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We read with considerable interest the study by Gusenbauer and Haddaway (Gusenbauer and Haddaway, 2020, Research Synthesis Methods, doi:10.1002/jrsm.1378) comparing the systematic search qualities of 28 search systems, including Google Scholar (GS) and PubMed. Google Scholar and PubMed are the two most popular free academic search tools in biology and chemistry, with GS being the number one search tool in the world. Those academics using GS as their principal system for literature searches may be unaware of research which enumerates five critical features for scientific literature tools that greatly influenced Gusenbauer's 2020 study. Using this list as the framework for a targeted comparison between just GS and PubMed, we found stark differences which overwhelmingly favored PubMed. In this comment, we show that by comparing the characteristics of the two search tools, features that are particularly useful in one search tool, but are missing in the other, are strikingly spotlighted. One especially popular feature that ubiquitously appears in GS, but not in PubMed, is the forward citation search found under every citation as a clickable Cited by N link. We seek to improve the PubMed search experience using two approaches. First, we request that PubMed add Cited by N links, making them as omnipresent as the GS links. Second, we created an open-source command-line tool, pmidcite, which is used alongside PubMed to give information to researchers to help with the choice of the next paper to examine, analogous to how GS's Cited by N links help to guide users. Find pmidcite at https://github.com/dvklopfenstein/pmidcite.

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Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interactions between nuclear lamina (NL) and the lamina-associated domains (LAD). Contact of individual LADs with the NL are dependent upon H3K9me2 introduced by G9a. The mechanisms governing the recruitment of G9a to distinct subcellular sites, into chromatin or to LAD, is not known. The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing cell-cycle progression and mitochondrial metabolism. Herein, we show that cyclin D1 enhanced H3K9 dimethylation though direct association with G9a. Endogenous cyclin D1 was required for the recruitment of G9a to target genes in chromatin, for G9a-induced H3K9me2 of histones, and for NL-LAD interaction. The finding that cyclin D1 is required for recruitment of G9a to target genes in chromatin and for H3K9 dimethylation, identifies a novel mechanism coordinating protein methylation.

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The biological interpretation of gene lists with interesting shared properties, such as up- or down-regulation in a particular experiment, is typically accomplished using gene ontology enrichment analysis tools. Given a list of genes, a gene ontology (GO) enrichment analysis may return hundreds of statistically significant GO results in a "flat" list, which can be challenging to summarize. It can also be difficult to keep pace with rapidly expanding biological knowledge, which often results in daily changes to any of the over 47,000 gene ontologies that describe biological knowledge. GOATOOLS, a Python-based library, makes it more efficient to stay current with the latest ontologies and annotations, perform gene ontology enrichment analyses to determine over- and under-represented terms, and organize results for greater clarity and easier interpretation using a novel GOATOOLS GO grouping method. We performed functional analyses on both stochastic simulation data and real data from a published RNA-seq study to compare the enrichment results from GOATOOLS to two other popular tools: DAVID and GOstats. GOATOOLS is freely available through GitHub: https://github.com/tanghaibao/goatools .

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The microtubule-binding integral 63 kD cytoskeleton-linking membrane protein (CLIMP-63; former name, p63) of the rough endoplasmic reticulum (ER) is excluded from the nuclear envelope. We studied the mechanism underlying this ER subdomain-specific localization by mutagenesis and structural analysis. Deleting the luminal but not cytosolic segment of CLIMP-63 abrogated subdomain-specific localization, as visualized by confocal microscopy in living cells and by immunoelectron microscopy using ultrathin cryosections. Photobleaching/recovery analysis revealed that the luminal segment determines restricted diffusion and immobility of the protein. The recombinant full-length luminal segment of CLIMP-63 formed alpha-helical 91-nm long rod-like structures as evident by circular dichroism spectroscopy and electron microscopy. In the analytical ultracentrifuge, the luminal segment sedimented at 25.7 S, indicating large complexes. The complexes most likely arose by electrostatic interactions of individual highly charged coiled coils. The findings indicate that the luminal segment of CLIMP-63 is necessary and sufficient for oligomerization into alpha-helical complexes that prevent nuclear envelope localization. Concentration of CLIMP-63 into patches may enhance microtubule binding on the cytosolic side and contribute to ER morphology by the formation of a protein scaffold in the lumen of the ER.

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The positioning and dynamics of organelles in eukaryotic cells critically depend on membrane-cytoskeleton interactions. Motor proteins play an important role in the directed movement of organelle membranes along microtubules, but the basic mechanism by which membranes stably interact with the microtubule cytoskeleton is largely unknown. Here we report that p63, an integral membrane protein of the reticular subdomain of the rough endoplasmic reticulum (ER), binds microtubules in vivo and in vitro. Overexpression of p63 in cell culture led to a striking rearrangement of the ER and to concomitant bundling of microtubules along the altered ER. Mutational analysis of the cytoplasmic domain of p63 revealed two determinants responsible for these changes: an ER rearrangement determinant near the N-terminus and a central microtubule-binding region. The two determinants function independently of one another as indicated by deletion experiments. A peptide corresponding to the cytoplasmic tail of p63 promoted microtubule polymerization in vitro. p63 is the first identified integral membrane protein that can link a membrane organelle directly to microtubules. By doing so, it may contribute to the positioning of the ER along microtubules.

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Further investigation of the targeting of the intracellular membrane lectin endoplasmic reticulum (ER)-Golgi intermediate compartment-53 (ERGIC-53) by site-directed mutagenesis revealed that its lumenal and transmembrane domains together confer ER retention. In addition we show that the cytoplasmic domain is required for exit from the ER indicating that ERGIC-53 carries an ER-exit determinant. Two phenylalanines at the C terminus are essential for ER-exit. Thus, ERGIC-53 contains determinants for ER retention as well as anterograde transport which, in conjunction with a dilysine ER retrieval signal, control the continuous recycling of ERGIC-53 in the early secretory pathway. In vitro binding studies revealed a specific phenylalanine-dependent interaction between an ERGIC-53 cytosolic tail peptide and the COPII coat component Sec23p. These results suggest that the ER-exit of ERGIC-53 is mediated by direct interaction of its cytosolic tail with the Sec23p.Sec24p complex of COPII and that protein sorting at the level of the ER occurs by a mechanism similar to receptor-mediated endocytosis or Golgi to ER retrograde transport.

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A young woman with a history of in utero exposure to distilbestrol was diagnosed with vaginal clear-cell adenocarcinoma. Management consisted of limited excision of the tumor followed by brachytherapy after transposition of the ovaries. The patient had a successful pregnancy after reimplantation of the ovaries in their normal position and right adnexectomy for Chlamydia infection. The child was delivered by cesarean section. This is probably the first case with a pregnancy after repositioning of the ovaries in Europe and perhaps even in the world.

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Analysis of the sounds transmitted from the outside world to the fetus have shown that the fetus receives sound of more than 40 décibels, regardless of the means of transmission or of the position of the mother. Below this threshold, many parameters are involved, such as the position of the mother, the method of sound transmission, but the mother's voice always seems to be have priority.

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A new intragalactophoric biopsy fitting is described, which consists of a modified dilator serving as curette and a needle-curette for aspiration. The new fitting has been used successfully and without complications in 26 cases. It has the advantage of providing larger specimens for cytological examination of ductal tumours of the breast.

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