bluuebunny/crossref_metadata_2025 huggingface dataset:
Min oscillations in bacteria as real-time reporter of environmental challenges at the single-cell level
Authors: Ortega Ingrid V. , Viela Felipe , Flors Cristina
Published: July 2023

Min oscillations are a fascinating mechanism used by
Escherichia coli
to find their middle. Beyond their biological role, they provide a convenient and relatively unexplored method to monitor the effect of sublethal environmental challenges on bacterial physiology in real-time and at the single-cell level. In this review, we discuss the original papers that put forward the idea of using Min oscillations as a reporting tool to monitor the effect of extracellular cationic compounds, including antibiotics. More recent work from our laboratory explores this tool to follow bacterial response to other challenges such as weak mechanical interactions with nanomaterials or photodynamic treatment. We discuss the physiological meaning of the changes in Min oscillation period, likely related to membrane potential dynamics, as well as the benefits and limitations of using oscillations as a reporter in fluorescence microscopy. Overall, Min oscillations are a useful addition to the fluorescence microscopy toolbox in order to visualize stress responses in
E. coli
, and have the potential to provide full mechanistic understanding of the events that lead to bacterial cell death in different contexts.
Seagrass production around artificial reefs is resistant to human stressors
Authors: Andskog Mona A. , Layman Craig , Allgeier Jacob E.
Published: July 2023

Primary production underpins most ecosystem services, including carbon sequestration and fisheries. Artificial reefs (ARs) are widely used for fisheries management. Research has shown that a mechanism by which ARs in seagrass beds can support fisheries and carbon sequestration is through increasing primary production via fertilization from aggregating fish excretion. Seagrass beds are heavily affected by anthropogenic nutrient input and fishing that reduces nutrient input by consumers. The effect of these stressors is difficult to predict because impacts of simultaneous stressors are typically non-additive. We used a long-term experiment to identify the mechanisms by which simultaneous impacts of sewage enrichment and fishing alter seagrass production around ARs across non-orthogonal gradients in human-dominated and relatively unimpacted regions in Haiti and The Bahamas. Merging trait-based measures of seagrass and seagrass ecosystem processes, we found that ARs consistently enhanced
per capita
seagrass production and maintained ecosystem-scale production despite drastic shifts in controls on production from human stressors. Importantly, we also show that coupled human stressors on seagrass production around ARs were additive, contrasting expectations. These findings are encouraging for conservation because they indicate that seagrass ecosystems are highly resistant to coupled human stressors and that ARs promote ecosystem services even in human-dominated ecosystems.
Negative interactions and virulence differences drive the dynamics in multispecies bacterial infections
Authors: Schmitz Désirée A. , Allen Richard C. , Kümmerli Rolf
Published: July 2023

Bacterial infections are often polymicrobial, leading to intricate pathogen–pathogen and pathogen–host interactions. There is increasing interest in studying the molecular basis of pathogen interactions and how such mechanisms impact host morbidity. However, much less is known about the ecological dynamics between pathogens and how they affect virulence and host survival. Here we address these open issues by co-infecting larvae of the insect model host
Galleria mellonella
with one, two, three or four bacterial species, all of which are opportunistic human pathogens. We found that host mortality was always determined by the most virulent species regardless of the number of species and pathogen combinations injected. In certain combinations, the more virulent pathogen simply outgrew the less virulent pathogen. In other combinations, we found evidence for negative interactions between pathogens inside the host, whereby the more virulent pathogen typically won a competition. Taken together, our findings reveal positive associations between a pathogen's growth inside the host, its competitiveness towards other pathogens and its virulence. Beyond being generalizable across species combinations, our findings predict that treatments against polymicrobial infections should first target the most virulent species to reduce host morbidity, a prediction we validated experimentally.
Patterns of host plant use do not explain mushroom body expansion in Heliconiini butterflies
Authors: Young Fletcher J. , Monllor Monica , McMillan W. Owen , Montgomery Stephen H.
Published: July 2023

The selective pressures leading to the elaboration of downstream, integrative processing centres, such as the mammalian neocortex or insect mushroom bodies, are often unclear. InHeliconiusbutterflies, the mushroom bodies are two to four times larger than those of their Heliconiini relatives, and the largest known in Lepidoptera. Heliconiini lay almost exclusively onPassiflora, which exhibit a remarkable diversity of leaf shape, and it has been suggested that the mushroom body expansion ofHeliconiusmay have been driven by the cognitive demands of recognizing and learning leaf shapes of local host plants. We test this hypothesis using two complementary methods: (i) phylogenetic comparative analyses to test whether variation in mushroom body size is associated with the morphological diversity of host plants exploited across the Heliconiini; and (ii) shape-learning experiments using six Heliconiini species. We found that variation in the range of leaf morphologies used by Heliconiini was not associated with mushroom body volume. Similarly, we find interspecific differences in shape-learning ability, butHeliconiusare not overall better shape learners than other Heliconiini. Together these results suggest that the visual recognition and learning of host plants was not a main factor driving the diversity of mushroom body size in this tribe.
Ecological predictors of interspecific variation in bird bill and leg lengths on a global scale
Authors: Xu Yu , Price Megan , Que Pinjia , Zhang Kai , Sheng Shang , He Xingcheng , Wen Zhixin , Wang Bin
Published: July 2023

Bills and legs are two vital appendages for birds, and they exhibit huge interspecific variation in form and function, yet no study has examined the global predictors of this variation. This study examined global gradients in the relative lengths of bird bills and tarsi (i.e. exposed leg parts) to body size across non-migratory birds, while accounting for phylogeny. We found that relative bill length and tarsus length were related to diet, habitat density, latitude, annual mean temperature, temperature variability and hand–wing index (HWI), a proxy for birds' flight efficiency. Among these factors, diet played a primary role in predicting bill length, with nectar-feeding pollinators, vertivores, invertivores and omnivores having longer bills; HWI emerged as the predominant predictor of tarsus length, wherein species with higher HWI had shorter tarsi. However, the effects of these factors differed between passerines and non-passerines, with some temperature-related effects exhibiting opposite trends between these two groups. Our findings highlight the compromise in adaptations for feeding, thermoregulation and flight performance between the two distinct appendages.
Malaria vaccines to moderate the impact of antibiotic resistance in endemic countries
Authors: Khan Maria , Khan Saba
Published: July 2023

Swift and widespread deployment of an efficient malaria vaccine in Pakistan, together with basic control and preventive measures, could significantly decrease the economic and healthcare burden caused by drug-resistant malaria. Moreover, the RTS,S/AS01 vaccine has provided a much needed breakthrough after decades of growth, as an innovative vaccine for malaria in phase 3 clinical trials and currently undergoing implementation studies. Vaccination is a potentially critical component of efforts to arrest the development and dissemination of antimicrobial resistance, although little is known about the impact vaccination may have within low- and-middle-income countries.
The impact of COVID-19 on community-dwelling people post-stroke and informal caregivers: a qualitative study
Authors: Dias Teresa , Cravo Patrícia , Santos Joana , Gomes Catarina , Santiago Marta , Pereira Carla Mendes
Published: July 2023

Background/ aims

Little is known about the experience of people post-stroke and their informal caregivers during the COVID-19 pandemic. The aim of this study was to understand the challenges faced by people post-stroke and informal caregivers during the pandemic, as well as the impact on their healthcare support, lifestyle, and self-care behaviors.

Methods

A multi-perspective qualitative study was undertaken, with semi-structured interviews being carried out to sixteen participants: eight stroke patients and eight informal caregivers, mostly performed online. Reflexive thematic analysis was used, with data being independently coded and categorized before consolidated into themes and subthemes.

Findings

Three themes were derived from the data analysis: i) Perceived impact of COVID-19 pandemic, ii) What helped? - strategies to manage the distress provoked by COVID-19, and iii) The value of rehabilitation and physical activity, with findings highlighting the negative psychological impact of the pandemic. In response to the perceived lack of support and access to health and social services, participants highlighted the use of digital approaches and professional support.

Conclusions

Findings suggest the importance of self-management support and/or digital content in order to mitigate the impact of COVID-19. The involvement of peers, family members, friends or others seems to be an important strategy to increase motivation in remote rehabilitation and physical activity.

Key points

-

Due to the impact of COVID-19 on people post-stroke and informal caregivers’ daily routines, both highlighted the importance of finding new and alternative ways of communicating, which included the use of digital approaches.

-

For some informal caregivers the pandemic was perceived as an opportunity to spend more time with the family and with the person with stroke.

-

People post-stroke admit having decreased their levels of physical activity during COVID-19 and increased the value given to rehabilitation and physical activity.

-

Involving peers or others, digitally or in-person, seems to be an important strategy when planning physical activity recommendations.
Household Vulnerability in the urban slums of Mumbai, India: Analysis of a large cross-sectional Survey
Authors: Deshmukh Devika , Basu Saurav , Negandhi Preeti , Sharma Jyoti , D’Aquino Luigi , Singh Vivek , Gadhari Mangesh , Venu Vaishali , Chandrasekar Rajeshwari , Gomare Mangala , Zodpey Sanjay
Published: July 2023

Background

Improving equitable health outcomes needs a further understanding of the social, economic, political, and legal determinants that shape human health and well-being, especially in the poor and marginalized communities in urban slums. Vulnerability represents a group of adverse social determinants that put a household at a greater risk of falling ill.

The objective of this study was to determine the magnitude of health, residential, social, and occupational vulnerabilities amongst households in two urban slums in Mumbai, assess the sociodemographic factors associated with health vulnerability, and ascertain the linkage between health vulnerability and other vulnerabilities.

Methods

A cross-sectional survey was conducted from May to August 2021 in the urban slums of Mumbai. One Urban Primary Health Center area each in two wards (M/East and G/North) of Mumbai city mostly inhabited by people living in slums was purposively selected. A total of 15,796 households were included in the vulnerability assessment survey. Four kinds of vulnerability (health, social, residential, and occupational) indices were created based on survey responses.

Results

High residential vulnerability was estimated in 73.5%, (95% C.I. 72.8, 74.2), high social vulnerability in 67.9% (95% C.I. 67.2, 68.7), and high occupational vulnerability in 59.5%, (95% C.I. 58.7, 60.2) households. The presence of health vulnerability was observed in 39.6% (95% C.I. 38.8, 40.4) households. On adjusted analysis, social, residential, and occupational vulnerability were all statistically significant predictors of health vulnerability (p<0.001). The health vulnerability increased by 0.492 units for each unit increase in social vulnerability, 0.605 for each unit increase in residential vulnerability and 0.081 unit for each unit increase in occupational vulnerability.

Conclusions

Health vulnerability is present in nearly four out of ten households in the urban slums of Mumbai, while a majority of the households experience residential, social, and occupational vulnerability. Overcrowding and poor ventilation were nearly universal, with high burden of poor sanitation and hygiene.
EXPLORING WOMEN’S PERSPECTIVES ON ABORTION LEGALIZATION IN NAMIBIA: INSIGHTS FROM RESIDENTS OF /GERERES, KEETMANSHOOP
Authors: Namukwambi Rauna , Sheehama Lovis , Sheehama Justice EK. , Nakambale Hilma N.
Published: July 2023

Introduction

Abortion is a globally controversial topic. Despite Namibia gaining independence in 1990, the country still upholds the apartheid inherited 1975 Abortion and Sterilization Act of South Africa, which places restrictions on abortion. There have been calls from many parliamentarians to legalize abortion on demand due to the alarming rate of backyard abortions that were putting Namibian women’s lives at risk. However, there is opposition from Pro-life advocates. This study assessed the perceptions of women in /Gereres, Keetmanshoop regarding the legalization of abortion in Namibia.

Methods

This study utilized a quantitative, descriptive cross-sectional design. A non-probability systematic sampling technique was used to select participants. A self-administered questionnaire was used to collect data. Participants’ perspectives were captured using structured three-point and five-point Likert scale checklists. Microsoft Excel was used to analyze data. Data were presented using frequency tables.

Results

The study revealed a variation of views from participants, mostly opposing the legalization of abortion in Namibia. Most women acknowledged that illegal abortion poses risks to women; however, they would not advocate for the legalization of abortion. Notably, several participants appeared to justify abortion in certain circumstances such as in cases of rape or incest, or if continuation of the pregnancy poses a health risk to the woman. Cultural and religious beliefs appeared to be major factors influencing women’s opposing views on abortion.

Conclusion

The study highlights the complex and diverse perspectives of women in /Gereres, Keetmanshoop regarding the legalization of abortion in Namibia. While recognizing the risks associated with illegal abortion, most participants opposed its legalization, which could mostly be attributed to cultural and religious beliefs. However, some participants acknowledged specific circumstances where abortion could be justified. This study provides women’s insights on the legalization of abortion in Namibia, useful for lawmakers, policymakers, and stakeholders in the field of reproductive health.
BCKDKrs14235 A allele is associated with milder motor impairment and altered network topology in Parkinson’s disease
Authors: Chen Zhichun , Wu Bin , Li Guanglu , Zhou Liche , Zhang Lina , Liu Jun
Published: July 2023

Background

A multitude of genetic variants confer a risk of Parkinson’s disease (PD), however, whether these risk variants affected the motor symptoms of PD patients remain largely elusive. The objective of this study is to investigate the effects ofBCKDKrs14235 (G > A), a risk variant associated with PD risk, on the motor manifestations and brain networks of PD patients.

Methods

PD patients (n = 146) receiving magnetic resonance imaging from Parkinson’s Progression Markers Initiative (PPMI) database were investigated. The effects ofBCKDKrs14235 on the motor manifestations and brain networks of PD patients were systematically evaluated.

Results

BCKDKrs14235 A allele was associated with milder motor symptoms in PD patients.BCKDKrs14235 significantly modified the topology of brain structural and functional network. The assortativity in structural network was negatively associated with rigidity in PD while the shortest path length of right pallidum was positively associated with Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) scores. The mediation analysis suggested that assortativity in structural network mediated the effects ofBCKDKrs14235 on rigidity and the shortest path length of right pallidum mediated the effects ofBCKDKrs14235 on UPDRS-III scores.

Conclusions

BCKDKrs14235 significantly shaped the motor impairment and network topology of PD patients. Differential network metrics mediated the effects ofBCKDKrs14235 on rigidity and UPDRS-III scores of PD patients. Future studies were required to identify the molecular mechanisms underlying the effects ofBCKDKrs14235 on motor impairment and brain network metrics of PD patients.
Shallow networks run deep: Peripheral preprocessing facilitates odor classification
Authors: Puri Palka , Wu Shiuan-Tze , Su Chih-Ying , Aljadeff Johnatan
Published: July 2023

The mammalian brain implements sophisticated sensory processing algorithms along multilayered (‘deep’) neural-networks. Strategies that insects use to meet similar computational demands, while relying on smaller nervous systems with shallow architectures, remain elusive. UsingDrosophilaas a model, we uncover the algorithmic role of odor preprocessing by a shallow network of compartmentalized olfactory receptor neurons. Each compartment operates as a ratiometric unit for specific odor-mixtures. This computation arises from a simple mechanism: electrical coupling between two differently-sized neurons. We demonstrate that downstream synaptic connectivity is shaped to optimally leverage amplification of a hedonic value signal in the periphery. Furthermore, peripheral preprocessing is shown to markedly improve novel odor classification in a higher brain center. Together, our work highlights a far-reaching functional role of the sensory periphery for downstream processing. By elucidating the implementation of powerful computations by a shallow network, we provide insights into general principles of efficient sensory processing algorithms.
Entanglement of AGE-RAGE axis in cardiac pathosis
Authors: Wasim Rufaida , Mahmood Tarique , Siddiqui Mohammed Haris , Wani Tanveer A. , Zargar Seema , Singh Aditya , Mohammed Saad , Ahsan Farogh , Wahajuddin Muhammad
Published: July 2023

Cardiovascular diseases are the major cause of death globally. Acute coronary syndrome is one of numerous cardiovascular illnesses, including advanced glycation end products (AGEs), which play an instrumental part in their development and progression. A substance with multiple pleiotropic characteristics is rosuvastatin. This study examined the cardioprotective effects of rosuvastatin in isoproterenol-induced myocardial injury, as well as the alterations in advanced glycation end products and their roles in cardiac damage. Rosuvastatin (10 mg/kg, orally) was given to male rats daily for 4 weeks, and on the 29th and 30th days, isoproterenol (85 mg/kg, subcutaneously) was administered to cause cardiac damage. Rats were euthanised on the 31st day, and various samples were collected for examination. Administration of isoproterenol increased cardiac mass, levels of cardiac damage markers, lipid oxidation, and collagen content in the heart. Additionally, it reduced the activities of SOD, CAT, GST, GR, and all other antioxidants. Additionally, isoproterenol raises levels of inflammatory markers including TNF-α and IL-6. It has been observed that advanced glycation end products rise along with heart injury. The AGE-RAGE cascade also messes with the injured heart’s echocardiogram. Additionally, histopathological alterations were noticed. According to the study, rosuvastatin has cardioprotective effects on the experimental model, which were supported by an array of physical, biochemical, and histological characteristics.

This study examined the cardioprotective effects of rosuvastatin in isoproterenol-induced myocardial injury, as well as the alterations in advanced glycation end products and their roles in cardiac damage. According to the study, rosuvastatin has cardioprotective effects on the experimental model, which were supported by a number of physiological, biochemical, and histological characteristics. By showing how the functional AGE/RAGE axis is inhibited following rosuvastatin medication, this work provides an etiologic theory involving rosuvastatin therapy in heart injury. These findings may also have practical significance since they highlight the intriguing possibility that rosuvastatin-induced modulation of AGE-RAGE signalling may represent a unique therapeutic approach for the prevention and treatment of other cardiovascular diseases.
Neural mechanism underlying preview effects and masked priming effects in visual word processing
Authors: Huang Xin , Wong Brian W. L. , Ng Hezul Tin-Yan , Sommer Werner , Dimigen Olaf , Maurer Urs
Published: July 2023

Two classic experimental paradigms – masked repetition priming and the boundary paradigm – have played a pivotal role in understanding the process of visual word recognition. Traditionally, these paradigms have often been employed by different communities of researchers, with their own long-standing research traditions. Nevertheless, a review of the literature suggests that the brain-electric correlates of word processing established with both paradigms may show interesting similarities, in particular with regard to the location, timing, and direction of N1 and N250 effects. However, as of yet, no direct comparison has been undertaken between both paradigms. In the current study, we used combined eye-tracking/EEG to perform such a within-subject comparison using the same materials (single Chinese characters) as stimuli. Our results show the typical early repetition effects of N1 and N250 for both paradigms. However, repetition effects in N250 (i.e., a reduced negativity following identical-word primes/previews as compared to different-word primes/previews) were larger in the boundary paradigm than with masked priming. For N1 effects, repetition effects were similar across the two paradigms showing a larger N1 after repetitions as compared to alternations. Therefore, the results indicate that at the neural level, a briefly presented and masked foveal prime produces qualitatively similar facilitatory effects on visual word recognition as a parafoveal preview before a saccade, although such effects appear to be stronger in the latter case.
An integrative proteomics approach identifies tyrosine kinase KIT as a novel therapeutic target for SPINK1-positive prostate cancer
Authors: Manzar Nishat , Khan Umar Khalid , Goel Ayush , Carskadon Shannon , Gupta Nilesh , Palanisamy Nallasivam , Ateeq Bushra
Published: July 2023

Elevated Serine Peptidase Inhibitor, Kazal type 1 (SPINK1) levels in ∼10-25% of prostate cancer (PCa) patients associate with aggressive phenotype, for which there are limited treatment choices and dismal clinical outcomes. Using an integrative proteomics approach involving label-free phosphoproteome and proteome profiling, we delineated the downstream signaling pathways involved in SPINK1-mediated tumorigenesis in PCa, and identified tyrosine kinase KIT as a highly enriched kinase. Furthermore, high to moderate levels of KIT expression was detected in ∼85% of SPINK1-positive PCa specimens. KIT signaling regulates SPINK1-associated oncogenesis, and treatment with KIT inhibitor reduces tumor growth and distant metastases in preclinical mice models. Mechanistically, KIT signaling modulates WNT/β-catenin pathway and confers stemness-related features in PCa. Notably, inhibiting KIT signaling restores AR/REST levels, forming a feedback loop enabling SPINK1 repression. Overall, we uncover the role of KIT signaling downstream of SPINK1 in maintaining lineage plasticity and provide new treatment modalities for advanced-stage SPINK1-positive subtype.
The evolution of competitive effectiveness and tolerance in populations ofDrosophila melanogasteradapted to chronic larval crowding at varying combinations of egg number and food volume
Authors: Venkitachalam Srikant , Temura Chinmay , Kokile Ramesh , Joshi Amitabh
Published: July 2023

The theory of density-dependent selection posits that genotypic fitness can vary depending on the population density. Several long-term selection experiments on outbred populations ofDrosophilaadapted to chronically high larval densities have shown that the most common evolutionary response of such rearing is an increase in larval competitive ability. Some authors have proposed that a better understanding of the evolution of competitive ability can be achieved by its partitioning into effectiveness and tolerance components. Effectiveness is the amount of competitive inhibition imposed by a competitor on another, whereas tolerance is the degree to which a competitor can withstand inhibition. In this study, we have explored the evolution of effectiveness and tolerance components of competitive ability using three sets of outbred populations ofD.melanogasteradapted to chronic larval crowding at different respective combinations of egg number, food volume and container dimensions. Effectiveness and tolerance were found to be dependent on the particular selection regime, the starting food amount and the trait used as the outcome of competition. Eclosion, dry biomass and dry weight per fly distributions over time indicated that competitive ability can also express itself in a time-dependent manner. The results suggest that larval competition and the evolution of competitive ability inDrosophilaare extremely nuanced.
Coordinated interplay between palmitoylation, phosphorylation and SUMOylation regulates kainate receptor surface expression
Authors: Yucel Busra P. , Al Momany Enaam M. , Evans Ashley J. , Seager Richard , Wilkinson Kevin A. , Henley Jeremy M.
Published: July 2023

Kainate receptors (KARs) are key regulators of neuronal excitability and synaptic transmission. KAR surface expression is tightly controlled in part by post-translational modifications (PTMs) of the GluK2 subunit. We have shown previously that agonist activation of GluK2-containing KARs leads to phosphorylation of GluK2 at S868, which promotes subsequent SUMOylation at K886 and receptor endocytosis. Furthermore, GluK2 has been shown to be palmitoylated. However, how the interplay between palmitoylation, phosphorylation and SUMOylation orchestrate KAR trafficking remains unclear. Here, we used a library of site-specific GluK2 mutants to investigate the interrelationship between GluK2 PTMs, and their impact on KAR surface expression. We show that GluK2 is basally palmitoylated and that this is decreased by kainate stimulation. Moreover, a non-palmitoylatable GluK2 mutant (C858/C871A) shows enhanced S868 phosphorylation and K886 SUMOylation under basal conditions and is insensitive to KA-induced internalisation. These results indicate that GluK2 palmitoylation contributes to stabilising KAR surface expression and that dynamic depalmitoylation promotes downstream phosphorylation and SUMOylation to mediate activity-dependent KAR endocytosis.

Significance Statement

Post-translational modifications (PTMs) are biochemical switches that control substrate protein properties and interactions. In consequence, PTMs are critical regulators of essentially all cellular pathways and are vital for eukaryotic cell survival. In the brain, among other roles, PTMs influence neuronal growth, differentiation, synaptic activity and plasticity. Kainate receptors (KARs) play core roles in all these processes and previous work has shown that the GluK2 subunit of KARs is subject to multiple PTMs. Here, using GluK2 as an exemplar protein, we delineate the sequence, coordination, and consequences of the PTMs palmitoylation, phosphorylation and SUMOylation on KAR surface expression. Our data show how the complex interplay between PTMs dynamically regulates synaptic proteins and neuronal function.
Inflammation plays a critical role in damage to the bronchiolar epithelium induced byTrueperella pyogenes in vitroandin vivo
Authors: Qin Lei , Meng Fandan , He Haijuan , Li Siqi , Zhang Hongliang , Sun Yuan , Zhang Wenlong , An Tongqing , Cai Xuehui , Wang Shujie
Published: July 2023

Trueperella pyogenescan cause severe pulmonary disease in swine, but the mechanism of pathogenesis is not well defined.T. pyogenes-induced damage to porcine bronchial epithelial cells (PBECs), porcine precision-cut lung slices (PCLS) and respiratory epithelium of mice remains unknown. In this study, we usedT. pyogenes20121 to infect PBECs in air-liquid interface conditions and porcine PCLS.T. pyogenescould adhere to, colonize and induce cytotoxic effect on PBECs and the luminal surface of bronchi in PCLS, which damaged the bronchiolar epithelium. Moreover, bronchiolar epithelial cells showed extensive degeneration in infected mice lungs. Furthermore, western blot showed the NOD-like receptor (NLR)/ C-terminal caspase recruitment domain (ASC)/caspase-1 axis and nuclear factor-kappa B (NF-κB) pathway were involved in inflammation in PCLS and lungs of mice, which also confirms PCLS provide a platform to analyze pulmonary immune response. Meanwhile, the levels of p-c-Jun N-terminal kinase (JNK), p-extracellular signal-regulated kinase (ERK) and p-protein kinase B (AKT) were increased significantly, which indicated the mitogen-activated protein kinase (MAPK) and Akt pathways were also involved of inflammation inT. pyogenes-infected mice. In addition, we usedT. pyogenes20121 to infect tumour necrosis factor alpha (TNF-α)-/-mice, the results indicated apoptosis and injury in respiratory epithelium of infected TNF-α-/-mice were alleviated. Thus, pro-inflammatory cytokine TNF-α played a role in apoptosis and respiratory epithelium injury of mice lungs. Collectively, our study provides an insight into the inflammatory injury induced byT. pyogenes, and suggests that blocking NLR or TNF-α may be a potential therapeutic strategy againstT. pyogenesinfection.
Changes in dorsomedial striatum activity mediate expression of goal-directed vs. habit-like cue-induced cocaine seeking
Authors: Bender Brooke N. , Stringfield Sierra J. , Torregrossa Mary M.
Published: July 2023

A preclinical model of cue exposure therapy, cue extinction, reduces cue-induced cocaine seeking when drug seeking is goal-directed but not habitual. Goal-directed and habitual behaviors differentially rely on the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), but the effects of cue extinction on dorsal striatal responses to cue-induced drug seeking are unknown. We used fiber photometry to examine how dorsal striatal intracellular calcium and extracellular dopamine activity differs between goal-directed and habitual cue-induced cocaine seeking and how it is impacted by cue extinction. Rats trained to self-administer cocaine paired with an audiovisual cue on schedules of reinforcement that promote goal-directed or habitual cocaine seeking had different patterns of dorsal striatal calcium and dopamine responses to cue-reinforced lever presses. Cue extinction reduced calcium and dopamine responses during subsequent drug seeking in the DMS, but not in the DLS. Therefore, cue extinction may reduce goal-directed behavior through its effects on the DMS, whereas habitual behavior and the DLS are unaffected.
The ecological consequences of microbial metabolic strategies in fluctuating environments
Authors: Wang Zihan , Goyal Akshit , Maslov Sergei
Published: July 2023

Microbes adopt a variety of metabolic strategies to consume resources in fluctuating environments, but most work has focused on understanding these strategies in the context of isolated species, rather than diverse natural communities. We systematically measure the feasibility, dynamical and structural stability of multispecies microbial communities adopting different metabolic strategies. Our results reveal key distinctions between the ecological properties of different metabolic strategies, showing that communities containing sequential utilizers are more resilient to resource fluctuations, but are less feasible than co-utilizing communities.
The effect of intercellular medium salinity on the dielectric constant of cell membranes and the excitation thresholds of the action potential
Authors: Shneider M. N. , Pekker M.
Published: July 2023

A mechanism for axon swelling and subsequent compression in the area of action potential passage is considered. It is shown that the dynamics of changes in the radius of the axon during the passage of the action potential can be explained by changes in osmotic pressure. Axon swelling occurs at the leading edge of the action potential when Na+ions flow from the extracellular electrolyte into the intracellular space, and subsequent compression occurs at the trailing edge during the ejection of K+ions. The change in dielectric constant of the axon membrane is also discussed, and a possible explanation for the decrease in the excitation threshold of the action potential with an increase in salinity of the external electrolyte is proposed.
Mechano-dependent sorbitol accumulation supports biomolecular condensate
Authors: Torrino Stephanie , Oldham William M , Tejedor Andrés R , Burgos Ignacio S. , Rachedi Nesrine , Fraissard Kéren , Chauvet Caroline , Sbai Chaima , O’Hara Brendan P. , Abélanet Sophie , Brau Frederic , Clavel Stephan , Collepardo-Guevara Rosana , Espinosa Jorge R. , Ben-Sahra Issam , Bertero Thomas
Published: July 2023

Biomolecular condensates regulate a wide range of cellular functions from signaling to RNA metabolism1, 2, yet, the physiologic conditions regulating their formation remain largely unexplored. Biomolecular condensate assembly is tightly regulated by the intracellular environment. Changes in the chemical or physical conditions inside cells can stimulate or inhibit condensate formation3–5. However, whether and how the external environment of cells can also regulate biomolecular condensation remain poorly understood. Increasing our understanding of these mechanisms is paramount as failure to control condensate formation and dynamics can lead to many diseases6, 7. Here, we provide evidence that matrix stiffening promotes biomolecular condensationin vivo. We demonstrate that the extracellular matrix links mechanical cues with the control of glucose metabolism to sorbitol. In turn, sorbitol acts as a natural crowding agent to promote biomolecular condensation. Usingin silicosimulations andin vitroassays, we establish that variations in the physiological range of sorbitol, but not glucose, concentrations, are sufficient to regulate biomolecular condensates. Accordingly, pharmacologic and genetic manipulation of intracellular sorbitol concentration modulates biomolecular condensates in breast cancer – a mechano-dependent disease. We propose that sorbitol is a mechanosensitive metabolite enabling protein condensation to control mechano-regulated cellular functions. Altogether, we uncover molecular driving forces underlying protein phase transition and provide critical insights to understand the biological function and dysfunction of protein phase separation.
Dynamics of Collagen Oxidation and Cross Linking in Regenerating and Irreversibly Infarcted Myocardium
Authors: Akam Eman A. , Bergemann David , Ridley Sterling J. , To Samantha , Andrea Brittany , Moon Brianna , Ma Hua , Zhou Yirong , Aguirre Aaron , Caravan Peter , Gonzalez-Rosa Juan Manuel , Sosnovik David E.
Published: July 2023

In mammalian hearts myocardial infarction produces a permanent collagen-rich scar. Conversely, in zebrafish a collagen-rich scar forms but is completely resorbed as the myocardium regenerates. The formation of cross-links in collagen hinders its degradation but cross-linking has not been well characterized in zebrafish hearts. Here, a library of fluorescent probes to quantify collagen oxidation, the first step in collagen cross-link (CCL) formation, was developed. Myocardial injury in mice or zebrafish resulted in similar dynamics of collagen oxidation in the myocardium in the first month after injury. However, during this time, mature CCLs such as pyridinoline and deoxypyridinoline developed in the murine infarcts but not in the zebrafish hearts. High levels of newly oxidized collagen were still seen in murine scars with mature CCLs. These data suggest that fibrogenesis remains dynamic, even in mature scars, and that the absence of mature CCLs in zebrafish hearts may facilitate their ability to regenerate.
pHusion: A robust and versatile toolset for automated detection and analysis of exocytosis
Authors: O’Shaughnessy Ellen C. , Lam Mable , Ryken Samantha E. , Wiesner Theresa , Lukasik Kimberly , Zuchero Bradley J , Leterrier Christophe , Adalsteinsson David , Gupton Stephanie L.
Published: July 2023

Exocytosis is a fundamental process used by eukaryotic cells to regulate the composition of the plasma membrane and facilitate cell-cell communication. To investigate the role exocytosis plays in neuronal morphogenesis, previously we developed computational tools with a graphical user interface (GUI) to enable the automatic detection and analysis of exocytic events (ADAE GUI) from fluorescence timelapse images. Though these tools have proven useful, we found that the code was brittle and not easily adapted to different experimental conditions. Here, we have developed and validated a robust and versatile toolkit, named pHusion, for the analysis of exocytosis written in ImageTank, a graphical programming language that combines image visualization and numerical methods. We tested this method using a variety of imaging modalities and pH-sensitive fluorophores, diverse cell types, and various exocytic markers to generate a flexible and intuitive package. Using pHusion, we show that VAMP3-mediated exocytosis occurs 30-times more frequently in melanoma cells compared with primary oligodendrocytes, that VAMP2-mediated fusion events in mature rat hippocampal neurons are longer lasting than those in immature murine cortical neurons, and that exocytic events are clustered in space yet random in time in developing cortical neurons.

Summary Statement

Exocytosis is an essential process by which cells change shape, alter membrane composition, and communicate with other cells. Though all eukaryotic cells carry out exocytosis, the regulation of vesicle fusion, the cargo of vesicles, and the role exocytosis plays in cell fate differ greatly across cell types. Here, we developed a flexible and robust set of tools to enable automatic identification and analysis of exocytic events across a wide range of cell types, vesicle types, and imaging conditions.
CST–Polα/Primase: the second telomere maintenance machine
Authors: Cai Sarah W. , de Lange Titia
Published: July 2023

It has been known for decades that telomerase extends the 3′ end of linear eukaryotic chromosomes and dictates the telomeric repeat sequence based on the template in its RNA. However, telomerase does not mitigate sequence loss at the 5′ ends of chromosomes, which results from lagging strand DNA synthesis and nucleolytic processing. Therefore, a second enzyme is needed to keep telomeres intact: DNA polymerase α/Primase bound to Ctc1–Stn1–Ten1 (CST). CST–Polα/Primase maintains telomeres through a fill-in reaction that replenishes the lost sequences at the 5′ ends. CST not only serves to maintain telomeres but also determines their length by keeping telomerase from overelongating telomeres. Here we discuss recent data on the evolution, structure, function, and recruitment of mammalian CST–Polα/Primase, highlighting the role of this complex and telomere length control in human disease.
Urban resilience for sustainable homeownership: the role of self-help in the ancient city of Benin, Nigeria
Authors: Ebekozien Andrew , Aigbavboa Clinton , Samsurijan Mohamad Shaharudin , Salman Ahmad , Amadi Godspower C.
Published: July 2023

Purpose

The organised self-help approach successfully enhances urban low-income earners' (LIE) homeownership in some developing countries. The technique can enhance urban resilience for sustainable LIE homeownership. There is a paucity of studies concerning sustainable homeownership for Nigeria's urban LIE through a self-help approach. The study investigated the housing needs of the urban LIE via organised self-help mechanisms and how the same can enhance urban resilience for sustainable homeownership in the Ancient City of Benin, Nigeria.

Design/methodology/approach

Given the unexplored nature of the issue, 20 face-to-face interviews were conducted with experts and analysed through a thematic approach.

Findings

Findings identified eleven main barriers faced by the urban LIE. This includes the absence of government housing policy, funding frameworks, urban land scarcity, high property development costs, naira devaluation, high-interest rates, inflation, bribery and corruption, lax mortgage sub-sector, high cost of infrastructure, and government bureaucracy.

Originality/value

This study will contribute to pioneering the role of organised self-help mechanisms in urban resilience for sustainable LIE homeownership in developing cities via a qualitative approach. Also, findings would significantly contribute to developing countries' sustainable housing and urban resilience literature.
Generations and the Future of Work: case study exploration of Business Stakeholder perspectives on Zillennials in the Northern Irish workplace
Authors: Moffett Stephanie Gabrielle , Bradley Laura , Hampton Alison , McGowan Pauric
Published: July 2023

Purpose

This research aims to better understand the Zillennial Generation within the workplace, specifically using the perspectives of Business Stakeholders within the context of Northern Ireland. Understanding the perceptions of Zillennials in the workplace is important due to their growing numbers and subsequent impact on the future of work.

Design/Methodology/Approach

A case study approach is used to gain a deeper understanding of stakeholder opinions and experiences of Zillennials. The authors draw on extant research and use semi-structured interviews to explore the experiences and views of stakeholders within three case firms employing Zillennials.

Findings

The study concludes that discrepancies can be seen between Zillennial performance and behaviour, compared with Business Stakeholder workplace expectations. Findings suggest that according to Business Stakeholders observations, Zillennials display some, but not all, attributes of Generation Z and Millennials. Business Stakeholders observations also reveal that Zillennials demonstrate some, but not all, entrepreneurial behaviours and competencies.

Originality/Value

While many studies focus on both Generation Z and Millennials, research focused on unique cusp generations is limited. No research has been conducted that investigates the perception of Zillennials within the context of Northern Ireland.
Investigating building information modelling (BIM) and lean construction: the potential BIM-lean interactions synergy and integration in the Jordanian construction industry
Authors: Aburumman Mohammad Omar , Sweis Rateb , Sweis Ghaleb J.
Published: July 2023

Purpose

The construction industry sector is developing rapidly, especially with the increasing pace of the Fourth Industrial Revolution in this sector. Construction projects can benefit from greater integration and collaboration between their technologies and processes to reap the advantages and keep pace with the recent significant technological and managerial techniques developments. Therefore, this study aims to delve into and investigate building information modeling (BIM) and Lean Construction (L.C.) with a concentration on the potential BIM–lean interactions synergy and integration in the Jordanian construction industry.

Design/methodology/approach

This study takes exploratory nature, followed by the deductive research approach, and is designed to be a mono-quantitative research methodology. Moreover, the sampling technique is non-probability convenience sampling, and the research strategy is implemented through a questionnaire used and analyzed by using Statistical Package for Social Science to conduct descriptive and inferential statistical analysis and verify the reliability and validity through proper tests.

Findings

The BIM–lean interactions synergy and integration findings revealed that eliminating waste (time, cost, resources), promoting continuous improvement (Kaizen) and standardizing as lean construction principles are the most significant and agreeable toward achieving BIM–lean interactions synergy. On the other hand, “High 3D Visualization Modelling” was the most significant BIM function, followed by “Rapid and Auto-Generation of Documents and Multiple Design Alternatives” and “Maintenance of Information and Design Model Integrity.” Moreover, based on the relative importance index (RII) values, “Lack of Technical Expertise in BIM-LEAN” is the most significant challenge with a 0.89 value of RII, followed by “Lack of Government Direction and Standard Guidelines” with a 0.88 value of RII and “Financial considerations” with a 0.83 value of RII.

Originality/value

This study will help provide a new detailed overview that investigates the effects and expected benefits of integrating BIM processes and technological functionalities with lean construction principles within a synergetic environment. Moreover, the study will increase the awareness of using new technologies and management approaches in the architectural, engineering and construction industry, seeking to achieve integration between these technologies to reach ideal results in terms of the outputs of construction operations.
The structural link between TQM practices and financial performance: the mediating role of operational performance
Authors: Adem Mulugeta Kebede , Virdi Sandeep Singh
Published: July 2023

Purpose

This study aims at examining the effect of total quality management (TQM) practices on the financial performance ISO 9001:2008 certified manufacturing companies in Ethiopia with a mediating role of operational performance.

Design/methodology/approach

A cross-sectional survey research was conducted to meet the purpose. Data used for the study were solely primary data and were collected from the top and middle-level managers of different departments and senior experts working under the production/operation and quality management units of the target organizations. Data were obtained from 302 participants working in 73 companies using a self-administered questionnaire. Structural equation modelling (SEM) technique was applied to test the hypotheses positing the structural link between TQM practices, operational performance and financial performance.

Findings

The findings show that TQM practices had a significant direct and positive effect on both operational performance and financial performance and that operational performance significantly affects financial performance. The bootstrapping output of the mediation analysis also established that operational performance partially mediates the causal link between TQM practices and financial performance.

Research limitations/implications

The empirical evidence provided by the present study provides helpful insights and guidance to managers to make a good deal of investment in maintaining enhanced performance outcomes under the operations stream that eventually would lead to better financial outcome.

Originality/value

Being one of the first attempts to empirically examine the structural linkages among TQM practices, operational performance and financial performance in Ethiopian manufacturing organizations, this paper provides strategic insights on the importance of implementing TQM practices in a holistic manner for the achievement of better performance outcomes.