Promoting Clinical Legal Education in India: A Case Study of the Citizen Participation Clinic

This Report is the product of a unique collaboration between the Good Governance and Citizen Participation Clinic at Jindal Global Law School and the Cornell International Human Rights Clinic at Cornell Law School. Students based in the Jindal Global Law School (Sonipat, India) and Cornell Law School (Ithaca, N.Y.) participated in a joint class using videoconferencing technology from January to May, 2012 and worked on preparing the Report. The Report points out that most law schools in India lack robust clinical legal education programs. Clinical legal education is essential to preparing law students to practice law effectively and promoting access to justice for marginalized groups. The report recommends that law schools mandate that trained faculty directly supervise students undertaking legal work, provide credit to students who engage in legal aid services, and ensure low student-teacher ratios in skills-based classes. Additionally, the report recommends that the Bar Council repeal its prohibition against professors and students practicing law before courts in India. The Report describes the key features of the Citizen Participation Clinic at Jindal. That clinic aims to address the disconnect between the Indian Constitution’s promise for a dignified life for every citizen and the reality of undignified human existence for the majority of the population, particularly in rural areas. That Clinic is one important example of a successful clinical model that can be adopted by other law schools in India to engage with their neighboring communities and to train law students in important lawyering skills

Promoting Clinical Legal Education in India: A Case Study of the Citizen Participation Clinic

This Report is the product of a unique collaboration between the Good Governance and Citizen Participation Clinic at Jindal Global Law School and the Cornell International Human Rights Clinic at Cornell Law School. Students based in the Jindal Global Law School (Sonipat, India) and Cornell Law School (Ithaca, N.Y.) participated in a joint class using videoconferencing technology from January to May, 2012 and worked on preparing the Report. The Report points out that most law schools in India lack robust clinical legal education programs. Clinical legal education is essential to preparing law students to practice law effectively and promoting access to justice for marginalized groups. The report recommends that law schools mandate that trained faculty directly supervise students undertaking legal work, provide credit to students who engage in legal aid services, and ensure low student-teacher ratios in skills-based classes. Additionally, the report recommends that the Bar Council repeal its prohibition against professors and students practicing law before courts in India. The Report describes the key features of the Citizen Participation Clinic at Jindal. That clinic aims to address the disconnect between the Indian Constitution’s promise for a dignified life for every citizen and the reality of undignified human existence for the majority of the population, particularly in rural areas. That Clinic is one important example of a successful clinical model that can be adopted by other law schools in India to engage with their neighboring communities and to train law students in important lawyering skills

Constructing abortion as a social problem: “Sex selection” and the British abortion debate

Between February 2012 and March 2015, the claim that sex selection abortion was taking place in Britain and that action needed to be taken to stop it dominated debate in Britain about abortion. Situating an analysis in sociological and social psychological approaches to the construction of social problems, particularly those considering “feminised” re-framings of anti-abortion arguments, this paper presents an account of this debate. Based on analysis of media coverage, Parliamentary debate and official documents, we focus on claims about grounds (evidence) made to sustain the case that sex selection abortion is a British social problem and highlight how abortion was problematised in new ways. Perhaps most notable, we argue, was the level of largely unchallenged vilification of abortion doctors and providers, on the grounds that they are both law violators and participants in acts of discrimination and violence against women, especially those of Asian heritage. We draw attention to the role of claims made by feminists in the media and in Parliament about “gendercide” as part of this process and argue that those supportive of access to abortion need to critically assess both this aspect of the events and also consider arguments about the problems of “medical power” in the light of what took place

Simultaneous deletion of Tet1 and Tet3 increases transcriptome variability in early embryogenesis

Dioxygenases of the TET (Ten-Eleven Translocation) family produce oxidized methylcytosines, intermediates in DNA demethylation, as well as new epigenetic marks. Here we show data suggesting that TET proteins maintain the consistency of gene transcription. Embryos lacking Tet1 and Tet3 (Tet1/3 DKO) displayed a strong loss of 5-hydroxymethylcytosine (5hmC) and a concurrent increase in 5-methylcytosine (5mC) at the eight-cell stage. Single cells from eight-cell embryos and individual embryonic day 3.5 blastocysts showed unexpectedly variable gene expression compared with controls, and this variability correlated in blastocysts with variably increased 5mC/5hmC in gene bodies and repetitive elements. Despite the variability, genes encoding regulators of cholesterol biosynthesis were reproducibly down-regulated in Tet1/3 DKO blastocysts, resulting in a characteristic phenotype of holoprosencephaly in the few embryos that survived to later stages. Thus, TET enzymes and DNA cytosine modifications could directly or indirectly modulate transcriptional noise, resulting in the selective susceptibility of certain intracellular pathways to regulation by TET proteins.J.K. was supported by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. W.A.P. was supported by the National Science Foundation predoctoral graduate research fellowship while this work was being performed, and subsequently by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. L.C. was the recipient of a Feodor-Lynen fellowship from the Alexander von Humboldt foundation. M.L. is supported by the Max Planck Society within its International Max Planck Research School for Computational Biology and Scientific Computing program (IMPRS-CBSC). A.T. was the recipient of an Irvington postdoctoral fellowship from the Cancer Research Institute. This work was supported by NIH R01 Grants AI044432 and HD065812 (to A.R.) and a Director’s New Innovator Award (DP2-OD-008646-01) (to S.K.).This is the author accepted manuscript. The final version is available from The National Academy of Sciences via http://dx.doi.org/10.1073/pnas.151051011

The Polycomb Protein and E3 Ubiquitin Ligase Ring1B Harbors an IRES in its Highly Conserved 5′ UTR

Ring1B is an essential member of the highly conserved Polycomb group proteins, which orchestrate developmental processes, cell growth and stem cell fate by modifying local chromatin structure. Ring1B was found to be the E3 ligase that monoubiquitinates histone H2A, which adds a new level of chromatin modification to Polycomb group proteins. Here we report that Ring1B belongs to the exclusive group of proteins that for their translation depend on a stable 5′ UTR sequence in their mRNA known as an Internal Ribosome Entry Site (IRES). In cell transfection assays the Ring1B IRES confers significantly higher expression levels of Ring1B than a Ring1B cDNA without the IRES. Also, dual luciferase assays show strong activity of the Ring1B IRES. Although our findings indicate Ring1B can be translated under conditions where cap-dependent translation is impaired, we found the Ring1B IRES to be cap-dependent. This raises the possibility that translational control of Ring1B is a multi-layered process and that translation of Ring1B needs to be maintained under varying conditions, which is in line with its essential role as an E3 ligase for monoubiquitination of histone H2A in the PRC1 Polycomb protein complex

Early Loss of Xist RNA Expression and Inactive X Chromosome Associated Chromatin Modification in Developing Primordial Germ Cells

The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges.We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb-group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27.We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome

Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples — including Xist, which orchestrates X chromosome inactivation — has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus

Evolutionary diversity and developmental regulation of X-chromosome inactivation

X-chromosome inactivation (XCI) results in the transcriptional silencing of one X-chromosome in females to attain gene dosage parity between XX female and XY male mammals. Mammals appear to have developed rather diverse strategies to initiate XCI in early development. In placental mammals XCI depends on the regulatory noncoding RNA X-inactive specific transcript (Xist), which is absent in marsupials and monotremes. Surprisingly, even placental mammals show differences in the initiation of XCI in terms of Xist regulation and the timing to acquire dosage compensation. Despite this, all placental mammals achieve chromosome-wide gene silencing at some point in development, and this is maintained by epigenetic marks such as chromatin modifications and DNA methylation. In this review, we will summarise recent findings concerning the events that occur downstream of Xist RNA coating of the inactive X-chromosome (Xi) to ensure its heterochromatinization and the maintenance of the inactive state in the mouse and highlight similarities and differences between mammals

Xist-dependent imprinted X inactivation and the early developmental consequences of its failure

The long noncoding RNA Xist is expressed from only the paternal X chromosome in mouse preimplantation female embryos and mediates transcriptional silencing of that chromosome. In females, absence of Xist leads to postimplantation lethality. Here, through single-cell RNA sequencing of early preimplantation mouse embryos, we found that the initiation of imprinted X-chromosome inactivation absolutely requires Xist. Lack of paternal Xist leads to genome-wide transcriptional misregulation in the early blastocyst and to failure to activate the extraembryonic pathway that is essential for postimplantation development. We also demonstrate that the expression dynamics of X-linked genes depends on the strain and parent of origin as well as on the location along the X chromosome, particularly at the first 'entry' sites of Xist. This study demonstrates that dosage-compensation failure has an effect as early as the blastocyst stage and reveals genetic and epigenetic contributions to orchestrating transcriptional silencing of the X chromosome during early embryogenesis.This work was funded by a fellowship of Région Ile-de-France (DIM STEMP OLE) to M.B., the Paris Alliance of Cancer Research Institutes (PACRI-ANR) to LS and ERC Advanced Investigator award (ERC-2010-AdG–No.250367), EU FP7 grants SYBOSS (EU 7th Framework G.A. no. 242129) and MODHEP (EU 7th Framework G.A. no. 259743), La Ligue, Fondation de France, Labex DEEP (ANR-11-LBX-0044) part of the IDEX Idex PSL (ANR-10-IDEX-0001-02 PSL) and ABS4NGS (ANR-11-BINF-0001) to E.H and France Genomique National infrastructure (ANR-10-INBS09) to EH, NS, EB