Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons.

Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 × 10-14). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 × 10-9; odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.

Parasite stress and pathogen avoidance relate to distinct dimensions of political ideology across 30 nations.

People who are more avoidant of pathogens are more politically conservative, as are nations with greater parasite stress. In the current research, we test two prominent hypotheses that have been proposed as explanations for these relationships. The first, which is an intragroup account, holds that these relationships between pathogens and politics are based on motivations to adhere to local norms, which are sometimes shaped by cultural evolution to have pathogen-neutralizing properties. The second, which is an intergroup account, holds that these same relationships are based on motivations to avoid contact with outgroups, who might pose greater infectious disease threats than ingroup members. Results from a study surveying 11,501 participants across 30 nations are more consistent with the intragroup account than with the intergroup account. National parasite stress relates to traditionalism (an aspect of conservatism especially related to adherence to group norms) but not to social dominance orientation (SDO; an aspect of conservatism especially related to endorsements of intergroup barriers and negativity toward ethnic and racial outgroups). Further, individual differences in pathogen-avoidance motives (i.e., disgust sensitivity) relate more strongly to traditionalism than to SDO within the 30 nations.

Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus score and not solely a consequence of aging.

OBJECTIVES: Evaluate the presence of minor salivary gland (SG) fibrosis in primary Sjögren's syndrome (pSS) as a function of disease pathology or a consequence of ageing. METHODS: Subjects with sicca symptoms attending a Sjögren's research clinic were classified by American European Consensus Group (AECG) criteria as either pSS or non-SS (nSS). Discovery (n=34 pSS, n=28 nSS) and replication (n=35 pSS, n=31 nSS) datasets were evaluated. Minor SG cross-sections from haematoxylin and eosin stained slides were imaged, digitally reconstructed and analysed for percent area fibrosis. Relationships between SG fibrosis, age, and clinical measures were evaluated using Spearman correlations. Association with SS was assessed by: ROC curve, Variable Selection Using Random Forests (VSURF) and uni- and bi-variate regression analyses. RESULTS: SS subjects had significantly more fibrotic tissue in their minor labial salivary glands (median 24.39%, range 5.12-51.67%) than nSS participants (median 16.7%, range 5.97-38.65%, p<0.0001); age did not differ between groups (average ± SD pSS 50.2 ±13.9 years, nSS 53.8±12.4 years). In both the discovery and replication data sets, multiple regression models showed that the area of minor salivary gland fibrosis predicted pSS significantly better than age alone. Age-corrected linear regression revealed that the area of minor salivary gland fibrosis positively associated with vanBijsterveld score (p=0.042) and biopsy focus score (p=0.002). ROC curve and VSURF analyses ranked fibrosis as a significantly more important variable for subject discrimination than age. CONCLUSIONS: SG fibrosis is an element of pSS pathology that is related to focus score and is not solely attributable to age.

Anti-La positive, anti-Ro negative subset of primary Sjögren's syndrome: anti-La is a reality but is the disease?

OBJECTIVES: To characterise the serological and clinical findings in primary Sjögren's syndrome in which anti-La was found without anti-Ro. We hypothesised that a significant portion of these are falsely negative for anti-Ro60. METHODS: Twenty-nine sera from primary Sjögren's syndrome patients were tested for antibodies directed against La and Ro. Anti-La was detected using bovine La treated with or without DNAase and RNAase to identify potential false positivity. Anti-Ro60 antibodies were detected using HEp-2000 substrate (in which cells are transfected with human Ro60) and HEp-2 substrate. Anti-Ro60 and Ro-52 were also tested by in vitro transcription/translation followed by immunoprecipitation assay. RESULTS: All 29 sera bound La, even after treatment with DNAase and RNAase. Of the 29 sera, 25 were unequivocally negative on HEp-2000 (1:40 dilution). Four samples were anti-Ro60 positive with a speckled pattern, three of the four at 1:320 dilution. Thus, false negative anti-Ro60 exists in a small fraction (14%) of the Ro-negative/La-positive primary Sjögren's patients. However, all the samples were negative for Ro60 and Ro52 by in vitro immunoprecipitation assay. Clinically these patients tended not to have salivary gland pathology characteristic of Sjögren's syndrome. CONCLUSIONS: We found only a small fraction of Ro negative/La positive sera to show positive HEp-2000 pattern. These subjects did not have characteristic findings on pathological examination of minor salivary glands, suggesting these subjects have a process distinct from Sjögren's syndrome.

Why (and When) Straight Women Trust Gay Men: Ulterior Mating Motives and Female Competition.

Previous findings indicate that heterosexual women experience a greater sense of comfort and trust in their friendships with gay men than in their friendships with heterosexual individuals. In the present studies, we tested a hypothesis that not only explains why women exhibit increased trust in gay men but also yields novel predictions about when (i.e., in what contexts) this phenomenon is likely to occur. Specifically, we propose that gay men's lack of motives to mate with women or to compete with them for mates enhances women's trust in gay men and openness to befriend them. Study 1 demonstrated that women placed greater trust in a gay man's mating-but not non-mating (e.g., career) advice-than in the same advice given by heterosexual individuals. Study 2 showed that women perceived a gay man to be more sincere in scenarios relevant to sexual and competitive mating deception. In Study 3, exposing women to a visualization of increased mating competition enhanced their trust in gay men; when mating competition was salient, women's trust in mating information from a gay man was amplified. Study 4 showed that women who perceived higher levels of mating competition were more open to befriending gay men. Together, these converging findings support our central hypothesis, which not only provides a distal explanation for the trust that straight women place in gay men, but also provides novel insights into previously unidentified contexts that facilitate the formation and strengthening of this unique bond.

Moringa oleifera functionalised sand - reuse with non-ionic surfactant dodecyl glucoside.

Moringa oleifera seeds are well known for their ability to cause flocculation in turbid water and facilitate bacterial inhibition. These effects are due to the cationic polypeptide MO2.1, which affects the surface charge of suspended particles and causes lysis of bacterial cells. However, the attachment of bacteria to MO2.1 prevents further bacterial attachment, reducing the effectiveness of the seeds. This research investigated the effect of surfactants on functionality and reuse of Moringa seeds to develop a sustainable water treatment technique. The seed extracts (MO2.1) were used with a functionalised sand system, and the sands were exposed to commercially available (ionic and non-ionic) surfactants, dodecyl glucoside and sodium dodecyl sulfate. Artificially polluted water contaminated with Escherichia coli was used to evaluate the efficiency of the system. The non-ionic surfactant was found to be effective at separating E. coli from the functionalised sand without the detachment of the MO2.1 and subsequent loss of the system efficiency. This was successfully repeated four times. The results demonstrated a sustainable, reusable technique to inhibit bacterial contamination in water.

The "appropriate" response to deprivation: Evolutionary and ethical dimensions.

Pepper & Nettle use an evolutionary framework to argue that "temporal discounting" is an appropriate response to low socioeconomic status (SES), or deprivation. We suggest some conceptual refinements to their "appropriate-response" perspective, with the hope that it usefully informs future research on and public policy responses to the relationship between deprivation and temporal discounting.

Contemporary evolutionary psychology and the evolution of intelligence.

Burkart et al.'s impressive synthesis will serve as a valuable resource for intelligence research. Despite its strengths, the target article falls short of offering compelling explanations for the evolution of intelligence. Here, we outline its shortcomings, illustrate how these can lead to misguided conclusions about the evolution of intelligence, and suggest ways to address the article's key questions.

Interaction between innate immunity and Ro52-induced antibody causes Sjögren's syndrome-like disorder in mice.

OBJECTIVES: Autoantibodies reactive with Ro52 are often found in sera of patients with Sjögren's syndrome (SS). This study was undertaken to investigate the role of Ro52-induced immune responses in pathogenesis of SS. METHODS: New Zealand Mixed (NZM) 2758 mice were immunised with Ro52 in alum adjuvant. Control mice were immunised either with maltose-binding protein or injected with alum alone. Mice were monitored for anti-Ro52 antibody, sialoadenitis and pilocarpine-induced salivation. Antibody binding to salivary gland (SG) cells was analysed in vivo and in vitro by immunofluorescence. Sera from immunised mice were passively transferred into untreated or alum injected NZM2758 mice. RESULTS: By day 30 post-immunisation, Ro52 immunised mice generated immunoprecipitating anti-Ro52 antibodies and they had the maximum drop in saliva production. Both Ro52 immunised and control mice showed evidence of mild sialoadenitis. However, only Ro52 immunised mice had antibody deposition in their SG. Passive transfer of Ro52-immune sera induced SG dysfunction in recipient mice, only if the recipients were primed with alum. In vitro, antibodies from Ro52-immune sera were internalised by a SG cell line and this uptake was inhibited by cytochalasin D treatment. CONCLUSIONS: Our data show for the first time that antibodies induced by Ro52 are capable of inducing SG dysfunction, and that this phenomenon is dependent on the activation of innate immunity. The mouse model described in this study implies that autoantibody deposition in the SG might be an important step in the induction of xerostomia and pathogenesis of SS.

Mating strategy, disgust, and food neophobia.

Food neophobia and disgust are commonly thought to be linked, but this hypothesis is typically implicitly assumed rather than directly tested. Evidence for the connection has been based on conceptually and empirically unsound measures of disgust, unpublished research, and indirect findings. This study (N = 283) provides the first direct evidence of a relationship between trait-level food neophobia and trait-level pathogen disgust. Unexpectedly, we also found that food neophobia varies as a function of sexual disgust and is linked to mating strategy. Using an evolutionary framework, we propose a novel hypothesis that may account for these previously undiscovered findings: the food neophilia as mating display hypothesis. Our discussion centers on future research directions for discriminatively testing this novel hypothesis.

Comparison of the American-European Consensus Group Sjogren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort.

OBJECTIVE: To compare the performance of the American-European Consensus Group (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjögren's Syndrome (SS) in a well-characterised sicca cohort, given ongoing efforts to resolve discrepancies and weaknesses in the systems. METHODS: In a multidisciplinary clinic for the evaluation of sicca, we assessed features of salivary and lacrimal gland dysfunction and autoimmunity as defined by tests of both AECG and ACR criteria in 646 participants. Global gene expression profiles were compared in a subset of 180 participants. RESULTS: Application of the AECG and ACR criteria resulted in classification of 279 and 268 participants with SS, respectively. Both criteria were met by 244 participants (81%). In 26 of the 35 AECG+/ACR participants, the minor salivary gland biopsy focal score was ≥1 (74%), while nine had positive anti-Ro/La (26%). There were 24 AECG-/ACR+ who met ACR criteria mainly due to differences in the scoring of corneal staining. All patients with SS, regardless of classification, had similar gene expression profiles, which were distinct from the healthy controls. CONCLUSIONS: The two sets of classification criteria yield concordant results in the majority of cases and gene expression profiling suggests that patients meeting either set of criteria are more similar to other SS participants than to healthy controls. Thus, there is no clear evidence for increased value of the new ACR criteria over the old AECG criteria from the clinical or biological perspective. It is our contention, supported by this report, that improvements in diagnostic acumen will require a more fundamental understanding of the pathogenic mechanisms than is at present available.

Subtraction color map of contrast-enhanced and unenhanced CT for the prediction of pancreatic necrosis in early stage of acute pancreatitis.

OBJECTIVE: The objective of our study was to evaluate the accuracy of subtraction color-map images created from contrast-enhanced CT (CECT) and unenhanced CT for the diagnosis of pancreatic necrosis in the early stage of acute pancreatitis. MATERIALS AND METHODS: Forty-eight patients underwent unenhanced CT and CECT within 72 hours from the onset of acute pancreatitis. Subtraction color-map images were created from unenhanced CT and CECT using a 3D nonrigid registration method. Three radiologists reviewed two image sets: CECT alone and subtraction color-map images in conjunction with CECT. Readers evaluated each image set for the presence of pancreatic necrosis. The reference standard for pancreatic necrosis was CT or MRI 1 week or more after the onset of acute pancreatitis. The performance of each image set for the prediction of pancreatic necrosis was calculated and compared using the McNemar test. RESULTS: Eleven of the 48 patients developed pancreatic necrosis. There were no technical failures creating the subtraction images. The sensitivity, specificity, and accuracy for predicting pancreatic necrosis with CECT were 64%, 97%, and 90%, respectively, for reader 1; 73%, 87%, and 83% for reader 2; and 73%, 87%, and 83% for reader 3. The sensitivity, specificity, and accuracy for predicting pancreatic necrosis with the subtraction color maps were 100%, 100%, and 100%, respectively, for reader 1; 100%, 95%, and 96% for reader 2; and 82%, 92%, and 90% for reader 3. Accuracy significantly improved with the addition of subtraction color maps compared with CECT alone for reader 1 (p = 0.03) and reader 2 (p = 0.02) but not for reader 3 (p = 0.37). CONCLUSION: A subtraction color map is accurate in the diagnosis of pancreatic necrosis in the early stage of acute pancreatitis.

Cognitive and neuroscientific perspectives of healthy ageing.

With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021-2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, and (c) the potential for cognitive training to slow this decline. We also examine ageing and cognition through multiple theoretical perspectives. We highlight critical unresolved issues, such as the disparate implications of subjective versus objective measures of cognitive decline and the insufficient evaluation of cognitive training programs. We suggest future research directions, and emphasise interdisciplinary collaboration to create a more comprehensive understanding of the factors that modulate cognitive ageing.

Biosorption of heavy metals in a photo-rotating biological contactor--a batch process study.

Metal removal potential of indigenous mining microorganisms from acid mine drainage (AMD) has been well recognised in situ at mine sites. However, their removal capacity requires to be investigated for AMD treatment. In the reported study, the capacity of an indigenous AMD microbial consortium dominated with Klebsormidium sp., immobilised in a photo-rotating biological contactor (PRBC), was investigated for removing various elements from a multi-ion synthetic AMD. The synthetic AMD was composed of major (Cu, Mn, Mg, Zn, Ca, Na, Ni) and trace elements (Fe, Al, Cr, Co, Se, Ag, Mo) at initial concentrations of 2 to 100 mg/L and 0.005 to 1 mg/L, respectively. The PRBC was operated for two 7-day batch periods under pH conditions of 3 and 5. The maximum removal was observed after 3 and 6 days at pH 3 and 5, respectively. Daily water analysis data demonstrated the ability of the algal-microbial biofilm to remove an overall average of 25-40 % of the major elements at pH 3 in the order of Na > Cu > Ca > Mg > Mn > Ni > Zn, whereas a higher removal (35-50 %) was observed at pH 5 in the order of Cu > Mn > Mg > Ca > Ni > Zn > Na. The removal efficiency of the system for trace elements varied extensively between 3 and 80 % at the both pH conditions. The batch data results demonstrated the ability for indigenous AMD algal-microbial biofilm for removing a variety of elements from AMD in a PRBC. The work presents the potential for further development and scale-up to use PBRC inoculated with AMD microorganisms at mine sites for first or secondary AMD treatment.

Evidence that the aesthetic preference for Hogarth's Line of Beauty is an evolutionary by-product.

In 1753, artist William Hogarth declared a specific S-shaped line to be the 'Line of Beauty' (LoB). Hogarth's assertion has had a profound impact on diverse fields over the past two and a half centuries. However, only one recent (2022) study has investigated whether Hogarth's assertion accurately captures humans' actual aesthetic preferences, and no research has explored why people find the LoB beautiful. We conducted two studies testing the hypothesis that the LoB's perceived beauty is an incidental by-product of cognitive systems that evolved to attend to fitness-relevant morphological features in people. In Study 1, we replicated the finding that female bodies whose lumbar curvature approximates the biomechanical optimum for dealing with the exigencies of pregnancy are rated as more attractive. In Study 2, we found that abstract lines extracted from these bodies were perceived as more beautiful than other lines. These results suggest that the preference for Hogarth's LoB is an incidental by-product of psychological mechanisms that evolved for other purposes. More broadly, these findings suggest that an evolutionary psychological approach - in particular the concept of evolutionary by-product - may be useful for understanding, explaining, and predicting people's aesthetic preferences for certain abstract symbols, which otherwise might seem arbitrary and inexplicable.

No Support for Two Hypotheses About the Communicative Functions of Displaying Disgust: Evidence From Turkey, Norway, Germany, and Croatia.

In recent years, researchers have discovered much about how disgust works, its neural basis, its relationship with immune function, its connection with mating, and some of its antecedents and consequents. Despite these advances in our understanding, an under-explored area is how disgust may be used to serve a communicative function, including how individuals might strategically downplay or exaggerate the disgust display in front of different audiences. Here, we generated two hypotheses about potential communicative functions of disgust, and tested these hypotheses in four countries (Turkey, Croatia, Germany, and Norway). We found no evidence in support of either hypothesis in any country. Discussion focuses on the likely falsity of the two central hypotheses, alternative interpretations of our findings, and directions for future research.

Lordosis in Humans.

Despite progress in attractiveness research, we have yet to identify many fitness-relevant cues in the human phenotype or humans' psychology for responding to them. Here, we test hypotheses about psychological systems that may have evolved to process distinct cues in the female lumbar region. The Fetal Load Hypothesis proposes a male preference for a morphological cue: lumbar curvature. The Lordosis Detection Hypothesis posits context-dependent male attraction to a movement: lordosis behavior. In two studies (Study 1 N: 102, Study 2 N: 231), we presented men with animated female characters that varied in their lumbar curvature and back arching (i.e., lordosis behavior). Irrespective of mating context, men's attraction increased as lumbar curvature approached the hypothesized optimum. By contrast, men experienced greater attraction to lordosis behavior in short-term than long-term mating contexts. These findings support both the Lordosis Detection and Fetal Load Hypotheses. Discussion focuses on the meaning of human lordosis and the importance of dynamic stimuli in attractiveness research.

Dysregulated long non-coding RNA in Sjögren's disease impacts both interferon and adaptive immune responses.

OBJECTIVE: Sjögren's disease (SjD) is an autoimmune disease characterised by inflammatory destruction of exocrine glands. Patients with autoantibodies to Ro/SSA (SjDRo+) exhibit more severe disease. Long non-coding RNAs (lncRNAs) are a functionally diverse class of non-protein-coding RNAs whose role in autoimmune disease pathology has not been well characterised. METHODS: Whole blood RNA-sequencing (RNA-seq) was performed on SjD cases (n=23 Ro/SSA negative (SjDRo-); n=27 Ro/SSA positive (SjDRo+) and healthy controls (HCs; n=27). Bioinformatics and pathway analyses of differentially expressed (DE) transcripts (log2 fold change ≥2 or ≤0.5; padj<0.05) were used to predict lncRNA function. LINC01871 was characterised by RNA-seq analyses of HSB-2 cells with CRISPR-targeted LINC01871 deletion (LINC01871-/ -) and in vitro stimulation assays. RESULTS: Whole blood RNA-seq revealed autoantibody-specific transcription profiles and disproportionate downregulation of DE transcripts in SjD cases relative to HCs. Sixteen DE lncRNAs exhibited correlated expression with the interferon (IFN)-regulated gene, RSAD2, in SjDRo+ (r≥0.65 or ≤-0.6); four antisense lncRNAs exhibited IFN-regulated expression in immune cell lines. LINC01871 was upregulated in all SjD cases. RNA-seq and pathway analyses of LINC01871-/ - cells implicated roles in cytotoxic function, differentiation and IFNγ induction. LINC01871 was induced by IFNγ in a myeloid cell line and regulated by calcineurin/NFAT pathway and T cell receptor (TCR) signalling in primary human T cells. CONCLUSION: LINC01871 influences expression of many immune cell genes and growth factors, is IFNγ inducible, and regulated by calcineurin signalling and TCR ligand engagement. Altered LINC01871 expression may influence the dysregulated T cell inflammatory pathways implicated in SjD.

Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.

Sjögren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.