bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Persistence of IgG Antibodies in recovered COVID-19 individuals at 18 months and the impact of two-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccination on the antibody response
Authors: Puya-Dehgani-Mobaraki  , Wang Chao , Floridi Alessandro , Floridi Emanuela , Zaidi Asiya K
Published: January 2022

This era of emerging variants needs a thorough evaluation of data on the long-term efficacy of immune responses in vaccinated as well as recovered individuals, to understand the overall evolution of the pandemic. In this study, we aimed to assess the dynamics of IgG titers over 18 months in n=36 patients from the Umbria region in Italy, who had a documented history of COVID-19 infection in March 2020, and then compared the impact of two-dose BNT162b2 (Pfizer-BioNTech) vaccination on the antibody titers of these patients with the ones who did not receive any dose of vaccine. This is the longest observation (March 2020-September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on the titers. Fixed-effect regression models were used for statistical analysis which could be also used to predict future titer trends. At 18 months, 97% participants tested positive for anti-NCP hinting towards the persistence of infection-induced immunity even for the vaccinated individuals. Our study findings demonstrate that while double dose vaccination boosted the IgG titers in recovered individuals 161 times, this “boost” was relatively short-lived. The unvaccinated recovered individuals, in contrast, continued to show a steady decline but detectable antibody levels. Further studies are required to re-evaluate the timing and dose regimen of vaccines for an adequate immune response in recovered individuals.
An excitatory-inhibitory fronto-cerebellar loop resolves the Stroop effect
Authors: Okayasu Moe , Inukai Tensei , Tanaka Daiki , Tsumura Kaho , Hosono Maho , Shintaki Reiko , Takeda Masaki , Nakahara Kiyoshi , Jimura Koji
Published: January 2022

The Stroop effect is a well-known behavioral phenomenon in humans that refers to robust interference between language and color information. Although this effect has long been studied, it remains unclear when the interference occurs and how it is resolved in the brain. By manipulating the verbality of stimulus perception and response generation, here we show that the Stroop effect occurs during perception of color-word stimuli and is resolved by a cross-hemispheric, excitatory-inhibitory functional loop involving the lateral prefrontal cortex and cerebellum. Humans performed a Stroop task and a control task in which the stimulus did not contain verbal information, and made a response either vocally or manually. The resolution of Stroop interference involved the lateral prefrontal cortex in the left hemisphere and the cerebellum in the right hemisphere, independently of whether the response was made vocally or manually. In contrast, such cross-hemispheric lateralization was absent during the non-verbal control task. Moreover, the prefrontal cortex amplified cerebellar activity, whereas the cerebellum suppressed prefrontal activity, and these effects were enhanced during interference resolution. These results suggest that this fronto-cerebellar loop involving language and cognitive systems regulates goal-relevant information to resolve the interference occurring during simultaneous perception of a word and color.
Decoding the activated stem cell phenotype of the vividly maturing neonatal pituitary
Authors: Laporte Emma , Hermans Florian , Vriendt Silke De , Vennekens Annelies , Lambrechts Diether , Nys Charlotte , Cox Benoit , Vankelecom Hugo
Published: January 2022

The pituitary represents the endocrine master regulator. In mouse, the gland undergoes vivid maturation immediately after birth. Here, we in detail portrayed the stem cell compartment of neonatal pituitary. Single-cell RNA-sequencing pictured an active gland, revealing proliferative stem as well as hormonal (progenitor) cell populations. The stem cell pool displayed a hybrid epithelial/mesenchymal phenotype, characteristic of development-involved tissue stem cells. Organoid culturing recapitulated the stem cells’ phenotype, interestingly also reproducing their paracrine activity. The pituitary stem cell-activating interleukin-6 (IL-6) advanced organoid growth, although the neonatal stem cell compartment was not visibly affected in IL-6-/- mice, likely due to cytokine family redundancy. Further transcriptomic analysis exposed a pronounced WNT pathway in the neonatal gland, shown to be involved in stem cell activation and to overlap with the (fetal) human pituitary transcriptome. Following local damage, the neonatal gland efficiently regenerates, despite absence of additional stem cell proliferation, or upregulated IL-6 or WNT expression, all in line with the already high stem cell activation status, thereby exposing striking differences with adult pituitary. Together, our study decodes the stem cell compartment of neonatal pituitary, exposing an activated state in the vividly maturing gland. Understanding stem cell activation is key to potential pituitary regenerative prospects.
Genetic control of KRAB-ZFP genes explains distal CpG-site methylation which associates with human disease phenotypes
Authors: Bretherick Andrew D. , Zeng Yanni , Walker Rosie M. , Hayward Caroline , Porteous David J. , Evans Kathryn L. , McIntosh Andrew M. , Kenneth Baillie J. , Haley Chris , Ponting Chris P.
Published: January 2022

Krüppel-associated box zinc finger proteins (KRAB-ZFPs) are the largest gene family of transcriptional regulators in higher vertebrates. We have developed a method for inferring these factors’ DNA binding-sites in vivo. We achieved this by combining the genome-wide association of methylation at 573,027 CpG-sites (meQTL) in blood and KRAB-ZFP RNA expression changes (eQTL). This method’s efficacy is clearly demonstrated by showing that the CpG-sites whose methylation is affected by KRAB-ZFP expression changes occur preferentially near KRAB-ZFP binding-sites in the HEK293T cell line. We found such an enrichment to be significant for 31% of factors tested. In addition, we found that binding-sites of many KRAB-ZFPs are significantly enriched (or sometimes depleted) in disease-associated CpG-sites. In total, 9% (11 of 125) of the traits tested, and 14% (32 of 222) of the factors (KRAB-ZFPs and TIF1-beta) tested, were enriched or depleted in one or more trait-factor pairing. Rheumatoid arthritis and human immunodeficiency virus (HIV) infection were associated with the largest number of KRAB-ZFP enrichments. There have been variable reports on the effects on HIV infection dynamics of transcription intermediary factor 1-beta (TIF1-beta, also known as KAP1 or TRIM28), a nuclear corepressor for KRAB-ZFPs. We provide evidence that KRAB-ZFP-independent effects of TIF1-beta are responsible for the decreased methylation of CpG-sites within its binding-sites that is observed in HIV infection. In conclusion, KRAB-ZFPs often affect CpG-site methylation within the proximity of their binding-sites, and CpG-sites within the binding-sites of KRAB-ZFPs are enriched for association with many traits, including rheumatoid arthritis and HIV infection.
A potent alpaca-derived nanobody that neutralizes SARS-CoV-2 variants
Authors: Weinstein Jules B. , Bates Timothy A. , Leier Hans C. , McBride Savannah K. , Barklis Eric , Tafesse Fikadu G.
Published: January 2022

The spike glycoprotein of SARS-CoV-2 engages with human angiotensin-converting enzyme 2 (ACE2) to facilitate infection. Here, we describe an alpaca-derived heavy chain antibody fragment (VHH), saRBD-1, that disrupts this interaction by competitively binding to the spike protein receptor-binding domain. We further generated an engineered bivalent nanobody construct engineered by a flexible linker, and a dimeric Fc conjugated nanobody construct. Both multivalent nanobodies blocked infection at picomolar concentrations and demonstrated no loss of potency against emerging variants of concern including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Epsilon (B.1.427/429), and Delta (B.1.617.2). saRBD-1 tolerates elevated temperature, freeze-drying, and nebulization, making it an excellent candidate for further development into a therapeutic approach for COVID-19.
Enterococcus faecalis antagonizes Pseudomonas aeruginosa growth in polymicrobial biofilms
Authors: Zhu Tan Casandra Ai , Lam Ling Ning , Biukovic Goran , Soh Eliza Ye-Chen , Toh Xiao Wei , Lemos José A. , Kline Kimberly A.
Published: January 2022

Enterococcus faecalis is often co-isolated with Pseudomonas aeruginosa in polymicrobial biofilm-associated infections of wounds and the urinary tract. As a defense strategy, the host innately restricts iron availability at infection sites. Despite their co-prevalence, the polymicrobial interactions of these two pathogens in iron- restricted conditions, such as those found in the host, remains unexplored. Here we show that E. faecalis inhibits P. aeruginosa growth within biofilms when iron is restricted. E. faecalis lactate dehydrogenase (ldh1) gives rise to L-lactate production during fermentative growth. We find that E. faecalis ldh1 mutant fails to inhibit P. aeruginosa growth. Additionally, we demonstrate that ldh1 expression is induced in iron-restricted conditions, resulting in increased lactic acid exported and consequently, a reduction in pH. Together, our results suggest that E. faecalis synergistically inhibit P. aeruginosa growth by decreasing environmental pH and L-lactate-mediated iron chelation. Overall, this study highlights that the microenvironment in which the infection occurs is important for understanding its pathophysiology.

IMPORTANCE

Many infections are polymicrobial and biofilm-associated in nature. Iron is essential for many metabolic processes and plays an important role in controlling infections, where the host restricts iron as a defense mechanism against invading pathogens. However, polymicrobial interactions between pathogens are underexplored in iron- restricted conditions. Here, we explore the polymicrobial interactions between commonly co-isolated E. faecalis and P. aeruginosa within biofilms. We find that E. faecalis modulates the microenvironment by exporting lactic acid which further chelates already limited iron, and also lowers the environmental pH to antagonize P. aeruginosa growth in iron-restricted conditions. Our findings provide insights into polymicrobial interactions between pathogens in an infection-relevant condition and how manipulating the microenvironment can be taken advantage of to better control infections.
SARS-CoV-2 Delta variant induces enhanced pathology and inflammatory responses in K18-hACE2 mice
Authors: Lee Katherine S. , Wong Ting Y. , Russ Brynnan P. , Horspool Alexander M. , Miller Olivia A. , Rader Nathaniel A. , Givi Jerome P. , Winters Michael T. , Wong Zeriel YA. , Cyphert Holly A. , Denvir James , Stoilov Peter , Barbier Mariette , Roan Nadia R. , Amin Md. Shahrier , Martinez Ivan , Bevere Justin R. , Damron F. Heath
Published: January 2022

The COVID-19 pandemic has been fueled by novel variants of concern (VOC) that have increased transmissibility, receptor binding affinity, and other properties that enhance disease. The goal of this study is to characterize unique pathogenesis of the Delta VOC strain in the K18-hACE2-mouse challenge model. Challenge studies suggested that the lethal dose of Delta was higher than Alpha or Beta strains. To characterize the differences in the Delta strain’s pathogenesis, a time-course experiment was performed to evaluate the overall host response to Alpha or Delta variant challenge. qRT-PCR analysis of Alpha- or Delta- challenged mice revealed no significant difference between viral RNA burden in the lung, nasal wash or brain. However, histopathological analysis revealed high lung tissue inflammation and cell infiltration following Delta- but not Alpha-challenge at day 6. Additionally, pro-inflammatory cytokines were highest at day 6 in Delta-challenged mice suggesting enhanced pneumonia. Total RNA-sequencing analysis of lungs comparing infected to uninfected mice revealed that Alpha-challenged mice have more total genes differentially activated, conversely, Delta-challenged mice have a higher magnitude of differential gene expression. Delta-challenged mice have increased interferon-dependent gene expression and IFN-γ production compared to Alpha. Analysis of TCR clonotypes suggested that Delta challenged mice have increased T-cell infiltration compared to Alpha challenged. Our data suggest that Delta has evolved to engage interferon responses in a manner that may enhance pathogenesis. Thein vivoandin silicoobservations of this study underscore the need to conduct experiments with VOC strains to best model COVID-19 when evaluating therapeutics and vaccines.

Importance

The Delta variant of SARS-CoV-2 is known to be more transmissible and cause severe disease in human hosts due to mutations in its genome that are divergent from previous variants of concern (VOC). Our study evaluates the pathogenesis of Delta in the K18-hACE2 mouse model compared to the Alpha VOC. We observed that relative to Alpha, Delta challenge results in enhanced inflammation and tissue damage with stronger antiviral responses. These observations provide insight into Delta’s unique pathogenesis.
Loss of Y in leukocytes as a risk factor for critical COVID-19 in men
Authors: Bruhn-Olszewska Bożena , Davies Hanna , Sarkisyan Daniil , Juhas Ulana , Rychlicka-Buniowska Edyta , Wójcik Magdalena , Horbacz Monika , Jąkalski Marcin , Olszewski Paweł , Westholm Jakub O. , Smialowska Agata , Wierzba Karol , Naluai Åsa Torinsson , Jern Niklas , Andersson Lars-Magnus , Järhult Josef D. , Filipowicz Natalia , Janson Eva Tiensuu , Rubertsson Sten , Lipcsey Miklós , Gisslén Magnus , Hultström Michael , Frithiof Robert , Dumanski Jan P.
Published: January 2022

COVID-19 shows an unexplained, strong male bias for severity and mortality. Loss of Y (LOY) in myeloid cells is a risk factor candidate in COVID-19 because of associations with many age-related diseases and its effect on transcription of immune genes. We report the highest levels of LOY in cells that are crucial for the development of severe COVID-19 phenotype, such as low-density neutrophils, granulocytes, and monocytes reaching 46%, 32%, and 29%, respectively, from men with critical COVID-19 (n=139). LOY in sorted subpopulations of leukocytes correlated with increased thrombocyte count, thromboembolic events, invasive mechanical ventilation and a history of vessel disease. In recovered patients, LOY decreased in whole blood and peripheral blood mononuclear cells. Moreover, sc-RNA-seq analysis of CD14+ monocytes from 30 COVID-19 males and 34 controls revealed pervasive transcriptional downregulation in LOY-cells, notably affecting HLA class I and II genes important for antigen presentation. The data support a link between LOY and emergency myelopoiesis as well as the role of LOY in modulation of COVID-19 severity. Our results might also be relevant for other viral infections showing similar male bias.
Serum extracellular vesicles trace COVID-19 progression and immune responses
Authors: Wai Yim Kevin Ho , Borgoni Simone , Chahwan Richard
Published: January 2022

Coronavirus disease 2019 (COVID-19) has transformed very quickly into a world pandemic with severe and unexpected consequences on human health. Concerted efforts to generate better diagnostic and prognostic tools have been ongoing. Research, thus far, has primarily focused on the virus itself or the direct immune response to it. Here, we propose extracellular vesicles (EVs) from serum liquid biopsies as a new and unique modality to unify diagnostic and prognostic tools for COVID-19 analyses. EVs are a novel player in intercellular signaling particularly influencing immune responses. We herein show that innate and adaptive immune EVs profiling, together with SARS-CoV-2 Spike S1+EVs provide a novel signature for COVID-19 infection. It also provides a unique ability to trace the co-existence of viral and host cell signatures to monitor affected tissues and severity of the disease progression. And provide a phenotypic insight into COVID-associated EVs.
Cross-sectional study to assess the efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies
Authors: Abella Eugenia , Trigueros Macedonia , Pradenas Edwards , Muñoz-Lopez Francisco , Garcia-Pallarols Francesc , Ben Azaiz Ben Lahsen Randa , Trinité Benjamin , Urrea Victor , Marfil Silvia , Rovirosa Carla , Puig Teresa , Grau Eulàlia , Chamorro Anna , Toledo Ruth , Font Marta , Palacín Dolors , Lopez-Segui Francesc , Carrillo Jorge , Prat Nuria , Mateu Lourdes , Clotet Bonaventura , Blanco Julià , Massanella Marta ,   KING cohort extension and CoronAVI@S studies
Published: January 2022

SARS-CoV-2 vaccination is the most effective strategy to protect patients with haematologic malignancies against severe COVID-19, but primary vaccine responses are less effective in this population. Here, we characterized the humoral responses following 3 months after mRNA-based vaccines in patients at different stages of the same plasma cell diseases, including monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma on first line therapy (MM), compared to a healthy control population matched by sex and age. We observed that plasmas from uninfected MM patients after 3 months post-vaccine have lower SARS-CoV-2 specific IgG and IgA antibodies and decreased neutralization capacity compared with MGUS and SMM individuals, and a group of healthy controls. Importantly, we detected significantly higher plasma neutralization capacity in MM individuals who recovered from COVID-19 compared to their uninfected counterparts, highlighting that hybrid immunity elicit stronger immune responses even in this immunocompromised population. In contrast to MM group, no differences in the vaccine-induced humoral response were observed between uninfected MGUS, SMM and healthy individuals. In conclusion, a booster vaccine dose is recommended in uninfected MM patients to develop an adequate and effective humoral response to SARS-CoV-2 vaccine.
Gene-based polygenic risk scores analysis of alcohol use disorder in African Americans
Authors: Lai Dongbing , Schwantes-An Tae-Hwi Linus , Abreu Marco , Chan Grace , Hesselbrock Victor , Kamarajan Chella , Liu Yunlong , Meyers Jacquelyn L. , Nurnberger John I , Plawecki Martin H. , Wetherill Leah , Schuckit Marc , Zhang Pengyue , Edenberg Howard J. , Porjesz Bernice , Agrawal Arpana , Foroud Tatiana
Published: January 2022

Genome-wide association studies (GWAS) in admixed populations such as African American (AA) have limited sample sizes, resulting poor performance of polygenic risk scores (PRS). Based on the observations that many disease-causing genes are shared between AA and European ancestry (EA) populations, and some disease-causing variants are located within boundaries of these genes, we proposed a novel gene-based PRS method (PRSgene) by using variants located in these shared disease-causing genes. Using AA GWAS of alcohol use disorder (AUD) from the Million Veteran Program and EA GWAS of problematic alcohol use as the discovery datasets, we identified 858 variants from 410 genes that were AUD-related in both AA and EA. PRSgenecalculated using these variants were significantly associated with AUD in three AA cohorts (P-values: 7.61E-05-6.27E-03; Betas: 0.15-0.21) and outperformed PRS calculated using all variants (P-values: 7.28E-03-0.16; Betas: 0.06-0.18). PRSgenewas also associated with AUD in an EA cohort (P-value=0.02, Beta=0.11). In AA, individuals in the highest PRSgenedecile had an Odds Ratio of 1.76 (95% CI: 1.32-2.34) to develop AUD compared to those in the lowest decile. The 410 genes were enriched in 54 Gene Ontology biological processes, including ethanol oxidation and processes involving synaptic system, which are known to be AUD-related. Additionally, 26 genes were targets of drugs to treat AUD or other diseases, but may be repurposed to treat AUD. Our study demonstrated that our gene-based PRS had improved performance in evaluating AUD risk in AA and provided new insight into identification of AUD genes.
Structural analysis of Red1 as a conserved scaffold of the RNA-targeting MTREC/PAXT complex
Authors: Foucher Anne-Emmanuelle , Touat-Todeschini Leila , Juarez-Martinez Ariadna B. , Laroussi Hamida , Karczewski Claire , Acajjaoui Samira , Soler-López Montserrat , Cusack Stephen , Mackereth Cameron D. , Verdel André , Kadlec Jan
Published: January 2022

To eliminate specific or aberrant transcripts, eukaryotic cells use nuclear RNA-targeting complexes that deliver them to the exosome for degradation. S. pombe MTREC complex, and its human counterpart PAXT, are key players in this mechanism. Red1 and hZFC3H1 function as scaffolds of these respective complexes. Here, we present an NMR structure of a helix-turn-helix domain of Red1 in complex with the N-terminus of Iss10 and show this interaction is required for proper cellular growth and meiotic mRNA degradation. We also report a crystal structure of a Red1-Ars2 complex that explains the mutually exclusive interactions of hARS2 with various “ED/EGEI/L” motif-possessing RNA regulators such as hZFC3H1, hFLASH or hNCBP3. Finally, we show that both Red1 and hZFC3H1 homo-dimerize via their coiled-coil regions indicating that MTREC and PAXT likely function as dimers. Our results, combining structures of three Red1 binding interfaces with in vivo studies, provide mechanistic insights into conserved features of MTREC/PAXT architecture.
Hedgehog regulation of epithelial cell state and morphogenesis in the larynx
Authors: Ramachandran Janani , Zhou Weiqiang , Bardenhagen Anna E. , Nasr Talia , Zorn Aaron M. , Ji Hongkai , Vokes Steven A.
Published: January 2022

The larynx enables speech while regulating swallowing and respiration. Larynx function hinges on the laryngeal epithelium which originates as part of the anterior foregut and undergoes extensive remodeling to separate from the esophagus and form vocal folds that interface with the adjacent trachea. Here we find that Sonic hedgehog (SHH) is essential for epithelial integrity in the larynx as well as the anterior foregut. During larynx-esophageal separation, lowShhexpression marks specific domains of actively remodeling epithelium that undergo an epithelial to mesenchymal transition (EMT) characterized by the induction of N-Cadherin and movement of cells out of the epithelial layer. Consistent with a role for SHH signaling in regulating this process,Shhmutants undergo an abnormal EMT throughout the anterior foregut and larynx, marked by a cadherin switch, movement out of the epithelial layer and cell death. Unexpectedly,Shhmutant epithelial cells are replaced by a new population ofPax-1expressing cells that form a rudimentary epithelium. These findings have important implications for interpreting the etiology of HH- dependent birth defects within the foregut. We propose that SHH signaling has a default role in maintaining epithelial identity throughout the anterior foregut and that regionalized reductions in SHH trigger epithelial remodeling.
Molecular basis of broad neutralization against SARS-CoV-2 variants including Omicron by a human antibody
Authors: Ju Bin , Zheng Qingbing , Guo Huimin , Fan Qing , Li Tingting , Song Shuo , Sun Hui , Shen Senlin , Zhou Xinrong , Cheng Lin , Xue Wenhui , Cui Lingyan , Zhou Bing , Ge Xiangyang , Wang Haiyan , Wang Miao , Li Shaowei , Xia Ningshao , Zhang Zheng
Published: January 2022

Omicron, a newly emerging SARS-CoV-2 variant, carried a large number of mutations in the spike protein leading to an unprecedented evasion from many neutralizing antibodies (nAbs). Here, we performed a head-to-head comparison of Omicron with other existing highly evasive variants in terms of their reduced sensitivities to antibodies, and found that Omicron variant is significantly more evasive than Beta and Mu variants. Of note, some key mutations occur in the conserved epitopes identified previously, especially in the binding sites of Class 4 nAbs, contributing to the increased Ab evasion. We also reported a broadly nAb (bnAb), VacW-209, which effectively neutralized all tested SARS-CoV-2 variants and even SARS-CoV. Finally, we determined six cryo-electron microscopy structures of VacW-209 complexed with the spike ectodomains of wild-type, Delta, Mu, C.1.2, Omicron, and SARS-CoV, and revealed the molecular basis of the broadly neutralizing activities of VacW-209 against SARS-CoV-2 variants. Overall, Omicron has once again raised the alarm over virus variation with significantly compromised neutralization. BnAbs targeting more conserved epitopes among variants will continue to play a key role in pandemic control and prevention.

One sentence summary

Structural and functional analyses reveal that a human antibody named VacW-209 confers broad neutralization against SARS-CoV-2 variants including Omicron by recognizing a highly conserved epitope.
NRP1 and furin as putative mediators of SARS-CoV-2 entry into human brain cells
Authors: Kumar Ashutosh , Narayan Ravi K. , Kumar Sujeet , Pareek Vikas , Kumari Chiman , Jha Rakesh K. , Prasoon Pranav
Published: January 2022

COVID-19 has prominent neurological manifestations including psychiatric symptoms, indicating significant synaptic pathology. Surprisingly, existing evidence suggests negligible expression of the key SARS-CoV-2 host cell entry mediators ACE2 and TMPRSS2 in human brain, which complicates understanding of the pathomechanisms of the neuropsychiatric manifestations in COVID-19. Recent studies suggested that an alternative host-cell entry receptor, NRP1, can mediate entry of furin cleaved SARS-CoV-2 spike proteins into the host cells. However, the role of NRP1 and furin in mediating SARS-CoV-2 entry in human brain cells has been least explored and remains a lacuna in the literature. We performed an in silico analysis of the transcriptomic and proteomic expressions of SARS-CoV-2 host-cell entry receptors and associated tissue proteases in human brain tissue, using the publically available databases. Based on the expression analysis, SARS-CoV-2 entry in human brain cells is likely to be mediated through NRP1 and furin.

Graphical Abstract
Probing the proton release by Photosystem II in the S1 to S2 high-spin transition
Authors: Boussac Alain , Sugiura Miwa , Sellés Julien
Published: January 2022

The stoichiometry and kinetics of the proton release were investigated during each transition of the S-state cycle in Photosystem II (PSII) from Thermosynechococcus elongatus containing either a Mn4CaO5 (PSII/Ca) or a Mn4SrO5 (PSII/Sr) cluster. The measurements were done at pH 6.0 and pH 7.0 knowing that, in PSII/Ca at pH 6.0 and pH 7.0 and in PSII/Sr at pH 6.0, the flash-induced S2-state is in a low-spin configuration (S2LS) whereas in PSII/Sr at pH 7.0, the S2-state is in a high-spin configuration (S2HS) in half of the centers. Two measurements were done; the time-resolved flash dependent i) absorption of either bromocresol purple at pH 6.0 or neutral red at pH 7.0 and ii) electrochromism in the Soret band of PD1 at 440 nm. The fittings of the oscillations with a period of four indicate that one proton is released in the S1 to S2HS transition in PSII/Sr at pH 7.0. It has previously been suggested that the proton released in the S2LS to S3 transition would be released in a S2LSTyrZ● → S2HSTyrZ● transition before the electron transfer from the cluster to TyrZ● occurs. The release of a proton in the S1TyrZ● →S2HSTyrZ transition would logically imply that this proton release is missing in the S2HSTyrZ● to S3TyrZ transition. Instead, the proton release in the S1 to S2HS transition in PSII/Sr at pH 7.0 was mainly done at the expense of the proton release in the S3 to S0 and S0 to S1 transitions. However, at pH 7.0, the electrochromism of PD1 seems larger in PSII/Sr when compared to PSII/Ca in the S3 state. This points to the complex link between proton movements in and immediately around the Mn4 cluster and the mechanism leading to the release of protons into the bulk.
Doderlin: Isolation and Characterization of a Broad-Spectrum Antimicrobial Peptide from Lactobacillus acidophilus
Authors: da Silva Bruna S. , Díaz-Roa Andrea , Yamane Erica S. , Hayashi Mirian A. F. , da Silva Junior Pedro Ismael
Published: January 2022

Lactobacillus acidophilus are Gram-positive bacteria distributed in diverse environments, and as being a component of the normal microbiota of gastrointestinal and urogenital tract, being relevant to humans. Classified as lactic acid bacteria, due to the pro-duction of lactic acid, Lactobacillus can also produce antimicrobial peptides (AMPs), which is a compound synthesized by all forms of life aiming for protecting themselves from threats and to increase their competitivity to survive in a specific environment. AMPs are molecules capable of inhibiting the growth of microorganisms and, due to the indiscriminate use of conventional antibiotics and the emergence of multi-resistant bacteria, they have become an alternative, not only for treating multi-resistant infections, but also for probiotic product confection and food conservation. Considering the rampant rise of resistance, the present study aimed to isolate and characterize antimicrobial peptides from Lactobacillus acidophilus extracts. Samples were obtained from Lactobacillus acid extract supernatant which was pre-fractionated on disposable cartridges, followed by a high-performance liquid chromatography (HPLC). The collected fractions were evaluated in a liquid growth inhibition assay where eight fractions antimicrobial activity were obtained. One of them was selected for further characterization by mass spectrometry (MS), due to its antimicrobial activity against Candida albicans and conclusive results in mass spectrometry analysis. This molecule was identified as a peptide having a molecular mass of 1788.01 Da, peptide sequence NEPTHLLKAFSKAGFQ, and named Doderlin. Interestingly, antimicrobial molecules isolated from L. acidophilus have already been described previously, but few reports in the literature describe an AMP effective against C. albicans as reported here. The results obtained suggest that this newly discovered molecule have a biological property with potential to be applied in pharmaceutical and food companies in the fight against contamination and/or for treating infections caused by microorganisms.

IMPORTANCE

Doderlin, this newly discovered molecule have a biological property with potential to be applied in pharmaceutical and food companies in the fight against contamination and/or for treating infections caused by microorganisms.
The developmental origin and the specification of the adrenal cortex in humans and cynomolgus monkeys
Authors: Cheng Keren , Seita Yasunari , Moriwaki Taku , Noshiro Kiwamu , Sakata Yuka , Hwang Young Sun , Torigoe Toshihiko , Saitou Mitinori , Tsuchiya Hideaki , Iwatani Chizuru , Hosaka Masayoshi , Ohkouchi Toshihiro , Watari Hidemichi , Umazume Takeshi , Sasaki Kotaro
Published: January 2022

Development of the adrenal cortex, a vital endocrine organ, originates in the adrenogonadal primordium, a common progenitor for both the adrenocortical and gonadal lineages in rodents. In contrast, we find that in humans and cynomolgus monkeys, the adrenocortical lineage originates in a temporally and spatially distinct fashion from the gonadal lineage, arising earlier and more anteriorly within the coelomic epithelium. The adrenal primordium arises from adrenogenic coelomic epithelium via an epithelial-to- mesenchymal-like transition, which then progresses into the steroidogenic fetal zone via both direct and indirect routes. Notably, we find that adrenocortical and gonadal lineages exhibit distinct HOX codes, suggesting distinct anterior-posterior regionalization. Together, our assessment of the early divergence of these lineages provides a molecular framework for understanding human adrenal and gonadal disorders.

One Sentence Summary

Specification of the adrenal cortex occurs in adrenogenic coelomic epithelium independent of gonadogenesis in humans and cynomolgus monkeys
High prevalence of long-term olfactory disorders in healthcare workers after COVID-19: a case-control study
Authors: Frasnelli Johannes , Tognetti Arnaud , Winter Anja L. , Thunell Evelina , Olsson Mats J. , Greilert Nina , Olofsson Jonas K. , Havervall Sebastian , Thålin Charlotte , Lundström Johan N.
Published: January 2022

Background

More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions. However, olfactory dysfunction was common already before the COVID-19 pandemic, making it necessary to also consider the existing baseline prevalence of olfactory dysfunction. To establish the adjusted prevalence of COVID-19 related olfactory dysfunction, we assessed smell function in healthcare workers who had contracted COVID-19 during the first wave of the pandemic using psychophysical testing.

Methods

Participants were continuously tested for SARS-CoV-2 IgG antibodies since the beginning of the pandemic. To assess the baseline rate of olfactory dysfunction in the population and to control for the possibility of skewed recruitment of individuals with prior olfactory dysfunction, consistent SARS-CoV-2 IgG naïve individuals were tested as a control group.

Results

Fifteen months after contracting COVID-19, 37% of healthcare workers demonstrated a quantitative reduction in their sense of smell, compared to only 20% of the individuals in the control group. Fifty-one percent of COVID-19-recovered individuals reported qualitative symptoms, compared to only 5% in the control group. In a follow-up study 2.6 years after COVID-19 diagnosis, 24% of all tested recovered individuals still experienced parosmia.

Conclusions

In summary, 65% of healthcare workers experienced parosmia/hyposmia 15 months after contracting COVID-19. When compared to a control group, the prevalence of olfactory dysfunction in the population increased by 41 percentage points. Parosmia symptoms were still lingering two-and-a half years later in 24% of SARS-CoV-2 infected individuals. Given the amount of time between infection and testing, it is possible that the olfactory problems may not be fully reversible in a plurality of individuals.
Finite-difference wave-propagation models for dispersive media: impact of space-time discretization
Authors: Zygiridis Theodoros , Kantartzis Nikolaos
Published: January 2022

Purpose

The computational accuracy and performance of finite-difference time-domain (FDTD) methods are affected by the implementation of approximating derivative formulae in diverse ways. This study aims to focus on FDTD models featuring material dispersion with negligible losses and investigates two specific aspects that, until today, are usually examined in the context of non-dispersive media only. These aspects pertain to certain abnormal characteristics of coarsely resolved electromagnetic waves and the selection of the proper time-step size, in the case of a high-order discretization scheme.

Design/methodology/approach

Considering a Lorentz medium with negligible losses, the propagation characteristics of coarsely resolved waves is examined first, by investigating thoroughly the numerical dispersion relation of a typical discretization scheme. The second part of the study is related to the unbalanced space-time errors in FDTD schemes with dissimilar space-time approximation orders. The authors propose a remedy via the suitable choice of the time-step size, based on the single-frequency minimization of an error expression extracted, again, from the scheme’s numerical dispersion formula.

Findings

Unlike wave propagation in free space, there exist two parts of the frequency spectrum where waves in a Lorentz medium experience non-physical attenuation and display non-changing propagation constants, due to coarse discretization. The authors also show that an optimum time-step size can be determined, in the case of the (2,4) FDTD scheme, which minimizes the selected error formula at a specific frequency point, promoting more efficient implementations.

Originality/value

Unique characteristics displayed by discretized waves, which have been known for non-dispersive media, are examined and verified for the first time in the case of dispersive materials, thus completing the comprehension of the space-time discretization impact on simulated quantities. In addition, the closed-form formula of the optimum time-step enables the efficient implementation of the (2,4) FDTD method, minimizing the detrimental influence of the low-order temporal integration.
An introduction to the parabolic equation method for electromagnetic wave propagation in tunnels
Authors: Rasool Hafiz Faiz , Qureshi Muhammad Ali , Aziz Abdul , Akhtar Zain Ul Abiden , Khan Usman Ali
Published: January 2022

Purpose

The purpose of this paper is to provide a brief introduction of the finite difference based parabolic equation (PE) modeling to the advanced engineering students and academic researchers.

Design/methodology/approach

A three-dimensional parabolic equation (3DPE) model is developed from the ground up for modeling wave propagation in the tunnel via a rectangular waveguide structure. A discussion of vector wave equations from Maxwell’s equations followed by the paraxial approximations and finite difference implementation is presented for the beginners. The obtained simulation results are compared with the analytical solution.

Findings

It is shown that the alternating direction implicit finite difference method (FDM) is more efficient in terms of accuracy, computational time and memory than the explicit FDM. The reader interested in maximum details of individual contributions such as the latest achievements in PE modeling until 2021, basic PE derivation, PE formulation’s approximations, finite difference discretization and implementation of 3DPE, can learn from this paper.

Research limitations/implications

For the purpose of this paper, a simple 3DPE formulation is presented. For simplicity, a rectangular waveguide structure is discretized with the finite difference approach as a design problem. Future work could use the PE based FDM to study the possibility of utilization of meteorological techniques, including the effects of backward traveling waves as well as making comparisons with the experimental data.

Originality/value

The proposed work is directly applicable to typical problems in the field of tunnel propagation modeling for both national commercial and military applications.
A comparative study of organizational commitment process in the private and public sectors
Authors: Boukamcha Fayçal
Published: January 2022

Purpose

The purpose of this paper is to shed light on the motivational process that leads to commitment development in the private and public sectors. It has been suggested that employee’s commitment is mainly predicted by job satisfaction and motivational factors such as internal communication, training, structural empowerment, incentive systems, transformational leadership and person–organization fit.

Design/methodology/approach

A comparative approach, between a set of private and public organizations, was undertaken. A survey was conducted on two random samples of workers belonging to both types of organizations.

Findings

The findings report a set of similarities and discrepancies between the private and the public organizations in terms of motivational factors that lead to job satisfaction and employees’ commitment.

Originality/value

This research brings additional value to the comparative literature on organizational analysis. It is one of the scarce comparative research in the North African context that deal with motivational factors at private and public workplaces.
Network traffic analysis through deep learning for detection of an army of bots in health IoT network
Authors: K. Geetha , S.H. Brahmananda
Published: January 2022

Purpose

IoT has a wide range of applications in the health-care sector and has captured the interest of many academic and industrial communities. The health IoT devices suffer from botnet attacks as all the devices are connected to the internet. An army of compromised bots may form to launch a DDoS attack, steal confidential data of patients and disrupt the service, and hence detecting this army of bots is paramount. This study aims to detect botnet attacks in health IoT devices using the deep learning technique.

Design/methodology/approach

This paper focuses on designing a method to protect health IoT devices from botnet attacks by constantly observing communication network traffic and classifying them as benign and malicious flow. The proposed algorithm analyzes the health IoT network traffic through implementing Bidirectional long-short term memory, a deep learning technique. The IoT-23 data set is considered for this research as it includes diverse botnet attack scenarios.

Findings

The performance of the proposed method is evaluated using attack prediction accuracy. It results in the highest accuracy of 84.8%, classifying benign and malicious traffic.

Originality/value

The proposed method constantly monitors the health IoT network to detect botnet attacks and classifies the traffic as benign or attack. The system is implemented using the BiLSTM algorithm and trained using the IoT-23 data set. The diversity of attack scenarios of the IoT-23 data set demonstrates the proposed algorithm's competence in detecting botnet types in a heterogeneous environment.
Integrated store service quality measurement scale in omni-channel retailing
Authors: Zhang Min , Li Yiwei , Sun Lin , Moustapha Farouk Adewale
Published: January 2022

Purpose

Brick-and-mortar store is an essential channel to deliver a seamless shopping experience and meet customer's dynamic needs in omni-channel retailing. This paper aims to understand customers' expectations of the integrated stores and develop a measurement scale to assess in-store service quality in omni-channel retailing.

Design/methodology/approach

Grounded theory methodology (GTM) is employed to obtain a clear picture of consumer expectations and preferences regarding the omni-channel brick-and-mortar integrated stores. Then, an integrated store service quality scale is proposed, refined and validated using a questionnaire survey and structural equation model (SEM).

Findings

The measurement scale is set to include seven dimensions: in-store environment, in-store technology, product information consistency, employee assistance, personalization, channel availability and instant gratification and return. The relationships among these seven dimensions and customer satisfaction and loyalty are also verified. According to SEM, product information consistency is more important for customer satisfaction while personalization contributes more to customer loyalty. The results demonstrate that by analysing the seven dimensions, retailers can better understand customers and further improve service quality.

Originality/value

This paper proposes a sufficient measurement scale for in-store service quality and fills the gap in omni-channel retailing by capturing its integration attribute.
Impact of perceived organizational support on organizational commitment of banking employees: role of work-life balance
Authors: Sheikh Aarif Mohd
Published: January 2022

Purpose

This paper aims to examine the relationship between perceived organizational support (POS) and work-life balance (WLB) in the context of the Indian banking sector and their subsequent impact on the commitment level of employees.

Design/methodology/approach

Data were collected from 617 banking employees holding different positions with a structured adapted questionnaire. The data analysis was done using structural equation modeling.

Findings

The results revealed a positive influence of POS on WLB. Moreover, this relationship has been found to be partially mediated by organizational commitment (OC).

Originality/value

This study augments the organizational behavior domain by identifying and empirically validating POS as an antecedent of WLB and OC as its consequence in the context of the Indian banking sector, where such studies are scant. The study also suggests the managerial and theoretical implications based on the findings.
Longitudinal approach to the study of corporate governance code and earnings management relationship: the case of Saudi Arabia
Authors: Grada Mohieddin Salem
Published: January 2022

Purpose

This paper investigates whether the introduction of the 2006 corporate governance code and subsequent amendments constrain corporate earnings management (EM) practices amongst listed companies in Saudi Arabia.

Design/methodology/approach

Accounting and corporate governance (CG) data were collected from annual financial reports of a sample of 108 listed companies from 2007 to 2019. Absolute value of discretionary accruals was regressed against tested CG determinants provided in the CG code. The authors also employed other econometric models to check potential endogeneities.

Findings

The overall results provide evidence that the 2006/2018 Saudi Arabia corporate governance code (SACGC) does not deter EM practices in public companies.

Practical implications

Regulators and other stakeholders should make a deliberate effort to improve the Saudi CG environment by focussing on governance aspects such as board and ownership structures to ensure the independence of the board to effectively perform its statutory roles, as EM practices persist in the system.

Originality/value

This paper extends the literature on the effectiveness of CG, by providing evidence that CG code does not effectively constrain EM activities in settings where CG structures may exist, but greater importance is attached to informal relationships and other considerations than formal CG mechanisms, as these features usually work against the potentials of the principles of good CG as in the case of Saudi Arabia.
Humanoid psychological sentiments and enigma of investment
Authors: Chishti Mazhar Farid , Bashir Rizwana , Mancinelli Tanja , Hussain Rana Tanveer
Published: January 2022

Purpose

The primary goal of this study is to look at the behavioral factors that influence an individual's decision to invest in the Pakistan Stock Exchange (PSX).

Design/methodology/approach

Existing behavioral finance theories serve as a foundation for hypotheses. Further hypotheses were investigated by disseminating questionnaire results from a number of individual Pakistani investors. Brokerage and asset management fund managers were also questioned in semi-structured interviews. The obtained data were analyzed using statistical package for the social sciences, and latent variables were identified using the structural equation model (SEM) and an asset management operating system (AMOS).

Findings

Individual investor investment decisions in the PSX are influenced by five behavioral factors: herding, market, prospect, overconfidence and gambler fallacy and anchoring-ability bias. The majority of the variables have a modest impact; however, the market component has a significant impact. Only three behavioral elements, herding, prospect and heuristic, are found to influence investment performance among the behavioral factors stated above. Heuristic habits have been discovered to have the greatest positive impact on investment performance.

Practical implications

This study is one of the few in Pakistan that looked at the factors that influence stock investment decisions using behavioral finance. Prior research has only considered the effects of a restricted number of behavioral characteristics on Pakistani individual investors; however, this study seeks to use a whole collection of behavioral factors to examine their impacts on Pakistani individual investors.

Research limitations

The focus of the study remains on the individual investor, whereas the impact of institutional investors on investment behavior could bring different outcomes.

Originality/value

This is among the few studies that investigated the impact of cognitive factors on investment decisions in the context of Pakistan and will help policy makers, opinion makers and individuals.