Altered hydroxymethylome in the substantia nigra of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, and aging and genetic and environmental exposure can contribute to its pathogenesis. DNA methylation has been suggested to play a pivotal role in neurodevelopment and neurodegenerative diseases. 5-hydroxymethylcytosine (5hmC) is generated through 5-methylcytosine (5mC) oxidization by ten-eleven translocation proteins and is particularly enriched in the brain. Although 5hmC has been linked to multiple neurological disorders, little is known about 5hmC alterations in the substantia nigra of patients with PD. To determine the specific alterations in DNA methylation and hydroxymethylation in PD brain samples, we examined the genome-wide profiles of 5mC and 5hmC in the substantia nigra of patients with PD and Alzheimer's disease (ad). We identified 4119 differentially hydroxymethylated regions (DhMRs) and no differentially methylated regions (DMRs) in the postmortem brains of patients with PD compared with those of controls. These DhMRs were PD-specific when compared with the results of AD. Gene ontology analysis revealed that several signaling pathways, such as neurogenesis and neuronal differentiation, were significantly enriched in PD DhMRs. KEGG enrichment analysis revealed substantial alterations in multiple signaling pathways, including phospholipase D (PLD), cAMP and Rap1. In addition, using a PD Drosophila model, we found that one of the 5hmC-modulated genes, PLD1, modulated α-synuclein toxicity. Our analysis suggested that 5hmC may act as an independent epigenetic marker and contribute to the pathogenesis of PD.

Adult-onset leukoencephalopathy with vanishing white matter with compound heterozygous EIF2B3 gene variants.

BACKGROUND: Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder affecting the white matter of the brain. It typically manifests during childhood, with clinical features including sudden and severe neurological deterioration triggered by stressors such as febrile illness, minor head trauma, or stressful events. Adult-onset cases of VWM are exceptionally uncommon. CASE PRESENTATION: In this case, we present an adult patient who exhibited late-onset progressive VWM characterized by ataxia, postural instability, cognitive impairment, and emotional disturbances. Comprehensive screening for endocrine, metabolic, tumor, and immunologic disorders yielded normal or negative results. Brain imaging revealed diffuse and confluent hyperintensity in the white matter on T2-weighted images, along with periventricular cavitations. Genetic testing confirmed the diagnosis of VWM, identifying two heterozygous variants in the eukaryotic translation initiation factor 2B subunit γ (EIF2B3) gene: a pathogenic variant, c.1037 T > C (p.I346T), and a variant of undetermined significance, c.22A > T (p.M8L). Upon a 2-year follow-up, the patient's symptoms deteriorated rapidly following a COVID-19 infection. CONCLUSIONS: In conclusion, we have presented a case of classical adult-onset VWM. Since there are no cures or definitive treatments for the disease, it's extremely important to focus on early diagnosis and the prevention of stressors to avoid acute deterioration.

Ethnicity-specific and overlapping alterations of brain hydroxymethylome in Alzheimer's disease.

5-Methylcytosine (5mC), generated through the covalent addition of a methyl group to the fifth carbon of cytosine, is the most prevalent DNA modification in humans and functions as a critical player in the regulation of tissue and cell-specific gene expression. 5mC can be oxidized to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) enzymes, which is enriched in brain. Alzheimer's disease (AD) is the most common neurodegenerative disorder, and several studies using the samples collected from Caucasian cohorts have found that epigenetics, particularly cytosine methylation, could play a role in the etiological process of AD. However, little research has been conducted using the samples of other ethnic groups. Here we generated genome-wide profiles of both 5mC and 5hmC in human frontal cortex tissues from late-onset Chinese AD patients and cognitively normal controls. We identified both Chinese-specific and overlapping differentially hydroxymethylated regions (DhMRs) with Caucasian cohorts. Pathway analyses revealed specific pathways enriched among Chinese-specific DhMRs, as well as the shared DhMRs with Caucasian cohorts. Furthermore, two important transcription factor-binding motifs, hypoxia-inducible factor 2α (HIF2α) and hypoxia-inducible factor 1α (HIF1α), were enriched in the DhMRs. Our analyses provide the first genome-wide profiling of DNA hydroxymethylation of the frontal cortex of AD patients from China, emphasizing an important role of 5hmC in AD pathogenesis and highlighting both ethnicity-specific and overlapping changes of brain hydroxymethylome in AD.

Aluminum sheet induced flower-like carbon nitride anchored with silver nanowires for highly efficient SERS detection of trace malachite green.

The sensitive detection of malachite green (MG) in aquaculture wastewater is necessary for its residual poses a great threat to the living systems. Herein, the flower-like C3N4 (f-C3N4) nanostructure induced by Al sheet in the hydrothermal process is constructed. Subsequently, Ag nanowires (AgNWs) supported on Al/f-C3N4 and the strong interaction between AgNWs and Al/f-C3N4 are confirmed by XPS, Raman spectroscopy, UV-vis diffuse reflectance and fluorescence spectroscopy. Importantly, the portable Al/f-C3N4/AgNWs substrate shows the outstanding SERS response for MG, which is attributed to enhanced electromagnetic effect of AgNWs on large amount of corrugated and creviced regions in the flower-like Al/f-C3N4 and the charge transfer among the components. Also, the prepared Al/f-C3N4 nanostructure provides large specific surface area and abundant "N" active sites for AgNWs, and the high enrichment ability of Al/f-C3N4 towards MG molecules by the strong π-π stacking interaction. The detection limit of Al/f-C3N4/AgNWs for MG is as low as 8.38 × 10-12 mol L-1. The substrate can be reproduced and reused for at least 7 cycles, and the activity can still be kept after laid up for 49 days. Importantly, it unfolds a good sensitivity and selectivity for MG in actual water sample. Results indicate that the Al/f-C3N4/AgNWs substrate has a promising potential in practical application for trace detection of MG.

Long-term consumption of alcohol exacerbates neural lesions by destroying the functional integrity of the blood-brain barrier.

Recently, increasing numbers of studies have shown that the consumption of large amounts of alcohol is a major risk factor for dementias, which has led to widespread concern about the harmful effects of alcohol consumption on health. However, the pathological changes in the brain caused by this habit are not clear. This study aimed to investigate the possible causes by determining the permeability of the blood-brain barrier (BBB), pathomorphological changes, the mRNA, and protein expressions of adhesion proteins and the concentrations of ß-amyloid (Aß) and some related functional proteins in the brains of C57BL/6 and APPswe/PS1dE9 mice before and after intragastric administration of alcohol for 2 months. The results showed that long-term consumption of alcohol aggravated cognitive decline, increased the permeability of the BBB, led to pathomorphological changes and downregulated some related structural proteins (zonula occludens-1, VE-cadherin, and occludin) and functional proteins (major facilitator superfamily domain-containing protein-2a (Mfsd2a), low-density lipoprotein receptor-related protein-1 (LRP1), receptor for advanced glycation end products (RAGE), and aquaporin-4 (AQP4)) in the BBB but did not increase the concentration of Aß1-42. These novel findings suggested that long-term consumption of alcohol induces neural lesions, which is related to the destruction of the integrity of the BBB.

GhKNL1 controls fiber elongation and secondary cell wall synthesis by repressing its downstream genes in cotton (Gossypium hirsutum).

Cotton which produces natural fiber materials for the textile industry is one of the most important crops in the world. Class II KNOX proteins are often considered as transcription factors in regulating plant secondary cell wall (SCW) formation. However, the molecular mechanism of the KNOX transcription factor-regulated SCW synthesis in plants (especially in cotton) remains unclear in details so far. In this study, we show a cotton class II KNOX protein (GhKNL1) as a transcription repressor functioning in fiber development. The GhKNL1-silenced transgenic cotton produced longer fibers with thicker SCWs, whereas GhKNL1 dominant repression transgenic lines displayed the opposite fiber phenotype, compared with controls. Further experiments revealed that GhKNL1 could directly bind to promoters of GhCesA4-2/4-4/8-2 and GhMYB46 for modulating cellulose synthesis during fiber SCW development in cotton. On the other hand, GhKNL1 could also suppress expressions of GhEXPA2D/4A-1/4D-1/13A through binding to their promoters for regulating fiber elongation of cotton. Taken together, these data revealed GhKNL1 functions in fiber elongation and SCW formation by directly repressing expressions of its target genes related to cell elongation and cellulose synthesis. Thus, our data provide an effective clue for potentially improving fiber quality by genetic manipulation of GhKNL1 in cotton breeding.

Molecular chaperones and Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive death of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies (LBs). Mutations in PD-related genes lead to neuronal pathogenesis through various mechanisms, with known examples including SNCA/α-synuclein (PAKR1), Parkin (PARK2), PINK1 (PARK6), DJ-1 (PARK7), and LRRK2 (PARK8). Molecular chaperones/co-chaperones are proteins that aid the folding of other proteins into a functionally active conformation. It has been demonstrated that chaperones/co-chaperones interact with PD-related proteins and regulate their function in PD. HSP70, HSP90 and small heat shock proteins can prevent neurodegeneration by regulating α-syn misfolding, oligomerization and aggregation. The function of chaperones is regulated by co-chaperones such as HSP110, HSP40, HOP, CHIP, and BAG family proteins. Parkin, PINK1 and DJ-1 are PD-related proteins which are associated with mitochondrial function. Molecular chaperones regulate mitochondrial function and protein homeostasis by interacting with these PD-related proteins. This review discusses critical molecular chaperones/co-chaperones and PD-related proteins which contribute to the pathogenesis of PD, hoping to provide new molecular targets for therapeutic interventions to thwart the disease progression instead of only bringing symptomatic relief. Moreover, appreciating the critical role of chaperones in PD can also help us screen efficient biomarkers to identify PD at an early stage.

Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor.

Essential tremor is one of the most common movement disorders. Despite its high prevalence and heritability, the genetic aetiology of essential tremor remains elusive. Up to now, only a few genes/loci have been identified, but these genes have not been replicated in other essential tremor families or cohorts. Here we report a genetic study in a cohort of 197 Chinese pedigrees clinically diagnosed with essential tremor. Using a comprehensive strategy combining linkage analysis, whole-exome sequencing, long-read whole-genome sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal GGC repeat expansion in the 5' region of the NOTCH2NLC gene that co-segregated with disease in 11 essential tremor families (5.58%) from our cohort. Clinically, probands that had an abnormal GGC repeat expansion were found to have more severe tremor phenotypes, lower activities of daily living ability. Obvious genetic anticipation was also detected in these 11 essential tremor-positive families. These results indicate that abnormal GGC repeat expansion in the 5' region of NOTCH2NLC gene is associated with essential tremor, and provide strong evidence that essential tremor is a family of diseases with high clinical and genetic heterogeneities.

The role of genetics in Parkinson's disease: a large cohort study in Chinese mainland population.

This study aimed to determine the mutational spectrum of familial Parkinson's disease and sporadic early-onset Parkinson's disease (sEOPD) in a mainland Chinese population and the clinical features of mutation carriers. We performed multiplex ligation-dependent probe amplification assays and whole-exome sequencing for 1676 unrelated patients with Parkinson's disease in a mainland Chinese population, including 192 probands from families with autosomal-recessive Parkinson's disease, 242 probands from families with autosomal-dominant Parkinson's disease, and 1242 sEOPD patients (age at onset ≤ 50). According to standards and guidelines from the American College of Medical Genetics and Genomics, pathogenic/likely pathogenic variants in 23 known Parkinson's disease-associated genes occurred more frequently in the autosomal-recessive Parkinson's disease cohort (65 of 192, 33.85%) than in the autosomal-dominant Parkinson's disease cohort (10 of 242, 4.13%) and the sEOPD cohort (57 of 1242, 4.59%), which leads to an overall molecular diagnostic yield of 7.88% (132 of 1676). We found that PRKN was the most frequently mutated gene (n = 83, 4.95%) and present the first evidence of an SNCA duplication and LRRK2 p.N1437D variant in mainland China. In addition, several novel pathogenic/likely pathogenic variants including LRRK2 (p.V1447M and p.Y1645S), ATP13A2 (p.R735X and p.A819D), FBXO7 (p.G67E), LRP10 (c.322dupC/p.G109Rfs*51) and TMEM230 (c.429delT/p.P144Qfs*2) were identified in our cohort. Furthermore, the age at onset of the 132 probands with genetic diagnoses (median, 31.5 years) was about 14.5 years earlier than that of patients without molecular diagnoses (i.e. non-carriers, median 46.0 years). Specifically, the age at onset of Parkinson's disease patients with pathogenic/likely pathogenic variants in ATP13A2, PLA2G6, PRKN, or PINK1 was significantly lower than that of non-carriers, while the age at onset of carriers with other gene pathogenic/likely pathogenic variants was similar to that of non-carriers. The clinical spectrum of Parkinson's disease-associated gene carriers in this mainland Chinese population was similar to that of other populations. We also detected 61 probands with GBA possibly pathogenic variants (3.64%) and 59 probands with GBA p.L444P (3.52%). These results shed insight into the genetic spectrum and clinical manifestations of Parkinson's disease in mainland China and expand the existing repertoire of pathogenic or likely pathogenic variants involved in known Parkinson's disease-associated genes. Our data highlight the importance of genetic testing in Parkinson's disease patients with age at onset < 40 years, especially in those from families with a recessive inheritance pattern, who may benefit from early diagnosis and treatment.

Drinking water temperature affects cognitive function and progression of Alzheimer's disease in a mouse model.

Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer's disease (AD). However, whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied. In this study, we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms. Cognitive function of mice was assessed using passive avoidance test, open field test, and Morris water maze. Wild-type Kunming mice receiving intragastric water (IW, 10 mL/kg, 2 times/day) at 0 °C for consecutive 15 days displayed significant cognitive defects accompanied by significant decrease in gain of body weight, gastric emptying rate, pepsin activity, and an increase in the energy charge in the cortex when compared with mice receiving the same amount of IW at 25 °C (a temperature mimicking most common drinking habits in human), suggesting the altered neuroenergetics may cause cognitive decline. Similarly, in the transgenic APPwse/PS1De9 familial AD mice and their age- and gender-matched wild-type C57BL/6 mice, receiving IW at 0 °C, but not at 25 °C, for 35 days caused a significant time-dependent decrease in body weight and cognitive function, accompanied by a decreased expression of PI3K, Akt, the glutamate/GABA ratio, as well as neuropathy with significant amyloid lesion in the cortex and hippocampus. All of these changes were significantly aggravated in the APPwse/PS1De9 mice than in the control C57BL/6 mice. These data demonstrate that daily beverage at 0 °C may alter brain insulin-mediated neuroenergetics, glutamate/GABA ratio, cause cognitive decline and neuropathy, and promote AD progression.

Regulatory changes in China on xenotransplantation and related products.

BACKGROUND: Given the persistence and the worldwide shortage of organs from both the deceased and living donors for clinical transplantation, pig organs or tissues hold immense promises for the patients on the waiting list, and xenotransplantation is deemed as one of the solutions to the organ shortage crisis. Indeed, the emerging gene editing technologies, such as CRISPR/Cas9, have led to tremendous progress in the generation of genetically modified pigs to overcome many barriers associated. METHOD: We presented a description of the xenotransplantation regulations in China and the related products. RESULT: Several groups in China have successfully generated transgenic pigs with the elimination of immune rejection or coagulation-related genes, and both pre-clinical and clinical studies have been reported. However, the pre-clinical evaluation and clinical application of porcine xenotransplantation raises ethical and regulatory considerations. Herein, in this review, we will summarize and discuss the progress in xenotransplantation in China and xenotransplantation-related products from the regulatory perspective. CONCLUSION: There has been remarkable progress in both the genetically modified pigs and pre-clinical studies in China, and China will be the first country to successfully fulfill the xenotransplantation from pig organ to human in the near future.

Photocatalytic activity and the electron transport mechanism of titanium dioxide microsphere/porphyrin implanted with small size copper.

To obtain efficient photocatalysts by coupling architectures, developing novel materials and elucidating the charge transport mechanism at the semiconductor interface are vital. Herein, a special nanocomposite (TiO2 microsphere/CuNPs/THPP) for photocatalytic hydrogen production was facilely fabricated with copper nanoparticles (CuNPs) as the interfacial linker of the TiO2 microspheres and meso-tetra(p-hydroxypheny)porphyrin (THPP). The assembly mode of the nanocomposite was studied in detail. It was found that the CuNPs implanted at the interface of the TiO2 microspheres and THPP can dramatically strengthen the interaction between the TiO2 microspheres and THPP, and improve the separation and transfer of photo-produced charges. Therefore, the nanocomposite displayed excellent performance for photocatalytic hydrogen production. Moreover, by recycling hydrogen production, it is demonstrated that the nanocomposite was a highly efficient and long-term stable photocatalyst. By investigating the energy band location and the charge transfer, the photocatalytic mechanism over the special nanocomposite was explored and proposed to explain the better activity of the TiO2 microsphere/CuNPs/THPP photocatalytic system. It will be helpful to provide deep insights into the construction of efficient photocatalytic systems.

Prolonged preoperative fasting and prognosis in critically ill gastrointestinal surgery patients.

BACKGROUND AND OBJECTIVES: This study aimed to assess the influence of prolonged preoperative fasting on prognosis in elective surgery. METHODS AND STUDY DESIGN: A retrospective, controlled study involving patients admitted to our surgical intensive care unit who underwent a gastrointestinal operation under general anesthesia. Patients were divided into regular preoperative fasting time (n=57) and prolonged preoperative fasting time (n=73) groups. Clinical data were collected including patients' demographics, intraoperative and postoperative operation time, volume of blood loss, intensive care unit stay, hospital stay, postoperative complications and other factors. RESULTS: Patients in the regular preoperative fasting time group had less duration of mechanical ventilation support after surgery [245 (177, 450) min vs 315 (210, 812) min (p=0.021)] and the postoperative myocardial injuries (myocardial injury 2 cases vs 11 cases, p=0.038) and reoperation percentages (reoperation 0 cases vs 7 cases, p=0.044) were lower compared to the prolonged preoperative fasting time group. In addition, patients in the regular preoperative fasting time group presented with a significantly shorter period of postoperative fasting time [6.0 (5.0, 8.0) vs 8.0 (6.0, 13.0), p=0.005]. CONCLUSIONS: Prolonged preoperative fasting time led to unfavorable outcomes after gastrointestinal operations. Thus, reducing preoperative fasting time is likely to accelerate postoperative recovery in gastrointestinal surgery patients.

Association of HIF1A and Parkinson's disease in a Han Chinese population demonstrated by molecular inversion probe analysis.

Parkinson's disease (PD) is a common neurodegenerative disorder with multiple factors contributing to disease pathogenesis. Previous studies implicated the involvement of the transcription factor hypoxia inducible factor 1 alpha (HIF1A) in PD through its transcriptional regulation of PD-associated genes. This study uses molecular inversion probes (MIPs) followed by high-throughput sequencing for the genetic analysis of HIF1A in a large cohort including 1692 ethnic Han Chinese PD patients and 1419 neurologically normal control subjects matched for age, gender, and ethnicity. Common HIF1A variant rs11549465 was found to be associated with increased late-onset PD (LOPD) risk (OR (95%CI) = 1.531(1.068-2.194), P = 0.03828 for trend test, P = 0.03948 for analyses using the allelic model and P = 0.04196 for logistic regression analyses (sex + age as covariates)). Though the gene-based variants burden test is negative, seven rare non-synonymous, predicted-pathogenic point variants were identified. In conclusion, our study further indicates that HIF1A plays a role in PD pathogenesis.

[Structure and function of DJ-1 and its role in Parkinson's disease].

Parkinson's disease (PD) is a neurodegenerative movement disorder mainly due to degeneration of dopaminergic neurons in the substantia nigra. Most PD cases are sporadic and only 5%-10% of patients carry mutations with inheritance. Among them, the mutation of DJ-1 is related to the autosomal recessive early-onset parkinsonism. DJ-1, the Parkinson's disease-related protein, plays important roles in different physiopathological processes, including oxidative stress, cell translocation and regulation of transcription and translation. DJ-1 is known to be widely expressed in different areas of brain, including hippocampus, amygdala, substantia nigra and cortical areas. Several researchers have tried to demonstrate the clinical and neuroimaging features of DJ-1 related parkinsonism. The DJ-1 knockout mouse model was established to further explore the mechanisms of different functions. Moreover, the search for different forms of DJ-1 as potential biomarkers of PD also provides guidance for its accurate diagnosis and treatment in the future.

The cotton ß-galactosyltransferase 1 (GalT1) that galactosylates arabinogalactan proteins participates in controlling fiber development.

Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. The carbohydrate moieties of AGPs were altered in fibers of GhGalT1 transgenic cotton. The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. An enzyme activity assay demonstrated that GhGalT1 is a ß-1,3-galactosyltransferase (ß-1,3-GalT) involved in biosynthesis of the ß-1,3-galactan backbone of the type-II AG glycans of AGPs. We also show that GhGalT1 can form homo- and heterodimers with other cotton GT31 family members to facilitate AG glycan assembly of AGPs. Thus, our data demonstrate that GhGalT1 influences cotton fiber development via controlling the glycosylation of AGPs, especially FLAs.

Pharmacological inhibition of the Notch pathway enhances the efficacy of androgen deprivation therapy for prostate cancer.

Although androgen deprivation therapy (ADT) is a standard treatment for metastatic prostate cancer, this disease inevitably recurs and progresses to ADT-resistant stage after this therapy. Accordingly, understanding the mechanism of resistance to ADT and finding new approach to enhance the efficacy of ADT may provide a major benefit to PCa patients. In our study, we found upregulated expression of Notch receptors is positive associated with ADT-resistance progression. Using fluorescent Notch signaling reporter system, we observed that endogenous Notch signaling could be activated after treatment of androgen deprivation in LNCaP cells via activation of Notch3. In addition, exogenous activation of the Notch signaling though Dox-induced overexpression of any Notch intracellular domains (NICD1-4) could enhance the resistance of PCa cells to ADT under ex vivo 3D culture conditions and upregulate expression of ADT resistance-associated phospho-p38 and Bcl-2 in LNCaP cells. As a result, pharmacological inhibition of the Notch pathway using γ-secretase inhibitor (GSI), DAPT, downregulated both phospho-p38 and Bcl-2 expression and significantly enhanced the efficacy of ADT in androgen sensitive PCa cells with impaired proliferation and 3D colony formation, increased apoptosis and remarkable inhibition of tumor growth in murine subcutaneous xenograft model. These results indicate that activated Notch signaling contributes to ADT resistance, and suggest that inhibition of the Notch pathway may be a promising adjuvant therapy of ADT for PCa.

BAG2 structure, function and involvement in disease.

Bcl2-associated athanogene 2 (BAG2) shares a similar molecular structure and function with other BAG family members. Functioning as a co-chaperone, it interacts with the ATPase domain of the heat shock protein 70 (dHsp70) through its BAG domain. It also interacts with many other molecules and regulates various cellular functions. An increasing number of studies have indicated that BAG2 is involved in the pathogenesis of various diseases, including cancers and neurodegenerative diseases. This paper is a comprehensive review of the structure, functions, and protein interactions of BAG2. We also discuss its roles in diseases, including cancer, Alzheimer's disease, Parkinson's disease and spinocerebellar ataxia type-3. Further research on BAG2 could lead to an understanding of the pathogenesis of these disorders or even to novel therapeutic approaches.

Idiopathic hypertrophic spinal pachymeningitis: a case report and review of literature.

PURPOSE: To report an unusual case of idiopathic hypertrophic spinal pachymeningitis (IHSP) with a review of relevant literature and to discuss the etiology, clinical features, imaging, treatment and prognosis of IHSP. METHODS: The case of a 44-year-old woman is reported. MEDLINE was used to search relevant literatures written in English since 2004. RESULTS: The patient suffered from progressive mild thoracic backache followed by truncal and lower extremity weakness, numbness and urinary retention. The diagnosis was confirmed by magnetic resonance (MR) imaging and histopathologic examination. Although she received corticosteroid therapy and decompressive surgery, the patient suffered a rapid relapse probably because of the withdrawal of postoperative steroid therapy. CONCLUSIONS: IHSP is a rare disease characterized by inflammatory hypertrophy of the dura mater without identifiable cause and featured clinical progress of radiculalgia to myelopathy. It is a diagnosis of exclusion. In our view, surgical decompression with postoperative steroid therapy may be optimal. Furthermore,we speculated that increased levels of protein and cell count in cerebrospinal fluid (CSF) might be positively related to the disease progression. High inflammatory signs or CSF protein and cell levels before surgery or postoperative residual lesions are possible reasons of poor prognosis in patients with IHSP.

Arabidopsis drought-induced protein Di19-3 participates in plant response to drought and high salinity stresses.

Di19 (drought-induced protein19) family is a novel type of Cys2/His2 zinc-finger proteins. In this study, Arabidopsis Di19-3 was functionally characterized. The experimental results revealed that AtDi19-3 is a transcriptional activator, and could bind to the TACA(A/G)T sequence. AtDi19-3 expression in plants was remarkably induced by NaCl, mannitol and abscisic acid (ABA). T-DNA insertion mutation of AtDi19-3 results in an increase in plant tolerance to drought and high salinity stresses and ABA, whereas overexpression of AtDi19-3 leads to a drought-, salt- and ABA-sensitive phenotype of the transgenic plants. In the presence of NaCl, mannitol or ABA, rates of seed germination and cotyledon greening in Atdi19-3 mutant were higher, but in AtDi19-3 overexpression transgenic plants were lower than those in wild type. Roots of Atdi19-3 mutant seedlings were longer, but those of AtDi19-3 overexpression transgenic seedlings were shorter than those of wild type. Chlorophyll and proline contents in Atdi19-3 mutant were higher, but in AtDi19-3 overexpression seedlings were lower than those in wild type. Atdi19-3 mutant showed greater drought-tolerance, whereas AtDi19-3 overexpression transgenic plants exhibited more drought-sensitivity than wild type. Furthermore, expression of the genes related to ABA signaling pathway was altered in Atdi19-3 mutant and AtDi19-3 transgenic plants. These data suggest that AtDi19-3 may participate in plant response to drought and salt stresses in an ABA-dependent manner.