Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth.

Capillary malformations are slow-flow vascular malformations that affect the microcirculation including capillaries and post capillary venules and can be associated with growth differences. Specifically, the association of capillary malformations with undergrowth is a vastly understudied vascular syndrome with few reports of genetic causes including PIK3CA, GNAQ, and GNA11. Recently, a somatic pathogenic variant in AKT3 was identified in one child with a cutaneous vascular syndrome similar to cutis marmorata telangiectatica congenita, undergrowth, and no neurodevelopmental features. Here, we present a male patient with a capillary malformation and undergrowth due to a somatic pathogenic variant in AKT3 to confirm this association. It is essential to consider that mosaic pathogenic variants in AKT3 can cause a wide spectrum of disease. There is a need for future studies focusing on capillary malformations with undergrowth to understand the underlying mechanism.

PET imaging characteristics of neuromuscular choristoma and associated desmoid-type fibromatosis.

BACKGROUND: Neuromuscular choristoma (NMC) is a rare peripheral nerve lesion characterized by abnormal presence of muscle within nerve. Associated desmoid-type fibromatosis (NMC-DTF) often develops. We report 18F-fluorodeoxyglucose positron emission tomography (FDG PET) characteristics of NMC and NMC-DTF and propose that increased FDG activity within NMCs may be associated with subclinical NMC-DTF or NMC-DTF "precursor" tissue. METHODS: Our institutional database was searched for all NMC cases. Inclusion criteria were 1) confirmed diagnosis of NMC with or without biopsy, and 2) available PET and MRI studies. PET data included SUVmax and SUVmean of NMCs, contralateral limb normal skeletal muscle and unaffected nerves, and SUVmax of NMC-DTF if present. SUV values were compared using paired t-test. A p value of < 0.05 was considered statistically significant. RESULTS: Our cohort consisted of 9 patients with NMC, 8 cases involving sciatic nerve and 1 of brachial plexus. On PET imaging, all NMC-affected nerve segments showed significantly higher FDG uptake (SUVmax/mean) compared to both contralateral normal nerve and normal skeletal muscle (all P < 0.05). Similar to sporadic DTF, NMC-DTF was highly FDG-avid (average SUVmax of 4.2). SUVmax in NMC with or without concurrent NMC-DTF did not differ (p = 0.76). Within NMC-affected nerve segment, FDG activity was relatively higher in areas with low T1/T2 MR signal. CONCLUSION: All NMCs were more FDG avid compared to both normal skeletal muscle and contralateral unaffected nerve, arguing against the presence of heterotopic muscle in NMC as the source of FDG avidity. FDG avidity within NMC may reflect subclinical NMC-DTF or a precursor lesion, as NMC-DTF are highly FDG-avid, and the highest regions of FDG avidity in NMC occurred in regions with MR characteristics associated with NMC-DTF (i.e., lower T1/T2 signal). We believe that the integration of FDG PET with serial MR imaging in patient follow up will clarify its utility in both detection and surveillance of NMC-DTF.

Segmental undergrowth is associated with pathogenic variants in vascular malformation genes: A retrospective case-series study.

Segmental overgrowth has been widely described in patients with congenital vascular anomalies. However, segmental undergrowth has been poorly characterized, and no large series of patients have been published. We present the clinical and molecular characteristics a cohort of 37 patients with vascular malformations and segmental undergrowth. True undergrowth was only considered when the musculoskeletal system was involved to avoid confusion with other causes of segmental reduction, as in lipodystrophy or the long-term osteopenia seen in patients with Servelle-Martorell syndrome. Deep high-throughput sequencing was performed in tissue samples from 20 patients using a custom panel. We identified three groups: undergrowth associated with (1) venous, (2) capillary-venous, and (3) lymphatic-capillary-venous malformations. Congenital or early childhood onset undergrowth can occur with or without associated overgrowth. Different likely pathogenic or pathogenic variants were detected in 13 of 20 (65%) tissue samples in the PIK3CA, TEK, GNAQ, or GNA11 genes. In conclusion, the eponymous Servelle-Martorell syndrome should not be used as a synonym for undergrowth. Segmental undergrowth should be considered a characteristic associated with vascular malformations. Patients with PIK3CA variants show all different combinations of overgrowth and undergrowth. Thus, the term PROS (PIK3CA-related overgrowth spectrum) does not cover the entire spectrum.

Misdiagnosis of capillary malformations in darker skin phototypes.

In the dermatologic medical literature, there is an underrepresentation of conditions in individuals of color. Due to the lack of representation, it may be harder for clinicians to recognize certain diagnoses in patients with darker skin phototypes leading to misdiagnosis and affecting overall patient management, outcomes, and satisfaction. Here, we present four Black or Indigenous People of Color who were initially referred for hyperpigmentation, hemihyperplasia, or café au lait spots and found to have syndromic capillary malformations.

Photosynthetic performance and growth responses of Liriope muscari (Decne.) L.H. Bailey (Asparagaceae) planted within poplar forests having different canopy densities.

BACKGROUND: Liriope muscari (Decne.) L.H. Bailey is a valuable horticultural and medicinal plant that grows under a range of light intensities, from high to low, in the understories of shrubs. To understand how this species adapts to these various environments, we selected two groups of lilyturf growing under poplar trees at two different spacings. Each group was divided into three types, open field, forest edge and shaded forest with high, medium and low irradiance levels, respectively, and then we examined their photosynthetic characteristics, physiology and biomasses. RESULTS: Light saturation point, light compensation point and in situ net photosynthetic rate (PN) were highest in lilyturf growing under high light. In contrast, lilyturf growing under low light had a higher apparent quantum yield and Chl a and b contents, indicating that they adapted to low light. Although the leaves of lilyturf growing under low light were small, their root tubers were heavier. CONCLUSIONS: The research demonstrates the eco-physiological basis of lilyturf's shade adaptation mechanism as indicated by photosynthetic activity, chlorophyll fluorescence, Chl a, Chl b and Car contents when grown under different irradiances. We believe that lilyturf is a shade-tolerant plant suitable for planting in undergrowth, but attention should be paid to the canopy density of the forest when interplanting. The findings presented here advance our understanding of the photosynthetic characteristics of understory plants and may assist in the optimization of irradiances in the future.

Clinical and genetic evaluation of six children with diffuse capillary malformation and undergrowth.

BACKGROUND: Diffuse capillary malformation with overgrowth (DCMO) has been well described. However, capillary malformation with undergrowth (CMU) has been less reported in the literature. OBJECTIVES: We sought to describe the clinical features and determine associated somatic mutations in patients with CMU. METHODS: We searched our multidisciplinary vascular anomalies clinic database for patients with CMU. Girth and length limb measurements were performed. In case of discrepancies in length, long leg radiograph studies were obtained. Whole-exome sequencing of blood and involved tissue DNA was carried out. RESULTS: We included six patients with CM and soft-tissue and bone undergrowth. CMs were patchy, reticulated, segmental, poorly demarcated, pink-red stains affecting the lower limb (five patients) or the whole hemibody (one patient). In five patients, the stain was diffuse, affecting more than one anatomic region. Prominent superficial veins were observed in three patients. Five patients presented with lower limb girth discrepancy; in three of them, there was also lower limb length discrepancy. In the remaining patient, only lower limb length discrepancy was found. Whole-exome sequencing from DNA tissue/blood detected previously described pathogenic somatic mutations on DDR2 (c.314G > A; p.Arg105His), GRHL2 (c.791A > G; p.Glu264Gly), and PIK3CA (c.2740G > A; p.Gly914Arg) genes. CONCLUSION: We propose the term "diffuse capillary malformation with undergrowth" for extensive reticular CMs associated with proportionate undergrowth. All our patients had a favorable outcome, and no genotype-phenotype association was found.

Intrauterine growth in chromatinopathies: A long road for better understanding and for improving clinical management.

BACKGROUND: Chromatinopathies are a heterogeneous group of genetic disorders caused by pathogenic variants in genes coding for chromatin state balance proteins. Remarkably, many of these syndromes present unbalanced postnatal growth, both under- and over-, although little has been described in the literature. Fetal growth measurements are common practice in pregnancy management and values within normal ranges indicate proper intrauterine growth progression; on the contrary, abnormalities in intrauterine fetal growth open the discussion of possible pathogenesis affecting growth even in the postnatal period. METHODS: Among the numerous chromatinopathies, we have selected six of the most documented in the literature offering evidence about two fetal overgrowth (Sotos and Weaver syndrome) and four fetal undergrowth syndromes (Bohring Opitz, Cornelia de Lange, Floating-Harbor, and Meier Gorlin syndrome), describing their molecular characteristics, maternal biochemical results and early pregnancy findings, prenatal ultrasound findings, and postnatal characteristics. RESULTS/CONCLUSION: To date, the scarce data in the literature on prenatal findings are few and inconclusive, even though these parameters may contribute to a more rapid and accurate diagnosis, calling for a better and more detailed description of pregnancy findings.

Structural and Dynamic Analyses of Pathogenic Variants in PIK3R1 Reveal a Shared Mechanism Associated among Cancer, Undergrowth, and Overgrowth Syndromes.

The PI3K enzymes modify phospholipids to regulate cell growth and differentiation. Somatic variants in PI3K are recurrent in cancer and drive a proliferative phenotype. Somatic mosaicism of PIK3R1 and PIK3CA are associated with vascular anomalies and overgrowth syndromes. Germline PIK3R1 variants are associated with varying phenotypes, including immunodeficiency or facial dysmorphism with growth delay, lipoatrophy, and insulin resistance associated with SHORT syndrome. There has been limited study of the molecular mechanism to unify our understanding of how variants in PIK3R1 drive both undergrowth and overgrowth phenotypes. Thus, we compiled genomic variants from cancer and rare vascular anomalies and sought to interpret their effects using an unbiased physics-based simulation approach for the protein complex. We applied molecular dynamics simulations to mechanistically understand how genetic variants affect PIK3R1 and its interactions with PIK3CA. Notably, iSH2 genetic variants associated with undergrowth destabilize molecular interactions with the PIK3CA receptor binding domain in simulations, which is expected to decrease activity. On the other hand, overgrowth and cancer variants lead to loss of inhibitory interactions in simulations, which is expected to increase activity. We find that all disease variants display dysfunctions on either structural characteristics or intermolecular interaction energy. Thus, this comprehensive characterization of novel mosaic somatic variants associated with two opposing phenotypes has mechanistic importance and biomedical relevance and may aid in future therapeutic developments.

A geographical perspective on the relationship between Impatiens spur lengths and bill lengths of sunbirds in Afrotropical mountains.

Trait matching-a correlation between the morphology of plants and their pollinators-has been frequently observed in pollination interactions. Different intensities of natural selection in individual regions should cause such correlations to be observable across different local assemblages. In this study, we focused on matching between spur lengths of the genus Impatiens and bill lengths of sunbirds in tropical Africa. For 25 mountain and island locations, we compiled information about the composition and traits of local Impatiens and sunbird assemblages. We found that assemblage mean and maximum values of bill lengths were positively correlated with mean and maximum spur lengths across locations. Moreover, our results suggest that the positive correlations hold only for forest sunbird assemblages sharing the same habitat with Impatiens species. We further show that long-billed sunbirds seem to locally match the morphology of multiple Impatiens plant species, not vice versa. Our observation implies that trait matching significantly contributes to structuring of Impatiens-sunbird pollination systems. We suggest that special habitat preferences together with spatial isolation of mountain environment might play a role in this case.

Response of plant diversity and soil physicochemical properties to different gap sizes in a Pinus massoniana plantation.

As one means of close-to-nature management, forest gaps have an important impact on the ecological service function of plantations. To improve the current situation of P. massoniana plantations, three different sizes of forest gaps (large gaps, medium gaps and small gaps) were established to observe whether gap setting can improve the soil fertility and plant diversity of forest plantations. The results showed that compared with the control, the soil organic matter content of different soil layers increased significantly in the medium forest gap and large forest gap. The content of soil organic matter in the surface layer of the middle gap had the largest increase (80.64%). Compared with the control, the content of soil-available potassium between different soil layers decreased significantly by 15.93% to 25.80%. The soil hydrolysable nitrogen reached its maximum under the medium gap. Soil moisture showed significant changes among different gap treatments, different soil layers and their interaction, decreasing significantly in large gaps and small gaps but increasing significantly in medium gaps. The soil bulk density decreased significantly compared with the control, and the surface soil reached the minimum in the medium gap. There were different plant species in forest gaps of different sizes, and shrub layer plants were more sensitive to gap size differences than herb layer plants. The plant diversity indices of the shrub layer increased significantly and showed a maximum under the medium gap. The plant diversity of the herb layer showed the opposite trend, and the Shannon-Wiener index, Simpson index and Pielou index were significantly lower than those of the control. RDA showed that different gap treatments had significant effects on the distribution of plants under the forest. Soil available potassium, soil moisture and soil bulk density affected the distribution and diversity of plants under the forest, serving as the limiting factors of plant growth. In forest management, if we strictly consider the improvement of plant diversity and soil physicochemical properties, these results suggest that a medium gap should be established in a plantation for natural restoration.

The Role of Forensic Botany in Reconstructing the Dynamics of Trauma from High Falls.

The analysis of botanical traces can be supportive, especially when the crime scene investigation and autopsy do not provide sufficient information. This issue arises most commonly in fatal falls from height. We report the case of a man found dead below a hill. The body showed traumatic injuries from a fall. During the scene investigation, a sampling of botanical elements was carried out on three zones of the hill called the point of loss of balance, the point of fall, and the point of impact. The botanical elements collected on the three zones were compared with those found on the victim and an autopsy was performed. The botanical analysis clarified the phases of falling, as well as allowing us to reconstruct the dynamics and the accidental manner of death.

Current and future potential distributions of three Dracaena Vand. ex L. species under two contrasting climate change scenarios in Africa.

Forest undergrowth plants are tightly connected with the shady and humid conditions that occur under the canopy of tropical forests. However, projected climatic changes, such as decreasing precipitation and increasing temperature, negatively affect understory environments by promoting light-demanding and drought-tolerant species. Therefore, we aimed to quantify the influence of climate change on the spatial distribution of three selected forest undergrowth plants, Dracaena Vand. ex L. species, D. afromontana Mildbr., D. camerooniana Baker, and D. surculosa Lindl., simultaneously creating the most comprehensive location database for these species to date. A total of 1,223 herbarium records originating from tropical Africa and derived from 93 herbarium collections worldwide have been gathered, validated, and entered into a database. Species-specific Maxent species distribution models (SDMs) based on 11 bioclimatic variables from the WorldClim database were developed for the species. HadGEM2-ES projections of bioclimatic variables in two contrasting representative concentration pathways (RCPs), RCP2.6 and RCP8.5, were used to quantify the changes in future potential species distribution. D. afromontana is mostly sensitive to temperature in the wettest month, and its potential geographical range is predicted to decrease (up to -63.7% at RCP8.5). Optimum conditions for D. camerooniana are low diurnal temperature range (6-8°C) and precipitation in the wettest season exceeding 750 mm. The extent of this species will also decrease, but not as drastically as that of D. afromontana. D. surculosa prefers high precipitation in the coldest months. Its potential habitat area is predicted to increase in the future and to expand toward the east. This study developed SDMs and estimated current and future (year 2050) potential distributions of the forest undergrowth Dracaena species. D. afromontana, naturally associated with mountainous plant communities, was the most sensitive to predicted climate warming. In contrast, D. surculosa was predicted to extend its geographical range, regardless of the climate change scenario.

Dinâmica do sub-bosque e do estado arbóreo de floresta tropical primária fragmentada na Amazônia Oriental1

The present paper aims at evaluating the forest dynamics - mainly that brought by natural regeneration -in a fragment of dense, terra firme tropical primary forest from 1998 through 1999, municipality of Peixe-Boi (PA). Three 1 ha permanent plots were marked off and every individual within having DBH 10 cm was registered. Individuals having DBH between 5 and 10cm were sampled out in an area of 6.000 m2, those having DBH between 2 and 5cm were sampled out in an area totaling 2.400 in2, and individuals having DBH under 2 cm were sampled in 240 m2. There are about 143.000 individuals ranging from seedlings to trees, of 337 species and 76 families. Mimosaceae was the family with higher diversity (44 species). Fourteen families occurred as an only species, including 7 families occurring also as an only individual. Considering the whole sample (that is, independently from diametric class) the egression of 56 species versus ingression of 68 was verified, producing a net gain of 12 species. The dynamics of species richeness in natural regeneration is remarkably intense, and the dynamics of abundance of natural regeneration, is more intense than that of floristic richeness. It was also observed that only one family left, while 14 other families entered, thus enriching biodiversity in almost 30%. The highest mortality verified was of Bauhinia cf. rutilans and Mabea aff speciosa (300 and 21 individuals). Rinorea negleta and Lecythis idatimon displayed the recruitment of 171 and 89 specimens. The recruitment/mortality rate was higher than one unit in all diametric classes. The proportion of seedlings needed to obtain a tree, a sapling and a stemlet is 297, 160 e 48 respectively. Richeness and abundance increased during the one year period, as did basal area and biomass.

Objetivou-se neste trabalho avaliar a dinâmica florestal, sobretudo da regeneração natural, em um fragmento de floresta tropical primária, entre 1998 c 1999, em Peixe-Boi (PA). Foram demarcadas três parcelas permanentes (1 ha cada) onde todos os indivíduos com DAP 10 cm foram registrados; os indivíduos com 10cm DAP 5cm foram amostrados em 6.000 m2, aqueles entre 5cm DAP 2cm em 2.400 m2 e com DAP 2cm em 240 m2. Foram estimados 143.000 indivíduos, desde plântulas até árvores pertencentes a 337 espécies e 76 famílias. Mimosaceae foi a família de maior riqueza (44 espécies); 14 famílias ocorreram com uma única espécie sendo que metade delas apresentaram também um único indivíduo. Independentemente da classe diamétrica verificou-se o egresso de 56 espécies versus o ingresso de 68, gerando um ganho líquido de 12 espécies. A dinâmica da composição e da abundância da regeneração natural foi muito intensa. Observou-se a saída de uma família face ao ingresso de outras 14, aumentando cm quase 30% o número de espécies. A maior mortalidade foi verificada em Bauhinia cf. rutilans e Mabea aff. speciosa (300 e 21 indivíduos). Rinorea negleta e Leçythis idatimon recrutaram 171 e 89 espécimes. A razão recrutamento/ mortalidade foi, em quaisquer das classes diamétricas, sempre superior a unidade. O estoque de mudas para se obter uma árvore, uma arvoreta e uma vara foi, respectivamente de 297, 160 e 48 mudas. O número de espécies e a abundância aumentaram no período, assim como a área basal e a biomassa.