Hydroclimate variability from western Iberia (Portugal) during the Holocene: insights from a composite stalagmite isotope record

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Thatcher, D. L., Wanamaker, A. D., Denniston, R. F., Asmerom, Y., Polyak, V. J., Fullick, D., Ummenhofer, C. C., Gillikin, D. P., & Haws, J. A. Hydroclimate variability from western Iberia (Portugal) during the Holocene: insights from a composite stalagmite isotope record. Holocene, (2020): 095968362090864, doi:10.1177/0959683620908648.Iberia is predicted under future warming scenarios to be increasingly impacted by drought. While it is known that this region has experienced multiple intervals of enhanced aridity over the Holocene, additional hydroclimate-sensitive records from Iberia are necessary to place current and future drying into a broader perspective. Toward that end, we present a multi-proxy composite record from six well-dated and overlapping speleothems from Buraca Gloriosa (BG) cave, located in western Portugal. The coherence between the six stalagmites in this composite stalagmite record illustrates that climate (not in-cave processes) impacts speleothem isotopic values. This record provides the first high-resolution, precisely dated, terrestrial record of Holocene hydroclimate from west-central Iberia. The BG record reveals that aridity in western Portugal increased secularly from 9.0 ka BP to present, as evidenced by rising values of both carbon (δ13C) and oxygen (δ18O) stable isotope values. This trend tracks the decrease in Northern Hemisphere summer insolation and parallels Iberian margin sea surface temperatures (SST). The increased aridity over the Holocene is consistent with changes in Hadley Circulation and a southward migration of the Intertropical Convergence Zone (ITCZ). Centennial-scale shifts in hydroclimate are coincident with changes in total solar irradiance (TSI) after 4 ka BP. Several major drying events are evident, the most prominent of which was centered around 4.2 ka BP, a feature also noted in other Iberian climate records and coinciding with well-documented regional cultural shifts. Substantially, wetter conditions occurred from 0.8 ka BP to 0.15 ka BP, including much of the ‘Little Ice Age’. This was followed by increasing aridity toward present day. This composite stalagmite proxy record complements oceanic records from coastal Iberia, lacustrine records from inland Iberia, and speleothem records from both northern and southern Spain and depicts the spatial and temporal variability in hydroclimate in Iberia.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported, in part, by the US National Science Foundation (Grants: #1804528 to ADW; #1804635 to RD; #1804132 to CCU; #1806025 to YA and VP; #1805163 to DPG; BCS-0455145, BCS-0612923, and BCS-1118155 to JAH)

Targeting targeted agents: open issues for clinical trial design

Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources

The importance of affective learning goals: lessons learned from the design and evolution of a geoscience course for preservice primary teachers

The challenges of teaching science to preservice elementary teachers include an overall negative attitude about science that translates to future teachers who do not teach science confidently and/or teach it superficially and hurriedly compared to other subjects. College-level science courses for preservice teachers have an opportunity to reverse this trend and help create teachers who are knowledgeable about science and enjoy teaching it. In this paper, we discuss the hybrid model of an online course and a hands-on, inquiry-based lab that was developed, implemented, and evolved over eight years. The lab activities, in particular, were developed to address both content and affective goals. These goals were to provide students with a solid foundation in Earth and Space Science content and to make them comfortable teaching science. An assessment of these goals shows that this course increased preservice teachers’ level of confidence to teach these topics, and students generally found the course to be enjoyable and the content to be useful to their future careers. More work needs to be done to assess the content knowledge of this group of students, highlighting the need for developing a validated instrument that covers the breadth of Earth and Space Science content included in the NGSS for elementary grades.This article is published as Thatcher, D.L., Cervato, C. & Kerton, C. The importance of affective learning goals: lessons learned from the design and evolution of a geoscience course for preservice primary teachers. SN Soc Sci 2, 207 (2022). https://doi.org/10.1007/s43545-022-00477-7. Posted with permission.This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/ by/4.0/

Linking the karst record to atmospheric, precipitation, and vegetation dynamics in Portugal

Cave deposits can be valuable sources of paleoclimate data, especially when atmospheric circulation patterns, precipitation variability, vegetation changes, and the chemical evolution of waters moving through the karst environment can be mechanistically linked to speleothem proxies. In particular, an evaluation of the factors that control the isotopic composition of precipitation and the evolution of rainwater during migration from the land surface to the cave are needed to robustly develop speleothems as hydroclimate-sensitive proxies. One area in which precipitation and atmospheric variability are closely linked is western Iberia, where rainfall is strongly influenced by the Azores High, part of the North Atlantic Oscillation (NAO) dipole. Therefore, in order to better characterize the factors that influence the isotopic composition of precipitation in Portugal and to evaluate the potential of using stalagmites from this region as hydroclimate (and NAO-sensitive) proxies, we investigated Global Network of Isotopes in Precipitation (GNIP) data from ten mainland Portugal sites spanning multiple decades. In addition, we use more than one hydrologic year of precipitation amount and isotope data from Buraca Gloriosa (BG), a cave in western Portugal, the site of on-going speleothem analyses, as well as six years of environmental monitoring from BG. We present an integrated analysis of rainfall and vegetation through the normalized difference vegetation index (NDVI) following extremely wet and dry winters. Summer vegetation density, related to the amount of precipitation in the preceding winter wet season, as well as prior calcite precipitation (PCP), would largely control the stable carbon isotopic signature (delta C-13) in stalagmites at BG. Cool season recharge is likely the dominant factor for the oxygen isotopic composition (delta O-18) of water percolating through the cave system, while amount effects exert the primary control on precipitation delta O-18 values. Based on HYSPLIT modeling, moisture sources overwhelmingly originate from the Atlantic Ocean as opposed to the Mediterranean or elsewherethus, variability in delta O-18 values in the precipitation (and, thus, by inference, those of the dripwater and stalagmites) are primarily reflecting changes in precipitation amount and not changing temperatures or source regions. Together these data constitute an important analysis of the controls of isotope proxies in Portuguese cave systems.US National Science FoundationNational Science Foundation (NSF) [1804528, 1804635, 1804132, 1805163]info:eu-repo/semantics/publishedVersio

<em>miR-153</em> Regulates SNAP-25, Synaptic Transmission, and Neuronal Development

<div><p>SNAP-25 is a core component of the trimeric SNARE complex mediating vesicle exocytosis during membrane addition for neuronal growth, neuropeptide/growth factor secretion, and neurotransmitter release during synaptic transmission. Here, we report a novel microRNA mechanism of SNAP-25 regulation controlling motor neuron development, neurosecretion, synaptic activity, and movement in zebrafish. Loss of <i>miR-153</i> causes overexpression of SNAP-25 and consequent hyperactive movement in early zebrafish embryos. Conversely, overexpression of <i>miR-153</i> causes SNAP-25 down regulation resulting in near complete paralysis, mimicking the effects of treatment with Botulinum neurotoxin. <i>miR-153</i>-dependent changes in synaptic activity at the neuromuscular junction are consistent with the observed movement defects. Underlying the movement defects, perturbation of <i>miR-153</i> function causes dramatic developmental changes in motor neuron patterning and branching. Together, our results indicate that precise control of SNAP-25 expression by <i>miR-153</i> is critically important for proper neuronal patterning as well as neurotransmission.</p> </div

<i>miR-153</i> mimics the effects of BoNT A.

<p>(A) Single cell embryos were injected as indicated and then at 27 hpf, exposed to Botulinum neurotoxin A (BoNT) for 30 minutes. After recovery for 1 hour, western blots were performed on embryo lysates using antibodies against SNAP-25 or α–tubulin. (B) Quantitation of SNAP-25 levels from A, n = 3. **, p<0.01 (C) Embryonic movement in the presence or absence of BoNT A. The number of twitches per minute was counted as in Fig. 1 for embryos treated as indicated. Significance was determined by comparing mock embryos to all other conditions using ANOVA with Dunnett’s post-test, n = 15. *, p<0.05.</p

<i>miR-153</i> is expressed in motor neurons.

<p>To enrich for motor neurons, heads were removed from 52 hpf embryos just posterior to the otic vesicle and trunks were dissociated to facilitate sorting of RFP+ and RFP- cells. RNA was isolated from these cell fractions and RT/PCR was performed to determine <i>miR-153</i> levels relative to U6 snRNA. Significance was determined by a two-tailed Student’s t-test with the error bars representing s.e.m.; p<0.02.</p