A small molecule that disrupts S. Typhimurium membrane voltage without cell lysis reduces bacterial colonization of mice

As pathogenic bacteria become increasingly resistant to antibiotics, antimicrobials with mechanisms of action distinct from current clinical antibiotics are needed. Gram-negative bacteria pose a particular problem because they defend themselves against chemicals with a minimally permeable outer membrane and with efflux pumps. During infection, innate immune defense molecules increase bacterial vulnerability to chemicals by permeabilizing the outer membrane and occupying efflux pumps. Therefore, screens for compounds that reduce bacterial colonization of mammalian cells have the potential to reveal unexplored therapeutic avenues. Here we describe a new small molecule, D66, that prevents the survival of a human Gram-negative pathogen in macrophages. D66 inhibits bacterial growth under conditions wherein the bacterial outer membrane or efflux pumps are compromised, but not in standard microbiological media. The compound disrupts voltage across the bacterial inner membrane at concentrations that do not permeabilize the inner membrane or lyse cells. Selection for bacterial clones resistant to D66 activity suggested that outer membrane integrity and efflux are the two major bacterial defense mechanisms against this compound. Treatment of mammalian cells with D66 does not permeabilize the mammalian cell membrane but does cause stress, as revealed by hyperpolarization of mitochondrial membranes. Nevertheless, the compound is tolerated in mice and reduces bacterial tissue load. These data suggest that the inner membrane could be a viable target for anti-Gram-negative antimicrobials, and that disruption of bacterial membrane voltage without lysis is sufficient to enable clearance from the host.     

Prefrontal Response and Frontostriatal Functional Connectivity to Monetary Reward in Abstinent Alcohol-Dependent Young Adults

Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant literature on reward-circuit function in addiction and suggest mechanisms for disrupted function in alcohol dependence.     

苎麻疫霉激发蛋白基因断裂现象初探

苎麻疫霉（PhytophthoraboehmeriaeSaw．）可分泌具有诱抗作用的激发蛋白（α－elicihn）,根据α－elicitin第24～30和56～63位保守区氨基酸推导的寡核苷酸引物序列,对苎麻疫霉基因组DNA进行特异PCR扩增反应,发现其扩增的DNA片段大于预计的片段。回收纯化的特异扩增DNA,并进行克隆和测序分析,结果表明特异扩增的elicihn基因亚克隆DNA为570hp,大于预计的117bp。在特异片段中,存在3个内含子将基因断裂成4个阅读框架,即ORF1、ORF2、ORF3和ORF4,其中ORF1和ORF4含有与引物相同的序列,但与其它序列与已克隆的elicihn基因无同源性。因此,芒麻疫霉基因组中的elicitin基因可能存在断裂现象。     

Hand-rearing baboons for laboratory investigations

To conduct laboratory studies in unsedated animals that were similar anatomically and physiologically to man, five full term baboons (four Papio cynocephalus anubis, one Papio cynocephalus cynocephalus) were hand-reared. These infants were used as unsedated animal models in short-term lung clearance studies conducted from birth to 2 years of age. The hand-rearing techniques described here encouraged the formation of an infant-human rearer bond that permitted us to control the level of expressed aggressive behavior as the infant matured. These techniques resulted in baboons which displayed subordinate behavior, showed positive reception to human contact (without evidence of negative stereotypic behavioral anomalies) and remained cooperative subjects for our investigations of short-term pulmonary clearance. The baboons generally were above average in weight in comparison to conspecifically-reared baboons of similar age, sex and species. Representative lung retention curves presented on one baboon demonstrate the feasibility of lung clearance studies in these hand-reared animals. Due to its suitability for unsedated studies, this baboon model may be considered for other types of laboratory investigations.     

Improved Heterojunction Quality in Cu2O-based Solar Cells Through the Optimization of Atmospheric Pressure Spatial Atomic Layer Deposited Zn1-xMgxO

Atmospheric pressure spatial atomic layer deposition (AP-SALD) was used to deposit n-type ZnO and Zn_1-xMg_xO thin films onto p-type thermally oxidized Cu₂O substrates outside vacuum at low temperature. The performance of photovoltaic devices featuring atmospherically fabricated ZnO/Cu₂O heterojunction was dependent on the conditions of AP-SALD film deposition, namely, the substrate temperature and deposition time, as well as on the Cu₂O substrate exposure to oxidizing agents prior to and during the ZnO deposition. Superficial Cu₂O to CuO oxidation was identified as a limiting factor to heterojunction quality due to recombination at the ZnO/Cu₂O interface. Optimization of AP-SALD conditions as well as keeping Cu₂O away from air and moisture in order to minimize Cu₂O surface oxidation led to improved device performance. A three-fold increase in the open-circuit voltage (up to 0.65 V) and a two-fold increase in the short-circuit current density produced solar cells with a record 2.2% power conversion efficiency (PCE). This PCE is the highest reported for a Zn_1-xMg_xO/Cu₂O heterojunction formed outside vacuum, which highlights atmospheric pressure spatial ALD as a promising technique for inexpensive and scalable fabrication of Cu₂O-based photovoltaics.     

EXPERIMENTAL INITIATION OF HAUSTORIA IN AGALINIS PURPUREA (SCROPHULARIACEAE)

The initiation and early developmental stages of the haustorium were studied in Agalinis purpurea (Scrophulariaceae). Plants were grown in a 0.9% agar inorganic medium with a 0.5% sucrose supplement. Root exudate collected from Lespedeza sericea induced the initiation of haustoria, with earliest stages evident in 6-12 hr. A 30-min exposure to exudate produced an increased frequency of haustoria and a 24-hr exposure yielded haustorial frequencies equal to the number that were initiated on control plants continuously exposed to root exudate for the 5-day growth period. The early cytological features of haustorial development are described and the possible significance of haustorial initiation in host recognition is discussed.