Febs Letters

doi: 10.1002/1873-3468.13830pmid: N/A

Christopher, Jana

doi: 10.1002/1873-3468.14143pmid: 34180058

In 2018, the community first observed scientific papers in the biomedical literature that seemed to display systematically fabricated data, pointing to the existence of paper mills: unofficial, potentially illegal organizations selling fake scientific manuscripts. In the present article, we share relevant information specifically about the ‘raw data’ associated with paper mill manuscripts. If a submitted manuscript displays clear indicators of potential paper mill involvement, we found that the raw data at close inspection often raise doubts about their authenticity. In the absence of real data, paper mills may need to fabricate raw data images when responding to requests from journals. Given the necessity to streamline production of fake manuscripts, the alleged raw data might be created using templates. Some potential methods for generating fake Western blot images are discussed. Paying close attention to image data, including graphs, diagrams, plots and tables, ideally at pre‐publication stage, can clearly help prevent publication of incorrect and fabricated information.

Jennings, Benjamin C.; Kornfeld, Stuart; Doray, Balraj; Briggs, John

doi: 10.1002/1873-3468.14109pmid: 33991349

The SARS‐CoV‐2 spike glycoprotein (spike) mediates viral entry by binding ACE2 receptors on host cell surfaces. Spike glycan processing and cleavage, which occur in the Golgi network, are important for fusion at the plasma membrane, promoting both virion infectivity and cell‐to‐cell viral spreading. We show that a KxHxx motif in the cytosolic tail of spike weakly binds the COPβ’ subunit of COPI coatomer, which facilitates some recycling of spike within the Golgi, while releasing the remainder to the cell surface. Although histidine (KxHxx) has been proposed to be equivalent to lysine within di‐lysine endoplasmic reticulum (ER) retrieval sequences, we show that histidine‐to‐lysine substitution (KxKxx) retains spike at the ER and prevents glycan processing, protease cleavage, and transport to the plasma membrane.

Baskaran, Padmamalini; Nazminia, Kara; Frantz, Justine; O’Neal, Jessica; Thyagarajan, Baskaran; Nagy, László

doi: 10.1002/1873-3468.14105pmid: 33977527

Transient receptor potential vanilloid subfamily 1 (TRPV1) is a non‐selective cation channel protein expressed in neuronal and non‐neuronal cells. Although TRPV1 is implicated in thermogenesis and diet‐induced obesity (DIO), its precise role remains controversial. TRPV1−/− mice are protected from DIO, while TRPV1 activation enhances thermogenesis to prevent obesity. To reconcile this, we fed wild‐type and TRPV1−/− mice for 32 weeks with normal chow or a high‐fat diet and analyzed the weight gain, metabolic activities, and thermogenic protein expression in white and brown fats. TRPV1−/− mice became obese, exhibited reduced locomotor activity, reduced energy expenditure, enhanced hepatic steatosis, and decreased thermogenic protein expression in adipose tissues. Our data reveal that lack of TRPV1 does not prevent obesity, but rather enhances metabolic dysfunction.

Parks, Steven Z.; Gao, Tian; Jimenez Awuapura, Natalia; Ayathamattam, Joseph; Chabosseau, Pauline L.; Kalvakolanu, Dhananjaya V.; Valdivia, Héctor H.; Rutter, Guy A.; Leclerc, Isabelle; Nakatogawa, Hitoshi

doi: 10.1002/1873-3468.14101pmid: 33960419

Sorcin is a calcium‐binding protein involved in maintaining endoplasmic reticulum (ER) Ca2+ stores. We have previously shown that overexpressing sorcin under the rat insulin promoter was protective against high‐fat diet‐induced pancreatic beta‐cell dysfunction in vivo. Activating transcription factor 6 (ATF6) is a key mediator of the unfolded protein response (UPR) that provides cellular protection during the progression of ER stress. Here, using nonexcitable HEK293 cells, we show that sorcin overexpression increased ATF6 signalling, whereas sorcin knock out caused a reduction in ATF6 transcriptional activity and increased ER stress. Altogether, our data suggest that sorcin downregulation during lipotoxic stress may prevent full ATF6 activation and a normal UPR during the progression of obesity and insulin resistance.

Yang, Shuhan; Kobayashi, Shuhei; Sekino, Kaname; Kagawa, Yoshiteru; Miyazaki, Hirofumi; Kumar Shil, Subrata; Abdulaziz Umaru, Banlanjo; Wannakul, Tunyanat; Owada, Yuji; Nagy, László

doi: 10.1002/1873-3468.14106pmid: 33982279

Bang, Gwantae; Ghil, Sungho; Nebreda, Angel

doi: 10.1002/1873-3468.14102pmid: 33959968

Lysophosphatidic acid (LPA) and lysophosphatidylinositol bind to the G protein‐coupled receptors (GPCRs) LPA and GPR55, respectively. LPA2, a type 2 LPA receptor, and GPR55 are highly expressed in colon cancer and involved in cancer progression. However, crosstalk between the two receptors and potential effects on cellular physiology are not fully understood. Here, using BRET analysis, we found that LPA2 and GPR55 interact in live cells. In the presence of both receptors, LPA2 and/or GPR55 activation facilitated co‐internalization, and activation of GPR55, uncoupled with Gαi, induced reduction of intracellular cAMP. Notably, co‐activation of receptors synergistically triggered further decline in the cAMP level, promoted cell proliferation, and increased the expression of cancer progression‐related genes, suggesting that physical and functional crosstalk between LPA2 and GRR55 is involved in cancer progression.

Wang, Er‐yi; Chen, Hao; Sun, Bao‐qing; Wang, Hui; Qu, Hui‐Qi; Liu, Yichuan; Sun, Xi‐zhuo; Qu, Jingchun; Fang, Zhang‐fu; Tian, Lifeng; Zeng, Yi‐feng; Huang, Shau‐Ku; Hakonarson, Hakon; Liu, Zhi‐gang; Ellmeier, Wilfried

Anand, Swadha; Bose, Chandrani; Kaur, Harrisham; Mande, Sharmila S.

doi: 10.1002/1873-3468.14107pmid: 33997973

Dysbiosis or imbalance in the gut microbiome has been correlated with the etiology of a number of diseases/disorders. Thus, gut microbial communities can potentially be utilized for assessing the health of the human gut. Although the taxonomic composition of the microbiomes is dependent on factors such as diet, lifestyle, and geography, these microbes perform a specific set of common functions in the gut. In this study, metabolic pathway‐based markers (agnostic to above‐mentioned factors) specific to commensals and those specific to pathogens are utilized as indicators of gut health. Furthermore, this gut health assessment requires only a small set of features rather than complete sequencing of metagenomes. The proposed scheme can also be used to design personalized biotherapeutics, depending on functional aspects observed in an individual.

Melwani, Pooja Kamal; Balla, Murali Mohan Sagar; S., Nishad; Padwal, Mahesh; Chaurasia, Rajesh Kumar; Basu, Bhakti; Ghosh, Anu; Pandey, Badri Narain; Huber, Lukas Alfons

doi: 10.1002/1873-3468.14108pmid: 33993482