The flora of Township Lagoon Nature Reserve and its management, Tunbridge, Tasmania

Township Lagoon Nature Reserve is 16 ha of remnant native grassland in the lowest rainfall area of Tasmania. A high proportion of rare and threatened species occurs within the reserve. They comprise four endangered species, including three endangered at the national level, four vulnerable species and eight rare species, seven of the above being daisies. There is a strong floristic affinity with the semi-arid mallee ground flora in northwestern Victoria and western New South Wales. The small grassland remnant comprises five floristic communities, the principal influences on floristic variation being exerted by soil factors, such as geology, pH and drainage, and past history of mechanical disturbance and rubbish dumping. Active conservation management, that is favourable to the continued existence of vulnerable and rare species, promotes normal ecosystem functions and prevents threatening processes, is essential

Evaluating downstream targets of cullin4-dependent E3 ligases and of D-type cyclins: implications for the dysregulation of ubiquitination and cell growth in cancer

Cyclin D1 and cullin4 (CUL4) are two proteins known to be upregulated in cancer. Cyclin D1 functions to regulate the cell division cycle and cell growth, while CUL4 assembles E3 ubiquitin ligase complexes that function to ubiquitinate target proteins, often marking them for degradation. However, the downstream effectors of their oncogenic activities are not fully characterized. Therefore, the aim of this study was to discover novel targets of the D-type cyclins and of CUL4, and to better describe the E3 ubiquitin ligase complexes assembled by CUL4. We identified the TSC1- TSC2 tumor suppressor complex, a key negative regulator of cell growth, as a cyclin D-interacting complex, and demonstrated that D-type cyclins could down-regulate the activity of TSC1-TSC2 by both CDK (Cyclin Dependent Kinase) -dependent and -independent mechanisms. In a separate line of studies, I conducted a genetic analysis of mutants of Cul4 and one of its putative substrate receptor molecules, Ddb1 (Damaged DNA Binding protein 1) in Drosophila, and established that CUL4DDB1 plays an essential role in cell growth, proliferation, and development. These studies suggested a number of novel substrates of the CUL4DDB1 ligase, and also served to clarify the role of CUL4DDB1 in controlling the degradation of the replication licensing factor CDT1/DUP during the cell cycle. Collectively, these analyses of the D-type cyclins and CUL4 broaden our understanding of the consequence of their disruption in cancer development

Oral Interview with Rosalba Arreaga

For My Interview with Rosalba Arreaga I learned a lot about her story, culture, and goals in life. Rosalba is an extraordinary, very nice, and hardworking woman, and her story is the proof. Rosalba and I talked in her restaurant, Valla Verde in Cincinnati. I think it was very nice and admirable of her to allow me to do an interview during her work. Rosalba\u27s story demonstrates the power of her faith, love, and working for a better life (for herself and her family). I want to say thank you so much to Rosalba for her time and sharing of her story of immigration to the United States. I hope you will appreciate and have as much interest in her story as I have

Treatment with an Angiopoietin-1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

AIM: Vasculotide (VT), an angiopoietin-1 mimetic peptide, exerts neuroprotective effects in type one diabetic (T1DM) rats subjected to ischemic stroke. In this study, we investigated whether delayed VT treatment improves long-term neurological outcome after stroke in T1DM rats. METHODS: Male Wistar rats were induced with T1DM, subjected to middle cerebral artery occlusion (MCAo) model of stroke, and treated with PBS (control), 2 µg/kg VT, 3 µg/kg VT, or 5.5 µg/kg VT. VT treatment was initiated at 24 h after stroke and administered daily (i.p) for 14 days. We evaluated neurological function, lesion volume, vascular and white matter remodeling, and inflammation in the ischemic brain. In vitro, we evaluated the effects of VT on endothelial cell capillary tube formation and inflammatory responses of primary cortical neurons (PCN) and macrophages. RESULTS: Treatment of T1DM-stroke with 3 µg/kg VT but not 2 µg/kg or 5.5 µg/kg significantly improves neurological function and decreases infarct volume and cell death compared to control T1DM-stroke rats. Thus, 3 µg/kg VT dose was employed in all subsequent in vivo analysis. VT treatment significantly increases axon and myelin density, decreases demyelination, decreases white matter injury, increases number of oligodendrocytes, and increases vascular density in the ischemic border zone of T1DM stroke rats. VT treatment significantly decreases MMP9 expression and decreases the number of M1 macrophages in the ischemic brain of T1DM-stroke rats. In vitro, VT treatment significantly decreases endothelial cell death and decreases MCP-1, endothelin-1, and VEGF expression under high glucose (HG) and ischemic conditions and significantly increases capillary tube formation under HG conditions when compared to non-treated control group. VT treatment significantly decreases inflammatory factor expression such as MMP9 and MCP-1 in macrophages subjected to LPS activation and significantly decreases IL-1β and MMP9 expression in PCN subjected to ischemia under HG conditions. CONCLUSION: Delayed VT treatment (24 h after stroke) significantly improves neurological function, promotes vascular and white matter remodeling, and decreases inflammation in the ischemic brain after stroke in T1DM rats

Evaluation of serum heat shock protein 70 concentration in women with recurrent miscarriages

Background. Heat shock proteins (Hsp) were discovered over 50 years ago and are commonly called ‘stress proteins’. Hsp proteins play an important role in a cell, in that they provide protection against cellstress factors and environmentally negative factors. The most conservative, and the best known, heat shock proteins are Hsp 70 subfamily proteins. It has been suggested that an increase of Hsp 70 in the blood during pregnancy has a negative impact. The aetiology of recurrent miscarriages in more than 60% of women remains unexplained. Therefore the aim of this study was to evaluate the usefulness of Hsp 70 assessment in the diagnosis of recurrent miscarriages.Material and methods. The study group consisted of 100 women (aged 36.0 ± 4.9 years) who had experienced repeated miscarriages. The reference group consisted of 60 women (aged 36.1 ± 3.6 years), who had been pregnant at least twice and who had given birth by a spontaneous labour without complications. Hsp 70 was determined in the serum.Results. We found no significant differences in the Hsp 70 concentration between the women with recurrent miscarriages and the reference group. While median serum Hsp 70 was the most elevated in the women with the highest number of miscarriages, this difference was not significant.Conclusion. Based on the obtained results, it is difficult to determine whether Hsp 70 plays a causative role in recurrent miscarriages. However, taking into account the fact that the role of Hsp 70 in the course of normal and pathological pregnancy is not yet completely understood, it may be worth expanding the study to include a larger group of women with recurrent miscarriages

Brain-Derived Microparticles (BDMPs) Contribute to Neuroinflammation and Lactadherin Reduces BDMP Induced Neuroinflammation and Improves Outcome After Stroke

Microparticles (MPs, ~size between 0.1 and 1 mm) are lipid encased containers derived from intact cells which contain antigen from the parent cells. MPs are involved in intercellular communication and regulate inflammation. Stroke increases secretion of brain derived MP (BDMP) which activate macrophages/microglia and induce neuroinflammation. Lactadherin (Milk fat globule–EGF factor-8) binds to anionic phospholipids and extracellular matrices, promotes apoptotic cell clearance and limits pathogenic antigen cross presentation. In this study, we investigate whether BDMP affects stroke-induced neuroinflammation and whether Lactadherin treatment reduces stroke initiated BDMP-induced neuroinflammation, thereby improving functional outcome after stroke. Middle aged (8–9 months old) male C57BL/6J mice were subjected to distal middle cerebral artery occlusion (dMCAo) stroke, and BDMPs were extracted from ischemic brain 24 h after dMCAo by ultracentrifugation. Adult male C57BL/6J mice were subjected to dMCAo and treated via tail vein injection at 3 h after stroke with: (A) +PBS (n = 5/group); (B) +BDMPs (1.5 × 108, n = 6/group); (C) +Lactadherin (400 μg/kg, n = 5/group); (D) +BDMP+Lactadherin (n = 6/group). A battery of neurological function tests were performed and mice sacrificed for immunostaining at 14 days after stroke. Blood plasma was used for Western blot assay. Our data indicate: (1) treatment of Stroke with BDMP significantly increases lesion volume, neurological deficits, blood brain barrier (BBB) leakage, microglial activation, inflammatory cell infiltration (CD45, microglia/macrophages, and neutrophils) into brain, inflammatory factor (TNFα, IL6, and IL1β) expression in brain, increases axon/white matter (WM) damage identified by decreased axon and myelin density, and increases inflammatory factor expression in the plasma when compared to PBS treated stroke mice; (2) when compared to PBS and BDMP treated stroke mice, Lactadherin and BDMP+Lactadherin treatment significantly improves neurological outcome, and decreases lesion volume, BBB leakage, axon/WM injury, inflammatory cell infiltration and inflammatory factor expression in the ischemic brain, respectively. Lactadherin treatment significantly increases anti-inflammatory factor (IL10) expression in ischemic brain and decreases IL1β expression in plasma compared to PBS and BDMP treated stroke mice, respectively. BDMP increases neuroinflammation and aggravates ischemic brain damage after stroke. Thus, Lactadherin exerts anti-inflammatory effects and improves the clearance of MPs to reduce stroke and BDMP induced neurological deficits

ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke

ATP-binding cassette transporter A1 (ABCA1) plays an important role in the regulation of apolipoprotein E (ApoE) and the biogenesis of high-density lipoprotein (HDL) cholesterol in the mammalian brain. Cholesterol is a major source for myelination. Here, we investigate whether ABCA1/ApoE/HDL contribute to myelin repair and oligodendrogenesis in the ischemic brain after stroke. Specific brain ABCA1-deficient (ABCA1(-B/-B)) and ABCA1-floxed (ABCA1(fl/fl)) control mice were subjected to permanent distal middle-cerebral-artery occlusion (dMCAo) and were intracerebrally administered (1) artificial mouse cerebrospinal fluid (CSF) as vehicle control, (2) human plasma HDL3, and (3) recombined human ApoE2 starting 24 h after dMCAo for 14 days. All stroke mice were sacrificed 21 days after dMCAo. The ABCA1(-B/-B)-dMCAo mice exhibit significantly reduced myelination and oligodendrogenesis in the ischemic brain as well as decreased functional outcome 21 days after stroke compared with ABCA1(fl/fl) mice; administration of human ApoE2 or HDL3 in the ischemic brain significantly attenuates the deficits in myelination and oligodendrogenesis in ABCA1(-B/-B)-dMCAo mice ( p \u3c 0.05, n = 9/group). In vitro, ABCA1(-B/-B) reduces ApoE expression and decreases primary oligodendrocyte progenitor cell (OPC) migration and oligodendrocyte maturation; HDL3 and ApoE2 treatment significantly reverses ABCA1(-B/-B)-induced reduction in OPC migration and oligodendrocyte maturation. Our data indicate that the ABCA1/ApoE/HDL signaling pathway contributes to myelination and oligodendrogenesis in the ischemic brain after stroke

Analysis of serum protein fractions from women with recurrent miscarriage

Recurrent miscarriage occurs in 1 - 5 % of women at reproductive age. The most common cause of recurrent miscarriage is chromosomal abnormalities of the embryo (41%), chromosomal aberrations parents (10%), anatomical abnormalities of the uterus (5%), infectious and hormonal factors. In about 25% of women, no cause of recurrent miscarriage is usually found. Therefore it seems important to study all factors possibly inducing pregnancy disorders. Objective: The aim of this study was to find a difference in serum protein fractions between women with primary and secondary recurrent miscarriage. Methods: The study group consisted of 52 women (aged 36.0±4.9) with recurrent miscarriage. Nine of them (17%) reported one earlier regular pregnancy ending with childbirth without complications. Control group comprised 30 non-pregnant women (aged 36.1±3.6), who had given vaginal birth to healthy children at least twice. Serum protein fractions were separated by electrophoresis in the SDS PAGE buffer system using a Mini PROTEAN 3 cell device. BioRad SDS PAGE Molecular Weight Standards covering mass range of 6.5-200 kDa were used as a reference. Gels were stained with Coomassie Blue R 250 solution. BioRad QuantityOne software was used for the assessment of molecular weight of each protein fraction. Results: Electrophoretic separation revealed 39 protein fractions of 10 243 kDa. Particularly interesting was a 38 kDa fraction present exclusively in serum of women with recurrent pregnancy, who had never given birth. Another fraction (74 kDa), not detected in the control group, was found in all women with recurrent pregnancy loss. Protein fractions of 76 and 151 kDa were present only in the control group. Conclusions: The presence of the protein fractions of low- or mid-weight in serum from women with recurrent miscarriage may potentially play a role in the pathomechanism of this disorder