Debates around the issues of knowledge of, and for, social work and other social justice–oriented professions are not uncommon. More prevalent are the discussions around the ways by which social work ...knowledge is obtained. In recent years, social work scholars have drawn on the epistemology of pragmatism to present a case for its value in the creation of knowledge for social work and other social justice–oriented professions. The primary focus of this essay is on providing a critical review and synthesis of the literature regarding pragmatism as a research paradigm. In this essay, we analyze the major philosophical underpinnings and methodological challenges associated with pragmatism, synthesize the works of scholars who have contributed to the understanding of pragmatism as a research paradigm, articulate our thoughts about how pragmatism fits within social work research, and illustrate how it is linked to the pursuit of social justice. This article brings together a variety of perspectives to argue that pragmatism has the potential to closely engage and empower marginalized and oppressed communities and provide hard evidence for the macro level discourse.
The Genetics of Primary Microcephaly Jayaraman, Divya; Bae, Byoung-Il; Walsh, Christopher A
Annual review of genomics and human genetics,
08/2018, Letnik:
19, Številka:
1
Journal Article
Recenzirano
Primary microcephaly (MCPH, for "microcephaly primary hereditary") is a disorder of brain development that results in a head circumference more than 3 standard deviations below the mean for age and ...gender. It has a wide variety of causes, including toxic exposures, in utero infections, and metabolic conditions. While the genetic microcephaly syndromes are relatively rare, studying these syndromes can reveal molecular mechanisms that are critical in the regulation of neural progenitor cells, brain size, and human brain evolution. Many of the causative genes for MCPH encode centrosomal proteins involved in centriole biogenesis. However, other MCPH genes fall under different mechanistic categories, notably DNA replication and repair. Recent gene discoveries and functional studies have implicated novel cellular processes, such as cytokinesis, centromere and kinetochore function, transmembrane or intracellular transport, Wnt signaling, and autophagy, as well as the apical polarity complex. Thus, MCPH genes implicate a wide variety of molecular and cellular mechanisms in the regulation of cerebral cortical size during development.
Resolving lineage relationships between cells in an organism is a fundamental interest of developmental biology. Furthermore, investigating lineage can drive understanding of pathological states, ...including cancer, as well as understanding of developmental pathways that are amenable to manipulation by directed differentiation. Although lineage tracking through the injection of retroviral libraries has long been the state of the art, a recent explosion of methodological advances in exogenous labelling and single-cell sequencing have enabled lineage tracking at larger scales, in more detail, and in a wider range of species than was previously considered possible. In this Review, we discuss these techniques for cell lineage tracking, with attention both to those that trace lineage forwards from experimental labelling, and those that trace backwards across the life history of an organism.
During prenatal brain development, ion channels are ubiquitous across several cell types, including progenitor cells and migrating neurons but their function has not been clear. In the past, ion ...channel dysfunction has been primarily studied in the context of postnatal, differentiated neurons that fire action potentials – notably ion channels mutated in the epilepsies – yet data now support a surprising role in prenatal human brain disorders as well. Modern gene discovery approaches have identified defective ion channels in individuals with cerebral cortex malformations, which reflect abnormalities in early-to-middle stages of embryonic development (prior to ubiquitous action potentials). These human genetics studies and recent in utero animal modeling work suggest that precise control of ionic flux (calcium, sodium, and potassium) contributes to in utero developmental processes such as neural proliferation, migration, and differentiation.
Developmental channelopathy is an ion channel disease with a pathophysiological origin during the gestational period.Human genetics studies reveal that individuals with dysfunctional sodium and glutamate channels can have improperly folded cerebral cortices.The gestational brain is comprised of diverse and transient cell types, including dividing and newly differentiated cells. Some of the mechanisms involved in developmental channelopathies during gestation are different from those acting postnatally during ion channel diseases.Ion channel mutations that result in greater excitability (gain-of-function) are often associated with human cortical malformations.
Genetic mutations causing human disease are conventionally thought to be inherited through the germ line from one's parents and present in all somatic (body) cells, except for most cancer mutations, ...which arise somatically. Increasingly, somatic mutations are being identified in diseases other than cancer, including neurodevelopmental diseases. Somatic mutations can arise during the course of prenatal brain development and cause neurological disease-even when present at low levels of mosaicism, for example-resulting in brain malformations associated with epilepsy and intellectual disability. Novel, highly sensitive technologies will allow more accurate evaluation of somatic mutations in neurodevelopmental disorders and during normal brain development.
People with rheumatoid arthritis (RA) identify pain as their most important symptom, one that often persists despite optimal control of inflammatory disease. RA pain arises from multiple mechanisms, ...involving inflammation, peripheral and central pain processing and, with disease progression, structural change within the joint. Consequently, RA pain has a wide range of characteristics-constant or intermittent, localized or widespread-and is often associated with psychological distress and fatigue. Dominant pain mechanisms in an individual are identified by critical evaluation of clinical symptoms and signs, and by laboratory and imaging tests. Understanding these mechanisms is essential for effective management, although evidence from preclinical models should be interpreted with caution. A range of pharmacological analgesic and immunomodulatory agents, psychological interventions and surgery may help manage RA pain. Pain contributes importantly to the clinical assessment of inflammatory disease activity, and noninflammatory components of RA pain should be considered when gauging eligibility for or response to biologic agents. Further randomized controlled trials are required to determine the optimal usage of analgesics in RA, and novel agents with greater efficacy and lower propensity for adverse events are urgently needed. Meanwhile, targeted use of existing treatments could reduce pain in people with RA.
During osteoarthritis (OA), angiogenesis is increased in the synovium, osteophytes and menisci and leads to ossification in osteophytes and the deep layers of articular cartilage. Angiogenic and ...antiangiogenic factors might both be upregulated in the osteoarthritic joint; however, vascular growth predominates, and the articular cartilage loses its resistance to vascularization. In addition, blood vessel growth is increased at--and disrupts--the osteochondral junction. Angiogenesis in this location is dependent on the creation of channels from subchondral bone spaces into noncalcified articular cartilage. Inflammation drives synovial angiogenesis through macrophage activation. Blood vessel and nerve growth are linked by common pathways that involve the release of proangiogenic factors, such as vascular endothelial growth factor, β-nerve growth factor and neuropeptides. Proangiogenic factors might also stimulate nerve growth, and molecules produced by vascular cells could both stimulate and guide nerve growth. As sensory nerves grow along new blood vessels in osteoarthritic joints, they eventually penetrate noncalcified articular cartilage, osteophytes and the inner regions of menisci. Angiogenesis could, therefore, contribute to structural damage and pain in OA and provide potential targets for new treatments.
The Solar Orbiter magnetometer Horbury, T. S.; O’Brien, H.; Carrasco Blazquez, I. ...
Astronomy & astrophysics,
10/2020, Letnik:
642
Journal Article
Recenzirano
Odprti dostop
The magnetometer instrument on the Solar Orbiter mission is designed to measure the magnetic field local to the spacecraft continuously for the entire mission duration. The need to characterise not ...only the background magnetic field but also its variations on scales from far above to well below the proton gyroscale result in challenging requirements on stability, precision, and noise, as well as magnetic and operational limitations on both the spacecraft and other instruments. The challenging vibration and thermal environment has led to significant development of the mechanical sensor design. The overall instrument design, performance, data products, and operational strategy are described.
A major unanswered question in neuroscience is whether there exists genomic variability between individual neurons of the brain, contributing to functional diversity or to an unexplained burden of ...neurological disease. To address this question, we developed a method to amplify genomes of single neurons from human brains. Because recent reports suggest frequent LINE-1 (L1) retrotransposition in human brains, we performed genome-wide L1 insertion profiling of 300 single neurons from cerebral cortex and caudate nucleus of three normal individuals, recovering >80% of germline insertions from single neurons. While we find somatic L1 insertions, we estimate <0.6 unique somatic insertions per neuron, and most neurons lack detectable somatic insertions, suggesting that L1 is not a major generator of neuronal diversity in cortex and caudate. We then genotyped single cortical cells to characterize the mosaicism of a somatic AKT3 mutation identified in a child with hemimegalencephaly. Single-neuron sequencing allows systematic assessment of genomic diversity in the human brain.
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▸ Whole-genome amplification and sequencing of single neurons from human brains ▸ Single-neuron genome-wide analysis of somatic L1 retrotransposition ▸ Somatic L1 insertions are infrequent in cerebral cortex and caudate nucleus ▸ Single-cell analysis of a somatic mutation causing malformation of the brain
Whole-genome sequencing of individual neurons from human brain shows that retrotransposition of the L1 element is infrequent. L1 insertions may thus generate some somatic mutations but are unlikely to account for neuronal diversity.
•SARS-CoV-2 viral loads peak from upper respiratory tract samples around symptom onset.•Viral loads from sputum samples may be higher than upper respiratory tract samples.•Viral loads appear to be ...similar between asymptomatic and symptomatic patients.•The prolonged virus detection in stool samples has unclear clinical significance.•Patients may not be infectious for the entire duration of virus detection.
To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity.
A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020.
We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance.
No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus.
There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.
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