Operation Nation-Building: How International Humanitarian Law Left Afghanistan Open on the Operating Table

Military campaigns often carry with them official names and underpinning objectives. In Afghanistan, these campaigns were known as Operation Enduring Freedom in 2001, and later, in 2015, as Operation Freedom Sentinel. In total, the United States and its allies remained in Afghan territory for 7,268 days, twenty years, in support of the “Global War on Terror.” Within that time, the democratic construction of a “free” Afghan society—also known as nation-building, regime change, or transformative military occupation—deeply transformed the status quo of the population. To the West, “Operation Nation-Building” became the most strategic and “hopeful alternative to the vision of the extremists.” Fast forward in 2021, however, this enterprise seemed to have failed entirely, for these very “extremists”—the Taliban—retook power immediately upon military withdrawal. Today, Afghanistan is facing an unprecedented humanitarian crisis with a very real risk of systemic collapse and hu- man catastrophe—thereby reversing what many considered twenty years of societal gains, especially in regard to women’s rights. As a legal backdrop to this forever war, International Humanitarian Law (“IHL”) and Human Rights Law complementarily attempted to protect civilians and ensure human dignity. This Note will solely focus on IHL. Indeed, by assuming that endings of “occupations” remain conducts that occur during war, the scope of this Note falls well within jus in bello considerations. Accordingly, this Note does not assess the legitimacy of the war itself (jus ad bellum), nor does it suggest precise guidelines on how to terminate war (jus post bellum)—although it might shed light on the manner in which these guidelines should be considered. Without debating over the legitimacy and legality of nation- building within the framework of IHL, this Note stands for the proposition that foreseeably disastrous endings of nation-building enterprises, once identified, should trigger an additional legal duty under IHL—one of reasonable care— toward the population that is about to be left behind. To back up this logic, this Note will take a hard look at hard law— mainly the Fourth Geneva Convention—and discuss legal vacuums along the way

Identification of Spectral Modifications Occurring during Reprogramming of Somatic Cells

Recent technological advances in cell reprogramming by generation of induced pluripotent stem cells (iPSC) offer major perspectives in disease modelling and future hopes for providing novel stem cells sources in regenerative medicine. However, research on iPSC still requires refining the criteria of the pluripotency stage of these cells and exploration of their equivalent functionality to human embryonic stem cells (ESC). We report here on the use of infrared microspectroscopy to follow the spectral modification of somatic cells during the reprogramming process. We show that induced pluripotent stem cells (iPSC) adopt a chemical composition leading to a spectral signature indistinguishable from that of embryonic stem cells (ESC) and entirely different from that of the original somatic cells. Similarly, this technique allows a distinction to be made between partially and fully reprogrammed cells. We conclude that infrared microspectroscopy signature is a novel methodology to evaluate induced pluripotency and can be added to the tests currently used for this purpose

Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance

The generation of induced pluripotent stem (iPS) cells holds great promise in regenerative medicine. The use of the transcription factors Oct4, Sox2, Klf4 and c-Myc for reprogramming is extensively documented, but comparatively little is known about soluble molecules promoting reprogramming. Here we identify the secreted cue Netrin-1 and its receptor DCC, described for their respective survival/death functions in normal and oncogenic contexts, as reprogramming modulators. In various somatic cells, we found that reprogramming is accompanied by a transient transcriptional repression of Netrin-1 mediated by an Mbd3/Mta1/Chd4-containing NuRD complex. Mechanistically, Netrin-1 imbalance induces apoptosis mediated by the receptor DCC in a p53-independent manner. Correction of the Netrin-1/DCC equilibrium constrains apoptosis and improves reprogramming efficiency. Our work also sheds light on Netrin-1s function in protecting embryonic stem cells from apoptosis mediated by its receptor UNC5b, and shows that the treatment with recombinant Netrin-1 improves the generation of mouse and human iPS cells

Rab27a: A Key to Melanosome Transport in Human Melanocytes

Normal pigmentation depends on the uniform distribution of melanin-containing vesicles, the melanosomes, in the epidermis. Griscelli syndrome (GS) is a rare autosomal recessive disease, characterized by an immune deficiency and a partial albinism that has been ascribed to an abnormal melanosome distribution. GS maps to 15q21 and was first associated with mutations in the myosin-V gene. However, it was demonstrated recently that GS can also be caused by a mutation in the Rab27a gene. These observations prompted us to investigate the role of Rab27a in melanosome transport. Using immunofluorescence and immunoelectron microscopy studies, we show that in normal melanocytes Rab27a colocalizes with melanosomes. In melanocytes isolated from a patient with GS, we show an abnormal melanosome distribution and a lack of Rab27a expression. Finally, reexpression of Rab27a in GS melanocytes restored melanosome transport to dendrite tips, leading to a phenotypic reversion of the diseased cells. These results identify Rab27a as a key component of vesicle transport machinery in melanocytes