Carolignans from the Aerial Parts of Euphorbia sikkimensis and Their Anti-HIV Activity

Seven new carolignans, including two pairs of enantiomers (±)-erythro-7′-methylcarolignan E (1a/1b) and (±)-threo-7′-methylcarolignan E (2a/2b), (+)-threo-carolignan E (3a), (+)-erythro-carolignan E (4a), and (−)-erythro-carolignan Z (5), together with four known lignans (3b, 4b, 6, and 7) and six polyphenols (8–13) were isolated from the aerial parts of Euphorbia sikkimensis. The structures of the new compounds were elucidated by spectroscopic analysis, and their absolute configurations were determined by electronic circular dichroism calculations. Seven of the isolates were examined for anti-HIV effects, and compounds 1a and 1b showed moderate anti-HIV activity with EC50 values of 6.3 and 5.3 μM

Pencirian jujukan genom mitokondria spesies Rafflesia (Rafflesiaceae) di Semenanjung Malaysia

Rafflesia terkenal sebagai tumbuhan yang menghasilkan bunga tunggal yang terbesar di dunia. Namun, ia semakin jarang ditemui dan ialah spesies dalam bahaya. Sistem pengelasan spesies Rafflesia ialah komponen penting dalam usaha pemuliharaan lazimnya bergantung kepada pencirian morfologi bunga. Walau bagaimanapun, pendekatan molekul, termasuk yang berasaskan kepada jujukan genom mitokondria (mtDNA), berupaya menyediakan kaedah pengelasan yang lebih berkesan. Untuk meneroka kemungkinan ini, jujukan mtDNA empat spesies Rafflesia di Semenanjung Malaysia, iaitu R. cantleyi, R. azlanii, R. kerrii dan R. sharifah-hapsahiae telah dihimpun dan dicirikan dalam kajian ini. Bacaan jujukan mtDNA untuk setiap spesies kajian pada mulanya telah ditentukan masing-masing daripada set data genom keseluruhan menggunakan pendekatan pemetaan berbantukan rujukan. Proses penghimpunan secara de novo dan perancahan kemudiannya telah dijalankan ke atas bacaan jujukan yang telah dikenal pasti untuk menghasilkan jujukan mtDNA bagi R. cantleyi (441,992 pb), R. azlanii (472,723 pb), R. kerrii (500,932 pb) dan R. sharifah-hapsahiae (453,747 pb). Seterusnya, anotasi mtDNA bagi setiap spesies telah mengenal pasti sekurang-kurangnya 31 gen pengekodan protein, enam gen tRNA dan tiga rRNA. Perbandingan gen mitokondria mendapati bahawa beberapa gen seperti cob, rpl10, mttB dan ccmB mempamerkan orientasi yang berbeza dalam spesies Rafflesia yang tertentu manakala analisis penjajaran jujukan berganda menunjukkan jujukan gen nad1 adalah berbeza antara keempat-empat spesies Rafflesia yang dikaji. Analisis filogenetik dengan menggunakan jujukan bagi tujuh gen pengekodan protein yang terpelihara berupaya membezakan spesies Rafflesia yang dikaji. Kesimpulannya, hasil pencirian jujukan mDNA menunjukkan bahawa jujukan gen mitokondria yang khusus berupaya membezakan spesies Rafflesia yang dikaji dan berpotensi untuk digunakan bagi tujuan pengenalpastian serta pengelasan spesies Rafflesia dalam usaha pemuliharaan organisma yang unik ini

p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis

Maintenance of telomere length and function is critical for the efficient proliferation of eukaryotic cells. Here, we examine the interactions between telomere dysfunction and p53 in cells and organs of telomerase-deficient mice. Coincident with severe telomere shortening and associated genomic instability, p53 is activated, leading to growth arrest and/or apoptosis. Deletion of p53 significantly attenuated the adverse cellular and organismal effects of telomere dysfunction, but only during the earliest stages of genetic crisis. Correspondingly, the loss of telomere function and p53 deficiency cooperated to initiate the transformation process. Together, these studies establish a key role for p53 in the cellular response to telomere dysfunction in both normal and neoplastic cells, question the significance of crisis as a tumor suppressor mechanism, and identify a biologically relevant stage of advanced crisis, termed genetic catastrophe

Nonlinear optical diode effect in a magnetic Weyl semimetal

Weyl semimetals have emerged as a promising quantum material system to discover novel electrical and optical phenomena, due to their combination of nontrivial quantum geometry and strong symmetry breaking. One crucial class of such novel transport phenomena is the diode effect, which is of great interest for both fundamental physics and modern technologies. In the electrical regime, giant electrical diode effect (the nonreciprocal transport) has been observed in Weyl systems. In the optical regime, novel optical diode effects have been theoretically considered but never probed experimentally. Here, we report the observation of the nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetic state of CeAlSi introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). By physically reversing the beam path, we show that the measured SHG intensity can change by at least a factor of six between forward and backward propagation over a wide bandwidth exceeding 250 meV. Supported by density-functional theory calculations, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of the extreme bandwidth. Intriguingly, the NODE directionality is directly controlled by the direction of magnetization. By utilizing the electronically conductive semimetallic nature of CeAlSi, we demonstrate current-induced magnetization switching and thus electrical control of the NODE in a mesoscopic spintronic device structure with current densities as small as 5 kA/cm$^2$. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials. The NODE also provides a way to measure the phase of nonlinear optical susceptibilities and further opens new pathways for the unidirectional manipulation of light such as electrically controlled optical isolators.Comment: 28 pages, 12 figure

Quantum metric nonlinear Hall effect in a topological antiferromagnetic heterostructure

Quantum geometry - the geometry of electron Bloch wavefunctions - is central to modern condensed matter physics. Due to the quantum nature, quantum geometry has two parts, the real part quantum metric and the imaginary part Berry curvature. The studies of Berry curvature have led to countless breakthroughs, ranging from the quantum Hall effect in 2DEGs to the anomalous Hall effect (AHE) in ferromagnets. However, in contrast to Berry curvature, the quantum metric has rarely been explored. Here, we report a new nonlinear Hall effect induced by quantum metric by interfacing even-layered MnBi2Te4 (a PT-symmetric antiferromagnet (AFM)) with black phosphorus. This novel nonlinear Hall effect switches direction upon reversing the AFM spins and exhibits distinct scaling that suggests a non-dissipative nature. Like the AHE brought Berry curvature under the spotlight, our results open the door to discovering quantum metric responses. Moreover, we demonstrate that the AFM can harvest wireless electromagnetic energy via the new nonlinear Hall effect, therefore enabling intriguing applications that bridges nonlinear electronics with AFM spintronics.Comment: 19 pages, 4 figures and a Supplementary Materials with 66 pages, 4 figures and 3 tables. Originally submitted to Science on Oct. 5, 202

Genetic Variants For Head Size Share Genes and Pathways With Cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer

How Can We Improve Oncofertility Care for Patients? A Systematic Scoping Review of Current International Practice and Models of Care

© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. BACKGROUND: Fertility preservation (FP) is an important quality of life issue for cancer survivors of reproductive age. Despite the existence of broad international guidelines, the delivery of oncofertility care, particularly amongst paediatric, adolescent and young adult patients, remains a challenge for healthcare professionals (HCPs). The quality of oncofertility care is variable and the uptake and utilization of FP remains low. Available guidelines fall short in providing adequate detail on how oncofertility models of care (MOC) allow for the real-world application of guidelines by HCPs. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the literature on the components of oncofertility care as defined by patient and clinician representatives, and identify the barriers, facilitators and challenges, so as to improve the implementation of oncofertility services. SEARCH METHODS: A systematic scoping review was conducted on oncofertility MOC literature published in English between 2007 and 2016, relating to 10 domains of care identified through consumer research: communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, training, supportive care during treatment, reproductive care after cancer treatment, psychosocial support and ethical practice of oncofertility care. A wide range of electronic databases (CINAHL, Embase, PsycINFO, PubMed, AEIPT, Education Research Complete, ProQuest and VOCED) were searched in order to synthesize the evidence around delivery of oncofertility care. Related citations and reference lists were searched. The review was undertaken following registration (International prospective register of systematic reviews (PROSPERO) registration number CRD42017055837) and guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). OUTCOMES: A total of 846 potentially relevant studies were identified after the removal of duplicates. All titles and abstracts were screened by a single reviewer and the final 147 papers were screened by two reviewers. Ten papers on established MOC were identified amongst the included papers. Data were extracted from each paper and quality scores were then summarized in the oncofertility MOC summary matrix. The results identified a number of themes for improving MOC in each domain, which included: the importance of patients receiving communication that is of a higher quality and in different formats on their fertility risk and FP options; improving provision of oncofertility care in a timely manner; improving access to age-appropriate care; defining the role and scope of practice of all HCPs; and improving communication between different HCPs. Different forms of decision aids were found useful for assisting patients to understand FP options and weigh up choices. WIDER IMPLICATIONS: This analysis identifies core components for delivery of oncofertility MOC. The provision of oncofertility services requires planning to ensure services have safe and reliable referral pathways and that they are age-appropriate and include medical and psychological oncofertility care into the survivorship period. In order for this to happen, collaboration needs to occur between clinicians, allied HCPs and executives within paediatric and adult hospitals, as well as fertility clinics across both public and private services. Training of both cancer and non-cancer HCPs is needed to improve the knowledge of HCPs, the quality of care provided and the confidence of HCPs with these consultations

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder