GAPscreener: An automatic tool for screening human genetic association literature in PubMed using the support vector machine technique

Background  

Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM), a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies.     

Development of a novel mammalian display system for selection of antibodies against membrane proteins

Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 10⁹ variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (K_D) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.     

Tagging of biomolecules with deuterated water (D2O) in commercially important microalgae

To understand the effect of any biomolecules in specific metabolic pathways in humans, bioavailability and for other basic understanding, stable isotopically-labelled biomolecules (preferably deuterated) is the fundamental pre-requisite. Production of deuterated biomolecules such as, astaxanthin, β-carotene, lutein, chlorophyll-a, and eicosapentaenoic acid (EPA, 20:5n-3) by metabolic tagging have been shown in commercially important microalgae, Haematococcus pluvialis and Phaeodactylum tricornutum. These microalgae were grown in appropriate optimized medium supplemented with 25 % (v/v) deuterated water. LC–MS analysis showed a maximum of 20, 25, 23, 24, and 27 % replacement of hydrogen by deuterium atoms respectively in astaxanthin, β-carotene, lutein, chlorophyll-a, and EPA. To our knowledge, this is the first report on the production of deuterated astaxanthin, chlorophyll-a and EPA by these microalgae.     

Efficiency of incision of an AP site within clustered DNA damage by the major human AP endonuclease.

A major DNA lesion induced by ionizing radiation and formed on removal of oxidized base lesions by various glycosylases is an apurinic/apyrimidinic site (AP site). The presence of an AP site within clustered DNA damage, induced following exposure to ionizing radiation or radiomimetic anticancer agents, may present a challenge to the repair machinery of the cell, if the major human AP endonuclease, HAP1, does not efficiently incise the AP site. In this study, specific oligonucleotide constructs containing an AP site located at several positions opposite to another damage [5,6-dihydrothymine (DHT), 8-oxoG, AP site, or various types of single strand breaks] on the complementary strand were used to determine the relative efficiency of the purified HAP1 protein in incising an AP site(s) from clustered DNA damage. A base damage (DHT and 8-oxoG) on the opposite strand has little or no influence on the rate of incision of an AP site by HAP1. In contrast, the presence of either a second AP site or various types of single strand breaks, when located one or three bases 3' to the base opposite to the AP site, has a strong inhibitory effect on the efficiency of incision of an AP site. The efficiency of binding of HAP1 to an AP site is reduced by approximately 1 order of magnitude if a single strand break (SSB) is located one or three bases 3' to the site opposite to the AP site on the complementary strand. If the AP site and either a SSB or a second AP site are located at any of the other positions relative to each other, a double strand break may result.     

Other Dark Sides of Resilience: Politics and Power in Community-Based Efforts to Strengthen Resilience

ABSTRACT

Oceanic people and places are increasingly labelled as either ‘resilient’ or ‘vulnerable’ to disasters and climate change. Resilience is often described in disaster discourse as a strategy designed to overcome vulnerability by helping communities to ‘bounce back’ in the wake of ‘natural’ disasters. Using ethnographic research conducted with Community Disaster and Climate Change Committees (CDCs) in Vanuatu in the wake of Tropical Cyclone Pam, this paper seeks to problematise disaster responses that see the ‘community’ as a space to be acted upon by outsiders, or where people will respond in a unified way to the challenges of rebuilding after disaster. Using political ecology framings this paper critiques the ideas of resilience that appear entrenched in community-based disaster and climate change adaptation discourse and practice in Oceania. Rather than presupposing resilience or vulnerability, this paper details the dispersal and distribution power and agency amongst individual actors and groups that either supported or manipulated, the distribution of goods by Community Disaster Committees. In this way, it moves beyond the limitations of conceptual framings of resilience in disaster management and climate change into a more considered appraisal of power, by exploring what James Ferguson has termed ‘the politics of distribution’ in the context of disaster.     

The relationship between the comb and social behaviour in laying hens

The question of whether attributes of the combs of laying hens have any consistent relationship with dominance behaviour has yet to be answered unequivocally. This study sought to address this by investigating whether a relationship existed between the competitive ability of hens within stable groups and the size or colour of their combs. Pullets (n = 120, Hy-line^® Variety Brown) were allocated randomly to eight groups of 15 hens for 32 weeks. Over this period the length and height of each hen's comb was measured regularly to estimate the total comb area and hens were weighed. In weeks 3-10 the aggressive interactions between hens in each group were observed to calculate a behavioural dominance score (David's score) for each hen. This score was based on the outcome of agonistic interactions with other group members; and accounts for the relative strengths of all opponents. Thus dominance scores reflected the competitive ability of hens from their overall within-group fighting success. The luminance, purity and dominant wavelength of the colour of each hen's comb was measured in week 27 using a telespectroradiometer. Hens with higher dominance scores had larger combs than those with lower dominance scores (gradient of slope = 0.008 ± 0.002, P < 0.001); this relationship was consistent across the experiment. There was no association between body weight and dominance score but there was a significant inverse relationship between dominance score and the dominant wavelength of the comb (gradient of slope = −0.067 ± 0.023, P < 0.01). This indicated that hens with combs perceived by humans as more yellow-red than pure red were generally more successful competitors. Further research is required to ascertain whether or not hens utilise this information on comb size and the underexplored area of comb colour to assess the competitive ability of their opponents.     

Anno genominis XX: 20 years of Arabidopsis genomics

Twenty years ago, the Arabidopsis thaliana genome sequence was published. This was an important moment as it was the first sequenced plant genome and explicitly brought plant science into the genomics era. At the time, this was not only an outstanding technological achievement, but it was characterized by a superb global collaboration. The Arabidopsis genome was the seed for plant genomic research. Here, we review the development of numerous resources based on the genome that have enabled discoveries across plant species, which has enhanced our understanding of how plants function and interact with their environments.

The publication of the Arabidopsis genome sequence 20 years ago has had an enormous impact on the global plant science community.     

Confronting the Naturalness of Disaster in the Pacific

ABSTRACT

This introduction sets out some of the key themes addressed by the papers in the special issue on ‘Confronting the Naturalness of Disaster in the Pacific’. Disasters are now widely understood not as ‘natural’ phenomena but as events or processes that unfold at the intersection between natural or artificial hazards and human populations. We review some of the effects of the naturalisation of disaster before turning to the ways in which Pacific disasters are defined through government, media and public discourses. These discourses feature their own distinctive accounts of possible forms of agency in the context of disaster, and draw on markedly different frames of reference in attributing cause and blame. Similarly, contrasting temporalities and spatialities are invoked in addressing disasters as bounded phenomena. We conclude with reflections on the nature of responses to disaster in the Pacific in the context of increasingly unstable cultural, economic and environmental grounds for action induced by global climate change     

Effectiveness of intrapartum fetal surveillance to improve maternal and neonatal outcomes: a systematic review and network meta-analysis

BACKGROUND:Cesarean delivery is the most common surgical procedure worldwide. Intrapartum fetal surveillance is routinely offered to improve neonatal outcomes, but the effects of different methods on the risk of emergency cesarean deliveries remains uncertain. We conducted a systematic review and network meta-analysis to evaluate the effectiveness of different types of fetal surveillance.METHODS:We searched MEDLINE, Embase and CENTRAL until June 1, 2020, for randomized trials evaluating any intrapartum fetal surveillance method. We performed a network meta-analysis within a frequentist framework. We assessed the quality and network inconsistency of trials. We reported primarily on intrapartum emergency cesarean deliveries and other secondary maternal and neonatal outcomes using risk ratios (RRs) and 95% confidence intervals (CIs).RESULTS:We included 33 trials (118 863 patients) evaluating intermittent auscultation with Pinard stethoscope/handheld Doppler (IA), cardiotocography (CTG), computerized cardiotocography (cCTG), CTG with fetal scalp lactate (CTG-lactate), CTG with fetal scalp pH analysis (CTG-FBS), CTG with fetal pulse oximetry (FPO-CTG), CTG with fetal heart electrocardiogram (CTG-STAN) and their combinations. Intermittent auscultation reduced the risk of emergency cesarean deliveries compared with other types of surveillance (IA v. CTG: RR 0.83, 95% CI 0.72–0.97; IA v. CTG-FBS: RR 0.71, 95% CI 0.63–0.80; IA v.CTG-lactate: RR 0.77, 95% CI 0.64–0.92; IA v. FPO-CTG: RR 0.75, 95% CI 0.65–0.87; IA v.FPO-CTG-FBS: RR 0.81, 95% CI 0.67–0.99; cCTG-FBS v. IA: RR 1.21, 95% CI 1.04–1.42), except STAN-CTG-FBS (RR 1.17, 95% CI 0.98–1.40). There was a similar reduction observed for emergency cesarean deliveries for fetal distress. None of the evaluated methods was associated with a reduced risk of neonatal acidemia, neonatal unit admissions, Apgar scores or perinatal death.INTERPRETATION:Compared with other types of fetal surveillance, intermittent auscultation seems to reduce emergency cesarean deliveries in labour without increasing adverse neonatal and maternal outcomes.

Cesarean delivery is the most common surgical procedure worldwide, performed to expedite delivery and avoid neonatal complications. Fetal surveillance is routinely offered to patients in labour to reduce the risk of adverse neonatal outcomes, as well as the risk of unnecessary emergency cesarean deliveries and other maternal interventions. Fetal surveillance aims to detect intrapartum hypoxia from acute or subacute adverse events in labour requiring medical intervention and to reduce the risk of serious complications such as neonatal cerebral palsy, hypoxic–ischemic encephalopathy or stillbirth.Monitoring the fetal heart rate to detect intrapartum hypoxia using simple surveillance techniques, such as the Pinard stethoscope, has been practised for decades.¹ Over the last 50 years, several newer surveillance methods have been evaluated, with varied uptake in practice.² Cardiotocography (CTG) remains the most common surveillance method used in high-risk pregnancies.³ However, given its limited accuracy, many researchers have evaluated its use in combination with other surveillance methods, such as fetal heart electrocardiogram (STAN), fetal scalp pH analysis (FBS) or fetal pulse oximetry (FPO), and with computer-aided decision models (cCTG) to improve its diagnostic value.^4–6 Despite extensive investment in clinical research, the overall effectiveness of such methods in improving maternal and neonatal outcomes remains debatable as stillbirth rates have plateaued worldwide, while cesarean delivery rates continue to rise.^7,8Existing meta-analyses evaluating different intrapartum fetal surveillance methods remain limited to head-to-head comparisons of monitoring techniques, without a comprehensive assessment of their effectiveness in improving maternal and neonatal pregnancy outcomes.^4,9–13 We conducted a systematic review of randomized trials and a network meta-analysis to evaluate the effectiveness of all available fetal surveillance methods in improving maternal and neonatal outcomes.