Engineering Nitrogenases for synthetic nitrogen fixation: From pathway engineering to directed evolution

Globally, agriculture depends on industrial nitrogen fertilizer to improve crop growth. Fertilizer production consumes fossil fuels and contributes to environmental nitrogen pollution. A potential solution would be to harness nitrogenases—enzymes capable of converting atmospheric nitrogen N2 to NH3 in ambient conditions. It is therefore a major goal of synthetic biology to engineer functional nitrogenases into crop plants, or bacteria that form symbiotic relationships with crops, to support growth and reduce dependence on industrially produced fertilizer. This review paper highlights recent work toward understanding the functional requirements for nitrogenase expression and manipulating nitrogenase gene expression in heterologous hosts to improve activity and oxygen tolerance and potentially to engineer synthetic symbiotic relationships with plants

Climate change and adaptation to social-ecological change: the case of indigenous people and culture-based fisheries in Sri Lanka

Rural coastal fishery systems in tropical island nations are undergoing rapid change. Using a case study from eastern Sri Lanka, this paper examines the ways in which indigenous Coastal-Vedda fishers experience and respond to such change. We conducted semi-structured interviews (n = 74), focus group discussions (n = 17, 98 participants), and key informant interviews (n = 38) over a 2-year period (2016–2019). The changes that most Coastal-Vedda fishers experience are disturbance from Sri Lankan ethnic war, changes in climate and the frequency and severity of natural disasters, increased frequency of human-elephant conflicts, increasingly unpredictable weather patterns, and transformation of the Coastal-Vedda due to social modernisation. We used a resilience-based conceptual framework focusing on place, human agency, collective action and collaboration, institutions, indigenous and local knowledge systems, and learning to examine fishers’ responses to rapid changes. We identified three community-level adaptive strategies used by the Coastal-Vedda: adaptive institutions with a multi-level institutional structure that facilitates collective action and collaboration, the use of culture-based fisheries (CBF), and diversification of livelihoods. We also recognized four place-specific attributes that shaped community adaptations: cultural identity and worldviews, co-management of CBF, flexibility in choosing adaptive options, and indigenous and local knowledge systems and learning. These adaptive strategies and place-specific attributes provide new insights for scientists, policymakers, and communities in the region, enabling them to more effectively work together to support community adaptation

Profile of the most common complaints for five health professions in Australia

© 2019 AHHA. Objective: The aims of this study were to profile the most common complaints and to examine whether any demographic factors are associated with receiving a complaint for five health professions in Australia. Methods: A national cohort study was conducted for all complaints received for medicine, nursing/midwifery, dentistry, pharmacy and psychology from 1 July 2012 to 31 December 2013 (18 months). Data were collected from the Australian Health Practitioner Regulation Agency (AHPRA), the New South Wales (NSW) Health Professional Councils' Authority and the NSW Health Care Complaints Commission. The frequency and risk of complaints were summarised for the five professions and by demographic information. Results: There were 545 283 practitioners registered with AHPRA between 1 July 2012 and 31 December 2013, consisting of 20 935 dentists, 101 066 medical practitioners, 363 040 nurses/midwives, 28 370 pharmacists and 31 872 psychologists. During the study period there were 12 616 complaints, corresponding to an annual rate of 1.5 per 100 practitioners. Complaints were most common for doctors and dentists (5% per annum per practitioner) and least common for nurses/midwives (0.5% per annum per practitioner). Sex (P < 0.01), age (P < 0.01) and country of birth (P < 0.01) were all associated with risk of complaint. The most common complaints were clinical care (44% of all complaints), medication (10%) and health impairment of the practitioner (8%). Types of complaints varied by profession, sex and age. Conclusions: The risk of a complaint is low, but varies by profession and demographics. The types of complaints also vary by profession and demographics. Differences between professions is most likely driven by their different work tasks and work environments. What is already known on this subject?: Although complaints are summarised annually from state and national health regulators, no overall national summary of complaints across professions exists. Thus, it is difficult to examine which complaints are most common, how professions differ from each other or what factors may be associated with risk and type of complaint. Previous studies have primarily focused on a single profession, such as medicine, where, for example, the number of prior complaints, sex, doctor speciality and age have been found to be associated with recurrent complaints. What does this paper add?: This paper is the first of this kind to provide a national summary of all complaints from five of the most common health professions in Australia. We found that regardless of profession, men were at least twice as likely to have a complaint made against them than women. We also found that the types of complaint differed between men and women. There were similarities across professions for the most common types of complaints, but clear differences between professions were also noted. Not surprising, clinical care was typically the most common type of complaint for the five professions, but somewhat surprising was the inclusion of health impairment as one of the most common types of complaints. What are the implications for practitioners?: Identifying the most common complaints, and the factors associated with these, may assist practitioners to understand their risk(s) of complaint and could potentially assist educators and regulators develop education programs that help reduce complaints

A framework for assessing community adaptation to climate change in a fisheries context

There is a rapidly growing body of scholarship on climate change adaptation in diverse contexts globally. Despite this, climate adaptation at the community level has not received adequate conceptual attention, and a limited number of analytical frameworks are available for assessing place-specific adaptations, particularly in a fisheries context. We use conceptual material from social-ecological systems (SES) resilience and human development resilience to build an integrated framework for evaluating community adaptations to climate change in a fisheries setting. The framework defines resilience as the combined result of coping, adapting, and transforming—recognizing resilience as a system’s capacity and as a process. This understanding of resilience integrates with the three development resilience concepts of resistance, rootedness, and resourcefulness to develop ‘place-based elements’ which refer to collective action, institutions, agency, and indigenous and local knowledge systems. The proposed framework can capture a local setting’s place-specific attributes relating to the well-being of individuals, households, and communities, and the through integration of SES and human development conceptualizations addresses some of the key critiques of the notion of resilience. We have proposed this framework for application in context-specific environments—including fisheries—as a means of assessing community adaptations

Experiences of Inpatient Bone Marrow Transplantation Nurses and Providers Using Electronic Symptom Reporting

Purpose To investigate the use of electronic patient-reported outcomes (PROs) to assess symptoms and how they can provide opportunities to clinicians to address symptoms in a timely manner to improve clinical care. As part of a larger study to evaluate whether providing standardized symptom reports to the medical team would decrease the time to treatment of reported symptoms in hematopoietic stem-cell transplant recipients, we assessed nurses’ and providers’ perceptions of electronic symptom reporting. Methods Semistructured interviews of RNs, MDs, NPs and PAs were conducted at an academic cancer center in the southeastern United States. Nurses’ and providers’ perceptions of electronic symptom reporting were explored. Interviews were audio-recorded, transcribed, and coded by two investigators to identify major themes. Results Fourteen RNs and seven providers (MDs, PAs, and NPs) participated in the interviews. Three main themes emerged from the interviews: electronic symptom reporting may improve assessment and care, integrating symptom reporting into nurse workflow presents difficulties, and there are barriers for completion of surveys. Conclusion The majority of nurses and providers believed that the inclusion of electronic symptom reporting in bone marrow transplantation inpatient units has the potential to improve care but that barriers to implementation remain

Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development

Cognitive reserve, presynaptic proteins and dementia in the elderly

Differences in cognitive reserve may contribute to the wide range of likelihood of dementia in people with similar amounts of age-related neuropathology. The amounts and interactions of presynaptic proteins could be molecular components of cognitive reserve, contributing resistance to the expression of pathology as cognitive impairment. We carried out a prospective study with yearly assessments of N=253 participants without dementia at study entry. Six distinct presynaptic proteins, and the protein–protein interaction between synaptosomal-associated protein 25 (SNAP-25) and syntaxin, were measured in post-mortem brains. We assessed the contributions of Alzheimer's disease (AD) pathology, cerebral infarcts and presynaptic proteins to odds of dementia, level of cognitive function and cortical atrophy. Clinical dementia was present in N=97 (38.3%), a pathologic diagnosis of AD in N=142 (56.1%) and cerebral infarcts in N=77 (30.4%). After accounting for AD pathology and infarcts, greater amounts of vesicle-associated membrane protein, complexins I and II and the SNAP-25/syntaxin interaction were associated with lower odds of dementia (odds ratio=0.36–0.68, P<0.001 to P=0.03) and better cognitive function (P<0.001 to P=0.03). Greater cortical atrophy, a putative dementia biomarker, was not associated with AD pathology, but was associated with lower complexin-II (P=0.01) and lower SNAP-25/syntaxin interaction (P<0.001). In conclusion, greater amounts of specific presynaptic proteins and distinct protein–protein interactions may be structural or functional components of cognitive reserve that reduce the risk of dementia with aging

Reconstructing the three-dimensional GABAergic microcircuit of the striatum

A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study