Cooling Holstein cows for 60 days prepartum in summer: effects on prepartum physiology, postpartum productivity, and calf growth.

Heat stress (HS) during the dry period of dairy cows in hot and dry conditions compromises the physiological status and mammary gland development of dairy cows, thereby negatively affecting milk component yield in the subsequent lactation. Our objective was to evaluate the effects of cooling Holstein cows under moderate or higher HS conditions (i.e., ambient temperature higher than 30 °C, with a temperature-humidity index of 78.2 units) during the dry period on prepartum physiological status, postpartum productivity, and calf growth. Twenty-four multiparous Holstein cows were divided into two groups: one with a cooling system based on spray and fans under a pen shade (CL, n = 12) and the other not-cooled (NC, n = 12). The cooling system operated 10 h/d (09:00-19:00 h) for 60 d prepartum. During the morning, rectal temperature and respiration frequency were lower in CL cows, but not in the afternoon, which was attributed to higher (P < 0.01) dry matter intake by CL cows. Total serum protein was higher (P < 0.01) in CL cows, but hemoglobin was higher in NC cows (P < 0.01), with no differences in other electrolytes, hormones, hematological components, and metabolites. Milk fat and fat and fat-protein corrected milk were higher (P < 0.05) in CL cows. Female and birth weight trended (P = 0.08) to be higher in CL cows. Cooling cows during the dry period had a limited effect on physiology prepartum but increased postpartum productivity of Holstein cows under hot and dry conditions.

Holstein heifers in desert climate: effect of coat color on physiological variables and prediction of rectal temperature.

Two hundred Holstein heifers were divided by hair coat color in black (n1 = 60), white (n2 = 62), and mixed (n3 = 78) to accomplish two objectives: (1) to compare physiological variables using an analysis of variance, and (2) to construct regression equations to predict rectal temperature. In each heifer, rectal temperature (RT), respiration frequency (RF), and body surface temperatures (obtained with infrared thermography in eye, nose, forehead, head, neck, ear, shoulder, flank, belly, leg, loin, rump, and vulva) were measured. Black heifers had more RF and RT (P < 0.01) than mixed and white coat heifers; white heifers had similar RT than mixed color heifers, but they exhibited less RF (P < 0.05). In general, black and mixed coat color heifers had higher BST (P < 0.01) than white heifers in the majority of the anatomical regions measured. For black coat heifers, the best regression model to predict RT included three predictor variables: [RT = 35.59 - 0.013 (RH) + 0.045 (RF) + 0.019 (TEar); R2 = 71%]. For white coat heifers, the best model included two predictor variables: [RT = 35.29 + 0.035 (RF) + 0.033 (TForehead); R2 = 71%]; and for mixed coat color heifers, the best model included two predictor variables: [RT = 35.07 + 0.022 (RF) + 0.038 (THead); R2 = 44%]. Heifers with dark hair coat color showed higher physiological constants than white heifers; the prediction of rectal temperature was more precise in heifers with well-defined hair coat color. Physiological and climatic variables, along with infrared thermography, represent an appropriate combination to predict rectal temperature in Holstein heifers with predominant white or black hair coat color.

Muscle fiber morphometry and physicochemical characteristics of the Longissimus thoracis muscle of hair male lambs fed zilpaterol hydrochloride and implanted with steroids.

Muscle fiber morphometry and physicochemical characteristics were evaluated in LT muscles obtained from entire male lambs treated with zilpaterol hydrochloride (ZH, 0 and 0.15 mg/kg body weight) and/or steroidal implant (SI, with and without trenbolone acetate/estradiol). ZH and SI acted synergistically to increase LT area, type-IIb fiber cross-sectional area and soluble collagen content, likewise to decrease metmyoglobin concentration and insoluble collagen content. Ash content and ultimate pH showed a decrease due to an antagonistic effect between ZH and SI. Content of total collagen, protein, fat, moisture, oxidized lipids and water-holding capacity were unaffected by ZH and SI. Supplemental ZH, but not SI, decreased all color parameters and tended to increase shear force. Overall, the SI implantation of male lambs followed by a ZH supplementation promoted greater LT hypertrophy, without affecting protein and fat content, and physicochemical characteristics in their meat.

A Genomic Snapshot of the SARS-CoV-2 Pandemic in the Balearic Islands.

Objective: To analyze the SARS-CoV-2 genomic epidemiology in the Balearic Islands, a unique setting in which the course of the pandemic has been influenced by a complex interplay between insularity, severe social restrictions and tourism travels. Methods: Since the onset of the pandemic, more than 2,700 SARS-CoV-2 positive respiratory samples have been randomly selected and sequenced in the Balearic Islands. Genetic diversity of circulating variants was assessed by lineage assignment of consensus whole genome sequences with PANGOLIN and investigation of additional spike mutations. Results: Consensus sequences were assigned to 46 different PANGO lineages and 75% of genomes were classified within a VOC, VUI, or VUM variant according to the WHO definitions. Highest genetic diversity was documented in the island of Majorca (42 different lineages detected). Globally, lineages B.1.1.7 and B.1.617.2/AY.X were identified as the 2 major lineages circulating in the Balearic Islands during the pandemic, distantly followed by lineages B.1.177/B.1.177.X. However, in Ibiza/Formentera lineage distribution was slightly different and lineage B.1.221 was the third most prevalent. Temporal distribution analysis showed that B.1 and B.1.5 lineages dominated the first epidemic wave, lineage B.1.177 dominated the second and third, and lineage B.1.617.2 the fourth. Of note, lineage B.1.1.7 became the most prevalent circulating lineage during first half of 2021; however, it was not associated with an increased in COVID-19 cases likely due to severe social restrictions and limited travels. Additional spike mutations were rarely documented with the exception of mutation S:Q613H which has been detected in several genomes (n = 25) since July 2021. Conclusion: Virus evolution, mainly driven by the acquisition and selection of spike substitutions conferring biological advantages, social restrictions, and size population are apparently key factors for explaining the epidemic patterns registered in the Balearic Islands.

Growth, carcass characteristics, cut yields and meat quality of lambs finished with zilpaterol hydrochloride and steroid implant.

Forty hairbreed male lambs were used to evaluate the effects of zilpaterol hydrochloride (ZH, 0 and 0.15 mg/kg BW) and steroid implant (SI, without and with 52.5 mg trenbolone acetate and 7.5 mg 17ß-estradiol) on feedlot performance, carcass characteristics, non-carcass components, wholesale cut yield, and meat quality. Supplemental ZH increased growth rate, feed efficiency, carcass weight, and dressing percentage, with no effect on wholesale cut yields. Feeding ZH increased muscle pH at 24 h. Supplemental ZH increased meat shear force, but decreased lightness, redness, and yellowness after frozen storage followed by a 14-day aging period. The SI administration increased dressing percentage and neck yield, but decreased testicle weight and meat redness, without affecting other variables. The LT area was greater with ZH + SI administration than with individual application of ZH or SI. Compared to individual administration, simultaneous application of ZH and SI did not result in improved growth performance, carcass traits and wholesale cut yields in hairbreed male lambs.

Effects of dietary ferulic acid on reproductive function and metabolism of pre-pubertal hairbreed ewes during the anestrous season.

This study aimed to evaluate the effects of dietary supplementation of ferulic acid (FA) on reproductive tract weight (RTW), ovarian activity and serum concentrations of some metabolites and thyroid hormones of pre-pubertal hairbreed ewe lambs during the natural anestrous season. Twenty Dorper x Pelibuey crossbred ewe lambs (initial body weight = 28.5 ±â€¯0.5 kg and age = 5.0 mo) were fed a basal diet and assigned to two treatments (n = 10) under randomized complete block design: FA supplementation to dosages of 0 (control) or 300 mg of FA/d animal-1. Females were treated with FA during 34 d and then slaughtered to evaluate RTW and ovary. Blood samples were collected at days 1 and 34 to determine serum concentrations of metabolites (i.e. glucose, cholesterol, triglycerides, urea and total protein) and thyroid hormones. Final weight, dry matter intake, and serum concentrations of metabolites (except glucose) and thyroid hormones were unaltered by FA. Compared to control, FA-fed ewe lambs had lower (P = 0.05) serum glucose level but higher (P ≤ 0.05) RTW, ovarian mass, number of larger follicles and corpus luteum (CL). While percentage of ewe lambs with small follicles and number of small follicles per female did not vary, percentage of ewe lambs with large follicles and CL increased (P = 0.02) with FA. In conclusion, FA supplementation improves the reproductive tract development and ovarian activity of pre-pubertal hairbreed ewe lambs during the natural anestrous season. An improvement in functionality of the glucose-insulin system could be related with this benefic effect of FA.

Pregnancy Outcomes Related to Mycophenolate Exposure in Female Kidney Transplant Recipients.

In 2012, the U.S. Food and Drug Administration issued guidelines advising kidney transplant recipients (KTRs) to discontinue mycophenolate (MPA) in preparation for pregnancy. Little is known about how this guidance has affected pregnancy and graft outcomes. The purpose of this retrospective cohort study was to investigate any association between the discontinuation of MPA and KTR pregnancy and graft outcomes. Data from the National Transplantation Pregnancy Registry included 382 cases in which KTRs managed on MPA became pregnant. Overall, 22 variables, including the time in which a KTR discontinued MPA, were assessed across four end points: miscarriages, birth defects, and 2- and 5-year postpartum graft loss. Birth defects and miscarriages were similar among KTRs who discontinued MPA >6 and <6 weeks prior to pregnancy and during the first trimester. In contrast, discontinuing MPA during the second trimester or later significantly increased the risk of miscarriages (odds ratio [OR] 9.35, 95% confidence interval [CI] 4.31-20.00, p < 0.001) and birth defects (OR 6.06, 95% CI 1.96-18.87, p = 0.002). Discontinuing MPA <6 weeks prior to pregnancy was associated with an increased risk of 5-year graft loss. For the fetus, there is value to discontinuing MPA anytime prior to the second trimester. Adhering to current guidelines does not negatively affect graft survival.

Effects of seasonal ambient heat stress (spring vs. summer) on physiological and metabolic variables in hair sheep located in an arid region.

Twenty Dorper × Pelibuey primiparous ewes were used to evaluate effects of seasonal ambient heat stress (i.e., spring vs. summer) on physiological and metabolic responses under production conditions in an arid region. Ten ewes experiencing summer heat stress (i.e., temperature = 34.8 ± 4.6 °C; THI = 81.6 ± 3.2 units) and 10 under spring thermoneutral conditions (temperature = 24.2 ± 5.4 °C; THI = 68.0 ± 4.8 units) were corralled together to measure rectal temperature, respiratory frequency, and skin temperatures at 0600, 1200, 1800, and 2400 h on four occasions over 40 days. Blood metabolite and electrolyte concentrations were also measured at 0600 and 1800 hours. Data were analyzed with a completely randomized design using repeated measurements in time. Rectal and skin temperatures, as well as respiratory frequency, were higher (P < 0.01) in summer than spring at all measured days. Blood serum glucose, cholesterol, triglycerides, and chlorine concentrations were lower (P < 0.01) in summer than spring at 0800 and 1800 hours. In contrast, summer heat stress increased (P < 0.01) blood urea and potassium concentrations at 0800 and 1800 hours. Compared with spring thermoneutral conditions, summer heat stress affected the physiological and metabolic status of hair breed ewes in an arid region, which included blood metabolite and electrolyte adjustments to efficiently cope with summer heat stress.

Mouse Models of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.

Stabilization of the third fibronectin type III domain of human tenascin-C through minimal mutation and rational design.

Non-antibody scaffolds are increasingly used to generate novel binding proteins for both research and therapeutic applications. Our group has developed the tenth fibronectin type III domain of human tenascin-C (TNfn3) as one such scaffold. As a scaffold, TNfn3 must tolerate extensive mutation to introduce novel binding sites. However, TNfn3's marginal stability (T(m) ∼ 59°C, ΔG(unfolding) = 5.7 kcal/mol) stands as a potential obstacle to this process. To address this issue, we sought to engineer highly stable TNfn3 variants. We used two parallel strategies. Using insights gained from structural analysis of other FN3 family members, we (1) rationally designed stabilizing point mutations or (2) introduced novel stabilizing disulfide bonds. Both strategies yielded highly stable TNfn3 variants with T(m) values as high as 83°C and ΔG(unfolding) values as high as 9.4 kcal/mol. Notably, only three or four mutations were required to achieve this level of stability with either approach. These results validate our rational design strategies and illustrate that substantial stability increases can be achieved with minimal mutation. One TNfn3 variant reported here has now been successfully used as a scaffold to develop two promising therapeutic molecules. We anticipate that other variants described will exhibit similar utility.

Effect of dietary microbially produced gamma-linolenic acid and plant extracts on enzymatic and non-enzymatic antioxidants in various broiler chicken organs.

Plant extracts and fungal fermented feed with gamma-linolenic acid-rich microbial oils are perspective additives for use in animal nutrition as appetite and digestion stimulants, stimulants of physiological functions, for the prevention and treatment for certain pathological conditions, and as antioxidants. The activity of antioxidant enzymes and the level of reduced glutathione were measured in the plasma and in liver, heart and kidney mitochondria after 42 days of feeding broiler chickens both regular and combination diets. These were selected based on our previous experience. The administration of agrimony and gamma-linolenic acid resulted in a significant decrease in superoxide dismutase activity in all four bodies in contrast to plant extracts. We conclude that the decrease in activity is due to decreased production, and hence dismutation, of superoxide radicals to peroxides followed by lower activity of glutathione peroxidase, which was not seen in the case of only plant extract administration. Generally, higher glutathione reductase activity would be in response to increased demands on reduced glutathione as a cofactor for the reaction catalysed by glutathione peroxidase and the utilization of glutathione itself. However, measured levels of reduced glutathione showed no change. The results argue against any oxidative stress conditions. The application of agrimony extract appears to be suitable for the antioxidant effect against peroxidation of gamma-linolenic acid. As the efficacy of measuring the effects of diets on the oxidative stability of meat caused by selected antioxidant enzymes is rather low, additional data from the experiment will be processed to clearly assess the influence of this combination of diets.

Primary obstructed megaureter (POM) in children.

UNLABELLED: The aim of this study was to analyze the results of surgical and conservative treatment of non-refluxing POM. In the period 2000-2009, 45 children (52 ureters) were treated, the average age was 5.8 months (±10.33), 24 children (26 ureters) by surgery (I) and 21 children (26 ureters) by conservative means (II). The average follow-up period was 73.8 (±32.91) and 30.85 months (±23.1) resp. Urine examination, USG, DTPA99mTc, biochemical testing, micturating cystouretography in all patients were performed. Significant difference was present in the occurrence of hydronephrosis of 0th, 3rd and 4th grade, p10 mm, p<0.01; and in the occurrence of normal and prolonged time T ½, p<0.01. The health condition was adjusted in 13 (54.20 %), improved on DTPA99mTc in 5 (20.85 %), non-improved in 3 (12.50 %), deteriorated in 1 (4.15 %) and unknown in 2 (8.3 %) patients. In the IInd group a significant difference was in case of occurrence of hydronephrosis of 0th, 2nd and 3rd grade, (p<0.01, or p=0.037 and p=0.011) and in occurrence of normal ureter, with ureter 0-5 mm and dilated ureter 5-10 mm, p<0.01. The condition at the end of the follow-up period was assessed DTPA99mTc as adjusted in 11 (52.39 %) patients, improved in 6 (28.57 %), unimproved in 3 (14.28 %) and no patient was assessed as having deteriorated and unknown in 1 (4.76 %). CONCLUSION: In patients with an impaired separate kidney function, early surgical treatment helps to minimize damage to the kidney function and prevents future complications (Tab. 6, Fig. 3, Ref. 32).

Deep Impact: excavating comet Tempel 1.

Deep Impact collided with comet Tempel 1, excavating a crater controlled by gravity. The comet's outer layer is composed of 1- to 100-micrometer fine particles with negligible strength (<65 pascals). Local gravitational field and average nucleus density (600 kilograms per cubic meter) are estimated from ejecta fallback. Initial ejecta were hot (>1000 kelvins). A large increase in organic material occurred during and after the event, with smaller changes in carbon dioxide relative to water. On approach, the spacecraft observed frequent natural outbursts, a mean radius of 3.0 +/- 0.1 kilometers, smooth and rough terrain, scarps, and impact craters. A thermal map indicates a surface in equilibrium with sunlight.

Relaxin and prostaglandin E(2) regulate interleukin 11 during human endometrial stromal cell decidualization.

Decidualization of endometrial stromal cells and IL-11 signaling are essential for embryo implantation in the mouse. We investigated the effects of relaxin (RLX) and prostaglandin E(2) (PGE(2)) on IL-11 secretion by human endometrial stromal cells (HESC) and during cAMP or medroxyprogesterone acetate (P)-induced decidualization. cAMP-decidualized HESC secreted high levels of IL-11. RLX, cAMP, or PGE(2) increased IL-11 mRNA and IL-11 secretion, with maximal response to RLX and cAMP. Addition of the cAMP/protein kinase A inhibitor Rp-adenosine-3,5-cyclic-monophosphorothioate to either RLX- or PGE(2)-treated cells decreased IL-11 secretion. Indomethacin treatment decreased IL-11 secretion, which was largely restored by cotreatment with PGE(2) or RLX. Cotreatment of HESC with RLX, PGE(2), or cAMP and estrogen plus P down-regulated IL-11 mRNA and IL-11 secretion at 24 h, before secretion of prolactin (decidualization marker). Addition of W147AIL-11 (IL-11 signaling inhibitor) reduced prolactin secretion stimulated by RLX or PGE(2) and estrogen plus P. This is the first demonstration that cAMP-decidualized HESC secrete IL-11 and that IL-11 mRNA and IL-11 secretion are regulated by RLX and PGE(2), partly via a cAMP/protein kinase A-dependent pathway. Blocking IL-11 signaling reduced RLX+P- or PGE(2)+P-induced decidualization, suggesting that RLX and PGE(2) act via IL-11. This is important in understanding implantation and regulation of fertility.

[Long-term results of retropubic vesicopexy in the treatment of urinary stress incontinence in women]. / Dlhodobé výsledky retropubickej vezikopexie v liecbe stresovej inkontinence mocu u zien.

OBJECTIVE: To evaluate long-term results of retropubic vesicopexy (e.g. direct suspension of the anterior and lateral walls of the bladder base) in the treatment of female stress urinary incontinence (SUI) caused by hypermobile urethra. DESIGN: Retrospective clinical study. SETTING: Department of Urology, Faculty of Medicine, University of P. J. Safarik, Kosice, Slovakia. METHODS: From a total of 44 females operated on between 1985-1992, 41 (93%) were available for the study (mean age 50 years, 28 pure SUI, 13 mixed incontinence). 18 (44%) patients had failed previous incontinence surgery. Based on the data collected by a detailed questionnaire as a success cure and/or significant improvement (max. 1 pad/day) of SUI have been considered. RESULTS: With a mean of 103 month follow-up period (48-160 months), 32 (78%) patients reported to have their SUI cured, another 5 (12%) significantly improved. Both persistent (8/13, 62%) and de novo urge incontinence (5/28, 18%) have shown to the main reasons for "partial" satisfaction only with the outcome of surgery. Perioperative bleeding requiring blood transfusion was the only serious complication met with this procedure (2 patients). CONCLUSION: Long-term results of vesicopexy is comparable with the effect of standard retropubic procedures like Burch colposuspension or MMK urethropexy. Technical simplicity, no risk of osteitis pubis as well as persisting micturition problems may be considered the main advantages of the procedure. Because of lower cure rate the procedure is less suitable for SUI type IIB.

Structure-function analysis of a phage display-derived peptide that binds to insulin-like growth factor binding protein 1.

Highly structured, peptide antagonists of the interaction between insulin-like growth factor 1 (IGF-I) and IGF binding protein 1 (IGFBP-1) have recently been discovered by phage display of naïve peptide libraries [Lowman, H. B., et al. (1998) Biochemistry 37, 8870--8878]. We now report a detailed analysis of the features of this turn-helix peptide motif that are necessary for IGFBP-1 binding and structural integrity. Further rounds of phage randomization indicate the importance of residues contributing to a hydrophobic patch on one face of the helix. Alanine-scanning substitutions confirm that the hydrophobic residues are necessary for binding. However, structural analysis by NMR spectroscopy indicates that some of these analogues are less well folded. Structured, high-affinity analogues that lack the disulfide bond were prepared by introducing a covalent constraint between side chains at positions i and i + 7 or i + 8 within the helix. Analogues based on this scaffold demonstrate that a helical conformation is present in the bound state, and that hydrophobic side chains in this helix, and residues immediately preceding it, interact with IGFBP-1. By comparison of alanine scanning data for IGF-I and the turn-helix peptide, we propose a model for common surface features of these molecules that recognize IGFBP-1.

Direct inhibition of caspase 3 is dispensable for the anti-apoptotic activity of XIAP.

XIAP is a mammalian inhibitor of apoptosis protein (IAP). To determine residues within the second baculoviral IAP repeat (BIR2) required for inhibition of caspase 3, we screened a library of BIR2 mutants for loss of the ability to inhibit caspase 3 toxicity in the yeast Schizosaccharomyces pombe. Four of the mutations, not predicted to affect the structure of the BIR fold, clustered together on the N-terminal region that flanks BIR2, suggesting that this is a site of interaction with caspase 3. Introduction of these mutations into full-length XIAP reduced caspase 3 inhibitory activity up to 500-fold, but did not affect its ability to inhibit caspase 9 or interact with the IAP antagonist DIABLO. Furthermore, these mutants retained full ability to inhibit apoptosis in transfected cells, demonstrating that although XIAP is able to inhibit caspase 3, this activity is dispensable for inhibition of apoptosis by XIAP in vivo.

Influence of curing on the adhesive and thermomechanical properties of an applied acrylic polymer.

The objective of the current study was to investigate the relationship between polymer adhesion and post-coating thermal treatment. A novel adhesion technique was used to quantify the adhesive properties of applied acrylic films. Differential scanning calorimetry was used to determine the glass transition temperature of the applied polymer. Post-coating thermal treatment, or curing, was found to significantly influence the adhesive and thermomechanical properties of the applied film coating. Adhesion of triethyl citrate-plasticized films to tablets increased during storage at elevated temperatures, equilibrating within four hours. The glass transition temperature of the applied triethyl citrate-plasticized coatings also increased during curing. Equilibration of polymer properties was found to be dependent on the hydrophobicity of the plasticizer incorporated into the coating formulation, with longer curing times required for films containing the hydrophobic plasticizer tributyl citrate. The curing temperature was shown to influence polymer properties, with stronger film-tablet adhesion and higher glass transition temperatures resulting when the coated tablets were stored at higher temperatures. Substrate hydrophobicity was also found to influence the curing process, suggesting that the mechanisms involved in film formation and polymer-substrate adhesion may contribute to the internal stresses within the film.

Cloning and characterization of the genes encoding the ankyrin repeat and SOCS box-containing proteins Asb-1, Asb-2, Asb-3 and Asb-4.

Members of the suppressor of cytokine signalling (SOCS) family of proteins have been shown to inhibit cytokine signalling via direct interactions with JAK kinases or activated cytokine receptors. In addition to their novel amino-terminal regions and SH2 domains that mediate these interactions, the SOCS proteins also contain carboxy-terminal regions of homology called the SOCS box. The SOCS box serves to couple SOCS proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Several other families of proteins also contain SOCS boxes but differ from the SOCS proteins in the type of domain or motif they contain upstream of the SOCS box. We report here the cloning, characterization, mapping and expression analysis of four members of the ankyrin repeat and SOCS box-containing (Asb) protein family.

Chopper, a new death domain of the p75 neurotrophin receptor that mediates rapid neuronal cell death.

The cytoplasmic juxtamembrane region of the p75 neurotrophin receptor (p75(NTR)) has been found to be necessary and sufficient to initiate neural cell death. The region was named "Chopper" to distinguish it from CD95-like death domains. A 29-amino acid peptide corresponding to the Chopper region induced caspase- and calpain-mediated death in a variety of neural and non-neural cell types and was not inhibited by signaling through Trk (unlike killing by full-length p75(NTR)). Chopper triggered cell death only when bound to the plasma membrane by a lipid anchor, whereas non-anchored Chopper acted in a dominant-negative manner, blocking p75(NTR)-mediated death both in vitro and in vivo. Removal of the ectodomain of p75(NTR) increased the potency of Chopper activity, suggesting that it regulates the association of Chopper with downstream signaling proteins.