Field: Medicine › GeneticsType: No effect foundArea: chronic lymphocytic leukemiaTarget: Activation-induced deaminase (AID)Stage: preclinical
Hypothesis
AID, which can remove DNA methylation, would change the methylation of disease-related genes in chronic lymphocytic leukemia cells and so change their expression.
What failed
After AID expression, only minor differences appeared at individual sites. There were no recurrent methylation changes at specific target sites and no change in global methylation.
Broken assumption
AID worsens chronic lymphocytic leukemia partly by demethylating and switching on disease-related genes.
Why
The abstract does not give a cause. AID's known effect in this leukemia seems to come through DNA mutation, not through demethylation.
Field: Medicine › PhysiologyType: No effect foundArea: alzheimer's diseaseTarget: LXR/RXR agonists (T0901317, bexarotene)Stage: preclinical
Hypothesis
Activating LXR or RXR receptors, which raise APOE and are reported to help clear amyloid beta, would lower amyloid beta 40 in the brain and spinal fluid of rats.
What failed
Treating normal rats for 3 or 7 days with the LXR agonist T0901317 or the RXR agonist bexarotene did not significantly change amyloid beta 40 in the brain or spinal fluid.
Broken assumption
Activating LXR or RXR receptors lowers brain amyloid beta.
Why
The abstract does not give a cause. Earlier rodent reports of lower amyloid beta did not hold in this study.
Field: Social Sciences › Sociology and Political ScienceType: Couldn't replicate a published resultArea: social psychologyTarget: Spatial distance primingStage: replication
Hypothesis
Plotting two points far apart on graph paper would make people feel less close to their family and change their calorie estimates, as Williams and Bargh (2008) reported.
What failed
Direct replications of both experiments, with experimenters who did not know each participant's condition, showed no sign of either priming effect.
Broken assumption
A brief cue of physical distance changes how close people feel to others.
Why
The abstract does not give a cause. The replications added blinding of the experimenter, which the originals may have lacked.
Field: Medicine › PhysiologyType: No effect foundArea: chronic postsurgical painTarget: Capsaicin 8% skin patchStage: randomized trial
Hypothesis
A high-dose capsaicin patch would reduce severe pain that persists after inguinal hernia repair.
What failed
In 46 patients, pain fell most at 1 month, but the difference from placebo did not reach the trial's significance level (P = 0.046 against P < 0.01). There was no difference at 2 or 3 months, and skin nerve fibre density did not change.
Broken assumption
Desensitising skin nerves with capsaicin relieves persistent pain after hernia repair.
Why
The abstract does not give a cause. The patch did not reduce the skin nerve fibres it is thought to act on.
Field: Neuroscience › NeurologyType: No effect foundArea: pain neuroscienceTarget: Single-pulse TMS virtual lesion of the motor cortexStage: exploratory
Hypothesis
A single pulse of transcranial magnetic stimulation (TMS) that briefly disrupts the primary motor cortex would change how painful a noxious heat stimulus feels.
What failed
Across three timing protocols (11 to 16 participants each), pain ratings with real TMS did not differ from sham TMS or from pain alone.
Broken assumption
A brief disruption of the motor cortex at the right moment changes the perception of acute pain.
Why
The authors call the study exploratory. Disrupting the motor cortex at these three time points did not interrupt pain processing.
Field: Immunology and Microbiology › ImmunologyType: No effect foundArea: insect immunityTarget: Drosophila Toll-9 receptorStage: preclinical
Hypothesis
Toll-9, the fruit fly receptor most similar to mammalian Toll-like receptors, would keep up a basal antimicrobial defence and help fight bacterial infection.
What failed
Flies with a complete loss of Toll-9 kept their basal antimicrobial response and mounted a normal immune response to bacterial infection.
Broken assumption
The fly receptor that looks most like mammalian Toll-like receptors also has an immune role.
Why
The abstract does not give a cause. Earlier over-expression results did not reflect what the receptor does at normal levels.
Field: Biochemistry, Genetics and Molecular Biology › Molecular BiologyType: Couldn't replicate a published resultArea: stem cell biologyTarget: Acid treatment to make STAP stem cellsStage: replication
Hypothesis
A 25-minute acid treatment (pH 5.7) would turn mouse blood cells into pluripotent stem cells, as Obokata et al. (2014) reported.
What failed
Acid-treated spleen cells from newborn Oct4-GFP mice did not express the stem cell marker Oct4-GFP after 3 to 6 days, and qPCR found no rise in Oct4, Sox2 or Nanog. Lung fibroblasts gave the same result.
Broken assumption
A simple stress such as acid can turn ordinary body cells into pluripotent stem cells.
Why
The abstract does not give a cause. The published method did not produce STAP cells.
Field: Neuroscience › Cellular and Molecular NeuroscienceType: No effect foundArea: myotonic dystrophy type 1Target: Serum microRNA biomarkersStage: full study
Hypothesis
MicroRNAs that are misregulated in the heart and muscle of people with myotonic dystrophy type 1 would also differ in their blood serum and could track the disease.
What failed
Of 175 serum microRNAs profiled, none differed by more than 2.6-fold between patients and controls. Six candidates (miR-103, miR-107, miR-21, miR-29a, miR-30c, miR-652) showed no consistent difference in validation.
Broken assumption
MicroRNA changes in diseased muscle and heart are reflected in blood serum.
Why
The abstract does not give a cause. Changes seen in diseased tissue did not show up in serum.
Field: Biochemistry, Genetics and Molecular Biology › Molecular BiologyType: No effect foundArea: innate immune memoryTarget: Polycomb group proteins as carriers of LPS memoryStage: preclinical
Hypothesis
Polycomb group proteins, which keep a memory of developmental signals in chromatin, would also keep a memory of earlier exposure to bacterial lipopolysaccharide (LPS) and change the response to a second exposure.
What failed
In reporter cells, neither a single nor repeated LPS pre-treatment changed how strongly LPS-responsive genes switched on after a second exposure.
Broken assumption
Polycomb-based chromatin memory also stores the memory of earlier immune stimulation.
Why
The abstract does not give a cause. Under these conditions the Polycomb system did not record LPS exposure.