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Clinical transplants of hematopoietic stem cells (HSC) can provide a lifesaving therapy for many hematological diseases; however, therapeutic applications are hampered by donor availability. In vivo , HSC exist in a specified microenvironment called the niche. While most studies of the niche focus on those residing in the bone marrow (BM), a better understanding of the fetal liver niche during development is vital to design human pluripotent stem cell (PSC) culture and may provide valuable insights with regard to expanding HSCs ex vivo for transplantation. This review will discuss the importance of the fetal liver niche in HSC expansion, a feat that occurs during development and has great clinical potential. We will also discuss emerging approaches to generate expandable HSC in cell culture that attain more complexity in the form of cells or organoid models in combination with engineering and systems biology approaches. Overall, delivering HSC by charting developmental principles will help in the understanding of the molecular and biological interactions between HSCs and fetal liver cells for their controlled maturation and expansion.

Transactive memory system (TMS) theory has been popularized in recent research on groups and other collectives. In this essay we outline current issues in TMS research and develop propositions that can be tested in future research. We describe issues concerning how researchers define and conceptualize TMSs, interpret the relationship between TMS measures and the TMS concept, and attend to the role of task type in TMS research. The potential to advance TMS research by incorporating multilevel and social network perspectives, reconsidering the role of information technology in supporting TMSs, and developing frameworks suited to complex, multiactivity tasks is considered.

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.

This study examined how transactive memory systems (TMSs) emerge and develop to affect the performance of knowledge-worker teams. Sixty-four MBA consulting teams (261 members) participated in the study. I proposed that the role and function of TMSs change to meet different task and knowledge demands during a project. Hypotheses predicting that TMSs emerge during a project-planning phase as a function of a team's initial conditions, and later develop and mature as a function of the nature and frequency of communication were generally supported, as were hypothesized relationships between TMSs and team performance and viability. Findings suggest that teams with initially distributed expertise and familiar members are more likely to develop a TMS. Frequent face-to-face communication also led to TMS emergence, but communication via other means had no effect. Teams with more established TMSs later benefited from face-to-face communication, but they were less helped by frequent communication via other means, suggesting that transactive retrieval processes may have been triggered during face-to-face communication and suppressed during other types of communication. TMSs were positively related to team viability and team performance, suggesting that developing a TMS is critical to the effectiveness of knowledge-worker teams.

Background The p66ShcA redox protein is the longest isoform of the Shc1 gene and is variably expressed in breast cancers. In response to a variety of stress stimuli, p66ShcA becomes phosphorylated on serine 36, which allows it to translocate from the cytoplasm to the mitochondria where it stimulates the formation of reactive oxygen species (ROS). Conflicting studies suggest both pro- and anti-tumorigenic functions for p66ShcA, which prompted us to examine the contribution of tumor cell-intrinsic functions of p66ShcA during breast cancer metastasis. Methods We tested whether p66ShcA impacts the lung-metastatic ability of breast cancer cells. Breast cancer cells characteristic of the ErbB2+/luminal (NIC) or basal (4T1) subtypes were engineered to overexpress p66ShcA. In addition, lung-metastatic 4T1 variants (4T1-537) were engineered to lack endogenous p66ShcA via Crispr/Cas9 genomic editing. p66ShcA null cells were then reconstituted with wild-type p66ShcA or a mutant (S36A) that cannot translocate to the mitochondria, thereby lacking the ability to stimulate mitochondrial-dependent ROS production. These cells were tested for their ability to form spontaneous metastases from the primary site or seed and colonize the lung in experimental (tail vein) metastasis assays. These cells were further characterized with respect to their migration rates, focal adhesion dynamics, and resistance to anoikis in vitro. Finally, their ability to survive in circulation and seed the lungs of mice was assessed in vivo. Results We show that p66ShcA increases the lung-metastatic potential of breast cancer cells by augmenting their ability to navigate each stage of the metastatic cascade. A non-phosphorylatable p66ShcA-S36A mutant, which cannot translocate to the mitochondria, still potentiated breast cancer cell migration, lung colonization, and growth of secondary lung metastases. However, breast cancer cell survival in the circulation uniquely required an intact p66ShcA S36 phosphorylation site. Conclusion This study provides the first evidence that both mitochondrial and non-mitochondrial p66ShcA pools collaborate in breast cancer cells to promote their maximal metastatic fitness.

Background Most wireless localization methods utilize only one means of detection for the surgeon, sufficient to localize a single small breast lesion for excision. Complex cases requiring bracketing of a larger lesion or localization of two or more close lesions can superimpose the signal from separate “seeds” with such methods. The lack of discernment between the localization “seeds” can disorient the surgeon, risking a missed lesion on excision and longer operative times. with the use of neoadjuvant chemotherapy prior to breast surgery, the necessity of localizing both a breast lesion and an axillary lymph node previously biopsied is becoming frequent. Case A 44 year‐old woman underwent neoadjuvant chmotherapy for a breast cancer the did not express estrogen receptor, progesterone receptor, or HER2 receptor. In establishing the extent of disease, a suspicious ipsilateral lymph node was biopsied and found to contain metastatic disease. She had an excellent response to the chemotherapy, with decreased size of the primary tumor and the previously biopsied lymph node. The patient desired breast conservation. The primary tumor and associated calcifications were bracketed using two different Smartclips™, with a third localizing the lymph node biopsied. Conclusion This report illustrates how the use of three SmartClips™, within the EnVisioTM system, allowed for separate tracking of each “seed” throughout a complex surgery in a patient following neoadjuvant chemotherapy. This resulted in successful resection of both the tumor and the tagged lymph node.

In a longitudinal quasi-field setting, we develop and test a compensatory process model of social network closure over time on the development of a transactive memory system (TMS) in groups. Although a great deal of research examines the effects of closure on organizational outcomes, that research does not describe the microprocesses that explain when, and under what conditions, closure is beneficial or detrimental. Results from our analysis of the microprocesses associated with TMSs revealed a negative direct effect of closure over time on TMS development and a simultaneous positive indirect effect of closure over time on TMS development driven by a transitive triadic social network structure. It is important to note that the mediating effect of the number of transitive triads on the relationship between closure and a TMS was predictive of subsequent group performance. Results from our study suggest that closure may be a double-edged sword and that the microprocesses associated with TMS development can explain closure’s disparate performance consequences.

This paper argues that an anonymous epigram about the commentator Crassicius marrying Cinna’s Zmyrna is a satirical poem playfully evoking the incest of Zmyrna in order to make a more pointed critique of the genre of commentary. The poem suggests that like Zmyrna herself, the Zmyrna is libidinous, an unfaithful and Catullan mistress who cannot be trusted by her commentator. The poem therefore invites the reader to think more broadly about the relationship between author and commentator and about issues of textual ownership. In antiquity, poems are often imagined as sexual partners, while conversely sex itself is conceptualised as a grammatical activity. Sexuality therefore becomes a site for thinking about grammar and literary criticism and the relationship of commentator to text.

Abstract This paper argues that an anonymous epigram about the commentator Crassicius marrying Cinna's Zmyrna is a satirical poem playfully evoking the incest of Zmyrna in order to make a more pointed critique of the genre of commentary. The poem suggests that like Zmyrna herself, the Zmyrna is libidinous, an unfaithful and Catullan mistress who cannot be trusted by her commentator. The poem therefore invites the reader to think more broadly about the relationship between author and commentator and about issues of textual ownership. In antiquity, poems are often imagined as sexual partners, while conversely sex itself is conceptualised as a grammatical activity. Sexuality therefore becomes a site for thinking about grammar and literary criticism and the relationship of commentator to text.

Using the methodology of system dynamics, we model the effects of disruptive events on learning and productivity in organizations. We leverage the learning-by-doing and transactive memory system theories to model the underpinnings of learning processes at the collective and individual levels. We simulate the impact of disruptive events on organizational productivity and performance, such as employee turnover, technological innovation, reorganization, and extreme events (such as natural disasters), which disrupt individual knowledge, collective knowledge, or both. Finally, we discuss implications of our findings for future research on organizational learning and productivity. One implication is that representing organizational learning by a single power-law learning curve or even by multiple noninteracting learning curves may be in many cases inadequate. Another is that disruptions to individual learning can be beneficial to organizations in the long run, whereas disruptions to collective learning are detrimental in the short and long run. We discuss the factors that might help organizations mitigate the negative effects of disruption so that learning can occur amid even the most disruptive events.