred spurious spikes upon the return of the fluorescence signal to baseline. As such, new approaches will be needed before spikes can be sensitively and accurately inferred from calcium data in inhibited neurons. We further suggest avoiding data analysis approaches that, by assuming non-negativity, ignore inhibited responses. Instead, we suggest a first exploratory step, using k-means or PCA for example, to detect whether meaningful negative deviations are present. Taking these steps will ensure that inhibition, as well as excitation, is detected in calcium imaging datasets.