The spread of modern humans across the globe has led to genetic adaptations to diverse local environments. Recent developments in genomic technologies, statistical analyses, and expanded sampled ...populations have led to improved identification and fine-mapping of genetic variants associated with adaptations to regional living conditions and dietary practices. Ongoing efforts in sequencing genomes of indigenous populations, accompanied by the growing availability of "-omics" and ancient DNA data, promises a new era in our understanding of recent human evolution and the origins of variable traits and disease risks.
Structural variants (SVs) play a crucial role in gene regulation, trait association, and disease in humans. SV genotyping has been extensively applied in genomics research and clinical diagnosis. ...Although a growing number of SV genotyping methods for long reads have been developed, a comprehensive performance assessment of these methods has yet to be done.
Based on one simulated and three real SV datasets, we performed an in-depth evaluation of five SV genotyping methods, including cuteSV, LRcaller, Sniffles, SVJedi, and VaPoR. The results show that for insertions and deletions, cuteSV and LRcaller have similar F1 scores (cuteSV, insertions: 0.69-0.90, deletions: 0.77-0.90 and LRcaller, insertions: 0.67-0.87, deletions: 0.74-0.91) and are superior to other methods. For duplications, inversions, and translocations, LRcaller yields the most accurate genotyping results (0.84, 0.68, and 0.47, respectively). When genotyping SVs located in tandem repeat region or with imprecise breakpoints, cuteSV (insertions and deletions) and LRcaller (duplications, inversions, and translocations) are better than other methods. In addition, we observed a decrease in F1 scores when the SV size increased. Finally, our analyses suggest that the F1 scores of these methods reach the point of diminishing returns at 20× depth of coverage.
We present an in-depth benchmark study of long-read SV genotyping methods. Our results highlight the advantages and disadvantages of each genotyping method, which provide practical guidance for optimal application selection and prospective directions for tool improvement.
Adaptive phenotypic plasticity, the ability of an organism to change its phenotype to match local environments, is increasingly recognized for its contribution to evolution. However, few empirical ...studies have explored the molecular basis of plastic traits. The East African cichlid fish Astatoreochromis alluaudi displays adaptive phenotypic plasticity in its pharyngeal jaw apparatus, a structure that is widely seen as an evolutionary key innovation that has contributed to the remarkable diversity of cichlid fishes. It has previously been shown that in response to different diets, the pharyngeal jaws change their size, shape and dentition: hard diets induce an adaptive robust molariform tooth phenotype with short jaws and strong internal bone structures, while soft diets induce a gracile papilliform tooth phenotype with elongated jaws and slender internal bone structures. To gain insight into the molecular underpinnings of these adaptations and enable future investigations of the role that phenotypic plasticity plays during the formation of adaptive radiations, the transcriptomes of the two divergent jaw phenotypes were examined. Our study identified a total of 187 genes whose expression differs in response to hard and soft diets, including immediate early genes, extracellular matrix genes and inflammatory factors. Transcriptome results are interpreted in light of expression of candidate genes—markers for tooth size and shape, bone cells and mechanically sensitive pathways. This study opens up new avenues of research at new levels of biological organization into the roles of phenotypic plasticity during speciation and radiation of cichlid fishes.
See also the Perspective by Young
Periprosthetic joint infection (PJI) is a severe complication of joint arthroplasty that causes significant pain and economic loss. This study aimed to determine whether the current evidence supports ...single-stage revision for PJI based on reinfection and reoperation rates.
We searched the PubMed, EBSCO, Medline, and Cochrane Library databases from inception to 30 May 2023 to identify studies that compared single-stage revision and two-stage revision for PJI. Data on reinfection and reoperation rates were pooled.
This meta-analysis included a total of 40 studies with 8711 patients. Overall, there was no significant difference between single- and two-stage revision regarding the postoperative reinfection rate and reoperation rate. Subgroup analysis by surgery period and different surgical sites revealed no difference between the two groups in the reinfection and reoperation rates.
Based on the available evidence, our study did not identify a significant difference in reinfection and reoperation rates between single- and two-stage revision for PJI. Given the limitations in inclusion/exclusion criteria and the observed heterogeneity, we acknowledge the complexity of drawing strong conclusions. Therefore, we suggest that the choice between single- and two-stage revision should be carefully considered on an individual basis, taking into account patient-specific factors and further research developments.
Introduction
Ceramide synthases (CERSes) are also known longevity assurance (LASS) genes. CERSes play important roles in the regulation of cancer progression. The CERS family is expressed in a ...variety of human tumours and is involved in tumorigenesis. They are closely associated with the progression of liver, breast, cervical, ovarian, colorectal, head and neck squamous cell, gastric, lung, prostate, oesophageal, pancreatic and blood cancers. CERSes play diverse and important roles in the regulation of cell survival, proliferation, apoptosis, migration, invasion, and drug resistance. The differential expression of CERSes in tumour and nontumour cells and survival analysis of cancer patients suggest that some CERSes could be used as potential prognostic markers. They are also important potential targets for cancer therapy.
Methods
In this review, we summarize the available evidence on the inhibitory or promotive roles of CERSes in the progression of many cancers. Furthermore, we summarize the identified upstream and downstream molecular mechanisms that may regulate the function of CERSes in cancer settings.
Butyrophilin Subfamily 3 Member A3 (BTN3A3) is a type I transmembrane protein belonging to the immunoglobulin (Ig) superfamily, which is expressed in many cancers. Clinical data show that ovarian ...cancer patients with high expression of
BTN3A3
have a longer survival time, but the mechanism of BTN3A3 in the occurrence and progression of ovarian cancer is still unclear. Here, we found that
BTN3A3
knockdown can promote the proliferation, migration and invasion of ovarian cancer cells, while overexpression of
BTN3A3
can inhibit the proliferation, migration and invasion of ovarian cancer cells. We analyzed the immunoprecipitated BTN3A3 complex by mass spectrometry and found that BTN3A3 binds to FGF2, and the overexpression of
BTN3A3
leads to a decrease in the protein level of FGF2, which in turn leads to a decrease in the level of phosphorylation of ERK1/2. By increasing the protein level of FGF2, it was found that the level of ERK1/2 phosphorylation also increased. Finally, the cancer promotion phenomenon caused by
BTN3A3
knockdown can be improved by using ERK1/2 inhibitor SCH772984. To sum up, BTN3A3 interacts with FGF2, which inhibits FGF2/ERK1/2 axis and ultimately inhibits the proliferation, migration and invasion of ovarian cancer cells. Our results suggest that BTN3A3 may be a prognostic marker and a potential therapeutic target for ovarian cancer.
Seahorses have a specialized morphology that includes a toothless tubular mouth, a body covered with bony plates, a male brood pouch, and the absence of caudal and pelvic fins. Here we report the ...sequencing and de novo assembly of the genome of the tiger tail seahorse, Hippocampus comes. Comparative genomic analysis identifies higher protein and nucleotide evolutionary rates in H. comes compared with other teleost fish genomes. We identified an astacin metalloprotease gene family that has undergone expansion and is highly expressed in the male brood pouch. We also find that the H. comes genome lacks enamel matrix protein-coding proline/glutamine-rich secretory calcium-binding phosphoprotein genes, which might have led to the loss of mineralized teeth. tbx4, a regulator of hindlimb development, is also not found in H. comes genome. Knockout of tbx4 in zebrafish showed a 'pelvic fin-loss' phenotype similar to that of seahorses.
Africa is the origin of modern humans within the past 300 thousand years. To infer the complex demographic history of African populations and adaptation to diverse environments, we sequenced the ...genomes of 92 individuals from 44 indigenous African populations.
Genetic structure analyses indicate that among Africans, genetic ancestry is largely partitioned by geography and language, though we observe mixed ancestry in many individuals, consistent with both short- and long-range migration events followed by admixture. Phylogenetic analysis indicates that the San genetic lineage is basal to all modern human lineages. The San and Niger-Congo, Afroasiatic, and Nilo-Saharan lineages were substantially diverged by 160 kya (thousand years ago). In contrast, the San and Central African rainforest hunter-gatherer (CRHG), Hadza hunter-gatherer, and Sandawe hunter-gatherer lineages were diverged by ~ 120-100 kya. Niger-Congo, Nilo-Saharan, and Afroasiatic lineages diverged more recently by ~ 54-16 kya. Eastern and western CRHG lineages diverged by ~ 50-31 kya, and the western CRHG lineages diverged by ~ 18-12 kya. The San and CRHG populations maintained the largest effective population size compared to other populations prior to 60 kya. Further, we observed signatures of positive selection at genes involved in muscle development, bone synthesis, reproduction, immune function, energy metabolism, and cell signaling, which may contribute to local adaptation of African populations.
We observe high levels of genomic variation between ethnically diverse Africans which is largely correlated with geography and language. Our study indicates ancient population substructure and local adaptation of Africans.
Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is a highly effective and well-tolerated antidiabetic drug. In addition to hypoglycemic effects, empagliflozin has many other ...effects, such as being hypotensive and cardioprotective. It also has anti-inflammatory and antioxidative stress effects in diabetic nephropathy. Several studies have shown that empagliflozin has anticancer effects. SGLT2 is expressed in a variety of cancer cell lines. The SGLT2 inhibitor empagliflozin has significant inhibitory effects on certain types of tumor cells, such as inhibition of proliferation, migration and induction of apoptosis. In conclusion, empagliflozin has promising applications in cancer therapy as a drug for the treatment of diabetes and heart failure. This article provides a brief review of the anticancer effects of empagliflozin.
Efficient upconversion (UC) microcrystals are important for the development of novel photonic markers, solid-state lasers, displays, etc. Herein, we report on greatly enhanced UC emission in β-NaYF
4
...:20Yb,2Er microcrystals via a simple ion-exchange reaction. The ion exchange accompanying with an ionic redistribution process is demonstrated. By simply controlling the amount of NaF (0–8.0 mmol), reaction temperature (140–220 °C), and duration (0–144 h), enormous enhancement of the UC emission up to ~4200 times is obtained compared with the pre-synthesized β-NaYF
4
:20Yb,2Er microcrystals. The decrease of body defects and change of local structure around lanthanide may account for the UC emission enhancement. This method may apply to other UC materials to increase the UC emission efficiency.
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