bluuebunny/crossref_metadata_2025_split huggingface dataset:
Slave Trade and Colonial Expansion Resulted in Strong Sex-Biased Admixture in South Africa
Authors: Schurz Haiko , Reynolds Austin W. , Meeks Gillian , Gravel Simon , Myrick Justin W. , Mendez Fernando L. , Werely Cedric J. , van Helden Paul D. , Hoal Eileen G. , Poznik G. David , Kim Minju , Uren Caitlin , Underhill Peter A. , Möller Marlo , Henn Brenna M. 
Published: September 2023

AbstractThe colonial-period arrival of Europeans in southern Africa is associated with strong sex-biased migration by which male settlers displaced indigenous Khoekhoe and San men. Simultaneously, the importation of South Asian, Indonesian and Eastern African slaves may have contributed female-biased migration to Cape Town and surrounding areas. We examine the spatial and temporal spread of sex-biased migration from the Cape northward into Namaqualand and the southern Kalahari using genetic data from more than 1,400 individuals. In all regions, admixture patterns were sex-biased, with evidence of a greater male contribution of European ancestry and greater female contribution of Khoe-San ancestry. While admixture among Khoe-San, European, equatorial African, and Asian groups has likely been continuous from the founding of Cape Town to present-day, we find that Khoe-San groups further north experienced a single pulse of European admixture 6-8 generations ago. European admixture was followed by additional Khoe-San gene flow, potentially reflecting an aggregation of indigenous groups due to disruption by colonial interlopers. Male migration into the northern frontier territories was not a homogenous group of expanding Afrikaners and slaves. The Nama show evidence of distinct founder effects and derive 15% of their male lineages from Asian men, a pattern absent in the ≠Khomani San. Khoe-San ancestry from the paternal line is greatly diminished in populations from Cape Town, the Cederberg Mountains and Upington, but remains more frequent in self-identified ethnically indigenous groups. Strikingly, we estimate that Khoe-San Y-chromosomes were experiencing unprecedented population growth at the time of European arrival. Our findings shed light on the patterns of admixture and the population history of South Africa as the colonial frontier expanded.
Merging Multi-OMICs with Proteome Integral Solubility Alteration Unveils Antibiotic Mode of Action
Authors: Maity Ritwik , Zhang Xuepei , Liberati Francesca Romana , Rossi Chiara Scribani , Cutruzzolà Francesca , Rinaldo Serena , Gaetani Massimiliano , Aínsa José Antonio , Sancho Javier 
Published: September 2023

AbstractAntimicrobial resistance is responsible for an alarming number of deaths, estimated at 5 million per year. To combat priority pathogens, likeHelicobacter pylori, the development of novel therapies is of utmost importance. Understanding the molecular alterations induced by medications is critical for the design of multi-targeting treatments capable of eradicating the infection and mitigating its pathogenicity. However, the application of bulk omics approaches for unraveling drug molecular mechanisms of action is limited by their inability to discriminate between target-specific modifications and off-target effects. This study introduces a multi-omics method to overcome the existing limitation. For the first time, the PISA assay is utilized in bacteria in the PISA-express format to link proteome solubility with different and potentially immediate responses to drug treatment, enabling us the resolution to understand target-specific modifications and off-target effects. This study introduces a comprehensive method for understanding drug mechanisms and optimizing the development of multi-targeting antimicrobial therapies.
Vitamin D deficiency and toxicity across 2018 to 2022 in several cities of Ecuador: interrupted time series and a cross-sectional study
Authors: Zurita-Salinas Camilo , Tello Betzabé , Dueñas-Espín Iván , Zurita Jeannete , Acosta William , León Cristina Aguilera , Andrade-Muñoz Andrés , Pareja-Maldonado José 
Published: September 2023

AbstractObjectivesto identify differences in mean vitamin D concentrations in samples obtained from a private laboratory in the city of Quito, and to explore their relationship with the pre-pandemic and pandemic periods spanning from 2018 to 2022.DesignA combination of an interrupted time series design and a retrospective cross-sectional approachSetting and participantsThe study involved 9,285 participants who had their 25-hydroxyvitamin D (25(OH)D) levels tested at a well-known private laboratory in Quito, Ecuador, from 2018 to 2022.Primary and secondary outcome measures: The 25(OH)D levels were analyzed and assessed for correlations with both age and the year in which the measurements were taken.ResultsThe mean 25-hydroxyvitamin D (25(OH)D) level was 27.53 ng/mL (± 14.11). Approximately 64.58% of participants had insufficient levels, below 20 ng/mL, and 0.62% showed potential harm from excess 25(OH)D, with levels over 100 ng/mL. The analysis indicated a significant monthly increase of 0.133 units in 25(OH)D levels (p=0.006). However, the period after March 2020, compared to before, saw a non-significant decrease of 1.605 units in mean 25(OH)D levels (p=0.477).ConclusionsThe study’s findings indicate a significant prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency, underscoring the necessity for preventative measures. Nevertheless, the rise in cases of vitamin D toxicity is concerning, emphasizing the importance of prudent vitamin D supplement prescriptions and public education against self-medication. For efficient resource allocation and targeting those with higher risks, it may be advantageous to concentrate vitamin D testing on specific population groups.
Control of cell fate specification and patterning by an ancestral microRNA
Authors: Aguilar-Cruz Adolfo , Flores-Sandoval Eduardo , Gutiérrez-Ramos Ximena , Lopez Omar Oltehua- , Dorantes-Acosta Ana E. , Trujillo Joshua T. , Kato Hirotaka , Ishizaki Kimitsune , Mosher Rebecca A. , Dolan Liam , Grimanelli Daniel , Haseloff Jim , Bowman John L. , Arteaga-Vazquez Mario A. 
Published: September 2023

ABSTRACTThe formation of an organized body requires the establishment and maintenance of cells with structural and functional distinctive characteristics. A central question in developmental biology is how changes in the regulation of genes drive cell specification and patterning1. microRNAs (miRNAs) are small non-coding RNAs that regulate development through mRNA cleavage and/or translational repression2. In plants, miRNAs regulate key aspects including growth, development, stem cell maintenance, vegetative phase change, leaf morphogenesis, floral organ formation and flowering time3. Biogenesis of plant miRNAs depends on the activity of DICER-LIKE 1 (DCL1), an RNase type III endonuclease that processes double stranded RNA to give rise to mature miRNAs4. The genomes of today’s flora contain at least one bona fide copy ofDCL15,6. UsingMarchantia polymorpha-a model bryophyte that allows comparative approaches to infer characteristics of the ancestral land plant-, we demonstrate that MpDCL1ais required for the biogenesis of miRNAs and uncovered a central role for miR166/Homeodomain Zipper Class III-regulated auxin synthesis in the specification of cell identity, patterning, meristem function, laminar expansion and the development of the body in the last common ancestor of extant land plants.
Structural basis for the allosteric regulation and dynamic assembly of DNMT3B
Authors: Lu Jiuwei , Fang Jian , Zhu Hongtao , Liang Kimberly Lu , Khudaverdyan Nelli , Song Jikui 
Published: September 2023

AbstractOligomerization of DNMT3B, a mammaliande novoDNA methyltransferase, critically regulates its chromatin targeting and DNA methylation activities. However, how the N-terminal PWWP and ADD domains interplay with the C-terminal methyltransferase (MTase) domain in regulating the dynamic assembly of DNMT3B remains unclear. Here, we report the cryo-EM structure of DNMT3B under various oligomerization states. The ADD domain of DNMT3B interacts with the MTase domain to form an autoinhibitory conformation, resembling the previously observed DNMT3A autoinhibition. Our combined structural and biochemical study further identifies a role for the PWWP domain and its associated ICF mutation in the allosteric regulation of DNMT3B tetramer, and a differential functional impact on DNMT3B by potential ADD-H3K4me0 and PWWP-H3K36me3 bindings. In addition, our comparative structural analysis reveals a coupling between DNMT3B oligomerization and folding of its substrate-binding sites. Together, this study provides mechanistic insights into the allosteric regulation and dynamic assembly of DNMT3B.
O-GlcNAcylation of YTHDF2 antagonizes ERK-dependent phosphorylation and inhibits lung carcinoma
Authors: Li Jie , Zhou Wen , Zhang Jianzhi , Ma Li , Lv Zhuan , Geng Yiqun , Chen Xing , Li Jing 
Published: September 2023

SUMMARYThe intracellular O-linked N-acetylglucosamine (O-GlcNAc) glycosylation mediates many signal transduction events and regulates tumorigenesis. Previously the RNA N6-methyladenosine (m6A) reader, YTH (YT521-B homology) domain 2 (YTHDF2), has been shown to be O-GlcNAcylated on Ser-263 during Hepatitis B virus (HBV) infection and promote HBV-related hepatocellular carcinoma. Herein we mapped YTHDF2 O-GlcNAcylation at Thr-49 via electron-transfer dissociation mass spectrometry under unperturbed conditions. We show that YTHDF2 Thr-49 O-GlcNAcylation antagonizes Extracellular-signal regulated kinase (ERK)-dependent phosphorylation at Ser-39 and promotes YTHDF2 degradation. The downstream signaling pathway of YTHDF2 in lung carcinoma are thus upregulated, which leads to the downregulation of c-Myc. We further used mouse xenograft models to show that YTHDF2-T49A mutants increased lung cancer mass and size. Our work reveals a key role of YTHDF2 O-GlcNAcylation in tumorigenesis and suggests that O-GlcNAcylation exerts distinct functions under different biological stress.
Potential Structural Biomarkers in 3D Images Validated by the First Functional Biomarker for Early Age-Related Macular Degeneration - ALSTAR2 Baseline
Authors: Fasih-Ahmad Sohaib , Wang Ziyuan , Mishra Zubin , Vatanatham Charles , Clark Mark E , Swain Thomas A. , Curcio Christine A. , Owsley Cynthia , Sadda SriniVas R , Hu Zhihong Jewel 
Published: September 2023

AbstractPurposeWhile intermediate and late age-Related Macular Degeneration (AMD) have been widely investigated, rare studies were focused on the pathophysiologic mechanism of early AMD. Delayed rod-mediated dark adaptation (RMDA) is the first functional biomarker for incident early AMD. The status of outer retinal bands on optical coherence tomography (OCT) may be potential imaging biomarkers and the purpose is to investigate the hypothesis that the integrity of interdigitation zone (IZ) may provide insight into the health of photoreceptors and retinal pigment epithelium (RPE) in early AMD.MethodsWe establish the structure-function relationship between ellipsoid zone (EZ) integrity and RMDA, and IZ integrity and RMDA in a large-scale OCT dataset from eyes with normal aging (n=237), early AMD (n=138), and intermediate AMD (n=101) by utilizing a novel deep-learning-derived algorithm with manual correction when needed to segment the EZ and IZ on OCT B-scans (57,596 B-scans), and utilizing the AdaptDx device to measure RMDA.ResultsOur data demonstrates that slower RMDA is associated with less preserved EZ (r = -0.334; p<0.001) and IZ area (r = -0.591; p<0.001), and decreased IZ thickness (r = -0.434; p<0.001). These associations are not apparent when considering normal eyes alone.ConclusionsThe association with IZ area and RMDA in large-scale data is biologically plausible because retinoid availability and transfer at the interface attributed to IZ is rate-limiting for RMDA. This study supports the hypothesis that the IZ integrity provides insight into the health of photoreceptors and RPE in early AMD and is a potential new imaging biomarker.
Incidence of Acute Watery Diarrhea among Internally Displaced People in Burhakaba Camps, Bay Region, Somalia
Authors: Jayte Mohamed , Dahir Maryan 
Published: September 2023

AbstractBackgroundAcute watery diarrhea (AWD) is a major public health issue among internally displaced persons (IDPs) in Somalia due to inadequate water, sanitation and hygiene (WASH) infrastructure and services, in crowded camps. This study aimed to determine the incidence and associated factors of AWD in IDP camps in Burhakaba, Bay region.MethodsA cross-sectional survey was conducted among 318 IDPs across 6 camps in Burhakaba town. Structured interviews collected data on demographics 7-day episodes of AWD, water sources, latrine access, hygiene practices, and food consumption. AWD incidence was calculated and bivariate analysis identified associated factors.ResultsThe overall AWD incidence was 16.7%. Children under 5 had the highest incidence, at 9.8% among under 1 year and 8.9% among 1-5 years. Use of open wells (p=0.026), lack of latrines (p=0.017), poor hand-washing practices (p=0.002), and reduced food intake (p<0.001) were significantly associated with higher AWD risk.ConclusionsTargeted intervention to improve water quality, sanitation coverage, hygiene practices, and food security are urgently needed to reduce the high AWD burden among IDPs in Burhakaba.
Exploring the relationship between food environment and preferences among school children in a low socio-economic community in Sri Lanka: A GIS based assessment
Authors: Senevirathne Chamil , Katulanda Prasad , de Silva Padmal , Prashadika Dilini , Senarathne Lalith 
Published: September 2023

AbstractFood environment in school neighborhood plays a crucial role in manipulating food choices of school children. This study investigated the relationship between food environment in neighborhood and dietary practices of government school students in a low socio-economic setting, Sri Lanka. This cross-sectional study surveyed the neighborhood food environment of selected schools (n=30) in Monaragala District, Sri Lanka, using Geographical Information System (GIS) data, and collected dietary information from a representative sample of school children (n=603). Chi-square and spearman correlation tests were performed using SPSS version 23.0 to estimate the associations between food environment and BMI of students, while ArcGIS 10.4.1 was used to analyze GIS data of the study.Majority of students (35.5%) were 15 years old and approximately 51% were females. Mean BMI of study participants was 18.14 (± 3.28). More than 90% of outlets within close proximity sold unhealthy foods. Consumption of confectionaries was 72.3% of students whereas healthy foods choices was ranged from 5% to 12%. A positive correlation between consuming unhealthy food and distance to the outlets from the school was observed (p<0.05). Risk of consuming low nutrition food found to be doubled (OR = 2.47, 95% CI: 1.52-3.89) among students studied in schools where larger proportion of energy dense food sold in closer proximity. In conclusion, density and the proximity of the outlets that sold food in low nutrients in school neighborhood environment were positively associated with choosing unhealthy food items by students.
Cancer diagnostic service use in people with HIV in South Africa: a cross-sectional study
Authors: Olago Victor , Nimako Gideon , Bartels Lina , Bohlius Julia , Dhokotera Tafadzwa , Egger Matthias , Singh Elvira , Sengayi-Muchengeti Mazvita 
Published: September 2023

AbstractObjectiveThe objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people with HIV (PWH) within South Africa (SA) using national laboratory database.DesignWe linked HIV and cancer laboratory data from 2004-2014 using supervised machine-learning algorithms. We performed a cross-sectional analysis comparing province where individuals accessed their HIV care versus where they had their cancer diagnosis.SettingWe used laboratory test records related to HIV diagnostics and care, such as CD4 cell counts and percentages, rapid tests, qualitative Polymerase Chain Reaction (PCR), antibody and antigen tests for HIV data that was documented as HIV positive and laboratory diagnosed cancer records from SA.Study populationOur study population consisted of HIV records from the National Health Laboratory Service (NHLS) that linked to cancer record at the National Cancer Registry (NCR) between 2004-2014.Primary and secondary outcomesWe linked HIV records from NHLS to cancer records at NCR in order to study the inherent characteristics of the population with both HIV and cancer.ResultsThe study population was 68,284 individuals with cancer and documented HIV related laboratory test. The median age at cancer diagnosis was 40 [IQR, 33-48] years for the study population with most cancers in PWH diagnosed in females 70.9% [n=46,313]. Of all the PWH and cancer, 25% (n=16,364 p < 0.001) sought treatment outside their province of residence with 60.7% (n=10,235) travelling to Gauteng. KZN had 46.6% (n=4,107) of its PWH getting cancer diagnosis in Gauteng. Western Cape had 95% (n=6,200) of PWH getting cancer diagnosis within the province.ConclusionsOur results showed health systems inequalities across provinces in South Africa with respect to cancer diagnosis. KZN for example had nearly half of the PWH getting cancer diagnosis outside the province while Western Cape is able to offer cancer diagnostic services to most of the PWH in the province. Gauteng is getting over burdened with referral for cancer diagnosis from other provinces. More effort is required to ensure equitable access to cancer diagnostic services within the country.Article SummaryStrengths and limitations of this studyWe mapped the facilities of cancer diagnosis versus HIV care facilities for the PWH seeking cancer diagnosis in South Africa.We compared PWH who sought treatment in their province of residence versus those who sought treatment outside their province of residence.We used HIV care facility’s addresses as a proxy for place of residence for PWH.We did not account for movement due to other reasons such as migration for better jobs and education.
Loss of cholesterol in Junctional Epidermolysis Bullosa skin identifies a key role for Laminin-332 in actomyosin mediated cholesterol transport
Authors: Jones Eleri. M. , Camera Emanuela. , Parzymies Piotr. , Marsh Supatra.T. , O’Shaughnessy Ryan.F. , Aumailley Monique. , McGrath John. A. , O’Toole Edel.A. , Caley Matthew. 
Published: September 2023

AbstractIndividuals with Junctional Epidermolysis Bullosa (JEB), a rare genetic skin disease characterised by loss of function mutations in the Laminin332 (Lam332), do not survive beyond their first birthday. Here we report that loss of Lam332 leads to absence of cholesterol lipid from the epidermisin vitroandin vivo. Stable knockdown of Lam332 chains (LAMA3, LAMB3 and LAMC2) was established using shRNA and were used to develop 3D skin equivalents. Changes in lipid synthesis were assessed by western blot analysis and immunohistochemistry. Findings were confirmed in an inducible mouse model of Lamα3 (Lama3flox/flox/K14CreERT) and in anonymized, archival human tissue: JEB skin and normal age-matched controls. Further lipid analysis was explored using lipidomics in 3D skin equivalents and mouse tissue. Cholesterol biosynthesis genes were increased with loss of Lam332in vitro, however a decrease in nile red lipid staining was observed in Lamα3 mouse (n = 6) and in JEB patient skin (n = 7). Further changes to the epidermal lipid profile with loss of Lam332 was confirmed with lipidomic analysis of Lamα3 mouse epidermis and Lam332 skin equivalents. Cholesterol transport within Lam332 KD keratinocytes was revealed to be disrupted, which in keratinocytes is dependent on the actomyosin network, which was reversed with recombinant human Lam332. In conclusion these findings suggest a role for Lam332 in lipid metabolism in the skin and a broader role in epidermal homeostasis and barrier formation. Restoration of cholesterol transport in JEB patients offers the potential to improve the skin barrier and survival.
Reconfiguration of brain-wide neural activity after early life adversity
Authors: Uselman Taylor W. , Jacobs Russell E. , Bearer Elaine L 
Published: September 2023

AbstractEarly life adversity (ELA) predisposes individuals to both physical and mental disorders lifelong. How ELA affects brain function leading to this vulnerability is under intense investigation. Research has begun to shed light on ELA effects on localized brain regions within defined circuits. However, investigations into brain-wide neural activity that includes multiple localized regions, determines relationships of activity between regions and identifies shifts of activity in response to experiential conditions is necessary. Here, we performed longitudinal manganese-enhanced magnetic resonance imaging (MEMRI) to image the brain in normally reared or ELA-exposed adults. Images were captured in the freely moving home cage condition, and short- and long-term after naturalistic threat. Images were analyzed with new computational methods, including automated segmentation and fractional activation or difference volumes. We found that neural activity was increased after ELA compared to normal rearing in multiple brain regions, some of which are involved in defensive and/or reward circuitry. Widely distributed patterns of neural activity, “brain states”, and their dynamics after threat were altered with ELA. Upon acute threat, ELA-mice retained heightened neural activity within many of these regions, and new hyperactive responses emerged in monoaminergic centers of the mid- and hindbrain. Nine days after acute threat, heightened neural activity remained within locus coeruleus and increased within posterior amygdala, ventral hippocampus, and dorso- and ventromedial hypothalamus, while reduced activity emerged within medial prefrontal cortical regions (prelimbic, infralimbic, anterior cingulate). These results reveal that functional imbalances arise between multiple brain-systems which are dependent upon context and cumulative experiences after ELA.Significance StatementEarly life adversity (ELA) is a crucial determinant of adult health. Yet, the neurobiological basis for this association remains elusive. Neural activity differs within localized brain regions in rodents who experienced ELA, yet how this localized activity contributes to overall brain states has hitherto been unknown. Here we used longitudinal manganese-enhanced MRI to reveal brain-wide activities altered by ELA compared to normal rearing. Advanced computational analyses unveiled widespread reconfiguration of segment-wise neural activity throughout the brain across a series of conditions: freely moving, experiencing threat or its aftermath. These brain state dynamics were unique to ELA. Reconfiguration of brain states after ELA, shown here for the first time, may underlie predisposition to mental and physical disorders after childhood adversity.