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Churches hold different views regarding the office of deacon and role of deacons in the church. Churches also use different terms for their social ministries. This lack of a common language regarding the church's diaconal ministry often creates confusion in the ecumenical discourse on the diaconate of the church. This article explores the hypothesis that the conceptualisation of a church's diaconal ministry is influenced by a specific frame of reference, be it a historical perspective, a specific theology or tradition. In this case study of the Dutch Reformed Church (DRC) it is shown how a specific historical and theological understanding of diaconal ministry determines not only this church's preference for the term 'service of compassion' but also its diaconal praxis. The article concludes with a suggestion to the DRC to consider the use of the concept diakonia in contemplation of more active participation in ecumenical disourses regarding the diaconate of the church. Intradisciplinary and/or interdisciplinary implications The article describes how a specific historical and theological understanding of diaconal ministry determines not only the DRC's preference for the term 'service of compassion' but also its diaconal praxis. The suggestion to more actively participate in developing a common understanding of diakonia ecumenically has implications for the DRC's ecclesiology, as well as its missional and social ministries.

Aicardi-Goutieres syndrome is a genetically determined encephalopathy that is associated with an increased production of interferon alpha, which in turn is central to the pathogenesis of systemic lupus erythematosus. Yanick Crow and colleagues now identify homozygous mutations in an interferon-inducible nuclear gene encoding SAMHD1 in AGS-affected individuals across several pedigrees and characterize its function in modulating an innate immune response. Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.

Key functions of antibodies, such as viral neutralisation, depend on high-affinity binding. However, viral neutralisation poorly correlates with antigen affinity for reasons that have been unclear. Here, we use a new mechanistic model of bivalent binding to study  >45 patient-isolated IgG1 antibodies interacting with SARS-CoV-2 RBD surfaces. The model provides the standard monovalent affinity/kinetics and new bivalent parameters, including the molecular reach: the maximum antigen separation enabling bivalent binding. We find large variations in these parameters across antibodies, including reach variations (22–46 nm) that exceed the physical antibody size (~15 nm). By using antigens of different physical sizes, we show that these large molecular reaches are the result of both the antibody and antigen sizes. Although viral neutralisation correlates poorly with affinity, a striking correlation is observed with molecular reach. Indeed, the molecular reach explains differences in neutralisation for antibodies binding with the same affinity to the same RBD-epitope. Thus, antibodies within an isotype class binding the same antigen can display differences in molecular reach, substantially modulating their binding and functional properties. Researchers developed an accurate model to analyse bivalent antibody binding. By analysing many SARS-CoV-2-specific antibodies, they found that their molecular reach can predict their neutralisation potency.

Background Pathogenic variants that occur in the familial breast cancer genes ( BRCA1/2 ) lead to truncated ineffective proteins in the majority of cases. These variants are mostly represented by small deletions/insertions, nonsense- and splice-site variants, although some larger pathogenic rearrangements occur. Currently, their contribution to familial breast cancer (BC) and ovarian cancer (OVC) in South Africa (SA) is unknown. Methods Seven hundred and forty-four patients affected with BC or OVC were screened for larger genomic rearrangements (LGRs) by means of multiplex ligation-dependent probe amplification or Next Generation Sequencing using the Oncomine™ BRCA research assay. Results The patients represented mostly medium to high-risk families, but also included lower risk patients without a family history of the disease, diagnosed at an early age of onset (< 40 years). Eight LGRs were detected (1.1%); seven in BRCA1 with a single whole gene deletion (WGD) detected for BRCA2 . These eight LGRs accounted for 8.7% of the 92 BRCA1/2 pathogenic variants identified in the 744 cases. The pathogenic LGRs ranged from WGDs to the duplication of a single exon. Conclusions Larger rearrangements in BRCA1/2 contributed to the overall mutational burden of familial BC and OVC in SA. Almost a quarter of all pathogenic variants in BRCA1 were LGRs (7/30, 23%). The spectrum observed included two WGDs, one each for BRCA1 and BRCA2 .

Purpose The purpose of this paper is to identify and define the certification lifecycle of laser powder bed fusion for aerospace applications from equipment acquisition and installation to production, part acceptance and continuous improvement activities. Design/methodology/approach A top–down systems engineering approach is performed consisting of concept development, requirements engineering and systems architecting. This approach is taken from the perspective of a production organization. Findings A certification roadmap is proposed that references industry requirements at the relevant phases of the roadmap. Each phase of the roadmap acts as a decision gate for progression to the next. Originality/value Qualification and certification of metal laser powder bed fusion is currently a challenge within the aerospace industry. From an aerospace point of view, the qualification and certification of this relatively new manufacturing process should not have to be any different from traditional manufacturing processes, although with extensive quality control and regulatory oversight. This paper proposes a means for fulfilling these requirements chronologically and provides guidance on ensuring such quality control throughout the manufacturing system lifecycle. This roadmap provides insight into the qualification and certification of laser powder bed fusion for aerospace applications and provides value for future industrial feasibility studies.

Mutations in the parkin gene are the most common cause of early-onset Parkinson’s disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain function, mitophagy, and mitochondrial dynamics. Human cellular models with parkin null mutations are particularly valuable for investigating the mitochondrial functions of parkin. However, published results reporting on patient-derived parkin-mutant fibroblasts have been inconsistent. This study aimed to functionally compare parkin-mutant fibroblasts from PD patients with wild-type control fibroblasts using a variety of assays to gain a better understanding of the role of mitochondrial dysfunction in PD. To this end, dermal fibroblasts were obtained from three PD patients with homozygous whole exon deletions in parkin and three unaffected controls. Assays of mitochondrial respiration, mitochondrial network integrity, mitochondrial membrane potential, and cell growth were performed as informative markers of mitochondrial function. Surprisingly, it was found that mitochondrial respiratory rates were markedly higher in the parkin-mutant fibroblasts compared to control fibroblasts (p = 0.0093), while exhibiting more fragmented mitochondrial networks ( p = 0.0304 ). Moreover, cell growth of the parkin-mutant fibroblasts was significantly higher than that of controls ( p = 0.0001 ). These unanticipated findings are suggestive of a compensatory mechanism to preserve mitochondrial function and quality control in the absence of parkin in fibroblasts, which warrants further investigation.

Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI) was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively.

There is a need to develop sustainably sourced products that can address the needs for improved water retention in soils, slow the release rate of fertilizers (to prevent leaching and downstream eutrophication), and control soil pH for use in agriculture. This article investigates the use of industrial kelp solid waste extracted alginate (IW) slurries to produce soil amendment beads, potentially improving soil water retention, acting as slow-release fertilizers (SRFs), and combined with limestone controls soil pH levels. Alginate extracted from the IW was determined to have a lower guluronic (G) to mannuronic (M) acid ratio than pure laboratory-grade (LG) alginate (0.36 vs. 0.53). Hydrogels produced from the IW alginate achieved significantly higher equilibrium swelling ratios (1 wt% IW = 1.80) than LG hydrogels with similar concentrations (1 wt% LG = 0.61). Hydrogel beads were impregnated with ammonium nitrate and potassium chloride to produce potential SRFs. The release rates of K+ and NO3− nutrients from the produced SRFs into deionised water were decreased by one order of magnitude compared to pure salts. The nutrient release rates of the IW-based SRFs were shown to be similar to SRFs produced from LG alginate. Hydrogel beads were impregnated with limestone, and it was determined that the alginate-based hydrogels could significantly decrease the nutrient release rate. Using industrial kelp solid waste extracted alginate slurries shows potential for soil amendments production. This report emphasises, for the first time, the use of a crude alginate product in soil amendment formation. Further, it demonstrates slower release rates and soil pH control.

Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506) administration has been shown to hasten recovery and improve functional outcomes after PNI repair. Unfortunately, high systemic levels of FK506 can result in adverse side effects. The localized administration of FK506 could provide the neuroregenerative benefits of FK506 while avoiding systemic, off-target side effects. This study investigates the utility of a novel FK506-impregnated polyester urethane urea (PEUU) nerve wrap to treat PNI in a previously validated rat infraorbital nerve (ION) transection and repair model. ION function was assessed by microelectrode recordings of trigeminal ganglion cells responding to controlled vibrissae deflections in ION-transected and -repaired animals, with and without the nerve wrap. Peristimulus time histograms (PSTHs) having 1 ms bins were constructed from spike times of individual single units. Responses to stimulus onsets (ON responses) were calculated during a 20 ms period beginning 1 ms after deflection onset; this epoch captures the initial, transient phase of the whisker-evoked response. Compared to no-wrap controls, rats with PEUU-FK506 wraps functionally recovered earlier, displaying larger response magnitudes. With nerve wrap treatment, FK506 blood levels up to six weeks were measured nearly at the limit of quantification (LOQ ≥ 2.0 ng/mL); whereas the drug concentrations within the ION and muscle were much higher, demonstrating the local delivery of FK506 to treat PNI. An immunohistological assessment of ION showed increased myelin expression for animals assigned to neurorrhaphy with PEUU-FK506 treatment compared to untreated or systemic-FK506-treated animals, suggesting that improved PNI outcomes using PEUU-FK506 is mediated by the modulation of Schwann cell activity.