bluuebunny/crossref_metadata_2025_split huggingface dataset:
FtsZ is essential until the late stage of constriction
Authors: Goodman Lauren C. Corbin , Erickson Harold P. 
Published: March 2022

1AbstractThere has been recent debate as to the source of constriction force during cell division. FtsZ can generate a constriction force on tubular membranes in vitro, suggesting it may generate the constriction force in vivo. However, another study showed that mutants of FtsZ did not affect the rate of constriction, whereas mutants of the PG assembly did, suggesting that PG assembly may push the constriction from the outside. Supporting this model, two groups found that cells that have initiated constriction can complete septation while the Z ring is poisoned with PC190723. PC19 arrests treadmilling but leaves FtsZ in place. We sought to determine if a fully assembled Z ring is necessary during constriction. To do this, we used a temperature sensitive FtsZ mutant, FtsZ84. FtsZ84 behaves as wild type at 30° C, but it disassembles from the Z ring within one min upon a temperature jump to 42° C. Following the temperature jump we found that cells in early constriction stop constricting. Cells that had progressed to the later stage of division finished constriction without a Z ring. These results show that in Escherichia coli, an assembled Z ring is essential for constriction except in the final stage, contradicting the simplest interpretation of previous studies using PC19.
Selective endocytosis controls slit diaphragm maintenance and dynamics
Authors: Lang Konrad , Milosavljevic Julian , Heinkele Helena , Chen Mengmeng , Gerstner Lea , Spitz Dominik , Kayser Séverine , Helmstädter Martin , Walz Gerd , Köttgen Michael , Spracklen Andrew , Poulton John , Hermle Tobias 
Published: March 2022

SUMMARYThe kidneys generate about 180 liters of primary urine per day by filtration of plasma. An essential part of the filtration barrier is the slit diaphragm, a multiprotein complex containing nephrin as major component. Filter dysfunction typically manifests with proteinuria and mutations in endocytosis regulating genes were discovered as causes of proteinuria. However, it is unclear how endocytosis regulates the slit diaphragm and how the filtration barrier is maintained without either protein leakage or filter clogging. Here we study nephrin dynamics in podocyte-like nephrocytes of Drosophila and show that selective endocytosis either by dynamin- or flotillin-mediated pathways regulates a stable yet highly dynamic architecture. Short-term manipulation of endocytic functions indicates that dynamin-mediated endocytosis of ectopic nephrin restricts slit diaphragm formation spatially while flotillin-mediated turnover of nephrin within the slit diaphragm is needed to maintain filter permeability by shedding of molecules bound to nephrin in endosomes. Since slit diaphragms cannot be studied in vitro and are poorly accessible in mouse models, this is the first analysis of their dynamics within the slit diaphragm multiprotein complex. Identification of the mechanisms of slit diaphragm maintenance will help to develop novel therapies for proteinuric renal diseases that are frequently limited to symptomatic treatment.
Presence or absence of a prefrontal sulcus is linked to reasoning performance during child development
Authors: Willbrand Ethan H. , Voorhies Willa I. , Yao Jewelia K. , Weiner Kevin S. , Bunge Silvia A. 
Published: March 2022

AbstractThe relationship between structural variability in late-developing association cortices like the lateral prefrontal cortex (LPFC) and the development of higher-order cognitive skills is not well understood. Recent findings show that the morphology of LPFC sulci predicts reasoning performance; this work led to the observation of substantial individual variability in the morphology of one of these sulci, the para-intermediate frontal sulcus (pimfs). Here, we sought to characterize this variability and assess its behavioral significance. To this end, we identified the pimfs in a developmental cohort of 72 participants, ages 6-18. When controlling for age, the presence or absence of the ventral component of the pimfs was associated with reasoning, as was the total surface area of pimfs. These findings show that multiple features of sulci can support the development of complex cognitive abilities and highlight the importance of considering individual differences in local morphology when exploring the neurodevelopmental basis of cognition.
A bivalent CMV vaccine formulated with human compatible TLR9 agonist CpG1018 elicits potent cellular and humoral immunity in HLA expressing mice
Authors: Dasari Vijayendra , Beckett Kirrilee , Horsefield Shane , Ambalathingal George , Khanna Rajiv 
Published: March 2022

AbstractThere is now convincing evidence that the successful development of an effective CMV vaccine will require improved formulation and adjuvant selection that is capable of inducing both humoral and cellular immune responses. Here, we have designed a novel bivalent subunit vaccine formulation based on CMV-encoded oligomeric glycoprotein B (gB) and polyepitope protein in combination with human compatible TLR9 agonist CpG1018. The polyepitope protein includes multiple minimal HLA class I-restricted CD8+ T cell epitopes from different antigens of CMV. This subunit vaccine generated durable anti-viral antibodies, CMV-specific CD4+ and CD8+ T cell responses in multiple HLA expressing mice. Antibody responses included broad TH1 isotypes (IgG2a, IgG2b and IgG3) and potently neutralized CMV infection in fibroblasts and epithelial cells. Furthermore, polyfunctional antigen-specific T cell immunity and antiviral antibody responses showed long-term memory maintenance. These observations argue that this novel vaccine strategy, if applied to humans, could facilitate the generation of robust humoral and cellular immune responses which may be more effective in preventing CMV-associated complications in various clinical settings.
Combining transgenesis with paratransgenesis to fight malaria
Authors: Huang Wei , Vega-Rodriguez Joel , Kizito Christopher , Cha Sung-Jae , Jacobs-Lorena Marcelo 
Published: March 2022

AbstractMalaria is among the deadliest infectious diseases and Plasmodium, the causative agent, needs to complete a complex development cycle in its vector mosquito for transmission to occur. Two promising strategies to curb transmission are transgenesis, consisting of genetically engineering mosquitoes to express anti-malarial effector molecules and paratransgenesis, consisting of introducing into the mosquito, commensal bacteria engineered to express anti-malarial effector molecules. Although both approaches restrict parasite development in the mosquito, it is not known how their effectiveness compares. Here we provide an in-depth assessment of transgenesis and paratransgenesis and evaluate the combination of the two approaches. Using the Q-system to drive gene expression, we engineered mosquitoes to produce and secrete two effectors – scorpine and the MP2 peptide – into the mosquito gut and salivary glands. We also engineered Serratia, a commensal bacterium capable to spread through mosquito populations, to secrete the same two effectors into the mosquito gut. Whereas both mosquito-based and bacteria-based approaches strongly reduced the oocyst and sporozoite intensity, a substantially stronger reduction of P. falciparum development was achieved when transgenesis and paratransgenesis were combined. Most importantly, transmission of P. berghei from infected to naïve mice was maximally inhibited by the combination of the two approaches. Combining these two strategies promise to become a powerful approach to combat malaria.SignificanceMalaria kills hundreds of thousand persons yearly. Clearly, new approaches are needed to fight this disease. Two promising approaches are based on the concept of genetically modifying the mosquito to make it a poor vector for the parasite: 1) transgenesis (engineering the mosquito to deliver anti-malarial compounds) and 2) paratransgenesis (engineering mosquito symbiotic bacteria to deliver anti-malarial compounds). The key questions addressed by this manuscript are: which of the two is the most promising approach? And because transgenesis and paratransgenesis are not mutually exclusive, would the combination of both be the most effective strategy? Our results argue for the combination of the two, showing the additive impact that these two strategies may have in controlling malaria transmission in the field.
Distinct gene expression by expanded clones of quiescent memory CD4+ T cells harboring intact latent HIV-1 proviruses
Authors: Weymar Georg H J , Bar-On Yotam , Oliveira Thiago Y. , Gaebler Christian , Ramos Victor , Hartweger Harald , Breton Gaëlle , Caskey Marina , Cohn Lillian B , Jankovic Mila , Nussenzweig Michel C 
Published: March 2022

SummaryAntiretroviral therapy controls but does not cure HIV-1 infection due to a reservoir of rare CD4+ T cells harboring latent proviruses. Little is known about the transcriptional program of latent cells. Here we report a novel strategy to enrich clones of latent cells carrying intact, replication- competent HIV-1 proviruses from blood based on their expression of unique T cell receptors. Latent cell enrichment enabled single cell transcriptomic analysis of 1,050 CD4+ T cells belonging to expanded clones harboring intact HIV-1 proviruses from 6 different individuals. The analysis revealed that most of these cells are T effector memory cells that are enriched for expression of HLA-DR, HLA-DP, CD74, CCL5, Granzymes A and K, cystatin F, LYAR and DUSP2. We conclude that expanded clones of latent cells carrying intact HIV-1 proviruses persist preferentially in a distinct CD4+ T cell population opening new possibilities for eradication.Graphical Abstract
Bioinformatic analyses of plasmid resistome changes in pOXA-48
Authors: Fordham Stephen , Mantzouratou Anna , Sheridan Elizabeth Anne 
Published: March 2022

AbstractInfections caused by carbapenem resistant Enterobacteriales (CPE) represent a significant threat in clinical settings. blaOXA-48 is one of the most frequent carbapenemase genes among Enterobacteriales. The blaOXA-48 is typically encoded on the prototypical IncL conjugative pOXA-48 plasmid. The pOXA-48 plasmid encodes only the blaOXA-48 resistance gene. However, aminoglycoside and extended spectrum β-lactamase (ESBL) resistance genes have also been detected on the same pOXA-48 plasmid backbone. These pOXA-48 plasmids encoding additional antimicrobial resistance (AMR) genes have been associated with both poor patient outcome and increased minimal inhibitory concentrations (MICs) to antibiotics including broad-spectrum cephalosporins.The blaOXA-48 gene was sourced from the pOXA-48 reference plasmid and set as a query using the BLASTn tool. Non-duplicate blaOXA-48 containing plasmids were downloaded, incompatibility typed and annotated for resistance genes using ResFinder 4.0. Bioinformatic analyses identified three distinct variants of the pOXA-48 plasmid encoding 4, 5, and 6 antimicrobial resistance genes. All plasmids encoded the ESBL blaCTX-M-14b, blaOXA-48 and either 2, 3 or 4 aminoglycoside resistance genes, in addition to conjugative transfer machinery. Plasmid variants 1 and 3 encoded aminoglycoside genes bracketed between IS26 and ISEc63 insertion elements, forming a potential transposon. The potential transposon structure had resemblance to the Tn5393 transposon (accession: M96392), including both aph(3’’)-Ib, aph(6)-Id genes, and a Tn3 resolvase. The IS element ISEcp1 lies upstream of blaCTX-M-14b. All three plasmid variants appear related. Notably, all pOXA-48 plasmid variants were identified in multiple countries. In particular, variant 1 including 6 AMR genes was detected in 7 unique countries.Plasmids encoding additional AMR genes were associated with clinical/surveillance samples suggesting antibiotic pressure in clinical settings may promote changes in the resistome of pOXA-48. Acquisition of pOXA-48 resistant plasmids carrying additional AMR genes beyond blaOXA-48 can change the resistome of susceptible isolates in a single-step, rendering previously susceptible strains refractory to almost all available treatment options.
Functional characterization of the thrombospondin-related paralogous proteins rhoptry discharge factor 1 and 2 unveils phenotypic plasticity in Toxoplasma gondii rhoptry exocytosis
Authors: Possenti Alessia , Di Cristina Manlio , Nicastro Chiara , Lunghi Matteo , Messina Valeria , Piro Federica , Tramontana Lorenzo , Cherchi Simona , Falchi Mario , Bertuccini Lucia , Spano Furio 
Published: March 2022

ABSTRACTTo gain access to the intracellular cytoplasmic niche essential for their growth and replication, apicomplexan parasites such as Toxoplasma gondii rely on the timely secretion of two types of apical organelles named micronemes and rhoptries. Rhoptry proteins are key to host cell invasion and remodelling, however, the molecular mechanisms underlying the thight control of rhoptry discharge are poorly understood. Here, we report the identification and functional characterization of two novel T. gondii thrombospondin-related proteins implicated in rhoptry exocytosis. The two proteins, already annotated as MIC15 and MIC14, were renamed rhoptry discharge factor 1 (RDF1) and rhoptry discharge factor 2 (RDF2) and found to be exclusive of the Coccidia class of apicomplexan parasites. Furthermore, they were shown to have a paralogous relationship and share a C-terminal transmembrane domain followed by a short cytoplasmic tail. Immunofluorescence analysis of T. gondii tachyzoites revealed that RDF1 presents a diffuse cytoplasmic localization not reminiscent of any know subcellular compartment, whereas RDF2 was not detected. Using a conditional knockout approach, we demonstrated that RDF1 loss caused a marked growth defect. The lack of the protein did not affect parasite gliding motility, host cell attachment, replication and egress, whereas invasion was dramatically reduced. Notably, while RDF1 depletion did not result in altered microneme exocytosis, rhoptry discharge was found to be heavily impaired. Interestingly, rhoptry secretion was partially reversed by spontaneous upregulation of the RDF2 gene in knockdown parasites grown under constant RDF1 repression. Collectively, our results identify RDF1 and RDF2 as additional key players in the pathway controlling rhoptry discharge. Furthermore, this study unveils a new example of compensatory mechanism contributing to phenotypic plasticity in T. gondii.
A novel quantitative trait locus implicates Msh3 in the propensity for genome-wide short tandem repeat expansions in mice
Authors: Maksimov Mikhail , Ashbrook David G. ,   BXD Sequencing Consortium, Villani Flavia , Colonna Vincenza , Mousavi Nima , Ma Nichole , Palmer Abraham A. , Gymrek Melissa 
Published: March 2022

AbstractShort tandem repeats (STRs) are a class of rapidly mutating genetic elements characterized by repeated units of 1 or more nucleotides. We leveraged whole genome sequencing data for 152 recombinant inbred (RI) strains from the BXD family derived from C57BL/6J and DBA/2J mice to study the effects of genetic background on genome-wide patterns of new mutations at STRs. We defined quantitative phenotypes describing the numbers and types of germline STR mutations in each strain and identified a locus on chromosome 13 associated with the propensity of STRs to expand. Several dozen genes lie in the QTL region, including Msh3, a known modifier of STR stability at pathogenic repeat expansions in mice and humans. Detailed analysis of the locus revealed a cluster of variants near the 5’ end of Msh3, including multiple protein-coding variants within the DNA mismatch recognition domain of MSH3, and a retrotransposon insertion overlapping an annotated exon. Additionally, gene expression analysis demonstrates co-localization of this QTL with expression QTLs for multiple nearby genes, including Msh3. Our results suggest a novel role for Msh3 in regulating genome-wide patterns of germline STR mutations and demonstrate that inherited genetic variation can contribute to variability in accumulation of new mutations across individuals.
Adaptive block backstepping control for a UAV performing lateral maneuvers under lateral c.g. uncertainty
Authors: Khanna Anukaran , Singh Neelaksh , Mukherjee Bijoy K. 
Published: March 2022

Purpose
Unmanned aerial vehicles (UAVs) have wide applications in surveillance and reconnaissance without risking human life. Due to unbalanced payload distribution or in-flight deployment, UAVs may undergo lateral center of gravity (c.g.) variations resulting in an asymmetric dynamic having significant longitudinal and lateral/directional coupling and hence more pronounced nonlinearity. Therefore, automatic control of UAVs becomes extremely difficult when it is forced to perform maneuvers under such imbalance in lateral mass distribution. The purpose of this paper is to design adaptive nonlinear control so that the UAV can perform some useful lateral/directional maneuver under lateral c.g. uncertainty.

Design/methodology/approach
First the nominal lateral/directional dynamics of a fixed-wing UAV is framed into strict feedback form and then the block backstepping approach is used to design the controller to execute horizontal turn and aileron roll maneuvers under no lateral c.g. variation. Thereafter, an adaptive block backstepping controller is designed to adapt to uncertainty in lateral c.g. position considering an approximate model of the asymmetric dynamics. The proposed adaptive scheme is validated against the same two maneuvers as considered for the nominal case.

Findings
First it is shown that the lateral/directional dynamics of a UAV can be converted to a block strict feedback form for executing some lateral/directional maneuvers. However, it was observed that the maneuver performance suffers significant performance degradation under lateral c.g. variations. To mitigate this issue, a simple and computationally inexpensive adaptive block backstepping scheme is proposed and validated. The adaptation law is further proved to be able to asymptotically estimate the actual c.g. location of the UAV.

Practical implications
The proposed control scheme allows the UAV to automatically adapt to lateral c.g. variations so that the intended maneuvers are performed without any noticeable loss in maneuver performance.

Originality/value
There are very few works available in the literature that address nonlinear control designs for executing specific lateral/directional maneuvers and, moreover, they consider symmetric UAVs or aircraft only. This paper addresses the practical problem of autonomous maneuvering for UAVs with unbalanced lateral mass distribution leading to shift of c.g. out of its plane of symmetry.
A case study on the effect of meteorological events on the efficiency of flight training organization
Authors: Tatli Ali , Bocu Erdogan , Filik Tansu , Karakoc Tahir Hikmet 
Published: March 2022

Purpose
The purpose of this study is to determine the meteorological events that affect flight training to make the training flight more efficient in a flight training organization (FTO) and to examine the effects of these events on FTO.

Design/methodology/approach
Within the scope of this study, the flight training given at Eskisehir Technical University Pilotage Department (ESTU-P) is discussed, and the effect of meteorological events on flight training in this FTO is evaluated.

Findings
When the two-year (2019–2020) flight training process of ESTU-P is examined, 45% of the flights planned for 2019, 25% of the flights planned for 2020 and 33% of the total flights in the two-year period could not be realized due to meteorological events. It is determined that this result naturally affects the efficiency of the FTO negatively. Meteorological events such as high temperature, fog and snow are among the main meteorological events that cause flight training to be interrupted.

Originality/value
This study will create a framework for FTOs that have been or will be established.
The green bond market and its use for energy efficiency finance in Africa
Authors: Taghizadeh-Hesary Farhad , Zakari Abdulrasheed , Alvarado Rafael , Tawiah Vincent 
Published: March 2022

PurposeThis study presents the state of green bond markets in Africa and green bond funds by some countries in the continent.Design/methodology/approachThe authors adopt a case study approach on four different kinds of countries, namely oil-rich economy, green bond innovator, renewable energy user and carbon vulnerability.FindingsThe authors found that Africa's green bond is still at the early stages. However, countries are using innovative ways that are adaptable to their current economic conditions and investment attractiveness in issuing green bonds. While some countries focus on central and local government bonds, others use corporate bonds, few combine government and corporate green bonds. Interestingly, the first green bond globally certified by the Climate Bonds Standard was issued by an Africa country in Africa. In some selected countries such as Nigeria, South Africa, Morocco, Namibia and Kenya, green bond markets have seen massive growth and have contributed to numerous infrastructural energy efficiency projects. To expand this market further in these countries, the authors recommend fostering a public–private partnership backed by policies and political will.Originality/valueThis study provides an original contribution to the green bond and its likelihood of driving energy efficiency in a continent that has attracted little to no attention in the literature.
Happiness at work through spiritual leadership: a self-determination perspective
Authors: Srivastava Shalini , Mendiratta Aparna , Pankaj Prabhat , Misra Richa , Mendiratta Rajat 
Published: March 2022

PurposeUpholding congruency with self-determination theory (SDT), the study intends to analyze the impact of spiritual leadership (SL) on happiness at work (HAW) via affective commitment (AC) and prosocial behavior (PSB) in the Indian service sector.Design/methodology/approachThe data were collected from 324 employees belonging to the service sector of north India. The study utilized AMOS and PROCESS (Hayes, 2013) to test the hypothesized model.FindingsThe findings provided considerable support for the hypothesized relationships between SL, AC, PSB and HAW. The findings advocate the positive association between SL and HAW routing through mediators such as AC and PSB.Research limitations/implicationsFuture research studies have the potential to dwell on the topic from a leader's perspective, i.e. the benefits derived through practicing spirituality. The present work in this field is focused on quantitative tools; more studies can be conducted through qualitative analysis. Future works can attempt to compare the differences amongst cultures and sectors concerning SL and its outcomes.Practical implicationsThe paper provides some relevant inputs for the Indian service sector to comprehend the criticality of SL in building long-lasting relationships amongst peers leading to creating sustainable and happy workplaces.Originality/valueThe study explores the relationship between SL and HAW which has neither been explored theoretically nor tested empirically.