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Fulltext Cross-Polarization Optical Coherence Tomography for Clinical Evaluation of Dermal Lesion Degrees in Vulvar Lichen Sclerosus

Potapov AL, Loginova MM, Moiseev AA, Radenska-Lopovok SG, Kuznetsov SS, Kuznetsova IA, et al.

Sovrem Tekhnologii Med, 2023;15(1):53-60.
PMID: 37388751 DOI: 10.17691/stm2023.15.1.06

The aim of the study was to identify different degrees of dermal lesions in vulvar lichen sclerosus (VLS) using cross-polarization optical coherence tomography (CP OCT) based on attenuation coefficient to detect disease early manifestations and to monitor the effectiveness of treatment.
MATERIALS AND METHODS: The study included 10 patients without pathology and 39 patients with VLS diagnosed histologically. CP OCT was performed in vivo on the inner surface of the labia minora, in the main lesion area. From each scanning point, a 3.4×3.4×1.25-mm3 3D data array was obtained in 26 s. CP OCT examination results were compared with histological examination of specimens stained with Van Gieson's picrofuchsin.Quantitative analysis of OCT images was performed by measuring the attenuation coefficient in co-polarization and cross-polarization. For visual analysis, color-coded charts were developed based on OCT attenuation coefficients.
RESULTS: According to histological examination, all patients with VLS were divided into 4 groups as per dermal lesion degree: initial (8 patients); mild (7 patients); moderate (9 patients); severe (15 patients). Typical features of different degrees were interfibrillary edema up to 250 μm deep for initial degree, thickened collagen bundles without edema up to 350 μm deep for mild degree, dermis homogenization up to 700 μm deep for moderate degree, dermis homogenization and total edema up to 1200 μm deep for severe degree.Pathological processes in dermis during VLS like interfibrillary edema and collagen bundles homogenization were visualized using CP OCT method based on values of attenuation coefficient in co- and cross-polarization channels. However, CP OCT method appeared to be less sensitive to changes of collagen bundles thickness not allowing to distinguish thickened collagen bundles from normal ones with enough statistical significance. The CP OCT method was able to differentiate all degrees of dermal lesions among themselves. OCT attenuation coefficients differed from normal condition with statistical significance for all degrees of lesions, except for mild.
CONCLUSION: For the first time, quantitative parameters for each degrees of dermis lesion in VLS, including initial degree, were determined by CP OCT method allowing to detect the disease at an early stage and to monitor the applied clinical treatment effectiveness.
Influence of oxyhydrogen gas retrofit into two-stroke engine on emissions and exhaust gas temperature variations

Kamarudin R, Ang YZ, Topare NS, Ismail MN, Mustafa KF, Gunnasegaran P, et al.

Heliyon, 2024 Mar 15;10(5):e26597.
PMID: 38434285 DOI: 10.1016/j.heliyon.2024.e26597

The generation of power and fuel sustainability that contributes to a cleaner output of exhaust gases is one of the most important objectives the world seeks. In this paper, oxyhydrogen gas is used to retrofit into a two-stroke engine. The water was electrolysed and generated a mixture of oxygen (O2) and hydrogen (H2) or known as oxyhydrogen (HHO) gas via an electrolytic dry cell generator. The HHO was retrofitted experimentally to investigate the engine emissions and exhaust gas temperature from a 1.5 kW gasoline engine. The engine was tested with different power ratings (84-720 W) to investigate the performance and emissions of the engine using gasoline followed by the addition of HHO. The emissions of CO and NOx were measured with different amounts of HHO added. The exhaust temperature was calculated as one of the variables to be considered in relation to pollution. The air-fuel ratios are varied from 12 to 20% in the experiment. The most appropriate air-fuel ratio needed to start the generator with the most environmentally friendly gas emission was analysed. The results showed that the addition of HHO to the engine is successful in reducing fuel consumption up to 8.9%. A higher percentage of HHO added also has improved the emissions and reduced exhaust gas temperature. In this study, the highest quantity of HHO added at 0.15% of the volume fraction reduced CO gas emission by up to 9.41%, NOx gas up to 4.31%, and exhaust gas temperature by up to 2.02%. Generally, adding oxyhydrogen gas has significantly reduced the emissions, and exhaust temperature and provided an eco-friendly environment.
Role of Platelet Activating Factor as a Mediator of Inflammatory Diseases and Preterm Delivery

Wahid HH, Anahar FN, Isahak NH, Mohd Zoharodzi J, Mohammad Khoiri SNL, Mohamad Zainal NH, et al.

Am J Pathol, 2024 Jun;194(6):862-878.
PMID: 38403163 DOI: 10.1016/j.ajpath.2024.01.018

Nearly 70% of preterm deliveries occur spontaneously, and the clinical pathways involved include preterm labor and preterm premature rupture of membranes. Prediction of preterm delivery is considered crucial due to the significant effects of preterm birth on health and the economy at both the personal and community levels. Although similar inflammatory processes occur in both term and preterm delivery, the premature activation of these processes or exaggerated inflammatory response triggered by infection or sterile factors leads to preterm delivery. Platelet activating factor (PAF) is a phosphoglycerylether lipid mediator of inflammation that is implicated in infections, cancers, and various chronic diseases and disorders including cardiovascular, renal, cerebrovascular, and central nervous system diseases. In gestational tissues, PAF mediates the inflammatory pathways that stimulate the effector mechanisms of labor, including myometrial contraction, cervical dilation, and fetal membrane rupture. Women with preterm labor and preterm premature rupture of membranes have increased levels of PAF in their amniotic fluid. In mice, the intrauterine or intraperitoneal administration of carbamyl PAF activates inflammation in gestational tissues, thereby eliciting preterm delivery. This review summarizes recent research on PAF as an important inflammatory mediator in preterm delivery and in other inflammatory disorders, highlighting its potential value for prediction, intervention, and prevention of these diseases.
Targeting notch-related lncRNAs in cancer: Insights into molecular regulation and therapeutic potential

Siddique R, Gupta G, Mgm J, Kumar A, Kaur H, Ariffin IA, et al.

Pathol Res Pract, 2024 May;257:155282.
PMID: 38608371 DOI: 10.1016/j.prp.2024.155282

Cancer is a group of diseases marked by unchecked cell proliferation and the ability for the disease to metastasize to different body areas. Enhancements in treatment and early detection are crucial for improved outcomes. LncRNAs are RNA molecules that encode proteins and have a length of more than 200 nucleotides. LncRNAs are crucial for chromatin architecture, gene regulation, and other cellular activities that impact both normal growth & pathological processes, even though they are unable to code for proteins. LncRNAs have emerged as significant regulators in the study of cancer biology, with a focus on their intricate function in the Notch signaling pathway. The imbalance of this pathway is often linked to a variety of malignancies. Notch signaling is essential for cellular functions like proliferation, differentiation, and death. The cellular response is shaped by these lncRNAs through their modulation of essential Notch pathway constituents such as receptors, ligands, and downstream effectors around it. Furthermore, a variety of cancer types exhibit irregular expression of Notch-related lncRNAs, underscoring their potential use as therapeutic targets and diagnostic markers. Gaining an understanding of the molecular processes behind the interaction between the Notch pathway and lncRNAs will help you better understand the intricate regulatory networks that control the development of cancer. This can open up new possibilities for individualized treatment plans and focused therapeutic interventions. The intricate relationships between lncRNAs & the Notch pathway in cancer are examined in this review.
Personalised management of Chronic Obstructive Pulmonary Disease (COPD): Malaysian consensus algorithm for appropriate use of inhaled corticosteroid (ICS) in COPD patients

Marzuki NM, Jaeb MZM, Ban A, Ismail AI, Ali IAH, Razali NM, et al.

Med J Malaysia, 2020 11;75(6):717-721.
PMID: 33219183

BACKGROUND: Regarding the long-term safety issues with the use of inhaled corticosteroids (ICS) and the clinical predominance of dual bronchodilators in enhancing treatment outcomes in chronic obstructive pulmonary disease (COPD), ICS is no longer a "preferred therapy" according to the Global Initiative for Chronic Obstructive Lung Disease except on top of a dual bronchodilator. This has necessitated a change in the current therapy for many COPD patients.
OBJECTIVE: To determine a standardised algorithm to reassess and personalise the treatment COPD patients based on the available evidence.
METHODS: A consensus statement was agreed upon by a panel of pulmonologists in from 11 institutes in Malaysia whose members formed this consensus group.
RESULTS: According to the consensus, which was unanimously adopted, all COPD patients who are currently receiving an ICS-based treatment should be reassessed based on the presence of co-existence of asthma or high eosinophil counts and frequency of moderate or severe exacerbations in the previous 12 months. When that the patients meet any of the aforementioned criteria, then the patient can continue taking ICS-based therapy. However, if the patients do not meet the criteria, then the treatment of patients need to be personalised based on whether the patient is currently receiving long-acting beta-agonists (LABA)/ICS or triple therapy.
CONCLUSION: A flowchart of the consensus providing a guidance to Malaysian clinicians was elucidated based on evidences and international guidelines that identifies the right patients who should receive inhaled corticosteroids and enable to switch non ICS based therapies in patients less likely to benefit from such treatments.
Recent Advances and Future Perspectives of Metal-Based Electrocatalysts for Overall Electrochemical Water Splitting

Hayat A, Sohail M, Ali H, Taha TA, Qazi HIA, Ur Rahman N, et al.

Chem Rec, 2022 Nov 21.
PMID: 36408911 DOI: 10.1002/tcr.202200149

Recently, the growing demand for a renewable and sustainable fuel alternative is contingent on fuel cell technologies. Even though it is regarded as an environmentally sustainable method of generating fuel for immediate concerns, it must be enhanced to make it extraordinarily affordable, and environmentally sustainable. Hydrogen (H2 ) synthesis by electrochemical water splitting (ECWS) is considered one of the foremost potential prospective methods for renewable energy output and H2 society implementation. Existing massive H2 output is mostly reliant on the steaming reformation of carbon fuels that yield CO2 together with H2 and is a finite resource. ECWS is a viable, efficient, and contamination-free method for H2 evolution. Consequently, developing reliable and cost-effective technology for ECWS was a top priority for scientists around the globe. Utilizing renewable technologies to decrease total fuel utilization is crucial for H2 evolution. Capturing and transforming the fuel from the ambient through various renewable solutions for water splitting (WS) could effectively reduce the need for additional electricity. ECWS is among the foremost potential prospective methods for renewable energy output and the achievement of a H2 -based economy. For the overall water splitting (OWS), several transition-metal-based polyfunctional metal catalysts for both cathode and anode have been synthesized. Furthermore, the essential to the widespread adoption of such technology is the development of reduced-price, super functional electrocatalysts to substitute those, depending on metals. Many metal-premised electrocatalysts for both the anode and cathode have been designed for the WS process. The attributes of H2 and oxygen (O2 ) dynamics interactions on the electrodes of water electrolysis cells and the fundamental techniques for evaluating the achievement of electrocatalysts are outlined in this paper. Special emphasis is paid to their fabrication, electrocatalytic performance, durability, and measures for enhancing their efficiency. In addition, prospective ideas on metal-based WS electrocatalysts based on existing problems are presented. It is anticipated that this review will offer a straight direction toward the engineering and construction of novel polyfunctional electrocatalysts encompassing superior efficiency in a suitable WS technique.
Discovery of oxindole-based FLT3 inhibitors as a promising therapeutic lead for acute myeloid leukemia carrying the oncogenic ITD mutation

Bender O, Shoman ME, Ali TFS, Dogan R, Celik I, Mollica A, et al.

Arch Pharm (Weinheim), 2023 Feb;356(2):e2200407.
PMID: 36403191 DOI: 10.1002/ardp.202200407

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC50 of 4.3 µM at 72 h while it was 8.7 µM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-β. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC50 values of 2.49 and 1.45 µM, respectively. Theoretical docking studies supported the compounds' ability to bind to the FLT3 ATP binding site with the formation of highly stable complexes as evidenced by molecular dynamics simulations. The designed compounds also provide suitable drug candidates with no violation of drug likeability rules.
A Targeted Review of Current Progress, Challenges and Future Perspective of g-C3 N4 based Hybrid Photocatalyst Toward Multidimensional Applications

Hayat A, Sohail M, Anwar U, Taha TA, Qazi HIA, Amina, et al.

Chem Rec, 2023 Jan;23(1):e202200143.
PMID: 36285706 DOI: 10.1002/tcr.202200143

The increasing demand for searching highly efficient and robust technologies in the context of sustainable energy production totally rely onto the cost-effective energy efficient production technologies. Solar power technology in this regard will perceived to be extensively employed in a variety of ways in the future ahead, in terms of the combustion of petroleum-based pollutants, CO2 reduction, heterogeneous photocatalysis, as well as the formation of unlimited and sustainable hydrogen gas production. Semiconductor-based photocatalysis is regarded as potentially sustainable solution in this context. g-C3 N4 is classified as non-metallic semiconductor to overcome this energy demand and enviromental challenges, because of its superior electronic configuration, which has a median band energy of around 2.7 eV, strong photocatalytic stability, and higher light performance. The photocatalytic performance of g-C3 N4 is perceived to be inadequate, owing to its small surface area along with high rate of charge recombination. However, various synthetic strategies were applied in order to incorporate g-C3 N4 with different guest materials to increase photocatalytic performance. After these fabrication approaches, the photocatalytic activity was enhanced owing to generation of photoinduced electrons and holes, by improving light absorption ability, and boosting surface area, which provides more space for photocatalytic reaction. In this review, various metals, non-metals, metals oxide, sulfides, and ferrites have been integrated with g-C3 N4 to form mono, bimetallic, heterojunction, Z-scheme, and S-scheme-based materials for boosting performance. Also, different varieties of g-C3 N4 were utilized for different aspects of photocatalytic application i. e., water reduction, water oxidation, CO2 reduction, and photodegradation of dye pollutants, etc. As a consequence, we have assembled a summary of the latest g-C3 N4 based materials, their uses in solar energy adaption, and proper management of the environment. This research will further well explain the detail of the mechanism of all these photocatalytic processes for the next steps, as well as the age number of new insights in order to overcome the current challenges.
Exploring the properties of Dy2O3-Y2O3 Co-activated telluro-borate glass: Structural, physical, optical, thermal, and mechanical properties

Thabit HA, Ismail AK, Mhareb MHA, Abdulmalik DA, I A, Al-Fakih AM, et al.

Heliyon, 2023 Jul;9(7):e18309.
PMID: 37539187 DOI: 10.1016/j.heliyon.2023.e18309

The successful application of glass-based materials in a wide range of scientific fields depends on the associated physical, optical, thermal, and mechanical properties. This article investigate the structural, Physical, thermal, optical, and mechanical properties of Dy2O3, Y2O3 co-activated telluro-borate glass developed using the melt-quenching method. The glassy quality and the elements component of the specimens were observed using XRD and EDX analyses. The addition of Y2O3 rise the glass density from 2.956 to 3.303 g/cm3 the refractive index from 2.5 to 2.7. These changes are due to the increase in polarizability and non-bridging oxygen (NBO). The photoluminescence (PL) spectra revealed a broad peak at 550 nm and additional weak emission peaks at 573 and 664 nm, respectively. While the observed broader peak can be linked to the convolution of Bi3+ ions transitions corresponding to the non-centrosymmetric site respectively, the weak emission bands are due to 4F9/2 → 6H13/2 and 4F9/2 → 6H11/2 Dy3+ transitions. Hence, the low symmetrical features of both Bi3+ and Dy3+ ions were confirmed. The increase in the Vickers hardness of the glass from 536.7 to 1366.9 indicates the influence of Y2O3 addition on the mechanical properties of the glasses. The findings help to improve our understanding of the behaviour of the glass composition and its prospective applications in disciplines such as photonic, and laser optics.
Fulltext Permeability and Antifouling Augmentation of a Hybrid PVDF-PEG Membrane Using Nano-Magnesium Oxide as a Powerful Mediator for POME Decolorization

Abdulsalam M, Che Man H, Goh PS, Yunos KF, Zainal Abidin Z, Isma M I A, et al.

Polymers (Basel), 2020 Mar 03;12(3).
PMID: 32138186 DOI: 10.3390/polym12030549

This study focused on developing a hydrophilic hybrid polyvinylidene fluoride (PVDF)-polyethylene glycol (PEG) hollow membrane by incorporating Nano-magnesium oxide (NMO) as a potent antifouling mediator. The Nano-hybrid hollow fibers with varied loading of NMO (0 g; 0.25 g; 0.50 g; 0.75 g and 1.25 g) were spun through phase inversion technique. The resultants Nano-hybrid fibers were characterized and compared based on SEM, EDX, contact angle, surface zeta-potential, permeability flux, fouling resistance and color rejection from palm oil mill effluent (POME). Noticeably, the permeability flux, fouling resistance and color rejection improved with the increase in NMO loading. PVDF-PEG with 0.50 g-NMO loading displayed an outstanding performance with 198.35 L/m2·h, 61.33 L/m2·h and 74.65% of water flux, POME flux and color rejection from POME, respectively. More so, a remarkable fouling resistance were obtained such that the flux recovery, reversible fouling percentage and irreversible fouling percentage remains relatively steady at 90.98%, 61.39% and 7.68%, respectively, even after 3 cycles of continuous filtrations for a total period of 9 h. However, at excess loading of 0.75 and 1.25 g-NMO, deterioration in the flux and fouling resistance was observed. This was due to the agglomeration of nanoparticles within the matrix structure at the excessive loading.
Fulltext Spatial scale changes the relationship between beta diversity, species richness and latitude

Sreekar R, Katabuchi M, Nakamura A, Corlett RT, Slik JWF, Fletcher C, et al.

R Soc Open Sci, 2018 Sep;5(9):181168.
PMID: 30839691 DOI: 10.1098/rsos.181168

The relationship between β-diversity and latitude still remains to be a core question in ecology because of the lack of consensus between studies. One hypothesis for the lack of consensus between studies is that spatial scale changes the relationship between latitude and β-diversity. Here, we test this hypothesis using tree data from 15 large-scale forest plots (greater than or equal to 15 ha, diameter at breast height ≥ 1 cm) across a latitudinal gradient (3-30o) in the Asia-Pacific region. We found that the observed β-diversity decreased with increasing latitude when sampling local tree communities at small spatial scale (grain size ≤0.1 ha), but the observed β-diversity did not change with latitude when sampling at large spatial scales (greater than or equal to 0.25 ha). Differences in latitudinal β-diversity gradients across spatial scales were caused by pooled species richness (γ-diversity), which influenced observed β-diversity values at small spatial scales, but not at large spatial scales. Therefore, spatial scale changes the relationship between β-diversity, γ-diversity and latitude, and improving sample representativeness avoids the γ-dependence of β-diversity.
Fulltext Two decades of neuroscience publication trends in Africa

Maina MB, Ahmad U, Ibrahim HA, Hamidu SK, Nasr FE, Salihu AT, et al.

Nat Commun, 2021 Jun 08;12(1):3429.
PMID: 34103514 DOI: 10.1038/s41467-021-23784-8

Neuroscience research in Africa remains sparse. Devising new policies to boost Africa's neuroscience landscape is imperative, but these must be based on accurate data on research outputs which is largely lacking. Such data must reflect the heterogeneity of research environments across the continent's 54 countries. Here, we analyse neuroscience publications affiliated with African institutions between 1996 and 2017. Of 12,326 PubMed indexed publications, 5,219 show clear evidence that the work was performed in Africa and led by African-based researchers - on average ~5 per country and year. From here, we extract information on journals and citations, funding, international coauthorships and techniques used. For reference, we also extract the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our dataset provides insights into the current state of African neuroscience research in a global context.
Fulltext Complete genome and proteome of Acholeplasma laidlawii

Lazarev VN, Levitskii SA, Basovskii YI, Chukin MM, Akopian TA, Vereshchagin VV, et al.

J Bacteriol, 2011 Sep;193(18):4943-53.
PMID: 21784942 DOI: 10.1128/JB.05059-11

We present the complete genome sequence and proteogenomic map for Acholeplasma laidlawii PG-8A (class Mollicutes, order Acholeplasmatales, family Acholeplasmataceae). The genome of A. laidlawii is represented by a single 1,496,992-bp circular chromosome with an average G+C content of 31 mol%. This is the longest genome among the Mollicutes with a known nucleotide sequence. It contains genes of polymerase type I, SOS response, and signal transduction systems, as well as RNA regulatory elements, riboswitches, and T boxes. This demonstrates a significant capability for the regulation of gene expression and mutagenic response to stress. Acholeplasma laidlawii and phytoplasmas are the only Mollicutes known to use the universal genetic code, in which UGA is a stop codon. Within the Mollicutes group, only the sterol-nonrequiring Acholeplasma has the capacity to synthesize saturated fatty acids de novo. Proteomic data were used in the primary annotation of the genome, validating expression of many predicted proteins. We also detected posttranslational modifications of A. laidlawii proteins: phosphorylation and acylation. Seventy-four candidate phosphorylated proteins were found: 16 candidates are proteins unique to A. laidlawii, and 11 of them are surface-anchored or integral membrane proteins, which implies the presence of active signaling pathways. Among 20 acylated proteins, 14 contained palmitic chains, and six contained stearic chains. No residue of linoleic or oleic acid was observed. Acylated proteins were components of mainly sugar and inorganic ion transport systems and were surface-anchored proteins with unknown functions.
The interspecific growth-mortality trade-off is not a general framework for tropical forest community structure

Russo SE, McMahon SM, Detto M, Ledder G, Wright SJ, Condit RS, et al.

Nat Ecol Evol, 2021 Feb;5(2):174-183.
PMID: 33199870 DOI: 10.1038/s41559-020-01340-9

Resource allocation within trees is a zero-sum game. Unavoidable trade-offs dictate that allocation to growth-promoting functions curtails other functions, generating a gradient of investment in growth versus survival along which tree species align, known as the interspecific growth-mortality trade-off. This paradigm is widely accepted but not well established. Using demographic data for 1,111 tree species across ten tropical forests, we tested the generality of the growth-mortality trade-off and evaluated its underlying drivers using two species-specific parameters describing resource allocation strategies: tolerance of resource limitation and responsiveness of allocation to resource access. Globally, a canonical growth-mortality trade-off emerged, but the trade-off was strongly observed only in less disturbance-prone forests, which contained diverse resource allocation strategies. Only half of disturbance-prone forests, which lacked tolerant species, exhibited the trade-off. Supported by a theoretical model, our findings raise questions about whether the growth-mortality trade-off is a universally applicable organizing framework for understanding tropical forest community structure.
Temporal population variability in local forest communities has mixed effects on tree species richness across a latitudinal gradient

Fung T, Chisholm RA, Anderson-Teixeira K, Bourg N, Brockelman WY, Bunyavejchewin S, et al.

Ecol Lett, 2020 Jan;23(1):160-171.
PMID: 31698546 DOI: 10.1111/ele.13412

Among the local processes that determine species diversity in ecological communities, fluctuation-dependent mechanisms that are mediated by temporal variability in the abundances of species populations have received significant attention. Higher temporal variability in the abundances of species populations can increase the strength of temporal niche partitioning but can also increase the risk of species extinctions, such that the net effect on species coexistence is not clear. We quantified this temporal population variability for tree species in 21 large forest plots and found much greater variability for higher latitude plots with fewer tree species. A fitted mechanistic model showed that among the forest plots, the net effect of temporal population variability on tree species coexistence was usually negative, but sometimes positive or negligible. Therefore, our results suggest that temporal variability in the abundances of species populations has no clear negative or positive contribution to the latitudinal gradient in tree species richness.
Assessing the spatial scale of synchrony in forest tree population dynamics

Chisholm RA, Fung T, Anderson-Teixeira KJ, Bourg NA, Brockelman WY, Bunyavejchewin S, et al.

Proc Biol Sci, 2024 Nov;291(2035):20240486.
PMID: 39564678 DOI: 10.1098/rspb.2024.0486

Populations of forest trees exhibit large temporal fluctuations, but little is known about the synchrony of these fluctuations across space, including their sign, magnitude, causes and characteristic scales. These have important implications for metapopulation persistence and theoretical community ecology. Using data from permanent forest plots spanning local, regional and global spatial scales, we measured spatial synchrony in tree population growth rates over sub-decadal and decadal timescales and explored the relationship of synchrony to geographical distance. Synchrony was high at local scales of less than 1 km, with estimated Pearson correlations of approximately 0.6-0.8 between species' population growth rates across pairs of quadrats. Synchrony decayed by approximately 17-44% with each order of magnitude increase in distance but was still detectably positive at distances of 100 km and beyond. Dispersal cannot explain observed large-scale synchrony because typical seed dispersal distances (<100 m) are far too short to couple the dynamics of distant forests on decadal timescales. We attribute the observed synchrony in forest dynamics primarily to the effect of spatially synchronous environmental drivers (the Moran effect), in particular climate, although pests, pathogens and anthropogenic drivers may play a role for some species.
Fulltext rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk

Liu J, Lončar I, Collée JM, Bolla MK, Dennis J, Michailidou K, et al.

Sci Rep, 2016 Nov 15;6:36874.
PMID: 27845421 DOI: 10.1038/srep36874

NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.
Fulltext Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women

Breast Cancer Association Consortium, Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, et al.

N Engl J Med, 2021 02 04;384(5):428-439.
PMID: 33471991 DOI: 10.1056/NEJMoa1913948

BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.
METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.
RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.
CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).
Fulltext Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

Dunning AM, Michailidou K, Kuchenbaecker KB, Thompson D, French JD, Beesley J, et al.

Nat Genet, 2016 Apr;48(4):374-86.
PMID: 26928228 DOI: 10.1038/ng.3521

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.
Fulltext Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindström S, et al.

Nat Genet, 2017 Dec;49(12):1767-1778.
PMID: 29058716 DOI: 10.1038/ng.3785

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

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