•Issues of paid and unpaid social reproductive work need to be aligned to sustain decent work agenda.•Growth indicators for SDG 8 targets neglect the value and costs of social reproduction.•Decent ...work agenda is unsustainable if it neglects persistent gender inequality globally (SDG 5).
SDG 8 calls for promoting ‘sustained, inclusive and sustainable economic growth, full and productive employment and decent work for all’. Even as it highlights the importance of labour rights for all, it also makes visible some significant tensions. We note, for example, that despite many critiques of narrow economic measures of growth, the focus here remains on GDP and per capita growth. This is problematic, we argue, because the GDP productive boundary excludes much of social reproductive work. This puts SDG8 in tension with SDG 5 which calls for the recognition of the value of unpaid care and domestic work. There has been a significant increase in the rate of working women in the formal and informal sector. However, there has not been a subsequent gender shift in the doing of social reproductive work. In this paper we argue SDG 8’s focus on decent work and economic growth is inadequate; that productive employment and decent work for all men and women by 2030 needs to take into account the value and costs of social reproduction. We trace key historical debates on work to argue that both gender and labour rights have to underpin SDG 8 if its promise of inclusive, sustainable and decent work is to be realized.
Empirical research that cannot be reproduced using the original dataset and software code (replication files) creates a credibility challenge, as it means those published findings are not verifiable. ...This study reports the results of a research audit exercise, known as the push button replication project, that tested a sample of studies that use similar empirical methods but span a variety of academic fields.
We developed and piloted a detailed protocol for conducting push button replication and determining the level of comparability of these replication findings to original findings. We drew a sample of articles from the ten journals that published the most impact evaluations from low- and middle-income countries from 2010 through 2012. This set includes health, economics, and development journals. We then selected all articles in these journals published in 2014 that meet the same inclusion criteria and implemented the protocol on the sample.
Of the 109 articles in our sample, only 27 are push button replicable, meaning the provided code run on the provided dataset produces comparable findings for the key results in the published article. The authors of 59 of the articles refused to provide replication files. Thirty of these 59 articles were published in journals that had replication file requirements in 2014, meaning these articles are non-compliant with their journal requirements. For the remaining 23 of the 109 articles, we confirmed that three had proprietary data, we received incomplete replication files for 15, and we found minor differences in the replication results for five.
The findings presented here reveal that many economics, development, and public health researchers are a long way from adopting the norm of open research. Journals do not appear to be playing a strong role in ensuring the availability of replication files.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Methylation is a fundamental mechanism used in Nature to modify the structure and function of biomolecules, including proteins, DNA, RNA, and metabolites. Methyl groups are predominantly installed ...into biomolecules by a large and diverse class of S-adenosyl methionine (SAM)-dependent methyltransferases (MTs), of which there are ∼200 known or putative members in the human proteome. Deregulated MT activity contributes to numerous diseases, including cancer, and several MT inhibitors are in clinical development. Nonetheless, a large fraction of the human MT family remains poorly characterized, underscoring the need for new technologies to characterize MTs and their inhibitors in native biological systems. Here, we describe a suite of S-adenosyl homocysteine (SAH) photoreactive probes and their application in chemical proteomic experiments to profile and enrich a large number of MTs (>50) from human cancer cell lysates with remarkable specificity over other classes of proteins. We further demonstrate that the SAH probes can enrich MT-associated proteins and be used to screen for and assess the selectivity of MT inhibitors, leading to the discovery of a covalent inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme implicated in cancer and metabolic disorders. The chemical proteomics probes and methods for their utilization reported herein should prove of value for the functional characterization of MTs, MT complexes, and MT inhibitors in mammalian biology and disease.
Despite the success of genomics in identifying new essential bacterial genes, there is a lack of sustainable leads in antibacterial drug discovery to address increasing multidrug resistance. Type IIA ...topoisomerases cleave and religate DNA to regulate DNA topology and are a major class of antibacterial and anticancer drug targets, yet there is no well developed structural basis for understanding drug action. Here we report the 2.1 A crystal structure of a potent, new class, broad-spectrum antibacterial agent in complex with Staphylococcus aureus DNA gyrase and DNA, showing a new mode of inhibition that circumvents fluoroquinolone resistance in this clinically important drug target. The inhibitor 'bridges' the DNA and a transient non-catalytic pocket on the two-fold axis at the GyrA dimer interface, and is close to the active sites and fluoroquinolone binding sites. In the inhibitor complex the active site seems poised to cleave the DNA, with a single metal ion observed between the TOPRIM (topoisomerase/primase) domain and the scissile phosphate. This work provides new insights into the mechanism of topoisomerase action and a platform for structure-based drug design of a new class of antibacterial agents against a clinically proven, but conformationally flexible, enzyme class.
Among the caspases that cause regulated cell death, a unique function for caspase-7 has remained elusive. Caspase-3 performs apoptosis, whereas caspase-7 is typically considered an inefficient ...back-up. Caspase-1 activates gasdermin D pores to lyse the cell; however, caspase-1 also activates caspase-7 for unknown reasons
. Caspases can also trigger cell-type-specific death responses; for example, caspase-1 causes the extrusion of intestinal epithelial cell (IECs) in response to infection with Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium)
. Here we show in both organoids and mice that caspase-7-deficient IECs do not complete extrusion. Mechanistically, caspase-7 counteracts gasdermin D pores and preserves cell integrity by cleaving and activating acid sphingomyelinase (ASM), which thereby generates copious amounts of ceramide to enable enhanced membrane repair. This provides time to complete the process of IEC extrusion. In parallel, we also show that caspase-7 and ASM cleavage are required to clear Chromobacterium violaceum and Listeria monocytogenes after perforin-pore-mediated attack by natural killer cells or cytotoxic T lymphocytes, which normally causes apoptosis in infected hepatocytes. Therefore, caspase-7 is not a conventional executioner but instead is a death facilitator that delays pore-driven lysis so that more-specialized processes, such as extrusion or apoptosis, can be completed before cell death. Cells must put their affairs in order before they die.
Caffeine is a widely used psychostimulant. In the brain, caffeine acts as a competitive, non-selective adenosine receptor antagonist of A1 and A2A, both known to modulate long-term potentiation ...(LTP), the cellular basis of learning and memory. Repetitive transcranial magnetic stimulation (rTMS) is theorized to work through LTP induction and can modulate cortical excitability as measured by motor evoked potentials (MEPs). The acute effects of single caffeine doses diminish rTMS-induced corticomotor plasticity. However, plasticity in chronic daily caffeine users has not been examined.
We conducted a
secondary covariate analysis from two previously published plasticity-inducing pharmaco-rTMS studies combining 10 Hz rTMS and D-cycloserine (DCS) in twenty healthy subjects.
In this hypothesis-generating pilot study, we observed enhanced MEP facilitation in non-caffeine users compared to caffeine users and placebo.
These preliminary data highlight a need to directly test the effects of caffeine in prospective well-powered studies, because in theory, they suggest that chronic caffeine use could limit learning or plasticity, including rTMS effectiveness.
Clock-Line-Mediated Sisyphus Cooling Chen, Chun-Chia; Siegel, Jacob L.; Hunt, Benjamin D. ...
Physical review letters,
08/2024, Letnik:
133, Številka:
5
Journal Article
Recenzirano
Odprti dostop
We demonstrate subrecoil Sisyphus cooling using the long-lived ^{3}P_{0} clock state in alkaline-earth-like ytterbium. A 1388-nm optical standing wave nearly resonant with the ^{3}P_{0}→^{3}D_{1} ...transition creates a spatially periodic light shift of the ^{3}P_{0} clock state. Following excitation on the ultranarrow clock transition, we observe Sisyphus cooling in this potential, as the light shift is correlated with excitation to ^{3}D_{1} and subsequent spontaneous decay to the ^{1}S_{0} ground state. We observe that cooling enhances the loading efficiency of atoms into a 759-nm magic-wavelength one-dimensional (1D) optical lattice, as compared to standard Doppler cooling on the ^{1}S_{0}→^{3}P_{1} transition. Sisyphus cooling yields temperatures below 200 nK in the weakly confined, transverse dimensions of the 1D optical lattice. These lower temperatures improve optical lattice clocks by facilitating the use of shallow lattices with reduced light shifts while retaining large atom numbers to reduce the quantum projection noise. This Sisyphus cooling can be pulsed or continuous and is applicable to a range of quantum metrology applications.We demonstrate subrecoil Sisyphus cooling using the long-lived ^{3}P_{0} clock state in alkaline-earth-like ytterbium. A 1388-nm optical standing wave nearly resonant with the ^{3}P_{0}→^{3}D_{1} transition creates a spatially periodic light shift of the ^{3}P_{0} clock state. Following excitation on the ultranarrow clock transition, we observe Sisyphus cooling in this potential, as the light shift is correlated with excitation to ^{3}D_{1} and subsequent spontaneous decay to the ^{1}S_{0} ground state. We observe that cooling enhances the loading efficiency of atoms into a 759-nm magic-wavelength one-dimensional (1D) optical lattice, as compared to standard Doppler cooling on the ^{1}S_{0}→^{3}P_{1} transition. Sisyphus cooling yields temperatures below 200 nK in the weakly confined, transverse dimensions of the 1D optical lattice. These lower temperatures improve optical lattice clocks by facilitating the use of shallow lattices with reduced light shifts while retaining large atom numbers to reduce the quantum projection noise. This Sisyphus cooling can be pulsed or continuous and is applicable to a range of quantum metrology applications.
Patient-Reported Outcomes in Cardiothoracic Surgery Subramanian, Melanie; Kozower, Benjamin D.; Brown, Lisa M. ...
The Annals of thoracic surgery,
January 2019, 2019-01-00, 20190101, Letnik:
107, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Current studies in cardiothoracic clinical research frequently fail to use end points that are most meaningful to patients, including measures associated with quality of life. Patient-reported ...outcomes (PROs) represent an underused but important component of high-quality patient-centered care. Our objective was to highlight important principles of PRO measurement, describe current use in cardiothoracic operations, and discuss the potential for and challenges associated with integration of PROs into large clinical databases.
We performed a literature review by using the PubMed/EMBASE databases. Clinical articles that focused on the use of PROs in cardiothoracic surgical outcomes measurement or clinical research were included in this review.
PROs measure the outcomes that matter most to patients and facilitate the delivery of patient-centered care. When effectively used, PRO measures have provided detailed and nuanced quality-of-life data for comparative effectiveness research. However, further steps are needed to better integrate PROs into routine clinical care.
Incorporation of PROs into routine clinical practice is essential for delivering high-quality patient-centered care. Future integration of PROs into prospectively collected registries and databases, including that The Society of Thoracic Surgeons National Database, has the potential to enrich comparative effectiveness research in cardiothoracic surgery.
Combining a dye-sensitized photoelectrochemical cell for hydrogen production based on a SnO sub(2) photoanode in series with a dye-sensitized photovoltaic solar cell using a TiO sub(2) photoanode ...yields a tandem system for the generation of H sub(2) from hydroquinone using only light energy and no applied electrical bias. To target distinct portions of the solar spectrum, a more blue-absorbing free base porphyrin and a more red-absorbing Si phthalocyanine chromophore are used at the two photoelectrodes. With incorporation of a suitable water oxidation catalyst, a similar approach could enable tandem photochemical water splitting without the need for p-type semiconductors.
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