Retraction Note: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Influences of approaching tropical cyclones on water vapor and aerosols in the atmospheric boundary layer of Guangdong-Hong Kong-Macau Greater Bay Area of China.

The outer circulation of tropical cyclones (TCs) on the western North Pacific has been reported to substantially influence the atmospheric environment over the Guangdong-Hong Kong-Macau Greater Bay Area (GBA) of China, whereas dynamic evolution and redistribution of water vapor and aerosol in the atmospheric boundary layer (ABL) responding to moving TCs have yet to be understood. This study aims to answer three key research questions related to the influences of the approaching TCs: (1) how do water vapor and aerosol particles over the GBA change during the TC approaching stage? (2) how does the ABL in terms of vertical wind structure respond to the approaching TCs? and (3) how does turbulence influence the vertical profile of aerosol during the approaching stage? Based on an intensive analysis of three-year reanalysis and Doppler LiDAR data, this study identified a dry-polluted time over the GBA when a TC was located at ~1000 km away on South China Sea. Before that, horizontal wind has consistently come from the northeast, creating a favorable condition for weak transboundary air pollution to the GBA. During the dry-polluted time, the highest surface PM2.5 concentration was resulted from the enhanced downdraft and early-stage wind shear, i.e., stronger wind started occurring at upper-level ABL, while the further turbulent mixing induced by wind shear enhancement and updrafts recovery pumped surface pollution upward to the upper level when TCs became closer. Our findings are expected to improve both weather and PM2.5 forecasts under the impacts of approaching TCs.

Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors.

Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirus-mediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

Subarachnoid haematoma after spinal anaesthesia mimicking transient radicular irritation: a case report and review.

I report a patient with a spinal subarachnoid haematoma after difficult spinal anaesthesia who presented with symptoms of radicular irritation, and who recovered with conservative management. Subarachnoid haematoma is rare after spinal anaesthesia; a literature review found nine cases. In the majority of these cases, spinal anaesthesia had been difficult and unsuccessful. Other risk factors included antiplatelet and anticoagulant therapy, and direct spinal cord trauma. All the previous cases required decompressive laminectomy.

Disordered T-cell development and T-cell malignancies in SCL LMO1 double-transgenic mice: parallels with E2A-deficient mice.

The gene most commonly activated by chromosomal rearrangements in patients with T-cell acute lymphoblastic leukemia (T-ALL) is SCL/tal. In collaboration with LMO1 or LMO2, the thymic expression of SCL/tal leads to T-ALL at a young age with a high degree of penetrance in transgenic mice. We now show that SCL LMO1 double-transgenic mice display thymocyte developmental abnormalities in terms of proliferation, apoptosis, clonality, and immunophenotype prior to the onset of a frank malignancy. At 4 weeks of age, thymocytes from SCL LMO1 mice show 70% fewer total thymocytes, with increased rates of both proliferation and apoptosis, than control thymocytes. At this age, a clonal population of thymocytes begins to populate the thymus, as evidenced by oligoclonal T-cell-receptor gene rearrangements. Also, there is a dramatic increase in immature CD44(+) CD25(-) cells, a decrease in the more mature CD4(+) CD8(+) cells, and development of an abnormal CD44(+) CD8(+) population. An identical pattern of premalignant changes is seen with either a full-length SCL protein or an amino-terminal truncated protein which lacks the SCL transactivation domain, demonstrating that the amino-terminal portion of SCL is not important for leukemogenesis. Lastly, we show that the T-ALL which develop in the SCL LMO1 mice are strikingly similar to those which develop in E2A null mice, supporting the hypothesis that SCL exerts its oncogenic action through a functional inactivation of E proteins.

Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions.

Nectin-2 is a cell adhesion molecule encoded by a member of the poliovirus receptor gene family. This family consists of human, monkey, rat, and murine genes that are members of the immunoglobulin gene superfamily. Nectin-2 is a component of cell-cell adherens junctions and interacts with l-afadin, an F-actin-binding protein. Disruption of both alleles of the murine nectin-2 gene resulted in morphologically aberrant spermatozoa with defects in nuclear and cytoskeletal morphology and mitochondrial localization. Homozygous null males are sterile, while homozygous null females, as well as heterozygous males and females, are fertile. The production by nectin-2(-/-) mice of normal numbers of spermatozoa containing wild-type levels of DNA suggests that Nectin-2 functions at a late stage of germ cell development. Consistent with such a role, Nectin-2 is expressed in the testes only during the later stages of spermatogenesis. The structural defects observed in spermatozoa of nectin-2(-/-) mice suggest a role for this protein in organization and reorganization of the cytoskeleton during spermiogenesis.

scid Thymocytes with TCRbeta gene rearrangements are targets for the oncogenic effect of SCL and LMO1 transgenes.

SCL and LMO1 were both discovered by virtue of their activation by chromosomaltranslocation in patients with T-cell acute lymphoblastic leukemia (T-ALL). Overexpression of SCL and LMO1 in the thymus of transgenic mice leads to T-ALL at a young age. scid (severe combined immunodeficient) mice are unable to efficiently recombine antigen receptor genes and consequently display a developmental block at the CD4-CD8- to CD4+CD8+ transition. To test the hypothesis that this developmental block would protect SCL/LMO1 transgenic mice from developing T-ALL, we crossed the SCL and LMO1 transgenes onto a scid background. The age of onset for T-ALL in the SCL/LMO1/scid mice was significantly delayed (P < 0.001) compared with SCL/LMO1/wild-type mice. Intriguingly, all of the SCL/LMO1/scid malignancies displayed clonal, in-frame TCRbeta gene rearrangements. Taken together, these findings suggest that the "leaky" scid thymocyte that undergoes a productive TCRbeta gene rearrangement is susceptible to the oncogenic action of SCL and LMO1 and additionally suggests that TCRbeta gene rearrangements may be required for the oncogenic action of SCL and LMO1.

NUP98 gene fusions in hematologic malignancies.

Acute leukemia is associated with a wide spectrum of recurrent, non-random chromosomal translocations. Molecular analysis of the genes involved in these translocations has led to a better understanding of both the causes of chromosomal rearrangements as well as the mechanisms of leukemic transformation. Recently, a number of laboratories have cloned translocations involving the NUP98 gene on chromosome 11p15.5, from patients with acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and T cell acute lymphoblastic leukemia (T-ALL). To date, at least eight different chromosomal rearrangements involving NUP98 have been identified. The resultant chimeric transcripts encode fusion proteins that juxtapose the N-terminal GLFG repeats of NUP98 to the C-terminus of the partner gene. Of note, several of these translocations have been found in patients with therapy-related acute myelogenous leukemia (t-AML) or myelodysplastic syndrome (t-MDS), suggesting that genotoxic chemotherapeutic agents may play an important role in generating chromosomal rearrangements involving NUP98.

Development and characterization of T cell leukemia cell lines established from SCL/LMO1 double transgenic mice.

We have established a panel of nine immortal cell lines from T cell malignancies which arose in mice transgenic for the SCL and LMO1 genes. Cells from the primary malignancies initially grew very slowly in vitro, loosely attached to a stromal layer, before gaining the ability to proliferate independently. Upon gaining the ability to proliferate in the absence of a stromal layer, these cell lines grew rapidly, doubling every 14-23 h, to a very high density, approaching 10(7) cells/ml. Whereas the tumors which arise in SCL/LMO1 double transgenic mice are typically diploid or pseudodiploid, the cell lines were all grossly aneuploid, suggesting the possibility that additional genetic events were selected for in vitro. Given that SCL and LMO1 gene activation are both commonly seen in human patients with T cell acute lymphoblastic leukemia, these cell lines may be a useful in vitro model for the human disease.

The impact of social cognitive variables on the initial level of depression and recovery.

Thirty-seven patients who fulfilled DSM-III-R criteria for Major Depressive Disorder were recruited for a double-blind controlled trial of Desipramine and placebo for 6 weeks. Data about social cognitive variables, including social adversities, investment in roles and goals, general social support and crisis support were collected. Crisis support had a moderating effect on the initial level of depression: the more crisis support the subjects had, the less depressed they were on recruitment. Initial level of depression, the experience of adversity and drugs all contributed significantly to recovery defined as Hamilton Rating for Depression less than 10 at week 6. When recovery was defined as Hamilton score halved or more than halved between week 2 and week 6, subjects' level of ideal emotional support, and whether they had experienced adversity in their most invested domains, contributed significantly to recovery, independent of any drug effects or the initial level of depression. The higher their level of ideal emotional support, the less was the chance of these subjects recovering. The findings of this study pointed to the importance of controlling for psycho-social variables in studies of response to treatment.

Dependency, matching adversities, length of survival and relapse in major depression.

This paper reports the 1-year follow-up of a sample of depressed patients. Social cognitive variables obtained during the index episode, including ideal emotional support, roles and goals investment in various domains and dysfunctional attitudes were used to predict subjects' likelihood for subsequent relapse. More subjects who experienced severe life events in the year were found to have relapsed. However, the predictive value of life events was improved if adversity was in the most invested domain according to the roles and goals questionnaire that subjects filled in during their index episode (matching adversity). Subjects who experienced matching adversity had a 3-fold chance of relapse compared with subjects with nonmatching adversity. The majority of the matching events were in the interpersonal domain. Levels of dysfunctional attitudes alone did not predict relapse. However, matching adversity and the dependency subscale of the dysfunctional attitude scale contributed significantly both to whether or not subjects relapsed and to the number of weeks subjects survived before they relapsed. The higher the level of dependency dysfunctional attitudes, the sooner subjects relapsed. The findings of the follow-up study supported the importance of psychological and social factors in determining relapse.

MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a heterogeneous disease despite its seemingly uniform pathology. Deconvolution of The Cancer Genome Atlas's GBM gene expression data has unveiled the existence of distinct gene expression signature underlying discrete GBM subtypes. Recent conflicting findings proposed that microRNA (miRNA)-10b exclusively regulates glioma growth or invasion but not both. We showed that silencing of miRNA-10b by baculoviral decoy vectors in a glioma cell line resembling the mesenchymal subtype of GBM reduces its growth, invasion and angiogenesis while promoting apoptosis in vitro. In an orthotopic human glioma mouse model, inhibition of miRNA-10b diminishes the invasiveness, angiogenicity and growth of the mesenchymal subtype-like glioma cells in the brain and significantly prolonged survival of glioma-bearing mice. We demonstrated that the pleiotropic nature of miRNA-10b was due to its suppression of multiple tumor suppressors, including TP53, FOXO3, CYLD, PAX6, PTCH1, HOXD10 and NOTCH1. In particular, siRNA-mediated knockdown experiments identified TP53, PAX6, NOTCH1 and HOXD10 as invasion regulatory genes in our mesenchymal subtype-like glioma cells. By interrogating the REMBRANDT, we noted that dysregulation of many direct targets of miRNA-10b was associated with significantly poorer patient survival. Thus, our study uncovers a novel role for miRNA-10b in regulating angiogenesis and suggests that miRNA-10b may be a pleiotropic regulator of gliomagenesis.

Psychosocial family intervention in schizophrenia: a review of empirical studies.

This paper reviews the recent empirical studies on psychosocial family intervention in schizophrenia. Six family educational intervention studies and five more intensive family work studies with 2-year follow-up have been included. A series of questions is asked relating to the effects of such interventions, the efficacy of the different educational models, the active ingredients of these multi-component treatment packages, and the contribution of this new generation of studies to our understanding of the mechanisms through which these interventions work. Suggestions for further research are made. Finally, from the published manuals, the common components of these diverse, multi-component treatment packages of different family-intervention studies are identified.

A questionnaire designed to assess roles and goals: a preliminary study.

Social-cognitive theories of depression predict that an individual is at more risk of becoming depressed if the individual's only dominant role or goal is disrupted by a life-event. This paper reports the development of an instrument which assesses the individual's important roles and goals; preliminary data are presented from two samples (sample 1 of elderly people, sample 2 of younger adults) taken from the age-sex registers of GP practices. The overall reliability of the questionnaire is good, and evidence was obtained for the predicted pattern of an overvalued role or goal being more likely to be correlated with depressive symptomatology.

Determinants of attenuation and temperature sensitivity in the type 1 poliovirus Sabin vaccine.

To identify determinants of attenuation in the poliovirus type 1 Sabin vaccine strain, a series of recombinant viruses were constructed by using infectious cDNA clones of the virulent type 1 poliovirus P1/Mahoney and the attenuated type 1 vaccine strain P1/Sabin. Intracerebral inoculation of these viruses into transgenic mice which express the human receptor for poliovirus identified regions of the genome that conferred reduced neurovirulence. Exchange of smaller restriction fragments and site-directed mutagenesis were used to identify the nucleotide changes responsible for attenuation. P1/Sabin mutations at nucleotides 935 of VP4, 2438 of VP3, and 2795 and 2879 of VP1 were all shown to be determinants of attenuation. The recombinant viruses and site-directed mutants were also used to identify the nucleotide changes which are involved in the temperature sensitivity of P1/Sabin. Determinants of this phenotype in HeLa cells were mapped to changes at nucleotides 935 of VP4, 2438 of VP3, and 2741 of VP1. The 3Dpol gene of P1/Sabin, which contains three amino acid differences from its parent P1/Mahoney, also contributes to the temperature sensitivity of P1/Sabin; however, mutants containing individual amino acid changes grew as well as P1/Mahoney at elevated temperatures, suggesting that either some combination or all three changes are required for temperature sensitivity. In addition, the 3'-noncoding region of P1/Sabin augments the temperature-sensitive phenotype conferred by 3Dpol. Although nucleotide 2741, 3Dpol, and the 3'-noncoding region of P1/Sabin contribute to the temperature sensitivity of P1/Sabin, they do not contribute to attenuation in transgenic mice expressing the poliovirus receptor, demonstrating that determinants of attenuation and temperature sensitivity can be genetically separated.

Family work with patients suffering from schizophrenia: the impact of training on psychiatric nurses' attitude and knowledge.

The effectiveness of family work with patients suffering from schizophrenia is well established. However, so far working with families has been carried out by highly skilled research workers. It is argued that training should be carried out to disseminate skills so that family work can be carried out routinely in clinical settings. This paper reports the impact of two pilot studies on psychiatric nurses. It was found that the trainees gained in knowledge about schizophrenia and schizophrenia family work. Furthermore, their attitudes and beliefs about schizophrenia and schizophrenia family work changed in the desired direction. The results suggest that it is possible to teach psychiatric nurses an effective model of family work for patients with schizophrenia.