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Multiciliated cells (MCCs) in the brain reside in the ependyma and the choroid plexus (CP) epithelia. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. Tumors of the CP are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP and atypical CPP are generally benign and can be resolved by surgery, CPC is a particularly aggressive and little understood cancer with a poor survival rate and a tendency for recurrence and metastasis. In contrast to MCCs in the CP epithelia, CPCs in humans are characterized by solitary cilia, frequent TP53mutations, and disturbances to multiciliogenesis program directed by the GMNC-MCIDAS transcriptional network. GMNC and MCIDAS are early transcriptional regulators of MCC fate differentiation in diverse tissues. Consistently, components of the GMNC-MCIDAS transcriptional program are expressed during CP development and required for multiciliation in the CP, while CPC driven by deletion of Trp53and Rb1in mice exhibits multiciliation defects consequent to deficiencies in the GMNC-MCIDAS program. Previous studies revealed that abnormal NOTCH pathway activation leads to CPP. Here we show that combined defects in NOTCH and Sonic Hedgehog signaling in mice generates tumors that are similar to CPC in humans. NOTCH-driven CP tumors are monociliated, and disruption of the NOTCH complex restores multiciliation and decreases tumor growth. NOTCH suppresses multiciliation in tumor cells by inhibiting the expression of GMNC and MCIDAS, while Gmnc-Mcidasoverexpression rescues multiciliation defects and suppresses tumor cell proliferation. Taken together, these findings indicate that reactivation of the GMNC-MCIDAS multiciliogenesis program is critical for inhibiting tumorigenesis in the CP, and it may have therapeutic implications for the treatment of CPC.

Day reporting centers have been used as an alternative to confinement for convicted felons and misdemenants, often with substance abuse problems. The authors studied the day reporting program in Vigo County, Indiana and made conclusions about which participant characteristics were predictors of success or failure in completing the program.

The vertebrate left–right axis is specified during embryogenesis by a transient organ: the left–right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left–right organizer metallopeptidase (CIROP). Here, we show that CIROPis specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROPmutations presenting with recessive situsanomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans.

Juvenile Restitution and Recidivism in a Midwestern County.--Author Sudipto Roy focuses on an important aspect of restitutive sentencing--what impact restitution has on lowering offender recidivism. Specifically, he reports on a study which examined the impact of restitution on juvenile offenders' recidivism after their successful exit from a restitution program established by the Superior Court of Lake County (Indiana). He found that the restitution program's impact on lowering recidivism was more effective with first-time offenders than repeat offenders.

Requirements for local and global planarization are becoming more stringent as a result of the increased numerical aperture and reduced depth of focus in deep-submicron lithography. Although numerous traditional planarization […]

In India, approximately 480,000 deaths occur annually from exposure to household air pollution from the use of biomass cooking fuels. Displacing biomass use with clean fuels, such as liquefied petroleum gas (LPG), can help reduce these deaths. Through government initiatives, most Indian households now own an LPG stove and one LPG cylinder. Many households, however, continue to regularly use indoor biomass-fueled mud stoves (chulhas) alongside LPG. Focusing on this population in rural Maharashtra, India, this study (N= 186) tests the effects of conditioning a sales offer for a spare LPG cylinder on a reversible commitment requiring initially disabling indoor chulhas. We find that almost all relevant households (>98%) were willing to accept this commitment. Indoor chulha use decreased by 90% (95% CI = 80% to 101%) when the sales offer included the commitment, compared to a 23% decrease (95% CI = 14% to 32%) without it. For both treatment groups, we find that 80% purchased the spare cylinder at the end of the study.

CMP is one of the fastest growing and most important planarization technologies for advanced multilevel interconnects [1-2]. Incomplete understanding of the subtle interactions between the wafer, pad, and slurry limits […]

Straightening of the body axis is a major morphogenetic event that produces the typical head-to-tail shape of the vertebrate embryo. Defects in axial straightening can lead to debilitating disorders such as idiopathic scoliosis, characterized by three-dimensional curvatures of the spine1. Although abnormal cerebrospinal fluid (CSF) flow has been implicated in the development of idiopathic scoliosis2, the molecular mechanisms operating downstream of CSF flow remain obscure. Here we show that, in zebrafish embryos, cilia-driven CSF flow transports adrenergic signals that induce urotensin neuropeptides in CSF-contacting neurons along the spinal cord. Urotensins activate their receptor on slow-twitch muscle fibers of the dorsal somite; the contraction of these fibers likely results in straightening of the body axis. Consistent with this, mutation of the urotensin receptor resulted in severe scoliosis in adult zebrafish, closely mimicking the human disorder. These findings suggest that disruption of urotensin signaling by impaired CSF flow could be a critical etiological factor underlying the pathology of idiopathic scoliosis.

ABSTRACTBackground:We performed a systematic review to evaluate factors affecting uptake of rotavirus vaccine amongst physicians, parents and health system.Methods:We identified 15 studies that met the inclusion criteria from 790 screened studies published between Jan 2005 to Jan 2016.Results:Perceived severity of rotavirus disease, efficacy of vaccine and recommendation by health authorities positively influenced uptake of vaccine amongst health care providers. Routine and timely vaccination with routine vaccines and availability of rotavirus vaccine in public health programme facilitated uptake. Family income, parental education and employment status positively influenced the decision to vaccinate by parents. Concerns about safety, high cost, additional workload and logistic problems in acquiring vaccine stocks were perceived as barriers.Conclusion:Improved awareness regarding the rotavirus vaccination amongst public and scientific community and strengthening of public health system for better and timely immunisation coverage are important factors to maximize uptake of rotavirus vaccine in India.

Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in DZIP1L, which encodes DAZ interacting protein 1-like, in patients with ARPKD. We further validated these findings through loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and to the distal ends of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. In agreement with a defect in the diffusion barrier, we found that the ciliary-membrane translocation of the PKD proteins polycystin-1 and polycystin-2 is compromised in DZIP1L-mutant cells. Together, these data provide what is, to our knowledge, the first conclusive evidence that ARPKD is not a homogeneous disorder and further establish DZIP1L as a second gene involved in ARPKD pathogenesis.

Primary cilia are essential for Hedgehog (Hh) signaling in mammals, and this requirement appears to be conserved in other vertebrates as well. Here, I review recent work that has scrutinized the evolution of the link between the Hh pathway and cilia, discuss what we have learnt from these studies and speculate on how this fascinating problem can be further explored.

Hedgehog proteins play an essential role during pattern formation in animal development and, increasingly, much of our appreciation of their modes of action is emanating from studies of their signalling mechanisms at the cellular level. Recent work has provided insights into how Hedgehog controls the cell cycle in a variety of circumstances. The data suggest that this influence may be direct and operates through interaction of the signalling pathway with cell cycle regulators at multiple points within the cell cycle. These new findings have profound implications in the context of clinical conditions — especially cancers — that arise from de-regulated cell proliferation in response to aberrant Hedgehog signalling activity.

Motile cilia defects impair cerebrospinal fluid (CSF) flow and can cause brain and spine disorders. The development of ciliated cells, their impact on CSF flow, and their function in brain and axial morphogenesis are not fully understood. We have characterized motile ciliated cells within the zebrafish brain ventricles. We show that the ventricles undergo restructuring through development, involving a transition from mono- to multiciliated cells (MCCs) driven by gmnc. MCCs co-exist with monociliated cells and generate directional flow patterns. These ciliated cells have different developmental origins and are genetically heterogenous with respect to expression of the Foxj1 family of ciliary master regulators. Finally, we show that cilia loss from the tela choroida and choroid plexus or global perturbation of multiciliation does not affect overall brain or spine morphogenesis but results in enlarged ventricles. Our findings establish that motile ciliated cells are generated by complementary and sequential transcriptional programs to support ventricular development.

This pilot study examined the usefulness of a program assessment instrument. The instrument contains 18 knowledge-based competencies that may be important for a successful criminal justice career. A single, nonforwarding mailing was sent to all 2,304 alumni of a program. The subjects reported that all but one of the competencies are important and that the department should have primary responsibility for teaching nine of the areas. The subjects also responded that they were well prepared in eight of the competency areas. The study concluded that the instrument, with some modifications, may be effective for assessing programs.

Victim Offender Reconciliation Program (VORP) is a specific form of conflict resolution between victims and offenders. Mediation and reconciliation make offenders accountable and responsible for their criminal acts and also committed to recompense their victims' damages. In addition, the process is expected to reduce recidivism among the participating offenders. This study explores the impact of the VORP juvenile restitution program operated by a private agency in Elkhart County, Indiana. Data was collected on 228 juveniles who participated in the program from January, 1987 to December, 1988; thereafter, they were followed through the end of 1990 for recidivism reports. The 'impact' of the program was measured in terms of offenders' repayments to their victims and offender recidivism.

The erect wing locus of the fruit fly Drosophila melanogaster encodes a protein, EWG, that shares extensive homology with the P3A2 DNA binding protein of sea urchin and a recently identified mammalian transcription factor. Loss-of-function erect wing alleles result in embryonic lethality. Viable alleles of erect wing cause severe abnormalities of the indirect flight muscles. We have analyzed the spatial pattern of erect wing expression in the developing indirect flight muscles during postembryonic development. EWG is detected, 10 hours after puparium formation, in myoblasts that will form the indirect flight muscles. The early events of muscle development are normal in ewg mutants. However, a few hours after the onset of erect wing expression in myoblasts, defects are seen in the developing indirect flight muscles which subsequently degenerate. We present results that show that the normal development of the indirect flight muscles requires erect wing expression in the progenitor myoblasts themselves. Finally, we examine the role of target muscles in the arborization of motor axons by studying the developing innervation to the flight muscle in erect wing mutants. Our study demonstrates, for the first time, a role for a regulatory gene expressed in imaginal myoblasts in Drosophila.

ABSTRACTCourt-ordered home detention and the use of electronic devices to monitor offender compliance has grown prodigiously over the last eleven years. Technological advancement has made practical the use of electronic monitors for home detention programs. On the one hand some programs using continuously monitoring electronic telemetry devices (active system) provide the most intensive supervision. On the other hand, some programs utilize electronic monitors to make programmed contacts with participants (passive system).

We have investigated the roles of homeotic selector genes in the migration and fusion of myoblasts, and in the differentiation of adult muscle fibres of Drosophila. Altering intrinsic homeotic identities of myoblasts does not affect their segment-specific migration patterns. By transplanting meso – and metathoracic myoblasts into the abdomen, we demonstrate that the fusion abilities of myoblasts are independent of their segmental identities. However, trans-planted thoracic myoblast nuclei are ‘entrained’ by those of the host abdominal muscles to which they fuse and are unable to ‘switch on’ a thoracic muscle-specific reporter gene. This process is likely to be mediated by homeotic repression because mis-expression of an abdominal muscle-specific homeotic gene, Ultrabithorax, in the thoracic muscles results in the repression of the thoracic muscle-specific reporter gene. Finally, we show that removal of Ultrabithorax function specifically from muscle cells of the first abdominal segment, results in the expression of thoracic muscle properties. Many of these functions of homeotic genes in muscle patterning in Drosophila could be conserved during myogenesis in other organisms.

Twist is required in Drosophila embryogenesis for mesodermal specification and cell-fate choice. We have examined the role of Twist and Notch during adult indirect flight muscle development. Reduction in levels of Twist leads to abnormal myogenesis. Notch reduction causes a similar mutant phenotype and reduces Twist levels. Conversely, persistent expression, in myoblasts, of activated Notch causes continued twist expression and failure of differentiation as assayed by myosin expression. The gain-of-function phenotype of Notch is very similar to that seen upon persistent twist expression. These results point to a relationship between Notch function and twist regulation during indirect flight muscle development and show that decline in Twist levels is a requirement for the differentiation of these muscles, unlike the somatic muscles of the embryo.

Multiparty quantum states are useful for a variety of quantum information and computation protocols. We define a multiparty entanglement measure based on local measurements on a multiparty quantum state and an entanglement measure averaged on the postmeasurement ensemble. Using the generalized geometric measure as the measure of multipartite entanglement for the ensemble, we demonstrate, in the case of several well-known classes of multipartite pure states, that the localized multipartite entanglement can exceed the entanglement present in the original state. We also show that measurement over multiple parties may be beneficial in enhancing localizable multipartite entanglement. We point out that localizable generalized geometric measure faithfully signals quantum critical phenomena in well-known quantum spin models even when considerable finite-size effect is present in the system. [ABSTRACT FROM AUTHOR]

No abstract received. [ABSTRACT FROM AUTHOR]

Computing entanglement of an arbitrary bipartite or multipartite mixed state is in general not an easy task as it usually involves complex optimization. Here we show that, exploiting symmetries of certain multiqudit mixed states, we can compute a genuine multiparty entanglement measure, the generalized geometric measure, for these classes of mixed states. The chosen states have different ranks and consist of an arbitrary number of parties. [ABSTRACT FROM AUTHOR]