Given the links between forest mycorrhizal strategy and carbon sequestration potential, the presence of mycorrhizal-mediated alternative stable states affects how we forecast forest composition, carbon sequestration and terrestrial climate feedbacks.Ectomycorrhizas and arbuscular mycorrhizas, the two most widespread plant-fungal symbioses, are thought to differentially influence tree species diversity, with positive plant-soil feedbacks favouring locally abundant ectomycorrhizal tree species and negative feedbacks promoting species coexistence and diversity in arbuscular mycorrhizal forests. While seedling recruitment studies and cross-biome patterns of plant diversity and mycorrhizal dominance support this hypothesis, it remains to be tested at the forest stand level over continental scales. Here, we analyse approximately 82,000 forest plots across the USA to show that both ectomycorrhizal-dominated and arbuscular mycorrhizal-dominated forests show relatively low tree diversity, while forests with a mixture of mycorrhizal strategies support a higher number of tree species. Our findings suggest that mycorrhizal dominance, rather than mycorrhizal type, shapes tree diversity in forests.

To establish a model to predict treatment outcome of periocular locally advanced basal cell carcinoma (POLA BCC) based on initial response to treatment with vismodegib (Erivedge

), a sonic hedgehog inhibitor.

Subgroup analysis of data from the STEVIE study database.

Analysis of medical history, treatment protocol, and treatment outcome of POLA BCC tumours in a STEVIE study population of 244 POLA BCC patients treated with ≥1 dose of vismodegib.

A predictive model for complete response (CR) was established based on the initial treatment response. A cutoff value of 20% reduction in tumour size at 3 months of treatment identified the patients with a high probability (82.76%) to achieve CR. A second cutoff value of 67.7% reduction in tumour size at 6 months of treatment improved the prediction to a 95.42% probability of a CR outcome.

A treatment model was constructed based on the prediction of a CR outcome and the initial response to vismodegib treatment at 3 and 6 months. The study result provide significant new insights can facilitate decision-making on treatment management according to tumour response in patients with POLA BCC.

A treatment model was constructed based on the prediction of a CR outcome and the initial response to vismodegib treatment at 3 and 6 months. The study result provide significant new insights can facilitate decision-making on treatment management according to tumour response in patients with POLA BCC.

Idiopathic intracranial hypertension (IIH) is a condition of raised intracranial pressure (ICP). Obstructive sleep apnoea (OSA) has been shown to cause episodic rises in ICP and is frequently reported in patients with IIH. The aim of this study is to identify the prevalence of OSA in a cohort of IIH patients.

We conducted a retrospective case notes review as part of a service evaluation of newly diagnosed IIH patients who were all referred for OSA screening with overnight pulse oximetry. The 3% oxygen desaturation index (3% ODI) was used to evaluate the presence and severity of OSA. The clinical outcomes of patients who received continuous positive airway pressure (CPAP) therapy as treatment for OSA were reviewed.

In our cohort of newly diagnosed IIH patients, the yield of overnight pulse oximetry as a screening tool was 48.6% for OSA and 15.3% for moderate to severe OSA. We found that age (p = 0.0008), BMI (p < 0.0001), vitamin B

(p = 0.0183), and a higher Epworth Sleep Score (p = 0.0269) correlated with more severe OSA. Eleven (10%) patients had CPAP therapy and those with good adherence alongside weight loss or medical therapy found improvements in symptoms of raised ICP.

We report the largest series of consecutive IIH patients screened for OSA using overnight pulse oximetry. The high rate of OSA highlights a potential role for the recognition and management of OSA in the IIH patient cohort. Further studies on the potential contribution of OSA as a cause of raised ICP in the IIH cohort is warranted.

We report the largest series of consecutive IIH patients screened for OSA using overnight pulse oximetry. The high rate of OSA highlights a potential role for the recognition and management of OSA in the IIH patient cohort. Further studies on the potential contribution of OSA as a cause of raised ICP in the IIH cohort is warranted.Autism spectrum disorders (ASD) are associated with defects in neuronal connectivity and are highly heritable. Genetic findings suggest that there is an overrepresentation of chromatin regulatory genes among the genes associated with ASD. ASH1 like histone lysine methyltransferase (ASH1L) was identified as a major risk factor for ASD. ASH1L methylates Histone H3 on Lysine 36, which is proposed to result primarily in transcriptional activation. However, how mutations in ASH1L lead to deficits in neuronal connectivity associated with ASD pathogenesis is not known. We report that ASH1L regulates neuronal morphogenesis by counteracting the catalytic activity of Polycomb Repressive complex 2 group (PRC2) in stem cell-derived human neurons. Depletion of ASH1L decreases neurite outgrowth and decreases expression of the gene encoding the neurotrophin receptor TrkB whose signaling pathway is linked to neuronal morphogenesis. The neuronal morphogenesis defect is overcome by inhibition of PRC2 activity, indicating that a balance between the Trithorax group protein ASH1L and PRC2 activity determines neuronal morphology. Thus, our work suggests that ASH1L may epigenetically regulate neuronal morphogenesis by modulating pathways like the BDNF-TrkB signaling pathway. Defects in neuronal morphogenesis could potentially impair the establishment of neuronal connections which could contribute to the neurodevelopmental pathogenesis associated with ASD in patients with ASH1L mutations.Canonically, EZH2 serves as the catalytic subunit of PRC2, which mediates H3K27me3 deposition and transcriptional repression. Here, we report that in acute leukaemias, EZH2 has additional noncanonical functions by binding cMyc at non-PRC2 targets and uses a hidden transactivation domain (TAD) for (co)activator recruitment and gene activation. Both canonical (EZH2-PRC2) and noncanonical (EZH2-TAD-cMyc-coactivators) activities of EZH2 promote oncogenesis, which explains the slow and ineffective antitumour effect of inhibitors of the catalytic function of EZH2. To suppress the multifaceted activities of EZH2, we used proteolysis-targeting chimera (PROTAC) to develop a degrader, MS177, which achieved effective, on-target depletion of EZH2 and interacting partners (that is, both canonical EZH2-PRC2 and noncanonical EZH2-cMyc complexes). Compared with inhibitors of the enzymatic function of EZH2, MS177 is fast-acting and more potent in suppressing cancer growth. This study reveals noncanonical oncogenic roles of EZH2, reports a PROTAC for targeting the multifaceted tumorigenic functions of EZH2 and presents an attractive strategy for treating EZH2-dependent cancers.Haematopoietic stem cells (HSCs) home to the bone marrow via, in part, interactions with vascular cell adhesion molecule-1 (VCAM1)1-3. Once in the bone marrow, HSCs are vetted by perivascular phagocytes to ensure their self-integrity. Here we show that VCAM1 is also expressed on healthy HSCs and upregulated on leukaemic stem cells (LSCs), where it serves as a quality-control checkpoint for entry into bone marrow by providing 'don’t-eat-me’ stamping in the context of major histocompatibility complex class-I (MHC-I) presentation. Although haplotype-mismatched HSCs can engraft, Vcam1 deletion, in the setting of haplotype mismatch, leads to impaired haematopoietic recovery due to HSC clearance by mononuclear phagocytes. Mechanistically, VCAM1 'don’t-eat-me’ activity is regulated by β2-microglobulin MHC presentation on HSCs and paired Ig-like receptor-B (PIR-B) on phagocytes. VCAM1 is also used by cancer cells to escape immune detection as its expression is upregulated in multiple cancers, including acute myeloid leukaemia (AML), where high expression associates with poor prognosis. In AML, VCAM1 promotes disease progression, whereas VCAM1 inhibition or deletion reduces leukaemia burden and extends survival. These results suggest that VCAM1 engagement regulates a critical immune-checkpoint gate in the bone marrow, and offers an alternative strategy to eliminate cancer cells via modulation of the innate immune tolerance.Twisted heterostructures of two-dimensional crystals offer almost unlimited scope for the design of new metamaterials. Here we demonstrate a room temperature ferroelectric semiconductor that is assembled using mono- or few-layer MoS2. These van der Waals heterostructures feature broken inversion symmetry, which, together with the asymmetry of atomic arrangement at the interface of two 2D crystals, enables ferroelectric domains with alternating out-of-plane polarization arranged into a twist-controlled network. The last can be moved by applying out-of-plane electrical fields, as visualized in situ using channelling contrast electron microscopy. The observed interfacial charge transfer, movement of domain walls and their bending rigidity agree well with theoretical calculations. Furthermore, we demonstrate proof-of-principle field-effect transistors, where the channel resistance exhibits a pronounced hysteresis governed by pinning of ferroelectric domain walls. Our results show a potential avenue towards room temperature electronic and optoelectronic semiconductor devices with built-in ferroelectric memory functions.To treat older patients with hypertension, it is important to detect cognitive impairment at an early stage because of its potential influence on treatment efficacy and functional prognosis. In this study, we aimed to identify the incidence and determinants of cognitive impairment in hypertensive patients aged 65 years and above who visited our outpatient clinic and were not previously diagnosed with cognitive impairment. Among 312 patients with hypertension, we found that 35% (n = 109) and 7.7% (n = 24) had cognitive impairment and dementia, respectively, as defined by the Mini-Mental State Examination (≤27 or ≤23, respectively). Patients with cognitive impairment were older, had lower levels of education, and had lower instrumental activities of daily living (IADL) scores than those without cognitive impairment. Multiple regression analysis revealed that age and IADL were associated with cognitive impairment in patients with hypertension. Regarding the treatment of hypertension, the office and home blood pressure levels, number of antihypertensive medications prescribed, and proportion of the use of each antihypertensive drug was equivalent between patients with and without cognitive impairment. Finally, patients with unrecognized cognitive impairment showed distinct clinical characteristics, including high antihypertensive medication burden and preserved IADL, when compared to hypertensive patients in the different cohorts of definitive mild cognitive impairment of a similar age. These findings suggest that older hypertensive patients are at a high risk of masked cognitive decline, even if they are functionally independent.