BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.

The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation. The mutations disrupted protein stability by interfering with homodimerization or by causing aggregation. We observed analogous lymphocyte defects in Bach2-heterozygous mice. More generally, we observed that genes that cause monogenic haploinsufficient diseases were substantially enriched for TFs and SE architecture. These findings reveal a previously unrecognized feature of SE architecture in Mendelian diseases of immunity: heterozygous mutations in SE-regulated genes identified by whole-exome/genome sequencing may have greater significance than previously recognized.

The latitudinal temperature gradient and its climate dependence as inferred from foraminiferal δ18O over the past 95 million years.

SignificanceThe temperature difference between low and high latitudes is one measure of the efficiency of the global climate system in redistributing heat and is used to test the ability of models to represent the climate system through time. Here, we show that the latitudinal temperature gradient has exhibited a consistent inverse relationship with global mean sea-surface temperature for at least the past 95 million years. Our results help reduce conflicts between climate models and empirical estimates of temperature and argue for a fundamental consistency in the dynamics of heat transport and radiative transfer across vastly different background states.

The enigma of Oligocene climate and global surface temperature evolution.

Falling atmospheric CO2 levels led to cooling through the Eocene and the expansion of Antarctic ice sheets close to their modern size near the beginning of the Oligocene, a period of poorly documented climate. Here, we present a record of climate evolution across the entire Oligocene (33.9 to 23.0 Ma) based on TEX86 sea surface temperature (SST) estimates from southwestern Atlantic Deep Sea Drilling Project Site 516 (paleolatitude ∼36°S) and western equatorial Atlantic Ocean Drilling Project Site 929 (paleolatitude ∼0°), combined with a compilation of existing SST records and climate modeling. In this relatively low CO2 Oligocene world (∼300 to 700 ppm), warm climates similar to those of the late Eocene continued with only brief interruptions, while the Antarctic ice sheet waxed and waned. SSTs are spatially heterogenous, but generally support late Oligocene warming coincident with declining atmospheric CO2 This Oligocene warmth, especially at high latitudes, belies a simple relationship between climate and atmospheric CO2 and/or ocean gateways, and is only partially explained by current climate models. Although the dominant climate drivers of this enigmatic Oligocene world remain unclear, our results help fill a gap in understanding past Cenozoic climates and the way long-term climate sensitivity responded to varying background climate states.

Refugees, asylum seekers, and practitioners' perspectives of embodied trauma: A comprehensive scoping review.

INTRODUCTION: Individuals seeking refuge and asylum commonly present to health care practitioners with embodiment of mental distress resulting from the traumatic nature of their migration experiences. The number of displaced individuals has doubled over the past decade due to the impacts of war, religious and political conflict, climate change, and COVID-19. Studies point towards the need for a comprehensive scoping review to fully explicate the concept of embodied trauma, bridging the gap between phenomenological lived experience and the many treatments available. OBJECTIVES: To inform psychotherapy guidelines by identifying the evidence for embodied trauma, clarifying key terms, examining how research is conducted, and identifying gaps in the knowledge. METHOD: A five-stage scoping review protocol was operationalized to explore and analyze the existing literature and associated terminology by (a) identifying the research question, (b) identifying the relevant literature, (c) selecting the studies, (d) charting the data, and (e) collating, summarizing, and reporting the results. RESULTS: Highlight the need for a clear definition of terms, the development of a culturally informed assessment and formulation for individuals experiencing embodied trauma, and reveal a gap in the research for the best treatment approach(es). CONCLUSION: Proposal of a clear definition of embodied trauma and key themes for future research including culturally informed care, psychosocial support, language considerations, relational belonging, and inclusion of sexual, spiritual, and existential factors, moving away from purely Westernized diagnoses and treatments towards culturally informed care. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The PhanSST global database of Phanerozoic sea surface temperature proxy data.

Paleotemperature proxy data form the cornerstone of paleoclimate research and are integral to understanding the evolution of the Earth system across the Phanerozoic Eon. Here, we present PhanSST, a database containing over 150,000 data points from five proxy systems that can be used to estimate past sea surface temperature. The geochemical data have a near-global spatial distribution and temporally span most of the Phanerozoic. Each proxy value is associated with consistent and queryable metadata fields, including information about the location, age, and taxonomy of the organism from which the data derive. To promote transparency and reproducibility, we include all available published data, regardless of interpreted preservation state or vital effects. However, we also provide expert-assigned diagenetic assessments, ecological and environmental flags, and other proxy-specific fields, which facilitate informed and responsible reuse of the database. The data are quality control checked and the foraminiferal taxonomy has been updated. PhanSST will serve as a valuable resource to the paleoclimate community and has myriad applications, including evolutionary, geochemical, diagenetic, and proxy calibration studies.

Outlook and adaptation in advanced cancer: a systematic review.

'Fighting spirit' in early-stage cancer comprises optimism about prognosis, a belief that the disease and/or its effects are controllable, and a determination to cope with the situation using various active coping methods. It is associated with better adjustment. In advanced cancer, the usefulness of this coping style is contentious. This systematic review identified eight studies that investigated these qualities in advanced cancer. They provided some evidence that positive attitude and self-efficacy may be associated with better emotional adjustment; active, problem-focused coping appears to be adaptive and avoidant coping maladaptive. However, major methodological flaws make any conclusions highly speculative. Further research in this area using larger samples and longitudinal design is required.