Afterthoughts | Complexities of Potency

Afterthoughts to themed perspectives on Complexities of Potency

Actions of Agonists, Fipronil and Ivermectin on the Predominant In Vivo Splice and Edit Variant (RDLbd, I/V) of the Drosophila GABA Receptor Expressed in Xenopus laevis Oocytes

Ionotropic GABA receptors are the targets for several classes of insecticides. One of the most widely-studied insect GABA receptors is RDL (resistance to dieldrin), originally isolated from Drosophila melanogaster. RDL undergoes alternative splicing and RNA editing, which influence the potency of GABA. Most work has focussed on minority isoforms. Here, we report the first characterisation of the predominant native splice variant and RNA edit, combining functional characterisation with molecular modelling of the agonist-binding region. The relative order of agonist potency is GABA> muscimol> TACA> β-alanine. The I/V edit does not alter the potency of GABA compared to RDLbd. Docking calculations suggest that these agonists bind and activate RDLbdI/V through a similar binding mode. TACA and β-alanine are predicted to bind with lower affinity than GABA, potentially explaining their lower potency, whereas the lower potency of muscimol and isoguvacine cannot be explained structurally from the docking calculations. The A301S (resistance to dieldrin) mutation reduced the potency of antagonists picrotoxin, fipronil and pyrafluprole but the I/V edit had no measurable effect. Ivermectin suppressed responses to GABA of RDLbdI/V, RDLbd and RDLbdI/VA301S. The dieldrin resistant variant also showed reduced sensitivity to Ivermectin. This study of a highly abundant insect GABA receptor isoform will help the design of new insecticides

Medicinal Mandala: Potency in Spatiality

This article explores the complexities of accomplishing potency, nüpa (nus pa), within a Tibetan healing, rejuvenation, and longevity ritual practice known as ‘medicinal accomplishment,’ mendrup (sman sgrub). The study is based on the observation and examination of the Light-Swirled Mendrup performed in the Tibetan exile Bonpo community in Nepal in 2012. The mendrup represents a meditative sādhana practice, which involves the production and consecration of ritual materia medica derived from the Tibetan medical Sowa Rigpa tradition as well as Buddhist tantric heritage. The article analyzes the generation of potency based on spatiality within the mendrup ritual—the potency of the ritual itself and of its main substance, the consecrated ritual materia medica referred to as ‘mendrup medicine.’ It argues that within its cosmological scheme, the mendrup ritual follows a spatial pattern of categorization of substances that impacts their potency based on their pharmacological properties and effects. This categorization reflects the ritual’s categorization of diseases. The ritual incorporates various spheres of knowledge into its notions of potency, such as medicine, pharmacy, and botany. The organizational cosmological scheme of the ritual, with its central mandala comprising the five directions and the five fundamental elements, structures the space of the ritual, and also its consecrated medicines. The scheme structures and generates the potency of the ‘mendrup medicine’ substance. Other aspects co-create the potency: the deities invoked, the acting religious figures and their blessings, suitable medicinal ingredients used, the right ‘fermenting agent,’ the depth of meditation of the performers, proper empowerment practices, and the time and space of the rite. This study shows that it is also the allocation of specific substances into particular spatial arrangements that makes them potent, especially in relation to the whole of the ritual space. The Bonpo Light-Swirled Mendrup creates this structure of potency through its fivefold mandalic scheme typical of tantric ritual

Are Potency and Actuality Compatible in Aristotle?

The belief that Aristotle opposes potency (dunamis) to actuality (energeia or entelecheia) has gone untested. This essay defines and distinguishes forms of the Opposition Hypothesis—the Actualization, Privation, and Modal—examining the texts and arguments adduced to support them. Using Aristotle’s own account of opposition, the texts appear instead to show that potency and actuality are compatible, while arguments for their opposition produce intractable problems. Notably, Aristotle’s refutation of the Megarian Identity Hypothesis applies with equal or greater force to the Opposition Hypothesis. For Aristotle, then, potency and actuality are compatible

The Use Of Coastal Potency In Learning Mathematics To Enhance Social Skills Of Junior Secondary School Students

Social skills of junior secondary school students in coastal area are still considered low due to the lack of interaction in mathematics learning. Interaction in coastal class can be done by using coastal potency problem. The objective of this study is to enhance students’ social skills by using coastal potency in learning of mathematics (CCTL). Junior secondary school sample is randomly selected from 10 classes in SMPN 5 Kendari. Two classes are randomly selected from the school sample, experiment class (CCTL) and control class (conventional teaching and learning, CVTL). Instrument that was used in this research is scale of social skills. Data are analyzed by using a qualitative-descriptive technique, one-sample T test, and independent-sample T test. Based on the result of data analysis, it can be concluded that the use of CCTL is significantly better than CVTL in enhancing the students’ social skills, however it’s still in the medium category. Keywords: coastal potency, social skills, coastal potency-based contextual teaching and learning (CCTL

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

BackgroundCompounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products.Hypothesis/objectivesThe initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies.AnimalsThirty-seven dogs treated with FDA-approved or compounded lomustine.MethodsDogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection.ResultsTwenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration.Conclusions and clinical importanceThese data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products

STUDI POTENSI TOLERANSI ISOLAT FUNGI LIMBAH COMBERAN \ud TERHADAP DETERGEN, SABUN MANDI DAN SABUN COLEK KAWASAN \ud PADAT HUNI DI KOTA MALANG

Detergent and Soap is cleanser of sintetic having negative impact to health either through is direct (physical contact) and also indirectly (residing in nature or environment in the form of waste). This research aim to to know chosen fungi isolate which most have lenient potency to detergent, toilet soap and soap of colek. This process is started with insulation of fungi of waste nature, namely waste of comberan by using selective media CZAPEK.DOX.AGAR fungi. found Isolate [is] later;then given letter code and number, namely B1, B2, B3,.....etc, where (B=Fungi, \ud 1,2,3...=jenis to). [Gift/ giving] of code pursuant to difference of characteristic of makroskopis and [is] microscopic the than fungi isolate. From 21 type of isolate found by isolate of rank pursuant to amount of colony many, chosen so that 7 isolate which later; then referred with \ud chosen isolate. ideally functioning soap and detergent as cleaner and also antiseptic and disinfectant to microorganisme specially fungi, but result of insulation indicate that there are fungi which not die, so that assumed by the fungi isolate lenient and can elaborate third the materials in nature. Research type the used is descriptive with approach of laboratory, where this \ud research aim to for description concerning lenient potency of chosen fungi isolate to detergent, toilet soap and soap of colek, later; then to know the tolerance potency test by using detergent, toilet soap and soap clean concentration 25%, 50%, 75% and 95%. Smaller assess zona diameter \ud pursue {progressively come near zero ( 0)}, hence is ever greater of its tolerance potency Result of research indicate that: (1) Pursuant to range assess zona diameter pursue smallestly, hence most isolate have potency to be lenient to detergent is B8 isolate, isolate having potency \ud most lenient to toilet soap is B4 isolate, while most isolate have lenient potency to soap of colek is B19 isolate. ( 2) Storey;Level resilience of isolate fungi, to detergent: B8, B21, B2, B4, B16, B19 and of B13, for the toilet soap of: B4, B19, B16, B13, B21, B2, and B8, while soap of colek:\ud B19, B13, B8, B2, B21, B4, and B16. found of lenient fungi isolate to detergentt, toilet soap and soap of colek, can give information in area of microbiological science in the effort yielding product of inokulum microbe capable to pregnant waste degredate third disinfectant type and \ud antiseptic

Evaluating frequency and quality of pathogen-specific T cells.

It is generally accepted that enumeration and characterization of antigen-specific T cells provide essential information about potency of the immune response. Here, we report a new technique to determine the frequency and potency of antigen-specific CD8 T cells. The assay measures changes of intracellular Ca(2+) in real time by fluorescent microscopy in individual CD8 T cells responding to cognate peptides. The T cells form continuous monolayer, enabling the cells to present the peptides to each other. This approach allows us to evaluate the kinetics of intracellular Ca(2+) signalling that characterizes the quality of T cell response. We demonstrate the usefulness of the assay examining the frequency and quality of cytomegalovirus-specific CD8 T cells from healthy donor and patient after haploidentical stem cell transplantation. The new assay has a potential to provide essential information determining the status of the immune system, disease morbidity, potency of therapeutic intervention and vaccine efficacy