Hasil untuk "Genetics"

J. Bishop

P. Hedrick

R. Roush, J. A. Mckenzie

Rachel Jones

R. Doerge

A. Scarpa, P. Capelli, I. Cataldo

H. Orr

J. Mattick

M. Farrer

C. Freitag

M. Rockman, L. Kruglyak

W. A. Guiguemde, A. Shelat, David C. Bouck et al.

Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library—many of which showed potent in vitro activity against drug-resistant P. falciparum strains—and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in several organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Our findings provide the scientific community with new starting points for malaria drug discovery.

S. Kathiresan, D. Srivastava

Reinhard Bürger

In this addendum we extend Theorem 4.6 on the negative binomial distribution in `Bounds for survival probabilities in supercritical Galton-Watson processes and applications to population genetics' (Journal of Mathematical Biology 92:40, 2026; arXiv:2503.21403). We prove that the fractional linear lower bound to the negative binomial generating function derived there is indeed valid for every $x\in[0,1]$, and not only for $x\in[0,P^\infty_{\rm NB}]$, where $P^\infty_{\rm NB}$ is the extinction probability of the associated Galton-Watson process.

Fanglan Wu, Yunxiao Zhao, Yicun Chen et al.

Flavonoids are not only widely applied in the food, pharmaceutical and cosmetic industries, but also possess diverse biological functions that play crucial roles in plant physiology, growth and development, and ecology. The camphor tree (Cinnamomum camphora (L.)) holds significant economic and ecological value; however, its flavonoid composition and the underlying biosynthetic mechanisms remain largely unexplored. In this study, widely targeted metabolomics and transcriptomics were integrated to comprehensively analyze the leaves of C. camphora. The results revealed significant metabolic differences among fresh leaves of different C. camphora chemotypes. with both DAMs and DEGs being significantly enriched in the flavonoid biosynthesis pathway. Quercetin-5-O-glucuronide, rhamnetin-3-O-glucoside, juglanin, catechin and (-)-epicatechin were identified as the major DAMs. Furthermore, the key enzymes involved in the flavonoid biosynthetic pathway, such as PAL, C4H, and 4CL, CHS, CHI, F3H, FLS, DFR, ANS, LAR, C3H, and HCT were identified. Among these, CcC4H1 was identified as a hub gene in co-expression network. Compared with the control, transient overexpression of CcC4H1 significantly increased the total flavonoid content in C. camphora leaves by 1.45-fold (reaching 2.42 mg/g), while significantly elevating the flavonoids compounds such as 8-C-methylquercetin 3-xyloside, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2S,3S,4 R,5S,6 R)-2,3,5-trihydroxy-6-methyloxan-4-yl]oxychromen-4-one, and rhamnetin-3-O-glucoside, with increases ranging from 1.88- to 22.79-fold. These findings provide important insights into the molecular regulation mechanisms of flavonoid biosynthesis in camphor trees and provide important information for the selection of varieties rich in flavonoids.

Elham Karimi, Shalaleh Abbasnezhad, Maedeh Arabpour et al.

ABSTRACT Background Retinoblastoma (RB) is a malignant eye tumor that predominantly affects children. Although survival rates have improved significantly due to advancements in treatment, subsequent malignant neoplasms (SMNs) continue to be major causes of death in both heritable and non‐heritable RB cases. These SMNs are often associated with mutations in the RB1 gene, as well as the effects of radiotherapy or chemotherapy. There are no previous reports of a nonhereditary RB survivor developing three sequential hematologic malignancies (AML, lymphoma, and ALL) over 20 years. Most secondary primary cancers (SPCs) in RB survivors are solid tumors, such as osteosarcoma, soft tissue sarcoma, and melanoma, with hematologic malignancies being far less common, especially as third or subsequent primary tumors. Case We report a case of a 21‐year‐old Iranian male who developed multiple distinct hematologic malignancies following retinoblastoma treatment. Using NGS, Sanger sequencing, and bioinformatic analysis, the possibility of germline mutations was surveyed. Conclusion Germline changes associated with malignancies were examined using next‐generation sequencing (NGS). There were no germline alterations discovered, suggesting no predisposition to develop cancer. Three pathogenic/likely pathogenic heterozygous variants were found in the patient by carrier screening. Absence of germline RB1 mutations or other hereditary cancer syndromes implicates treatment‐related factors (chemotherapy/radiotherapy) as the primary driver of sequential malignancies. Nonhereditary retinoblastoma (RB) survivors have a lower risk of secondary malignancies (SMNs) compared to their hereditary counterparts. Chemotherapy, especially alkylating agents, increases the risk of secondary acute myelogenous leukemia (AML) and other leukemias and lymphomas due to its mutagenic effects and genetic factors. Although RB survivors rarely develop secondary cancers, the limited patient numbers and short follow‐up periods may influence SPC risk assessments. Continuous monitoring and personalized follow‐up care are crucial for managing long‐term risks in these survivors. This research emphasizes the essential importance of ongoing monitoring and follow‐up for survivors of retinoblastoma (RB) to identify and address secondary malignancies (SMNs), improve the management of long‐term complications, and enhance both life expectancy and quality of life.

Manuel Fuertes-Recuero, José L. López-Hernández, Alejandra Ramírez-Lago et al.

Chimpanzees (<i>Pan troglodytes</i>) rescued from the illegal wildlife trade often suffer from chronic, traumatic injuries that require specialized and prolonged medical treatment in wildlife rehabilitation centers. We present the case report of a two-year-old male chimpanzee admitted at the Tchimpounga Chimpanzee Rehabilitation Center in the Republic of Congo with a chronic periorbital abscess, likely caused by a machete wound sustained during the poaching of his mother. Despite receiving extended antimicrobial therapy, his condition was never fully controlled and progressed to a chronic orbital infection, causing him discomfort and producing chronic purulent discharge. Enucleation was performed under general anesthesia using ketamine and medetomidine, with surgical approach adapted to the distinctive orbital anatomy of chimpanzees. During the procedure, ligation of the optic nerve and ophthalmic vessels was required due to the confined orbital apex and extensive vascularization, ensuring adequate haemostasias and procedural safety. The chimpanzee made an uneventful postoperative recovery, resuming normal feeding and social behavior within 48 h, with complete wound healing occurring within two weeks. This case report highlights the importance of prompt surgical intervention when conservative medical management fails to resolve refractory ocular infections in chimpanzees. It also emphasizes the importance of specific anesthetic protocols, refined surgical techniques and tailored postoperative care in wildlife rehabilitation centers. Documenting and sharing detailed case reports such as this contributes to the limited veterinary literature on great ape surgery and supports evidence-based clinical decision-making to improve the welfare and treatment outcomes of rescued chimpanzees.

Aparna Mariyam Thomas, Guilherme G. Verocai, John Soghigian et al.

The caribou (Rangifer tarandus sspp.) is a keystone wildlife species in northern ecosystems that plays a central role in the culture, spirituality and food security of Indigenous People. The Arctic is currently experiencing an unprecedented rate of climate change, including warming temperatures and altered patterns of precipitation. These environmental changes can facilitate the transmission of arthropod-borne parasites, such as filarioid nematodes.Filarioids are an important cause of morbidity and occasional mortality in Rangifer in Fennoscandia, however, much of the ecology and epidemiology of these parasites in caribou in North America, including Canada, remains unknown. We aimed to determine the parasitic diversity and geographic distribution of filarioid nematodes in three Canadian designatable units (DU) of caribou (barren-ground, boreal and Dolphin &amp; Union) from Northwest Territories, Nunavut and Newfoundland &amp; Labrador. Genomic DNA extracted from 768 blood samples was screened for filarioid nematodes using real-time PCR. The positive samples were Sanger sequenced to identify the parasite present. Based on the sequencing results, we identified Setaria yehi and Onchocerca cervipedis s.l. We then standardized a TaqMan probe based duplex droplet digital PCR (ddPCR) protocol for the simultaneous detection of S. yehi and O. cervipedis s.l. Based on real-time PCR results, 8/768 samples were positive. Setaria yehi and O. cervipedis s.l. were present in 4 separate samples (0.5%) each. Using ddPCR, 68/192 samples were positive (35.4%). Setaria yehi DNA was detected in 57/192 positive samples (29.7%), O. cervipedis s.l. DNA was present in 22/192 samples (11.5%) and 11/192 samples (5.7%) had co-infections. Setaria yehi was detected in all three DUs tested. Onchocerca cervipedis s.l. were found in barren-ground and boreal caribou, but not from the Dolphin and Union caribou.Through this broad-based survey and through developing and implementing advanced molecular methodologies, we have documented the apparent distribution and diversity of S. yehi and O. cervipedis s.l. in parts of three Canadian DUs of caribou. The knowledge gained from this study provides baseline data and methodology for the further elucidation of the epidemiology of these parasites in North America.

Gül Özbilen Acar, Filiz Özen, Halil İbrahim Yıldırım et al.

Objective: The goal of this study was to investigate the expression patterns and potential relationship of the Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-raf proto-oncogene (BRAF) genes in nasal polyposis (NP). Methods: Twenty-nine patients were included in the study. Small punch biopsies were collected from nasal polyps during each operation and immediately frozen in liquid nitrogen. Punch biopsies were also taken during surgery from the inferior turbinate or the septum mucosa of the patients as a control group, and these samples were also frozen. Total ribonucleic acid (RNA) was isolated using TRIzol reagent. The gene expression analyses of the KRAS and BRAF genes were performed by the real-time polymerase chain reaction method. Results: When compared to control subjects, KRAS nasal polyp gene expression increased in 21, but decreased in eight of the 29 patients. This statistical analysis revealed a statistically significant difference between the nasal polyp group and the controls (p=0.023). Like KRAS, a decrease was observed in BRAF gene expression in six, and an increase in 23 patients (p=0.011). Conclusion: Our findings suggest a potential association between BRAF and KRAS genes expression and NP, but further studies are needed to confirm this relationship. This finding suggests that the genetic background of NP could be a contributing factor, with the BRAF and KRAS mutations playing a role.

Xue Du, Duoxi Li, Luya Jia et al.

Chicken semen cryopreservation is crucial for utilizing high-quality cockerel genetics, but semen is highly sensitive to cryoinjury, leading to poor preservation outcomes. This study aimed to establish a theoretical foundation for selecting cockerels for semen cryopreservation through serum testing and to improve semen quality via DNA methylation editing. Semen and serum samples were collected from 102 Xiaoshan cockerels, with semen cryopreserved and thawed following standardized protocols. Post-thaw semen quality and serum testosterone (T) levels were assessed. Eight cockerels were selected based on motile sperm quality, and whole-genome bisulfite sequencing (WGBS) was used to analyze sperm DNA methylation. The results showed a significant positive correlation between serum T levels and sperm motility. There were notable differences in sperm motility and serum T levels between high-quality and low-quality semen groups but no differences in estradiol (E₂), superoxide dismutase (SOD), or glutathione peroxidase (GSH-Px) levels. A total of 217 differentially methylated regions (DMRs) and 116 differentially methylated genes (DMGs) were identified. Key genes such as <i>PRKACB</i> (protein kinase, cAMP-dependent, catalytic, beta) and <i>ACSL1</i> (long-chain-fatty-acid--CoA ligase 1) were associated with sperm motility. These findings provide important insights for improving semen cryopreservation and contribute to breeding practices and the development of cryoprotectants.