Moving up the sanitation ladder with the help of microfinance in urban Malawi

Abstract We carried out a stated preference survey in Malawi to examine whether access to microfinance for sanitation would significantly increase the proportion of households upgrading to improved pit latrines or alternative improved sanitation technologies (urine diverting dry toilet, fossa alterna, pour flush). We presented a range of sanitation options at local market prices, initially without and then with a real microfinance option, to 1,300 households sampled across 27 low-income urban settlements in the two largest cities, Lilongwe and Blantyre. When we gave respondents a microfinance option, the proportion of households stating an intention to install improved and unimproved pit latrines decreased significantly, while the proportion stating an intention to upgrade to alternative improved sanitation technologies increased significantly. However, households in the lowest wealth quintile were more likely to state a preference for unimproved pit latrines, suggesting that the benefits of microfinance for sanitation may not accrue equally across wealth strata. Organisations seeking to improve access to safely managed sanitation by promoting alternative sanitation technologies would succeed if households have access to affordable alternative sanitation technologies and microfinance for sanitation. However, poorer households would need more affordable improved sanitation technologies, flexible microfinance options and possibly targeted subsidies to gain access to safely managed sanitation.</jats:p

Disrupted hippocampal sharp-wave ripple-associated spike dynamics in a transgenic mouse model of dementia.

This is the peer reviewed version of the article, which has been published in final form at DOI: 10.1113/jphysiol.2014.282889. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Neurons within the CA1 region of the hippocampus are co-activated during high frequency (100-250 Hz) sharp wave ripple (SWR) activity in a manner that likely drives synaptic plasticity and promotes memory consolidation. In this study we have used a transgenic mouse model of dementia (rTg4510 mice) which overexpresses a mutant form of tau protein, to examine the effects of tauopathy on hippocampal SWRs and associated neuronal firing. Tetrodes were used to record simultaneous extracellular action potentials and local field potentials from the dorsal CA1 pyramidal cell layer of 7-8 month old wild-type and rTg4510 mice at rest in their home cage. At this age point these mice exhibit neurofibrillary tangles, neurodegeneration and cognitive deficits. Epochs of sleep or quiet restfulness were characterised by minimal locomotor activity and a low theta/delta ratio in the local field potential power spectrum. SWRs detected off-line were significantly lower in amplitude and had an altered temporal structure in rTg4510 mice. Nevertheless, the average frequency profile and duration of the SWRs were relatively unaltered. Putative interneurons displayed significantly less temporal and phase locking to SWRs in rTg4510 mice, whilst putative pyramidal neurons showed increased temporal and phase locking to SWRs. These findings indicate there is reduced inhibitory control of hippocampal network events and points to a novel mechanism which may contribute to impairments in memory consolidation in this model of dementia. This article is protected by copyright. All rights reserved.Alzheimer’s Research UKMedical Research Counci

Inhibitory synapse formation in a co-culture model incorporating GABAergic medium spiny neurons and HEK293 cells stably expressing GABAA receptors.

Inhibitory neurons act in the central nervous system to regulate the dynamics and spatio-temporal co-ordination of neuronal networks. GABA (γ-aminobutyric acid) is the predominant inhibitory neurotransmitter in the brain. It is released from the presynaptic terminals of inhibitory neurons within highly specialized intercellular junctions known as synapses, where it binds to GABAA receptors (GABAARs) present at the plasma membrane of the synapse-receiving, postsynaptic neurons. Activation of these GABA-gated ion channels leads to influx of chloride resulting in postsynaptic potential changes that decrease the probability that these neurons will generate action potentials. During development, diverse types of inhibitory neurons with distinct morphological, electrophysiological and neurochemical characteristics have the ability to recognize their target neurons and form synapses which incorporate specific GABAARs subtypes. This principle of selective innervation of neuronal targets raises the question as to how the appropriate synaptic partners identify each other. To elucidate the underlying molecular mechanisms, a novel in vitro co-culture model system was established, in which medium spiny GABAergic neurons, a highly homogenous population of neurons isolated from the embryonic striatum, were cultured with stably transfected HEK293 cell lines that express different GABAAR subtypes. Synapses form rapidly, efficiently and selectively in this system, and are easily accessible for quantification. Our results indicate that various GABAAR subtypes differ in their ability to promote synapse formation, suggesting that this reduced in vitro model system can be used to reproduce, at least in part, the in vivo conditions required for the recognition of the appropriate synaptic partners and formation of specific synapses. Here the protocols for culturing the medium spiny neurons and generating HEK293 cells lines expressing GABAARs are first described, followed by detailed instructions on how to combine these two cell types in co-culture and analyze the formation of synaptic contacts

Nest visitors of Vespula wasps and their potential use for biological control in an invaded range

The common and the German wasp, Vespula vulgaris and V. germanica, have proved to be prolific invasive species capable of degrading local ecosystems and costing invaded countries millions of dollars annually. Despite clear incentive, control strategies are yet to have any significant deleterious impact on invasive populations. Several species of arthropods are known to inhabit Vespula nests and feed upon developing larvae as either parasitoids or predators. Recent control strategies propose the use of such parasitoids as agents of biocontrol against invasive wasps (Volucella inanis in particular). Despite a general understanding of parasitoid ecology, some aspects such as prevalence, distribution, and behaviour remain limited. Here, we surveyed natural enemy prevalence in wasp nests over the period of three years and we tested larvae prey preference of two Volucella species, V. inanis and V. zonaria towards Vespula wasps. We find V. inanis to be the most prevalent of four prominent candidates for Vespid biocontrol—V. inanis, V. zonaria, Sphecophaga vesparum, and Metoecus paradoxus. Using two-choice assays, we find larvae of V. inanis to have slight yet significant prey preference for V. vulgaris larvae over V. germanica larvae, whilst V. zonaria display no preference. Furthermore, V. inanis were not averse to still predating upon V. germanica, doing so in 41% of trials. Prior exposure has no effect on the prey-preference. Our work provides experimental evidence that V. inanis is a promising candidate for biocontrol of invasive Vespula wasps, as the larvae predate on both target species of Vespula and display no exclusive preference among them

Complex patterns of gene fission in the eukaryotic folate biosynthesis pathway

This is the final version. Available on open access from Oxford University Press via the DOI in this recordShared derived genomic characters can be useful for polarizing phylogenetic relationships, for example, gene fusions have been used to identify deep-branching relationships in the eukaryotes. Here, we report the evolutionary analysis of a three-gene fusion of folB, folK, and folP, which encode enzymes that catalyze consecutive steps in de novo folate biosynthesis. The folK-folP fusion was found across the eukaryotes and a sparse collection of prokaryotes. This suggests an ancient derivation with a number of gene losses in the eukaryotes potentially as a consequence of adaptation to heterotrophic lifestyles. In contrast, the folB-folK-folP gene is specific to a mosaic collection of Amorphea taxa (a group encompassing: Amoebozoa, Apusomonadida, Breviatea, and Opisthokonta).Next, we investigated the stability of this character.We identified numerous gene losses and a total of nine gene fission events, either by break up of an open reading frame (four events identified) or loss of a component domain (five events identified). This indicates that this three gene fusion is highly labile. These data are consistent with a growing body of data indicating gene fission events occur at high relative rates. Accounting for these sources of homoplasy, our data suggest that the folB-folK-folP gene fusion was present in the last common an castor of Amoebozoa and Opisthokonta but absent inthe Metazoa including the human genome. Comparative genomic data of these genes provides an important resource for designing therapeutic strategies targeting the de novo folate biosynthesis pathway of a variety of eukaryotic pathogens such as Acanthamoeba castellanii.Society of General MicrobiologyTula Foundation (The Centre for Comparative Genomics and Evolutionary Bioinformatics at Dalhousie University)Gordon and Betty Moore FoundationLeverhulme TrustRoyal SocietyNatural Environment Research Council (NERC)Biotechnology and Biological Sciences Research Council (BBSRC

Refining the indications for scapula tip in mandibular reconstruction

Mandibular reconstruction in osteoradionecrosis or salvage surgery can often be complicated by the lack of suitable recipient vessels in the ipsilateral neck and the associated requirement for significant extraoral skin reconstruction. The scapula tip with its long vascular pedicle and option of a chimeric soft tissue component offers a versatile reconstructive solution in such cases. This article reports four consecutive cases of mandibular reconstruction with poor ipsilateral vascular options and additional soft tissue requirements in which the scapula tip was justified and preferred. The blood supply to the lateral scapula through the circumflex scapular system is well established in the literature and this would be the preferred reconstruction in class I mandibular defects associated with a significant soft tissue requirement. The scapula tip would suit cases where the ipsilateral recipient vessels are compromised, and so justify the potential for mandibular reconstruction with inferior bone stock

Altered intrinsic pyramidal neuron properties and pathway-specific synaptic dysfunction underlie aberrant hippocampal network function in a mouse model of Tauopathy.

Final published version of article. This article is freely available online through the J Neurosci Author Open Choice option.The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. SIGNIFICANCE STATEMENT: Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention.Medical Research Council (MRC)Royal SocietyAlzheimer's Research United Kingdo

Liver transplantation for type I and type IV glycogen storage disease

Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1–5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Postoperative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types T and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting

Orthogonal Bases of Invariants in Tensor Models

Representation theory provides a suitable framework to count and classify invariants in tensor models. We show that there are two natural ways of counting invariants, one for arbitrary rank of the gauge group and a second, which is only valid for large N. We construct bases of invariant operators based on the counting, and compute correlators of their elements. The basis associated with finite N diagonalizes the two-point function of the theory and it is analogous to the restricted Schur basis used in matrix models. We comment on future lines of investigation.Comment: Two overlapping but independent results are merged to a joint work. 16 pages, 1 tabl