Tree Responses to Moderate and Extreme Drought in the Northeastern United States

Climate change is expected to lead to novel drought conditions in the Northeastern United States. Therefore, experimental studies that mimic these conditions are crucial to understand the potential impact on forests. Further, recent large scale dendrochronological studies suggest that spring and summer droughts may immediately impact tree growth while fall droughts may cause delayed impacts on growth the following growing season. Therefore, in this study, we investigated the impacts of six-week-long spring, summer, and fall droughts on the physiology and intra-annual growth on 288 saplings of six tree species native to the Northeastern United States. These species (deciduous broadleaf angiosperms, hereafter “broadleaf”: Acer rubrum L., Betula papyrifera Marsh., Prunus serotina Ehrh.; and coniferous evergreen gymnosperms, hereafter “conifer”: Juniperus virginiana L., Pinus strobus L., and Thuja occidentalis L.) represent different anticipated drought tolerances and projected abundances with climate change according to previous studies. Additionally, we used experimental dry-downs of seventy-one leafy shoots and seventeen xylem segments to assess how structural and physiological adaptations of each species relate to water use during an extreme drought. We observed marked differences in how the growth patterns of these six species responded to seasonal droughts. Spring and summer droughts generally caused height growth rate reductions for all species. Negative impacts on height growth were stronger for trees that had higher water-use and therefore experienced drought sooner. Importantly, some species such as A. rubrum, Pr. serotina, and T. occidentalis were able to compensate for these height growth reductions during spring and summer droughts with more rapid post-drought height growth. We also found that spring and summer droughts for Pr. serotina, Pi. strobus, and T. occidentalis resulted in reductions in diameter growth rates but only post-drought. Interestingly, these three species were not able to compensate for this decrease in diameter growth, which remained low throughout the rest of the growing season. These high-resolution data on intra-annual growth rates of trees in response to seasonal droughts reveal details about the growth phenology that supports and extends our understanding of annual resolution tree ring studies at larger scales. In the benchtop dry-down experiment that simulated an extreme drought, we found that leafy shoots of conifer species dried more slowly than leafy shoots of broadleaf species. In general, conifer species lost water at equal rates between leaves and stems. In contrast, deciduous species lost water very quickly and experienced larger reductions in leaf water content compared to stem water content. We saw evidence of drought-deciduousness in our greenhouse experiment where B. papyrifera was the fastest to dry-down, and in two instances, its cambia remained hydrated enough to re-flush an additional cohort of leaves post-drought. On the other hand, conifers were slow to dry-down in the greenhouse experiment, only experiencing moderate drought by the end of each drought period. The clear division in response between fast-drying broadleaved deciduous angiosperm species and slow-drying needle-leaved evergreen conifers may be partly driven by lower leaf area per shoot of conifer species, which we observed in the simulated extreme drought experiment. In the mixed wood forests common in the northeastern United States, stands may respond to drought in different ways depending on the species present. For example, we observed very different responses to growth and to some extent, recovery, in our species, and in a stand with species showing different responses, competitive dynamics may be altered among these species as the climate continues to change. Acknowledging that tree responses to drought as individuals and as communities may not align will be important moving forward from studies like these, which define drought responses of individual species, to studies which observe drought responses of entire forests

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.The Fenland Study is funded by the Medical Research Council (MC_U106179471) and Wellcome Trust

Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein

Purpose Although haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized clinical, molecular, and functional spectra of ANKRD11 missense variants. Methods We collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome. We assessed pathogenicity of variants through in silico analyses and cell-based experiments. Results We identified 20 unique, mostly de novo, ANKRD11 missense variants in 29 individuals, presenting with syndromic neurodevelopmental disorders similar to KBG syndrome caused by ANKRD11 protein truncating variants or 16q24.3 microdeletions. Missense variants significantly clustered in repression domain 2 at the ANKRD11 C-terminus. Of the 10 functionally studied missense variants, 6 reduced ANKRD11 stability. One variant caused decreased proteasome degradation and loss of ANKRD11 transcriptional activity. Conclusion Our study indicates that pathogenic heterozygous ANKRD11 missense variants cause the clinically recognizable KBG syndrome. Disrupted transrepression capacity and reduced protein stability each independently lead to ANKRD11 loss-of-function, consistent with haploinsufficiency. This highlights the diagnostic relevance of ANKRD11 missense variants, but also poses diagnostic challenges because the KBG-associated phenotype may be mild and inherited pathogenic ANKRD11 (missense) variants are increasingly observed, warranting stringent variant classification and careful phenotyping

Studies on Arabic Dialectology and Sociolinguistics

This volume contains over fifty articles related to various fields of modern Arabic dialectology. All the articles are revised and enhanced versions of papers read on the 12th Conference of the Association Internationale de Dialectologie Arabe (AIDA) held in Marseille in June 2017. Since its first conference in Paris in 1993, AIDA members gather every two years in different country. The collection of the AIDA proceedings offer an updated insight of the development of the field. During the past few decadesthe the study of Arabic dialects has become an important branch of research covering a wide range of subjects from phonological analyses, morphosyntax, semantics to pragmatics, sociolinguistics, folk linguistics, studies on literacy and writings, cultural and artistic practices, etc. As many articles of this volume illustrate, the study of Arabic dialects explores different aspects of the languages and cultures of the contemporary Arab world. A remarkable feature is the growing and constant participation of young scholars from all around the globe

Children living with HIV in Europe: do migrants have worse treatment outcomes?

Objectives: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. Methods: Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered: (i) severe immunosuppression-for-age; (ii) viraemic viral load (≥ 400 copies/mL) at 1 year after ART initiation; and (iii) AIDS/death after ART initiation. The effect of migrant status was assessed using univariable and multivariable logistic and Cox models. Results: Of 2620 children included across 12 European countries, 56% were migrants. At ART initiation, migrant children were older than domestic-born children (median 6.1 vs. 0.9 years, p < 0.001), with slightly higher proportions being severely immunocompromised (35% vs. 33%) and with active tuberculosis (2% vs. 1%), but a lower proportion with an AIDS diagnosis (14% vs. 19%) (all p < 0.001). At 1 year after beginning ART, a lower proportion of migrant children were viraemic (18% vs. 24%) but there was no difference in multivariable analysis (p = 0.702), and no difference in severe immunosuppression (p = 0.409). However, there was a trend towards higher risk of AIDS/death in migrant children (adjusted hazard ratio = 1.51, 95% confidence interval: 0.96–2.38, p = 0.072). Conclusions: After adjusting for characteristics at ART initiation, migrant children have virological and immunological outcomes at 1 year of ART that are comparable to those who are domestic-born, possibly indicating equity in access to healthcare in Europe. However, there was some evidence of a difference in AIDS-free survival, which warrants further monitoring

Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein

PURPOSE: Although haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized clinical, molecular, and functional spectra of ANKRD11 missense variants. METHODS: We collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome. We assessed pathogenicity of variants through in silico analyses and cell-based experiments. RESULTS: We identified 20 unique, mostly de novo, ANKRD11 missense variants in 29 individuals, presenting with syndromic neurodevelopmental disorders similar to KBG syndrome caused by ANKRD11 protein truncating variants or 16q24.3 microdeletions. Missense variants significantly clustered in repression domain 2 at the ANKRD11 C-terminus. Of the 10 functionally studied missense variants, 6 reduced ANKRD11 stability. One variant caused decreased proteasome degradation and loss of ANKRD11 transcriptional activity. CONCLUSION: Our study indicates that pathogenic heterozygous ANKRD11 missense variants cause the clinically recognizable KBG syndrome. Disrupted transrepression capacity and reduced protein stability each independently lead to ANKRD11 loss-of-function, consistent with haploinsufficiency. This highlights the diagnostic relevance of ANKRD11 missense variants, but also poses diagnostic challenges because the KBG-associated phenotype may be mild and inherited pathogenic ANKRD11 (missense) variants are increasingly observed, warranting stringent variant classification and careful phenotyping

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming