bluuebunny/crossref_metadata_2025 huggingface dataset:
Migration and Urbanization Trends and Family Wellbeing in Canada: A Focus on Disability and Indigenous Issues
Authors: Hilbrecht Margo , Keating Norah
Published: January 2024

Discussions of migration and urbanization in Canada and many other nations typically focus on the experiences of individuals. By doing so, the importance of their family relationships and circumstances may be overlooked. A failure to account for broader family networks has wellbeing consequences for both the people who migrate and/or move to urban locations and their family members who have stayed behind. Beyond the individual-level focus, policies related to migration are usually developed as population-level initiatives. This means that families that are considered vulnerable or at-risk due to certain health and/or demographic factors can remain unnoticed and their special needs unaccounted for. The experiences of these families during migration and urbanization merit greater attention so that policy makers and support services can ensure more equitable opportunities and better family wellbeing outcomes. This paper explores migration and urbanization in Canada in relation to family wellbeing with attention to two at-risk population groups: families with a member who has a disability and families that identify as Indigenous. Both groups experience exclusion, that is, systematic actions resulting in being overlooked, ignored, and at-risk. Indigenous families have endured a long history of colonialism, racism, and oppression (Saul, 2014), resulting in a legacy of grievous harm to families and the chronic underfunding of support services such as healthcare, housing, and child welfare (Government of Canada, 2018a; Truth and Reconciliation Commission of Canada, 2015). Families in which there is a member with a disability1 require ready access to affordable healthcare and related services to ensure appropriate support, which is linked to the wellbeing of all family members.
DESIGN OF SOLAR ENERGY-BASED ESSENTIAL OIL DISTILLATION DEVICE USING PHOTOVOLTAIC METHOD AS A SOURCE OF ELECTRICITY FOR HEATER
Authors: Prayogi M.akbar , Hafidh Muhammad
Published: January 2024

In this study, we tried to design a distillation device using a solar cell to generate electricity which would later be used as a heating source. The highest yield obtained was 21.58% by distillation for 6 hours and 4 days of drying time. The highest patchouli oil density value was obtained at 4 days of drying time with 6 hours of operating time. While the lowest density value of Patchouli oil was obtained at 2 days of drying time at 6 hours of operating time. From the results of the analysis using GC-MS showed the presence of identified chemical compounds including azulene, seychellene and several other compounds, based on the GC-MS results obtained 31.75% patcholi alcohol, and 20.50% azulene. According to International Market Standards, patchouli alcohol content should be higher than 30%, therefore this material meets the Indonesian National Standard (SNI) and besides that the physical and chemical properties of Patchouli oil are produced from the distillation process by utilizing sunlight using solar cells (photovoltaic). From these results it can be seen that the Patchouli oil that has been produced during this research can be sold in the market because it meets the Indonesian National Standard.
THE EFFECT OF CHITOSAN ADDITION ON ECO-FRIENDLY PLASTIC BASED ON PLAPCL
Authors: Alfatasya Dinda , Habsah Nurul
Published: January 2024

Research on making eco-friendly plastic has been developed because it is environmentally friendly and renewable. In this research, the manufacture of eco-friendly plastic from Polylactic Acid ( PLA) and Polycaprolactone ( PCL) with the addition of chitosan as a filler . The purpose of this study was to study and determine the effect of mixing variations in chitosan composition PLA on PCL the mechanical properties of eco-friendly plastics using a hot press at 2000C for 1 hour. The variations of PLA/ PCL are 2/8 g, 3/7 g, 5/5 g, 7/3 g and 8/2 g while the composition of chitosan is 0,2 g, 0,3 g, 0,4 g, 0,5 gand 0,6 g. The characteristics of eco-friendly plastics can be seen from the biodegradation test, tensile strength test, elongation test, functional group test and plastic film morphology test. The results of the characterization of eco-friendly plastics with optimal performance were the composition PLA/PCLChitosan 8/2/0.6 gram yielded 38.8% for the biodegradation test, the tensile strength value was 42.53 MPa, the elongation percentage was 6.96%. While the functional groups contained are the N – H, C – H, C = O and C – O groups. The results of the identification of the functional groups show that no new functional groups are formed, but only a mixing process without any reaction on the constituent materials. Based on the morphological test results showed that the sample has a smooth surface. However, there is still insoluble chitosan because the mixing process is not homogeneous.
A Comprehensive Review and Investigation of Business Models
Authors: Lee Alvin
Published: January 2024

The formulation and execution of a business model significantly influence the achievement and durability of a company. The business model serves as a strategic framework encompassing components such as value proposition, revenue streams, market segmentation, and core operations. Companies must possess a profound comprehension of the crucial components within their business models due to the constantly evolving and intricate nature of the business environment. Market dynamics, technological advancements, and shifts in customer behavior are influential elements in the evolution of company concepts. The value proposition is the primary factor in determining why customers should select a company's products or services. The analysis of business models highlights the significance of establishing distinctive characteristics and advantages that offer additional value to customers. Market analysis and client segmentation assist organizations in comprehending customer requirements and inclinations. Customizing marketing strategies and product offers for each market group is an essential step towards attaining increased relevance and attractiveness. Research on business models emphasizes the significance of expanding revenue streams and effectively handling risk. Companies should evaluate several pricing strategies and income streams in order to enhance their ability to respond to market fluctuations. Cost analysis and operational efficiency are crucial factors in defining a business's cost-competitiveness. Companies can enhance efficiency by identifying opportunities for improvement through a thorough understanding of the fundamental activities that underpin their business model. Utilizing technology and innovation is crucial for sustaining competitiveness and staying relevant. Enterprises must consistently seek opportunities to enhance operational procedures, create novel offerings, and adjust to technological advancements.
Analysis and Study of Candlestick Indicators in Stock Trading
Authors: Mardianti Nayla
Published: January 2024

Candlestick analysis is an invaluable tool in technical analysis for understanding stock price movements. Candlesticks provide a clear visual representation of changes in stock prices over a certain period of time. The color and shape of the candlesticks provide a direct indication of buyer and seller sentiment. A series of candlesticks with continuously light colored bodies indicates an uptrend, while continuously dark colored bodies indicate a downtrend. This helps traders identify the direction of overall price movement. Candlestick patterns, such as doji, engulfing, harami, and others, provide signals about potential changes in price direction or trend continuation. Traders can use these patterns in conjunction with other factors to make better trading decisions. The length of the candlestick's shadow or wick gives an indication of market volatility. A long shadow indicates high volatility or significant movement during that period. Although candlestick analysis provides valuable insight, wise risk management remains the key to success in stock trading. Trading decisions should be based on comprehensive analysis and a deep understanding of market conditions. By combining candlestick analysis with other analytical tools, as well as implementing good risk management, traders can increase their chances of success and make more informed decisions in the dynamic stock market.
Les contraintes, un a priori, des droits : tentative de mise en oeuvre d’une démarche antécédente
Authors: Bergé Jean-Sylvestre
Published: January 2024

Le droit entretient des liens étroits avec l’idée de contrainte. Une théorie des contraintes juridiques a même été proposée. Il s’est agi de caractériser la contrainte d’un point de vue strictement interne au droit. Cette contribution propose d’envisager une démarche qualifiée « d’antécédente ». Cette démarche consiste schématiquement à sortir du droit pour tenter de mieux y revenir. Le résultat de sa mise en œuvre pourrait alors être le suivant : les contraintes s’analysent comme un a priori des différentes formes de droits.
Special types of morphisms in the category C_{R-IFM}
Authors:   Department of Mathematics, D.A.V. College, Sharma P. K. , Chandni  ,   Lovely Professional University, Bharadwaj Nitin ,   Lovely Professional University
Published: January 2024

The aim of this paper is to introduce two special type of morphisms, namely Retraction and Coretraction in the category (CR-IFM) of intuitionistic fuzzy modules. We obtain the condition under which a morphism in CR-IFM, that is an intuitionistic fuzzy R-homomorphism, to be a retraction or a coretraction. Then, we acquire some equivalent statements for these two morphisms. Further, we study free, projective and injective objects in CR-IFM and establish their relation with morphism in CR-IFM and retraction, coretraction.
DNA damage signaling in Drosophila macrophages modulates systemic cytokine levels in response to oxidative stress
Authors: Hersperger Fabian , Meyring Tim , Weber Pia , Chhatbar Chintan , Monaco Gianni , Dionne Marc S , Paeschke Katrin , Prinz Marco , Groß Olaf , Classen Anne-Kathrin , Kierdorf Katrin
Published: January 2024

Environmental factors, infection, or injury can cause oxidative stress in diverse tissues and loss of tissue homeostasis. Effective stress response cascades, conserved from invertebrates to mammals, ensure reestablishment of homeostasis and tissue repair. Hemocytes, the Drosophila blood-like cells, rapidly respond to oxidative stress by immune activation. However, the precise signals how they sense oxidative stress and integrate these signals to modulate and balance the response to oxidative stress in the adult fly are ill-defined. Furthermore, hemocyte diversification was not explored yet on oxidative stress. Here, we employed high-throughput single nuclei RNA-sequencing to explore hemocytes and other cell types, such as fat body, during oxidative stress in the adult fly. We identified distinct cellular responder states in plasmatocytes, the Drosophila macrophages, associated with immune response and metabolic activation upon oxidative stress. We further define oxidative stress-induced DNA damage signaling as a key sensor and a rate-limiting step in immune-activated plasmatocytes controlling JNK-mediated release of the pro-inflammatory cytokine unpaired-3. We subsequently tested the role of this specific immune activated cell stage during oxidative stress and found that inhibition of DNA damage signaling in plasmatocytes, as well as JNK or upd3 overactivation, result in a higher susceptibility to oxidative stress. Our findings uncover that a balanced composition and response of hemocyte subclusters is essential for the survival of adult Drosophila on oxidative stress by regulating systemic cytokine levels and cross-talk to other organs, such as the fat body, to control energy mobilization.
Identification of 1600 replication origins in S. cerevisiae
Authors: Foss Eric J. , Lichauco Carmina , Gatbonton-Schwager Tonibelle , Gonske Sara J. , Lofts Brandon , Lao Uyen , Bedalov Antonio
Published: January 2024

There are approximately 500 known origins of replication in the yeast genome, and the process by which DNA replication initiates at these locations is well understood. In particular, these sites are made competent to initiate replication by loading of the Mcm replicative helicase prior to the start of S phase; thus, “a site to which MCM is bound in G1” might be considered to provide an operational definition of a replication origin. By fusing a subunit of Mcm to micrococcal nuclease, a technique referred to as “Chromatin Endogenous Cleavage”, we previously showed that known origins are typically bound by a single Mcm double hexamer, loaded adjacent to the ARS consensus sequence (ACS). Here we extend this analysis from known origins to the entire genome, identifying candidate Mcm binding sites whose signal intensity varies over at least 3 orders of magnitude. Published data quantifying the production of ssDNA during S phase showed clear evidence of replication initiation among the most abundant 1600 of these sites, with replication activity decreasing in concert with Mcm abundance and disappearing at the limit of detection of ssDNA. Three other hallmarks of replication origins were apparent among the most abundant 5,500 sites. Specifically, these sites (1) appeared in intergenic nucleosome-free regions that were flanked on one or both sides by well-positioned nucleosomes; (2) were flanked by ACSs; and (3) exhibited a pattern of GC skew characteristic of replication initiation. Furthermore, the high resolution of this technique allowed us to demonstrate a strong bias for detecting Mcm double-hexamers downstream rather than upstream of the ACS, which is consistent with the directionality of Mcm loading by Orc that has been observed
in vitro
. We conclude that, if sites at which Mcm double-hexamers are loaded can function as replication origins, then DNA replication origins are at least 3-fold more abundant than previously assumed, and we suggest that replication may occasionally initiate in essentially every intergenic region. These results shed light on recent reports that as many as 15% of replication events initiate outside of known origins, and this broader distribution of replication origins suggest that S phase in yeast may be less distinct from that in humans than is widely assumed.
Analysis of NIH K99/R00 Awards and the Career Progression of Awardees
Authors: Woitowich Nicole C , Hengel Sarah R , Solis Christopher , Vilgalys Tauras P , Babdor Joel , Tyrrell Daniel J
Published: January 2024

Many postdoctoral fellows and scholars who hope to secure tenure-track faculty positions in the United States apply to the National Institutes of Health (NIH) for a Pathway to Independence Award. This award has two phases (K99 and R00) and provides funding for up to five years. Using NIH data for the period 2006-2022, we report that ∼230 K99 awards were made every year, representing up to ∼$250 million annual investment. About 40% of K99 awardees were women and ∼89% of K99 awardees went on to receive an R00 award annually. Institutions with the most NIH funding produced the most recipients of K99 awards and recruited the most recipients of R00 awards. The time between a researcher starting an R00 award and receiving a major NIH award (such as an R01) ranged between 4.6 and 7.4 years, and was significantly longer for women, for those who remained at their home institution, and for those hired by an institution that was not one of the 25 institutions with the most NIH funding. Shockingly, there has yet to be a K99 awardee at a historically Black college or university. We go on to show how K99 awardees flow to faculty positions, and to identify various factors that influence the future success of individual researchers and, therefore, also influence the composition of biomedical faculty at universities in the US.
Tailoring Tfh Profiles Enhances Antibody Persistence to a Clade C HIV-1 Vaccine in Rhesus Macaques
Authors: Verma Anil , Hawes Chase E , Elizaldi Sonny R , Smith Justin C. , Rajasundaram Dhivyaa , Pedersen Gabriel Kristian , Shen Xiaoying , Williams LaTonya D , Tomaras Georgia D. , Kozlowski Pamela A. , Amara Rama R. , Iyer Smita S.
Published: January 2024

CD4 T follicular helper cells (T
fh
) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into T
fh
subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the T
fh
profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a T
fh
1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and T
fh
polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) T
fh
1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA)+QS-21 adjuvant predominantly induced GC T
fh
1 cells. While the generation of GC T
fh
1/17 cells with CAF01 and GC T
fh
1 cells with MPLA+QS-21 induced comparable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml-MPLA; 5500; CAF01, 2155; p <0.05). Notably, interferon γ+ Env-specific T
fh
responses were consistently higher with gp140 in MPLA+QS-21 and positively correlated with Env antibody persistence. These findings suggest that vaccine platforms maximizing GC T
fh
1 induction promote persistent Env antibodies, important for protective immunity against HIV.
Neuroendocrine Gene Expression Coupling of Interoceptive Bacterial Food Cues to Foraging Behavior of C. elegans
Authors: Boor Sonia A. , Meisel Joshua D. , Kim Dennis H.
Published: January 2024

Animal internal state is modulated by nutrient intake, resulting in behavioral responses to changing food conditions. The neural mechanisms by which internal states are generated and maintained are not well understood. Here, we show that in the nematode
Caenorhabditis elegans,
distinct cues from bacterial food – interoceptive signals from the ingestion of bacteria and gustatory molecules sensed from nearby bacteria – act antagonistically on the expression of the neuroendocrine TGF-beta ligand DAF-7 from the ASJ pair of sensory neurons to modulate foraging behavior. A positive-feedback loop dependent on the expression of
daf-7
from the ASJ neurons acts to promote transitions between roaming and dwelling foraging states and influence the persistence of roaming states. SCD-2, the
C. elegans
ortholog of mammalian Anaplastic Lymphoma Kinase (ALK), which has been implicated in the central control of metabolism of mammals, functions in the AIA interneurons to regulate foraging behavior and cell-non-autonomously control the expression of DAF-7 from the ASJ neurons. Our data establish how a dynamic neuroendocrine
daf-7
expression feedback loop regulated by SCD-2 functions to couple sensing and ingestion of bacterial food to foraging behavior. We further suggest that this neuroendocrine feedback loop underlies previously characterized exploratory behaviors in
C. elegans
. Our data suggest that the expression of
daf-7
from the ASJ neurons contributes to and is correlated with an internal state of “unmet need” that regulates exploratory foraging behavior in response to bacterial cues in diverse physiological contexts.
The delayed kinetics of Myddosome formation explains why amyloid-beta aggregates trigger Toll-like receptor 4 less efficiently than lipopolysaccharide
Authors: Li Bing , Suresh Prasanna , Brelstaff Jack , Kedia Shekhar , Bryant Clare E , Klenerman David
Published: January 2024

The Myddosome is a key innate immune signalling platform. It forms at the cell surface and contains MyD88 and IRAK proteins which ultimately coordinate the production of pro-inflammatory cytokines. Toll-like receptor 4 (TLR4) signals via the Myddosome when triggered by lipopolysaccharide (LPS) or amyloid-beta (Aβ) aggregates but the magnitude and time duration of the response are very different for reasons that are unclear. Here, we followed the formation of Myddosomes in live macrophages using local delivery of TLR4 agonist to the cell surface and visualisation with 3D rapid light sheet imaging. This was complemented by super-resolution imaging of Myddosomes in fixed macrophages to determine the size of the signalling complex at different times after triggering. Myddosomes formed more rapidly after LPS than in response to sonicated Aβ 1–42 fibrils (80 vs 372 s). The mean lifetimes of the Myddosomes were also shorter when triggered by LPS compared to sonicated Aβ fibrils (170 and 220 s), respectively. In both cases, a range of Myddosome of different sizes (50–500 nm) were formed. In particular, small round Myddosomes around 100 nm in size formed at early time points, then reduced in proportion over time. Collectively, our data suggest that compared to LPS the multivalency of Aβ fibrils leads to the formation of larger Myddosomes which form more slowly and, due to their size, take longer to disassemble. This explains why sonicated Aβ fibrils results in less efficient triggering of TLR4 signalling and may be a general property of protein aggregates.
Caspase-1 activates gasdermin A in non-mammals
Authors: Billman Zachary P. , Kovacs Stephen B. , Wei Bo , Kang Kidong , Cissé Ousmane H. , Miao Edward A.
Published: January 2024

Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles and birds gave rise to GSDMA-D in mammals. Uniquely in our tree, amphibian, reptile and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals.We demonstrate that amphibians, reptiles and birds engage pyroptosis using caspase-1 and GSDMA, filling an evolutionary gap in which caspase-1 cleaves GSDME in fish and GSDMD in mammals.
Antimicrobial activity of iron-depriving pyoverdines against human opportunistic pathogens
Authors: Vollenweider Vera , Rehm Karoline , Chepkirui Clara , Pérez-Berlanga Manuela , Polymenidou Magdalini , Piel Jörn , Bigler Laurent , Kümmerli Rolf
Published: January 2024

The global rise of antibiotic resistance calls for new drugs against bacterial pathogens. A common approach is to search for natural compounds deployed by microbes to inhibit competitors. Here we show that the iron chelating pyoverdines, siderophores produced by environmental
Pseudomonas
spp., have strong antibacterial properties by inducing iron starvation and growth arrest in pathogens. A screen of 320 natural
Pseudomonas
isolates used against 12 human pathogens uncovered several pyoverdines with particularly high antibacterial properties and distinct chemical characteristics. The most potent pyoverdine effectively reduced growth of the pathogens
Acinetobacter baumannii
,
Klebsiella pneumoniae
and
Staphylococcus aureus
in a concentration- and iron-dependent manner. Pyoverdine increased survival of infected
Galleria mellonella
host larvae, and showed low toxicity for the host, mammalian cell lines, and erythrocytes. Furthermore, experimental evolution combined with whole-genome sequencing revealed reduced potentials for resistance evolution compared to an antibiotic. Thus, pyoverdines from environmental strains could become new sustainable antibacterials against human pathogens.
Tissue-resident natural killer cells support survival in pancreatic cancer through promotion of cDC1-CD8 T activity
Authors: Go Simei , Demetriou Constantinos , Valenzano Giampiero , Hughes Sophie , Lanfredini Simone , Ferry Helen , Arbe-Barnes Edward , Sivakumar Shivan , Bashford-Rogers Rachel , Middleton Mark R , Mukherjee Somnath , Morton Jennifer , Jones Keaton , Neill Eric O
Published: January 2024

The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC) prevents tumor control and strategies to restore anti-cancer immunity (i.e. by increasing CD8 T-cell activity) have had limited success. Here, we demonstrate how inducing localized physical damage using ionizing radiation (IR) unmasks the benefit of immunotherapy by increasing tissue-resident natural killer (trNK) cells that support CD8 T activity. Our data confirms that targeting mouse orthotopic PDAC tumors with IR together with CCR5 inhibition and PD1 blockade reduces E-cadherin positive tumor cells by recruiting a hypoactive NKG2D-ve NK population, phenotypically reminiscent of trNK cells, that supports CD8 T-cell involvement. We show an equivalent population in human single-cell RNA sequencing (scRNA-seq) PDAC cohorts that represents immunomodulatory trNK cells that could similarly support CD8 T-cell levels in a cDC1-dependent manner. Importantly, a trNK signature associates with survival in PDAC and other solid malignancies revealing a potential beneficial role for trNK in improving adaptive anti-tumor responses and supporting CCR5 inhibitor (CCR5i)/αPD1 and IR-induced damage as a novel therapeutic approach.
Chemotherapy activates inflammasomes to cause inflammation-associated bone loss
Authors: Wang Chun , Kaur Khushpreet , Xu Canxin , Abu-Amer Yousef , Mbalaviele Gabriel
Published: January 2024

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, doxorubicin activated the absent in melanoma (AIM2) and NLR family pyrin domain containing 3 (NLRP3) inflammasomes in macrophages and neutrophils, causing inflammatory cell death pyroptosis and NETosis, which correlated with its leukopenic effects. Moreover, the effects of this chemotherapeutic agent on cytokine secretion, cell demise, and bone loss were attenuated to various extent in conditions of AIM2 and/or NLRP3 insufficiency. Thus, we found that inflammasomes are key players in bone loss caused by doxorubicin, a finding that may inspire the development of a tailored adjuvant therapy that preserves the quality of this tissue in patients treated with this class of drugs.
A conserved cell-pole determinant organizes proper polar flagellum formation
Authors: Arroyo-Pérez Erick E , Hook John C , Alvarado Alejandra , Wimmi Stephan , Glatter Timo , Thormann Kai , Ringgaard Simon
Published: January 2024

The coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear. In this study, we discovered a novel protein called FipA that is required for normal FlhF activity and function in polar flagellar synthesis. We demonstrated that membrane-localized FipA interacts with FlhF and is required for normal flagellar synthesis in Vibrio parahaemolyticus, Pseudomonas putida, and Shewanella putrefaciens, and it does so independently of the polar localization mediated by HubP. FipA exhibits a dynamic localization pattern and is present at the designated pole before flagellar synthesis begins, suggesting its role in licensing flagellar formation. This discovery provides insight into a new pathway for regulating flagellum synthesis and coordinating cellular organization in bacteria that rely on polar flagellation and FlhF-dependent localization.
Maternal smoking DNA methylation risk score associated with health outcomes in offspring of European and South Asian ancestry
Authors: Deng Wei Q. , Cawte Nathan , Campbell Natalie , Azab Sandi M. , de Souza Russell J , Lamri Amel , Morrison Katherine M. , Atkinson Stephanie A. , Subbarao Padmaja , Turvey Stuart E. , Moraes Theo J. , Teo Koon K. , Mandhane Piush , Azad Meghan B. , Simons Elinor , Pare Guillaume , Anand Sonia S.
Published: January 2024

Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here we propose the first cord blood DNAm score to capture the epigenetic signature of maternal smoking. We first examined the association between individual CpGs and cigarette smoking during pregnancy in two White European birth cohorts (n = 763), and smoking exposure in the White European and the South Asian birth cohorts (n = 887). Several previously reported genes for maternal smoking were supported, with the strongest and most consistent signal from the
GFI1
gene (
ps
< 5×10
-5
). Leveraging previously reported CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was internally validated in one of the European-origin cohorts. This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth. The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (
p
=1.04×10
-23
) and self-reported smoking exposure (
p
=6.56×10
-8
) in White Europeans, but not with self-reported exposure (
p
> 0.05) in South Asians. The same score was consistently associated with smaller birth size (
p
=1.19×10
-6
) and lower birth weight (
p
=8.79×10
-7
) in the combined South Asian and White European cohorts. This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, even minimal smoking exposure in South Asian mothers who were not active smokers showed a DNAm signature of small body size and low birthweight in newborns.
Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B
Authors: Ballmer Daniel , Akiyoshi Bungo
Published: January 2024

The chromosomal passenger complex (CPC) is an important regulator of cell division, which shows dynamic subcellular localization throughout mitosis, including kinetochores and the spindle midzone. In traditional model eukaryotes such as yeasts and humans, the CPC consists of the catalytic subunit Aurora B kinase, its activator INCENP, and the localization module proteins Borealin and Survivin. Intriguingly, Aurora B and INCENP as well as their localization pattern are conserved in kinetoplastids, an evolutionarily divergent group of eukaryotes that possess unique kinetochore proteins and lack homologs of Borealin or Survivin. It is not understood how the kinetoplastid CPC assembles nor how it is targeted to its subcellular destinations during the cell cycle. Here, we identify two orphan kinesins, KIN-A and KIN-B, as bona fide CPC proteins in Trypanosoma brucei, the kinetoplastid parasite that causes African sleeping sickness. KIN-A and KIN-B form a scaffold for the assembly of the remaining CPC subunits. We show that the C-terminal unstructured tail of KIN-A interacts with the KKT8 complex at kinetochores, while its N-terminal motor domain promotes CPC translocation to spindle microtubules. Thus, the KIN-A:KIN-B complex constitutes a unique ‘two-in-one’ CPC localization module, which directs the CPC to kinetochores from S phase until metaphase and to the central spindle in anaphase. Our findings highlight the evolutionary diversity of CPC proteins and raise the possibility that kinesins may have served as the original transport vehicles for Aurora kinases in early eukaryotes.
Dynamic localization of the chromosomal passenger complex is controlled by the orphan kinesin KIN-A in the kinetoplastid parasite Trypanosoma brucei
Authors: Ballmer Daniel , Akiyoshi Bungo
Published: January 2024

The chromosomal passenger complex (CPC) is an important regulator of cell division, which shows dynamic subcellular localization throughout mitosis, including kinetochores and the spindle midzone. In traditional model eukaryotes such as yeasts and humans, the CPC consists of the catalytic subunit Aurora B kinase, its activator INCENP, and the localization module proteins Borealin and Survivin. Intriguingly, Aurora B and INCENP as well as their localization pattern are conserved in kinetoplastids, an evolutionarily divergent group of eukaryotes that possess a unique set of kinetochore proteins and lack homologs of Borealin or Survivin. It is not understood how the kinetoplastid CPC assembles or how it is targeted to its subcellular destinations during the cell cycle. Here, we identify two orphan kinesins, KIN-A and KIN-B, as bona fide CPC proteins in
Trypanosoma brucei
, the causative agent of African sleeping sickness. By employing biochemical, structural, and cell biological approaches, we demonstrate that KIN-A and KIN-B serve as the scaffold for the assembly of the remaining CPC subunits. Kinetochore localization of the CPC depends on the KKT7 – KKT8 complex pathway, with the C-terminal unstructured tail of KIN-A serving as a key interaction partner for the KKT8 complex. Our data therefore show that, unlike other eukaryotes that take advantage of histone modifications for centromere recruitment, trypanosomes rely on kinetochore proteins to recruit the CPC onto kinetochores. Furthermore, the kinesin motor activity of KIN-A promotes chromosome alignment in prometaphase and CPC translocation to the central spindle upon anaphase onset. Thus, KIN-A constitutes a unique ‘two-in-one’ CPC localization module, directing the CPC to kinetochores (from S phase until metaphase) via its C-terminal tail, and to the central spindle (in anaphase) via its N-terminal kinesin motor domain. Our findings highlight the evolutionary diversity of CPC proteins and raise the possibility that kinesins may have served as the original transport vehicles for Aurora B kinases in early eukaryotes.
Pain persists in mice lacking both Substance P and CGRPα signaling
Authors: MacDonald Donald Iain , Jayabalan Monessha , Seaman Jonathan , Nickolls Alec , Chesler Alexander
Published: January 2024

The neuropeptides Substance P and CGRPα have long been thought important for pain sensation. Both peptides and their receptors are expressed at high levels in pain-responsive neurons from the periphery to the brain making them attractive therapeutic targets. However, drugs targeting these pathways individually did not relieve pain in clinical trials. Since Substance P and CGRPα are extensively co-expressed we hypothesized that their simultaneous inhibition would be required for effective analgesia. We therefore generated
Tac1
and
Calca
double knockout (DKO) mice and assessed their behavior using a wide range of pain-relevant assays. As expected, Substance P and CGRPα peptides were undetectable throughout the nervous system of DKO mice. To our surprise, these animals displayed largely intact responses to mechanical, thermal, chemical, and visceral pain stimuli, as well as itch. Moreover, chronic inflammatory pain and neurogenic inflammation were unaffected by loss of the two peptides. Finally, neuropathic pain evoked by nerve injury or chemotherapy treatment was also preserved in peptide-deficient mice. Thus, our results demonstrate that even in combination, Substance P and CGRPα are not required for the transmission of acute and chronic pain.
Performance of tree-building methods using a morphological dataset and a well-supported Hexapoda phylogeny
Authors: Francisco Barbosa Felipe , Mermudes José Ricardo M. , Russo Claudia A. M.
Published: January 2024

Recently, many studies have addressed the performance of phylogenetic tree-building methods (maximum parsimony, maximum likelihood, and Bayesian inference), focusing primarily on simulated data. However, for discrete morphological data, there is no consensus yet on which methods recover the phylogeny with better performance. To address this lack of consensus, we investigate the performance of different methods using an empirical dataset for hexapods as a model. As an empirical test of performance, we applied normalized indices to effectively measure accuracy (normalized Robinson–Foulds metric, nRF) and precision, which are measured via resolution, one minus Colless’ consensus fork index (1-CFI). Additionally, to further explore phylogenetic accuracy and support measures, we calculated other statistics, such as the true positive rate (statistical power) and the false positive rate (type I error), and constructed receiver operating characteristic plots to visualize the relationship between these statistics. We applied the normalized indices to the reconstructed trees from the reanalyses of an empirical discrete morphological dataset from extant Hexapoda using a well-supported phylogenomic tree as a reference. Maximum likelihood and Bayesian inference applying the k-state Markov (Mk) model (without or with a discrete gamma distribution) performed better, showing higher precision (resolution). Additionally, our results suggest that most available tree topology tests are reliable estimators of the performance measures applied in this study. Thus, we suggest that likelihood-based methods and tree topology tests should be used more often in phylogenetic tree studies based on discrete morphological characters. Our study provides a fair indication that morphological datasets have robust phylogenetic signal.
Estudio comparativo de cash cost entre CODELCO y las mineras privadas operando en Chile
Authors:   , Molina Alvial Eduardo Javier
Published: January 2024

La creación de la minera estatal “Corporación Nacional del Cobre” (CODELCO) en Chile durante 1974 fue el hito principal con el que culminó el proceso de nacionalización del cobre en el país, aprobado por el Congreso Nacional por unanimidad en 1971. Tras casi 50 años de su fundación no existen, sin embargo, estudios comparativos de costos operacionales, o “cash cost”, que permitan comparar el comportamiento que Codelco tuvo frente a estos con el comportamiento que tuvieron las empresas mineras privadas operando en Chile. De acuerdo con la literatura, existe una línea de pensamiento que adjudica a las empresas estatales una menor competitividad que las empresas privadas. Esta hipótesis será revisada en esta investigación. Para esto, se estudiaron los objetivos y razón de ser de CODELCO para identificar si la minimización de costos es uno de sus objetivos o si se han desarrollado proyectos para disminuirlos. Esta tesis analiza estos factores. También se realizó un estudio econométrico entre CODELCO y 7 empresas privadas para evaluar la respuesta de su cash cost ante variables como el precio del cobre, precio del molibdeno y la inercia de los costos. Los resultados de este estudio indican que CODELCO es una empresa competitiva frente a las mineras privadas de Chile en cuanto a que la empresa estatal tiene respuestas y tiempos de reacción similares ante las variables evaluadas en comparación con sus contrapartes privadas. Ello confirma que el objetivo sostenido por CODELCO de mantenerse como una empresa competitiva, tuvo como una de sus bases, acciones que le permitieron mantener sus niveles de “costos cash” comparables con aquellos de sus principales competidores privados.
La relación de la identidad social con la satisfacción de necesidades psicológicas básicas: Un estudio en la comunidad Trans chilena
Authors:   , Claramunt Carrasco Natalie Angélica
Published: January 2024

Marco teórico: Las personas Trans enfrentan altos niveles de estigmatización y discriminación, lo que genera estrés crónico y problemas de salud mental, tanto a nivel mundial como en el caso de Chile. La perspectiva de la identidad social aún no es abordada en este tipo de población y puede aportar en este campo. Por esto, se tuvo como objetivo describir y correlacionar identidad social (IS) y satisfacción de necesidades psicológicas fundamentales (SNPF) en personas Trans en Chile, utilizando el modelo de tres factores de la identidad social de Cameron y el modelo de amenaza temporal de necesidades de Williams. Metodología: Se realizó un análisis secundario de datos a partir de una encuesta sobre indicadores de salud y acceso a servicios de salud. Se trabajó con dos variables: la escala de IS y SNPF, y varios datos demográficos. La muestra consistió en 129 participantes Trans mayores de 18 años. El análisis incluyó estadísticas descriptivas y análisis de regresión lineal para conocer la relación entre la SNPB y los IS. Resultado: Los resultados apoyan las hipótesis de que la IS predice significativamente la SNPB. Además, se identifica que la edad en conjunto con la IS también es un predictor de SNPB.
Diseño y desarrollo de un programa de capacitación para potenciar la autogestión emocional de líderes
Authors:   ,   Pontificia Universidad Católica de Chile. Escuela de Psicología, Morales Toro Paula Antonia
Published: January 2024

Los líderes se ven constantemente expuestos a emociones, y dada la naturaleza de su trabajo que implica la interacción humana más que otros cargos (Yukl, 2008), cobra relevancia el concepto de autogestión emocional. Esta corresponde a la capacidad para controlar o redirigir impulsos y estados de ánimo disruptivos y la tendencia a suspender el juicio y pensar antes de actuar (Goleman, 2009; Goleman, 2016). Un líder que autogestiona adecuadamente sus emociones será más capaz de gestionar las emociones ajenas y dará el ejemplo a sus subordinados (Arana, 2012; Goleman, 2016), lo que mejorará tanto su efectividad como líder como los resultados colectivos (Afrifa et al., 2021), incluso organizacionales. Sin embargo, se ha encontrado una falta de literatura y de capacitaciones respecto al fomento de la autogestión emocional en líderes. Por tanto, el presente trabajo tiene como objetivo diseñar y desarrollar un programa de talleres para propiciar el desarrollo de la autogestión emocional en personas en cargos de liderazgo, el cual será el principal aporte. Además de considerar aspectos de la autogestión emocional y el desarrollo del mindfulness, se consideró información sobre cómo es una capacitación efectiva. Para esto, se revisó la literatura disponible y se realizaron entrevistas a 10 profesionales de recursos humanos, líderes y expertos en liderazgo e/o inteligencia emocional. De esta manera, con la información levantada también se buscó aportar al diseño y desarrollo del programa. Los resultados indican que el trabajo de un líder es demandante al tener requerimientos internos y externos. Las emociones más frecuentes en los líderes serían satisfacción, frustración, pasión, agobio, tensión y estrés, y quienes han trabajado su emocionalidad tendrían mayores probabilidades de instalar emociones “positivas” en sus equipos que quienes no. Además, se encontró que la autogestión emocional es fundamental para relacionarse con otras personas y regular sus emociones, y para instalar un ambiente de equipo que propicie la productividad. Sumado a lo anterior, se halló que un programa debe contemplar las etapas de gestión del cambio, y el taller debe realizarse en base a un diagnóstico particular, con relatores experimentados, abordando contenidos de autoliderazgo en actividades reflexivas y prácticas. Para asegurar la efectividad del taller, es importante hacer seguimiento a lo realizado. Por último, se halló que la autogestión emocional no se trabaja mucho en Chile, y si se trabaja, es en solo algunos segmentos de las empresas. Considerando esta información, se generaron 2 talleres: uno de autoconsciencia emocional y otro de autogestión emocional. Los talleres fueron diseñados y desarrollados para ser experienciales, auto-reflexivos y participativos.