Human Origin Research Articles

Protein-Based Nanocarriers and Nanotherapeutics for Infection and Inflammation.

Infectious and inflammatory diseases are one of the leading causes of death globally. The status quo has become more prominent with the onset of the coronavirus disease 2019 (COVID-19) pandemic. To combat these potential crises, proteins have been proven as highly efficacious drugs, drug targets, and biomarkers. On the other hand, advancements in nanotechnology have aided efficient and sustained drug delivery due to their nano-dimension-acquired advantages. Combining both strategies together, the protein nanoplatforms are equipped with the advantageous intrinsic properties of proteins as well as nanoformulations, eloquently changing the field of nanomedicine. Proteins can act as carriers, therapeutics, diagnostics, and theranostics in their nanoform as fusion proteins or as composites with other organic/inorganic materials. Protein-based nanoplatforms have been extensively explored to target the major infectious and inflammatory diseases of clinical concern. The current review comprehensively deliberated proteins as nanocarriers for drugs and nanotherapeutics for inflammatory and infectious agents, with special emphasis on cancer and viral diseases. A plethora of proteins from diverse organisms have aided in the synthesis of protein-based nanoformulations. The current study specifically presented the proteins of human and pathogenic origin to dwell upon the field of protein nanotechnology, emphasizing their pharmacological advantages. Further, the successful clinical translation and current bottlenecks of the protein-based nanoformulations associated with the infection-inflammation paradigm have also been discussed comprehensively. SIGNIFICANCE STATEMENT: This review discusses the plethora of promising protein-based nanocarriers and nanotherapeutics explored for infectious and inflammatory ailments, with particular emphasis on protein nanoparticles of human and pathogenic origin with reference to the advantages, ADME (absorption, distribution, metabolism, and excretion parameters), and current bottlenecks in development of protein-based nanotherapeutic interventions.

Establishment and characterization of a canine chondrosarcoma cell line: Mango

In the global progress of bone tumor research, established stable and long-lasting transgenic chondrosarcoma (CSA) cell lines are rare, mainly of murine and human origin, while the establishment of canine CSA cell lines has yet to be reported. This study established a canine CSA cell line to facilitate the basic clinical study of canine CSA. Fifty five cases of canine osteolytic disease were collected, and more than 10 bone tumor samples from dogs with typical clinical signs were used for primary cell culture. A cell line with stable passaging for more than 100 generations and mouse tumorigenic ability was successfully cultured. According to the clinical characteristics of the dog and the histopathological results of the primary tumor, CSA was diagnosed, and the CSA cell line was designated Mango. Immunohistochemical (IHC) results showed that the immunoreactivity of bone gamma-carboxyglutamate protein (BGLAP), secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALPL), vimentin (VIM) and S100 were positive. However, the immunoreactivity of pan-cytokeratin (PCK), chromogranin A (CGA), and platelet endothelial cell adhesion molecule-1 (CD31) was negative. Immunofluorescence (IF) results showed that the protein expressions in the Mango cell line were consistent with the IHC identification of the primary tumor. The Mango cell line’s doubling time was 43.92 h, and the cell formation rate exceeded 20%. There were abnormal chromosome numbers, hetero staining with toluidine blue, and certain calcification abilities. It could be passaged stably and continuously without changing the cell morphology and characteristics. In vivo, the cells were successfully injected into the nude mice model with a tumorigenic rate of 100%. The immunophenotype of the xenograft tumor was consistent with that of the primary tumor. Therefore, we effectively established a canine CSA cell line. As a promising cell material, this cell line can be used to construct a tumor-bearing model conducive to the subsequent basic research of canine CSA. Moreover, because of its similarity to human CSA, the animal model of CSA is also indispensable for investigating human CSA.

Circulation of enterotoxigenic Escherichia coli (ETEC) isolates expressing CS23 from the environment to clinical settings.

Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of infant diarrhea in low- and middle-income countries (LMICs). Diarrheal pathogens are transmitted through environmental reservoirs; however, the bacterial clones that spread across the human-environment interface remain unexplored. We aimed to determine the relationship and clonal dissemination of ETEC between children with diarrhea and polluted water samples from a local river in La Paz, Bolivia. By using WGS and the PhenePlates phenotypic system to analyze ETEC strains, we showed that ST218 and ST410 LT+STh ETEC expressing the colonization factor (CF) CS23 were found with high frequency in both samples. The CS23 ETEC isolates were found within several STs, E. coli phylogroups, and across ETEC lineages. Comparative genomic evaluation and PhenePlate screening of globally distributed clinical ETEC strains suggest that the CS23 gene is likely carried on plasmids acquired independently of the bacterial chromosomal background. Clinical strains were more often multidrug-resistant (MDR) than environmental isolates and harbored the class 1 integron-integrase gene intI1 next to the MDR cassettes. Retrospective analysis of antibiotic resistance in ETEC revealed a high frequency of MDR in clinical isolates. The LT+STh CS23 environmental ETEC isolates, showed an increased biofilm ability at environmental temperature, equal cytotoxicity, and significantly lower adherence to human epithelial cells compared to ETEC expressing other CFs. Together, we suggest that CS23 is more prevalent in ETEC than previously estimated, and the Choqueyapu River is a reservoir for LT+STh CS23 ETEC containing strains capable of causing diarrheal cases in children. IMPORTANCE The importance of clean water cannot be overstated. It is a vital resource for maintaining health and well-being. Unfortunately, water sources contaminated with fecal discharges from animal and human origin due to a lack of wastewater management pose a significant risk to communities, as they can become a means of transmission of pathogenic bacteria like enterotoxigenic E. coli (ETEC). ETEC is frequently found in polluted water in countries with a high prevalence of diarrheal diseases, such as Bolivia. This study provides novel insights into the circulation of ETEC between diarrheal cases and polluted water sources in areas with high rates of diarrheal disease. These findings highlight the Choqueyapu River as a potential reservoir for emerging pathogens carrying antibiotic-resistance genes, making it a crucial area for monitoring and intervention. Furthermore, the results demonstrate the feasibility of a low-cost, high-throughput method for tracking bacterial pathogens in low- and middle-income countries, making it a valuable tool for One Health monitoring efforts.

Modeling of African population history using f-statistics is biased when applying all previously proposed SNP ascertainment schemes.

f-statistics have emerged as a first line of analysis for making inferences about demographic history from genome-wide data. Not only are they guaranteed to allow robust tests of the fits of proposed models of population history to data when analyzing full genome sequencing data-that is, all single nucleotide polymorphisms (SNPs) in the individuals being analyzed-but they are also guaranteed to allow robust tests of models for SNPs ascertained as polymorphic in a population that is an outgroup in a phylogenetic sense to all groups being analyzed. True "outgroup ascertainment" is in practice impossible in humans because our species has arisen from a substructured ancestral population that does not descend from a homogeneous ancestral population going back many hundreds of thousands of years into the past. However, initial studies suggested that non-outgroup-ascertainment schemes might produce robust enough results using f-statistics, and that motivated widespread fitting of models to data using non-outgroup-ascertained SNP panels such as the "Affymetrix Human Origins array" which has been genotyped on thousands of modern individuals from hundreds of populations, or the "1240k" in-solution enrichment reagent which has been the source of about 70% of published genome-wide data for ancient humans. In this study, we show that while analyses of population history using such panels work well for studies of relationships among non-African populations and one African outgroup, when co-modeling more than one sub-Saharan African and/or archaic human groups (Neanderthals and Denisovans), fitting of f-statistics to such SNP sets is expected to frequently lead to false rejection of true demographic histories, and failure to reject incorrect models. Analyzing panels of SNPs polymorphic in archaic humans, which has been suggested as a solution for the ascertainment problem, has limited statistical power and retains important biases. However, by carrying out simulations of diverse demographic histories, we show that bias in inferences based on f-statistics can be minimized by ascertaining on variants common in a union of diverse African groups; such ascertainment retains high statistical power while allowing co-analysis of archaic and modern groups.

The Origin of Humanity and Evolution: Science and Scripture in Conversation

The Origin of Humanity and Evolution: Science and Scripture in Conversation

Aggressive Mimicry and the Evolution of the Human Cognitive Niche

The evolutionary origins of deception and its functional role in our species is a major focus of research in the science of human origins. Several hypotheses have been proposed for its evolution, often packaged under either the Social Brain Hypothesis, which emphasizes the role that the evolution of our social systems may have played in scaffolding our cognitive traits, and the Foraging Brain Hypothesis, which emphasizes how changes in the human dietary niche were met with subsequent changes in cognition to facilitate foraging of difficult-to-acquire foods. Despite substantive overlap, these hypotheses are often presented as competing schools of thought, and there have been few explicitly proposed theoretical links unifying the two. Utilizing cross-cultural data gathered from the Human Relations Area Files (HRAF), we identify numerous (n = 357) examples of the application of deception toward prey across 145 cultures. By comparing similar behaviors in nonhuman animals that utilize a hunting strategy known as aggressive mimicry, we suggest a potential pathway through which the evolution of deception may have taken place. Rather than deception evolving as a tactic for deceiving conspecifics, we suggest social applications of deception in humans could have evolved from an original context of directing these behaviors toward prey. We discuss this framework with regard to the evolution of other mental traits, including language, Theory of Mind, and empathy.

Integration of Omics Data and Network Models to Unveil Negative Aspects of SARS-CoV-2, from Pathogenic Mechanisms to Drug Repurposing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 health emergency, affecting and killing millions of people worldwide. Following SARS-CoV-2 infection, COVID-19 patients show a spectrum of symptoms ranging from asymptomatic to very severe manifestations. In particular, bronchial and pulmonary cells, involved at the initial stage, trigger a hyper-inflammation phase, damaging a wide range of organs, including the heart, brain, liver, intestine and kidney. Due to the urgent need for solutions to limit the virus' spread, most efforts were initially devoted to mapping outbreak trajectories and variant emergence, as well as to the rapid search for effective therapeutic strategies. Samples collected from hospitalized or dead COVID-19 patients from the early stages of pandemic have been analyzed over time, and to date they still represent an invaluable source of information to shed light on the molecular mechanisms underlying the organ/tissue damage, the knowledge of which could offer new opportunities for diagnostics and therapeutic designs. For these purposes, in combination with clinical data, omics profiles and network models play a key role providing a holistic view of the pathways, processes and functions most affected by viral infection. In fact, in addition to epidemiological purposes, networks are being increasingly adopted for the integration of multiomics data, and recently their use has expanded to the identification of drug targets or the repositioning of existing drugs. These topics will be covered here by exploring the landscape of SARS-CoV-2 survey-based studies using systems biology approaches derived from omics data, paying particular attention to those that have considered samples of human origin.

Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells in vitro and improves cardiomyopathy in vivo.

Cardiovascular diseases particularly myocardial infarction (MI) are the leading cause of mortality and morbidity around the globe. As cardiac tissue possesses very limited regeneration potential, therefore use of a potent small molecule, inhibitor Wnt production-4 (IWP-4) for stem cell differentiation into cardiomyocytes could be a promising approach for cardiac regeneration. Wnt pathway inhibitors may help stem cells in their fate determination towards cardiomyogenic lineage and provide better homing and survival of cells in vivo. Mesenchymal stem cells (MSCs) derived from the human umbilical cord have the potential to regenerate cardiac tissue, as they are easy to isolate and possess multilineage differentiation capability. IWP-4 may promote the differentiation of MSCs into the cardiac lineage. To evaluate the cardiac differentiation ability of IWP-4 and its subsequent in vivo effects. Umbilical cord tissue of human origin was utilized to isolate the MSCs which were characterized by their morphology, immunophenotyping of surface markers specific to MSCs, as well as by tri-lineage differentiation capability. Cytotoxicity analysis was performed to identify the optimal concentration of IWP-4. MSCs were treated with 5 μM IWP-4 at two different time intervals. Differentiation of MSCs into cardiomyocytes was evaluated at DNA and protein levels. The MI rat model was developed. IWP-4 treated as well as untreated MSCs were implanted in the MI model, then the cardiac function was analyzed via echocardiography. MSCs were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) dye for tracking, while the regeneration of infarcted myocardium was examined by histology and immunohistochemistry. MSCs were isolated and characterized. Cytotoxicity analysis showed that IWP-4 was non-cytotoxic at 5 μM concentration. Cardiac specific gene and protein expression analyses exhibited more remarkable results in fourteen days treated group that was eventually selected for in vivo transplantation. Cardiac function was restored in the IWP-4 treated group in comparison to the MI group. Immunohistochemical analysis confirmed the homing of pre-differentiated MSCs that were labeled with DiI cell labeling dye. Histological analysis confirmed the significant reduction in fibrotic area, and improved left ventricular wall thickness in IWP-4 treated MSC group. Treatment of MSCs with IWP-4 inhibits Wnt pathway and promotes cardiac differentiation. These pre-conditioned MSCs transplanted in vivo improved cardiac function by cell homing, survival, and differentiation at the infarcted region, increased left ventricular wall thickness, and reduced infarct size.

Hypothesis-generating analysis of the impact of non-damaging metabolic acidosis on the transcriptome of different cell types: Integrated stress response (ISR) modulation as general transcriptomic reaction to non-respiratory acidic stress?

Extracellular pH is an important parameter influencing cell function and fate. Microenvironmental acidosis accompanies different pathological situations, including inflammation, hypoxia and ischemia. Research focussed mainly on acidification of the tumour micromilieu and the possible consequences on proliferation, migration and drug resistance. Much less is known regarding the impact of microenvironmental acidosis on the transcriptome of non-tumour cells, which are exposed to local acidosis during inflammation, hypoxia, ischemia or metabolic derailment. In the present hypothesis-generating study, we investigated the transcriptional impact of extracellular acidosis on five non-tumour cell types of human and rat origin, combining RNA-Sequencing and extensive bioinformatics analyses. For this purpose, cell type-dependent acidosis resiliences and acidosis-induced transcriptional changes within these resilience ranges were determined, using 56 biological samples. The RNA-Sequencing results were used for dual differential-expression analysis (DESeq and edgeR) and, after appropriate homology mapping, Gene Ontology enrichment analysis (g:Profiler), Ingenuity Pathway Analysis (IPA®), as well as functional enrichment analysis for predicted upstream regulators, were performed. Extracellular acidosis led to substantial, yet different, quantitative transcriptional alterations in all five cell types. Our results identify the regulator of the transcriptional activity NCOA5 as the only general acidosis-responsive gene. Although we observed a species- and cell type-dominated response regarding gene expression regulation, Gene Ontology enrichment analysis and upstream regulator analysis predicted a general acidosis response pattern. Indeed, they suggested the regulation of four general acidosis-responsive cellular networks, which comprised the integrated stress response (ISR), TGF-β signalling, NFE2L2 and TP53. Future studies will have to extend the results of our bioinformatics analyses to cell biological and cell physiological validation experiments, in order to test the refined working hypothesis here.

The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment.

The onset and progression of oral cancer are accompanied by a dynamic interaction with the host immune system, and the immune cells within the tumor microenvironment play a pivotal role in the development of the tumor. By exploring the cellular immunity of oral cancer, we can gain insight into the contribution of both tumor cells and immune cells to tumorigenesis. This understanding is crucial for developing effective immunotherapeutic strategies to combat oral cancer. Studies of cancer immunology present unique challenges in terms of modeling due to the extraordinary complexity of the immune system. With its multitude of cellular components, each with distinct subtypes and various activation states, the immune system interacts with cancer cells and other components of the tumor, ultimately shaping the course of the disease. Conventional two-dimensional (2D) culture methods fall short of capturing these intricate cellular interactions. Mouse models enable us to learn about tumor biology in complicated and dynamic physiological systems but have limitations as the murine immune system differs significantly from that of humans. In light of these challenges, three-dimensional (3D) culture systems offer an alternative approach to studying cancer immunology and filling the existing gaps in available models. These 3D culture models provide a means to investigate complex cellular interactions that are difficult to replicate in 2D cultures. The direct study of the interaction between immune cells and cancer cells of human origin offers a more relevant and representative platform compared to mouse models, enabling advancements in our understanding of cancer immunology. This review explores commonly used 3D culture models and highlights their significant contributions to expanding our knowledge of cancer immunology. By harnessing the power of 3D culture systems, we can unlock new insights that pave the way for improved strategies in the battle against oral cancer.

Preanalytical variables influencing the interpretation and reporting of biological tests on blood samples of living and deceased donors for human body materials.

With the present paper, the Working Group on Cells, Tissues and Organs and other experts of the Superior Health Council of Belgium aimed to provide stakeholders in material of human origin with advice on critical aspects of serological and nucleic acid test (NAT) testing, to improve virological safety of cell- and tissue and organ donation. The current paper focusses on a number of preanalytical variables which can be critical for any medical biology examination: (1) sampling related variables (type of samples, collection of the samples, volume of the sample, choice of specific tubes, identification of tubes), (2) variables related to transport, storage and processing of blood samples (transport, centrifugation and haemolysis, storage before and after centrifugation, use of serum versus plasma), (3) variables related to dilution (haemodilution, pooling of samples), and (4) test dependent variables (available tests and validation). Depending on the type of donor (deceased donor (heart-beating or non-heart beating) versus living donor (allogeneic, related, autologous), and the type of donated human material (cells, tissue or organs) additional factors can play a role: pre- and post-mortem sampling, conditions of sampling (e.g. morgue), haemodilution, possibility of retesting.

A new ape from Türkiye and the radiation of late Miocene hominines

Fossil apes from the eastern Mediterranean are central to the debate on African ape and human (hominine) origins. Current research places them either as hominines, as hominins (humans and our fossil relatives) or as stem hominids, no more closely related to hominines than to pongines (orangutans and their fossil relatives). Here we show, based on our analysis of a newly identified genus, Anadoluvius, from the 8.7 Ma site of Çorakyerler in central Anatolia, that Mediterranean fossil apes are diverse, and are part of the first known radiation of early members of the hominines. The members of this radiation are currently only identified in Europe and Anatolia; generally accepted hominins are only found in Africa from the late Miocene until the Pleistocene. Hominines may have originated in Eurasia during the late Miocene, or they may have dispersed into Eurasia from an unknown African ancestor. The diversity of hominines in Eurasia suggests an in situ origin but does not exclude a dispersal hypothesis.

Comparative genomic analysis of a multidrug-resistant ExPEC strain IITR156 isolated from the confluence of three Indian rivers

Extra intestinal pathogenic Escherichia coli (ExPEC) with the potential to cause a wide range of infections in extra-intestinal sites is emerging threat to human health. Earlier studies have explored genomic characteristics of ExPEC isolates of human, avian, and porcine origin but genomic studies of environmental ExPEC isolates are very scarce. The environmental isolate, Escherichia coli IITR156 isolated in this study from the Triveni Sangam water sample showed resistance to antibiotics belonging to different classes including penicillin, beta-lactam combination agent, macrolide, cephalosporin, fluoroquinolone and aminoglycoside. Strain IITR156 was found to be harbouring plentitude of antibiotic resistant genes (ARGs) such as blaOXA-1, blaTEM-1, blaCTX-M-15, aac(3)-IIc and aac(6′)-Ib-cr, virulence genes including chuA, chuS, ybtA, ybtE, ybtP, epcA, and epcB, heavy metal resistant genes (HMRGs) such as arsRBC, cusB, cusF, cutA, tehA, nikABC, rcnA, rcnB, zraP, zitB, and zupT . Many of the ARGs and virulence genes were carried by mobile genetic elements such as genomic islands, transposons and plasmids indicating horizontal acquisition of genes. Comparative genomic analysis revealed that the strain IITR156 is closely related to other E. coli with ST 8881 isolated from human clinical samples. The presence of clinically relevant ARGs and virulence genes in an environmental isolate and its close relatedness to clinical isolates raise concerns and warrant immediate public attention.

Design, Synthesis, In Silico Studies and In Vitro Evaluation of New Indole- and/or Donepezil-like Hybrids as Multitarget-Directed Agents for Alzheimer's Disease.

Alzheimer's disease (AD) is considered a complex neurodegenerative condition which warrants the development of multitargeted drugs to tackle the key pathogenetic mechanisms of the disease. In this study, two novel series of melatonin- and donepezil-based hybrid molecules with hydrazone (3a-r) or sulfonyl hydrazone (5a-l) fragments were designed, synthesized, and evaluated as multifunctional ligands against AD-related neurodegenerative mechanisms. Two lead compounds (3c and 3d) exhibited a well-balanced multifunctional profile, demonstrating intriguing acetylcholinesterase (AChE) inhibition, promising antioxidant activity assessed by DPPH, ABTS, and FRAP methods, as well as the inhibition of lipid peroxidation in the linoleic acid system. Compound 3n, possessing two indole scaffolds, showed the highest activity against butyrylcholinesterase (BChE) and a high selectivity index (SI = 47.34), as well as a pronounced protective effect in H2O2-induced oxidative stress in SH-SY5Y cells. Moreover, compounds 3c, 3d, and 3n showed low neurotoxicity against malignant neuroblastoma cell lines of human (SH-SY5Y) and murine (Neuro-2a) origin, as well as normal murine fibroblast cells (CCL-1) that indicate the in vitro biocompatibility of the experimental compounds. Furthermore, compounds 3c, 3d, and 3n were capable of penetrating the blood-brain barrier (BBB) in the experimental PAMPA-BBB study. The molecular docking showed that compound 3c could act as a ligand to both MT1 and MT2 receptors, as well as to AchE and BchE enzymes. Taken together, those results outline compounds 3c, 3d, and 3n as promising prototypes in the search of innovative compounds for the treatment of AD-associated neurodegeneration with oxidative stress. This study demonstrates that hydrazone derivatives with melatonin and donepezil are appropriate for further development of new AChE/BChE inhibitory agents.

White‐faced and Black‐faced ibises foraging on predictable anthropogenic food subsidies in Patagonia, Argentina

AbstractWaste associated with human activities can benefit opportunistic species at the individual and population levels but could also expose them to pathogens or toxins. We provide information on unreported foraging habits of White‐faced ibis (Plegadis chihi) and Black‐faced ibis (Theristicus melanopis) in the Chubut River Valley, an urban and agricultural landscape in eastern Patagonia, Argentina. Both species were recorded during monthly counts made between February and June 2021 at anthropogenic food sources along the lower river valley, although almost exclusively at those sites offering waste from livestock production. This is the first record of both species foraging at this type of food source of human origin. White‐faced and Black‐faced ibises were present in numbers that varied between 2 and 679 individuals and between 1 and 18 individuals, respectively, depending on the site and month. Both species were recorded walking over carcasses and viscera and probing into these remains or on the soft soil surrounding the ponds where liquids generated by rendering processes were disposed. Given the current growth in livestock production in the area, further monitoring and assessment at other months of the year are needed to adequately interpret the species trophic ecology and the potential conflicts with human populations.

Arboviral Risk Associated with Solid Organ and Hematopoietic Stem Cell Grafts: The Prophylactic Answers Proposed by the French High Council of Public Health in a National Context.

Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, most arboviruses can be transmitted via accessory routes. Products of human origin (labile blood products, solid organs, hematopoietic stem cells, tissues) present a risk of contamination for the recipient if the donation is made when the donor is viremic. Mainland France and its overseas territories are exposed to a complex array of imported and endemic arboviruses, which differ according to their respective location. This narrative review describes the risks of acquiring certain arboviral diseases from human products, mainly solid organs and hematopoietic stem cells, in the French context. The main risks considered in this study are infections by West Nile virus, dengue virus, and tick-borne encephalitis virus. The ancillary risks represented by Usutu virus infection, chikungunya, and Zika are also addressed more briefly. For each disease, the guidelines issued by the French High Council of Public Health, which is responsible for mitigating the risks associated with products of human origin and for supporting public health policy decisions, are briefly outlined. This review highlights the need for a "One Health" approach and to standardize recommendations at the international level in areas with the same viral epidemiology.

The grassy ecosystems of Madagascar in context: Ecology, evolution, and conservation

Societal Impact StatementMadagascar is famous for its unique forests and their fauna. Most of the island is covered by flammable grassy ecosystems long considered to be of human origin and threatening the remaining forests. Yet new studies show that many plants and animals of the grassy systems are unique to Madagascar and restricted to these open habitats. Open grassy ecosystems have markedly different management requirements from forests and bring different contributions to society. We argue that the grassy ecosystems can benefit Madagascar if understood and managed wisely using expanded knowledge bases that also include collaboration with locals.SummaryUntil recently, nearly all research and interests in Madagascar focused on forested habitats. To help place Madagascar's grassy ecosystems in context, we provide a summary of the origin, development, and evolution of open tropical, C4 grassy ecosystems elsewhere, especially those from Africa; we summarize similarities and differences with the distribution of C3 and C4 grasses in the Malagasy landscape, their plant traits, and inferences on the evolutionary legacy of grasses. We also discuss the animal communities that use and have coevolved in these grassy systems; to help resolve controversies over the pre‐settlement extent of grassy ecosystems, we suggest a variety of complementary geochemical, palaeobotanical, and molecular genetic tools that have been effectively used elsewhere to untangle forest/grassy ecosystem mosaics and the ecological and evolutionary processes that influence them. Many of these tools can and should be employed in Madagascar to fully understand the spatio‐temporal dynamics of open, grassy, and closed forest systems across the island; as regards conservation, we discuss the ecosystem services provided by grassy systems, which are too often ignored in general, not only as a biome, vis‐à‐vis forests, but also for their global importance as a carbon sink and role they play in water management and providing goods to local villagers. We conclude by outlining the necessary research to better manage open ecosystems across Madagascar without threatening endangered forest ecosystems.

Agricultural impacts on lowland tropical streams detected through leaf litter decomposition

Stream ecosystems are highly vulnerable to changes in land use and vegetation in their catchments for two reasons: firstly, they receive inputs of nutrients, contaminants and sediments through runoff; and secondly, terrestrial leaf litter is the major basal resource supporting their food webs. Leaf litter decomposition by microorganisms and detritivores is thus a key stream ecosystem process, and a valuable functional indicator of impacts associated to agriculture and other alterations of human origin. Here, we investigated the joint effects of land use changes associated to agriculture (low, medium and high intervention areas: LI, MI and HI, respectively) in a tropical lowland catchment in Panama, through a decomposition experiment using three leaf litter types differing in nativeness (Ficus insipida, native to the study area; Alnus acuminata, native to Panama but not present in the study area; and Musa balbisiana, exotic to Panama). Lowland tropical areas are often poor in litter-consuming detritivores, and we accordingly observed a high contribution of microorganisms to total decomposition (>60% on average). However, only in the presence of detritivores, decomposition of Alnus discriminated among different degrees of agricultural intervention, being higher at the LI area. Leaf litter of the native Ficus showed higher microbial decomposition than the other types, possibly in relation to a home-field advantage effect. Despite the scarcity of detritivores in tropical lowland streams compared to tropical highland or temperate streams, our study indicates that their activity reflects impacts of land use change on these streams and they should therefore be included in assessments of anthropogenic impacts.

Human Fossils from the First Quarter of the 21st Century

Significant discoveries have been made from the first quarter of this Century in the field of evolutionary biology to redefine the human evolution. Discoveries present the morphological variability in fossil forms and indicate the valuable role of that particular continent in tracing the human origin. This article presents a general review of the human fossils found so far of this century that force us to rethink about the current concept of human origin. Most of the fossils have been found in East Africa, South Africa, Central Africa, Russia, Israel and Indonesia. Some of these are related to Australopithecus afarensis, some to Aus. africanus while some to Neanderthal. A complete human skeleton remains has been found from Ethiopia (Middle Awash region) and named as Ardipithecus ramidus is believed to be the common ancestor of humans and chimpanzees. Naser Ramla from Israelis considered as an ancestor of Neanderthals because it used stone tool production technology to make tools. Some fossils share features of both Australopithecus and early Homo, such as Orrorin tugenesis and Homo naledi. Australopithecus deyremeda is considered as an extinct species of Australopithecine. Some of these are contemporary of modern humans, such as Homo florensis, whose complete skeleton has been found from the Flores island of Indonesia and it has also been considered as an Asian descendant of Homoerectus. Denisovans found in Russia's Denisova cave is considered as a new species, it belongs to the Lower Middle Palaeolithic period, so it is also considered to be related to Neanderthal, although its fossil remains include only digit bone, 4 tooth, parts of jaw and long bones and parietal part of the cranium.

A highly antigenic fragment within the zoonotic Cryptosporidium parvum Gp900 glycoprotein (Domain 3) is absent in human restricted Cryptosporidium species.

We identified a fragment (Domain 3-D3) of the immunodominant sporozoite surface glycoprotein of the zoonotic parasite Cryptosporidium gp900, which is absent C. hominis and C. parvum anthroponosum. The fragment is highly antigenic and is able to effectively differentiate between zoonotic C. parvum and species/genotypes that infect preferentially humans. D3 detection provides a serological tool to determine whether the source of human cryptosporidiosis is of animal or human origin. We demonstrate this in experimentally challenged piglets, mice, rats, and alpaca. We speculate that the absence of this fragment from the C. hominis and C. parvum anthroponosum gp900 protein may play a key role in their host restriction.