The short-chain dehydrogenase/reductase (SDR) superfamily represents one of the largest protein superfamilies known to date. Enzymes of this family usually catalyse NAD(P)(H) dependent reactions with ...a substrate spectrum ranging from polyols, retinoids, steroids and fatty acid derivatives to xenobiotics. We have currently identified 73 SDR superfamily members within the human genome. A status report of the human SDR superfamily is provided in terms of 3D structure determination, co-factor preferences, subcellular localisation and functional annotation. A simple scoring system for measuring structural and functional information (SFS score) has also been introduced to monitor the status of 5 key metrics. Currently there are 17 SDR members with an SFS score of zero indicating that almost a quarter of the human SDR superfamily lacks substantial functional annotation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
42.
Neutralizing the HIV Reservoir Marsden, Matthew D.; Zack, Jerome A.
Cell,
08/2014, Volume:
158, Issue:
5
Journal Article
Peer reviewed
Open access
Halper-Stromberg et al. use a humanized mouse model to demonstrate that broadly neutralizing antibodies, when administered with a combination of HIV latency activators, can reduce persistent HIV ...reservoirs, as measured by plasma virus rebound. Their results support the use of broadly neutralizing antibodies in HIV-reservoir-purging strategies.
Halper-Stromberg et al. use a humanized mouse model to demonstrate that broadly neutralizing antibodies, when administered with a combination of HIV latency activators, can reduce persistent HIV reservoirs, as measured by plasma virus rebound. Their results support the use of broadly neutralizing antibodies in HIV-reservoir-purging strategies.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Microplastics (MPs) are of increasing concern for filter feeding marine and freshwater species. Additionally MPs can sorb hydrophobic contaminants from the water, potentially providing an additional ...pathway of exposure of aquatic species to contaminants. An acute 48 h laboratory study was conducted to investigate the effects of microplastics and triclosan, both individually and combined, on New Zealand's green-lipped mussel, Perna canaliculus. Biomarkers included clearance rate, oxygen uptake, byssus production; and superoxide dismutase (SOD) activity, glutathione-S-transferase (GST) activity and lipid peroxidation in the gill tissue. Microplastics and triclosan, both individually and combined significantly decreased oxygen uptake and byssus production. These physiological responses were not observed when the microplastics were spiked with triclosan. Triclosan, both alone and spiked to microplastics, increased mussel oxidative stress markers including SOD activity and lipid peroxidation. An enhanced effect was observed on the SOD enzyme activity when mussels were exposed to microplastics spiked with triclosan. No effects on the biochemical biomarkers were observed for mussels exposed to microplastic only. Microplastics enhanced the uptake of triclosan in mussel tissue compared with triclosan only treatments indicating that microplastics potentially provide an additional pathway of exposure to hydrophobic contaminants.
•Mussels (Perna canaliculus) were exposed for 48 hours to triclosan and polyethylene microbeads both singly and combined.•Microplastics increased whole mussel concentrations of triclosan.•Microplastics decreased oxygen uptake and bysuss thread production.•SOD activity was enhanced for mussels exposed to triclosan spiked microplastics.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In recent years there has been increasing interest in oscillatory neural activity in the CNS and in the role that such activity may have in motor control. It is thought that physiological tremor may ...be a manifestation in the periphery of such central oscillatory activity and that some pathological tremors are the result of derangement of these oscillators. This review re-evaluates both early and recent studies on physiological and pathological tremors and other peripheral oscillations in order to gain a new perspective on the nature and function of their central progenitors. This approach, namely using tremor as a `window' into the function of central oscillations, is particularly suited to human investigations because of the obvious limitations of direct central recording. It is argued that physiological tremor is likely to be multifactorial in origin, with contributions not only from CNS 10-Hz range oscillatory activity, but also from motor unit firing properties, mechanical resonances and reflex loop resonances. Different origins are likely to dominate under different conditions. While some pathological tremors appear to arise as a distortion of central or peripheral components of physiological tremor, others arise de novo, such as the pathological oscillation of 3- to 6-Hz parkinsonian tremor. CNS oscillations outside the 10-Hz range are also found to modulate limb activity in normal individuals, and oscillatory activity exists in other motor systems such as eye movements. Finally, it is shown how studies of peripheral oscillations may help develop hypotheses on the role of CNS oscillations in motor control, including the proposed `binding' function of synchronized oscillations and the possibility that motor signals could be coded by frequency of modulating oscillation as well as by synaptic connectivity.
The basal ganglia play a role in controlling movement. The motor circuits within the striato-pallidal complex are thought to facilitate desired movement and inhibit unwanted movement through their ...influence via thalamus, mainly on precentral motor cortical regions. Lesions in the motor thalamus, or in the globus pallidus, therefore might be expected to impair voluntary movement. But stereotaxic lesions in patients with Parkinson's disease directed at the motor thalamus verified at autopsy, and lesions in the globus pallidus, which improve rigidity and tremor, apparently do not worsen parkinsonian hypokinesia and bradykinesia; nor do they regularly cause dyskinesias. Reasons for this discrepancy are reviewed. It is concluded that the motor circuits of the basal ganglia are part of a distributed motor system which can operate, albeit imperfectly, in the absence of striato-pallido-thalamo-cortical feedback. There may, however, be subtle defects in motor performance after thalamic and pallidal lesions which have escaped attention. Further consideration leads to two hypotheses concerning normal basal ganglia motor function. First, it seems most likely that it is a pause in firing of medial pallidal and substantia nigra reticulata neurons that, by disinhibition of thalamic targets, permits movements generated by cortical motor areas. An increase in firing of medial pallidal neurons, which so far has been the major focus of attention, may be more concerned with inhibition of unwanted movement. Secondly, we suggest that the basal ganglia play a particular role in motor control. A change in firing of medial pallidal neurons appears to occur too late to initiate a new movement. However, the motor circuit within the striato-pallidal system routinely receives a continuous delayed read-out of cortical motor activity and issues an output directed via thalamus mainly to premotor cortical regions. This may permit the routine automatic execution of sequences of movements generated in cortical motor areas. There is evidence that other regions of the striatum respond to significant external or internal cues as dictated by their cortical inputs, the significance being determined by memory, novelty, emotional and other contexts. We suggest that such events capture the attention of the non-motor striatum, which then interrupts the routine operation of the motor circuit, perhaps at the level of the medial pallidum and substantia nigra pars reticulata, to permit new cortical motor action.
Co-contraction and overflow of EMG activity of inappropriate muscles are typical features of all dystonic movements whether voluntary or involuntary. Voluntary movements are slow and more variable ...than normal, and there is particular difficulty switching between component movements of a complex task. Reduced spinal cord and brainstem inhibition is common to many reflex studies (long-latency reflexes, cranial reflexes and reciprocal inhibition). These reflex abnormalities may contribute to the difficulties in voluntary movements but cannot be causal as they can occur outside the clinically involved territory. Clinical and neurophysiological studies have emphasized the possible role of sensory feedback in the generation of dystonic movements. Abnormalities of cortical and basal ganglia function have been described in functional imaging and neurophysiological studies of patients with dystonia and in animal models of primary dystonia. Studies of cortical function have shown reduced preparatory activity in the EEG before the onset of voluntary movements, whilst magnetic brain stimulation has revealed changes in motor cortical excitability. Functional imaging of the brain in primary dystonia has suggested reduced pallidal inhibition of the thalamus with consequent overactivity of medial and prefrontal cortical areas and underactivity of the primary motor cortex during movements. These findings are supported by preliminary neuronal recordings from the globus pallidus and the thalamus at the time of stereotaxic surgery in patients with dystonia. All this evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata). This causes altered thalamic control of cortical motor planning and executive areas, and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms.
Highly active antiretroviral therapy (HAART) can potently suppress human immunodeficiency virus (HIV) replication and prevent progression to AIDS. However, HAART does not cure infected patients. ...Instead, HIV persists in latently infected CD4+ T cells and various cryptic cellular reservoirs. Hence, under current therapy regimens, patients must continue taking HAART for the remainder of their lives. Eliminating residual replication-competent virus is critical if eradication of HIV is to be achieved. While this challenge is formidable, we describe here a number of innovative approaches intended to further deplete HIV in HAART-treated patients. New antiretroviral drugs that target different viral proteins and stages of the virus life cycle, compounds that enhance anti-HIV immune responses and novel gene therapy approaches may each play a role in improving long-term suppression of the virus. Moreover, methods for more specifically and efficiently inducing HIV from latency and eliminating the newly activated host cells are also under development.
Estuarine bivalves are exposed to spatial and temporal variations in salinity and seston quality and quantity. This is the first study to investigate the effects of salinity reduction and ...phytoplankton availability on the survival, health and growth of a burrowing bivalve. The intertidal clam Austrovenus stutchburyi survived 6 wk of laboratory storage in dilute seawater (20ppt) at 15 degree C. In salinities below 14ppt, and at low phytoplankton concentrations (<10 mu g chl a l super(-1)), clams lost weight and mortality occurred within 4 wk of exposure. With high phytoplankton availability (>20 mu g chl a l super(-1)), some clams survived 6 wk exposure to 7ppt. Salinity and quality of seston over 5 shellfish beds varied both amongst and within sites. Chl a concentration at high tide was variable between sites, but was generally below 8 mu g l super(-1). Seston total particulate matter (TPM) ranged from 25 to 400 mg l super(-1), and particulate organic matter (POM) from 3 to 31 mg l super(-1). Clams transplanted to other sites in the estuary quickly adapted to new environmental conditions. Average growth rates of clams caged at 4 estuary sites for 6 mo (October 1997 to April 1998) were low, between 0.17 and 0.35 mm mo super(-1). Total length increment correlated positively with low-tide temperature, salinity and average chl a concentration. After 2 mo, there was a direct linear relationship between transplanted clam standard condition index (Cl sub(shell)) and length increment. The integrated laboratory and field studies confirm that salinity dilution, together with low phytoplankton availability, reduces growth and condition of this shallow- burrowing estuarine clam.
Full text
Available for:
BFBNIB, NUK, PNG, UL, UM, UPUK
The African malaria vector, Anopheles gambiae, is characterized by multiple polymorphic chromosomal inversions and has become widely studied as a system for exploring models of speciation. Near ...complete reproductive isolation between different inversion types, known as chromosomal forms, has led to the suggestion that A. gambiae is in early stages of speciation, with divergence evolving in the face of considerable gene flow. We compared the standard chromosomal arrangement (Savanna form) with genomes homozygous for j, b, c, and u inversions (Bamako form) in order to identify regions of genomic divergence with respect to inversion polymorphism. We found levels of divergence between the two sub-taxa within some of these inversions (2Rj and 2Rb), but at a level lower than expected and confined near the inversion breakpoints, consistent with a gene flux model. Unexpectedly, we found that the majority of diverged regions were located on the X chromosome, which contained half of all significantly diverged regions, with much of this divergence located within exons. This is surprising given that the Bamako and Savanna chromosomal forms are both within the S molecular form that is defined by a locus near centromere of X chromosome. Two X-linked genes (a heat shock protein and P450 encoding genes) involved in reproductive isolation between the M and S molecular forms of A. gambiae were also significantly diverged between the two chromosomal forms. These results suggest that genes mediating reproductive isolation are likely located on the X chromosome, as is thought to be the case for the M and S molecular forms. We conclude that genes located on the sex chromosome may be the major force driving speciation between these chromosomal forms of A. gambiae.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Crustaceans, like all aquatic invertebrates, take up and accumulate metals from a wide range of sources and the trace metal concentrations within their tissues and bodies show great variability. ...Trace metal uptake in crustaceans occurs from the water and food, either of which may be affected by the physico-chemical properties of the sediment. Accumulated metal concentrations in amphipods are contrasted with those of other crustaceans and examples are given to show how external and internal factors affect bioaccumulation. One of the major pathways for the uptake of trace metals is from solution directly through permeable surfaces including the gills. Changes in salinity and oxygen tension can modify the uptake characteristics from solution particularly in the case of interstitial water within sediments. Infaunal amphipods have direct contact with the sediment and the bioavailabilities of trace metals depend on the strength of the metal binding which is determined by a combination of properties including grain size, organic content, the presence of metals such as lead and iron as well as other ambient environmental conditions. Metal concentrations within amphipod bodies reflect the bioavailabilities of trace metals in their habitat. Body size is one of the major factors contributing to individual variability in trace metal concentrations within species. For some amphipod species, there are differences in trace metal accumulation with gender, breeding and developmental stage. In amphipods, accumulated body metal concentrations are the best biomarkers for environmental metal availabilities. Metal accumulation affects the ecology of crustaceans as a consequence of the energy costs associated with excreting and/or detoxifying the incoming metals. If the costs are significant, then this may result in reduced growth and reproduction. The effects of accumulated metals on communities have yet to be determined. Accumulated metals in crustacean prey species may be transferred along the food chain, but biomagnification in fish appears unlikely. One of the main ecological challenges is the need to link molecular biomarkers with ecologically relevant life history characteristics including growth, survival, reproduction and recruitment.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
