•A consensus was reached on an updated definition of LGMD, and current sub-types were evaluated by application of the updated definition.•Consensus was reached on the most useful LGMD classification ...system that also allowed space for further discoveries of new sub-types.•Potential ramifications of the new definition and classification of LGMD for patients were discussed and several action points around how to disseminate this proposal were identified.
Pseudogenes have long been labeled as "junk" DNA, failed copies of genes that arise during the evolution of genomes. However, recent results are challenging this moniker; indeed, some pseudogenes ...appear to harbor the potential to regulate their protein-coding cousins. Far from being silent relics, many pseudogenes are transcribed into RNA, some exhibiting a tissue-specific pattern of activation. Pseudogene transcripts can be processed into short interfering RNAs that regulate coding genes through the RNAi pathway. In another remarkable discovery, it has been shown that pseudogenes are capable of regulating tumor suppressors and oncogenes by acting as microRNA decoys. The finding that pseudogenes are often deregulated during cancer progression warrants further investigation into the true extent of pseudogene function. In this review, we describe the ways in which pseudogenes exert their effect on coding genes and explore the role of pseudogenes in the increasingly complex web of noncoding RNA that contributes to normal cellular regulation.
We compare laser Doppler vibrometry (LDV) and digital image correlation (DIC) for use in full-field vibration and modal testing. This was done using a simultaneously measured 3D displacement field on ...a flat 7-in. corner-supported metal plate using pseudorandom excitation via a shaker. We complete a detailed comparison between the techniques and discuss the pros and cons of each. The results show that either technique can be used for quantifying the modal information with the LDV providing better out-of-plane displacement resolution and equivalent in-plane resolution. The strain calculation is considered better in the DIC approach due to the direct tie to the surface displacements. While the LDV does not lose its place as the gold standard for modal testing, DIC has introduced a new and competitive approach that will have significant advantages in certain testing regimes.
Photolysis of the non-steroidal anti-inflammatory drug ibuprofen was studied by exposure to a solar simulator in solutions of fulvic acid (FA) isolated from Pony Lake, Antarctica; Suwannee River, GA, ...USA; and Old Woman Creek, OH, USA. At an initial concentration of 10 μM, ibuprofen degrades by direct photolysis, but the presence of FA significantly increases reaction rates. These reactions proceeded up to 6× faster in FA solutions at lower ibuprofen concentrations (0.1 μM), but the rates are highly dependent upon DOM composition. Incomplete quenching of the reaction in the presence of isopropanol suggests that the hydroxyl radical is only partially responsible for ibuprofen’s photodegradation in FA solutions, and other reactive transients likely play an important role. Liquid chromatography-quadrupole time-of-flight mass spectrometry and NMR spectroscopy reveal the formation of multiple photoproducts, with three byproducts identified as 1-(4-isobutylphenyl)ethanol, isobutylacetophenone, and a phenol derivative. Pony Lake FA significantly increases the production of the major byproduct relative to yields produced by direct photolysis and the other two FA. Thus, the photolytic fate of ibuprofen in sunlit waters is affected by its initial concentration and the source of dissolved organic matter present.
► Ibuprofen photodegradation occurs slowly in water and is enhanced in the presence of fulvic acids. ► The composition of fulvic acids influences ibuprofen’s transformation pathway and kinetics. ► Enhanced photoreactivity of ibuprofen at low initial concentration (0.1 μM) in the presence of fulvic acids was observed. ► Multiple photoproducts were identified including isobutylacetophenone, a precursor used in the synthesis of ibuprofen.
Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) ...and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin ligase complex, is the primary target by which IMiDs mediate anticancer and teratogenic effects. Here we identify a ubiquitin-independent physiological chaperone-like function of CRBN that promotes maturation of the basigin (BSG; also known as CD147) and solute carrier family 16 member 1 (SLC16A1; also known as MCT1) proteins. This process allows for the formation and activation of the CD147-MCT1 transmembrane complex, which promotes various biological functions, including angiogenesis, proliferation, invasion and lactate export. We found that IMiDs outcompete CRBN for binding to CD147 and MCT1, leading to destabilization of the CD147-MCT1 complex. Accordingly, IMiD-sensitive MM cells lose CD147 and MCT1 expression after being exposed to IMiDs, whereas IMiD-resistant cells retain their expression. Furthermore, del(5q) MDS cells have elevated CD147 expression, which is attenuated after IMiD treatment. Finally, we show that BSG (CD147) knockdown phenocopies the teratogenic effects of thalidomide exposure in zebrafish. These findings provide a common mechanistic framework to explain both the teratogenic and pleiotropic antitumor effects of IMiDs.
The current experimental study (N = 546) compares the effect of exposure to a television news story with a positive and negative tone on anti-immigrant attitudes and carry-over effects to uninvolved ...immigrant groups. Results reveal that exposure to a “negatively” valenced news story about North African immigrants increased negative attitudes toward that same group. Importantly, however, we find carry-over effects of exposure to a “positively” valenced news story about North African immigrants to attitudes toward uninvolved immigrant groups. Together, these findings show that the effect of exposure to television news tone has more ramifications than previously thought, and that the impact of exposure to a positive or negative news story differs for direct effects vis-à-vis carry-over effects.
Although an emerging body of literature has advanced our knowledge of how monoracial parents can support their multiracial children in understanding the ethnic-racial identities they hold, there is a ...dearth of research exploring how parents socialize their children towards antiracism. Drawing from ten interviews with monoracial parents of multiracial children, this paper illuminates how parents leverage multiracial socialization practices, as identified in previous academic research, to instill an antiracist orientation in their children. Using consensual qualitative analyses, we find that although all parents had a vested interest in the wellbeing and identity development of their multiracial children, parents qualitatively differed in their ability and willingness to instill an antiracist orientation in their children. Specifically, parents in our sample exhibited five approaches to multiracial socialization, ranging from those that reinforced dominant racial ideologies to those that explicitly aimed to prepare youth to become antiracist activists. We also describe how monoracial parents’ lived experiences are implicated in their engagement in multiracial socialization practices, especially those that better position them to prepare their children to engage in antiracism. Our findings illuminate how monoracial parents may engage in a repertoire of strategies in order to foster antiracism in multiracial children, molding the next generation of “antiracist disruptors.”
Clinician-led training through tactile and verbal guidance to improve muscle activity and joint motion are a common but understudied focus of therapeutic interventions for shoulder pain. The purpose ...of this study was to determine if clinician guidance changes scapulothoracic muscle activity and kinematics compared to unguided shoulder exercises.
Eleven participants with shoulder pain were studied. Electromyographic (EMG) sensors were placed on the serratus anterior and upper and lower trapezii. Scapulothoracic and sternoclavicular kinematics were collected using electromagnetic sensors. Five common resisted shoulder exercises were performed with the following guidance: unguided, combined (verbal and tactile cues), and verbal guidance only. One-way repeated measures ANOVAs determined the effect of guidance versus unguided conditions for each exercise.
Nine of ten combinations of exercise and guidance techniques demonstrated a significant effect of guidance for either muscle activity or joint kinematics. The guidance condition with the most frequent significant improvements across all variables was the combined condition. The exercises with the most frequent significant improvements across all variables were the external rotation exercises. Variables improved most frequently were: upper:lower trapezius EMG ratio (up to 11%), sternoclavicular elevation (up to 6°) and scapulothoracic internal rotation positioning (up to 8°), and sternoclavicular retraction displacement (up to 5°).
Shoulder muscle activity and kinematics during exercises can be modified by tactile and verbal guidance. Most improvements in muscle activity occurred with verbal guidance during external rotation exercises. Most improvements in joint positioning and movement occurred with combined guidance during external rotation exercises.
Prosecuting anti-immigration party leaders for hate speech is theorized to yield electoral ramifications. We assess to what extent these trials are mediatized and whether news visibility of hate ...speech prosecution affects levels of anti-immigration party support. We compare four Western European countries (Belgium, France, Germany and the Netherlands) for which aggregate-level media and public opinion data are combined. We find that hate speech trials were highly mediatized, and dominated the headlines for protracted periods. This short-term news attention drives general news visibility for anti-immigration party actors. Thus, news about hate speech prosecution of anti-immigration politicians creates a reinforcing spiral of attention by increasing the general newsworthiness of a political actor. The findings seem to point to the cautious conclusion that hate speech prosecution is either directly or indirectly related to increased electoral support. While in France and Germany, general news visibility of anti-immigration party actors is associated with higher levels of electoral support, in the Netherlands and Belgium, news about hate speech prosecution has a weak and direct positive relationship with anti-immigration party support. This finding yields implications for political communication strategies of parties by suggesting that hate speech prosecution does not undermine the electoral performance of anti-immigration parties. In fact, initiating legal actions yields unintended effects by granting these parties a media platform.
Parties usually argue in favour or against a government coalition based on party considerations in terms of projected policy implementation, power in office and vote maximization – that is, the ...‘policy, office, votes’ triad. So far, however, it remains unclear which claims mainstream parties invoke to motivate their choice to rule or not rule with populist parties. Adopting the ‘policy, voter, office’ triad, this article examines mainstream parties' Twitter claims on ruling with populist parties in Austria, Belgium, Germany and the Netherlands (2006–2021, N = 1,919). Mainstream parties mainly reject ruling with (mostly radical right) populist parties. To justify unwillingness, policy-based motives referring to the populist parties' extremist nature trump motives on office-seeking and vote maximization. To justify willingness, predominantly office-seeking motivations are invoked. Party characteristics (ideology, incumbency status, size) and context, however, shape these claims. This study sheds light on mainstream parties' patterns of political communication on coalition formation with populist parties.
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