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The COVID-19 pandemic was unprecedented in scope and nature, altering everyday life for people across the United States. One major change involved how schools provided educational services. Prior to the pandemic, schools used in-person instruction as their service delivery model for educational and education-related services, such as services for the blind and visually impaired. To document the effects of this historic event, an exploratory survey through Qualtrics was conducted on the perceptions of (a) teachers of students with visual impairments and (b) orientation and mobility specialists in four categories: service delivery models, student demographics, instruction and engagement, and preparation and training. Percentages were calculated with closed questions, and open-ended responses were used to clarify the data. There were some significant post-hoc correlations between ability to provide educational services and instructional delivery models. The results have implications for practitioners and professionals working in higher education.

To produce abundant cell culture samples to generate large, standardized image datasets of human induced pluripotent stem (hiPS) cells, we developed an automated workflow on a Hamilton STAR liquid handler system. This was developed specifically for culturing hiPS cell lines expressing fluorescently tagged proteins, which we have used to study the principles by which cells establish and maintain robust dynamic localization of cellular structures. This protocol includes all details for the maintenance, passage and seeding of cells, as well as Matrigel coating of 6-well plastic plates and 96-well optical-grade, glass plates. We also developed an automated image-based hiPS cell colony segmentation and feature extraction pipeline to streamline the process of predicting cell count and selecting wells with consistent morphology for high-resolution three-dimensional (3D) microscopy. The imaging samples produced with this protocol have been used to study the integrated intracellular organization and cell-to-cell variability of hiPS cells to train and develop deep learning-based label-free predictions from transmitted-light microscopy images and to develop deep learning-based generative models of single-cell organization. This protocol requires some experience with robotic equipment. However, we provide details and source code to facilitate implementation by biologists less experienced with robotics. The protocol is completed in less than 10 h with minimal human interaction. Overall, automation of our cell culture procedures increased our imaging samples’ standardization, reproducibility, scalability and consistency. It also reduced the need for stringent culturist training and eliminated culturist-to-culturist variability, both of which were previous pain points of our original manual pipeline workflow.

Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challenge owing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behaviours that they determine1,2. Here we reduced this complexity by focusing on cellular organization—a key readout and driver of cell behaviour3,4—at the level of major cellular structures that represent distinct organelles and functional machines, and generated the WTC-11 hiPSC Single-Cell Image Dataset v1, which contains more than 200,000 live cells in 3D, spanning 25 key cellular structures. The scale and quality of this dataset permitted the creation of a generalizable analysis framework to convert raw image data of cells and their structures into dimensionally reduced, quantitative measurements that can be interpreted by humans, and to facilitate data exploration. This framework embraces the vast cell-to-cell variability that is observed within a normal population, facilitates the integration of cell-by-cell structural data and allows quantitative analyses of distinct, separable aspects of organization within and across different cell populations. We found that the integrated intracellular organization of interphase cells was robust to the wide range of variation in cell shape in the population; that the average locations of some structures became polarized in cells at the edges of colonies while maintaining the ‘wiring’ of their interactions with other structures; and that, by contrast, changes in the location of structures during early mitotic reorganization were accompanied by changes in their wiring.

Introduction and Methods We do not have an accurate count of the number of teachers of students with visual impairments working in the field, and it is a difficult number to estimate. As part of a national survey, states were contacted to estimate how many teachers of students with visual impairments are working in the United States and compared to the estimate developed by the National Plan for Training Personnel to Serve Children with Blindness and Low Vision (NPTP) in 2000.Results and Discussion The estimate calculated from this process is very similar to the estimate from NPTP (2000), indicating that there are roughly the same number of teachers of students with visual impairments in the field now as there were 20 years ago.

The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different projections from the basolateral amygdala (BLA) are potentiated following reward or punishment learning1–7. However, we do not yet understand how valence-specific information is routed to the BLA neurons with the appropriate downstream projections, nor do we understand how to reconcile the sub-second timescales of synaptic plasticity8–11with the longer timescales separating the predictive cues from their outcomes. Here we demonstrate that neurotensin (NT)-expressing neurons in the paraventricular nucleus of the thalamus (PVT) projecting to the BLA (PVT-BLA:NT) mediate valence assignment by exerting NT concentration-dependent modulation in BLA during associative learning. We found that optogenetic activation of the PVT-BLA:NT projection promotes reward learning, whereas PVT-BLA projection-specific knockout of the NT gene (Nts) augments punishment learning. Using genetically encoded calcium and NT sensors, we further revealed that both calcium dynamics within the PVT-BLA:NT projection and NT concentrations in the BLA are enhanced after reward learning and reduced after punishment learning. Finally, we showed that CRISPR-mediated knockout of the Ntsgene in the PVT-BLA pathway blunts BLA neural dynamics and attenuates the preference for active behavioural strategies to reward and punishment predictive cues. In sum, we have identified NT as a neuropeptide that signals valence in the BLA, and showed that NT is a critical neuromodulator that orchestrates positive and negative valence assignment in amygdala neurons by extending valence-specific plasticity to behaviourally relevant timescales.

Familial hyperparathyroidism is not uncommon in clinical endocrine practice. It encompasses a spectrum of disorders including multiple endocrine neoplasia types 1 (MEN1) and 2A, hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric [...]

Bone marrow is a hematopoietic site harboring multiple populations of myeloid cells in different stages of differentiation. Murine bone marrow eosinophils are traditionally identified by Siglec‐F(+) staining using flow cytometry, whereas neutrophils are characterized by Ly6G(+) expression. However, using flow cytometry to characterize bone marrow hematopoietic cells in wild‐type mice, we found substantial gray areas in identification of these cells. Siglec‐F(+) mature eosinophil population constituted only a minority of bone marrow Lin(+)CD45(+) pool (5%). A substantial population of Siglec‐F(−) cells was double positive for neutrophil marker Ly6G and eosinophil lineage marker, IL‐5Rα. This granulocyte population with mixed neutrophil and eosinophil characteristics is typically attributable to neutrophil pool based on neutral granule staining and expression of Ly6G and myeloid peroxidase. It is distinct from Lineage(−) myeloid progenitors or Siglec‐F(+)Ly6G(+) maturing eosinophil precursors, and can be accurately identified by Lineage(+) staining and positive expression of markers IL‐5Rα and Ly6G. At 15–50% of all CD45(+) hematopoietic cells in adult mice (percentage varies by sex and age), this is a surprisingly dominant population, which increases with age in both male and female mice. RNA‐seq characterization of these cells revealed a complex immune profile and the capacity to secrete constituents of the extracellular matrix. When sorted from bone marrow, these resident cells had neutrophilic phenotype but readily acquired all characteristics of eosinophils when cultured with G‐CSF or IL‐5, including expression of Siglec‐F and granular proteins (Epx, Mbp). Surprisingly, these cells were also able to differentiate into Ly6C(+) monocytes when cultured with M‐CSF. Herein described is the discovery of an unexpected hematopoietic flexibility of a dominant population of multipotent myeloid cells, typically categorized as neutrophils, but with the previously unknown plasticity to contribute to mature pools of eosinophils and monocytes. Characterization of neutrophil‐like Lin(+)Ly6G(+)IL‐5Rα(+) population in normal murine bone marrow reveals its unexpected myeloid plasticity with substantial potential to differentiate to mature eosinophils and monocytes

The COVID-19 pandemic has affected our lives in numerous ways. How youth have been impacted by the pandemic and which preexisting factors best relate to COVID-19 responses are of high importance for effective identification and treatment of those most vulnerable. Youth with pre-pandemic mental health difficulties such as attention-deficit/hyperactivity disorder (ADHD) could be at risk for worse well-being during and after the pandemic.

Homoleptic transition-metal complexes of 2,2’:6′,2″-terpyridine (terpy) and substituted derivatives of the form [M(R-terpy)2]2+display a wide range of redox potentials that correlate well to the Hammett parameter of the terpy substituents. Less is known about the impact of incorporating a phenyl spacer between the functional group responsible for controlling the electron density of terpy and how that translates to metal complexes of the form [M(4′-aryl-terpy)2]2+, where M = Mn, Fe, Co, Ni, and Zn. Herein, we report our studies on these complexes revealed a good correlation of redox potentials of both metal- and ligand-centered events with the Hammett parameters of the aryl substituents, regardless of aryl-substitution pattern (i.e., the presence of multiple functional groups, combinations of withdrawing and donating functional groups). The phenyl spacer results in 60–80% attenuation of electron density as compared to the 4′-substituted terpy analogue, depending on the metal and redox couple analyzed. Density functional theory calculations performed on a simple model system revealed a strong correlation between the Hammett parameters and lowest unoccupied molecular orbital energies of the corresponding substituted pyridine models, thus serving as an inexpensive predictive tool when coupled with electrochemical data. Overall, these data suggest that such ligand modifications may be used in combination with previous approaches to further fine-tune the redox potentials of homoleptic transition-metal complexes, which may have applications in photochemical and electrochemical catalytic processes.

Since the legalization of marijuana in several U.S. states in 2012, there has been concern about increases in the development of cannabis use disorder (CUD). The current study examined rates of CUD in Colorado college students who reported regular marijuana use and assessed a range of factors associated with CUD symptoms, including coping motives, concentrate/dab use, mental health concerns (depression, anxiety), age of regular marijuana use, and alcohol use. College students were recruited from a mid-sized university and completed a baseline assessment that included a marijuana urine screen. Participants reported a median of five CUD symptoms and 90% met criteria for CUD. After adjusting for covariates, the age of regular marijuana use was negatively associated with the number of CUD symptoms, while the average daily alcohol drinks was positively associated with the number of symptoms. Prevention and intervention efforts at the university level should be increased to reduce negative outcomes associated with problem marijuana use.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)1. The development of a vaccine is likely to take at least 12–18 months, and the typical timeline for approval of a new antiviral therapeutic agent can exceed 10 years. Thus, repurposing of known drugs could substantially accelerate the deployment of new therapies for COVID-19. Here we profiled a library of drugs encompassing approximately 12,000 clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate therapeutic drugs for COVID-19. We report the identification of 100 molecules that inhibit viral replication of SARS-CoV-2, including 21 drugs that exhibit dose–response relationships. Of these, thirteen were found to harbour effective concentrations commensurate with probable achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod2–4and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825 and ONO 5334. Notably, MDL-28170, ONO 5334 and apilimod were found to antagonize viral replication in human pneumocyte-like cells derived from H9 human embryonic stem cell lines, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19.

Eosinophils are often cited as playing roles in wound healing and epithelial remodeling; however, the exact triggers and mechanisms of such activity remain poorly understood. Eosinophils show the remarkable capacity to partner with coagulation, which is a highly conserved biologic system evolved to protect an organism from injury by promoting hemostasis and tissue repair. Eosinophils contribute directly by producing key factors in coagulation (tissue factor, thrombin) and fibrinolysis (plasminogen). Moreover, they have been shown to interact with other players in these cascades, such as fibrinogen and the urokinase‐type plasminogen activator/urokinase‐type plasminogen activator receptor system, which further promotes coagulation and fibrinolysis. Although primarily thought of in the contexts of blood clotting and vascular repair, coagulation and fibrinolytic systems play key roles within tissue, in particular during epithelial injury and remodeling. Chronic inflammation and remodeling frequently associate with pro‐thrombotic and pro‐coagulation state. There is a striking association between eosinophils and dysregulated coagulation in animal models and human disease. This review will examine the mechanistic links between eosinophils and the coagulation system in the context of epithelial injury and repair, as well as evidence for this interaction in heart disease, type 2 inflammatory diseases, and cancer. Collectively, multiple emerging studies summarized in this review elucidate an overlooked, but potentially fundamental, biologic mechanism to engage eosinophils in processes of epithelial injury and repair. Review on tissue activation of the coagulation and fibrinolytic pathways as bridging eosinophils with processes of epithelial remodeling.

Reflection involves taking the time to deeply consider a past situation and examine areas of weakness or confusion. It allows identification of learning needs and the development of an action plan to improve future experiences. The aim of this study was to assess second‐year dental students’ ability to reflect in writing on a clinical rotation when prompted with a guided reflection template. The 76 second‐year dental students enrolled in a periodontics clinical rotation course at one U.S. dental school in 2016‐17 completed two reflective writing exercises during the semester. A total of 144 journals (after excluding incomplete journals) were analyzed individually by two evaluators following a rubric developed by Kember. This rubric combined Mezirow's seven levels of reflection into four categories: Habitual Action (HA), Understanding (U), Reflection (R), and Critical Reflection (CR). The first two categories are examples of non‐reflective thoughts, and the latter two are reflective. The two sets of journals were also compared. On average, the journals contained 0.2% HA, 15.9% U, 73.8% R, and 10.1% CR, averaging 16.1% non‐reflective thoughts and 83.9% reflective thoughts. Comparison of the students’ first journal submissions to their second showed that the first journals averaged a higher percentage of reflective thought than the second journals: 85.2% vs. 82.7%, respectively. However, the first journals showed a lower average percentage of critical reflection than the second journals: 9.3% vs. 11.3%, respectively. Overall, a high degree of reflection was found in these students’ journals after rotation in periodontics clinic, suggesting that reflective journaling can serve as a useful learning exercise to promote continual improvement during clinical training.

Introduction: Not much is known about the writing skills of students with visual impairments, and this research is often limited to subgroups of the population or subskills. A more comprehensive approach to research on the writing skills of students with visual impairments is needed.Methods: Researchers used a cross-sectional design to examine the writing of students with visual impairments in Nebraska, attempting to include as many students as possible aged from 4 to 21 years. Fifty students participated. All students were given the Essay Composition subtest of the Wechsler Individualized Achievement Test (third edition), with modified instructions. Essays were scored on number of words, essay elements, and mechanics. Descriptive statistics and statistical comparisons of groups are provided.Results: Mean scores of the overall sample and subgroups fell within the average range when compared to normative samples. There were no statistical differences between students who were blind and students with low vision and no statistical differences between writing modality. There were statistical differences between students with multiple disabilities and others. Results suggest substantial heterogeneity in the sample.Discussion: Results suggest some students with visual impairments write as well as do their sighted peers. These results are complicated by heterogeneity and do not imply anything about the writing ability of individual students.Implications for practitioners: Teachers should avoid making assumptions about the writing potential of specific students. Students with visual impairments in this study scored comparably to a normative sample, and students with multiple disabilities may be able to participate in writing activities in a variety of ways.

Abstract Objective--To determine the performance of the ICD/AIS MAP ([C] E J MacKenzie et al) as a method of classifying injury severity for children. Methods--Data on all children less than [...]

Intestinal microbial dysbiosis has been described in individuals with an HIV-1 infection and may underlie persistent inflammation in chronic infection, thereby contributing to disease progression. Herein, we induced an HIV-1-like intestinal dysbiosis in rhesus macaques (Macaca mulatta) with vancomycin treatment and assessed the contribution of dysbiosis to SIV disease progression. Dysbiotic and control animals had similar disease progression, indicating that intestinal microbial dysbiosis similar to that observed in individuals with HIV is not sufficient to accelerate untreated lentiviral disease progression.

Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial‐mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal‐derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situhematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non‐immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial–mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non‐immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease. Review on the two‐way communication between tissue and eosinophils, discussing eosinophil heterogeneity in the framework of biological processes occurring in different tissue states.

Previous work indicated that activation of D1-like dopamine receptors (D1DRs) in the nucleus accumbens shell promoted cocaine seeking through a process involving the activation of PKA and GluA1-containing AMPA receptors (AMPARs). A-kinase anchoring proteins (AKAPs) localize PKA to AMPARs leading to enhanced phosphorylation of GluA1. AKAP150, the most well-characterized isoform, plays an important role in several forms of neuronal plasticity. However, its involvement in drug addiction has been minimally explored. Here we examine the role of AKAP150 in cocaine reinstatement, an animal model of relapse. We show that blockade of PKA binding to AKAPs in the nucleus accumbens shell of Sprague–Dawley rats attenuates reinstatement induced by either cocaine or a D1DR agonist. Moreover, this effect is specific to AKAP150, as viral overexpression of a PKA-binding deficient mutant of AKAP150 also impairs cocaine reinstatement. This viral-mediated attenuation of cocaine reinstatement was accompanied by decreased phosphorylation of GluA1-containing AMPARs and attenuated AMPAR eEPSCs. Collectively, these results suggest that AKAP150 facilitates the reinstatement of cocaine-seeking behavior by amplifying D1DR/PKA-dependent AMPA transmission in the nucleus accumbens.

Abstract

The sperm of Yellow Perch Perca flavescensof two different age‐classes, age 0 and 3, were cryopreserved using two different cryoprotectants (dimethylsulfoxide [DMSO] and methanol [MetOH]) with two freezing methods (pellet and vial). The viability and quality of the progenies obtained from fertilization with cryopreserved sperm were then examined. The motility of Walleye Sander vitreus sperm was examined following cryopreservation and ultraviolet (UV) irradiation, with the aim of using heterologous cryopreserved sperm to inseminate Yellow Perch eggs to ensure gynogenesis. The first experiment compared the motility of fresh sperm and pellet method cryopreserved sperm devoid of salmon seminal plasma. Despite the high motility of fresh sperm—75% and 100%—of males age 0 and 3, respectively, the postthaw motility of seminal plasma devoid cryopreserved sperm was 0%. The second experiment addressed the efficiency of pellet and vial freezing methods with DMSOand MetOHsupplemented with salmon seminal plasma. Cryopreserved sperm was thawed and motility measured. Sperm motility was not significantly different between pellet (13.3 ± 10.4%) and vial (10.3 ± 12.9%) methods in the absence of sperm extender; however, sperm motility of the pellet method was further improved (20 ± 8.7%) with the addition of sperm extender after thawing, while motility of the vial method sperm (10 ± 7.1%) was not. Cryopreserved sperm was further evaluated based on fertilization rate and ultimate survival and growth of larvae and juveniles through 14 d posthatch. Effects of UVexposure on fresh and pellet method cryopreserved sperm following UVirradiation were also examined. The motility of control sperm cryopreserved with DMSOand MetOH, and UV‐exposed sperm cryopreserved with DMSOdecreased from 100% motility before cryopreservation (fresh sperm) to 75% following cryopreservation, while UV‐exposed sperm cryopreserved with MetOHdecreased from 100% to 50%. This experiment provides significant new data to improve the effectiveness of straightforward cryopreservation techniques for Yellow Perch.

There is a relationship between the rate at which the 'grey matter' of the brain, the front main folded surface part (the cortex), consumes sugar (glucose) and damage to a certain part of the brain beneath this part (the nucleus basalis of Meynert). A few days after damage on one side of the brain to the nucleus basalis, both sides of the grey matter of the brain consume significantly less sugar, but sugar consumption returns to normal over a few months. In certain parts (frontal, temporal, and parietal lobes) of the brain on the side that is damaged, there is a decrease in production of a substance (choline acetyltransferase) which facilitates transmission of nerve impulses. The less the brain is damaged, the smaller the drop in production of this substance and in consumption of sugar. The reason both sides of the brain consume less sugar while only one side produces less of the acetyltransferase enzyme is probably because damage to one side reduces the number of tasks the brain as a whole attempts to perform. The nerves of the brain eventually adjust to their damaged condition and start to work normally again. This may all be relevant to similar brain malfunctions that occur in Alzheimer's disease.

In winter 2013, a sea ice breakout in the Beaufort Sea produced extensive fracturing and contributed to record ice export. Rheinlænder et al. (2022, https://doi.org/10.1029/2022GL099024) simulated this event using the neXtSIM sea ice model, reproducing a realistic progression of lead opening and ice drift following the track of an anticyclone. Their simulations indicate strong winds and thin ice are key factors in breakouts. We discuss observational records giving additional insight into the mechanisms controlling breakout events, including the role of wind direction. Breakouts are common and have occurred under weaker winds than in 2013 and in thicker ice of previous decades. During 2013 and other events, patterns of lead opening during breakout followed changes in wind direction relative to the coast with anticyclone position. For skillful predictions of future breakouts, models must reproduce this behavior, and their performance should be assessed across a range of wind and ice conditions. In winter, the Beaufort Sea is covered by a layer of sea ice that is usually frozen against the southern and eastern coastlines that bound the sea. When winds continuously blow from east to west away from these boundaries, the ice cover can tear apart and rapidly drift away from the coasts in what is called a breakout event. The prediction of such dynamic events is important for those who navigate the region. Rheinlænder et al. (2022, https://doi.org/10.1029/2022GL099024) recently used the neXtSIM sea ice model to simulate realistic ice cracking and drift during an exceptionally strong breakout that occurred in 2013. The authors highlighted strong winds and thin sea ice as key factors for breakout. We use observational records to provide additional insight into processes during Beaufort breakouts. Records of many similar events demonstrate that breakouts are common under weather patterns that produce east‐to‐west winds, even for weaker winds and thicker ice than in 2013. Across observed events, wind direction influences sea ice fracturing patterns and breakout timing. To ensure that model predictions of future sea ice breakouts are accurate, simulations should be compared against observations of multiple recorded events that span a range of wind and ice conditions. Observational data provide context for a 2013 Beaufort Sea (BS) breakout simulated with the neXtSIM model by Rheinlænder et al. (2022, https://doi.org/10.1029/2022GL099024)While the 2013 event was exceptional, winter sea ice breakout is common under anticyclonic winds including in years with thicker ice packsWind direction relative to the coast influences the timing and location of lead opening during breakout in the BS Observational data provide context for a 2013 Beaufort Sea (BS) breakout simulated with the neXtSIM model by Rheinlænder et al. (2022, https://doi.org/10.1029/2022GL099024) While the 2013 event was exceptional, winter sea ice breakout is common under anticyclonic winds including in years with thicker ice packs Wind direction relative to the coast influences the timing and location of lead opening during breakout in the BS

Proper repair of DNA double-strand breaks is essential to the maintenance of genomic stability and avoidance of genetic disease. Organisms have many ways of repairing double-strand breaks, including the use of homologous sequences through homology-directed repair. While homology-directed repair is often error free, in single-strand annealing homologous repeats flanking a double-strand break are annealed to one another, leading to the deletion of one repeat and the intervening sequences. Studies in yeast have shown a relationship between the length of the repeat and single-strand annealing efficacy. We sought to determine the effects of homology length on single-strand annealing in Drosophila, as Drosophilauses a different annealing enzyme (Marcal1) than yeast. Using an in vivo single-strand annealing assay, we show that 50 base pairs are insufficient to promote single-strand annealing and that 500–2,000 base pairs are required for maximum efficiency. Loss of Marcal1 generally followed the same homology length trend as wild-type flies, with single-strand annealing frequencies reduced to about a third of wild-type frequencies regardless of homology length. Interestingly, we find a difference in single-strand annealing rates between 500-base pair homologies that align to the annealing target either nearer or further from the double-strand break, a phenomenon that may be explained by Marcal1 dynamics. This study gives insights into Marcal1 function and provides important information to guide the design of genome engineering strategies that use single-strand annealing to integrate linear DNA constructs into a chromosomal double-strand break.

The association made between the meaning, spelling, and pronunciation of a word has been shown to help children remember the meanings of words. The present study addressed whether the presence of a target word in Braille during instruction facilitated vocabulary learning more efficiently than an auditory-only instructional condition. The authors used an adapted alternating treatments single-case experimental design with three students with visual impairments who read Braille, collecting data on definition recall and spelling during each session. Data on definition recall were used to determine mastery. The results of this study are not consistent with previous findings with students who read print. Visual analyses of the data indicated that participants reached mastery in both conditions, but all three reached mastery on definition recall in fewer sessions in the auditory-only condition. Spellings of words were learned in the flashcard condition only, and possible implications of this are discussed. The difference in the unit of recognition and working memory load between reading Braille and reading print is discussed as one possible explanation.

I AM SORRY that my first letter to Maclean's isn't about something more substantial, but I just have to let you know how irritated I was by two references in [...]

Here we present a study on the presence of physisorbed water on the surface of aligned carbon nanotubes (CNTs) in ambient conditions, where the wet CNT array mass can be more than 200% larger than that of dry CNTs, and modeling indicates that a water layer >5 nm thick can be present on the outer CNT surface. The experimentally observed nonlinear and non-monotonic dependence of the mass of adsorbed water on the CNT packing (volume fraction) originates from two competing modes. Physisorbed water cannot be neglected in the design and fabrication of materials and devices using nanowires/nanofibers, especially CNTs, and further experimental and ab initiostudies on the influence of defects on the surface energies of CNTs, and nanowires/nanofibers in general, are necessary to understand the underlying physics and chemistry that govern this system.

Introduction This study evaluated whether children with visual impairments who receive repeated reading instruction exhibit an increase in their oral reading rate and comprehension and a decrease in oral reading error rates.Methods A single-subject, changing-criterion design replicated across three participants was used to demonstrate the association between a repeated reading intervention and the oral reading rate, comprehension, and error rate.Results Visual analysis of the data indicates that there was a functional relation between repeated reading and oral reading rate for two participants, and a functional relation between repeated reading and comprehension for all participants. There was not a functional relation between repeated oral reading and error rate.Discussion Based on the results of this study, repeated reading appears to be an effective practice for some students with visual impairments.Implications for practitioners Teachers and parents can engage children in repeated reading activities in an effort to develop automaticity in reading and to improve oral reading rates.

While corporate sustainability is interpreted broadly to mean ensuring success in the present without compromising the future, a well-accepted workable definition has remained elusive. Sustainability is often defined using a set of criteria or metrics that address the recognised environmental, social, and economic pillars of sustainability. However, standard metrics fail to account for how companies deal with operational challenges to their sustainability and viability. As a 175 year old diesel engine manufacturer, Navistar, Inc. has developed a model to address not only the three pillars of sustainability but also its significant business challenges, including those related to health concerns over its diesel products and environmental and employee legacies. Featuring a commitment to sustainable innovation and product stewardship and reliance on sound science, Navistar’s sustainability model has evolved in response to its unique operating environment. This model illustrates the benefits of designing sustainability strategies to address specific business challenges rather than a standard set of criteria.

The anaphase-promoting complex (APC), a large evolutionarily conserved ubiquitin ligase complex, regulates cell cycle progression through mitosis and G1. Here, we present data suggesting that APC-dependent cell cycle progression relies on a specific set of posttranslational histone-modifying enzymes. Multiple APC subunit mutants were impaired in total and modified histone H3 protein content. Acetylated H3K56 (H3K56Ac) levels were as reduced as those of total H3, indicating that loading histones with H3K56Acis unaffected in APC mutants. However, under restrictive conditions, H3K9Acand dimethylated H3K79 (H3K79me2) levels were more greatly reduced than those of total H3. In a screen for histone acetyltransferase (HAT) and histone deacetylase (HDAC) mutants that genetically interact with the apc5CA(chromatin assembly) mutant, we found that deletion of GCN5 or ELP3 severely hampered apc5CAtemperature-sensitive (ts) growth. Further analyses showed that (i) the elp3Δ gcn5Δ double mutant ts defect was epistatic to that observed in apc5CAcells; (ii) gcn5Δ and elp3Δ mutants accumulate in mitosis; and (iii) turnover of the APC substrate Clb2 is not impaired in elp3Δ gcn5Δ cells. Increased expression of ELP3 and GCN5, as well as genes encoding the HAT Rtt109 and the chromatin assembly factors Msi1 and Asf1, suppressed apc5CAdefects, while increased APC5 expression partially suppressed elp3Δ gcn5Δ growth defects. Finally, we demonstrate that Gcn5 is unstable during G1and following G1arrest and is stabilized in APC mutants. We present our working model in which Elp3/Gcn5 and the APC work together to facilitate passage through mitosis and G1. To progress into S, we propose that at least Gcn5 must then be targeted for degradation in an APC-dependent fashion.

We studied the potential neuroprotective effects of halothane and desflurane, compared with the awake state, on infarct size following 2 h of intraluminal middle cerebral artery occlusion (MCAo) and 22 h of reperfusion.

A new series of ligands with a novel phosphine−aminophosphine ligation design as depicted in structure 1 has been prepared on a ferrocenylethyl backbone. These BoPhoz ligands of structure 2 have afforded exceedingly high activity and enantioselectivity in the rhodium-catalyzed asymmetric hydrogenation of dehydro-α-amino acid derivatives, itaconic acids, and α-ketoesters. These air-stable ligands are readily prepared from cost-effective and non-pyrophoric intermediates.