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The phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a grouping of related genetic disorders that has been linked to germline mutations in the PTEN gene. These disorders include Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome, adult Lhermitte–Duclos disease, and autism spectrum disorders associated with macrocephaly. The majority of the clinical information available on PHTS, however, is related to individuals diagnosed with CS. There is still much to be learned about this disorder, since diagnostic criteria for CS were only established in 1996, before the identification of the PTEN gene, and were based primarily on features seen in cases reported in the existing literature. More recently, however, data from several large series of patients have shown that a number of the clinical features associated with PTEN mutations are either more or less common than previously reported. In addition, we now know that only about 30–35% of patients meeting clinical diagnostic criteria for Cowden syndrome actually have a detectable PTEN mutation. Thus, our understanding of PTEN-related diseases and their management has evolved significantly over time. The United States National Comprehensive Cancer Network (NCCN) has produced and regularly updates practice guidelines which include clinical diagnostic criteria as well as guidelines for PTEN testing and management of patients with mutations. This review will summarize the overall literature on PHTS as well as recent findings which are broadening our understanding of this set of disorders.

Phosphorus (P) is a macronutrient that plays a crucial role in critical plant functions. Phosphate transporters (PHTs) ensure the acquisition and translocation of Pi in the plant, thereby playing a key role in maintaining normal plant growth under Pi deficiency conditions. In Brachypodium distachyon , the grass model system, the function of individual PHT genes, remains largely unknown. Here, we identified the complete PHT gene family in B. distachyon , for the first time, and analyzed their expression profiles under Pi deficiency. Overall, 25 PHT genes in B. distachyon ( BdPHTs ) were identified, which were divided into four clades (PHT1-4). BdPHT genes were found to be unevenly distributed across the five chromosomes. Both segmental and tandem duplication events contributed to PHT gene expansion in B. distachyon which underwent a strong purifying selection . Moreover, exon–intron organization and motif composition were conserved within each PHT group consolidating the classification of the phylogenetic tree. Motif composition differs among the four PHT groups, indicating their functional divergence. Gene expression analysis using real-time quantitative PCR revealed that two BdPHT1 genes ( BdPHT1.9 and BdPHT1.10 ) were upregulated in leaves, and seven ( BdPHT1.9 , BdPHT1.8 , BdPHT1.7 , BdPHT1.11 , BdPHT1.12 , BdPHT1.5 , and BdPHT1.13 ) in roots under P deficiency suggesting their involvement in P uptake and translocation. Therefore, these results lay the foundation for future functional analyses in B. distachyon to improve P deficiency tolerance in B. distachyon and other cereals.

The conceptual development of the EUropean DEMOnstration fusion reactor (EU-DEMO) envisages a series of modifications aimed at improving the design of the reactor and its plant systems and triggering iterative calculation procedures for an organic development of the project itself. The present work fits into this context, focusing on a critical evaluation of the shielding performances of the tokamak building structures surrounding the primary coolant system for the water-cooled breeding blanket concept. As yardstick to measure the cooling loop shielding features the assessment was based around the water activation product which generally drives the size of the secondary shield walls in water-cooled fusion reactors, namely the 16N isotope, and the numerical analyses were centered onto the 2022 configuration of the Primary Heat Transport System (PHTS) for the Water Cooled Lithium Lead Breeding Blanket (BB) concept. Research activity was articulated in two main phases. A first stage where the following quantities were assessed: (i) production rates of 16N within the BB cooling water and (ii) spatial distribution of 16N across the entire cooling loop. A final phase where photonic calculations were performed to evaluate the spatial distribution of the absorbed dose rate in the neighborhood of the cooling loop. The preparatory phase was necessary to set up the volumetric gamma source in the different regions of the primary circuit. Distribution of 16N within the PHTS was obtained through a dedicated 1-D transport analysis, while particle transport simulations have followed a computational approach based on the Monte Carlo method adopting the Monte Carlo N-Particle code (MCNP5-1.60). Results highlighted some critical issue and shortcomings in the layout of the PHTS as well as in the approach followed to develop the cooling loop shielding. Models, assumptions and analysis results are herein reported and a critical discussion on needed design modifications is presented.

Background Phosphorus (P) is an indispensable mineral element which plays crucial roles in plant development and production. While it is widely acknowledged that phosphate transporters (PHT) facilitate the absorption of P, detailed identification and characterization of the PHT genes in Orychophragmus violaceus remains unexplored. Results Here, a total of 22 OvPHT genes were identified from high-quality genome of O. violaceus and could be categorized into four distinct subfamilies, based on the phylogenetic analysis. Synteny analysis revealed that the OvPHT gene family underwent nine segmental duplication events and two tandem duplication events. Additionally, a detailed analysis of the Ka/Ks ratios indicated that these duplicated gene pairs primarily experienced purifying selection. Expression patterns of these OvPHT genes across various tissues, including leaves, roots, stems, and flowers, showed differential but partial-overlapping patterns. OvPHT1 members were predominantly expressed in roots and induced by P starvation. Conversely, OvPHT4 members showed high expression levels in all tested tissues, except for roots; the expression levels of OvPHT2 and OvPHT3 members were mainly detected in leaves and flowers, respectively. Moreover, OvPHT1;1 was localized in the plasma membrane. Overexpression of OvPHT1;1 in rice could enhance P uptake under low-P condition. Conclusion In summary, this systematic analysis provides detailed information for a better understanding of OvPHT genes and identifies candidate genes for further exploration of P-efficient utilization in O. violaceus .

This work presents a thermohydraulic analysis of a postulated accident involving the rupture of the breeder primary cooling loop inside a heat exchanger (once through steam generator). After the detection of the loss of pressure inside the primary loop, a plasma shutdown is actuated with a consequent plasma disruption, isolation of the secondary loop, and shutoff of the pumps in the primary; no other safety counteractions are postulated. The objective of the work is to analyze the pressurization of the primary and secondary sides to show that the accidental overpressure in the two sides of the steam generators is safely accommodated. Furthermore, the effect of the plasma disruption on the FW, in terms of temperatures, should be analyzed. Lastly, the time transients of the pressures and temperatures in the HX and BB for a time span of up to 36 h should be obtained to assess the effect of the decay heat over a long period. A full nodalization of the OTSG was realized together with a simplified nodalization of the whole PHTS BB loop. The code utilized was MELCOR for fusion version 1.8.6. The accident was simulated by activating a flow path which directly connected one section of the primary with the parallel section of the secondary side. It is shown here that the pressures and the temperatures inside the whole PHTS system remain below the safety thresholds for the whole transient.

PTEN hamartoma tumour syndrome (PHTS), a rare disease caused by germline heterozygous PTEN variants, is associated with multi-organ/tissue overgrowth, autism spectrum disorder and increased cancer risk. Phenotypic variability in PHTS is partly due to diverse PTEN variants and the protein's multifaceted functions. PTEN is primarily a phosphatidylinositol(3,4,5)trisphosphate (PIP3) phosphatase regulating PI3K/AKT signalling but also maintains chromosomal stability through nuclear functions such as double-stranded (ds)DNA damage repair. Here, we show that PTEN-R173C, a pathogenic variant frequently found in PHTS and somatic cancer, has elevated PIP3 phosphatase activity that effectively regulates canonical PI3K/AKT signalling. However, PTEN-R173C is unstable and excluded from the nucleus. We generated Pten+/R173C mice which developed few tumours during their lifetime, aligning with normal PI3K/AKT signalling. However, they exhibited lymphoid hyperplasia, macrocephaly and brain abnormalities, associated with impaired nuclear functions of PTEN-R173C, demonstrated by reduced dsDNA damage repair. We integrated PHTS patient data with our mouse model results, and propose that defective nuclear functions of PTEN variants can predict the onset of PHTS phenotypes and that late-onset cancer in these individuals may arise from secondary genetic alterations, facilitated by compromised dsDNA repair.

Phosphorus (P), an essential nutrient required by plants often becomes the limiting factor for plant growth and development. Plants employ various mechanisms to sense the continuously changing P content in the soil. Transcription factors, such as SHORT ROOT (SHR), AUXIN RESPONSE FACTOR19 (ARF19), and ETHYLENE-INSENSITIVE3 (EIN3) regulate the growth of primary roots, root hairs, and lateral roots under low P. Crop improvement strategies under low P depend either on improving P acquisition efficiency or increasing P utilization. The various phosphate transporters (PTs) are involved in the uptake and transport of P from the soil to various plant cellular organelles. A plethora of regulatory elements including transcription factors, microRNAs and several proteins play a critical role in the regulation of coordinated cellular P homeostasis. Among these, the well-established P starvation signaling pathway comprising of central transcriptional factor phosphate starvation response (PHR), microRNA399 (miR399) as a long-distance signal molecule, and PHOSPHATE 2 (PHO2), an E2 ubiquitin conjugase is crucial in the regulation of phosphorus starvation responsive genes. Under PHR control, several classes of PHTs, microRNAs, and proteins modulate root architecture, and metabolic processes to enable plants to adapt to low P. Even though sucrose and inositol phosphates are known to influence the phosphorus starvation response genes, the exact mechanism of regulation is still unclear. In this review, a basic understanding of P homeostasis under low P in plants and all the above aspects are discussed.

Purpose PTEN hamartoma tumor syndrome (PHTS) comprises a group of rare genetic conditions caused by germline mutations in PTEN gene and characterized by development of both benign and malignant lesions in many body tissues. In this study, we aimed to evaluate the incidence of thyroid findings in both adult and pediatric PHTS patients. Methods A retrospectively analysis conducted in 19 (13 adult and 6 pediatric) patients with PHTS, all confirmed with genetic testing, observed from 2015 to 2021 at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico. Results We found a thyroid involvement in 12 adult patients (92%): 11 patients had benign lesions (85%) and the remaining developed a follicular thyroid carcinoma (8.3%). The median age at time of the first available record was 30 years. Among benign lesions, multinodular goiter was the most observed finding (10/11, 91%). Only 1 out of 6 (16%) pediatric patients was diagnosed with a thyroid lesion (unifocal lesion in mild lymphocytic thyroiditis) at the age of 8 years. Conclusions Thyroid disorders affected nearly all adult PHTS patients, but a much lower proportion of pediatric patients. We discuss about the natural history of thyroid involvement, age of PHTS clinical onset, and optimized surveillance.

Increased hereditary cancer risk is one of the hallmarks of PTEN Hamartoma Tumor Syndrome (PHTS) which is caused by a pathogenic germline variant in PTEN . Case reports and some cohort studies have described ovarian cancer (OC) in PHTS patients. Previously, we observed an enrichment of non-serous OC in PHTS compared to sporadic cases (3% vs 1%). However, ovarian cancer is currently not considered a PHTS-related cancer. The aim of this study was to describe five PHTS patients with a pathogenic germline variant in PTEN with non-serous OC. Three of the non-serous OCs were mucinous carcinomas (49, 51 and 52 years) and two were malignant germ cell tumors (8 and 15 years) and all were diagnosed before genetic testing and PHTS diagnosis. In addition to OC, the described patients developed other PHTS-related benign and malignant lesions. We provide further evidence that non-serous ovarian cancer, especially mucinous, endometrioid and malignant germ cell tumors should be further investigated as potential PHTS-related cancers.

(1) Background/Objectives: Women with PTEN hamartoma tumor syndrome (PHTS) face a significantly increased risk of breast cancer (up to 66%) and a high prevalence of benign breast lesions (30–75%), which can complicate cancer detection and underscore the need for effective surveillance strategies. This study aimed to evaluate the imaging characteristics of breast cancers and benign breast lesions using magnetic resonance imaging (MRI) and mammography, with the goal of improving early cancer detection, reducing unnecessary biopsies, and guiding future surveillance protocols. (2) Methods: This retrospective single-institution study included 65 PHTS women aged ≥18 years (2001–2021), 39 of whom participated in a high-risk breast cancer surveillance program. Imaging features of breast cancers from MRI and mammography (when available) and of benign breast lesions from MRI only were assessed independently by two breast radiologists and correlated with pathology reports. Sensitivity and performance of MRI and mammography in detecting breast cancers and benign breast lesions were analyzed using descriptive statistics and correlation analyses, with significance set at p < 0.05. (3) Results: Imaging was available for re-evaluation for 17 breast cancers (with MRI available for 10 cases and mammography for 15 cases) diagnosed in 11 women and 31 benign breast lesions (with MRI available for 29 cases and mammography for 26 cases) in 16 women. MRI identified 90% (9/10) of the breast cancers for which it was available as suspicious, with malignant features retrospectively identifiable in 50% of baseline scans. In comparison, mammography identified only 40% (6/15) of breast cancers and was notably less effective in women with dense breast tissue. For benign breast lesions, MRI identified all lesions (29/29), while mammography underperformed, correctly identifying only 58% (15/26). However, ambiguous enhancement features on MRI occasionally posed challenges in distinguishing between benign breast lesions and malignancies. (4) Conclusions: MRI significantly outperformed mammography in accurately characterizing both breast cancers and benign breast lesions in women with PHTS, particularly in younger women with dense breast tissue. These findings reinforce the critical role of MRI as the primary surveillance tool for this high-risk population, given that breast cancers in women with PHTS tend to exhibit typical malignant features on MRI. However, they also highlight the importance of careful interpretation of MRI findings for benign breast lesions and the need for additional strategies to minimize unnecessary interventions.