CTC1‐STN1 coordinates G‐ and C‐strand synthesis to regulate telomere length

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145241/1/acel12783.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145241/2/acel12783_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145241/3/acel12783-sup-0001-FigS1-S4.pd

Association and interactions between mixed exposure to trace elements and the prevalence of kidney stones: a study of NHANES 2017–2018

BackgroundThe association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between elements are unclear. The aim of this study was to explore the association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between the elements.MethodsA total of 1,244 participants (139 kidney stone formers and 1,105 non-stone former participants) in NHANES 2017–2018 were included. The exposure to trace elements was evaluated by measuring their concentration in urine samples. Three methods, Logistic regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR), were used for analysis.ResultsAccording to the results from qgcomp and BKMR, a negative association was found between exposure to the 13 trace elements and the prevalence of kidney stones [OR = 0.50 (0.32, 0.78)]. Subgroup analysis revealed that Co, As, and iodine in the whole population, Co, As, and Ni in males, and Cs, iodine, and Sb in females, were most strongly associated with kidney stones. Kidney stone was found to be positively correlated with Co and negatively correlated with the other elements. Besides, there were significant interactions between Ni and Pb in the whole population, Co and iodine in males, and Pb and iodine in females.ConclusionThere was a negative association between exposure to the mixture of 13 trace elements and the prevalence of kidney stones

Pathogenesis and therapeutic implications of EBV-associated epithelial cancers

Epstein-Barr virus (EBV), one of the most common human viruses, has been associated with both lymphoid and epithelial cancers. Undifferentiated nasopharyngeal carcinoma (NPC), EBV associated gastric cancer (EBVaGC) and lymphoepithelioma-like carcinoma (LELC) are amongst the few common epithelial cancers that EBV has been associated with. The pathogenesis of EBV-associated NPC has been well described, however, the same cannot be said for primary pulmonary LELC (PPLELC) owing to the rarity of the cancer. In this review, we outline the pathogenesis of EBV-associated NPC and EBVaGCs and their recent advances. By drawing on similarities between NPC and PPLELC, we then also postulated the pathogenesis of PPLELC. A deeper understanding about the pathogenesis of EBV enables us to postulate the pathogenesis of other EBV associated cancers such as PPLELC

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family

Improvement of a highly sensitive and specific whole-cell biosensor by adding a positive feedback amplifier

In this study, we designed a Cd2+ whole-cell biosensor with both positive and negative feedback cascade amplifiers in Pseudomonas putida KT2440 (LTCM) based on our previous design with only a negative feedback amplifier (TCM). The results showed that the newly developed biosensor LTCM was greatly improved compared to TCM. Firstly, the linear response range of LTCM was expanded while the maximum linear response range was raised from 0.05 to 0.1 μM. Meanwhile, adding a positive feedback amplifier further increased the fluorescence output signal of LTCM 1.11–2.64 times under the same culture conditions. Moreover, the response time of LTCM for detection of practical samples was reduced from 6 to 4 h. At the same time, LTCM still retained very high sensitivity and specificity, while its lowest detection limit was 0.1 nM Cd2+ and the specificity was 23.29 (compared to 0.1 nM and 17.55 in TCM, respectively). In summary, the positive and negative feedback cascade amplifiers effectively improved the performance of the biosensor LTCM, resulting in a greater linear response range, higher output signal intensity, and shorter response time than TCM while retaining comparable sensitivity and specificity, indicating better potential for practical applications

Regulation of Replication Stress in Alternative Lengthening of Telomeres by Fanconi Anaemia Protein

Fanconi anaemia (FA)-related proteins function in interstrand crosslink (ICL) repair pathways and multiple damage repair pathways. Recent studies have found that FA proteins are involved in the regulation of replication stress (RS) in alternative lengthening of telomeres (ALT). Since ALT cells often exhibit high-frequency ATRX mutations and high levels of telomeric secondary structure, high levels of DNA damage and replicative stress exist in ALT cells. Persistent replication stress is required to maintain the activity of ALT mechanistically, while excessive replication stress causes ALT cell death. FA proteins such as FANCD2 and FANCM are involved in the regulation of this balance by resolving or inhibiting the formation of telomere secondary structures to stabilize stalled replication forks and promote break-induced repair (BIR) to maintain the survival of ALT tumour cells. Therefore, we review the role of FA proteins in replication stress in ALT cells, providing a rationale and direction for the targeted treatment of ALT tumours

The Gain of Function of p53 Mutant p53S in Promoting Tumorigenesis by Cross-talking with H-RasV12

The loss of wild type p53 tumor suppressive function and oncogenic gain-of-function of p53 mutants have been showing important implications in tumorigenesis. The p53N236S (p53N239S in human, p53S) mutation has been shown to lose wild type p53 function by yeast assay. However, its gain of function is still not clear. By gel shift assay, we showed that mutant p53S had lost its DNA binding ability to its target promoters. Further real-time PCR data confirmed that p53S had lost the function of regulating the transcription of p21 Cip1/Waf1, cyclin G, PUMA, and Bax in response to 10Gy irradiation. These data confirmed the loss of function of p53S in mammalian cells. By xenograft assay, we showed that the p53S per se was not oncogenic enough to form tumor, however, cooperating with H-RasV12, p53S could dramatically promote tumorigenesis in p53 null MEFs. Further study showed that co-expression of p53S and H-RasV12 could increase the expression level of H-RasV12 and partially eliminate the elevation of stress response proteins such as Chk2, &#947;-H2AX, Hsp70, Rb, p16Ink4a caused by either p53S or H-RasV12. These data suggested that p53S cross-talked with H-RasV12 and reduced the cellular stress response to oncogenic signals, which facilitated the cell growth and tumorigenesis. Together these data provided the molecular basis for the cooperation of p53S and H-RasV12 and revealed the gain of function of p53S in cross-talking with H-RasV12. This study revealed an important aspect of gain of function for p53 mutant, therefore might shed light on the clinical strategy in targeting p53 mutant.</p

Evolution of spatial network structure for land-use carbon emissions and carbon balance zoning in Jiangxi Province: A social network analysis perspective

Exploring the spatial network structure of land-use carbon emissions (LUCE) and the carbon balance in developing regions is pivotal for climate change mitigation in these areas. Using socio-economic and land-use data from 2000 to 2020, this study focused on Jiangxi Province as a representative case to elucidate the spatial network structure of LUCE and conduct carbon balance zoning. The primary findings were as follows: (1) The LUCE distribution in Jiangxi Province demonstrated a spatial pattern with high values in the northwest and low values in the southeast. An increasing trend was observed in the total amount of LUCE. Furthermore, there were evident regional differences in the Ecological Support Coefficient (ESC), indicating a weakening regional carbon sink capacity. (2) The spatial network structure of LUCE was intricate but stable. Although the gravitational interactions of LUCE between cities have intensified, overall network connectivity remained moderately correlated, indicating a prominent regional development imbalance. (3) There was a pronounced “core-periphery” structure in the LUCE spatial correlation network. Northern Jiangxi was the “core” of the network, taking an “initiator” role, whereas most cities in southern Jiangxi played a “passive” role, and resided at the “periphery” of the network. The inter-regional LUCE network exhibited pronounced spatial spillover, with inter-block correlations surpassing those within blocks. (4) By leveraging empirical data and spatial metrics, we categorized Jiangxi Province into five distinct carbon balance zoning types and subsequently proposed land-use optimization strategies. From the perspective of social network analysis (SNA), this study offers methodological insights into low-carbon development and synergistic emission reduction in developing regions