Binding('tagging') of a virus-specific oligonucleotide 'sticker' to RNA transcripts copied from PCR products caused retardation of transcript mobility in gel. This enables detection of specific sequences within the RNA transcripts, and a virus strain (PVY(NTN)) could thus be positively identified. We have demonstrated further that oligonucleotides that contained virus sequences originated from different genomic locations varied in their inhibitory effect on the rate of transcript migration in gel; thus, the most effective oligonucleotide could be chosen. Combinations of different strain-specific oligonucleotides had additive retarding effects on transcript migration. The conditions for annealing oligonucleotides to the RNA transcripts were studied, including concentrations of oligonucleotides and salt. A higher electrophoresis temperature (up to 45 degrees C) reduced the gel retardation phenomena, which indicated a conformation mechanism. The applicability of 'tagging' of RNA transcripts with a strain-specific oligonucleotide for virus strain differentiation is discussed.

The role of the immune system in the progression of experimental nephrotoxic serum nephritis (NTN) in rats has been evaluated. Proteinuria and renal functional impairment during the sub-acute phase of the disease determined the long-term prognosis of the nephritis regardless of the humoral autologous antibody levels. In contrast to the acute, immune mediated glomerulonephritis, chronic glomerular scarring in NTN proceeds independently of the host immune response.

By immunization with rabbit immunoglobulins and the injection of a subnephritogenic dose of rabbit nephrotoxic serum (NTS), accelerated-type nephrotoxic serum nephritis (NTN) was induced in heterozygous (rnu/+) rats but not in athymic nude (rnu/rnu) rats. By transferring rat antibody against rabbit immunoglobulins, marked proteinuria was induced also in nude rats (202.0 +/- 98.4 mg/day on day 3) as in rnu/+ rats (122.6 +/- 35.3 mg/day on day 3). No marked differences in histological findings could be found between both groups. The most marked increase in the number of intraglomerular infiltrating cells was observed in heterozygous rats indicating that the presence of thymus-derived cells leads to the accumulation of more cells in glomeruli. We conclude that humoral immunity alone is enough to accelerate the pathogenic mechanism which induces glomerular injury with heavy proteinuria in this model.

Degradation and synthesis of the collagen portion (CLP) of the glomerular basement membrane (GBM) in glomeruli of rats with nephrotoxic nephritis (NTN) were determined in vivo and in vitro. Degradation of CLP in rats with NTN was only increased during the first 24 h after induction of NTN. After 24 h, the half-life of CLP in NTN rats (16.9 days) was not significantly different from that in the controls 15.6 days). The loss of CLP during the first 24 h is accompanied by an increased synthesis, measured in vivo and in vitro. The increased synthesis, however, does not seem to be sufficiently high to result in accumulation of CLP-like material in NTN. Since degradation and synthesis of CLP was not altered during the later phase of NTN, it is unlikely that chronic proteinuria is the result of an ongoing abnormal turnover of CLP.

OBJECTIVE

To explore the effects of mild hypothemia on hemodynamics of systemic and renal of dog with septic shock.

METHODS

40 healthy dogs were randomly and evenly divided into the normal temperature non-infected group (NTNS), normal temperature infected group (NTS), hypothermia non-infected group (MHNS) and hypothermia infected group (MHS). NTS and MHS were pumped through the femoral vein of Escherichia coli (E.coli 1 × 10⁹ cfu/ml) by 0.5 ml·kg⁻¹·h⁻¹, producting septic shock model with high-power cycle. Combining with blood pump devices and low temperature thermostat bath, the MHNS and MHS implemented extracorporeal blood cooling method to maintain the blood in temperature (33 ± 1) °C. 0, 24, 48, 72 h point, tested specimens from femoral vein for renal function. In the 0-72 h. Pulse indicates the continuous cardiac output monitor (PiCCO) monitored systemic hemodynamics on each time point. In the 0-72 h, color Doppler ultrasound (CDFI) measured renal hemodynamic on each time point.

RESULTS

There was an increase of SBP (P<0.05), SVR [(2 415 ± 651) dyn·s·cm⁻⁵ vs (1 613 ± 223) dyn·s·cm⁻⁵, P=0.01] and RI (P=0.04) in the MHS group comparing with the NTS group from 24 to 72 h. CO [(3.58 ± 0.44) L/min vs (4.18 ± 0.60) L/min, P=0.04], HR and PSV was decreased in the MHS group. BUN [(8.6 ± 1.6) mmol/L vs (21.2 ± 4.8) mmol/L, P<0.01] and Scr [(167.6 ± 31.2) µmol/L vs (383.8 ± 35.2) µmol/L, P<0.01] was decreased in MHS group comparing with the NTS group. There was a positively correlation between CO and PSV in the canine model of septic shock (P<0.01); and CO was negatively correlated with RI (P<0.01).

CONCLUSIONS

In this canine model of septic shock, hypothermia can stable systemic and renal hemodynamics, and improve kidney function.

The distribution of heparan sulfate proteoglycan (HS-PG) was examined electron microscopically by the high iron diamine (HID) method in puromycin aminonucleoside (PAN) nephrosis, accelerated Masugi nephritis (NTN), and serum sickness nephritis induced by bovine serum albumin (BSA nephritis) in the rat. In PAN nephrosis rats, no change was observed in the distribution of HS-PG in the lamina rara externa (LRE) of the glomerular basement membrane (GBM) throughout the experiment. In NTN rats, however, the loss of HS-PG was observed, and it was associated with subepithelial electron dense deposits formed possibly by serum sickness mechanism, but not with inflammatory cell infiltration. In BAS nephritis, immune deposits were seen in mesangial, subendothelial, intramembranous and subepithelial areas. The deposits in the former three areas seemed to have little reciprocity with the loss of HS-PG and proteinuria. Urinary protein increased in accordance with the development of subepithelial deposits and the loss of HS-PG in the area of the deposits in the LRE. These results indicate that HS-PG could be preserved even in marked proteinuric states in morphologically intact basement membrane, but altered and lost distribution of HS-PG associated with subepithelial immune deposits could in turn result in the development of proteinuria.

BACKGROUND

Necrotizing glomerular lesions are a feature of severe glomerulonephritis. Unlike apoptosis, cellular necrosis has the potential to release damage-associated proteins into the microenvironment, thereby potentiating inflammation. Until recently necrosis was thought to be an unregulated cellular response to injury. However, recent evidence suggests that under certain circumstances receptor mediated necrosis occurs in response to death ligand signalling, one form of which is termed necroptosis. RIPK3, a receptor interacting protein, is a limiting step in the intracellular signalling pathway of necroptosis. A non-redundant role for RIPK3 has been implicated in mouse models of renal ischaemia reperfusion injury and toxic renal injury. The aim of this study was to investigate the role of RIPK3 in nephrotoxic nephritis (NTN), a model of immune complex glomerulonephritis in mice.

METHODS

We induced NTN in RIPK3-/- and WT mice, comparing histology and renal function in both groups.

RESULTS

There was no improvement in urinary albumin creatinine ratio, serum urea, glomerular thrombosis or glomerular macrophage infiltration in the RIPK3-/- mice compared to WT. There was also no difference in number of apoptotic cells in glomeruli as measured by TUNEL staining between the RIPK3-/- and WT mice.

CONCLUSIONS

The data suggests that RIPK3 is not on a critical pathway in the pathogenesis of nephrotoxic nephritis.

Gene Ontology (GO) is a controlled vocabulary of terms that describe molecule function, biological roles and cellular locations of gene products (i.e., proteins and RNAs), it hierarchically organizes more than 43,000 GO terms via the direct acyclic graph. A gene is generally annotated with several of these GO terms. Therefore, ac- curately predicting the association between genes and massive terms is a difficult challenge. To combat with this challenge, we propose an matrix factorization based approach called NMFGO. NMFGO stores the available GO annotations of genes in a gene-term association matrix and adopts an ontological structure based taxonomic similarity measure to capture the GO hierarchy. Next, it factorizes the association matrix into two low-rank matrices via nonnegative matrix factorization regularized with the GO hierarchy. After that, it employs a semantic similarity based k nearest neighbor classifier in the low-rank matrices approximated sub- space to predict gene functions. Empirical study on three model species (S. cerevisiae, H. sapiens and A. thaliana) shows that NMFGO is robust to the input parameters and achieves significantly better prediction performance than GIC, TO, dRW-kNN and NtN, which were re-implemented based on the instructions of the original papers. The supplementary file and demo codes of NMFGO are available at http://mlda.swu.edu.cn/codes.php?name=NMFGO.

Neurturin (NTN) can improve the function and delay the rate of degeneration of dopaminergic neurons in Parkinson's disease (PD). However, its method of delivery to the central nervous system has not been established. Adenoviral vectors have been widely applied in gene therapy because of their high-efficiency gene transfer, easy manipulation, and safety. We used replication-defective adenovirus type 5 (Ad5) to construct a recombinant viral vector encoding full-length human NTN (Ad-NTN) and amplified Ad-NTN and the control (Ad-lacZ) in HEK 293 cells. NTN-specific expression in the Ad-NTN-infected HEK 293 cells was detected by RT-PCR and the immunofluorescent assay. However, no NTN expression was detected in the Ad-lacZ-infected HEK 293 cells. After incubation with the Ad-NTN-infected conditioned medium (CM), the dorsal root ganglia of chicken embryos examined in vitro exhibited radial neurite outgrowth around the ganglia. However, incubation with the Ad-lacZ-infected or blank CM resulted in a short or absent nerve process and the growth of only a few fibroblasts. Our findings indicated that recombinant Ad-NTN was specifically expressed in the host cells, and the expressed NTN possessed biological activity.

The Ca2+-pumping ATPase of erythrocyte plasma membranes of hypertensive humans (HTN) show, in the absence of calmodulin, a low Vmax comparable to that of the enzyme of the erythrocyte membranes of normotensive humans (NTN). Although the addition of calmodulin (1.5 micrograms per ml) increased the maximum activity of the calcium pump of membranes of HTN and NTN individuals by at least 2-fold and 4-fold, respectively, the activator protein partially purified from the erythrocytes of HTN individuals enhanced the activity of the enzyme in a fashion similar to that of the protein obtained from the haemolysate of NTN individuals. A determination of the dependence of the activity of the pump on concentration of ATP revealed that the Km (ATP) of the enzyme of membranes of HTN individuals is 52% higher than that of the enzyme of membranes of NTN individuals, while the Vmax (1.75 +/- 0.28 mumol ATP mg protein-1 h-1) of the pump is 46% lower in the membranes of HTN humans than that of the enzyme of membranes of normal individuals (3.25 +/- 0.42 mumol ATP mg protein-1 h-1). It seems likely from these results that elevated erythrocyte Ca2+ concentration associated with essential hypertension may be due to a defective interaction between the Ca2+-pumping ATPase and the calmodulin Ca2+ complex.

Two different 3D porous metal-organic frameworks, [Zn4O(NTN)2]·10DMA·7H2O (SNU-150) and [Zn5(NTN)4(DEF)2][NH2(C2H5)2]2·8DEF·6H2O (SNU-151), are synthesized from the same metal and organic building blocks but in different solvent systems, specifically, in the absence and the presence of a small amount of acid. SNU-150 is a doubly interpenetrated neutral framework, whereas SNU-151 is a non-interpenetrated anionic framework containing diethylammonium cations in the pores. Comparisons of the N2, H2, CO2, and CH4 gas adsorption capacities as well as the CO2 adsorption selectivity over N2 and CH4 in desolvated SNU-150' (BET: 1852 m(2) g(-1)) and SNU-151' (BET: 1563 m(2) g(-1)) samples demonstrate that the charged framework is superior to the neutral framework for gas storage and gas separation, despite its smaller surface area and different framework structure.

OBJECTIVE

To investigate the role of NF-kappaB/IkappaB signal pathway in mediating the expression of monocyte chemoattractant protein-1 (MCP-1) in experimental rat glomerulonephritis.

METHODS

Nephrotoxic serum nephritis (NTN) was induced by injection of anti-GBM antibody into the tail veins of rats. Electrophoretic mobility shift assay (EMSA) and Western Blot were used to detect the activation of NF-kappaB, nuclear translocation of p65 subunit and degradation of IkappaBalpha and IkappaBbeta in rat renal tissue. MCP-1 expression in glomeruli and renal tubules was also assessed by immunohistochemistry and ribonuclease protection assay. This was further correlated with the activation of NF-kappaB.

RESULTS

There was an obvious expression of MCP-1 in glomeruli and renal tubules. Significant up-regulation of NF-kappaB activation, nuclear translocation of p65 subunit, and degradation of IkappaBalpha and IkappaBbeta were also observed in NTN rat renal tissue, as compared to the control group. A positive correlation was noted between NF-kappaB activation and MCP-1 expression.

CONCLUSIONS

NF-kappaB/IkappaB signal pathway may play an important pathogenetic role in glomerulonephritis, with mediating the expression of MCP-1.

NTN Swiss Biotech™ brings together the Swiss Biotech Association SBA, which is involved in regulatory, financial and legal issues, and biotechnet Switzerland, which is active in translational R&D, to provide a technology base for joint projects. Biotechnet aims to push promising domains by creating topic-oriented platforms that enable academia and industry to work together to produce R&D results of major importance to society and the economy. The first activity initiated by biotechnet is the Antibiotics Platform that has now been launched.

Ancestral β-subunit (Anbu) is homologous to HslV and 20S proteasomes. Based on its phylogenetic distribution and sequence clustering, Anbu has been proposed as the "ancestral" form of proteasomes. Here, we report biochemical data, small-angle X-ray scattering results, negative-stain electron microscopy micrographs and a crystal structure of the Anbu particle from Yersinia bercovieri (YbAnbu). All data are consistent with YbAnbu forming defined 12-14 subunit multimers that differ in shape from both HslV and 20S proteasomes. The crystal structure reveals that YbAnbu subunits form tight dimers, held together in part by the Anbu specific C-terminal helices. These dimers ("protomers") further assemble into a low-rise left-handed staircase. The lock-washer shape of YbAnbu is consistent with the presence of defined multimers, X-ray diffraction data in solution and negative-stain electron microscopy images. The presented structure suggests a possible evolutionary pathway from helical filaments to highly symmetric or pseudosymmetric multimer structures. YbAnbu subunits have the Ntn-hydrolase fold, a putative S1 pocket and conserved candidate catalytic residues Thr1, Asp17 and Lys32(33). Nevertheless, we did not detect any YbAnbu peptidase or amidase activity. However, we could document orthophosphate production from ATP catalyzed by the ATP-grasp protein encoded in the Y. bercovieri Anbu operon.

Self-activation through two-step intra-molecular cleavages is of great importance for the synthesis of mature and functional cephalosporin acylase in the N-terminal nucleophile (Ntn) hydrolase superfamily. A synthetic gene for cephalosporin C acylase (sCPCAcy) from Pseudomonas sp. SE83 was overexpressed, and the self-activated sCPCAcy was produced in Escherichia coli JM109(DE3)/pET28-sCPCAcy. The first autoproteolytic cleavage site of Pre-sCPCAcy was determined to be G239-S240 according to the common features of Ntn hydrolases. The second cleavage site was identified as A232-S233 by C-terminus tandem MS/MS analysis of the purified α-subunit, which released a 7-aa spacer peptide with the generation of the α and β subunits of the mature sCPCAcy. The effect of the cleavage-site-flanking residues in the α-C-terminal region of sCPCAcy on its activation and characteristics was further evaluated. Residue G229 was found to be crucial for the first cleavage of Pre-sCPCAcy. Deletions in the α-C-terminal region were performed, and 14 mutant proteins were constructed. The majority of the fragment-deleted mutant proteins completely lost their activity due to failure of the first autocleavage, but this loss was not observed in mutant proteins D2 (227-AM-228 deletion) and D4 (212-ADLA-215 deletion), which formally activated into mature sCPCAcy with high activity. The Kcat/Km values of mutant proteins D2 and D4 were 46% and 102% higher than that of the original control, respectively.

A 2 × 2 factorial design was used to study the effect of tenderization and liquid smoke on sensory and physical attribution of a fully cooked restructured pork item. The lean and fat mass was removed intact within 30 min postmortem from sow carcasses and assigned to a tenderized or non-tenderized treatment with and without liquid smoke. The four treatment groups were: non-tenderized, no liquid smoke (NTNS); non-tenderized with liquid smoke (NTS); tenderized, no liquid smoke (TNS); and tenderized with liquid smoke (TS). Mechanical tenderization was accomplished 1 h postmortem and the two original portions were subdivided for a 1% acid-neutralized liquid smoke treatment. Total processing time from exsanguination to a fully cooked product was 8 h. There were no differences (P>0.05) among any of the treatments for cohesiveness, juiciness, flavor or connective tissue scores or cooking loss. The TNS treatment had higher (P<0.06) tension values as determined by Instron measurements than the NTNS treatment. There were initially no practical differences between TBA values for fresh-frozen and cooked-frozen restructured pork. However, after 30 d of storage (-23°C), the cooked-frozen product had significantly higher TBA values than fresh-frozen product.

Potato virus Y (PVY) is a significant threat to potato production in Mexico. The presence of recombinant strains of PVY circulating in potato has been reported in the country, but no systematic study on the genetic diversity of PVY in potato and prevalence of PVY strains has been conducted yet. Here, we report on a series of surveys in seed potato production areas in two states in Mexico, Chihuahua and Jalisco, between 2011 and 2019. PVY was detected through the period of nine years in multiple potato cultivars in both states, often remaining asymptomatic in the most popular cultivars, such as Fianna and Agata. When typed to strain, all PVY samples studied were found to have N-serotype, and were all identified molecularly as isolates of the same recombinant strain, PVY^NTN. Five of these PVY isolates were tested on tobacco, where they induced vein necrosis supporting the molecular typing. This identification was also confirmed biologically on differential potato cultivars, where one PVY^NTN isolate from the 2013 survey triggered the hypersensitive resistance conferred by the Nz_tbr gene in the cv. Maris Bard. Seven of these Mexican PVY^NTN isolates, collected between 2013 and 2019, including two PVY isolates from potato tubers exhibiting potato tuber necrotic ringspot disease, were subjected to whole genome sequencing and found to show a typical PVY^NTNa recombinant structure. When subjected to phylogenetic analysis, Mexican PVY^NTN sequences clustered in more than three separate clades, suggesting multiple introductions of PVY^NTN in the country. The wide circulation of the PVY^NTN strain in Mexican potato should be taken into account by the potato producers, to develop mitigation strategies for this PVY strain associated with tuber necrotic symptoms.

Keywords: Causal Agent; Crop Type; Pathogen detection; Pathogen diversity; Subject Areas; Vegetables; Viruses and viroids.

All 22 rabbits injected with sheep globulin containing high titres of antibodies to rabbit glomerular basement membrane (GBM)--nephrotoxic globulin (NTG)--developed antibodies to sheep IgG. Despite this only 15 rabbits developed obvious autologous phase injury. Eleven days after injection of NTG titres of autologous antibody to sheep IgG were similar in rabbits with and without definite autologous phase injury but were detected earlier and rose significantly more rapidly in those with autologous phase injury. In experiments on heterologous phase injury after intravenous injection of NTG, binding of defined amounts of nephrotoxic antibodies (NTAb) to the GBM after bolus injection caused significantly more injury, assessed by proteinuria, than binding of similar amounts of NTAb after infusion of NTG over 3 h (P less than 0.02 Student's paired t-test). In in vitro experiments, aliquots of homogenized rabbit kidney taken 2 days after injection of NTG bound appreciable amounts of rabbit anti-sheep Ig whereas homogenates of kidneys taken 20 days after NTG showed no such binding. These results show that the rate of deposition of NTAb in kidney influences the severity of injury in heterologous and autologous phases of NTN and that antigenic sites or heterologous IgG fixed to the GBM become saturated during the autologous phase of injury.

Parkinson's disease (PD) is a chronic, progressive disease of the central nervous system (CNS), characterized by a slow loss of dopaminergic neurons in the substantia nigra, leading to significant decrease in dopamine (DA) levels in the striatum. Currently used drugs, such as levodopa (L-DOPA), amantadine, dopamine agonists (D) or anticholinergic drugs, are not effective enough, and do not eliminate the causes of disease. Many research centers are conducting research on new forms of currently used drugs (e.g. Duodopa, XP21279, IPX066), new drugs of already known groups (e.g. safinamide), medicines that suppress side effects of L-DOPA (e.g. AFQ056, fipamezole), and, finally, compounds with a novel mechanism of action (e.g. PMY50028, A2A receptor antagonists). A lot of scientific reports indicate an important role of A2A receptors in the regulation of the central movement system, so a new group of compounds - selective antagonists of A2A receptors (e.g. istradefylline, preladenant, SYN115) - has been developed and their potential use in PD has been examined. Clinical studies of A2A receptor antagonists have shown that this group of compounds can shorten off periods and at the same time they do not worsen dyskinesias in patients with PD. Moreover, there is ongoing research on new forms of treatment, such as gene therapy. Attempts to apply the viral vector AAV-2, which will be able to infect neurons with a variety of genes, including the gene of glutamate decarboxylase (GAD), neurturin (NTN), or aromatic L-amino acid decarboxylase, are currently being carried out. The results of phase I and II clinical studies showed some efficacy of this form of treatment, but the method requires further studies. An analysis of potential future therapies of Parkinson's disease suggests that some progress in this field has been made.

BACKGROUND

There is a perception that the training pathway for oral and maxillofacial surgery (OMFS) is unduly long and arduous, as consultant oral and maxillofacial surgeons must be doubly qualified (that is, hold degrees in medicine and dentistry) and be holders of two higher fellowships.

METHODS

We reviewed the data regarding the average age of National Training Number (NTN) holders and GMC data on the year of first registration and the year of entry onto a specialist surgical list for all 9 surgical specialties.

RESULTS

The results showed the average age of the surgical SpR populations ranged from 33.5 to 38.2 years with an average age of 36.14 years. OMFS SpR's average age is 37.69 years. The GMC data showed the average number of months from full to specialist registration ranged from 90.83 months to 135.24 months, with OMFS surgeons having the lowest average.

CONCLUSIONS

These data suggest that OMFS surgeons are of a similar age to other surgeons whilst in training. In addition, they have the shortest transit time between full GMC registration and entry onto the specialist list. The length of this training even with dual qualification is similar to other surgical specialties.

The purpose of this study was to determine if alpha 1-adrenergic receptor blockade alters the hemodynamic response to exercise in young (less than 25 yr) male borderline hypertensives differently than in young normotensives. Five hypertensive (HTN, MAP greater than 105 mmHg) and 7 normotensive (NTN, MAP less than 95 mmHg) college-age males underwent two 30 min bouts of cycle ergometry exercise at 50% VO2pk in a warm (25 degrees C, 50% rh) environment; one following alpha 1-receptor blockade with prazosin (PRAZ) and the other following placebo administration (PLAC). During resting PLAC and compared to NTN, HTN exhibited an elevated cardiac index (CI, p = .002), similar HR and elevated total peripheral resistance index (TPRI, p = .015). During resting PRAZ, CI and TPRI were similar but HR was higher (p = .013) in HTN than NTN. While reduced during PRAZ, resting MAP was higher in HTN than NTN (p = .007) for both trials. With exercise and PLAC, CI was higher (p = .029) while HR and TPRI were similar for HTN compared to NTN. With PRAZ, the exercise CI, TPRI and HR responses were similar for both groups. Exercise MAP was blunted in both groups with PRAZ. While not differing significantly between groups for each treatment, MAP was stable for NTN while it declined after 10 min of exercise in HTN. The elevated CI seen in exercising HTN with PLAC was removed with PRAZ; the exercise response was otherwise unaltered by alpha 1-blockade. Consequently, these data suggest that young male hypertensives have an elevated blood pressure due to an elevated CI incompletely offset by a reduced TPRI. While alpha 1-blockade lowers MAP by lowering CI, the MAP response to exercise remains unaltered.

To determine whether alpha1-blockade affects the forearm vascular resistance responses to lower body negative pressure (LBNP) in borderline hypertensives, six hypertensives (HTN; mean arterial pressure [MAP] = 109.9 +/- 1.7 mm Hg, mean +/- SE) and seven normotensives (NTN; MAP = 81.5 +/- 1.4 mm Hg) underwent exposures of LBNP at pressures of -10, -20, and -40 mm Hg during systemic alpha1-receptor blockade (BLK) and during placebo (PLA). Resting forearm vascular resistance (FVR) was greater in HTN than in NTN during PLA (34.8 +/- 5.4 v 17.5 +/- 3.1 units; P < .05), but not during BLK (28.1 +/- 5.2 v 25.3 +/- 9.9 units). When expressed as a percentage of resting FVR, LBNP evoked an increased FVR (P < .001) that did not differ significantly between BLK and PLA in either group. FVR was higher (P < .001) in HTN than in NTN throughout both trials; at -40 mm Hg of LBNP during BLK, the increase in FVR was greater (P < .05) in HTN than in NTN (131 +/- 42 v 48 +/- 15%). MAP (relative to resting) was maintained throughout LBNP during PLA but, at -40 mm Hg, was lower (P < .01) during BLK for both groups. HR was elevated in BLK and was increased at -40 mm Hg (P < .01) for each group in each trial. This increase was greater during BLK (P < .05). These data suggest that borderline hypertensives have a greater vasoconstrictor response to LBNP than do normotensives and alpha1-blockade does not appear to attenuate this response.

The Swiss biotech landscape seems to be on a healthy footing: There are many imaginative start-ups, we have first-class hospitals, highly advanced clinical research and the availability of a great deal of capital. But we have no reason to rest on our laurels as countries like the USA lead the field. We must lay down the tracks today to remain an attractive country and maintain our ranking among the 10 best locations.