ALADIN is Required for the Production of Fertile Mouse Oocytes

Asymmetric cell divisions depend on the precise placement of the spindle apparatus. In mammalian oocytes, spindles assemble close to the cell's center, but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygously null for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages, including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is compromised due to problems in spindle orientation and anchoring at the first meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in vitro are unable to support embryonic development beyond the two-cell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions

Towards reconciling structure and function in the nuclear pore complex

The spatial separation between the cytoplasm and the cell nucleus necessitates the continuous exchange of macromolecular cargo across the double-membraned nuclear envelope. Being the only passageway in and out of the nucleus, the nuclear pore complex (NPC) has the principal function of regulating the high throughput of nucleocytoplasmic transport in a highly selective manner so as to maintain cellular order and function. Here, we present a retrospective review of the evidence that has led to the current understanding of both NPC structure and function. Looking towards the future, we contemplate on how various outstanding effects and nanoscopic characteristics ought to be addressed, with the goal of reconciling structure and function into a single unified picture of the NPC

ECOSTRESS: NASA's next generation mission to measure evapotranspiration from the International Space Station

The ECOsystem Spaceborne Thermal Radiometer Experiment on Space Station ECOSTRESS) was launched to the International Space Station on June 29, 2018. The primary science focus of ECOSTRESS is centered on evapotranspiration (ET), which is produced as level‐3 (L3) latent heat flux (LE) data products. These data are generated from the level‐2 land surface temperature and emissivity product (L2_LSTE), in conjunction with ancillary surface and atmospheric data. Here, we provide the first validation (Stage 1, preliminary) of the global ECOSTRESS clear‐sky ET product (L3_ET_PT‐JPL, version 6.0) against LE measurements at 82 eddy covariance sites around the world. Overall, the ECOSTRESS ET product performs well against the site measurements (clear‐sky instantaneous/time of overpass: r2 = 0.88; overall bias = 8%; normalized RMSE = 6%). ET uncertainty was generally consistent across climate zones, biome types, and times of day (ECOSTRESS samples the diurnal cycle), though temperate sites are over‐represented. The 70 m high spatial resolution of ECOSTRESS improved correlations by 85%, and RMSE by 62%, relative to 1 km pixels. This paper serves as a reference for the ECOSTRESS L3 ET accuracy and Stage 1 validation status for subsequent science that follows using these data

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Zoofolkloristika: Prvi uvidi na putu prema novoj disciplini

The author notes that new, more complex researches of connections between animals, nature and connections to humans are needed in Slovenian and European folklore, literature and cultural studies, due to new ecological and ethical findings in the wider social and cultural environment and a changing order of the world, which has moved the focus from anthropocentrism into ecocentrism. The discussion builds upon various theoretical discourses, new concepts and multidisciplinary knowledge, to create the foundations, guidelines and directions for a new academic discipline of zoofolkloristics. Furthermore, new theoretical and analytical discourses should enable zoofolkloristics to provide an insight into changes in human attitudes to animals, in both folklore and within traditional and contemporary ritual practices, or their redefinition, and at the same time exert influence upon legal safety of non-human subjectivities.Autorica polazi od tvrdnje da su potrebna nova, kompleksnija istraživanja veza između životinja, prirode i poveznica s ljudima u slovenskoj i europskoj folkloristici, znanosti o književnosti i kulturnim studijima, zbog novih ekoloških i etičkih uvida u širu društveno-kulturnu okolinu i promjene u svijetu, koje su dovele do promjene od antropocentrizma k ekocentrizmu. U radu se na temelju različitih teorijskih diskursa, novih pojmova i multidisciplinarnog znanja stvaraju temelji, smjernice i pravci istraživanja u novoj znanstvenoj disciplini zoofolkloristike. Autorica tvrdi da bi etnologija, folkloristika i znanost o književnosti mogle imati ključnu ulogu u razvoju ekološke svijesti, znanstvenih terenskih istraživanja i kulturne ekologije te tako omogućiti prelazak iz ekologije u eshatologiju. Rad započinje opisom percepcije životinja i odnosa ljudi i životinja, gdje autorica govori o temeljnim pojmovima koji utječu na uvođenje ove nove znanstvene discipline, kao što su: životinja kao ispitanik, individualni pristup životinji, sinantropski i antropofilni pogled na čovjeka i životinju te antropomorfizam. Zatim se govori o povijesnim i suvremenim filozofsko-antropološkim diskursima o ljudskom pogledu na životinju te o teoriji specizma. Autorica razmatra predmet nove discipline te kaže da je u centru istraživanja životinja u folkloru u najširem mogućem smislu, u svim sferama narodne kulture, što se proučava iz novih gledišta, nove percepcije i recepcije; u pjesmama, pričama, bajkama, basnama, predajama, poslovicama, izrekama, zagonetkama, šalama, narodnom jeziku, kulturnim praksama, narodnom teatru, mitologiji, narodnoj medicini pa čak i u narodnoj glazbi. Nadalje, autorica daje pregled kulturnih istraživanja životinja u Europi i Sloveniji, te pokazuje da su rasprave o životinjama uglavnom objavljivane u 21. stoljeću, što bi moglo označavati da je riječ o prelasku u novu paradigmu ili čak i novu ontologiju. Autorica se bavi metodološkim i teorijskim pitanjima i pravcima u zoofolklorističkim istraživanjima koje klasificira prema kritičkom diskursu. Rad završava pregledom ciljeva zoofolkloristike, za koju tvrdi da ne bi smjela postati znanstvena disciplina koja nema aktivan utjecaj na društvenopolitički prostor u kojem koegzistiraju ljudski i ne-ljudski subjektiviteti

In vitro nuclear interactome of the HIV-1 Tat protein

<p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

Upscaling wetland methane emissions from the FLUXNET‐CH4 eddy covariance network (UpCH4 v1.0): model development, network assessment, and budget comparison

Wetlands are responsible for 20%–31% of global methane (CH4) emissions and account for a large source of uncertainty in the global CH4 budget. Data-driven upscaling of CH4 fluxes from eddy covariance measurements can provide new and independent bottom-up estimates of wetland CH4 emissions. Here, we develop a six-predictor random forest upscaling model (UpCH4), trained on 119 site-years of eddy covariance CH4 flux data from 43 freshwater wetland sites in the FLUXNET-CH4 Community Product. Network patterns in site-level annual means and mean seasonal cycles of CH4 fluxes were reproduced accurately in tundra, boreal, and temperate regions (Nash-Sutcliffe Efficiency ∼0.52–0.63 and 0.53). UpCH4 estimated annual global wetland CH4 emissions of 146 ± 43 TgCH4 y−1 for 2001–2018 which agrees closely with current bottom-up land surface models (102–181 TgCH4 y−1) and overlaps with top-down atmospheric inversion models (155–200 TgCH4 y−1). However, UpCH4 diverged from both types of models in the spatial pattern and seasonal dynamics of tropical wetland emissions. We conclude that upscaling of eddy covariance CH4 fluxes has the potential to produce realistic extra-tropical wetland CH4 emissions estimates which will improve with more flux data. To reduce uncertainty in upscaled estimates, researchers could prioritize new wetland flux sites along humid-to-arid tropical climate gradients, from major rainforest basins (Congo, Amazon, and SE Asia), into monsoon (Bangladesh and India) and savannah regions (African Sahel) and be paired with improved knowledge of wetland extent seasonal dynamics in these regions. The monthly wetland methane products gridded at 0.25° from UpCH4 are available via ORNL DAAC (https://doi.org/10.3334/ORNLDAAC/2253)

Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_297