The Search for Invariance: Repeated Positive Testing Serves the Goals of Causal Learning

Positive testing is characteristic of exploratory behavior, yet it seems to be at odds with the aim of information seeking. After all, repeated demonstrations of one’s current hypothesis often produce the same evidence and fail to distinguish it from potential alternatives. Research on the development of scientific reasoning and adult rule learning have both documented and attempted to explain this behavior. The current chapter reviews this prior work and introduces a novel theoretical account—the Search for Invariance (SI) hypothesis—which suggests that producing multiple positive examples serves the goals of causal learning. This hypothesis draws on the interventionist framework of causal reasoning, which suggests that causal learners are concerned with the invariance of candidate hypotheses. In a probabilistic and interdependent causal world, our primary goal is to determine whether, and in what contexts, our causal hypotheses provide accurate foundations for inference and intervention—not to disconfirm their alternatives. By recognizing the central role of invariance in causal learning, the phenomenon of positive testing may be reinterpreted as a rational information-seeking strategy

Sinteza i biološko djelovanje novih supstituiranih derivata tiazolin-kinolina

5-Acyl-8-hydroxyquinoline-2-(3\u27-substituted-4\u27-aryl-2,3-dihydrothiazol-2\u27-ylide- ne)hydrazones, 5a-e to 10a-c, were prepared by the reaction of the appropriate 5-acyl-8-hydroxyquinoline-4-substituted thiosemicarbazones 3a-e and phenacyl bromides 4a-e. Structures of the new compounds were verified on the basis of spectral and elemental analyses. Twenty-eight new compounds were tested for their possible antimicrobial activities. Most of the tested compounds showed weak to moderate antibacterial activity against most of the bacterial strains used in comparison with gatifloxacin as a reference drug. The test compounds showed weak to moderate antifungal activity against tested fungi in comparison with ketoconazole as a reference drug. On the other hand, the newly synthesized compounds were tested for their anti-inflammatory effects and most of them showed good to excellent anti-inflammatory activity compared to indomethacin. Moreover, ulcerogenicity and the median lethal dose (LD50) of the most active anti-inflammatory compounds 6b and 9e were determined in mice; they were non-toxic at doses up to 400 mg kg-1 after i.p. administration.5-Acil-8-hidroksikinolin-2-(3\u27-supstituirani-4\u27-aril-2,3-dihidrotiazol-2\u27-ilid- ne)hidrazoni 5a-e do 10a-c pripravljeni su reakcijom odgovarajućih 5-acil-8-hidroksikinolin-4-supstituiranih tiosemikarbazona 3a-e i fenacil bromida 4a-e. Strukture novih spojeva potvrđene su na temelju spektralnih i elementarnih analiza. Dvadeset osam novih spojeva testirano je na potencijalno antimikrobno djelovanje. Većina spojeva pokazuje slabo do umjereno antibakterijsko djelovanje protiv većine testiranih bakterijskih sojeva u usporedbi s gatifloksacinom kao referentim lijekom, te slabo do umjereno antifungalno djelovanje protiv gljivica u usporedbi s ketokonazolom kao referentnim lijekom. Testovi na protuupalno djelovanje pokazuju da većina spojeva posjeduje dobro ili snažno protuupalno djelovanje u usporedbi s indometacinom. Ulcerogeno djelovanje i srednje letalne doze (LD50) najaktivnijih spojeva 6b i 9e određeni su na miševima. Rezultati pokazuju da su netoksični u dozama do 400 mg kg-1 nakon i.p. primjene

Confirmation bias in the utilization of others' opinion strength

Humans tend to discount information that undermines past choices and judgments. This confirmation bias has significant impact on domains ranging from politics to science and education. Little is known about the mechanisms underlying this fundamental characteristic of belief formation. Here we report a mechanism underlying the confirmation bias. Specifically, we provide evidence for a failure to use the strength of others' disconfirming opinions to alter confidence in judgments, but adequate use when opinions are confirmatory. This bias is related to reduced neural sensitivity to the strength of others' opinions in the posterior medial prefrontal cortex when opinions are disconfirming. Our results demonstrate that existing judgments alter the neural representation of information strength, leaving the individual less likely to alter opinions in the face of disagreement

Artesunate induces necrotic cell death in schwannoma cells

Established as a potent anti-malaria medicine, artemisinin-based drugs have been suggested to have anti-tumour activity in some cancers. Although the mechanism is poorly understood, it has been suggested that artemisinin induces apoptotic cell death. Here, we show that the artemisinin analogue artesunate (ART) effectively induces cell death in RT4 schwannoma cells and human primary schwannoma cells. Interestingly, our data indicate for first time that the cell death induced by ART is largely dependent on necroptosis. ART appears to inhibit autophagy, which may also contribute to the cell death. Our data in human schwannoma cells show that ART can be combined with the autophagy inhibitor chloroquine (CQ) to potentiate the cell death. Thus, this study suggests that artemisinin-based drugs may be used in certain tumours where cells are necroptosis competent, and the drugs may act in synergy with apoptosis inducers or autophagy inhibitors to enhance their anti-tumour activity

Effect of arbuscular mycorrhizal (AM) colonization on terpene emission and content of Artemisia annua L.

Plant roots interact with a wide variety of rhizospheric microorganisms, including bacteria and the symbiontic arbuscular mycorrhizal (AM) fungi. The mycorrhizal symbiosis represents a series of complex feedbacks between plant and fungus regulated by their physiology and nutrition. Despite the widespread distribution and ecological significance of AM symbiosis, little is known about the potential of AM fungi to affect plant VOC metabolism. The purpose of this study was to investigate whether colonization of plant roots by AM fungi and associated soil microorganisms affects VOC emission and content of Artemisia annua L. plants (Asteraceae). Two inoculum types were evaluated: one consisted of only an arbuscular mycorrhizal (AM) fungus species (Glomus spp.), and the other was a mixture of different Glomus species and associated soil bacteria. Inoculated plants were compared with non-inoculated plants and with plants supplemented with extra phosphorus (P) to obtain plants of the same size as mycorrhizal plants, thus excluding potentially-confounding mycorrhizal effects on shoot growth. VOC emissions of Artemisia annua plants were analyzed by leaf cuvette sampling followed by off-line measurements with pre-concentration and gas chromatography mass spectrometry (GC-MS). Measurements of CO2 and H2O exchanges were conducted simultaneously. Several volatile monoterpenes were identified and characterized from leaf emissions of Artemisia annua L. by GC-MS analysis. The main components identified belong to different monoterpene structures: alpha-pinene, beta-pinene, camphor, 1,8-cineole, limonene, and artemisia ketone. A good correlation between monoterpene leaf concentration and leaf emission was found. Leaf extracts included also several sesquiterpenes. Total terpene content and emission was not affected by AM inoculation with or without bacteria, while emission of limonene and artemisia ketone was stimulated by this treatment. No differences were found among treatments for single monoterpene content, while accumulation of specific sesquiterpenes in leaves was altered in mycorrhizal plants compared to control plants. Growth conditions seemed to have mainly contributed to the outcome of the symbiosis and influenced the magnitude of the plant response. These results highlight the importance of considering the below-ground interaction between plant and soil for estimating VOC emission rates and their ecological role at multitrophic level

A short educational intervention diminishes causal illusions and specific paranormal beliefs in undergraduates

Cognitive biases such as causal illusions have been related to paranormal and pseudoscientific beliefs and, thus, pose a real threat to the development of adequate critical thinking abilities. We aimed to reduce causal illusions in undergraduates by means of an educational intervention combining training-in-bias and training-in-rules techniques. First, participants directly experienced situations that tend to induce the Barnum effect and the confirmation bias. Thereafter, these effects were explained and examples of their influence over everyday life were provided. Compared to a control group, participants who received the intervention showed diminished causal illusions in a contingency learning task and a decrease in the precognition dimension of a paranormal belief scale. Overall, results suggest that evidence-based educational interventions like the one presented here could be used to significantly improve critical thinking skills in our students

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds