Ethics-testing an eating disorder recovery memoir: a pre-publication experiment.

Background: Narratives (including memoirs and novels) about eating disorders (EDs) are typically published with the intention to benefit readers, but survey evidence suggests that reading such narratives with an active ED may more often be harmful than helpful. To reduce the probability of inadvertent harm and learn more about how narrative reading and EDs interact, a pre-publication study was designed to determine whether or not a recovery memoir should be published.

Methods: 64 participants with a self-reported ED read either the experimental text (The Hungry Anorexic [HA]) or a control text (Ten Zen Questions [TZ]) over a roughly two-week period.

Language about the future on social media as a novel marker of anxiety and depression: A big-data and experimental analysis.

Anxiety and depression negatively impact many. Studies suggest depression is associated with future time horizons, or how "far" into the future people tend to think, and anxiety is associated with temporal discounting, or how much people devalue future rewards. Separate studies from linguistics and economics have shown that how people refer to future time predicts temporal discounting.

Five studies evaluating the impact on mental health and mood of recalling, reading, and discussing fiction.

Does reading fiction improve mental health and well-being? We present the results of five studies that evaluated the impact of five forms of exposure to fiction. These included the effects of recalling reading fiction, of being prescribed fiction, of discussing fiction relative to non-fiction, and of discussing literary fiction relative to best-seller fiction. The first three studies directly recruited participants; the final two relied on scraped social media data from Reddit and Twitter.

Quantitative methods for group bibliotherapy research: a pilot study.

Background: Bibliotherapy is under-theorized and under-tested: Its purposes and implementations vary widely, and the idea that 'reading is good for you' is often more assumed than demonstrated. One obstacle to developing robust empirical and theoretical foundations for bibliotherapy is the absence of analytical methods capable of providing sensitive yet replicable insights into complex textual material. This pilot study offers a proof-of-concept for new quantitative methods including VAD (valence-arousal-dominance) modelling of emotional variance and doc2vec modelling of linguistic similarity.

Thinking avant la lettre: A Review of 4E Cognition.

The "4E" approach to cognition argues that cognition does not occur solely in the head, but is also , , , or by way of extra-cranial processes and structures. Though very much in vogue, 4E cognition has received relatively few critical evaluations. By reflecting on two recent collections, this article reviews the 4E paradigm with a view to assessing its strengths and weaknesses.

Gene editing and CRISPR in the clinic: current and future perspectives.

Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases which require cell modification in vivo.

Fictional narrative as a variational Bayesian method for estimating social dispositions in large groups.

Modelling intentions in large groups is cognitively costly. Not alone must first order beliefs be tracked ('what does A think about X?'), but also beliefs about beliefs ('what does A think about B's belief concerning X?'). Thus linear increases in group size impose non-linear increases in cognitive processing resources.

The Lancaster Sensorimotor Norms: multidimensional measures of perceptual and action strength for 40,000 English words.

Sensorimotor information plays a fundamental role in cognition. However, the existing materials that measure the sensorimotor basis of word meanings and concepts have been restricted in terms of their sample size and breadth of sensorimotor experience. Here we present norms of sensorimotor strength for 39,707 concepts across six perceptual modalities (touch, hearing, smell, taste, vision, and interoception) and five action effectors (mouth/throat, hand/arm, foot/leg, head excluding mouth/throat, and torso), gathered from a total of 3,500 individual participants using Amazon's Mechanical Turk platform.

Culture and mood disorders: the effect of abstraction in image, narrative and film on depression and anxiety.

Can cultural representations be used to therapeutic effect in the treatment of mood disorders like depression and anxiety? This article develops a theoretical framework that outlines how this might be achieved by way of mid-level cultural metrics that allow otherwise heterogeneous forms of representation to be grouped together. Its prediction is that abstract representations-as measured by Shannon entropy-will impact positively on anxiety, where concrete representations will positively impact on depression. The background to the prediction comes from construal level theory, a branch of social psychology that deals with the effects of abstraction on psychological distance; the types of cultural representations analysed include image, narrative and film.

Delivering CRISPR: a review of the challenges and approaches.

Gene therapy has long held promise to correct a variety of human diseases and defects. Discovery of the Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR), the mechanism of the CRISPR-based prokaryotic adaptive immune system (CRISPR-associated system, Cas), and its repurposing into a potent gene editing tool has revolutionized the field of molecular biology and generated excitement for new and improved gene therapies. Additionally, the simplicity and flexibility of the CRISPR/Cas9 site-specific nuclease system has led to its widespread use in many biological research areas including development of model cell lines, discovering mechanisms of disease, identifying disease targets, development of transgene animals and plants, and transcriptional modulation.

Functional Benefits of (Modest) Alcohol Consumption.

Alcohol use has a long and ubiquitous history. Despite considerable research on the misuse of alcohol, no one has ever asked why it might have become universally adopted, although the conventional view assumes that its only benefit is hedonic. In contrast, we suggest that alcohol consumption was adopted because it has social benefits that relate both to health and social bonding.

Women favour dyadic relationships, but men prefer clubs: cross-cultural evidence from social networking.

The ability to create lasting, trust-based friendships makes it possible for humans to form large and coherent groups. The recent literature on the evolution of sociality and on the network dynamics of human societies suggests that large human groups have a layered structure generated by emotionally supported social relationships. There are also gender differences in adult social style which may involve different trade-offs between the quantity and quality of friendships.

Inference or enaction? The impact of genre on the narrative processing of other minds.

Do narratives shape how humans process other minds or do they presuppose an existing theory of mind? This study experimentally investigated this problem by assessing subject responses to systematic alterations in the genre, levels of intentionality, and linguistic complexity of narratives. It showed that the interaction of genre and intentionality level are crucial in determining how narratives are cognitively processed. Specifically, genres that deployed evolutionarily familiar scenarios (relationship stories) were rated as being higher in quality when levels of intentionality were increased; conversely, stories that lacked evolutionary familiarity (espionage stories) were rated as being lower in quality with increases in intentionality level.

Structure-based design of supercharged, highly thermoresistant antibodies.

Mutation of surface residues to charged amino acids increases resistance to aggregation and can enable reversible unfolding. We have developed a protocol using the Rosetta computational design package that "supercharges" proteins while considering the energetic implications of each mutation. Using a homology model, a single-chain variable fragment antibody was designed that has a markedly enhanced resistance to thermal inactivation and displays an unanticipated ≈30-fold improvement in affinity.

Llama-derived single domain antibodies specific for Abrus agglutinin.

Llama derived single domain antibodies (sdAb), the recombinantly expressed variable heavy domains from the unique heavy-chain only antibodies of camelids, were isolated from a library derived from llamas immunized with a commercial abrin toxoid preparation. Abrin is a potent toxin similar to ricin in structure, sequence and mechanism of action. The selected sdAb were evaluated for their ability to bind to commercial abrin as well as abrax (a recombinant abrin A-chain), purified abrin fractions, Abrus agglutinin (a protein related to abrin but with lower toxicity), ricin, and unrelated proteins.

Human Mre11/human Rad50/Nbs1 and DNA ligase IIIalpha/XRCC1 protein complexes act together in an alternative nonhomologous end joining pathway.

Recent studies have implicated a poorly defined alternative pathway of nonhomologous end joining (alt-NHEJ) in the generation of large deletions and chromosomal translocations that are frequently observed in cancer cells. Here, we describe an interaction between two factors, hMre11/hRad50/Nbs1 (MRN) and DNA ligase IIIα/XRCC1, that have been linked with alt-NHEJ. Expression of DNA ligase IIIα and the association between MRN and DNA ligase IIIα/XRCC1 are altered in cell lines defective in the major NHEJ pathway.

Molecular disruption of RAD50 sensitizes human tumor cells to cisplatin-based chemotherapy.

Platinum-based drugs that induce DNA damage are commonly used first-line chemotherapy agents for testicular, bladder, head and neck, lung, esophageal, stomach, and ovarian cancers. The inherent resistance of tumors to DNA damage often limits the therapeutic efficacy of these agents, such as cisplatin. An enhanced DNA repair and telomere maintenance response by the Mre11/Rad50/Nbs1 (MRN) complex is critical in driving this chemoresistance.

Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair.

Mre11 forms the core of the multifunctional Mre11-Rad50-Nbs1 (MRN) complex that detects DNA double-strand breaks (DSBs), activates the ATM checkpoint kinase, and initiates homologous recombination (HR) repair of DSBs. To define the roles of Mre11 in both DNA bridging and nucleolytic processing during initiation of DSB repair, we combined small-angle X-ray scattering (SAXS) and crystal structures of Pyrococcus furiosus Mre11 dimers bound to DNA with mutational analyses of fission yeast Mre11. The Mre11 dimer adopts a four-lobed U-shaped structure that is critical for proper MRN complex assembly and for binding and aligning DNA ends.

Inhibition of the 5' to 3' exonuclease activity of hEXO1 by 8-oxoguanine.

The mismatch repair pathway is responsible for maintaining genomic stability by correcting base-base mismatches and insertion/deletion loops that arise mainly via replication errors. Additionally, the mismatch repair pathway performs a central role in the cellular response to both alkylation and reactive oxygen species induced DNA damage. An important step in mismatch processing is the recruitment of hEXO1, a 5' to 3' exonuclease, by hMSH2-hMSH6 to remove the nascent DNA strand.

Dimerization of the Rad50 protein is independent of the conserved hook domain.

The Mre11 complex (Mre11-Rad50-Nbs1) is involved in a diverse array of DNA metabolic processes including the response to DNA double-strand breaks (DSBs). The structure of Rad50 plays a key role in the DNA-binding and end-bridging activity of the complex. An interesting feature within the central portion of the Rad50 protein is the Rad50 hook region that is defined by the highly conserved CXXC motif.

Radiosensitization of head/neck squamous cell carcinoma by adenovirus-mediated expression of the Nbs1 protein.

Purpose: Local failure and toxicity to adjacent critical structures is a significant problem in radiation therapy of cancers of the head and neck. We are developing a gene therapy based method of sensitizing head/neck squamous cell carcinoma (HNSCC) to radiation treatment. As patients with the rare hereditary disorder, Nijmegen breakage syndrome, show radiation sensitivity we hypothesized that tumor-specific disruption of the function of the Nbs1 protein would lead to enhanced cellular sensitivity to ionizing radiation.

Defective p53 response and apoptosis associated with an ataxia-telangiectasia-like phenotype.

Ataxia-telangiectasia mutated (ATM), the protein defective in ataxia-telangiectasia, plays a central role in DNA damage response and signaling to cell cycle checkpoints. We describe here a cell line from a patient with an ataxia-telangiectasia-like clinical phenotype defective in the p53 response to radiation but with normal ATM activation and efficient downstream phosphorylation of other ATM substrates. No mutations were detected in ATM cDNA.

Mechanisms of eukaryotic DNA double strand break repair.

For all cells, a DNA double strand break (DSB) is a dangerous lesion that can have profound consequences for the genome. If a DSB is encountered during mitosis, chromosomal separation may be adversely affected. Alternatively, during S phase a DSB may cause replication fork stalling or collapse.

Proliferating hemangioma of infancy: successful treatment with topical 5% imiquimod cream.

A 4-month-old girl had a proliferating hemangioma of infancy (infantile hemangioma) affecting the chest wall. The lesion had appeared 1 week after birth, demonstrating both superficial and deep components, and was rapidly enlarging. It had become painful and superficially eroded.