Reducing neuroinflammation by delivery of IL‐10 encoding lentivirus from multiple‐channel bridges

The spinal cord is unable to regenerate after injury largely due to growth‐inhibition by an inflammatory response to the injury that fails to resolve, resulting in secondary damage and cell death. An approach that prevents inhibition by attenuating the inflammatory response and promoting its resolution through the transition of macrophages to anti‐inflammatory phenotypes is essential for the creation of a growth permissive microenvironment. Viral gene delivery to induce the expression of anti‐inflammatory factors provides the potential to provide localized delivery to alter the host inflammatory response. Initially, we investigated the effect of the biomaterial and viral components of the delivery system to influence the extent of cell infiltration and the phenotype of these cells. Bridge implantation reduces antigen‐presenting cell infiltration at day 7, and lentivirus addition to the bridge induces a transient increase in neutrophils in the spinal cord at day 7 and macrophages at day 14. Delivery of a lentivirus encoding IL‐10, an anti‐inflammatory factor that inhibits immune cell activation and polarizes the macrophage population towards anti‐inflammatory phenotypes, reduced neutrophil infiltration at both day 7 and day 28. Though IL‐10 lentivirus did not affect macrophages number, it skewed the macrophage population toward an anti‐inflammatory M2 phenotype and altered macrophage morphology. Additionally, IL‐10 delivery resulted in improved motor function, suggesting reduced secondary damage and increased sparing. Taken together, these results indicate that localized expression of anti‐inflammatory factors, such as IL‐10, can modulate the inflammatory response following spinal cord injury, and may be a key component of a combinatorial approach that targets the multiple barriers to regeneration and functional recovery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134909/1/btm210018.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134909/2/btm210018_am.pd

Black Girls Speak STEM: Counterstories of Informal and Formal Learning Experiences

This study presents the interpretations and perceptions of Black girls who participated in I AM STEM – a community-based informal science, technology, engineering, and mathematics (STEM) program. Using narrative inquiry, participants generated detailed accounts of their informal and formal STEM learning experiences. Critical race methodology informed this research to portray the dynamic and complex experiences of girls of color, whose stories have historically been silenced and misrepresented. The data sources for this qualitative study included individual interviews, student reflection journals, samples of student work, and researcher memos, which were triangulated to produce six robust counterstories. Excerpts of the counterstories are presented in this article. The major findings of this research revealed that I AM STEM ignited an interest in STEM learning through field trips and direct engagement in scientific phenomena that allowed the girls to become agentic in continuing their engagement in STEM activities throughout the year. This call to awaken the voices of Black girls to speak casts light on their experiences and challenges as STEM learners ⎯ from their perspectives. The findings confirm that when credence and counterspaces are given to Black girls, they are poised to reveal their luster toward STEM learning. This study provided a space for Black girls to reflect on their STEM learning experiences, formulate new understandings, and make connections between the informal and formal learning environments within the context of their everyday lives, thus offering a more holistic approach to STEM learning that occurs across settings and over a lifetime

Occurrence of Typhoid Fever Complications and Their Relation to Duration of Illness Preceding Hospitalization: A Systematic Literature Review and Meta-analysis.

BACKGROUND:Complications from typhoid fever disease have been estimated to occur in 10%-15% of hospitalized patients, with evidence of a higher risk in children and when delaying the implementation of effective antimicrobial treatment. We estimated the prevalence of complications in hospitalized patients with culture-confirmed typhoid fever and the effects of delaying the implementation of effective antimicrobial treatment and age on the prevalence and risk of complications. METHODS:A systematic review and meta-analysis were performed using studies in the PubMed database. We rated risk of bias and conducted random-effects meta-analyses. Days of disease at hospitalization (DDA) was used as a surrogate for delaying the implementation of effective antimicrobial treatment. Analyses were stratified by DDA (DDA <10 versus ≥10 mean/median days of disease) and by age (children versus adults). Differences in risk were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity and publication bias were evaluated with the I2 value and funnel plot analysis, respectively. RESULTS:The pooled prevalence of complications estimated among hospitalized typhoid fever patients was 27% (95% CI, 21%-32%; I2 = 90.9%, P < .0001). Patients with a DDA ≥ 10 days presented higher prevalence (36% [95% CI, 29%-43%]) and three times greater risk of severe disease (OR, 3.00 [95% CI, 2.14-4.17]; P < .0001) than patients arriving earlier (16% [95% CI, 13%- 18%]). Difference in prevalence and risk by age groups were not significant. CONCLUSIONS:This meta-analysis identified a higher overall prevalence of complications than previously reported and a strong association between duration of symptoms prior to hospitalization and risk of serious complications

Rhabdovirus Matrix Protein Structures Reveal a Novel Mode of Self-Association

The matrix (M) proteins of rhabdoviruses are multifunctional proteins essential for virus maturation and budding that also regulate the expression of viral and host proteins. We have solved the structures of M from the vesicular stomatitis virus serotype New Jersey (genus: Vesiculovirus) and from Lagos bat virus (genus: Lyssavirus), revealing that both share a common fold despite sharing no identifiable sequence homology. Strikingly, in both structures a stretch of residues from the otherwise-disordered N terminus of a crystallographically adjacent molecule is observed binding to a hydrophobic cavity on the surface of the protein, thereby forming non-covalent linear polymers of M in the crystals. While the overall topology of the interaction is conserved between the two structures, the molecular details of the interactions are completely different. The observed interactions provide a compelling model for the flexible self-assembly of the matrix protein during virion morphogenesis and may also modulate interactions with host proteins

Extreme events are more likely to affect the breeding success of lesser kestrels than average climate change

Climate change is predicted to severely impact interactions between prey, predators and habitats. In Southern Europe, within the Mediterranean climate, herbaceous vegetation achieves its maximum growth in middle spring followed by a three-month dry summer, limiting prey availability for insectivorous birds. Lesser kestrels (Falco naumanni) breed in a time-window that matches the nestling-rearing period with the peak abundance of grasshoppers and forecasted climate change may impact reproductive success through changes in prey availability and abundance. We used Normalised Difference Vegetation Index (NDVI) as a surrogate of habitat quality and prey availability to investigate the impacts of forecasted climate change and extreme climatic events on lesser kestrel breeding performance. First, using 14 years of data from 15 colonies in Southwestern Iberia, we linked fledging success and climatic variables with NDVI, and secondly, based on these relationships and according to climatic scenarios for 2050 and 2070, forecasted NDVI and fledging success. Finally, we evaluated how fledging success was influenced by drought events since 2004. Despite predicting a decrease in vegetation greenness in lesser kestrel foraging areas during spring, we found no impacts of predicted gradual rise in temperature and decline in precipitation on their fledging success. Notwithstanding, we found a decrease of 12% in offspring survival associated with drought events, suggesting that a higher frequency of droughts might, in the future, jeopardize the recent recovery of the European population. Here, we show that extreme events, such as droughts, can have more significant impacts on species than gradual climatic changes, especially in regions like the Mediterranean Basin, a biodiversity and climate change hotspotinfo:eu-repo/semantics/publishedVersio

Cation disorder in ferroelectric Aurivillius phases of the type Bi₂ANb₂O₉ (A = Ba, Sr, Ca)

The structures of the ferroelectric two-layer Aurivillius phases Bi(2)ANb(2)O(9) (A = Ba, Sr, Ca) have been refined using a combination of X-ray and neutron powder diffraction data. Bi2BaNb2O9 is not significantly distorted from idealised symmetry and has been refined in tetragonal space group I4/mmm, n = 3.9362(1) and c = 25.6582(7) Angstrom. The Sr and Ca compounds have been refined in orthorhombic space group A2(1)am, with a = 5.5193(3), b = 5.5148(3), c = 25.0857(6) Angstrom and a = 5.4833(1), b = 5.4423(1), c = 24.8984(6) Angstrom, respectively. The orthorhombic distortion increases with decreasing A(2+) cation size and originates from bonding requirements at the perovskite A site, in agreement with previous work. However, in contrast to earlier work, we find a partial mixing of Bi and A cations on their respective sites, which increases in the order Ca &lt; Sr &lt; Ba. This effect is also discussed in terms of bonding requirements at the metal sites and bond valence sum analysis. The combined use of X-ray and neutron powder diffraction data is found to be essential in determining this subtle effect, which may have important consequences in the interpretation of the ferroelectric behaviour of this family of materials.</p

Cation disorder in ferroelectric Aurivillius phases of the type Bi₂ANb₂O₉ (A = Ba, Sr, Ca)

The structures of the ferroelectric two-layer Aurivillius phases Bi(2)ANb(2)O(9) (A = Ba, Sr, Ca) have been refined using a combination of X-ray and neutron powder diffraction data. Bi2BaNb2O9 is not significantly distorted from idealised symmetry and has been refined in tetragonal space group I4/mmm, n = 3.9362(1) and c = 25.6582(7) Angstrom. The Sr and Ca compounds have been refined in orthorhombic space group A2(1)am, with a = 5.5193(3), b = 5.5148(3), c = 25.0857(6) Angstrom and a = 5.4833(1), b = 5.4423(1), c = 24.8984(6) Angstrom, respectively. The orthorhombic distortion increases with decreasing A(2+) cation size and originates from bonding requirements at the perovskite A site, in agreement with previous work. However, in contrast to earlier work, we find a partial mixing of Bi and A cations on their respective sites, which increases in the order Ca &lt; Sr &lt; Ba. This effect is also discussed in terms of bonding requirements at the metal sites and bond valence sum analysis. The combined use of X-ray and neutron powder diffraction data is found to be essential in determining this subtle effect, which may have important consequences in the interpretation of the ferroelectric behaviour of this family of materials.</p