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While the mechanisms by which chemical signals control cell fate have been well studied, the impact of mechanical inputs on cell fate decisions is not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmission to the nucleus regulates epidermal cell fate. Using a molecular biosensor, we find that tension on the nucleus through linker of nucleoskeleton and cytoskeleton (LINC) complexes requires integrin engagement in undifferentiated epidermal stem cells and is released during differentiation concomitant with decreased tension on A-type lamins. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiation in vivo and in vitro and influence accessibility of epidermal differentiation genes, suggesting that force transduction from engaged integrins to the nucleus plays a role in maintaining keratinocyte progenitors. This work reveals a direct mechanotransduction pathway capable of relaying adhesion-specific signals to regulate cell fate.

Apoptosis and clearance of apoptotic cells via efferocytosis are evolutionarily conserved processes that drive tissue repair. However, the mechanisms by which recognition and clearance of apoptotic cells regulate repair are not fully understood. Here, we use single-cell RNA sequencing to provide a map of the cellular dynamics during early inflammation in mouse skin wounds. We find that apoptotic pathways and efferocytosis receptors are elevated in fibroblasts and immune cells, including resident Lyve1 + macrophages, during inflammation. Interestingly, human diabetic foot wounds upregulate mRNAs for efferocytosis pathway genes and display altered efferocytosis signaling via the receptor Axl and its ligand Gas6 . During early inflammation in mouse wounds, we detect upregulation of Axl in dendritic cells and fibroblasts via TLR3-independent mechanisms. Inhibition studies in vivo in mice reveal that Axl signaling is required for wound repair but is dispensable for efferocytosis. By contrast, inhibition of another efferocytosis receptor, Timd4, in mouse wounds decreases efferocytosis and abrogates wound repair. These data highlight the distinct mechanisms by which apoptotic cell detection coordinates tissue repair and provides potential therapeutic targets for chronic wounds in diabetic patients. Our skin is constantly exposed to potential damage from the outside world, and it is vital that any injuries are repaired quickly and effectively. Diabetes and many other health conditions can hamper wound healing, resulting in chronic wounds that are both painful and at risk of becoming infected, which can lead to serious illness and death of patients. After an injury to the skin, the wound becomes inflamed as immune cells rush to the site of injury to fight off infection and clear the wound of dead cells and debris. Some of these dead cells will have died by a highly controlled process known as apoptosis. These so-called apoptotic cells display signals on their surface that nearby healthy cells recognize. This triggers the healthy cells to eat the apoptotic cells to remove them from the wound. Previous studies have linked changes in cell death and the removal of dead cells to chronic wounds in patients with diabetes, but it remains unclear how removing dead cells from the wound affects healing. Justynski et al. used a genetic technique called single-cell RNA sequencing to study the patterns of gene activity in mouse skin cells shortly after a wound. The experiments found that, as the area around the wound started to become inflamed, the wounded cells produced signals of apoptosis that in turn triggered nearby healthy cells to remove them. Other signals relating to the removal of dead cells were also widespread in the mouse wounds and treating the wounds with drugs that inhibit these signals resulted in multiple defects in the healing process. Further experiments used the same approach to study samples of tissue taken from foot wounds in human patients with or without diabetes. This revealed that several genes involved in the removal of dead cells were more highly expressed in the wounds of diabetic patients than in the wounds of other individuals. These findings indicate that for wounds to heal properly it is crucial for the body to detect and clear apoptotic cells from the wound site. Further studies building on this work may help to explain why some diabetic patients suffer from chronic wounds and help to develop more effective treatments for them.

The “eshiret” (‘eşîret in the romanized Kurmanji Kurdish alphabet) is a highly variable and situated concept and social and political entity in Kurdistan, the homeland of ethnic Kurdish people. This essay is based on regular ethnographic fieldwork I have been conducting in part of Kurdistan, the Kurdistan Region of Iraq. My first research stint was in the mid-1990s, and I was there most recently in 2016. During the early period of my research, I had a great deal of contact with people in nonurban settings for whom an eshiret may be an important social category and contributor to individual identity.

Anthropologist Diane E. King has written about everyday life in the Kurdistan Region of Iraq, which covers much of the area long known as Iraqi Kurdistan. Following the overthrow of Saddam Hussein's Ba'thist Iraqi government by the United States and its allies in 2003, Kurdistan became a recognized part of the federal Iraqi system. The Region is now integrated through technology, media, and migration to the rest of the world. Focusing on household life in Kurdistan's towns and villages, King explores the ways that residents connect socially, particularly through patron-client relationships and as people belonging to gendered categories. She emphasizes that patrilineages (male ancestral lines) seem well adapted to the Middle Eastern modern stage and viceversa. The idea of patrilineal descent influences the meaning of refuge-seeking and migration as well as how identity and place are understood, how women and men interact, and how \"politicking\" is conducted. In the new Kurdistan, old values may be maintained, reformulated, or questioned. King offers a sensitive interpretation of the challenges resulting from the intersection of tradition with modernity. Honor killings still occur when males believe their female relatives have dishonored their families, and female genital cutting endures. Yet, this is a region where modern technology has spread and seemingly everyone has a mobile phone. Households may have a startling combination of illiterate older women and educated young women. New ideas about citizenship coexist with older forms of patronage. King is one of the very few scholars who conducted research in Iraq under extremely difficult conditions during the Saddam Hussein regime. How she was able to work in the midst of danger and in the wake of genocide is woven throughout the stories she tells.Kurdistan on the Global Stageserves as a lesson in field research as well as a valuable ethnography.

In this article, I use border crossings between Syria, Turkey, and Iraq during the period from 1995 to 2006 to examine the modern state, identity, and territory at border crossing points. Borderlands represent a site where the core powers of states can display the reach, scope, face, and preferred expressions of their identities. Border crossing points between modern states that make strong ethnolinguistic and/or ethnosectarian identity assertions, as do the states on which I focus here, are often charged sites where the state may seek to impose a certain identity category on an individual, an identity that the individual may or may not claim. Kurdistan, the non-state area recognized by Kurds as their ethnic /national home, arcs across the states, and most of the people meeting at the borders are ethnically Kurdish. The state may deny hybridity, or use hybridity, especially multilingualism, for its own purposes. Ethnolinguistic and other collective identity categories in Syria, Turkey, and Iraq are assigned according to patrilineal descent, which means that singular categories are passed from one generation to the next. These categories are made much less malleable by their reliance on descent claims through one parent. In such a milieu, ethnic identities may be a factor to a greater degree than if their state systems allowed for more ethnic flexibility and hybridity.

In this article, we present a model of gender within patrilineal descent for a broad region covering Asia, Europe, and North Africa. We develop the concept of \"lineal masculinity\" a perceived ontological essence that flows to and through men over the generations. It is especially expressed through people's notions of the past, present, and future of their patrilineages. We elaborate lineal masculinity in terms of male achievement, lineage founders, lineage segmentation, and male reproduction. Our model offers cross-cultural analysis and so provides an alternative to the position of strong cultural relativism in kinship and gender studies.

The proinflammatory cytokine interleukin-20 (IL-20) may exert the majority of its activity in the skin. We examined the effect of various treatments including several forms of phototherapy on IL-20 expression using cultured normal human epithelial keratinocytes (NHEK). Broadband UVB light, recombinant (r) IL-1 and rIL-8 increased, while hydrocortisone reduced, NHEK supernatant IL-20 levels. Elevation of NHEK IL-20 mRNA and maximal supernatant IL-20 levels occurred with a UVB light dose (40 mJ cm−2) that reduced cell viability by approximately 50%. While this UVB light dose also elevated supernatant IL-1α and IL-8 levels, antibody neutralization studies indicated that neither of these cytokines was directly responsible for this increase in IL-20 expression. However, the elevation in IL-20 levels was fully inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB-203580, suggesting involvement of this stress signaling pathway in this UVB light response. Photodynamic therapy (PDT) with the photosensitizer lemuteporfin, UVA light, cisplatin, lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) or recombinant interferon-γ (rIFN-γ) either had little effect or decreased NHEK supernatant IL-20 levels. Reduced IL-20 levels paralleled the cytotoxic actions of PDT, UVA light or cisplatin and the antiproliferative effect of rIFN-γ. Neither rIL-20 supplementation nor anti-IL-20 antibody treatments affected cell viability indicating that soluble IL-20 did not affect the short-term survival of UVB light-irradiated NHEK. Stimulation of IL-20 expression in keratinocytes by UVB light suggests that this cytokine might participate in skin responses to this ever-present environmental factor and potentially has a role in UV light-associated dermatoses.

This article examines the phenomenon of Iraqi Kurdish out-migration to the West between 1991 and 2003. It argues that migrants looked to the West and Westerners as potential patrons and were incited to migrate by their conceptualizations of patronage and clientage roles. Iraqi Kurdish migrants to the West constituted one of the largest flows of asylum-seeking clandestine migrants in the world by the late 1990s. European governments first accepted their asylum claims as \"legitimate,\" but later accused the migrants of being a \"problem\" and ceased granting asylum to most applicants. This article demonstrates how participants in the Iraqi Kurdish body politic posture themselves as clients and formulate the ideal roles of patrons in the migration process based on prior experience as clients of the state, tribal leaders, and other figures. Patronage and clientage roles provide both an interpretive frame and a motivator for the act of migrating.