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PubMed2002

An analysis of the effects of subjective and objective instruction forms on mock-juries' murder/manslaughter distinctions.

Defendants' emotions at the time of their crimes may potentially serve as mitigating circumstances in murder/manslaughter cases. The present study examined whether differences between two forms of instructions given juries in such cases affected mockjuries' murder/manslaughter distinctions. Jurors' reasons for their verdicts and definitions of murder and manslaughter were also compared. In addition, three factors found to be predictive of murder/manslaughter distinctions in previous research were evaluated. It was found that, though instruction forms affected jurors' stated reasons for their verdicts and their definitions of murder and manslaughter, they did not significantly affect murder/manslaughter distinctions. Defendants were most likely to be convicted of murder if they had a history of violence with the victim and dwelt upon their emotions. We suggest jurors likely construe instructions given them to fit their a priori understandings of murder, manslaughter, and the potentially mitigating role of defendants' emotions.

Adult↗

PubMed2002

Water relations and gas exchange in poplar and willow under water stress and elevated atmospheric CO2.

Predictions of shifts in rainfall patterns as atmospheric [CO2] increases could impact the growth of fast growing trees such as Populus spp. and Salix spp. and the interaction between elevated CO2 and water stress in these species is unknown. The objectives of this study were to characterize the responses to elevated CO2 and water stress in these two species, and to determine if elevated CO2 mitigated drought stress effects. Gas exchange, water potential components, whole plant transpiration and growth response to soil drying and recovery were assessed in hybrid poplar (clone 53-246) and willow (Salix sagitta) rooted cuttings growing in either ambient (350 &mgr;mol mol-1) or elevated (700 &mgr;mol mol-1) atmospheric CO2 concentration ([CO2]). Predawn water potential decreased with increasing water stress while midday water potentials remained unchanged (isohydric response). Turgor potentials at both predawn and midday increased in elevated [CO2], indicative of osmotic adjustment. Gas exchange was reduced by water stress while elevated [CO2] increased photosynthetic rates, reduced leaf conductance and nearly doubled instantaneous transpiration efficiency in both species. Dark respiration decreased in elevated [CO2] and water stress reduced Rd in the trees growing in ambient [CO2]. Willow had 56% lower whole plant hydraulic conductivity than poplar, and showed a 14% increase in elevated [CO2] while poplar was unresponsive. The physiological responses exhibited by poplar and willow to elevated [CO2] and water stress, singly, suggest that these species respond like other tree species. The interaction of [CO2] and water stress suggests that elevated [CO2] did mitigate the effects of water stress in willow, but not in poplar.

Journal Article↗

PubMed1997

Why listeners hear less than they are told: attentional load and the teller-listener extremity effect.

Prior research (T. Gilovich, 1987; M. Inman, A. Reichl, & R. Baron, 1993) indicated that individuals (tellers) who directly observe an actor (on video tape) rate that actor less extremely than other individuals (listeners) who hear the tellers' secondhand accounts of the actor's actions. Evidence has suggested that this teller-listener effect is due at least in part to listeners' failure to encode and consider mitigating circumstances contributing to the actors' actions (Inman et al., 1993). The present research examined several explanations for this phenomenon. Study 1 found stronger teller-listener differences (and less recall of mitigating information) when listeners heard the teller's account in the presence of noise. Studies 2 and 3 found listener's interpretations to be more extreme when the verbal accounts they heard were verbally disorganized. These results support an attentional load explanation for teller-listener differences.

Attention↗

PubMed2003

Less guilty by reason of adolescence: developmental immaturity, diminished responsibility, and the juvenile death penalty.

The authors use a developmental perspective to examine questions about the criminal culpability of juveniles and the juvenile death penalty. Under principles of criminal law, culpability is mitigated when the actor's decision-making capacity is diminished, when the criminal act was coerced, or when the act was out of character. The authors argue that juveniles should not be held to the same standards of criminal responsibility as adults, because adolescents' decision-making capacity is diminished, they are less able to resist coercive influence, and their character is still undergoing change. The uniqueness of immaturity as a mitigating condition argues for a commitment to a legal environment under which most youths are dealt with in a separate justice system and none are eligible for capital punishment.

Adolescent↗

PubMed2003

Effects of energy availability on immediate and delayed emotional reactions to work events.

This study focuses on daily work events as proximal stimuli for discrete emotional reactions and suggests that availability of energy resources required for coping with goal-disruptive events, or for capitalizing on new opportunities offered by goal-enhancing events, influences intensity of emotional reactions. Using experience-sampling methodology with a sample of hospital residents, it is shown that negative emotion and fatigue following disruptive events are intensified when only limited energy resources are available due to current workload. However, positive emotions, promoted by goal-enhancing events, are mitigated due to inability to capitalize on new opportunities or challenges. Aftereffects of work events reveal that the energizing effect of goal-enhancing events mitigates end-of-day fatigue and negative emotion on high-workload days, although the effect of disruptive events is diminished by the end of such days, apparently because of lesser conspicuity against a background of high workload. Theoretical and practical implications are discussed.

Adult↗

PubMed2006

Intentions in teasing: when "just kidding" just isn't good enough.

Teasing is ambiguous. Although the literal content of a tease is, by definition, negative, seldom do teasers intend for their tease to be taken literally. Toward this aim, teasers often attempt to mitigate the negative surface content of the tease by communicating via gesture, facial expression, or tone of voice that they are "just kidding." The research presented here suggests that such attempts often fall on deaf ears. Despite teasers' attempts to mitigate the tease, targets are often unaware of--and unmoved by--the teaser's benign intentions. As a result, teasers and targets systematically differ in their perceptions of teasing: Although it is often seen as innocent and playful by the teaser, it tends to be construed as considerably more malicious by the target.

Adolescent↗

PubMed2000

Culpable control and the psychology of blame.

A culpable control model is advanced to describe the conditions that encourage as well as mitigate blame and to assess the process by which blame and mitigation occur. The fundamental assumptions of the model are that evidence concerning harmful events is scrutinized for its contribution to personal control and spontaneously evaluated for its favorableness or unfavorableness. Spontaneous evaluations encourage a blame-validation mode of processing in which evidence concerning the event is reviewed in a manner that favors ascribing blame to the person or persons who evoke the most negative affect or whose behavior confirms unfavorable expectations. The author delineates the elements of perceived control and then discusses spontaneous evaluation influences on control and blame assessments. The blame-validation process is described next. Finally, the culpable control model is compared with extant theories of blame and responsibility and its basic tenets summarized.

Humans↗

PubMed2025

Design of precision therapeutics for a CKD risk allele by targeting Shroom3-Rock interaction.

Enhancer variants in Shroom3 associate with renal fibrosis (TIF), but with reduced albuminuria. Detailed mechanisms for these pleiotropic effects are unclear. Here, we focus on identifying the specific profibrotic Shroom3 motif and separating this from its anti-proteinuric function. Given the role for Rho-kinases (Rock) in TIF, and the interaction of Rock with Shroom3 ASD2-domain, we hypothesized that Shroom3-mediated Rock-activation is crucial for profibrotic function. To test this, we develop transgenic tools that overexpress wild-type- (WT-Sh3) or ASD2-domain deletion- Shroom3 (ASD2Δ-Sh3). During TIF, Shroom3 and Rock co-expression occur in injured tubular cells and fibroblasts. In tubular- & fibroblast- lines, ASD2Δ-Sh3 overexpression reduce Rock activation, and pro-fibrotic/pro-inflammatory transcripts downstream of TGFβ1/Wnt/Ctnnb1-signaling vs WT-Sh3. In vivo, inducible global-, or tubular-specific-, but not fibroblast-specific-, ASD2Δ-Sh3 overexpression mitigate TIF, vs WT-Sh3 overexpression. Importantly, ASD2Δ-Sh3 mice do not develop albuminuria, while overexpression of a distinct Fyn-binding deficient mutant Shroom3 (FBDM-Sh3) induces albuminuria. We then develop small molecule inhibitors of Shroom3-Rock interaction (P2Is) and confirm Rock inhibition with these agents in WT-Sh3 cell lines. Our lead P2I from these studies, BT1137, mitigates Rock-activation, profibrotic signaling and TIF in WT-Sh3 mice. Hence, we delineate the profibrotic Shroom3 motif and develop therapeutics for kidney disease from Shroom3 excess.

Animals↗

PubMed2026

Chemometric insights into Lactiplantibacillus plantarum effects on onion (Allium cepa L.) metabolism and antidiabetic activity under cadmium stress.

Cadmium (Cd) is a toxic heavy metal that causes severe physiological damage in plants, inhibiting growth and ultimately reducing crop yield. Lactic acid bacteria regulate Cd availability through bioaccumulation and biosorption. This study evaluated the Cd tolerance of Lactiplantibacillus plantarum 10CH by determining its survival capacity under Cd stress and its potential to mitigate Cd-induced stress in onion (Allium cepa L.). The bacterial strain tolerated Cd concentrations up to 100 µM, and whole-genome sequencing identified genes involved in Cd biosorption, accumulation, and efflux. Exposure of onion to increasing CdCl2 concentrations significantly reduced root and shoot biomass. Inoculation with Lb. plantarum 10CH alleviated Cd stress at 100 µM, enhancing root and shoot biomass, reducing Cd accumulation, lowering oxidative damage markers, and stimulating antioxidant enzyme activities. Metabolic profiling revealed that Cd stress significantly reduced primary metabolites and amino acids, particularly at 100 µM, while bacterial inoculation restored key amino acids and peptides, including arginine, tyrosine, and glutamic acid. Chemometric analysis using unsupervised (PCA) and supervised (OPLS-DA) models revealed clear metabolite variation among untreated, Cd-stressed, and bacterial inoculated Cd-stressed onion leaves. Furthermore, leaf extracts exhibited α-glucosidase inhibitory activity, with the highest activity in control plants (IC50 = 425.2 ± 0.5 µg/mL). Cd-stressed plants showed moderate antidiabetic activity, which was significantly reduced by bacterial inoculation. Overall, these findings demonstrate that Lb. plantarum 10CH can survive under Cd stress and alleviates Cd-induced stress in onion, highlighting its potential as a bioinoculant to mitigate heavy metal stress.

Onions↗

PubMed1998

Increased susceptibility of gastric mucosa to ulcerogenic stimulation in diabetic rats--role of capsaicin-sensitive sensory neurons.

1. We examined the gastric mucosal blood flow (GMBF) and ulcerogenic responses following barrier disruption induced by sodium taurocholate (TC) in diabetic rats and investigated the role of capsaicin-sensitive sensory neurons in these responses. 2. Animals were injected streptozotocin (STZ: 70 mg kg(-1), i.p.) and used after 5, 10 and 15 weeks of diabetes with blood glucose levels of > 350 mg dl(-1). The stomach was mounted on an ex-vivo chamber under urethane anaesthesia and exposed to 20 mM TC plus 50 mM HCl for 30 min in the presence of omeprazole. Gastric transmucosal potential difference (PD), GMBF, and luminal acid loss (H+ back-diffusion) were measured before and after exposure to 20 mM TC, and the mucosa was examined for lesions 90 min after TC treatment. 3. Mucosal application of TC caused PD reduction in all groups; the degree of PD reduction was similar between normal and diabetic rats, although basal PD values were lower in diabetic rats. In normal rats, TC treatment caused luminal acid loss, followed by an increase of GMBF, resulting in minimal damage in the mucosa. 4. The increased GMBF responses associated with H+ back-diffusion were mitigated in STZ-treated rats, depending on the duration of diabetes, and severe haemorrhagic lesions occurred in the stomach after 10 weeks of diabetes. 5. Intragastric application of capsaicin increased GMBF in normal rats, but such responses were mitigated in STZ diabetic rats. The amount of CGRP released in the isolated stomach in response to capsaicin was significantly lower in diabetic rats when compared to controls. 6. The deleterious influences on GMBF and mucosal ulcerogenic responses in STZ-diabetic rats were partially but significantly antagonized by daily insulin (4 units rat(-1)) treatment. 7. These results suggest that the gastric mucosa of diabetic rats is more vulnerable to acid injury following barrier disruption, and this change is insulin-sensitive and may be partly accounted for by the impairment of GMBF response associated with acid back-diffusion and mediated by capsaicin-sensitive sensory neurons.

Animals↗

PubMed1998

Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation.

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.

Adult↗

PubMed1999

Pre-treatment of transplant bone marrow cells with hydrocortisone and cyclosporin A alleviates graft-versus-host reaction in a murine allogeneic host-donor combination.

The aim of the study was to alleviate graft-versus-host reaction (GVHR) by pre-treatment of the bone marrow (BM) transplant with hydrocortisone (HC) and cyclosporin A (CsA) in C57BL/6J (donor) --> CBA/J (recipient) mouse combination. BM cells were exposed to HC and CsA for 1 h at 37 degrees C and then injected into lethally irradiated (9.5 Gy) mice at a dose of 2 x 10(6) BM cells/mouse. Haematopoietic recovery was assessed on day 12, and survival was followed for 100 days. Combinations of 1000 microg/ml HC and 100 microg/ml CsA, and 100 microg/ml HC and 10 microg/ml CsA significantly reduced MLR and additively mitigated GVHR in vivo, achieving 40% and 26% survival rates, respectively. However, HC and CsA altered neither the peripheral blood cell counts nor in vitro and in vivo BM cell clonogenic potential. Additional studies have shown that HC and CsA blocked con A-driven differentiation of CD8+ and CD4+ CD8+ lymph node cells (LNC) and progression of LNC to S + G2/M cell cycle phases, and inhibited IL-1, IL-2 and TGF-beta while enhancing GM-CSF gene expression in BM cells. Taken together, these data indicate that the pre-treatment of the BM transplant with HC and CsA results in inactivation of GVHR effector cells and mitigation of GVHR while sparing BM repopulating capacity.

Animals↗

PubMed2002

Role of microecology in chronic inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are chronic conditions of unknown etiology. Current therapy mitigates the severity of acute bouts of mucosal inflammation but an eradication therapy is lacking. Growing incidence of IBD is associated with social development. Epidemiology suggests a relationship between the establishment of the individual gut flora and the risk of developing IBD. Patients show an impaired tolerance towards commensal bacteria of the resident flora. Unrestrained activation of the intestinal immune system against some commensal bacteria appears to be responsible for the characteristic relapsing course of these diseases. Wide-spectrum antibiotic therapy reduces bacterial load and mitigates intestinal inflammation in human IBD and in animal models. Current research aims at the identification of probiotics for bacterial antagonism therapies. Probiotics are living microorganisms which upon ingestion in certain numbers exert health benefits beyond inherent basic nutrition. Colonization with a Lactobacillus reuteri strain can prevent the development of colitis in genetically susceptible mice. Other studies have used a bacterium genetically engineered to secrete the antiinflammatory cytokine IL-10 and demonstrated a therapeutic effect in animal models of colitis. Moreover, some probiotics may naturally exhibit antiinflammatory properties when interacting with the human gut mucosa. Prebiotics such as inulin have also been shown to prevent colonic inflammation in animal models. Preliminary clinical trials with probiotics in IBD are encouraging. Probiotics offer a valuable tool for the prevention and control of inflammatory bowel diseases.

Animals↗

PubMed1999

Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice.

OBJECTIVE: To test the hypothesis that nicotine not only activates uncoupling protein1 (UCP1) in brown adipose tissue (BAT), but also induces UCP1 in white adipose tissue (WAT), which contributes to the mitigation of obesity in obese mice. DESIGN: Weights of the whole body, the gastrocnemius muscle, interscapular BAT and subcutaneous and retroperitoneal WAT, food intake and the mRNA and protein of UCP1 in these tissues were measured and immunohistochemistry using antiserum against UCP1 was also performed in obese yellow KK mice treated with nicotine for 6 months and control mice treated with physiological saline. RESULTS: Obese mice treated with nicotine for 6 months, compared with those injected with saline, weighed significantly less (P < 0.01) and had smaller subcutaneous and retroperitoneal WAT pads (P < 0.01), while obese mice that received nicotine ate less (P < 0.05) than those injected with saline. In mice treated with nicotine, the mRNA and protein of UCP1 was detected not only in BAT, but also in subcutaneous and retroperitoneal WATs. Immunohistochemically, the BAT of obese mice contained large lipid droplets and appeared rather WAT-like, but changed to typical brown adipocytes after nicotine treatment. The fat pads of nicotine-treated mice contained many multilocular cells that were positive for UCP1. CONCLUSION: Nicotine not only activates UCP1 in BAT, but also induces UCP1 in WAT and decreases food intake, which contributes to the mitigation of obesity.

Adipocytes↗

PubMed2025

Retinal hypoxia reversal with PLGA-oxygen nanobubbles.

Pathologies associated with retinal hypoxia, including diabetic retinopathy, central/branch retinal artery occlusion (CRAO/BRAO), central/branch retinal vein occlusion (CRVO/BRVO), retinopathy of prematurity, sickle cell retinopathy, etc., have limited effective therapeutic intervention strategies. To address this shortcoming, herein we propose a biocompatible and biodegradable poly (lactic-co-glycolic acid) shell-based oxygen nanobubbles (PLGA-ONBs) platform, formulated with PLGA, polyvinyl alcohol (PVA), and NaHCO3. The formulation of a novel PLGA-ONBs was proposed, and the synthesis process was optimized with respect to dependent (sonication power, PVA, and NaHCO3 concentrations) and response (hydrodynamic diameter and oxygen capacity) variables. The optimized formulation has a concentration of (13.8 ± 0.01) × 1010 particles per ml with a hydrodynamic diameter of 142.83 ± 11.46 nm, and oxygen loading capacity of 47.2 ± 2.4 mg L-1. After 4 weeks of storage, the ONBs were found to have an oxygen concentration of 38.9 ± 2.9 mg L-1, indicating excellent oxygen retention capability. The PLGA-ONBs tested in vitro in Muller and R28 retinal cell lines demonstrated excellent biocompatibility and potential to mitigate hypoxia. In addition, the PLGA-ONBs treatment on hypoxic cells demonstrated restoration of mRNA expression of three key hypoxic genes (HIF-1α, PAI-1, and VEGF-A) to normoxic states, indicating hypoxia reversal potential. Biosafety of the PLGA-ONBs was demonstrated in a rabbit model, demonstrating promise in clinical translation. The PLGA-ONBs developed exhibited excellent oxygen loading and retention, potential in hypoxia mitigation, and a safety profile that could be a promising route to treating ischemic diseases of the eye.

Polylactic Acid-Polyglycolic Acid Copolymer↗

PubMed2001

A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist.

Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP receptor (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling system may exert important paracrine and/or autocrine functions, such as in hair growth control. Chemotherapy-induced alopecia - one of the fundamental unsolved problems of clinical oncology - is driven in part by defined abnormalities in hair follicle cycling. We have therefore explored the therapeutic potential of a PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a mouse model of cyclophosphamide-induced alopecia. Intraperitoneal administration of the agonist PTH(1-34) or the antagonists PTH(7-34) and PTHrP(7-34) significantly altered the follicular response to cyclophosphamide in vivo. PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the degree of follicle damage and retarding the onset of cyclophosphamide-induced alopecia. PTH(1-34), in contrast, forced hair follicles into "dystrophic catagen", associated with enhanced intrafollicular apoptosis. We had previously shown that an induced shift in the follicular damage-response towards "dystrophic catagen" mitigates cyclophosphamide-induced alopecia, whereas a shift towards "dystrophic catagen" initially enhanced the hair loss, yet subsequently promoted accelerated hair follicle recovery. Therefore, this study in an established animal model of chemotherapy-induced alopecia, which closely mimics human chemotherapy-induced alopecia, strongly encourages the exploration of PTH/PTHrP-R agonists and antagonists as novel therapeutic agents in chemotherapy-induced alopecia.

Alopecia↗

PubMed2000

Influence of environmental factors on virus detection by RT-PCR and cell culture.

The effects of clay, humic acid, u.v. light and shellfish tissue residues on the detection of poliovirus type 2 from environmental samples by culture and RT-PCR were investigated. RT-PCR showed 10-100 times greater sensitivity for PV2 detection in the absence of sample contaminants than did culture by plaque assay in BGM cell monolayers. Bentonite clay (100-1000 mg l-1) and shellfish tissue residues reduced virus detection by plaque assay, but the effect of bentonite was mitigated by simple elution procedures. Bentonite clay, humic acid (5-150 mg l-1) and mussel tissue reduced virus detection by RT-PCR by between 1 and 8 logs, although this was mitigated in part by elution and Sephadex filtration of extracts. Sephadex filtration of samples reduced culturable PV2 by 32-50%. Exposure of PV2 in water to u.v. light reduced culturability of PV2 but not detection by RT-PCR. This study demonstrates that virus detection in environmental samples is strongly influenced by naturally occurring substances and disinfection approaches. The accuracy of results of viral analyses of this nature should be carefully scrutinized with respect to sample constituents.

Animals↗

PubMed1996

Antibabesial effect of the immunomodulator AS101 in mice: role of increased production of nitric oxide.

The immunomodulator AS101 has been shown to induce cell proliferation and to increase the secretion of a variety of cytokines. In the present study we evaluated the effect of AS101 on the pathogenicity of B. rodhaini infected mice. In order to clarify its mechanism of action we studied the ability of AS101 to activate neutrophils and macrophages, both of which inhibit parasite growth. More specifically, we studied the ability of AS101 to induce secretion of nitric oxide (NO). We found that AS101 protects mice from babesiosis in a time and dose dependent manner. At 10 and 20 micrograms/injection, two weeks prior to parasites, AS101 significantly increased the number of neutrophils and more than doubled the survival rate of infected mice. Similarly, at these concentrations when injected one month, or at 20 micrograms, injected 24 h before parasites. AS101 mitigated the course of infection and reduced by half the peak of parasitaemia. At 0.1 microgram/ml AS101 induced the secretion of significantly higher levels of NO in vitro than control. This was abrogated by adding the NO synthase inhibitor. NG-monomethyl-L-arginine. In vivo the antiparasitic protection of AS101 was abrogated by another NO synthase inhibitor, aminoguanidine. We found that AS101, partly by elevating levels of NO, can significantly mitigate the course of infection and thus increase survival, and may therefore be proven as an effective antiparasitic drug.

Adjuvants, Immunologic↗