Two sides of the coin:Feedback-driven landscape formation results in trade-off between establishment and resilience of marram grass

Habitat-modifying plants engineer biogeomorphic landscapes through self-reinforcing interactions with their physical environment, or so-called ‘biogeomorphic feedbacks’. Nevertheless, benefits can vary across a biogeomorphic landscape gradient and between plant-life stages. For instance, European marram grass forms dunes by trapping sediments which triggers plant growth, in turn promoting sediment trapping. Yet, by increasing dune height and vegetation cover, marram grass mitigates sediment dynamics, inhibiting sediment-growth feedbacks, which ultimately leads to its demise. However, little is known about how dune formation affects the growth and survival of marram grass at different life stages. Therefore, we performed a two-level field experiment testing the effect of position on marram grass across the biogeomorphological dune gradient (beach, foredune, backdune) on (i) the establishment success of juvenile transplants and (ii) the resilience of mature plants to disturbance by above-ground biomass removal, over one growing season. Although juvenile transplants grew similarly well across the dune gradient, significantly fewer beach transplants (67%) survived compared to the foredune- and backdune transplants. Conversely, survival of mature disturbed marram grass (100%) was unaffected, yet recovery was highest at the beach and significantly decreased across the dune gradient. We could link these opposing responses to habitat modification. In heavily modified dune habitats sediment stabilization aided juvenile establishment, whereas the high sediment dynamics of unmodified beaches facilitated adult resilience indicating dune formation invokes a trade-off between establishment and resilience. Our findings highlight the importance of assessing life stage-dependent differences in environmental requirements of habitat-modifying plants to understand population dynamics and landscape-forming processes

A global analysis of how human infrastructure squeezes sandy coasts

Coastal ecosystems provide vital services, but human disturbance causes massive losses. Remaining ecosystems are squeezed between rising seas and human infrastructure development. While shoreline retreat is intensively studied, coastal congestion through infrastructure remains unquantified. Here we analyse 235,469 transects worldwide to show that infrastructure occurs at a median distance of 392 meter from sandy shorelines. Moreover, we find that 33% of sandy shores harbour less than 100 m of infrastructure-free space, and that 23–30% of this space may be lost by 2100 due to rising sea levels. Further analyses show that population density and gross domestic product explain 35–39% of observed squeeze variation, emphasizing the intensifying pressure imposed as countries develop and populations grow. Encouragingly, we find that nature reserves relieve squeezing by 4–7 times. Yet, at present only 16% of world’s sandy shores have a protected status. We therefore advocate the incorporation of nature protection into spatial planning policies

Clinical Utility of a Unique Genome-Wide DNA Methylation Signature for KMT2A-Related Syndrome

Wiedemann–Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition associated with hypertrichosis cubiti, short stature, and characteristic facies caused by pathogenic variants in the KMT2A gene. Clinical features can be inconclusive in mild and unusual WDSTS presentations with variable ID (mild to severe), facies (typical or not) and other associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Interpretation and classification of rare KMT2A variants can be challenging. A genome-wide DNA methylation episignature for KMT2A-related syndrome could allow functional classification of variants and provide insights into the pathophysiology of WDSTS. Therefore, we assessed genome-wide DNA methylation profiles in a cohort of 60 patients with clinical diagnosis for WDSTS or Kabuki and identified a unique highly sensitive and specific DNA methylation episignature as a molecular biomarker of WDSTS. WDSTS episignature enabled classification of variants of uncertain significance in the KMT2A gene as well as confirmation of diagnosis in patients with clinical presentation of WDSTS without known genetic variants. The changes in the methylation profile resulting from KMT2A mutations involve global reduction in methylation in various genes, including homeobox gene promoters. These findings provide novel insights into the molecular etiology of WDSTS and explain the broad phenotypic spectrum of the disease.</p

Affected Experiencers

Numerous languages permit an NP that is not selected by the verb to be added to a clause, with several different possible interpretations. We divide such non-selected arguments into possessor, benefactive, attitude holder, and affected experiencer categories, on the basis of syntactic and semantic differences between them. We propose a formal analysis of the affected experiencer construction. In our account, a syntactic head Aff(ect) introduces the experiencer argument, and adds a conventional implicature to the effect that any event of the type denoted by its syntactic sister is the source of the experiencer’s psychological experience. Hence, our proposal involves two tiers of meaning: the at-issue meaning of the sentence, and some not-at-issue meaning (an implicature). A syntactic head can introduce material on both tiers. Additionally, we allow two parameters of variation: (i) the height of the attachment of Aff, and (ii) how much of the semantics is at-issue and how much is an implicature. We show that these two parameters account for the attested variation across our sample of languages, as well as the significant commonalities among them. Our analysis also accounts for significant differences between affected experiencers and the other types of non-selected arguments, and we also note a generalization to the effect that purely not-at-issue non-selected arguments can only be weak or clitic pronouns

Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities

PURPOSE: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsufficiency. METHODS: Three individuals with intellectual disability and iris anomalies and truncating de novo PRR12 variants were described previously. We add 21 individuals with similar PRR12 variants identified via matchmaking platforms, bringing the total number to 24. RESULTS: We observed 12 frameshift, 6 nonsense, 1 splice-site, and 2 missense variants and one patient with a gross deletion involving PRR12. Three individuals had additional genetic findings, possibly confounding the phenotype. All patients had developmental impairment. Variable structural eye defects were observed in 12/24 individuals (50%) including anophthalmia, microphthalmia, colobomas, optic nerve and iris abnormalities. Additional common features included hypotonia (61%), heart defects (52%), growth failure (54%), and kidney anomalies (35%). PrediXcan analysis showed that phecodes most strongly associated with reduced predicted PRR12 expression were enriched for eye- (7/30) and kidney- (4/30) phenotypes, such as wet macular degeneration and chronic kidney disease. CONCLUSION: These findings support PRR12 haploinsufficiency as a cause for a novel disorder with a wide clinical spectrum marked chiefly by neurodevelopmental and eye abnormalities

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called episignatures ). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual