The group A streptococcal collagen‐like protein‐1, Scl1, mediates biofilm formation by targeting the extra domain A‐containing variant of cellular fibronectin expressed in wounded tissue

Wounds are known to serve as portals of entry for group A Streptococcus (GAS). Subsequent tissue colonization is mediated by interactions between GAS surface proteins and host extracellular matrix components. We recently reported that the streptococcal collagen‐like protein‐1, Scl1, selectively binds the cellular form of fibronectin (cFn) and also contributes to GAS biofilm formation on abiotic surfaces. One structural feature of cFn, which is predominantly expressed in response to tissue injury, is the presence of a spliced variant containing extra domain A (EDA/EIIIA). We now report that GAS biofilm formation is mediated by the Scl1 interaction with EDA‐containing cFn. Recombinant Scl1 proteins that bound cFn also bound recombinant EDA within the C‐C’ loop region recognized by the α₉β₁ integrin. The extracellular 2‐D matrix derived from human dermal fibroblasts supports GAS adherence and biofilm formation. Altogether, this work identifies and characterizes a novel molecular mechanism by which GAS utilizes Scl1 to specifically target an extracellular matrix component that is predominantly expressed at the site of injury in order to secure host tissue colonization.     

Bumetanide Enhances Phenobarbital Efficacy in a Rat Model of Hypoxic Neonatal Seizures

Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na⁺-K⁺-2 Cl⁻ cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABA_A receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in E_GABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.     

Chance and change in British Long-tailed field mice: (Apodemus sylvaticus)

The Long-tailed field mouse ( Apodemus sylvaticus (L.)) has undergone a marked degree of racial differentiation on the islands of the north-west Atlantic (Iceland, Shetland, and the Hebrides). The differences have arisen as a result of the colonization of these islands after the Pleistocene by small numbers of animals carrying alleles in different proportions to those in the parental population. In contrast, the populations on some islands to the south of Britain (Jersey and Guernsey in the Channel Isles, and St. Mary's in the Isles of Scilly) are similar to A. sylvaticus from the mainland of Britain, and are likely to represent the descendants of mice which survived the Ice Ages ( A. sylvaticus populations on the smaller islands–Alderney, Sark, Herm and Tresco–differ markedly from their closest relatives, and probably represent the results of recolonization following extinction in the same way as on the glaciated islands to the north).
On the mainland of Britain there is a fairly clear distinction between two groups: western and central populations, and eastern ones (which have closer affinities to French mice than western British ones). It is suggested that the two mainland British "races" may have diverged in Pleistocene refuges. Since no pelage or size genes are involved in the divergence, it would not be expected that they would be taxonomically distinct.
The data on which these conclusions are based derive from the incidence of 20 nonmetrical variants in the skulls of 1096 mice from 22 series.     

Ingestion of sugar diets correlates with spike activity in labellar chemosensilla of the flesh-fly, Neobellieria (= Sarcophaga ) bullata

Abstract .Female 2-day-old Neobellieria (= Sarcophaga ) bullata (Parker) (Diptera: Sarcophagidae) were exposed to different concentrations of sucrose, glucose and fructose in a single-choice potometer, and the volume ingested in the first hour was measured. Nerve spike activity in response to the same sugars was recorded from medium labellar taste hairs of similar flies by tip-recording. Two classes of chemosensory cells responded to sucrose, glucose and fructose. Cell 1 showed an increasing spike activity with sugar concentration, whereas cell 2 did not; cell 1 was identified as the 'sugar cell'.
For both spike activity in cell 1 and feeding, sucrose was the most stimulatory sugar. The dose–response curves for glucose and fructose crossed over at about 200 m m . At higher concentrations, glucose was more stimulatory for both cell 1 and for feeding, and at lower concentrations, fructose. The pattern of spike activity supports a separate location on the sensory cells of receptors for pyranose and fructose forms of sugar. The strong correlation between volume ingested and spike activity indicates that sugar feeding is controlled by sensory input from the 'sugar' cells of labellar chemosensilla. Moreover, the results suggest that the flies do not distinguish between these sugars except by apparent 'sweetness'.