Cytoplasmic BK\u3csub\u3eCa\u3c/sub\u3e channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons

High single-channel conductance K+ channels, which respond jointly to membrane depolarization and micromolar concentrations of intracellular Ca2+ ions, arise from extensive cell-specific alternative splicing of pore-forming α-subunit mRNAs. Here, we report the discovery of an endogenous BKCa channel α-subunit intron-containing mRNA in the cytoplasm of hippocampal neurons. This partially processed mRNA, which comprises ≈10% of the total BKCa channel α-subunit mRNAs, is distributed in a gradient throughout the somatodendritic space. We selectively reduced endogenous cytoplasmic levels of this intron-containing transcript by RNA interference without altering levels of the mature splice forms of the BKCa channel mRNAs. In doing so, we could demonstrate that changes in a unique BKCa channel α-subunit introncontaining splice variant mRNA can greatly impact the distribution of the BKCa channel protein to dendritic spines and intrinsic firing properties of hippocampal neurons. These data suggest a new regulatory mechanism for modulating the membrane properties and ion channel gradients of hippocampal neurons

Impact of functional status on outcomes of simultaneous pancreas-kidney transplantation: Risks and opportunities for patient benefit

Background. The impact of functional status on survival among simultaneous pancreas-kidney transplant (SPKT) candidates and recipients is not well described. Methods. We examined national Scientific Registry of Transplant Recipients (SRTR) data for patients listed for SPKT in the United States (2006-2019). Functional status was categorized by center-reported Karnofsky Performance Score (KPS). We used Cox regression to quantify associations of KPS at listing and transplant with subsequent patient survival, adjusted for baseline patient and transplant factors (adjusted hazard ratio,(95% LCL)aHR(95%UCL)). We also explored time-dependent associations of SPKT with survival risk after listing compared with continued waiting in each functional status group. Results. KPS distributions among candidates (N = 16 822) and recipients (N = 10 316), respectively, were normal (KPS 80-100), 62.0% and 57.8%; capable of self-care (KPS 70), 23.5% and 24.7%; requires assistance (KPS 50-60), 12.4% and 14.2%; and disabled (KPS 10-40), 2.1% and 3.3%. There was a graded increase in mortality after listing and after transplant with lower functional levels. Compared with normal functioning, mortality after SPKT rose progressively for patients capable of self-care (aHR,(1.00)1.18(1.41)), requiring assistance (aHR,(1.06)1.31(1.60)), and disabled (aHR,(1.10)1.55(2.19)). In time-dependent regression, compared with waiting, SPKT was associated with 2-fold mortality risk within 30 days of transplant. However, beyond 30 days, SPKT was associated with reduced mortality, from 52% for disabled patients (aHR,(0.26)0.48(0.88)) to 70% for patients with normal functioning (aHR,(0.26)0.30(0.34)). Conclusions. While lower functional status is associated with increased mortality risk among SPKT candidates and recipients, SPKT can provide long-term survival benefit across functional status levels in those selected for transplant

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Agency, Values, and Well-Being: A Human Development Model

This paper argues that feelings of agency are linked to human well-being through a sequence of adaptive mechanisms that promote human development, once existential conditions become permissive. In the first part, we elaborate on the evolutionary logic of this model and outline why an evolutionary perspective is helpful to understand changes in values that give feelings of agency greater weight in shaping human well-being. In the second part, we test the key links in this model with data from the World Values Surveys using ecological regressions and multi-level models, covering some 80 societies worldwide. Empirically, we demonstrate evidence for the following sequence: (1) in response to widening opportunities of life, people place stronger emphasis on emancipative values, (2) in response to a stronger emphasis on emancipative values, feelings of agency gain greater weight in shaping people’s life satisfaction, (3) in response to a greater impact of agency feelings on life satisfaction, the level of life satisfaction itself rises. Further analyses show that this model is culturally universal because taking into account the strength of a society’s western tradition does not render insignificant these adaptive linkages. Precisely because of its universality, this is indeed a ‘human’ development model in a most general sense

Review of the cultivation program within the National Alliance for Advanced Biofuels and Bioproducts

The cultivation efforts within the National Alliance for Advanced Biofuels and Bioproducts (NAABB)were developed to provide four major goals for the consortium, which included biomass production for downstream experimentation, development of new assessment tools for cultivation, development of new cultivation reactor technologies, and development of methods for robust cultivation. The NAABB consortium test beds produced over 1500 kg of biomass for downstream processing. The biomass production included a number of model production strains, but also took into production some of the more promising strains found through the prospecting efforts of the consortium. Cultivation efforts at large scale are intensive and costly, therefore the consortium developed tools and models to assess the productivity of strains under various environmental conditions, at lab scale, and validated these against scaled outdoor production systems. Two new pond-based bioreactor designs were tested for their ability to minimize energy consumption while maintaining, and even exceeding, the productivity of algae cultivation compared to traditional systems. Also, molecular markers were developed for quality control and to facilitate detection of bacterial communities associated with cultivated algal species, including the Chlorella spp. pathogen, Vampirovibrio chlorellavorus,which was identified in at least two test site locations in Arizona and New Mexico. Finally, the consortium worked on understanding methods to utilize compromised municipal waste water streams for cultivation. This review provides an overview of the cultivation methods and tools developed by the NAABB consortium to produce algae biomass, in robust low energy systems, for biofuel production

In Search of a Trade Mark: Search Practices and Bureaucratic Poetics

Trade marks have been understood as quintessential ‘bureaucratic properties’. This article suggests that the making of trade marks has been historically influenced by bureaucratic practices of search and classification, which in turn were affected by the possibilities and limits of spatial organisation and technological means of access and storage. It shows how the organisation of access and retrieval did not only condition the possibility of conceiving new trade marks, but also served to delineate their intangible proprietary boundaries. Thereby they framed the very meaning of a trade mark. By advancing a historical analysis that is sensitive to shifts, both in actual materiality and in the administrative routines of trade mark law, the article highlights the legal form of trade mark as inherently social and materially shaped. We propose a historical understanding of trade mark law that regards legal practice and bureaucratic routines as being co-constitutive of the very legal object itself