Soft tissue losses from tumor removal, trauma, aging, and congenital malformation affect millions of people each year. Existing options for soft tissue restoration have several drawbacks: Surgical options such as the use of autologous tissue flaps lead to donor site defects, prosthetic implants are prone to foreign body response leading to fibrosis, and fat grafting and dermal fillers are limited to small-volume defects and only provide transient volume restoration. In addition, large-volume fat grafting and other tissue-engineering attempts are hampered by poor vascular ingrowth. Currently, there are no off-the-shelf materials that can fill the volume lost in soft tissue defects while promoting early angiogenesis. Here, we report a nanofiber-hydrogel composite that addresses these issues. By incorporating interfacial bonding between electrospun poly(ε-caprolactone) fibers and a hyaluronic acid hydrogel network, we generated a composite that mimics the microarchitecture and mechanical properties of soft tissue extracellular matrix. Upon subcutaneous injection in a rat model, this composite permitted infiltration of host macrophages and conditioned them into the pro-regenerative phenotype. By secreting pro-angiogenic cytokines and growth factors, these polarized macrophages enabled gradual remodeling and replacement of the composite with vascularized soft tissue. Such host cell infiltration and angiogenesis were also observed in a rabbit model for repairing a soft tissue defect filled with the composite. This injectable nanofiber-hydrogel composite augments native tissue regenerative responses, thus enabling durable soft tissue restoration outcomes.

Background: Women and ethnic minorities remain underrepresented in science, technology, engineering, and math (STEM) fields. The goal of this pilot study is to better understand the beliefs and experiences of underrepresented US students pursuing STEM. Our focus was to gain insights into their mentorship experiences and preferences regarding having mentors who are gender and ethnicity matched. Environmental and psychological factors associated with participants' decision to pursue STEM, such as family influences, academic mindsets, and attitudes towards STEM, were also studied. Methods: We developed a survey tool based on published literature and established instruments, including measures of STEM belonging, science identity, and growth mindset, as well as measures assessing students' views on their STEM participation. We surveyed members of a STEM-focused non-profit who were in college, graduate school, or were recent graduates.Results: Forty-eight adults currently pursuing STEM responded to the survey. The majority (71%) were female and nearly all (96%) identified as an ethnic minority. Most reported knowing someone of their same gender (68%) or ethnicity (66%) with a STEM career who served as a role model. The majority (54%) stated that meeting a STEM professional of their own gender and ethnicity would be effective encouragement to pursue STEM. A similar percentage (56%) believed that media exposure to gender-and ethnicity-matched STEM professionals would be effective encouragement. Most (73%) demonstrated a growth mindset and had strong family support to pursue STEM (68%). Only two-thirds (66%) felt they belonged in STEM careers, and 30% agreed that people in their STEM classes are a lot like them. Conclusion: This study contributes additional information on the views and experiences of diverse students actively pursuing STEM. Most participants indicated the importance of meeting and being mentored in STEM by those of their same gender and ethnicity, either in person or through media. Future educational efforts to increase STEM diversity should consider students' mentorship preferences and facilitate interactions with matched-background mentors accordingly, with consideration given to the use of media. Educators should focus on inclusive learning by highlighting the accomplishments of diverse STEM professionals, to help strengthen feelings of STEM belonging.

No abstract

BackgroundRetroviruses selectively package two copies of their unspliced genomes by what appears to be a dimerization-dependent RNA packaging mechanism. Dimerization of human immunodeficiency virus Type-1 (HIV-1) genomes is initiated by “kissing” interactions between GC-rich palindromic loop residues of a conserved hairpin (DIS), and is indirectly promoted by long-range base pairing between residues overlapping the gag start codon (AUG) and an upstream Unique 5′ element (U5). The DIS and U5:AUG structures are phylogenetically conserved among divergent retroviruses, suggesting conserved functions. However, some studies suggest that the DIS of HIV-2 does not participate in dimerization, and that U5:AUG pairing inhibits, rather than promotes, genome dimerization. We prepared RNAs corresponding to native and mutant forms of the 5′ leaders of HIV-1 (NL4-3 strain), HIV-2 (ROD strain), and two divergent strains of simian immunodeficiency virus (SIV; cpz-TAN1 and -US strains), and probed for potential roles of the DIS and U5:AUG base pairing on intrinsic and NC-dependent dimerization by mutagenesis, gel electrophoresis, and NMR spectroscopy.ResultsDimeric forms of the native HIV-2 and SIV leaders were only detectable using running buffers that contained Mg2+, indicating that these dimers are more labile than that of the HIV-1 leader. Mutations designed to promote U5:AUG base pairing promoted dimerization of the HIV-2 and SIV RNAs, whereas mutations that prevented U5:AUG pairing inhibited dimerization. Chimeric HIV-2 and SIV leader RNAs containing the dimer-promoting loop of HIV-1 (DIS) exhibited HIV-1 leader-like dimerization properties, whereas an HIV-1NL4-3 mutant containing the SIVcpzTAN1 DIS loop behaved like the SIVcpzTAN1 leader. The cognate NC proteins exhibited varying abilities to promote dimerization of the retroviral leader RNAs, but none were able to convert labile dimers to non-labile dimers.ConclusionsThe finding that U5:AUG formation promotes dimerization of the full-length HIV-1, HIV-2, SIVcpzUS, and SIVcpzTAN1 5′ leaders suggests that these retroviruses utilize a common RNA structural switch mechanism to modulate function. Differences in native and NC-dependent dimerization propensity and lability are due to variations in the compositions of the DIS loop residues rather than other sequences within the leader RNAs. Although NC is a well-known RNA chaperone, its role in dimerization has the hallmarks of a classical riboswitch.