Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans.

Download Full-text

House sparrows do not exhibit a preference for the scent of potential partners with different MHC-I allele numbers and genetic distances

10.1101/2022.01.11.475834 ◽

2022 ◽

Author(s):

Luisa Amo ◽

Guillermo Amo de Paz ◽

Johanna Kabbert ◽

Annie Machordom

Keyword(s):

Amino Acid ◽

House Sparrow ◽

Allelic Diversity ◽

Genetic Distances ◽

Immune Recognition ◽

House Sparrows ◽

Mhc I ◽

Mhc Genes ◽

Functional Variants ◽

Amino Acid Variants

MHC genes play a fundamental role in immune recognition of pathogens and parasites. Therefore, females may increase offspring heterozygosity and genetic diversity by selecting MHC genetically compatible or heterozygous males. In birds, several studies suggest that MHC genes play a role in mate choice, and recent evidence suggest that olfaction may play a role in such discrimination. Previous studies indicated that house sparrow females with low allelic diversity prefer males with higher diversity in MHC-I alleles. Here, we directly explored whether both house sparrow females and males could estimate by scent the number in MHC amino acid and functional variants as well as the level of MHC-I similarity or dissimilarity of potential partners. Our results show that neither females nor males exhibit a preference related to the number of MHC-I amino acid variants or functional variants or in relation to MHC amino acid or functional similarity of potential partners, suggesting that MHC-I is not detected through olfaction. Further studies are needed to understand the mechanisms responsible for MHC-I based mate discrimination in birds.

Download Full-text

Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽

10.3390/cancers13020350 ◽

2021 ◽

Vol 13 (2) ◽

pp. 350

Author(s):

Julianty Frost ◽

Mark Frost ◽

Michael Batie ◽

Hao Jiang ◽

Sonia Rocha

Keyword(s):

Gene Expression ◽

Hypoxia Inducible Factor ◽

Transcriptional Regulator ◽

Hydroxylase Activity ◽

Control Of Gene Expression ◽

Prolyl Hydroxylases ◽

Chromatin Organisation ◽

Sense And Respond ◽

Almost All ◽

And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

Download Full-text

The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22052472 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2472

Author(s):

Carl Randall Harrell ◽

Valentin Djonov ◽

Vladislav Volarevic

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune Cells ◽

Tissue Repair ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Multipotent Stem Cells ◽

Tissue Repair And Regeneration ◽

Almost All ◽

And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

Download Full-text

Actively revealing card attack on card-based protocols

Natural Computing ◽

10.1007/s11047-020-09838-8 ◽

2021 ◽

Author(s):

Ken Takashima ◽

Daiki Miyahara ◽

Takaaki Mizuki ◽

Hideaki Sone

Keyword(s):

Secure Computation ◽

Malicious Attack ◽

Formal Framework ◽

Almost All ◽

And Function

AbstractIn 1989, den Boer presented the first card-based protocol, called the “five-card trick,” that securely computes the AND function using a deck of physical cards via a series of actions such as shuffling and turning over cards. This protocol enables a couple to confirm their mutual love without revealing their individual feelings. During such a secure computation protocol, it is important to keep any information about the inputs secret. Almost all existing card-based protocols are secure under the assumption that all players participating in a protocol are semi-honest or covert, i.e., they do not deviate from the protocol if there is a chance that they will be caught when cheating. In this paper, we consider a more malicious attack in which a player as an active adversary can reveal cards illegally without any hesitation. Against such an actively revealing card attack, we define the t-secureness, meaning that no information about the inputs leaks even if at most t cards are revealed illegally. We then actually design t-secure AND protocols. Thus, our contribution is the construction of the first formal framework to handle actively revealing card attacks as well as their countermeasures.

Download Full-text

Soil ammonia-oxidizing archaea in a paddy field with different irrigation and fertilization managements

Scientific Reports ◽

10.1038/s41598-021-93898-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Limin Wang ◽

Dongfeng Huang

Keyword(s):

Ammonia Oxidation ◽

Chemical Properties ◽

Paddy Soils ◽

Soil Nitrification ◽

Treated Soil ◽

Ammonia Oxidizing Archaea ◽

Rice Yields ◽

Traditional Irrigation ◽

Almost All ◽

And Function

AbstractBecause ammonia-oxidizing archaea (AOA) are ubiquitous and highly abundant in almost all terrestrial soils, they play an important role in soil nitrification. However, the changes in the structure and function of AOA communities and their edaphic drivers in paddy soils under different fertilization and irrigation regimes remain unclear. In this study, we investigated AOA abundance, diversity and activity in acid paddy soils by a field experiment. Results indicated that the highest potential ammonia oxidation (PAO) (0.011 μg NO 2 - –N g-1 d.w.day-1) was found in T2 (optimal irrigation and fertilization)—treated soils, whereas the lowest PAO (0.004 μg NO 2 - –N g-1 d.w.day-1) in T0 (traditional irrigation)- treated soils. Compared with the T0—treated soil, the T2 treatment significantly (P < 0.05) increased AOA abundances. Furthermore, the abundance of AOA was significantly (P < 0.01) positively correlated with pH, soil organic carbon (SOC), and PAO. Meanwhile, pH and SOC content were significantly (P < 0.05) higher in the T2—treated soil than those in the T1 (traditional irrigation and fertilization)- treated soil. In addition, these two edaphic factors further influenced the AOA community composition. The AOA phylum Crenarchaeota was mainly found in the T2—treated soils. Phylogenetic analysis revealed that most of the identified OTUs of AOA were mainly affiliated with Crenarchaeota. Furthermore, the T2 treatment had higher rice yield than the T0 and T1 treatments. Together, our findings confirm that T2 might ameliorate soil chemical properties, regulate the AOA community structure, increase the AOA abundance, enhance PAO and consequently maintain rice yields in the present study.

Download Full-text

STEM-17. NOT ALL GBM STEM CELLS ARE EQUAL: IMPLICATIONS FOR RESEARCH AND THERAPY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.834 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii199-ii200

Author(s):

Luciano Galdieri ◽

Arijita Jash ◽

Olga Malkova ◽

Diane Mao ◽

Jian Campian ◽

...

Keyword(s):

Stem Cells ◽

Phenotypic Diversity ◽

Treatment Resistance ◽

Surface Markers ◽

Mass Cytometry ◽

Pathway Activation ◽

Almost All ◽

And Function ◽

Activation Status

Abstract Glioblastoma (GBM) kills almost all patients within 2 years. A subpopulation of cells, GBM stem cells (GSCs), contributes to treatment resistance and recurrence. A major therapeutic goal is to kill GSCs, but no targeted therapy yet exists. Since their discovery, GSCs have been isolated using single surface markers, such as CD15, CD44, CD133, and a-6 integrin. It remains unknown how these single surface marker-defined GSC populations compare to each other in terms of signal transduction and function and whether expression of different combinations of these markers is associated with distinct phenotypes. Using mass cytometry and fresh operating room specimens, we found that 15 distinct GSC subpopulations exist in vivo and they differ in their MEK/ERK, WNT, and AKT pathway activation status. In culture, some subpopulations were lost and previously undetectable ones materialized. GSCs highly expressing all four surface markers had the greatest self-renewal capacity and in vivo tumorigenicity as well as the strongest WNT pathway activation. This work highlights the signaling and phenotypic diversity in GSC subpopulations, together suggesting that not all GSCs are equivalent. These observations should be considered when studying GSCs in the laboratory, with implications for the development of treatments that target GSCs and prevent tumor recurrence in patients.

Download Full-text

Inter-Basal and Septal Connections of Papillary Muscles - An Anatomical Rationale for Rhythmic Opening of AV Valves - A Multicentric Medical College Based Cross Sectional Study

Journal of Evidence Based Medicine and Healthcare ◽

10.18410/jebmh/2021/523 ◽

2021 ◽

Vol 8 (31) ◽

pp. 2865-2869

Author(s):

Praveen Mulki Shenoy ◽

Amith Ramos ◽

Narasimha Pai ◽

Bharath Shetty ◽

Aravind Pallipady Rao

Keyword(s):

Left Ventricle ◽

Papillary Muscle ◽

Interventricular Septum ◽

Cross Sectional Study ◽

Papillary Muscles ◽

Cross Sectional ◽

Medical College ◽

Moderator Band ◽

Almost All ◽

And Function

BACKGROUND The papillary muscle basal connections have significant clinical implications. Variety of studies done on its morphology and function by various specialists in different departments. A close look on these revealed the interconnections of papillary muscles to one another and to the interventricular septum of both ventricles is related to uncoordinated contractions of papillary muscles, leading to hyper or hypokinesia or prolapse or even its rupture. METHODS Our study done in 25 formalin soaked hearts revealed after the deep and meticulous dissection, reflecting the walls of ventricles laterally the numerous interconnections of papillary muscles at its bases and IVS. Ventricles are opened by inverted ‘L’ shaped incision and its reflected more laterally till all the papillary muscles is visible in one frame after incising the moderator band. The connections were noted, measured, photographed, tabulated, compared with similar studies and analysed with experts with respective fields. RESULTS Almost all the specimens did have the interconnections. Further the post mortem findings of the cardiac related deaths with involvement of papillary muscles suggest damage to such ‘bridges’. The moderator band extensions to the base of right APM, and its extension to the posterior groups is noted in all the specimens. The bridge from the IVS to bases of both the groups of papillary muscles is noted in left ventricle. In90% of specimens the one PPM is found to be loosely connected, more so in left ventricle. CONCLUSIONS We are of a conclusion that such basal interconnections and to the interventricular septum are responsible for rhythmic contractions of papillary muscles of both ventricles. Since the AV valves have to open simultaneously, interconnections becomes mandatory as the impulse has to reach it before it reaches the trabeculae carniae. One of the Posterior papillary muscles is loosely connected to other papillary muscles, may be the reason for its rupture, more so in left ventricle. KEYWORDS Papillary Muscle, Interbasal Connection, Moderator Band, Valvular Prolapse, AV Valves

Download Full-text

Delineating urban functional regions by considering interaction cohesiveness and function diversity

Abstracts of the ICA ◽

10.5194/ica-abs-1-198-2019 ◽

2019 ◽

Vol 1 ◽

pp. 1-1

Author(s):

Fei-Ying Kuo ◽

Tzai-Hung Wen

Keyword(s):

Public Transportation ◽

Urban System ◽

Market Area ◽

Functional Region ◽

Trip Purpose ◽

Functional Regions ◽

Human Movements ◽

Local Labour ◽

Almost All ◽

And Function

<p><strong>Abstract.</strong> A functional region is usually defined as a region characterized by not only interaction cohesiveness but also function diversity. The former indicates that places within a region should share a cohesive interacting pattern of human movements, such as commute or daily travel; the latter means that the places should possess diverse functions like residence, commerce, etc. Due to these two characteristics, people living and moving in one region can acquire almost all their daily needs, and they do not need to frequently move to other regions. In other words, a functional region resembles a life circle. Based on this definition, many previous studies have developed different methods to analyse human flow data so that they can properly profile different types of functional regions like Local labour market area (LLMA) or daily urban system (DUS), which helps people better understand how functional regions compose an area. Existing methods have considered interaction cohesiveness in a functional region, but function diversity is ignored. This is because these studies only used specific-purpose-trip data, such as journey to work or to shop. These kinds of trips describe people moving from their home to their office or to shopping malls, so each trip has an inherent distinction of functions between its origin and destination; thus, a functional region consisting of these trips indirectly owns function diversity. However, this framework has some problems. First, it cannot profile a functional region shaped by composite functions, for only one trip purpose can be taken into account each time. Second, collecting the data of specific-purpose trips needs either some questionnaires or some surveys, so it is often costly and time consuming. Finally, the purpose-unrecorded-trip data provided by rapidly developed smart card systems in several countries can be collected quickly, yet it cannot properly profile functional regions through the aforementioned framework due to the lack of trip purposes. Therefore, we propose a new spatial partitioning algorithm which can simultaneously consider both interaction cohesiveness and function diversity in profiling functional regions. Compared with previous methods, the proposed algorithm can better profile functional regions from many purpose-unrecorded-trip data based on the inclusion of land-use data. Our results provide deeper insights for understanding how various functions of lands and human movements together shape the boundary of a region. It could be significant reference for developing policies for urban planning or public transportation management.</p>

Download Full-text

The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin

eLife ◽

10.7554/elife.03300 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 113

Author(s):

Bargavi Thyagarajan ◽

Jesse D Bloom

Keyword(s):

Amino Acid ◽

H1n1 Influenza ◽

Influenza Hemagglutinin ◽

Functional Variants ◽

Viral Hemagglutinin ◽

Before And After ◽

Amino Acid Mutations ◽

And Function ◽

Phylogenetic Models ◽

Better Than

Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.

Download Full-text

How important risk analysis of plastic pollution in coastal area? Case study in Masohi, Central Maluku

E3S Web of Conferences ◽

10.1051/e3sconf/202020002014 ◽

2020 ◽

Vol 200 ◽

pp. 02014

Author(s):

Bachtiar W Mutaqin ◽

Muh Aris Marfai ◽

Muhammad Helmi ◽

Nurhadi Nurhadi ◽

Muhammad Rizali Umarella ◽

...

Keyword(s):

Public Awareness ◽

Coastal Areas ◽

Plastic Waste ◽

Small Island ◽

Marine Biota ◽

Plastic Pollution ◽

Short Period ◽

Almost All ◽

And Function ◽

Interdisciplinary Study

Human pressure on the coastal and aquatic surrounding ecosystem in Indonesia, through plastic waste, is increasing, considering that 60 % of the approximately 250 million people live in the coastal areas. Plastic waste originating from human activities has become a massive problem in almost all the small island and coastal regions, especially in the eastern part of Indonesia. This condition is caused by poor waste management and a lack of public awareness in disposing of waste in its place, including in an area known as its marine biodiversities and marine tourism spots like Masohi in Central Maluku. Also, the composition of waste is dominated by plastic waste that cannot be decomposed in a short period, continue circulated on the ocean currents, and will be deposited in coastal areas. Furthermore, some plastic waste will break down into micro-plastics that pollute not only the environment but also marine biota, which are often consumed by humans. This situation profoundly affects the sustainability and function of aquaecosystem services in coastal areas. Therefore, a comprehensive policy and regulation, and interdisciplinary study for analysing vulnerable coastal ecosystem, and mitigating the potential risk of plastic pollution in Masohi, Central Maluku are essential to be conducted.

Download Full-text