A Splicing Mutation in the Novel Mitochondrial Protein DNAJC11 Causes Motor Neuron Pathology Associated with Cristae Disorganization, and Lymphoid Abnormalities in Mice

Mitochondrial structure and function is emerging as a major contributor to neuromuscular disease, highlighting the need for the complete elucidation of the underlying molecular and pathophysiological mechanisms. Following a forward genetics approach with N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we identified a novel mouse model of autosomal recessive neuromuscular disease caused by a splice-site hypomorphic mutation in a novel gene of unknown function, DnaJC11. Recent findings have demonstrated that DNAJC11 protein co-immunoprecipitates with proteins of the mitochondrial contact site (MICOS) complex involved in the formation of mitochondrial cristae and cristae junctions. Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity, limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early lethality. Neuropathological analysis showed severe vacuolation of the motor neurons in the spinal cord, originating from dilatations of the endoplasmic reticulum and notably from mitochondria that had lost their proper inner membrane organization. The causal role of the identified mutation in DnaJC11 was verified in rescue experiments by overexpressing the human ortholog. The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane whereas putative additional isoforms displayed differential submitochondrial localization. Moreover, we showed that DNAJC11 is assembled in a high molecular weight complex, similarly to mitofilin and that downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa cells. Our findings provide the first mouse mutant for a putative MICOS protein and establish a link between DNAJC11 and neuromuscular diseases

Thermal Behavior of Monocrystalline Silicon Solar Cells: A Numerical and Experimental Investigation on the Module Encapsulation Materials

This research outlines the numerical predictions of the heat distribution in solar cells, accompanied by their empirical validation. Finite element thermal models of five laminated silicon solar photovoltaic cells were firstly established using a simulation software (ANSYS®). The flexible laminated solar cells under study are made of a highly transparent frontsheet, a silicon cell between two encapsulants, and a backsheet. Different combinations of layers (i.e., materials and thicknesses) were taken into account in order to analyze their effect on thermal behavior. Thermal properties of materials were derived in accordance with the literature. Similarly, boundary conditions, loads, and heat losses by reflection and convection were also specified. The solar cells were tested using solar lamps under standard conditions (irradiance: 1000W/m2; room-temperature: 25°C) with real-time temperatures measured by a thermal imager. This analysis offers an interpretation of how temperature evolves through the solar cell and, consequently, how the design choice can influence the cells' efficiency

Phytochemical and Ecological Analysis of Two Varieties of Hemp (Cannabis sativa L.) Grown in a Mountain Environment of Italian Alps

Hemp (Cannabis sativa L.) is a multifunctional crop that is capable of prompt environmental adaptation. In this study, a monoecious cultivar (Futura 75) and a dioecious one (Finola) were tested in a mountain area in Valsaviore (Rhaetian Alps, Italy; elevation: 1,100 m a.s.l.) during the growing season 2018. Phytochemical behavior was evaluated by different analytical approaches: HPLC-high-resolution mass spectrometry, SDS-PAGE LC-MS/MS, HS-SPME GC-MS, and GC-FID in order to obtain complete profile of two varieties cultivated in altitude. CSR functional strategy used for ecological evaluation revealed that both genotypes are mainly competitors, although Finola is more stress tolerator (C:S:R = 57:26:17%) than Futura (C:S:R = 69:15:16%). The Finola inflorescences were characterized by higher quantities of \u3b2-ocimene and \u3b1-terpinolene, while \u3b1- and f-pinene accompanied by extremely high f-myrcene were found as predominant in Futura. Both varieties were rich in sesquiterpenes (45 recognized) among which trans-caryophyllene and \u3b1-humulene were the most abundant. Total tetrahydrocannabinol level was lower than 0.1%, while the most abundant cannabinoid was cannabidiolic acid (CBDA): 2.3% found in Finola vs. 2.7% revealed for Futura. The level of corresponding neutral form, cannabidiol, varied drastically: 0.27% (Finola) vs. 0.056% (Futura). Finola showed the unique cannabinoid profile with unexpectedly high cannabidivarin, 2-fold higher that corresponding acidic analogue, whereas the particularity of Futura 75 was the occurrence of cannabigerolic acid (CBGA) in the quantities that was double than those exposed for Finola. The seeds from both chemovars proved to be rich in polyunsaturated fatty acids, and Finola showed a higher ratio \u3c96/\u3c93. No difference was found in the protein content, and the SDS-PAGE profile was similar. The most abundant protein was edestin, followed by heat shock protein 70, f-conglycinin, and vicilin. In conclusion, comprehensive phytochemical and ecological study of two fiber-type varieties cultivated in Italian Alps displayed specific, legal, and safe cannabinoids profile, followed by particular terpene composition, polyunsaturated fatty acids content, and favorable protein profile. This postulates that geographical provenience of hemp should be considered in selecting a variety that would be suitable for a specific end-use nutraceutical application

Numerical study of oil spill in the Patos lagoon under flood and ebb conditions

Facing great obstacles to eradicate environmental hazards generated by oil spills, it is crucial to establish actions against such accidents. In this context, the focus of this study is to analyze oil spills at the harbor region of Rio Grande, Rio Grande do Sul. The Easy Coupling Oil System (ECOS) model was used to model the oil spills under different environmental conditions simulated by the hydrodynamic model Telemac-3D, with the intention to identify the main forces controlling the movement of the oil slicks over a year of averaged hydrodynamic conditions from 2003 to 2015. The computational domain comprises the Patos Lagoon, the harbor area of Rio Grande and the Southern Brazilian Shelf. For the oil spill simulations, eight distinct events were defined considering both flood and ebb conditions in the estuarine region of the Patos Lagoon. The oil spill simulations showed that, in ebb conditions, the oil slick movement is mainly ruled by the currents, moving towards the outflow. After a few hours, the wind action makes the slick move towards the margins of the waterway. In flood conditions, on the other hand, the oil slick drifts to the interior of the estuary, following the dominant currents and the local winds

Universal Probability-Free Conformal Prediction

We construct universal prediction systems in the spirit of Popper's falsifiability and Kolmogorov complexity and randomness. These prediction systems do not depend on any statistical assumptions (but under the IID assumption they dominate, to within the usual accuracy, conformal prediction). Our constructions give rise to a theory of algorithmic complexity and randomness of time containing analogues of several notions and results of the classical theory of Kolmogorov complexity and randomness.Comment: 27 page

Fluoroscopy usage in contemporary interventional electrophysiology: Insights from a European registry

Background: Fluoroscopy has been an essential part of every electrophysiological procedure since its inception. However, till now no clear standards regarding acceptable x-ray exposure nor recommendation how to achieve them have been proposed. Hypothesis: Current norms and quality markers required for optimal clinical routine can be identified. Methods: Centers participating in this Europe-wide multicenter, prospective registry were requested to provide characteristics of the center, operators, technical equipment as well as procedural settings of consecutive cases. Results: Twenty-five centers (72% university clinics, with a mean volume of 526 ± 348 procedures yearly) from 14 European countries provided data on 1788 cases [9% diagnostic procedures (DP), 38% atrial fibrillation (AF) ablations, 44% other supraventricular (SVT) ablations, and 9% ventricular ablations (VT)] conducted by 95 operators (89% male, 41 ± 7 years old). Mean dose area product (DAP) and time was 304 ± 608 cGy*cm2, 3.6 ± 4.8 minutes, 1937 ± 608 cGy*cm2, 15.3 ± 15.5 minutes, 805 ± 1442 cGy*cm2, 10.6 ± 10.7 minutes, and 1277 ± 1931 cGy*cm2, 10.4 ± 12.3 minutes for DP, AF, SVT, and VT ablations, respectively. Seven percent of all procedures were conducted without any use of fluoroscopy. Procedures in the lower quartile of DAP were performed more frequently by female operators (OR 1.707, 95%CI 1.257-2.318, P =.001), in higher-volume center (OR 1.001 per one additional procedure, 95%CI 1.000-1.001, P =.002), with the use of 3D-mapping system (OR 2.622, 95%CI 2.053-3.347, P <.001) and monoplane x-ray system (OR 2.945, 95%CI 2.149-4.037, P <.001). Conclusion: Exposure to ionizing radiation varies widely in daily practice for all procedure. Significant opportunities for harmonization of exposure toward the lower range has been identified

A Multiset Rewriting Model for Specifying and Verifying Timing Aspects of Security Protocols

Catherine Meadows has played an important role in the advancement of formal methods for protocol security verification. Her insights on the use of, for example, narrowing and rewriting logic has made possible the automated discovery of new attacks and the shaping of new protocols. Meadows has also investigated other security aspects, such as, distance-bounding protocols and denial of service attacks. We have been greatly inspired by her work. This paper describes the use of Multiset Rewriting for the specification and verification of timing aspects of protocols, such as network delays, timeouts, timed intruder models and distance-bounding properties. We detail these timed features with a number of examples and describe decidable fragments of related verification problems