Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

DNA repair, genome stability and cancer: a historical perspective

The multistep process of cancer progresses over many years. The prevention of mutations by DNA repair pathways led to an early appreciation of a role for repair in cancer avoidance. However, the broader role of the DNA damage response (DDR) emerged more slowly. In this Timeline article, we reflect on how our understanding of the steps leading to cancer developed, focusing on the role of the DDR. We also consider how our current knowledge can be exploited for cancer therapy

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study

BACKGROUND: Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs) in exhaled air of patients with non-small cells lung cancer (NSCLC), by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and analyses were repeated three weeks after the NSCLC patients underwent lung surgery. METHODS: The subjects' breath was collected in a Teflon(® )bulb that traps the last portion of single slow vital capacity. The 13 VOCs selected for this study were concentrated using a solid phase microextraction technique and subsequently analysed by means of gas cromatography/mass spectrometry. RESULTS: The levels of the selected VOCs ranged from 10(-12 )M for styrene to 10(-9 )M for isoprene. None of VOCs alone discriminated the study groups, and so it was not possible to identify one single chemical compound as a specific lung cancer biomarker. However, multinomial logistic regression analysis showed that VOC profile can correctly classify about 80 % of cases. Only isoprene and decane levels significantly decreased after surgery. CONCLUSION: As the combination of the 13 VOCs allowed the correct classification of the cases into groups, together with conventional diagnostic approaches, VOC analysis could be used as a complementary test for the early diagnosis of lung cancer. Its possible use in the follow-up of operated patients cannot be recommended on the basis of the results of our short-term nested study

A literature-based similarity metric for biological processes

BACKGROUND: Recent analyses in systems biology pursue the discovery of functional modules within the cell. Recognition of such modules requires the integrative analysis of genome-wide experimental data together with available functional schemes. In this line, methods to bridge the gap between the abstract definitions of cellular processes in current schemes and the interlinked nature of biological networks are required. RESULTS: This work explores the use of the scientific literature to establish potential relationships among cellular processes. To this end we haveused a document based similarity method to compute pair-wise similarities of the biological processes described in the Gene Ontology (GO). The method has been applied to the biological processes annotated for the Saccharomyces cerevisiae genome. We compared our results with similarities obtained with two ontology-based metrics, as well as with gene product annotation relationships. We show that the literature-based metric conserves most direct ontological relationships, while reveals biologically sounded similarities that are not obtained using ontology-based metrics and/or genome annotation. CONCLUSION: The scientific literature is a valuable source of information from which to compute similarities among biological processes. The associations discovered by literature analysis are a valuable complement to those encoded in existing functional schemes, and those that arise by genome annotation. These similarities can be used to conveniently map the interlinked structure of cellular processes in a particular organism

A Conceptual Analysis of Autistic Masking: Understanding the Narrative of Stigma and the Illusion of Choice

Autistic masking is an emerging research area that focuses on understanding the conscious or unconscious suppression of natural autistic responses and adoption of alternatives across a range of domains. It is suggested that masking may relate to negative outcomes for autistic people, including late/missed diagnosis, mental health issues, burnout, and suicidality. This makes it essential to understand what masking is, and why it occurs. In this conceptual analysis, we suggest that masking is an unsurprising response to the deficit narrative and accompanying stigma that has developed around autism. We outline how classical social theory (i.e., social identity theory) can help us to understand how and why people mask by situating masking in the social context in which it develops. We draw upon the literature on stigma and marginalization to examine how masking might intersect with different aspects of identity (e.g., gender). We argue that although masking might contribute toward disparities in diagnosis, it is important that we do not impose gender norms and stereotypes by associating masking with a “female autism phenotype.” Finally we provide recommendations for future research, stressing the need for increased understanding of the different ways that autism may present in different people (e.g., internalizing and externalizing) and intersectionality. We suggest that masking is examined through a sociodevelopmental lens, taking into account factors that contribute toward the initial development of the mask and that drive its maintenance

ER-Alpha-cDNA As Part of a Bicistronic Transcript Gives Rise to High Frequency, Long Term, Receptor Expressing Cell Clones

Within the large group of Estrogen Receptor alpha (ERα)-negative breast cancer patients, there is a subgroup carrying the phenotype ERα−, PR−, and Her2−, named accordingly “Triple-Negative” (TN). Using cell lines derived from this TN group, we wished to establish cell clones, in which ERα is ectopically expressed, forming part of a synthetic lethality screening system. Initially, we generated cell transfectants expressing a mono-cistronic ERα transcription unit, adjacent to a separate dominant selectable marker transcription unit. However, the yield of ERα expressing colonies was rather low (5–12.5%), and only about half of these displayed stable ectopic ERα expression over time. Generation and maintenance of such cell clones under minimal exposure to the ERα ligand, did not improve yield or expression stability. Indeed, other groups have also reported grave difficulties in obtaining ectopic expression of ERα in ERα-deficient breast carcinoma cells. We therefore switched to transfecting these cell lines with pERα-IRES, a plasmid vector encoding a bicistronic translation mRNA template: ERα Open Reading Frame (ORF) being upstream followed by a dominant-positive selectable marker (hygroR) ORF, directed for translation from an Internal Ribosome Entry Site (IRES). Through usage of this bicistronic vector linkage system, it was possible to generate a very high yield of ERα expressing cell clones (50–100%). The stability over time of these clones was also somewhat improved, though variations between individual cell clones were evident. Our successful experience with ERα in this system may serve as a paradigm for other genes where ectopic expression meets similar hardships

Consequences of lower extremity and trunk muscle fatigue on balance and functional tasks in older people: A systematic literature review

<p>Abstract</p> <p>Background</p> <p>Muscle fatigue reduces muscle strength and balance control in young people. It is not clear whether fatigue resistance seen in older persons leads to different effects. In order to understand whether muscle fatigue may increase fall risk in older persons, a systematic literature review aimed to summarize knowledge on the effects of lower extremity and trunk muscle fatigue on balance and functional tasks in older people was performed.</p> <p>Methods</p> <p>Studies were identified with searches of the PUBMED and SCOPUS data bases.</p> <p>Papers describing effects of lower extremity or trunk muscle fatigue protocols on balance or functional tasks in older people were included. Studies were compared with regards to study population characteristics, fatigue protocol, and balance and functional task outcomes.</p> <p>Results</p> <p>Seven out of 266 studies met the inclusion criteria. Primary findings were: fatigue via resistance exercises to lower limb and trunk muscles induces postural instability during quiet standing; induced hip, knee and ankle muscle fatigue impairs functional reach, reduces the speed and power of sit-to-stand repetitions, and produces less stable and more variable walking patterns; effects of age on degree of fatigue and rate of recovery from fatigue are inconsistent across studies, with these disparities likely due to differences in the fatigue protocols, study populations and outcome measures.</p> <p>Conclusion</p> <p>Taken together, the findings suggest that balance and functional task performance are impaired with fatigue. Future studies should assess whether fatigue is related to increased risk of falling and whether exercise interventions may decrease fatigue effects.</p