Note that in this missive, Carreira does not impose his own rules on Guido, but those of Caltech. In fact, sources assured me that such work practices were and still are perfectly standard at Caltech. Working in the lab late and on weekends was normal, everyone had to do it, as the sources said. Caltech used to be infamous for people working ungodly hours. Sometimes, lights were on in the labs even at 2 AM on a Saturday morning. Other US elite universities were not really much better, or same. (New JACS EiC Erick Carreira: “correct your work-ethic immediately” SEPTEMBER 6, 2020 For Better Science)
A statement from Prof. Erick Carreira:
“I regret writing this letter, as it in no way reflects my leadership approach today. I have made peace with those impacted by the letter. (1/3)
Whether I am leading a lab or leading a journal, I am committed to promoting a sustainable and positive cultural shift in our industry.” – Erick Carreira (3/3)
There are many texts on the philosophy of science and scientific method that deal extensively with the hypothesis but, in short, we can describe it as ‘a reasonable scientific proposal’. It is not a statement of fact but a statement that takes us just beyond known information and anticipates the next logical step in a sequence of supportable precepts. The hypothesis has to have two attributes to be useful in scientific investigation: it must fit the known information and it must be testable. To comply with the first attribute, you the scientist have to read and understand the literature. To comply with the second, you have to do an experiments. In essence, the paper you are about to write concerns nothing other than those two things. You can see why the hypothesis is so central to scientific writing. (強調のため一部太字 引用元：David Lindsay, Scientific Writing = Thinking in Words, page 7)
Neuronal oscillations have been hypothesized to play an important role in cognition and its ensuing behavior, but evidence that links a specific neuronal oscillation to a discrete cognitive event is largely lacking. We measured neuronal activity in the entorhinal-hippocampal circuit while mice performed a reward-based spatial working memory task. During the memory retention period, a transient burst of high gamma synchronization preceded an animal’s correct choice in both prospective planning and retrospective mistake correction, but not an animal’s incorrect choice. Optogenetic inhibition of the circuit targeted to the choice point area resulted in a coordinated reduction in both high gamma synchrony and correct execution of a working-memory-guided behavior. These findings suggest that transient high gamma synchrony contributes to the successful execution of spatial working memory. Furthermore, our data are consistent with an association between transient high gamma synchrony and explicit awareness of the working memory content. (強調のため一部太字 引用元：Cell 157(4):845-857の要旨)
Given that LPA is known to activate cortical contractility via the Rho/Rock pathway, we hypothesized that a mechanical polarization mechanism of the cell cortex could trigger the transformation of progenitor cells into stable-bleb cells (Carvalho et al., 2013). To test this hypothesis, we treated stable-bleb cells with the Rho kinase inhibitor Y-27632 or the myosin-II inhibitor Blebbistatin (Figure 2C). Treated cells lost their characteristic polarization, supporting a critical role for Rho/Rock-mediated cortical contractility in driving stable-bleb cell transformation. (強調のため一部太字 引用元：Cell 160(4):673-685のResultsセクションの一部)
Since computational modeling suggests that a failure to segregate protein damage may result in a reduced fitness (Erjavec et al., 2008) and functions crucial for cellular fitness are often performed by parallel partly redundant pathways, we hypothesized that machineries involved in the partitioning of protein aggregates could be identified by systematically screening for genetic interactions between SIR2 and nonessential and essential genes using synthetic genetic arrays (SGA) analysis ( Tong et al., 2001 and Tong et al., 2004). Using this approach, we found that cells lacking Sir2p share many genetic interactions with the conditional actin mutant, which is a result of sir2Δ cells showing a defect in CCT-chaperonin-dependent folding of actin. （強調のため一部太字 引用元：Cell 140(2):257-267 イントロダクション）
Given the potential for nutrients to stimulate inflammatory pathways and the importance of keeping these pathways in check, we hypothesized that previously unrecognized counterregulatory mechanisms might exist to protect cells from activation of inflammatory pathways during physiological fluctuations in nutrient exposure or in nutrient-rich conditions. We reasoned that a factor participating in such a coordinating mechanism between nutrient and inflammatory responses would be expected to meet several criteria: (1) the gene product should be present in tissue types responsible for nutrient clearance from blood, such as adipose tissue; (2)expression or activity should be regulated by both nutritional and inflammatory stimuli; (3) the factor should regulate inflammatory signaling components and/or gene expression (cells or tissues lacking such a factor would then exhibit excess or prolonged inflammation in response to challenges by both nutrients and inflammatory mediators); (4) the factor should regulate cellular metabolism, and its absence should result in impaired cellular metabolic function; and (5) through regulation of metabolic function in particular cell types and organs, the factor should also impact systemic metabolism. In this study, we identify six-transmembrane protein of prostate 2 (STAMP2) as a factor meeting these criteria. （強調のため一部太字 引用元：Cell 129(3):537-548 イントロダクション）
…At present, two theories attempt to link airway epithelial ion transport to lung defense and predict how mutations in CFTR adversely affect these relationships. One theory, the “hypotonic (low salt) ASL/defensin” hypothesis, postulates that normal airway epithelia are covered by an ASL with a [NaCl] sufficiently low (≤ 50 mM NaCl) to activate defensins and create an antimicrobial “shield” on airway surfaces (31, 38 and 10). Generation of a low [NaCl], hypotonic ASL reflects selective transepithelial absorption of salt but not water from ASL, presumably a consequence of putative airway epithelial water impermeability or surface forces (31, 44 and 46). Defensin inactivation by iso- or hypertonic ASL (i.e., [NaCl] > 100 mM) in CF is postulated to reflect the Cl− impermeability of CF epithelial cells (38 and 10). The second theory, the “isotonic volume transport/mucus clearance hypothesis,” predicts that airway epithelia regulate the volume (height) of ASL by isotonic ion and water transport to optimize mucus clearance (Boucher 1994a). In CF, the rate of isotonic ion and water (volume) transport is abnormally high, which is predicted to reduce ASL volume, concentrate mucus, and lead to abnormal mucus transport and retention of tenacious mucus masses (plaques) in airways that serve as the nidus of infection (14 and 5).
… By measuring ASL ion composition, we tested key predictions of the hypotonic (low salt) ASL/defensin hypothesis: (1) that normal airway epithelia generate and maintain hypotonic (or low salt) solutions on airway surfaces, and (2) that CF airway surface liquid is isotonic (Joris et al. 1993) or hypertonic (with excess salt) (Gilljam et al. 1989). A second series of experiments tested key aspects of the isotonic hypothesis: (1) that normal airway epithelia are isotonic volume-absorbing epithelia that produce an isotonic ASL; (2) that CF airway epithelia absorb volume isotonically at abnormally high rates; and (3) that mucus transport is deranged by depletion of the ASL through excessive isotonic volume absorption. （強調のため一部太字 引用元：Cell 95(7):1005-1015のイントロダクションの一部を抜粋）
Good science would pit theory A against theories B, C, D and E with an experiment where each theory gave different predictions. （引用元：Nakagawa and Cuthill. Effect size, confidence interval and statistical significance: a practical guide for biologists. Biol. Rev. (2007), 82, pp. 591–605. doi:10.1111/j.1469-185X.2007.00027.x）
当初は仮説Aを検証すべく始めた研究だが、実際のデータを眺めてみると、仮説Bのほうがよりよく説明できるようだ――仮にこうなってしまっても、心配はい らない。すべての事項を書き出し、仮説・目的・データの最適たるコンビネーションを選びとればよい。完成した論文上での研究目的と、仕事に取り掛かる理由 付けとしての研究目的は、往々にして異なるものだ。良質な科学といえども、大抵は日和見主義的・修正主義的なものだ。(Whitesides’ Group: Writing a paper 化学者のつぶやき Chemi-station)