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PubMed1988

Modified assay for true and apparent metabolisable energy based on tube feeding.

1. To improve the accuracy with which true metabolisable energy (TME) values of feedingstuffs are determined, a modification to the assay based on tube-feeding is proposed. 2. To ensure that the gastrointestinal tracts of the experimental birds are as empty as possible at the start of the assay it is recommended that the normal food is withdrawn 48 h before tube-feeding. 3. In order to partly alleviate the effects of starvation, all birds are given two doses of 25 g glucose (as an aqueous solution) about 40 and 16 h before tube-feeding. Birds, from which endogenous energy losses are to be derived, are fed 50 g glucose rather than given no food. 4. All birds are given 50 ml water by tube about 32 h after feeding to overcome any effects induced by low water intake. 5. A comparison of the two procedures with 8 feedingstuffs showed that the mean coefficient of variation was reduced from 5.5% to 1.5% for TME and from 4.7% to 1.8% for TME.

Animal Feed↗

PubMed1999

Energy utilisation of carbohydrate, fat and protein sources in newly hatched broiler chicks.

1. TME, TMEn and metabolisability (TME/gross energy) of energy-yielding foodstuffs were determined in 1, 3 and 10 d old broiler chicks, using the assay method developed by Murakami et al. (1994), in order to characterise energy utilisation during the 10 d after hatching. 2. TME, TMEn and metabolisability of dextrin and starch were low in chicks aged 1 d, and increased with age up to 10 d. Energy values of glucose and maltose at days 1 and 3 could not be determined because of the sudden death of birds soon after the feeding. TMEn and metabolisability of cereal sources were lower in d-old chicks than in those aged 3 and 10 d. At all ages, maize was better utilised than wheat and sorghum. 3. In the fat sources (coconut oil, beef tallow and safflower oil) no age dependency was observed in TME, TMEn and metabolisability. 4. Bioavailability of soyabean meal and fish meal was lower at 1 d than at 3 d and 10 d. Energy utilisation from casein was the highest among the protein sources tested and it was not age dependent. 5. It is concluded that energy utilisation of carbohydrate and protein sources during 10 d post-hatch tended to increase with age. Among the energy yielding foodstuffs fat sources seem to be better utilised, with no age dependency.

Animals↗

PubMed1982

The effects of age, dietary fat and bile salts, and feeding rate on apparent and true metabolisable energy values in chickens.

1. Apparent (AME) and true (TME) metabolisable energy values of four diets, containing 50 or 150 g animal fat or maize oil/kg, were estimated in young and adult chickens. The diets were given with and without a supplement of 5 g bile salts/kg. Three feeding rates, ad libitum, and 1/6th or 1/3rd of ad libitum were compared. 2. In younger birds, endogenous energy losses were higher when measured in starved birds than when estimated by regression analysis. 3. In young birds, feeding rate had no effect on AME of diets containing 50 g lipids/kg but it significantly affected TME. These results were reversed in adults. AME and TME values of diets containing 150 g lipids/kg were affected by the feeding rate in both young and adult birds. 4. Bile salts increased metabolisable energy values of diets containing high concentrations of saturated fatty acids and their effect was more pronounced in young birds.

Age Factors↗

PubMed2003

A systematic overview of radiation therapy effects in rectal cancer.

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for rectal cancer is based on data from 42 randomized trials and 3 meta-analyses. Moreover, data from 36 prospective studies, 7 retrospective studies and 17 other articles were used. A total of 131 scientific articles are included, involving 25 351 patients. The results were compared with those of a similar overview from 1996 including 15 042 patients. The conclusions reached can be summarized thus: The results after rectal cancer surgery have improved during the past decade. It is likely that local failure rates after 5 years of follow-up at hospitals adopting the TME-concept (TME = total mesorectal excision) have decreased from about 28% to 10-15%. Preoperative radiotherapy at biological effective doses above 30 Gy decreases the relative risk of a local failure by more than half (50-70%). Postoperative radiotherapy decreases the risk by 30-40% at doses that generally are higher than those used preoperatively. There is strong evidence that preoperative radiotherapy is more effective than postoperative. There is moderate evidence that preoperative radiotherapy significantly decreases the local failure rate (from 8% to 2% after 2 years) also with TME. There is strong evidence that preoperative radiotherapy improves survival (by about 10%). There is no evidence that postoperative radiotherapy improves survival. There is some indication that survival is prolonged when postoperative radiotherapy is combined with concomitant chemotherapy. Preoperative radiotherapy at adequate doses can be given with low acute toxicity. Higher, and unacceptable acute toxicity has been seen in some preoperative radiotherapy trials using suboptimal techniques. Postoperative radiotherapy can also be given with acceptable acute toxicity. The long-term consequences of radiotherapy appear to be limited with adequate radiation techniques, although they have been less extensively studied. Longer follow-up periods are needed before firm conclusions can be drawn. Peroperative radiotherapy, preferably preoperative since it is more effective, is routinely recommended for most patients with rectal cancer since it can substantially decrease the risk of a local failure and increases survival. In a primarily non-resectable tumour, preoperative radiotherapy can cause tumour regression allowing subsequent radical surgery. This therapy is routinely indicated. Whether radiochemotherapy is more efficient than radiotherapy alone is not clear, since the results of four small randomized trials are partly conflicting. Preoperative radiotherapy, frequently combined with chemotherapy, has been used to increase the chances of sphincter-preserving surgery in low-lying tumours. The literature is inconclusive with respect to how frequently this occurs. Radiotherapy frequently produces symptom relief in patients with rectal cancer not amendable to surgery.

Adult↗

PubMed2025

A novel glycogene-related signature for prognostic prediction and immune microenvironment assessment in kidney renal clear cell carcinoma.

BACKGROUND: Kidney Renal Clear Cell Carcinoma (KIRC) is a prevalent urinary malignancies worldwide. Glycosylation is a key post-translational modification that is essential in cancer progression. However, its relationship with prognosis, tumour microenvironment (TME), and treatment response in KIRC remains unclear. METHOD: Expression profiles and clinical data were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Consensus clustering, Cox regression, and LASSO regression analyses were conducted to develop an optimal glycogene-related signature. The prognostic relevance of this molecular signature was rigorously analyzed, along with its connections to tumour microenvironment (TME), tumour mutation burden, immune checkpoint activity, cancer-immunity cycle regulation, immunomodulatory gene expression patterns, and therapeutic response profiles. Validation was performed using real-world clinical specimens, quantitative PCR (qPCR), and immunohistochemistry (IHC), supported by cohort analyses from the Human Protein Atlas (HPA) database. RESULTS: A glycogene-associated prognostic scoring system was established to categorize patients into risk-stratified subgroups. Patients in the high-risk cohort exhibited significantly poorer survival outcomes (p < 0.001). By incorporating clinicopathological variables into this framework, we established a predictive nomogram demonstrating strong calibration and a concordance index (C-index) of 0.78. The high-risk subgroup displayed elevated immune infiltration scores (p < 0.001), upregulated expression of immune checkpoint-related genes (p < 0.05), and an increased frequency of somatic mutations (p = 0.043). The risk score positively correlated with cancer-immunity cycle activation and immunotherapy-related signals. The high-risk groups also showed associations with T cell exhaustion, immune-activating genes, chemokines, and receptors. Drug sensitivity analysis revealed that low-risk patients were more sensitive to sorafenib, pazopanib, and erlotinib, whereas high-risk individuals responded better to temsirolimus (p < 0.01). qPCR and IHC analyses consistently revealed distinct expression patterns of MX2 and other key genes across the risk groups, further corroborated by the HPA findings. CONCLUSION: This glycogene-based signature provides a robust tool for predicting prognosis, TME characteristics, and therapeutic responses in KIRC, offering potential clinical utility in patient management.

Humans↗

PubMed2002

New approaches in the management of rectal carcinoma result in reduced local recurrence rate and improved survival.

OBJECTIVE: To find out whether total mesorectal excision (TME) technique alone or combined with preoperative radiotherapy reduces local recurrence rate and improves survival. DESIGN: Partly retrospective (the first period), partly prospective (the second period) study. SETTING: University hospital, Helsinki, Finland. SUBJECTS: 144 patients between 1980 and 1990 and 61 patients between 1991 and 1997 with rectal cancer, who underwent major curative surgery. INTERVENTIONS: A conventional surgical technique was used during the first period and TME alone or combined with preoperative radiotherapy when appropriate during the second period. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality, local recurrence rate, and 5-year survival. RESULTS: After anterior resection 4/76 of the patients (5%) during the first period and 8/43 (19%) during the second period developed anastomotic leaks. Operative 30-day mortality was 1% (n = 1) and 0, respectively. Actuarial local recurrence rate was 17% in the first period and 9% in the second period. Actuarial crude 5-year survival improved from 55% to 78% and cancer-specific survival from 67% to 86% between the two study periods. CONCLUSIONS: Despite an increased number of anastomotic complications TME is safe. Refinement of the surgical technique together with preoperative radiotherapy yields lower local recurrence rates and an improved survival compared with conventional surgery alone.

Actuarial Analysis↗

PubMed2000

Effect of age of turkeys on the metabolisable energy of different foodstuffs.

1. True metabolisable energy (TME) of various foodstuffs were determined in turkeys at 3, 9 and 17 weeks of age. 2. TME of soyabean meal did not change with age but TME of wheat and maize was 13% higher in 17-week-old turkeys than in 3- and 9-week-old birds. 3. These differences should be taken into account when formulating diets for turkeys.

Aging↗

PubMed2000

True metabolisable energy, heat increment and net energy values of two high fibre foodstuffs in cockerels.

1. The yields of true metabolisable energy (TME) and net energy (NE) from chaya leaf meal and wheatfeed were mcasured in tube-fed cockerels. 2. TME, 5.76 MJ/kg, from chava leaf meal was lower than from wheatfeed, 8.39 MJ/kg. The total heat increment attributable to the feeding of chaya leaf meal was 1-7 times greater than that of wheatfeed. 3. The net efficiency of utilisation of ME (k) from chaya leaf meal was 0.64, while that from wheatfeed was 0.86. The role of different chemical composition, especially the high fibre content of the materials, is discussed. 4. The metabolisable energy and net energy values derived from chava leaf meal represented 0.34 and 0.23 respectively of its gross energy content. The combination of lower TME and lower net efficiency of utilisation led to chaya having a NE value, 3.86 MJ/kg, which was only 0.53 that of wheatfeed.

Animal Feed↗

PubMed2026

Local gene editing of fibroblasts in tumors reveals a new cancer-associated fibroblast state.

Fibroblasts play critical roles in regulating cellular relationships during tissue homeostasis, immunity, and tumor biology at multiple sites. However, tools to perturb fibroblasts at just one site in vivo are limited, restricting our understanding of how these cellular relationships act locally. We optimized local gene editing of fibroblasts in mouse tumor models to investigate how fibroblast perturbations affect the tumor microenvironment (TME). By knocking out receptors Osmr, Tgfbr2, or Il1r1 on cancer-associated fibroblasts (CAFs), we uncover that TGFBR2 signaling loss induces the emergence of a new Col18a1hi CAF cell state that is associated with worse survival in pancreatic cancer patients. Combinatorial gene KOs in CAFs reveals a circuit where these Col18a1hi CAFs reshape the TME by recruiting Siglec-Fhi neutrophils via Cxcl5 expression, and where this Col18a1hi CAF cell state is dependent on TNFR1 and canonical Wnt signaling. Together, a fast, affordable, and modular engineering method is demonstrated, allowing discovery of modified fibroblast identities and local intercellular relationships in the TME.

Animals↗

PubMedDate not supplied

Intersexual differences in energy expenditure of Anolis carolinensis lizards during breeding and postbreeding seasons.

Although the amount of energy that males and females invest in reproduction is an integral component of theories explaining the evolution of particular mating strategies, few studies have actually determined the amount of energy that each sex allocates to reproduction. We compared how energy is expended by male and female Anolis carolinensis lizards during both the breeding and postbreeding seasons. We used laboratory respirometry to determine resting metabolic rates (RMRs) of inactive, freshly captured lizards and the doubly labeled water technique to determine field metabolic rates (FMRs) of free-ranging lizards. Both RMRs and FMRs were influenced by body mass but not by sex. Season did not influence FMRs; however, RMRs of both sexes increased approximately 40% from the breeding to the postbreeding season. The seasonal increase in RMRs was attributed to a postreproductive increase in feeding rate and specific dynamic action. We used RMRs, FMRs, and thermal profiles of lizards to calculate energy budgets for breeding and postbreeding seasons. Energy budgets partitioned daily field energy (DFE; calculated from FMRs) into daily activity energy (DAE) and daily resting energy (DRE; calculated from RMRs). Energy expended for reproduction was estimated as DAE during the breeding season plus egg production (for females). Despite males having 40% greater body mass, females expended 46% more energy for reproduction than did males (906 and 619 J/d, respectively). Total metabolizable energy (TME=DFE+egg production for females) expended during the breeding season was similar for males and females (1,280 and 1,365 J/d, respectively). Although TME of females decreased 44% from the breeding to the postbreeding season (1,365 vs. 766 J/d), TME of males was similar during both seasons (1,280 vs. 1,245 J/d). There were both seasonal and sexual differences in DRE and DAE. Compared with most lizards from semiarid/desert habitats, A. carolinensis in a temperate habitat expends more total energy during the breeding season, allocates more energy to eggs, and appears to have more total energy available for reproduction.

Analysis of Variance↗

PubMed2003

Laparoscopic total mesorectal excision: a consecutive series of 100 patients.

OBJECTIVE: To analyze total mesorectal excision (TME) for rectal cancer by the laparoscopic approach during a prospective nonrandomized trial. SUMMARY BACKGROUND DATA: Improved local control and survival rates in the treatment of rectal cancer have been reported after TME. METHODS: The authors conducted a prospective consecutive series of 100 laparoscopic TMEs for low and mid-rectal tumors. All patients had a sphincter-saving procedure. Case selection, surgical technique, and clinical and oncologic results were reviewed. RESULTS: The distal limit of rectal neoplasm was on average 6.1 (range 3-12) cm from the anal verge. The mean operative time was 250 (range 110-540) minutes. The conversion rate was 12%. Excluding the patient who stayed 104 days after a severe fistula and reoperation, the mean postoperative stay was 12.05 (range 5-53) days. The 30-day mortality was 2% and the overall postoperative morbidity was 36%, including 17 anastomotic leaks. Of 87 malignant cases, 70 (80.4%) had a minimum follow-up of 12 months, with a median follow-up of 45.7 (range 12-72) months. During this period 18.5% (13/70) died of cancer and 8.5% (6/70) are alive with metastatic disease. The port-site metastasis rate was 1.4% (1/70): a rectal cancer stage IV presented with a parietal recurrence at 17 months after surgery. The locoregional pelvic recurrence rate was 4.2% (3/70): three rectal cancers stage III at 19, 13, and 7 postoperative months. CONCLUSIONS: Laparoscopic TME is a feasible but technically demanding procedure (12% conversion rate). This series confirms the safety of the procedure, while oncologic results are at present comparable to the open published series with the limitation of a short follow-up period. Further studies and possibly randomized series will be necessary to evaluate long-term clinical outcome in cancer patients.

Adenocarcinoma↗

PubMed2007

A prospective pathologic analysis using whole-mount sections of rectal cancer following preoperative combined modality therapy: implications for sphincter preservation.

OBJECTIVE: The aims of this study were to use a comprehensive whole-mount pathologic analysis to characterize microscopic patterns of residual disease, as well as circumferential and distal resection margins, in rectal cancer treated with preoperative CMT; and to identify clinicopathologic factors associated with residual disease. SUMMARY BACKGROUND DATA: Recent studies have shown that preoperative combined modality therapy (CMT) for rectal cancer enhances rates of sphincter preservation. However, the efficacy of preoperative CMT in conjunction with a total mesorectal excision (TME)-based resection, in terms of resection margins using whole-mount sections, has not been reported. Furthermore, since patterns of residual disease and extent of distal spread following preoperative CMT are largely unknown, intraoperative determination of distal rectal transection remains a surgical challenge. METHODS: We prospectively accrued 109 patients with endorectal ultrasound (ERUS)-staged, locally advanced rectal cancer (T2-T4 and/or N1), located a median distance of 7 cm from the anal verge, requiring preoperative CMT, and undergoing a TME-based resection. Comprehensive whole-mount pathologic analysis was performed, with particular emphasis on extent of residual disease, margin status, and intramural tumor extension. Clinicopathologic factors associated with residual disease were identified. RESULTS: A sphincter-preserving resection was feasible in 87 patients (80%), and in all 109 patients, distal margins were negative (median, 2.1 cm; range, 0.4-10 cm). Intramural extension beyond the gross mucosal edge of residual tumor was observed in only 2 patients (1.8%), both < or =0.95 cm. There were no positive circumferential margins (median, 10 mm; range, 1-28 mm), although 6 were less than or equal to 1 mm. On multivariate analysis, residual disease was observed more frequently in distally located tumors (distance from anal verge <5 cm) (P = 0.03). CONCLUSION: Our comprehensive pathologic analysis suggests that, following preoperative CMT and a TME-based resection, distal margins of 1 cm may provide for complete removal of locally advanced rectal cancer. Although residual cancer following preoperative CMT was more likely in the setting of distally located tumors, occult tumor beneath the mucosal edge was rare and, when present, limited to less than 1 cm. Our results extend the indications for sphincter preservation, as distal resection margins of only 1 cm may be acceptable for rectal cancer treated with preoperative CMT.

Adenocarcinoma↗

PubMed1994

Transmissible mink encephalopathy species barrier effect between ferret and mink: PrP gene and protein analysis.

Experimental infection of transmissible mink encephalopathy (TME) in two closely related mustelids, black ferret (Mustela putorius furo) and mink (Mustela visa), revealed differences in their susceptibility to the TME agent. When challenged with the Stetsonville TME agent, a longer incubation period was observed in ferrets (28 to 38 months) than mink (4 months). Western blot analysis of ferret and mink prion proteins (PrP) demonstrated no detectable differences between the proteins. Northern blot analysis of ferret brain RNA indicated that PrP mRNA abundance is similar in infected and uninfected individuals. We amplified the PrP coding region from ferret DNA using the polymerase chain reaction and compared the deduced amino acid sequence of the ferret PrP gene with the mink PrP gene. This comparison revealed six silent base changes and two amino acid changes between mink and ferret: Phe-->Lys at codon 179 and Arg-->Gln at codon 224, respectively. These changes may indicate the region of PrP that is responsible for the species barrier effect between mink and ferret.

Amino Acid Sequence↗

PubMed2004

Residual urine volume after total mesorectal excision: an indicator of pelvic autonomic nerve preservation? Results of a case-control study.

OBJECTIVE: The rate of bladder dysfunctions after total mesorectal excision (TME) for rectal cancer can be decreased by bilateral pelvic autonomic nerve preservation (PANP). However, it is not clear yet, how often partial nerve impairment may lead to bladder dysfunction. It was the aim of a case-control study, to examine the residual urine volume in patients before and after TME with and without complete PANP, in order to clarify, whether this parameter allows conclusions on the quality of PANP. PATIENTS AND METHODS: Regarding bladder function, a case group (n = 26) without complete PANP was compared with a control group (n = 26) with complete identification and nerve preservation according to standadized intra-operative documentation. Twenty-six match pairs were established, identical regarding gender, wall infiltration depth, tumour site, operation procedure and operation extent. Rates of neoadjuvant therapy, R0-classification, anastomotic leakage, wound and urinary tract infection were equally distributed for both the case- and control group (P > 0.05). Residual urine volume was pre- and post-operatively determined by sonography. RESULTS: Pre-operatively, residual urine volumes differed neither between the pairs nor between both groups with and without nerve preservation. In the case group with incomplete PANP there was a difference between pre- and post-operative residual urine volume (median; quartil: 2.5 ml; 0.0-32.5 ml vs 130 ml; 0.0-317 ml; P = 0.001). In the control group there was no difference (median; quartile: 0.0 ml; 0.0-20 ml vs 15.5 ml; 0.0-62.0 ml; P = 0.07). The difference between the postoperatively measured volumes of the case and control group were significant (P = 0.001). With residual urine volume = 100 ml, the risk of incomplete PANP was 14 times higher (odds ratio). CONCLUSIONS: Residual urine volume is an indicator of the completeness of PANP during TME. It should be determined pre- and post-operatively, and besides the recording of the neurogenic bladder, serve as a quality control.

Adult↗

PubMed2001

Use of live and inactivated vaccines in the control of West Nile fever in domestic geese.

The recent epizootic of West Nile fever in Israel affected predominantly young domestic geese between three and eight weeks old. Clinically, the birds presented paralytic signs while morbidity and mortality were severe in affected flocks. The condition was encountered from early September through late November on goose farms located throughout the country. Losses incurred by goose flocks were sufficiently great as to warrant investigation of ways to protect young geese against the neurological form of the disease. We have conducted a series of vaccination trials in which three-week old geese were immunized with an attenuated, commercial flavivirus vaccine derived from Israel turkey meningoencephalitis virus (TME). Birds were challenged two weeks later with a low Vero cell passage of West Nile virus by the intracerebral route. In a second group of experiments, inactivated and live TME vaccines were given in tandem at an interval of two weeks and challenged two weeks later. The third vaccination trial was based on West Nile virus (WNV) harvested from infant mouse brain, inactivated with formalin and oil adjuvanted. A single injection given either subcutaneously or intramuscularly resulted in 75% protection of the vaccinated groups, while two injections spaced two weeks apart resulted in 94% protection. Groups of geese, vaccinated at the farms and challenged under controlled conditions in the laboratory, showed levels of protection ranging from 39% to 72% for TME vaccine and 52% and 80% for WNV vaccine. The lower levels of protection are attributable to flocks being affected with intercurrent infections at the time of vaccination.

Animals↗

PubMed2026

SLA2 is Associated With Immune evasion and Exhaustion of CD8+ T Cells in Gastric Cancer.

The Src-like adaptor 2 (SLA2) functions as a negative regulator of T cell receptor signalling. However, its involvement in the tumour microenvironment (TME) of gastric cancer (GC) remains unexplored. In this study, we found that SLA2 expression was significantly elevated in GC tissues, and a high level of SLA2 was associated with poor prognosis in GC patients. Bioinformatics analyses revealed a close association between SLA2 and TME in GC. Single-cell RNA sequencing analysis indicated that SLA2 was significantly enriched in CD8+ T cells in GC tissues. Functional validation demonstrated that SLA2 overexpression contributed to the exhaustion of CD8+ T cells by suppressing their proliferation, upregulating the expression of exhaustion markers, reducing the secretion of effector cytokines (IFN-γ and TNF-α) and impairing cytotoxic function. SLA2 knockdown in in vitro-generated exhausted CD8 T cells significantly alleviated T cell exhaustion. Mechanistically, we found that inverse promoter methylation and active histone marks (H3K27ac, H3K4me3 and H3K4me1) may regulate SLA2 expression. Our findings suggest that SLA2 may modulate the TME and promote immune evasion via CD8+ T cell exhaustion in GC.

Humans↗

PubMed1992

Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent.

Transmissible mink encephalopathy (TME) has been transmitted to Syrian golden hamsters, and two strains of the causative agent, HYPER (HY) and DROWSY (DY), have been identified that have different biological properties. During scrapie, a TME-like disease, an endogenous cellular protein, the prion protein (PrPC), is modified (to PrPSc) and accumulates in the brain. PrPSc is partially resistant to proteases and is claimed to be an essential component of the infectious agent. Purification and analysis of PrP from hamsters infected with the HY and DY TME agent strains revealed differences in properties of PrPTME sedimentation in N-lauroylsarcosine, sensitivity to digestion with proteinase K, and migration in polyacrylamide gels. PrPC and HY PrPTME can be distinguished on the basis of their relative solubilities in detergent and protease sensitivities. PrPTME from DY-infected brain tissue shared solubility characteristics of PrP from both uninfected and HY-infected tissue. Limited protease digestion of PrPTME revealed strain-specific migration patterns upon polyacrylamide gel electrophoresis. Prolonged proteinase K treatment or N-linked deglycosylation of PrPTME did not eliminate such differences but demonstrated the PrPTME from DY-infected brain was more sensitive to protease digestion than HY PrPTME. Antigenic mapping of PrPTME with antibodies raised against synthetic peptides revealed strain-specific differences in immunoreactivity in a region of the amino-terminal end of PrPTME containing amino acid residues 89 to 103. These findings indicate that PrPTME from the two agent strains, although originating from the same host, differ in composition, conformation, or both. We conclude that PrPTME from the HY and DY strains undergo different posttranslational modifications that could explain differences in the biochemical properties of PrPTME from the two sources. Whether these strain-specific posttranslational events are directly responsible for the distinct biological properties of the HY and DY agent strains remains to be determined.

Animals↗

PubMed1994

Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy.

The molecular basis of strain variation in scrapie diseases is unknown. The only identified component of the agent is the posttranslationally modified host prion protein (PrPSc). The biochemical and physical properties of PrP from two strains of transmissible mink encephalopathy (TME), called hyper (HY) and drowsy (DY), were compared to investigate if PrP heterogeneity could account for strain diversity. The degradation rate of PrPTME digested with proteinase K was found to be strain specific and correlated with inactivation of the TME titer. Edman protein sequencing revealed that the major N-terminal end of HY PrPTME commenced at least 10 amino acid residues prior to that of DY PrPTME after digestion with proteinase K. Analysis of the brain distribution of PrPTME exhibited a strain-specific pattern and localization of PrPTME to the perikarya of specific neuron populations. Our findings are consistent with HY and DY PrPTME having distinct protein conformations and/or strain-specific ligand interactions that influence PrPTME properties. We propose that PrPTME conformation could play a role in targeting TME strains to different neuron populations in which strain-specific formation occurs. These data are consistent with the idea that PrPTME protein structure determines the molecular basis of strain variation.

Amino Acid Sequence↗