The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages

Macrophage actin-associated tyrosine phosphorylated protein (MAYP) belongs to the Pombe Cdc15 homology (PCH) family of proteins involved in the regulation of actin-based functions including cell adhesion and motility. In mouse macrophages, MAYP is tyrosine phosphorylated after activation of the colony-stimulating factor-1 receptor (CSF-1R), which also induces actin reorganization, membrane ruffling, cell spreading, polarization, and migration. Because MAYP associates with F-actin, we investigated the function of MAYP in regulating actin organization in macrophages. Overexpression of MAYP decreased CSF-1-induced membrane ruffling and increased filopodia formation, motility and CSF-1-mediated chemotaxis. The opposite phenotype was observed with reduced expression of MAYP, indicating that MAYP is a negative regulator of CSF-1-induced membrane ruffling and positively regulates formation of filopodia and directional migration. Overexpression of MAYP led to a reduction in total macrophage F-actin content but was associated with increased actin bundling. Consistent with this, purified MAYP bundled F-actin and regulated its turnover in vitro. In addition, MAYP colocalized with cortical and filopodial F-actin in vivo. Because filopodia are postulated to increase directional motility by acting as environmental sensors, the MAYP-stimulated increase in directional movement may be at least partly explained by enhancement of filopodia formation.     

Factors Affecting Women's Autonomous Decision Making In Research Participation Amongst Yoruba Women Of Western Nigeria

Research is a global enterprise requiring participation of both genders for generalizable knowledge; advancement of science and evidence based medical treatment. Participation of women in research is necessary to reduce the current bias that most empirical evidence is obtained from studies with men to inform health care and related policy interventions. Various factors are assumed to limit autonomy amongst the Yoruba women of western Nigeria. This paper seeks to explore the experience and understanding of autonomy by the Yoruba women in relation to research participation. Focus is on factors that affect women's autonomous decision making in research participation. An exploratory qualitative approach comprising four focus group discussions, 42 in‐depth interviews and 14 key informant interviews was used. The study permits a significant amount of triangulation, as opinions of husbands and religious leaders are also explored. Interviews and discussions were audiotaped and transcribed verbatim. Content analysis was employed for data analysis. Findings show that concepts of autonomy varied amongst the Yoruba women. Patriarchy, religion and culture are conceived to have negative impact on the autonomy of women in respect to research participation. Among the important findings are: 1) male dominance is strongly emphasized by religious leaders who should teach equality, 2) while men feel that by making decisions for women, they are protecting them, the women on the other hand see this protection as a way of limiting their autonomy. We recommend further studies to develop culturally appropriate and workable recruitment methods to increase women's participation in research.     

Pombe Cdc15 homology (PCH) proteins: coordinators of membrane-cytoskeletal interactions

Cellular adhesion, motility, endocytosis, exocytosis and cytokinesis involve the coordinated reorganization of the cytoskeleton and of the plasma membrane. The 'Pombe Cdc15 homology' (PCH) family of adaptor proteins has recently been shown to coordinate the membrane and cytoskeletal dynamics involved in these processes by curving membranes, recruiting dynamin and controlling the architecture of the actin cytoskeleton. Mutations in PCH family members or proteins that interact with them are associated with autoinflammatory, neurological or neoplastic diseases. Here, we review the nature, actions and disease associations of the vertebrate PCH family members, highlighting their fundamental roles in the regulation of processes involving membrane-cytoskeletal interactions.     

CSF-1 Receptor Signaling in Myeloid Cells

The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We review, the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R.The glycoprotein, colony-stimulating factor-1 (CSF-1), also known as macrophage-CSF (M-CSF), was the first of the CSFs to be purified (Stanley and Heard 1977) and was shown to stimulate the formation of colonies of macrophages (Stanley et al. 1978). This led to the identification (Guilbert and Stanley 1980) and purification (Yeung et al. 1987) of the CSF-1 receptor (CSF-1R) and the demonstration that it possessed intrinsic tyrosine kinase activity (Yeung et al. 1987). It was subsequently shown to be identical to the c-fms proto-oncoprotein (Sherr et al. 1985) previously studied by Sherr and colleagues (Rettenmier et al. 1985). The c-fms cDNA was cloned and shown to encode a typical class III receptor tyrosine kinase (RTK) (Coussens et al. 1986).The CSF-1R plays a central role in many diseases. Dominant inactivating mutations in the CSF-1R lead to adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (Rademakers et al. 2011; Nicholson et al. 2013). Inappropriate expression of the CSF-1R contributes to the development of leukemias and lymphomas, and autocrine and paracrine regulation of the CSF-1R enhances the progression and metastasis of solid tumors (reviewed in Pollard 2009; Chitu and Stanley 2014). In addition, regulation through the CSF-1R contributes to chronic inflammatory diseases (reviewed in Chitu and Stanley 2006; Chitu et al. 2012). This review focuses on the CSF-1R regulation and signaling in cells of the myeloid lineage.     

A Wireless Brain-Machine Interface for Real-Time Speech Synthesis

Background

Brain-machine interfaces (BMIs) involving electrodes implanted into the human cerebral cortex have recently been developed in an attempt to restore function to profoundly paralyzed individuals. Current BMIs for restoring communication can provide important capabilities via a typing process, but unfortunately they are only capable of slow communication rates. In the current study we use a novel approach to speech restoration in which we decode continuous auditory parameters for a real-time speech synthesizer from neuronal activity in motor cortex during attempted speech.

Methodology/Principal Findings

Neural signals recorded by a Neurotrophic Electrode implanted in a speech-related region of the left precentral gyrus of a human volunteer suffering from locked-in syndrome, characterized by near-total paralysis with spared cognition, were transmitted wirelessly across the scalp and used to drive a speech synthesizer. A Kalman filter-based decoder translated the neural signals generated during attempted speech into continuous parameters for controlling a synthesizer that provided immediate (within 50 ms) auditory feedback of the decoded sound. Accuracy of the volunteer''s vowel productions with the synthesizer improved quickly with practice, with a 25% improvement in average hit rate (from 45% to 70%) and 46% decrease in average endpoint error from the first to the last block of a three-vowel task.

Conclusions/Significance

Our results support the feasibility of neural prostheses that may have the potential to provide near-conversational synthetic speech output for individuals with severely impaired speech motor control. They also provide an initial glimpse into the functional properties of neurons in speech motor cortical areas.     

Association of vegetative antigens with the spores of Clostridium sporogenes

Clean spores of Clostridium sporogenes stored for two years continued to elicit the production of specific antibodies in immunized rabbits. Disintegrated spores stimulated not only antibodies specific for the spore component, but also those directed against 'H' and 'O' antigens of the sporangium cells.     

Autonomy and Reproductive Rights of Married Ikwerre Women in Rivers State,Nigeria

A woman’s lack of or limited reproductive autonomy could lead to adverse health effects, feeling of being inferior, and above all being unable to adequately care for her children. Little is known about the reproductive autonomy of married Ikwerre women of Rivers State, Nigeria. This study demonstrates how Ikwerre women understand the terms autonomy and reproductive rights and what affects the exercise of these rights. An exploratory research design was employed for this study. A semi-structured interview schedule was used to conduct thirty-four in-depth interviews and six focus group discussions with purposively sampled educated, semi-educated, and uneducated Ikwerre women in monogamous or polygynous marriages. The collected data was analysed qualitatively with MAXQDA 11 using open and axial coding. The interviews and focus group responses reveal a low level of awareness of autonomy and reproductive rights amongst the Ikwerre women in Nigeria. While some educated women were aware of their reproductive rights, cultural practices were reported to limit the exercise of these rights. Participants reported that Ikwerre culture is a patriarchal one where married women are expected to submit and obey their husbands in all matters; and a good married woman according to Ikwerre standard is one who complies with this culture. Women’s refusal of sexual advances from their husbands is described as not being acceptable in this culture; and hence rape in marriage is not recognized in Ikwerre culture. Education and awareness creation on the importance of women’s reproductive autonomy could improve their reproductive rights and autonomy in marital settings. Overcoming the patriarchal aspects of Ikwerre culture—for example, the greater value placed on male children than female children and treating women as incompetent individuals—is necessary to promote gender equality as well as help improve women’s reproductive autonomy.