[Analysis of epidemiological characteristics of pulmonary tuberculosis patients in Fengtai District, Beijing City from 2011 to 2021].

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Fengtai District from 2011 to 2021. Methods: A retrospective study was conducted, the data of PTB patients in Fengtai District from 2011 to 2021 were collected in Chinese disease prevention and Control Information System, which included etiological classification, gender, age, occupation, onset time, demographic information etc. the epidemiological characteristics of reported PTB patients was analysis. Results: A total of 10 342 cases of PTB were reported from 2011 to 2021 in Fengtai District, with an average annual reported incidence rate of 42.87/ 100 000. The incidence rate was the highest in 2012(75.89/100 000), and significantly declined from 2013, which declined to 29.70/100 000 in 2017. It showed a slow rise from 2018 to 2021. The difference was statistically significant (χ2=1 471.77,P<0.001).There were 2 975 cases of etiologic positive PTB from 2011 to 2021, and 76 cases of Rifampicin-resistant PTB from 2017 to 2021. The ratio of male cases to female was 1.75, the average annual incidence rate of male (53.94/100 000) was higher, than female(31.57/100 000).(χ2=704.01,P<0.001). Among all age groups, 25-29 years group, 20-24 years group and 30-34 years group had the highest proportion, which were 1 506 cases (14.56%) , 1 292 cases (12.49%) and 1 024 cases (9.90%) respectively. The average annual incidence rate was the lowest in the group less than 10 years old (1.43/100 000), and the highest in the group 85 years old and over (195.20/100 000), the difference was statistically significant(χ2=3164.24, P<0.001). The top occupations from high to low were housework and unemployment (2 917 cases, 28.21%), retirees (2 308 cases, 22.32%), workers (1 047 cases, 10.12%), cadres and staff (950 cases, 9.19%), farmers (860 cases, 8.32%), business services (698 cases, 6.75%), teachers and students (455 cases, 4.40%). Conclusion: From 2011 to 2021, the incidence rate of PTB was decreased from 2012 to 2017, and slowly increased lately in Fengtai District. The epidemiological characteristics of PTB vary in different age and gender.

Response to Lynch et al: On measuring head motion and effects of head molds during fMRI.

We recently presented evidence indicating limited efficacy of custom-molded headcases in reducing head motion in two naturalistic experimental contexts - passive movie watching, and speaking in the scanner (Jolly et al., 2020). In a commentary on this work, Lynch et al (2020) present additional data that support the original findings of (Power et al., 2019) and raise several potential issues with our recent work. We appreciate the opportunity to address these criticisms and raise additional points that should be considered when interpreting these conflicting findings. We do not believe that their criticisms diminish the value of our work, but instead, along with this reply, help better elucidate the key factors researchers should consider to make the most informed choice about their own research protocols.

Custom-molded headcases have limited efficacy in reducing head motion during naturalistic fMRI experiments.

Effectively minimizing head motion continues to be a challenge for the collection of functional magnetic resonance imaging (fMRI) data. The use of individual-specific custom molded headcases is a promising solution to this issue, but there has been limited work to date. In the present work, we examine the efficacy of headcases in a larger group of participants engaged in naturalistic scanning paradigms including: long movie-watching scans (~20 to 45min) and a recall task that involved talking aloud inside the MRI. Unlike previous work, we find that headcases do not reliably reduce motion during movie viewing compared to alternative methods such as foam pillows or foam pillows plus medical tape. Surprisingly, we also find that motion is worse when participants talk aloud while wearing headcases. These differences appear to be driven by large, brief rotations of the head as well as translations in the z-plane as participants speak. Smaller, constant head movements appear equivalent with or without headcases. The largest reductions in head motion are observable when participants were situated with both foam pillows and medical tape. Altogether, this work suggests that in a healthy adult population, custom-molded headcases may provide limited efficacy in reducing head motion beyond existing tools available to researchers. We hope this work can help improve the quality of custom headcases, motivate the investigation of additional solutions, and provide additional information about head motion in naturalistic contexts.

Simultaneous Nodal Superconductivity and Time-Reversal Symmetry Breaking in the Noncentrosymmetric Superconductor CaPtAs.

By employing a series of experimental techniques, we provide clear evidence that CaPtAs represents a rare example of a noncentrosymmetric superconductor which simultaneously exhibits nodes in the superconducting gap and broken time-reversal symmetry (TRS) in its superconducting state (below T_{c}≈1.5 K). Unlike in fully gapped superconductors, the magnetic penetration depth λ(T) does not saturate at low temperatures, but instead it shows a T^{2} dependence, characteristic of gap nodes. Both the superfluid density and the electronic specific heat are best described by a two-gap model comprising of a nodeless gap and a gap with nodes, rather than by single-band models. At the same time, zero-field muon-spin relaxation spectra exhibit increased relaxation rates below the onset of superconductivity, implying that TRS is broken in the superconducting state of CaPtAs, hence indicating its unconventional nature. Our observations suggest CaPtAs to be a new remarkable material that links two apparently disparate classes, that of TRS-breaking correlated magnetic superconductors with nodal gaps and the weakly correlated noncentrosymmetric superconductors with broken TRS, normally exhibiting only a fully gapped behavior.

Time-Reversal Symmetry Breaking in Re-Based Superconductors.

To trace the origin of time-reversal symmetry breaking (TRSB) in Re-based superconductors, we performed comparative muon-spin rotation and relaxation (µSR) studies of superconducting noncentrosymmetric Re_{0.82}Nb_{0.18} (T_{c}=8.8 K) and centrosymmetric Re (T_{c}=2.7 K). In Re_{0.82}Nb_{0.18}, the low-temperature superfluid density and the electronic specific heat evidence a fully gapped superconducting state, whose enhanced gap magnitude and specific-heat discontinuity suggest a moderately strong electron-phonon coupling. In both Re_{0.82}Nb_{0.18} and pure Re, the spontaneous magnetic fields revealed by zero-field µSR below T_{c} indicate time-reversal symmetry breaking and thus unconventional superconductivity. The concomitant occurrence of TRSB in centrosymmetric Re and noncentrosymmetric ReT (T=transition metal), yet its preservation in the isostructural noncentrosymmetric superconductors Mg_{10}Ir_{19}B_{16} and Nb_{0.5}Os_{0.5}, strongly suggests that the local electronic structure of Re is crucial for understanding the TRSB superconducting state in Re and ReT. We discuss the superconducting order parameter symmetries that are compatible with the experimental observations.

The SLE-associated Pbx1-d isoform acts as a dominant-negative transcriptional regulator.

Pbx1 is a transcription factor involved in multiple cellular processes, including the maintenance of self-renewal of hematopoietic progenitors. We have shown that the CD4(+) T-cell expression of a novel splice isoform of Pbx1, Pbx1-d, is associated with lupus susceptibility in the NZM2410 mouse and in lupus patients. The function of Pbx1 in T cells is unknown, but the splicing out of the DNA-binding domain in Pbx1-d predicts a dominant-negative function. In support of this hypothesis, we have shown that Pbx1-d transduction accelerates differentiation of MC3T3-E1 osteoblast pregenitors and mimics the effect of short hairpin RNA silencing of Pbx1. Conversely, Pbx1-d transduction reduced the expression of Sox3, a gene strongly transactivated by Pbx1, and Pbx1-d did not bind the Sox3 promoter. These results constitute a first step towards the understanding on how Pbx1-d contributes to systemic autoimmunity in the NZM2410 mouse model as well as in lupus patients.

Multivariate spatial feature selection in fMRI.

Multivariate neuroimaging analyses constitute a powerful class of techniques to identify psychological representations. However, not all psychological processes are represented at the same spatial scale throughout the brain. This heterogeneity is apparent when comparing hierarchically organized local representations of perceptual processes to flexible transmodal representations of more abstract cognitive processes such as social and affective operations. An open question is how the spatial scale of analytic approaches interacts with the spatial scale of the representations under investigation. In this article, we describe how multivariate analyses can be viewed as existing on a spatial spectrum, anchored by searchlights used to identify locally distributed patterns of information on one end, whole brain approach used to identify diffuse neural representations at the other and region-based approaches in between. We describe how these distinctions are an important and often overlooked analytic consideration and provide heuristics to compare these different techniques to choose based on the analyst's inferential goals.

The morphologic correlation between vortex transformation and upper critical field line in opal-based nanocomposites.

In this study, we investigate metallic nanocomposites to elucidate the properties of nanostructured conventional superconductors. Liquid tin, indium, and mercury are loaded into opal matrices by high pressure up to 10 kbar. The opal templates preserve the 3D dendritic morphology of confined superconducting metals to model a dendritic second phase with particular grain shape in bulk superconductors observed by a DualBeam microscope. We carry out measurements of the dc and ac magnetizations to study the superconducting phase diagrams, vortex dynamics, and impact of grain morphology in the opal composites. Besides, we apply the small-angle neutron scattering (SANS) to deny a regular vortex structure. The phase diagrams reveal an enhanced upper critical field Hc2(0) and curvature crossover in the upper critical field line. We also calculate the vortex activation barriers Ua and observe a transformation in the vortex system. According to the field dependence of Ua, the vortex structure transformation highly correlates with the curvature crossover in the upper critical field line. Our observations suggest that the similarity in the normalized phase diagrams and field dependences of Ua in the three nanocomposites is owing to their particular morphology of confinement.

[Chimeric antigen receptors T cells for treatment of 48 relapsed or refractory acute lymphoblastic leukemia children: long term follow-up outcomes].

Objective: To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors. Methods: Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis. Results: No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ2=4.968, P=0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate (P<0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% (RR=3.433, 95% CI 1.333-8.844, P=0.011) and not bridge to HSCT (RR=4.996, 95% CI 1.852-13.474, P=0.001) were the independent risk factors. Conclusion: The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.

Nodeless superconductivity in the cage-type superconductor Sc5Ru6Sn18 with preserved time-reversal symmetry.

We report the single-crystal synthesis and detailed investigations of the cage-type superconductor Sc5Ru6Sn18, using powder x-ray diffraction (XRD), magnetization, specific-heat and muon-spin relaxation (µSR) measurements. Sc5Ru6Sn18 crystallizes in a tetragonal structure (space group I41/acd) with lattice parameters a = 1.387(3) nm and c = 2.641(5) nm. Both DC and AC magnetization measurements prove the type-II superconductivity in Sc5Ru6Sn18 with T c ≈ 3.5(1) K, a lower critical field [Formula: see text] = 157(9) Oe and an upper critical field, [Formula: see text] = 26(1) kOe. The zero-field electronic specific-heat data are well fitted using a single-gap BCS model, with [Formula: see text] = 0.64(1) meV. The Sommerfeld constant γ varies linearly with the applied magnetic field, indicating s-wave superconductivity in Sc5Ru6Sn18. Specific-heat and transverse-field (TF) µSR measurements reveal that Sc5Ru6Sn18 is a superconductor with strong electron-phonon coupling, with TF-µSR also suggesting a single-gap s-wave character of the superconductivity. Furthermore, zero-field µSR measurements do not detect spontaneous magnetic fields below T c, hence implying that time-reversal symmetry is preserved in Sc5Ru6Sn18.

Low temperature magnetic properties of Nd2Ru2O7.

We present magnetic susceptibility, heat capacity, and neutron diffraction measurements of polycrystalline Nd2Ru2O7 down to 0.4 K. Three anomalies in the magnetic susceptibility measurements at 146, 21 and 1.8 K are associated with an antiferromagnetic ordering of the Ru4+ moments, a weak ferromagnetic signal attributed to a canting of the Ru4+ and Nd3+ moments, and a long-range-ordering of the Nd3+ moments, respectively. The long-range order of the Nd3+ moments was observed in all the measurements, indicating that the ground state of the compound is not a spin glass. The magnetic entropy of Rln2 accumulated up to 5 K, suggests the Nd3+ has a doublet ground state. Lattice distortions accompany the transitions, as revealed by neutron diffraction measurements, and in agreement with earlier synchrotron x-ray studies. The magnetic moment of the Nd3+ ion at 0.4 K is estimated to be 1.54(2)µ B and the magnetic structure is all-in all-out as determined by our neutron diffraction measurements.

Gene expression from both intronless and intron-containing Rous sarcoma virus clones is specifically inhibited by anti-sense RNA.

To distinguish the inhibitory effect of anti-sense RNA on translation from the effect on splicing, a plasmid (pLC32) was constructed from a cDNA clone of the Rous sarcoma virus (RSV) envelope gene (env) mRNA. Transcription of this plasmid results in the synthesis of RNA identical to the RSV env gene mRNA which does not require splicing to be expressed. Plasmids derived from pLC32 were also constructed in which the env gene coding sequence and 5' noncoding leader sequences were inserted in the opposite orientation relative to the RSV long terminal repeats (LTRs). pLC32 DNA transfected by the calcium phosphate coprecipitation technique efficiently rescued infectious virus from quail cells infected with an RSV mutant deleted in the env gene [R(-)Q cells], indicating that the intron sequences are dispensable in env gene expression. When the inverted constructs were cotransfected with pLC32, significantly less infectious virus was produced. The extent of the inhibition depended upon the concentration ratio of the two plasmids. The maximum inhibition (80%) occurred when the ratio of inverted constructs to pLC32 was 12:1. The inhibition is specific for the inverted orientation since cotransfection of pLC32 with several other plasmids containing viral LTRs and defective src and env genes at similar concentrations did not inhibit the production of infectious virus. In addition, the inverted constructs did not interfere with the expression of an LTR-driven chloramphenicol acetyltransferase gene. When cotransfected with a wild-type Prague A RSV DNA plasmid (pJD100), the inverted constructs also greatly inhibited expression and replication of virus in R(-)Q quail cells. These data suggest that the specific inhibition is caused by hybridization of complementary RNA transcribed from the inverted constructs to the env mRNA, thereby blocking its expression. The fact that expression of both intron-containing and intronless clones are inhibited to the same extent suggest that inhibition by anti-sense RNA from the env exon regions does not act at the level of RNA splicing.

Presence of negative and positive cis-acting RNA splicing elements within and flanking the first tat coding exon of human immunodeficiency virus type 1.

The human immunodeficiency virus type 1 (HIV-1) RNA follows a complex splicing pathway in which a single primary transcript either remains unspliced or is alternatively spliced to more than 30 different singly and multiply spliced mRNAs. We have used an in vitro splicing assay to identify cis elements within the viral genome that regulate HIV-1 RNA splicing. A novel splicing regulatory element (SRE) within the first tat coding exon has been detected. This element specifically inhibits splicing at the upstream 3' splice site flanking this tat exon. The element only functions when in the sense orientation and is position dependent when inserted downstream of a heterologous 3' splice site. In vivo, an HIV-1 SRE mutant demonstrated a decrease in unspliced viral RNA, increased levels of single- and double-spliced tat mRNA, and reduced levels of env and rev mRNAs. In addition to the negative cis-acting SRE, the flanking 5' splice site downstream of the first tat coding exon acts positively to increase splicing at the upstream 3' splice sites. These results are consistent with hypotheses of bridging interactions between cellular factors that bind to the 5' splice site and those that bind at the upstream 3' splice site.

Application of monitored natural attenuation to remediate a petroleum-hydrocarbon spill site.

Contamination of groundwater by petroleum-hydrocarbons is a serious environmental problem. The Monitored Natural Attenuation (MNA) approach is a passive remediation to degrade and dissipate groundwater contaminants in situ. In this study, a full-scale natural bioremediation investigation was conducted at a gasoline spill site. Results show that concentrations of major contaminants (benzene, toluene, ethylbenzene, and xylenes) dropped to below detection limit before they reached the downgradient monitor well located 280 m from the spill location. The results also reveal that natural biodegradation was the major cause of the observed contaminant reduction. The calculated natural first-order attenuation rates for BTEX and 1,2,4-trimethylbenzene (1,2,4-TMB) ranged from 0.051 (benzene) to 0.189 1/day (1,2,4-TMB). Evidence for the occurrence of natural attenuation includes the following: (1) depletion of dissolved oxygen, nitrate, and sulfate; (2) production of dissolved ferrous iron, sulfide, and CO2; (3) decreased BTEX concentrations and BTEX as carbon to TOC ratio along the transport path; (4) increased alkalinity and microbial populations; (5) limited spreading of the BTEX plume; and (6) preferential removal of certain BTEX components along the transport path. Additionally, the biodegradation capacity (44.73 mg/L) for BTEX and 1,2,4-TMB was much higher than other detected contaminants within the plume. Hence, natural attenuation can effectively contain the plume, and biodegradation processes played an important role in contaminant removal.

Self-renewal capacity of leukemic blast progenitor cells.

A review is presented of experimental information pertaining to the characteristics of a procedure designed to quantitate the capacity for self-renewal in clonogenic cells of human acute myeloblastic leukemia. In a series of 44 previously untreated patients, a significant correlation (p less than 0.01) was seen between low capacity for self-renewal and successful remission induction. Three cytotoxic drugs (Adriamycin, 1-beta-D-arabinofuranosylcytosine, and N-[4-(19-acridinylamino)-3-methoxyphenyl]-methanesulfonamide) were tested for preferential effect against self-renewal events. Surviving clonogenic cells to these agents had, respectively, unchanged, lower, and higher capacity for self-renewal. The implications of such drug properties are discussed.

Granulocyte-macrophage colony-stimulating factor and B7-2 combination immunogene therapy in an allogeneic Hu-PBL-SCID/beige mouse-human glioblastoma multiforme model.

Glioblastoma multiforme is the most common primary central nervous system neoplasm. Its dismal prognosis has led to investigation of new treatment strategies such as immunogene therapy. We transduced the human glioblastoma cell line D54MG in vitro with genes encoding the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), the T cell co-stimulatory molecule B7-2, or both (in a bicistronic vector) via retroviral vectors. Therapeutic gene expression by D54MG was high after transduction and selection (30 ng/10(6) cells/day for GM-CSF and > 2 orders of magnitude fluorescence shift on flow cytometry for B7-2). The effect of GM-CSF and/or B7-2 transduction on D54MG tumor growth in vivo was monitored in a novel allogeneic human peripheral blood lymphocyte-severe combined immunodeficiency mouse (Hu-PBL-SCID) model. GM-CSF- or B7-2-transduced tumors showed growth suppression in hu-PBL-reconstituted mice compared to untransduced and/or unreconstituted controls. Growth suppression was greatest for B7-2. Furthermore, vaccination with irradiated GM-CSF/B7-2-transduced tumor cells markedly inhibited growth of wild-type tumors at distant sites. Thus, this study illustrates a potential gene therapy strategy for glioblastoma multiforme patients using GM-CSF and/or B7-2 transduced tumor vaccines. Although extension of these allogeneic studies to an autologous system is critical, this is the first demonstration of in vivo efficacy of combination GM-CSF and B7-2 immunogene therapy for human glioblastoma multiforme.

Genetically modified dermal keratinocytes express high levels of transforming growth factor-beta1.

In an attempt to genetically modify cultured keratinocytes with transforming growth factor-beta1 (TGF-beta1), which has been proven to be one of the most important cytokines involved in wound healing, two constructs were made. One, designated pG3Z:K14-TGF-beta1, is a plasmid in which the expression of TGF-beta1 is driven by the keratin 14 promoter. The other, designated pLin-TGF-beta1, is a retroviral vector in which the retroviral 5' long-terminal repeat promoter drives expression. In both constructs, the deletion of a small fragment of the noncoding region of the TGF-beta1 gene was made to differentiate the transcript from that for endogenously expressed TGF-beta1. Different types of cells were transfected with the pG3Z:K14-TGF-beta1 construct using the calcium phosphate method. The pLin-TGF-beta1 construct was propagated in a retroviral packaging cell line and conditioned medium that contained high titers of the virus was used to transduce keratinocytes or other types of cells grown in standard culture. Northern analysis, used to evaluate the expression of TGF-beta1 mRNA in the pG3Z:K14-TGF-beta1 transfected keratinocyte C1-177 cell line, showed a smaller TGF-beta1 transcript compared with that endogenously expressed by dermal fibroblasts. The level of TGF-beta1 protein evaluated by enzyme-linked immunosorbent assay was significantly higher in medium conditioned by either the K14-TGF-beta1 transfected or the pLin-TGF-beta1 transduced keratinocytes, compared with that obtained from control cells; however, the level of TGF-beta1 protein was unchanged in cultures of pG3Z:K14-TGF-beta1 transfected nonkeratinocyte cells such as fetal and adult fibroblasts. Using the mink lung epithelial cell growth inhibition assay, we found an increase in TGF-beta1 activity in conditioned medium from the pG3Z:K14-TGF-beta1 transfected cells. To evaluate possible paracrine effects of the keratinocyte derived TGF-beta1, a coculture system was established with pLin-TGF-beta1 transduced keratinocytes grown in the upper chamber and dermal fibroblasts in the lower chamber. The results showed that TGF-beta1 released from keratinocytes diffused to the lower chamber where it stimulated collagen production by dermal fibroblasts. In summary, we demonstrate here that primary cultured keratinocytes can be genetically modified to express high levels of TGF-beta1 and suggest that this offers a potential approach for the therapy of dermal lesions such as nonhealing wounds.

Predictors of long-term smoking cessation in head and neck cancer patients.

Cigarette smoking is a major risk factor for head and neck cancer, and individuals who continue to smoke past diagnosis and treatment are at elevated risk for further disease. In a randomized controlled trial, a state of the art provider-delivered smoking cessation intervention was compared to a usual care advice control condition. The intervention consisted of surgeon- or dentist-delivered advice to stop smoking, a contracted quit date, tailored written materials, and booster advice sessions. Subjects were 186 patients with newly diagnosed first primary squamous cell carcinomas of the upper aerodigestive tract who had smoked cigarettes within the past year. At randomization, 88.2% of subjects were current smokers. At 12-month follow-up, 70.2% of subjects completing the trial (n = 114) were continuous abstainers; among baseline smokers alone the continuous abstinence (CA) rate was 64.6%. The cotinine validation rate at 12 months was 89.6%. Modeling techniques were utilized in order to derive expected CA rates, which included noncompleter subjects (n = 72). The CA rate expected at 1 year for the entire patient population was 64.2%, and for smokers alone the expected CA rate was 59.4%. Logistic regression analysis carried out on baseline smokers identified predictors of 12-month CA status. These included medical treatment, stage of change, age, nicotine dependence, and race. The intervention effect was not significant, although the sign of the effect was positive. Based on these findings, we recommend systematic brief advice to stop smoking for head and neck cancer patients, with a stepped care approach for patients less able to quit.

The molecular genetics of lentiviral vectors--current and future perspectives.

Gene therapy is a promising endeavor for the treatment of disease in the 21st century. The key to capitalize on this venture lies in the availability of efficient gene transfer and expression tools. Viral vectors are useful vehicles for the delivery of foreign genes into target cells, and retroviral vectors have been popular because of their ability to integrate into the host cell genome and maintain persistent gene expression. Recent studies of the human immunodeficiency virus (HIV) have demonstrated that lentiviruses, members of the retroviral family, have the ability to infect cells at both mitotic and post-mitotic stages of the cell cycle. This article aims to analyze the molecular genetics, review existing systems and applications, and address problems as well as potential future developments of the lentiviral vector systems.

Striatal dopamine nerve terminal markers but not nigral cellularity are reduced in spinocerebellar ataxia type 1.

We previously reported markedly reduced (-76%) dopamine (DA) levels in the putamen of seven patients with spinocerebellar ataxia type 1 (SCA1) who had no evidence of nigral cell loss or parkinsonism. To determine whether the DA reduction was accompanied by loss of DA nerve terminals, we measured levels of the DA transporter ([3H]WIN, 35,428 binding; DA transporter protein) and the vesicular monoamine transporter ([3H]DTBZ binding) in the putamen of these patients. As compared with the controls (n = 14), mean putamen concentrations of [3H]WIN 35,428 binding (-45%), dopamine transporter protein (-61%), and [3H]DTBZ binding (-48%) were significantly reduced in this SCA1 subgroup. We conclude that the degeneration in nigrostriatal DA neurons begins at the nerve ending in SCA1.