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result(s) for
"Malia, R"
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Does plant apparency matter? Thirty years of data provide limited support but reveal clear patterns of the effects of plant chemistry on herbivores
by
R. Malia Fincher
,
Lee A. Dyer
,
Angela M. Smilanich
in
Adaptation, Physiological
,
Bayes Theorem
,
Bayesian meta‐analysis
2016
According to the plant-apparency hypothesis, apparent plants allocate resources to quantitative defenses that negatively affect generalist and specialist herbivores, while unapparent plants invest more in qualitative defenses that negatively affect nonadapted generalists. Although this hypothesis has provided a useful framework for understanding the evolution of plant chemical defense, there are many inconsistencies surrounding associated predictions, and it has been heavily criticized and deemed obsolete.
We used a hierarchical Bayesian meta-analysis model to test whether defenses from apparent and unapparent plants differ in their effects on herbivores. We collected a total of 225 effect sizes from 158 published papers in which the effects of plant chemistry on herbivore performance were reported.
As predicted by the plant-apparency hypothesis, we found a prevalence of quantitative defenses in woody plants and qualitative defenses in herbaceous plants. However, the detrimental impacts of qualitative defenses were more effective against specialists than generalists, and the effects of chemical defenses did not significantly differ between specialists and generalists for woody or herbaceous plants.
A striking pattern that emerged from our data was a pervasiveness of beneficial effects of secondary metabolites on herbivore performance, especially generalists. This pattern provides evidence that herbivores are evolving effective counteradaptations to putative plant defenses.
Journal Article
Preclinical assessment of MAGMAS inhibitor as a potential therapy for pediatric medulloblastoma
2024
Medulloblastoma is the most common malignant brain tumor in children. It has WNT-driven, SHH-driven/ TP53 mutant, SHH-driven/ TP53 wildtype, and non-WNT/non-SHH subgroups. MAGMAS (Mitochondrial Associated Granulocyte Macrophage colony-stimulating factor Signaling molecules) encodes a mitochondrial import inner membrane translocase subunit and is responsible for the translocation of matrix proteins across the inner membrane. We previously reported that a small molecule MAGMAS inhibitor, BT9, decreases cell proliferation, migration, and oxidative phosphorylation in adult glioblastoma cell lines. The aim of our study was to investigate whether the chemotherapeutic effect of BT9 can be extended to pediatric medulloblastoma. Methods: DAOY (SHH driven/tp53 mutant) and D425 (non-SHH group 3) were treated with BT9. For in vitro analysis, cell proliferation, death, migration, invasion, and metabolic activity were assessed using MTT assay, TUNEL staining, scratch wound assay, Matrigel invasion chambers, and seahorse assay, respectively. A D425 orthotopic xenograft mouse model was used to evaluate BT9 efficacy in vivo . Results: BT9 treatment resulted in a significant decrease in cell proliferation (DAOY, 24 hours IC50: 3.6 μM, 48 hours IC50: 2.3 μM, 72 hours IC50: 2.1 μM; D425 24 hours IC50: 3.4 μM, 48 hours IC50: 2.2 μM, 72 hours IC50: 2.1 μM) and a significant increase in cell death (DAOY, 24 hours p = 0.0004, 48 hours p<0.0001; D425, 24 hours p = 0.0001, 48 hours p = 0.02). In DAOY cells, 3 μM BT9 delayed migration and significantly reduced DAOY and D425 cell invasion (p < 0.0001). It also modified mitochondrial respiratory function in both medulloblastoma cell lines. Compared to control, however, BT9 administration did not improve survival in a D425 orthotopic xenograft mouse model. Conclusions: Our in vitro data showed BT9 antitumor efficacy in DAOY and D425 cell lines, suggesting that BT9 may represent a promising targeted therapeutic in pediatric medulloblastoma. These data, however, need to be further validated in animal models.
Journal Article
Traffic management of intersection with more than four road segments
2019
Simpang Tujuh Ulee Kareng is one of the intersection that are crowded by local people who always doing movement in this area. The method of this research to calculated level of service this intersection by using SIDRA Intersection as a software, then it will merger of intersection be four road segments. The result and discussion of this intersection for existing condition based on Degree of Saturation (DS) for JD's street is F. DS for TICI's street is A. DS for LG's street is A, DS for LR's street is B, DS for MT's street is A, DS for KR's street is C, and DS for TIBPKP's street is D. After the geometric merger into four road segments in unsignalized condition, DS for JD's street and TIBPKP's street is E, DS for TICI's street is A, DS for LG's street and LR's street is F, and DS for MT's street and KR's street is F. For signalized condition, DS for JD's street merger with TIBPKP's street is E, DS for TICI's street is E, DS for LG's street merger with LR's street is E, and DS for MT's street merger with KR's street is F.
Journal Article
Developing community-based preventive interventions in Hong Kong: a description of the first phase of the family project
by
Stewart, Sunita M
,
Fabrizio, Cecilia S
,
Hirschmann, Malia R
in
Acceptability
,
Adolescent
,
Biostatistics
2012
Background
This paper describes the development of culturally-appropriate family-based interventions and their relevant measures, to promote family health, happiness and harmony in Hong Kong. Programs were developed in the community, using a collaborative approach with community partners. The development process, challenges, and the lessons learned are described. This experience may be of interest to the scientific community as there is little information currently available about community-based development of brief interventions with local validity in cultures outside the West.
Methods
The academic-community collaborative team each brought strengths to the development process and determined the targets for intervention (parent-child relationships). Information from expert advisors and stakeholder discussion groups was collected and utilized to define the sources of stress in parent-child relationships.
Results
Themes emerged from the literature and discussion groups that guided the content of the intervention. Projects emphasized features that were appropriate for this cultural group and promoted potential for sustainability, so that the programs might eventually be implemented at a population-wide level. Challenges included ensuring local direction, relevance and acceptability for the intervention content, engaging participants and enhancing motivation to make behavior changes after a brief program, measurement of behavior changes, and developing an equal partner relationship between academic and community staff.
Conclusions
This work has public health significance because of the global importance of parent-child relationships as a risk-factor for many outcomes in adulthood, the need to develop interventions with strong evidence of effectiveness to populations outside the West, the potential application of our interventions to universal populations, and characteristics of the interventions that promote dissemination, including minimal additional costs for delivery by community agencies, and high acceptability to participants.
Journal Article
A Brief Parenting Intervention to Enhance the Parent–Child Relationship in Hong Kong: Harmony@Home
by
Hirschmann, Malia R.
,
Stewart, Sunita M.
,
Lam, Tai Hing
in
Acceptability
,
Adolescents
,
Asian culture
2013
There is a dearth of high-level evidence for brief programs designed to promote positive parent–child relationships in nonwestern cultures. We present a pilot randomized controlled trial of a four-session intervention to enhance the parenting skills that promote a positive relationship with pre-adolescent children in Hong Kong. Our intervention, Harmony@Home, utilized Cunningham’s culturally appropriate coping modeling, problem-solving approach to change parental behavior. Our objective was to evaluate the feasibility, acceptability and initial evidence of benefit of the intervention. We blindly randomized 150 Hong Kong parents of children 10–13 years of age to (a) a Harmony@Home intervention group, (b) a waitlist control group, or (c) a third active intervention which shared the control group. Immediately following the intervention, we report increases in satisfaction with the parent–child relationship, one of the targeted parenting behaviors and family harmony, for the Harmony@Home group versus control group. However, only the results from satisfaction with the parent–child relationship were significant at 3-months post intervention. Most respondents reported high levels of program satisfaction. The results provide preliminary evidence that this parenting intervention is culturally acceptable for a nonwestern general population, is feasible for implementation in a community setting and shows evidence of benefit. This intervention is concordant with public health priorities because of the global importance of the parent–child relationship as a protective factor for adolescent outcomes, the need for culturally-appropriate interventions for nonwestern populations, and design characteristics that promote dissemination.
Journal Article
Bringing scientific rigor to community-developed programs in Hong Kong
2012
Background
This paper describes efforts to generate evidence for community-developed programs to enhance family relationships in the Chinese culture of Hong Kong, within the framework of community-based participatory research (CBPR).
Methods
The CBPR framework was applied to help maximize the development of the intervention and the public health impact of the studies, while enhancing the capabilities of the social service sector partners.
Results
Four academic-community research teams explored the process of designing and implementing randomized controlled trials in the community. In addition to the expected cultural barriers between teams of academics and community practitioners, with their different outlooks, concerns and languages, the team navigated issues in utilizing the principles of CBPR unique to this Chinese culture. Eventually the team developed tools for adaptation, such as an emphasis on building the relationship while respecting role delineation and an iterative process of defining the non-negotiable parameters of research design while maintaining scientific rigor. Lessons learned include the risk of underemphasizing the size of the operational and skills shift between usual agency practices and research studies, the importance of minimizing non-negotiable parameters in implementing rigorous research designs in the community, and the need to view community capacity enhancement as a long term process.
Conclusions
The four pilot studies under the FAMILY Project demonstrated that nuanced design adaptations, such as wait list controls and shorter assessments, better served the needs of the community and led to the successful development and vigorous evaluation of a series of preventive, family-oriented interventions in the Chinese culture of Hong Kong.
Journal Article
Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal and heparin-treated antiphospholipid syndrome pregnancies
by
Mackie, I
,
Kingdom, J
,
Farquharson, R
in
Antibodies, Antiphospholipid - blood
,
Anticoagulants - administration & dosage
,
antiphospholipid syndrome
2002
Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombosis and recurrent miscarriage. We assessed levels of coagulation activation markers and aPL during normal pregnancy and in women with the antiphospholipid syndrome (aPS). Fluctuations in aPL levels were observed in all patients with aPS. No particular pattern of antibody positivity, or fluctuation in aPL level, was associated with poor pregnancy outcome. A significant increase was observed in levels of factor Xlla (FXIIa; P < 0.001), factor VIIa (FVIIa, P < 0.001), thrombin antithrombin complexes (TAT; P < 0.001), prothrombin fragment F1.2 (F1.2; P < 0.001) and D-dimer (DD; P < 0.05) during normal pregnancy. Factor VIIa, TAT, F1.2 and DD increased significantly before 20 weeks gestation, while a statistically significant increase in FXIIa levels was first detected between weeks 20 and 30 of gestation. In pregnant women with aPS, increases in FXIIa were similar to those in normal pregnancy, but increased FVIIa levels were not observed until after 30 weeks gestation. Similar to normal pregnancy, increased levels of TAT and F1.2 were detected in aPS pregnancies before 20 weeks gestation, but increased DD were not observed until after week 20. Surprisingly, women with aPS receiving low molecular weight heparin prophylaxis had significantly higher (P = 0.02) levels of TAT (median 8.6; interquartile range (IQR) 6.5-20.8) between weeks 20 and 30 of gestation compared to the normal pregnant population (median 5.9; IQR 4.7-7.9), thus indicating increased thrombin generation in women with aPS in mid-pregnancy.
Journal Article
White Rage in America: An Overview from a Depth Perspective
2022
The purpose of this research is to explore the following question: What are the factors that give rise to white violence? A hermeneutic methodology was employed. This study finds that the aggressive and violent behaviors of the white collective in the United States are the result of cultural complexes, trauma, denial of the feminine principle in favor of the masculine approach, the problem of power and how it leads to othering, and archetypal possession by the Germanic god Wotan.
Dissertation
Preclinical assessment of MAGMAS inhibitor as a potential therapy for pediatric medulloblastoma
by
Bautista, Malia R
,
Fowler, Christie D
,
Lepe, Javier J
in
Animal models
,
Antitumor activity
,
Brain tumors
2024
Medulloblastoma, the most common pediatric brain malignancy, has Sonic Hedgehog (SHH) and non-SHH group3 subtypes. MAGMAS (Mitochondrial Associated Granulocyte Macrophage colony-stimulating factor Signaling molecules) encode for mitochondrial import inner membrane translocase subunit and is responsible for translocation of matrix proteins across the inner membrane. We previously reported that a small molecule MAGMAS inhibitor, BT9, decreases cell proliferation, migration, and oxidative phosphorylation in adult glioblastoma cell lines. The aim of our study was to investigate whether the chemotherapeutic effect of BT9 can be extended to pediatric medulloblastoma.
Multiple in vitro assays were performed using human DAOY (SHH activated tp53 mutant) and D425 (non-SHH group 3) cells. The impact of BT9 on cellular growth, death, migration, invasion, and metabolic activity were quantified using MTT assay, TUNEL staining, scratch wound assay, Matrigel invasion chambers, and seahorse assay, respectively. Survival following 50mg/kg BT9 treatment was assessed
in immunodeficient mice intracranially implanted with D425 cells.
Compared to control, BT9 treatment led to a significant reduction in medulloblastoma cell growth (DAOY, 24hrs IC50: 3.6uM, 48hrs IC50: 2.3uM, 72hrs IC50: 2.1uM; D425 24hrs IC50: 3.4uM, 48hrs IC50: 2.2uM, 72hrs IC50: 2.1uM) and a significant increase in cell death (DAOY, 24hrs p=0.0004, 48hrs p<0.0001; D425, 24hrs p=0.0001, 48hrs p=0.02). In DAOY cells, 3uM BT9 delayed migration, and significantly decreased DAOY and D425 cells invasion (p < 0.0001). Our
study, however, did not extend survival in xenograft mouse model of group3 medulloblastoma compared to vehicle-treated controls.
Our
data showed BT9 antitumor efficacy in DAOY and D425 cell lines suggesting that BT9 may represent a promising targeted therapeutic in pediatric medulloblastoma. These data, however, need to be further validated in animal models.
Journal Article
Potentially prothrombotic abnormalities of coagulation in benign intracranial hypertension
by
Malia, R
,
Leach, M
,
Davies-Jones, G A
in
Biological and medical sciences
,
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
,
Medical sciences
1997
OBJECTIVE: Benign intracranial hypertension (BIH) may be caused by intracranial venous sinus thrombosis. Cerebral angiograms may, however, be normal in patients with BIH that are associated with conditions with an increased risk of venous thrombosis. This raises the possibility that unrecognised non-occlusive venous thrombus might impede CSF drainage. This study therefore examined the strength of the association between risk factors for thrombosis and BIH. METHODS: The incidence of prothrombotic abnormalities among a mixed prospectively and retrospectively investigated cohort of 38 patients with BIH, was compared with healthy obese subjects, and patients with other neurological diseases. Prothrombotic abnormalities investigated included anticardiolipin antibodies, lupus anticoagulant, antithrombin III, proteins C and S, plasma fibrinogen, kaolin cephalin clotting time, prothrombin time, and full blood counts. RESULTS: Evidence for the presence of an antiphospholipid antibody was found in 32% of cases. Cases of familial deficiency of antithrombin III, thrombocytosis, and polycythaemia were also noted. Additionally, an increased concentration of plasma fibrinogen was found in 26%. A coagulation abnormality was more often detectable in those subjects with normal or low body mass index and in those tested within six months of onset. CONCLUSION: There is a thrombotic pathogenesis in some cases of BIH.
Journal Article