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Background Post-stroke upper limb (UL) motor improvement is associated with adaptive neuroplasticity and motor learning. Both intervention-related (including provision of intensive, variable, and task-specific practice) and individual-specific factors (including the presence of genetic polymorphisms) influence improvement. In individuals with stroke, most commonly, polymorphisms are found in Brain Derived Neurotrophic Factor (BDNF), Apolipoprotein (APOE) and Catechol-O-Methyltransferase (COMT). These involve a replacement of cystine by arginine (APOEε4) or valines by 1 or 2 methionines (BDNF:val 66 met, met 66 met; COMT:val 158 met; met 158 met). However, the implications of these polymorphisms on post-stroke UL motor improvement specifically have not yet been elucidated. Objective Examine the influence of genetic polymorphism on post-stroke UL motor improvement. Design Systematic Review and Meta-Analysis. Methods We conducted a systematic search of the literature published in English language. The modified Downs and Black checklist helped assess study quality. We compared change in UL motor impairment and activity scores between individuals with and without the polymorphisms. Meta-analyses helped assess change in motor impairment (Fugl Meyer Assessment) scores based upon a minimum of 2 studies/time point. Effect sizes (ES) were quantified based upon the Rehabilitation Treatment Specification System as follows: small (0.08-0.18), medium (0.19 -0.40) and large (≥0.41). Results We retrieved 10 (4 good and 6 fair quality) studies. Compared to those with BDNF val 66 met and met 66 met polymorphism, meta-analyses revealed lower motor impairment (large ES) in those without the polymorphism at intervention completion (0.5, 95% CI: 0.11-0.88) and at retention (0.58, 95% CI:0.06-1.11). The presence of CoMT val 158 met or met 158 met polymorphism had similar results, with lower impairment (large ES ≥1.5) and higher activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOEε4 form did not influence UL motor improvement. Conclusion Polymorphisms with the presence of 1 or 2 met alleles in BDNF and COMT negatively influence UL motor improvement. Registration https://osf.io/wk9cf/ .

A two-component undergraduate laboratory experience has been developed by students in a senior level capstone course. The first component is a 3 h laboratory experience dedicated to the rapid synthesis of a metal-organic framework (MOF-808) in aqueous solution using readily available reagents and equipment. During the second component, MOF-808 was characterized via a suite of instruments: powder X-ray diffraction (PXRD), thermal gravimetric analysis (TGA), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). In addition, quantitative [superscript 19]F{[superscript 1]H} NMR spectroscopy was utilized to quantify the amount of perfluorobutanesulfonate (PFBS), one example of a poly- or perfluoroalkyl substance (aka PFAS), adsorbed from solution. The two 3 h laboratory experiences were subsequently deployed in a foundation level inorganic chemistry course. This two-component, multi-instrument lab experience provides students an opportunity to synthesize a modern porous solid and utilize it in an emerging application of MOF science.

This article explores how doctoral graduates in Aotearoa New Zealand are being impacted by the COVID-19 pandemic. A survey captured the employment and mobility situations of doctoral graduates from 2019 to early 2021 from six of the eight universities in NZ. The 406 survey responses were analysed using descriptive statistics, as well as drawing on Cognitive Information Processing (CIP) theory in an inductive analysis of freeform comments. Most respondents were aspiring to academic careers, but the pandemic led to the loss of job offers for 19.2% and altered career plans for 60.6%. Family circumstances impacted career decisions for 21.4% and these were complicated by mobility difficulties with border closures and visa issues. The impacts of the pandemic on careers were significantly greater for international graduates. The qualitative analysis revealed themes of uncertainty, complications, pragmatism and academia. Using CIP, it is apparent that the pandemic has created a more complex job environment and heightened stress and anxiety over career and mobility options. As shown in our conceptual model, NZ universities need to better prepare graduates for the landscape of career possibilities, making students aware of their attributes, supporting their wellbeing, and helping them navigate the complexity of the current job environment.

Background:. In recent years, self-tanners have become a well-liked alternative to sun tanning and tanning bed usage, as strikingly similar results can be achieved without the harmful side effects of ultraviolet exposure. Objective:. The aim of this study is to investigate the presence and prevalence of potential allergens in the most popular self-tanning products. Methods:. Five major retailers in the United States were evaluated, from which 17 different brands and 44 unique self-tanning products were analyzed. The ingredients in each self-tanning product were compared with 80 and 36 notable contact allergens taken from the North American Contact Dermatitis Group and Food and Drug Administration–approved T.R.U.E (Thin-Layer Rapid Use Epicutaneous Patch Test), respectively. Results:. We found that contact allergens are frequently present in self-tanning products; allergens especially common are propylene glycol, linalool, polysorbate, d-limonene, benzyl alcohol, tocopherol (vitamin E), fragrances, and other scented botanicals. On average, each self-tanner we analyzed contained 11.86 allergens. Limitations:. The limitation is that commercial names could not be eliminated from the analysis, introducing potential bias. Conclusion:. While self-tanning products are a safer alternative to tanning bed use or sunbathing, consumers and clinicians alike must be aware that they may cause an allergic reaction of the skin for some users.

Designing spray-dried particles for inhalation aims at specific physicochemical properties including a respirable aerodynamic diameter and adequate powder dispersibility. Leucine, an amphiphilic amino acid, has been shown to aid in optimizing bulk powder properties. Mannitol, a model crystalline active and common bulking agent, was co-sprayed with leucine at several excipient ratios, ethanol/water ratios, and spray dryer outlet temperatures in order to experimentally probe the underlying particle formation mechanisms in this binary crystalline system. During the droplet drying of two crystallizing components, the material that nucleates first will preferentially enrich the surface. It is desired to have a completely crystalline leucine shell to improve powder properties, however, mannitol competes with leucine for the surface depending on excipient concentration and manufacturing parameters. The resulting particles were studied initially and at a two-month timepoint via solid state characterization, visual analysis, and particle size analysis in order to detect changes in bulk powder properties. It was determined that, similar to systems where only leucine can crystallize, initial leucine saturation in the formulation dictates powder characteristics.

A life-threatening manifestation of Covid-19 infection is a cytokine storm that requires hospitalization and supplemental oxygen. Various strategies to reduce inflammatory cytokines have had some success in limiting cytokine storm and improving survival. Agonists of adenosine A2A receptors (A2AR) reduce cytokine release from most immune cells. Apadenoson is a potent and selective anti-inflammatory adenosine analog that reduces inflammation. When administered by subcutaneous osmotic pumps to mice infected with SARS CoV-2, Apadenoson was found to improve the outcomes of infection as measured by a decrease in weight loss, improved clinical symptoms, reduced levels of proinflammatory cytokines and chemokines in bronchial lavage (BAL) fluid, and enhanced survival of K18-hACE2 transgenic mice. These results support further examination of A2AR agonists as therapies for treating cytokine storm due to COVID-19.

Logic‐gated engineered cells are an emerging therapeutic modality that can take advantage of molecular profiles to focus medical interventions on specific tissues in the body. However, the increased complexity of these engineered systems may pose a challenge for prediction and optimization of their behavior. Here we describe the design and testing of a flow cytometry‐based screening system to rapidly select functional inhibitory receptors from a pooled library of candidate constructs. In proof‐of‐concept experiments, this approach identifies inhibitory receptors that can operate as NOT gates when paired with activating receptors. The method may be used to generate large datasets to train machine learning models to better predict and optimize the function of logic‐gated cell therapeutics. [ABSTRACT FROM AUTHOR]

Background: Post-stroke upper limb (UL) motor improvement is associated with adaptive neuroplasticity and motor learning. Both intervention-related (including provision of intensive, variable, and task-specific practice) and individual-specific factors (including the presence of genetic polymorphisms) influence improvement. In individuals with stroke, most commonly, polymorphisms are found in Brain Derived Neurotrophic Factor (BDNF), Apolipoprotein (APOE) and Catechol-O-Methyltransferase (COMT). These involve a replacement of cystine by arginine (APOEε4) or valines by 1 or 2 methionines (BDNF:val66met, met66met; COMT:val158met; met158met). However, the implications of these polymorphisms on post-stroke UL motor improvement specifically have not yet been elucidated. Objective: Examine the influence of genetic polymorphism on post-stroke UL motor improvement. Design: Systematic Review and Meta-Analysis. Methods: We conducted a systematic search of the literature published in English language. The modified Downs and Black checklist helped assess study quality. We compared change in UL motor impairment and activity scores between individuals with and without the polymorphisms. Meta-analyses helped assess change in motor impairment (Fugl Meyer Assessment) scores based upon a minimum of 2 studies/time point. Effect sizes (ES) were quantified based upon the Rehabilitation Treatment Specification System as follows: small (0.08-0.18), medium (0.19 -0.40) and large (≥0.41). Results: We retrieved 10 (4 good and 6 fair quality) studies. Compared to those with BDNF val66met and met66met polymorphism, meta-analyses revealed lower motor impairment (large ES) in those without the polymorphism at intervention completion (0.5, 95% CI: 0.11-0.88) and at retention (0.58, 95% CI:0.06-1.11). The presence of CoMT val158met or met158met polymorphism had similar results, with lower impairment (large ES ≥1.5) and higher activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOEε4 form did not influence UL motor improvement. Conclusion: Polymorphisms with the presence of 1 or 2 met alleles in BDNF and COMT negatively influence UL motor improvement. Registration: https://osf.io/wk9cf/. Plain language summary: This research paper focuses on the impact of variations in DNA sequence in certain genes on improvement seen in the arms in people who have had a stroke. In this study, we studied the role of 3 genes previously identified as having variations in DNA sequence. The authors searched published research articles from 2000 onwards and selected articles that satisfied certain criteria. We then checked the quality of the selected papers. Next, we combined common data from same tests used to examine motor improvement in the arms to check if there was an overall effect. A total of 10 papers were found. The selected articles were either good or moderate in quality. Variations in DNA structure in 2 out of the 3 genes studied affected the ability to improve the use of the arms in daily life after a stroke. Such information can have important implications in the extent of recovery that is possible after a stroke. It can also be helpful to decide the best rehabilitation options that can be offered to help maximize their ability to use the arms after a stroke. [ABSTRACT FROM AUTHOR]

Investigations into the mechanisms of injury and repair in fibroproliferative disease require consideration of the spatial heterogeneity inherent in the disease. Most scoring of fibrotic remodeling in preclinical animal models relies on the modified Ashcroft score, which is an ordinal rubric of macroscopic resolution. The obvious limitations of manual histopathologic scoring have generated an unmet need for unbiased, repeatable scoring of fibroproliferative burden in tissue. Using computer vision approaches on immunofluorescence imaging of the extracellular matrix component laminin, we generated a robust and repeatable quantitative remodeling scorer. In the bleomycin lung injury model, the quantitative remodeling scorer shows significant agreement with the modified Ashcroft scale. This antibody-based approach is easily integrated into larger multiplex immunofluorescence experiments, which we demonstrate by testing the spatial apposition of tertiary lymphoid structures to fibroproliferative tissue, a poorly characterized phenomenon observed in both human interstitial lung diseases and preclinical models of lung fibrosis. The tool reported in this article is available as a stand-alone application that is usable without programming knowledge. [ABSTRACT FROM AUTHOR]

Background: Fetal alcohol spectrum disorders (FASD) represent a leading cause of non-genetic neuropathologies. Recent preclinical evidence from suggests that prenatal ethanol exposure (PrEE), like other environmental exposures, may have a significant, transgenerational impact on the offspring of directly exposed animals, including altered neocortical development at birth and behavior in peri-pubescent mice. How these adverse behavioral outcomes are manifested within the brain at the time of behavioral disruption remains unknown.Methods: A transgenerational mouse model of FASD was used to generate up to a third filial generation of offspring to study. Using a multi-modal battery of behavioral assays, we assessed motor coordination/function, sensorimotor processing, risk-taking behavior, and depressive-like behavior in postnatal day (P) 20 pre-pubescent mice. Additionally, sensory neocortical area connectivity using dye tracing, neocortical gene expression using in situ RNA hybridization, and spine density of spiny stellate cells in the somatosensory cortex using Golgi-Cox staining were examined in mice at P20.Results: We found that PrEE induces behavioral abnormalities including abnormal sensorimotor processing, increased risk-taking behavior, and increased depressive-like behaviors that extend to the F3 generation in 20-day old mice. Assessment of both somatosensory and visual cortical connectivity, as well as cortical RZRβ expression in pre-pubescent mice yielded no significant differences among any experimental generations. In contrast, only directly-exposed F1 mice displayed altered cortical expression of Id2 and decreased spine density among layer IV spiny stellate cells in somatosensory cortex at this pre-pubescent, post weaning age.Conclusion: Our results suggest that robust, clinically-relevant behavioral abnormalities are passed transgenerationally to the offspring of mice directly exposed to prenatal ethanol. Additionally, in contrast to our previous findings in the newborn PrEE mouse, a lack of transgenerational findings within the brain at this later age illuminates the critical need for future studies to attempt to discover the link between neurological function and the described behavioral changes. Overall, our study suggests that multi-generational effects of PrEE may have a substantial impact on human behavior as well as health and well-being and that these effects likely extend beyond early childhood.

The asymmetric imidazolium salt [Ru[(dmbpy).sub.2][(bpip)]([PF.sub.6]).sub.3] (bpip = 1-benzyl-3-isopropyl-1H-imidazo[4,5-f][1,10]phenanthrolinium) was prepared by a four-step synthetic route. The isotopomer labelled with [.sup.13]C at the C2 position of bpip was prepared from 1,10-phenanthroline-5,6-diamine and triethyl orthoformate-(formyl-[.sup.13]C). Deprotonation at low temperatures in acetonitrile using [KO.sup.t]Bu and KHMDS were monitored by NMR to investigate the formation of the free N-heterocyclic carbene. Key words: ruthenium, polypyridyl, [.sup.13]C labelling, N-heterocyclic carbene, photocatalyst. Nous avons prepare le sel d'imidazolium asymetrique, le [Ru[(dmbpy).sub.2][(bpip)]([PF.sub.6]).sub.3] (bpip = 1-benzyl-3-isopropyl-1Himidazo [4,5f][1,10]phenanthrolinium), par une voie de synthese en quatre etapes. L'isotopomere marque au [.sup.13]C a la position C2 du ligand bpip a ete prepare a partir de la 1,10-phenanthroline-5,6-diamine et de l'orthoformiate d'ethyle-(formiate-[.sup.13]C). Nous avons suivi par RMN la deprotonation a basse temperature dans l'acetonitrile effectuee a l'aide du [KO.sup.t]Bu et du KHMDS afin d'etudier la formation du carbene N-heterocyclique libre. [Traduit par la Redaction] Mots-cles : ruthenium, polypyridyl, marquage au [.sup.13]C, carbene N-heterocyclique, photocatalyseur., Introduction A highly investigated method to store solar energy is artificial photosynthesis. (1,2) Water and sunlight are converted into [H.sub.2] and [O.sub.2], or water, sunlight, and [CO.sub.2] are converted into [...]

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counterintuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfvén waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, α = 2 as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed >600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: preflare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that α = 1.63 ± 0.03. This is below the critical threshold, suggesting that Alfvén waves are an important driver of coronal heating.

The displacement of a river to a new position within its adjacent floodplain is called avulsion, and here we examine how a newly recognized style, called retrogradational avulsion, affects the surrounding floodplain in tropical rainforests using remote sensing. Retrogradational avulsions begin with a channel blockage that causes self‐propagating upstream dechannelization and flooding. While this flooding results in vegetation die‐off and floodplain sedimentation, few quantitative measurements of disturbance by retrogradational avulsions exist. Here, we first focus on land‐cover change following a single retrogradational avulsion in Papua New Guinea from 2012 to 2021. During the avulsion, the river dechannelized 892 m upstream, and the parent channel width doubled. Using maximum likelihood image classification, we observed healthy vegetation fluctuated around 4.3 km2, vegetation regrowth peaked in 2017 at 3.2 km2, dead vegetation peaked in 2013 at 2.1 km2, and visible extent of deposited sediment was greatest in 2015 at 0.44 km2. We also examined 19 other retrogradational avulsions in Papua New Guinea and South America using NDVI. The area of floodplain disturbance (i.e., vegetation die‐off and possible sedimentation) for each avulsion ranged from <1 to >13 km2 and scaled with the dechannelization area. Comparing our plan‐view disturbance results with FABDEM digital‐elevation data and ICESat‐2 surface elevation measurements, we hypothesize floodplain disturbance extent is a function of topographic relief. Our results also suggest that retrogradational avulsions, on average, perturb larger areas of forest compared to blowdowns, suggesting this might be an important disturbance regime that influences gap‐filling regeneration in tropical rainforests. [ABSTRACT FROM AUTHOR]

Designing spray-dried particles for inhalation aims at specific physicochemical properties including a respirable aerodynamic diameter and adequate powder dispersibility. Leucine, an amphiphilic amino acid, has been shown to aid in optimizing bulk powder properties. Mannitol, a model crystalline active and common bulking agent, was co-sprayed with leucine at several excipient ratios, ethanol/water ratios, and spray dryer outlet temperatures in order to experimentally probe the underlying particle formation mechanisms in this binary crystalline system. During the droplet drying of two crystallizing components, the material that nucleates first will preferentially enrich the surface. It is desired to have a completely crystalline leucine shell to improve powder properties, however, mannitol competes with leucine for the surface depending on excipient concentration and manufacturing parameters. The resulting particles were studied initially and at a two-month timepoint via solid state characterization, visual analysis, and particle size analysis in order to detect changes in bulk powder properties. It was determined that, similar to systems where only leucine can crystallize, initial leucine saturation in the formulation dictates powder characteristics. [ABSTRACT FROM AUTHOR]

"[T]he great security against a gradual concentration of the several powers in the same department consists in giving to those who administer each department the necessary constitutional means and personal [...]

Type I spiral ganglion neurons (SGNs) are the auditory afferents that transmit sound information from cochlear inner hair cells (IHCs) to the brainstem. These afferents consist of physiological subtypes that differ in their spontaneous firing rate (SR), activation threshold, and dynamic range and have been described as low, medium, and high SR fibers. Lately, single-cell RNA sequencing experiments have revealed three molecularly defined type I SGN subtypes. The extent to which physiological type I SGN subtypes correspond to molecularly defined subtypes is unclear. To address this question, we have generated mouse lines expressing CreERT2 in SGN subtypes that allow for a physiological assessment of molecular subtypes. We show that Lypd1-CreERT2 expressing SGNs represent a well-defined group of neurons that preferentially innervate the IHC modiolar side and exhibit a narrow range of low SRs. In contrast, Calb2-CreERT2 expressing SGNs preferentially innervate the IHC pillar side and exhibit a wider range of SRs, thus suggesting that a strict stratification of all SGNs into three molecular subclasses is not obvious, at least not with the CreERT2 tools used here. Genetically marked neuronal subtypes refine their innervation specificity onto IHCs postnatally during the time when activity is required to refine their molecular phenotype. Type I SGNs thus consist of genetically defined subtypes with distinct physiological properties and innervation patterns. The molecular subtype-specific lines characterized here will provide important tools for investigating the role of the physiologically distinct type I SGNs in encoding sound signals. [ABSTRACT FROM AUTHOR]

Throughout history, English and American courts have adapted traditional equitable doctrines and remedies to new social, economic, and technological circumstances. This traditional approach to equity traces to England's High Court of Chancery in the seventeenth century, and federal courts in the United States have applied it since the founding, fashioning new forms of equitable relief to break labor strikes, desegregate schools, redraw electoral maps, and prevent the enforcement of unconstitutional laws. Yet despite its pedigree, the Supreme Court has abandoned this traditional approach to equity over the past two decades. Today, the Court limits federal courts to the doctrines and remedies that were available in historical courts of equity--either in 1789, at the time of the founding, or before 1938, when the Federal Rules of Civil Procedure merged law and equity in federal court. This new approach freezes equity in time, forbidding judge-driven change and leaving all future modifications to Congress. This Article proposes an alternative to the Supreme Court's approach, turning not to equity's history but rather to its function. The traditional approach to equity that prevailed until the middle of the twentieth century is hard to square with modern-day skepticism of judge-made law. But as recent scholarship shows, equity still has a role to play in today's legal systems, where it can counter bad-faith attempts to exploit the law's generality and prospectivity. A better account of the federal equity power would permit federal courts to update traditional equitable doctrines and remedies, but only where needed to address these kinds of complex problems. Accordingly, while the federal courts should not treat their equity powers as an all-purpose remedial authority, they should use them to address problems like Texas's S.B. 8, which the state designed specifically to circumvent the Constitution's then-in-force protections for abortion. [ABSTRACT FROM AUTHOR]

Noxious stimuli or injury can trigger long-lasting sensitization to non-nociceptive stimuli (referred to as allodynia in mammals). Long-term potentiation (LTP) of nociceptive synapses has been shown to contribute to nociceptive sensitization (hyperalgesia) and there is even evidence of heterosynaptic spread of LTP contributing to this type of sensitization. This study will focus on how activation of nociceptors elicits heterosynaptic LTP (hetLTP) in non-nociceptive synapses. Previous studies in the medicinal leech (Hirudo verbana) have demonstrated that high-frequency stimulation (HFS) of nociceptors produces both homosynaptic LTP as well as hetLTP in non-nociceptive afferent synapses. This hetLTP involves endocannabinoid-mediated disinhibition of non-nociceptive synapses at the presynaptic level, but it is not clear if there are additional processes contributing to this synaptic potentiation. In this study, we found evidence for the involvement of postsynaptic level change and observed that postsynaptic N-methyl-d-aspartate (NMDA) receptors (NMDARs) were required for this potentiation. Next, Hirudo orthologs for known LTP signaling proteins, CamKII and PKCζ, were identified based on sequences from humans, mice, and the marine mollusk Aplysia. In electrophysiological experiments, inhibitors of CamKII (AIP) and PKCζ (ZIP) were found to interfere with hetLTP. Interestingly, CamKII was found to be necessary for both induction and maintenance of hetLTP, whereas PKCζ was only necessary for maintenance. These findings show that activation of nociceptors can elicit a potentiation of non-nociceptive synapses through a process that involves both endocannabinoid-mediated disinhibition and NMDAR-initiated signaling pathways. NEW & NOTEWORTHY Pain-related sensitization involves increases in signaling by non-nociceptive sensory neurons. This can allow non-nociceptive afferents to have access to nociceptive circuitry. In this study, we examine a form of synaptic potentiation in which nociceptor activity elicits increases in non-nociceptive synapses. This process involves endocannabinoids, "gating" the activation of NMDA receptors, which in turn activate CamKII and PKCζ. This study provides an important link in how nociceptive stimuli can enhance non-nociceptive signaling related to pain. [ABSTRACT FROM AUTHOR]