Challenges to New Testament theology: an attempt to justify the enterprise

In this thesis I survey and examine major challenges presented to the enterprise of writing a New Testament theology. I argue that the challenges, although weighty, are not convincing. In a programmatic way, I also put forward arguments in favour o f the thesis, that the enterprise may be justified.I accept the proposal that New Testament theology should be a historical enterprise (W.Wrede, H.Raisanen). I argue that a historian may describe the theological content o f the New Testament and that this should be the task o f the enterprise. Theology here does not mean the theology o f the modern interpreter, but the theology o f the N ew Testament itself. Theology should be understood as a broad term: it should include beliefs o f the early Christians, as well as practices in connection with their beliefs. The theology o f the early Christians should not be separated from their religious experience.As historians we have to study all the available evidence, and historians may justify the study o f the theology o f the New Testament if they find that early Christianity had a basic theology, which was generally adhered to, and that this basic theology was represented in writings held to be authoritative.I argue (against W .Bauer and H.Koester) that what was later called "orthodoxy" was the earliest form o f Christianity. Christians not adhering to the theology o f the orthodox became regarded as heretics.I challenge the view that the canon came into existence as a late decision o f the church. Rather, we can trace the beginnings o f a canonical development to the first century. Indeed, the N ew Testament authors may have written with an awareness o f authority which was on the same level as that o f the Old Testament prophets. (Excursus: The Temple Scroll had a canonical status in Qumran.)I take issue with the view that New Testament theology can only be a description of the manifold theologies of the New Testament (E.Kasemann,H.Braun). There are differences, but I argue that the differences do not amount to irreconcilable contradictions. (Exegetical excursus: Acts 2,36 is not evidence for an adoptionist Christology in early Christianity; Eph 2,15 does not teach the abolition of the whole Old Testament Law.) The early Christians may have shared a basic theology that consisted in statements of a credal type.A survey of recent contributions to New Testament theology suggests that the enterprise may include the theological reasoning of the modern interpreter; and that the historical character may be complemented by other approaches, for example those drawn from the study of literary theory and of the social sciences (B.S. Childs, R.Morgan, H.Hübner, P.Stuhlmacher). However, I propose that the enterprise may be earned out and justified without these further developments

Equiangular Lines and Spherical Codes in Euclidean Space

A family of lines through the origin in Euclidean space is called equiangular if any pair of lines defines the same angle. The problem of estimating the maximum cardinality of such a family in $\mathbb{R}^n$ was extensively studied for the last 70 years. Motivated by a question of Lemmens and Seidel from 1973, in this paper we prove that for every fixed angle $\theta$ and sufficiently large $n$ there are at most $2n-2$ lines in $\mathbb{R}^n$ with common angle $\theta$. Moreover, this is achievable only for $\theta = \arccos(1/3)$. We also show that for any set of $k$ fixed angles, one can find at most $O(n^k)$ lines in $\mathbb{R}^n$ having these angles. This bound, conjectured by Bukh, substantially improves the estimate of Delsarte, Goethals and Seidel from 1975. Various extensions of these results to the more general setting of spherical codes will be discussed as well.Comment: 24 pages, 0 figure

Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells

Rapamycin (rapa)-induced heterodimerization of the FRB domain of the mammalian target of rapa and FKBP12 was used to translocate a phosphoinositide 5-phosphatase (5-ptase) enzyme to the plasma membrane (PM) to evoke rapid changes in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) levels. Rapa-induced PM recruitment of a truncated type IV 5-ptase containing only the 5-ptase domain fused to FKBP12 rapidly decreased PM PtdIns(4,5)P2 as monitored by the PLCδ1PH-GFP fusion construct. This decrease was paralleled by rapid termination of the ATP-induced Ca2+ signal and the prompt inactivation of menthol-activated transient receptor potential melastatin 8 (TRPM8) channels. Depletion of PM PtdIns(4,5)P2 was associated with a complete blockade of transferrin uptake and inhibition of epidermal growth factor internalization. None of these changes were observed upon rapa-induced translocation of an mRFP-FKBP12 fusion protein that was used as a control. These data demonstrate that rapid inducible depletion of PM PtdIns(4,5)P2 is a powerful tool to study the multiple regulatory roles of this phospholipid and to study differential sensitivities of various processes to PtdIns(4,5)P2 depletion

Investigation of the Biomass and Nutrient Content of Green Manuring Plants as Second Crops in Hungary

The growth, and the development and trends of the nutrient content parameters of three different plant species (Phacelia tanacecifolia,Sinapis alba, Raphanus sativus) grown as secondary crops for green manure, as a function of two different fertiliser doses (0 kg/ha N; 50kg/ha N), was studied under unfavourable site conditions at the Crop Production and Biomass Utilisation Demonstration Centre of theSzent István University, Gödöllő, Hungary. The application of the small, 50 kg/ha dose of nitrogen increased the biomass yield in eachcase, to 2.78-3.11 times that of the control field. The dry matter content of the produce increased only by 2.11-2.66 times, as the watercontent of the green manure plants also increased as a result of the nitrogen supplement. The increased amount of nitrogen boosted theavailability of all of the other macro elements for the plants. In view of the present findings it can be recommend the application of somenitrogen fertiliser in the given site before growing some crop for use as green manure in all cases but where the straw after cereals is left onthe soil surface nitrogen should be applied to alleviate the pentosan effect and to increase the uptake of macro elements

Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-golgi junctions

Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex craniofacial, dental, cutaneous, and limb abnormalities combined with intellectual disability. Mutations in the PTDSS1 gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, were described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels. Here we show that expression of mutant PSS1 enzymes decreased phosphatidylinositol 4-phosphate (PI4P) levels both in the Golgi and the plasma membrane (PM) by activating the Sac1 phosphatase and altered PI4P cycling at the PM. Conversely, inhibitors of PI4KA, the enzyme that makes PI4P in the PM, blocked PS synthesis and reduced PS levels by 50% in normal cells. However, mutant PSS1 enzymes alleviated the PI4P dependence of PS synthesis. Oxysterol-binding protein-related protein 8, which was recently identified as a PI4P-PS exchanger between the ER and PM, showed PI4P-dependent membrane association that was significantly decreased by expression of PSS1 mutant enzymes. Our studies reveal that PS synthesis is tightly coupled to PI4P-dependent PS transport from the ER. Consequently, PSS1 mutations not only affect cellular PS levels and distribution but also lead to a more complex imbalance in lipid homeostasis by disturbing PI4P metabolism

GraphMineSuite: Enabling High-Performance and Programmable Graph Mining Algorithms with Set Algebra

We propose GraphMineSuite (GMS): the first benchmarking suite for graph mining that facilitates evaluating and constructing high-performance graph mining algorithms. First, GMS comes with a benchmark specification based on extensive literature review, prescribing representative problems, algorithms, and datasets. Second, GMS offers a carefully designed software platform for seamless testing of different fine-grained elements of graph mining algorithms, such as graph representations or algorithm subroutines. The platform includes parallel implementations of more than 40 considered baselines, and it facilitates developing complex and fast mining algorithms. High modularity is possible by harnessing set algebra operations such as set intersection and difference, which enables breaking complex graph mining algorithms into simple building blocks that can be separately experimented with. GMS is supported with a broad concurrency analysis for portability in performance insights, and a novel performance metric to assess the throughput of graph mining algorithms, enabling more insightful evaluation. As use cases, we harness GMS to rapidly redesign and accelerate state-of-the-art baselines of core graph mining problems: degeneracy reordering (by up to >2x), maximal clique listing (by up to >9x), k-clique listing (by 1.1x), and subgraph isomorphism (by up to 2.5x), also obtaining better theoretical performance bounds

T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

Introduction: The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract. Methods: This study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017–2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated–) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups. Results: Pre–RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+). Conclusion: The evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults

Distinct Subsets of Anti-Pulmonary Autoantibodies Correlate with Disease Severity and Survival in Severe COVID-19 Patients

Autoantibodies targeting the lung tissue were identified in severe COVID-19 patients in this retrospective study. Fifty-three percent of 104 patients developed anti-pulmonary antibodies, the majority of which were IgM class, suggesting that they developed upon infection with SARS-CoV-2. Anti-pulmonary antibodies correlated with worse pulmonary function and a higher risk of multiorgan failure that was further aggravated if 3 or more autoantibody clones were simultaneously present (multi-producers). Multi-producer patients were older than the patients with less or no autoantibodies. One of the identified autoantibodies (targeting a pulmonary protein of ~ 50 kDa) associated with worse clinical outcomes, including mortality. In summary, severe COVID-19 is associated with the development of lung-specific autoantibodies, which may worsen the clinical outcome. Tissue proteome-wide tests, such as the ones applied here, can be used to detect autoimmunity in the post-COVID state to identify the cause of symptoms and to reveal a new target for treatment

The majority of severe COVID-19 patients develop anti-cardiac autoantibodies

Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens. Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients. Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, p = 0.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, p = 0.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, p = 0.03) and IgM (10%, p < 0.01) type anti-cardiac autoantibodies than that in COVID-19 patients. Furthermore, we detected changes in the anti-cardiac autoantibody profile in 7 COVID-19 patients during hospital treatment. Surprisingly, the presence of these anti-cardiac autoantibodies did not affect the clinical outcome and the prevalence of the autoantibodies did not differ between the elderly (over 65 years) and the patients younger than 65 years of age. Our results demonstrate that the majority of hospitalized COVID-19 patients produce novel anti-cardiac IgM autoantibodies. COVID-19 also reactivates resident IgG autoantibodies. These autoantibodies may promote autoimmune reactions, which can complicate post-COVID recuperation, contributing to post-acute sequelae of COVID-19 (long COVID)