The completion of the Mammalian Gene Collection (MGC)

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide

The clinical spectrum of lipodermatosclerosis

Lipodermatosclerosis refers to the skin induration and hyperpigmentation of the legs that often occurs in patients who have venous insufficiency. Lipodermatosclerosis has also been termed hypodermitis sclewdermiformis and appears to be similar if not-identical to the recently described sclerosing panniculitis of the leg. There has been much confusion about the nature, clinical course, and treatment of lipodermatosclerosis. We believe that lipodermatosclerosis has an acute, inflammatory phase and a chronic, fibrotic stage, although a spectrum exists. Direct immunofluorescence studies of early and late lesions are helpful in that they show dermal pericapillary fibrin deposits without other immunoreactants, Treatment of lipodermatosclerosis consists of compression therapy with either graded stockings or elastic bandages. We and others have found that the anabolic steroid stanozolol improves this condition rapidly and consistently

Fingolimod (FTY720) is not protective in the subacute MPTP mouse model of Parkinson's disease and does not lead to a sustainable increase of brain-derived neurotrophic factor

Parkinson's disease (PD) is characterized by the loss of midbrain dopaminergic neurons and aggregates of α‐synuclein termed Lewy bodies. Fingolimod (FTY720) is an agonist of sphingosine‐1 phosphate receptors and an approved oral treatment for multiple sclerosis. Fingolimod elevates brain‐derived neurotrophic factor (BDNF), an important neurotrophic factor for dopaminergic neurons. BDNF and fingolimod are beneficial in several animal models of PD. In order to validate the therapeutic potential of fingolimod for the treatment of PD, we tested its effect in the subacute MPTP mouse model of PD. MPTP or vehicle was applied i.p. in doses of 30 mg/kg MPTP on five consecutive days. In order to recapitulate the combination of dopamine loss and α‐synuclein aggregates found in PD, MPTP was first administered in Thy1‐A30P‐α‐synuclein transgenic mice. Fingolimod was administered i.p. at a dose of 0.1 mg/kg every second day. Nigrostriatal degeneration was assayed by stereologically counting the number of dopaminergic neurons in the substantia nigra pars compacta, by analysing the concentration of catecholamines and the density of dopaminergic fibres in the striatum. MPTP administration produced a robust nigrostriatal degeneration, comparable to previous studies. Unexpectedly, we found no difference between mice with and without fingolimod treatment, neither at baseline, nor at 14 or 90 days after MPTP. Also, we found no effect of fingolimod in the subacute MPTP mouse model when we used wildtype mice instead of α‐synuclein transgenic mice, and no effect with an increased dose of 1 mg/kg fingolimod administered every day. In order to explain these findings, we analysed BDNF regulation by fingolimod. We did find an increase of BDNF protein after a single injection of fingolimod 0.1 or 1.0 mg/kg, but not after multiple injections, indicating that the BDNF response to fingolimod is unsustainable over time. Taken together we did not observe a neuroprotective effect of fingolimod in the subacute MPTP mouse model of PD. We discuss possible explanations for this discrepancy with previous findings and conclude fingolimod might be beneficial for the nonmotor symptoms of PD