Publications by authors named "B Peter"

277 Publications

Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry.

Nature 2021 Apr 7;592(7853):253-257. Epub 2021 Apr 7.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.

Modern humans appeared in Europe by at least 45,000 years ago, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania and Siberia who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common.
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http://dx.doi.org/10.1038/s41586-021-03335-3DOI Listing
April 2021

Influence of patella height after patella fracture on clinical outcome: a 13-year period.

Arch Orthop Trauma Surg 2021 Apr 6. Epub 2021 Apr 6.

Department of Trauma Surgery, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany.

Introduction: The incidence of patella fracture is statistically low (0.5-1.5%) compared to other fractures of the extremities [Patella fractures 76(10):987-997, 2005]. In the latter research, patella fractures if treated surgically present an overall inferior functional outcome. Little is known about the influence of the postoperative patella height on the clinical outcome. Therefore, the aim of our study was to analyse the influence of the patella height on the patients' functional outcome after surgery.

Methods: In this retrospective study the in-house trauma register of our level I University trauma center was screened for patients suffering patella fractures treated surgically. Patella height of the same patients was evaluated on lateral X-rays using the Insall-Salvati Ratio (ISR). The patients' X-rays were analyzed at two time points for the ISR, whereas group A presents ISR data right after surgery and group B data at the latest follow up (minimum 6 weeks). The change of mean ISR at both time points was tested for significance. The functional outcome was measured by the "Munich Knee Questionaire" (MKQ). These MKQ results of different patella heights and fracture types were compared.

Results: The screening of our in-house trauma register revealed 375 patients between the years 2003 and 2016. Out of these 54 patients (34f, 20 m) were enrolled. In detail the follow-up time for ISR between group A and B accounted for a mean of 503.8 ± 655.7 days. The MKQ was assessed at a mean of 1367.0 ± 1042.8 days after surgery. According to the AO-classification 10% AO.34 type B and 90% AO.34 type C fractures were found. Group A showed in 9.1% a patella baja and in 27.3% a patella alta compared to group B presenting 20.0% patella baja and 14.5% patella alta. There was no significant difference in functional outcome referring to the MKQ in patella alta (MKQ 69.0% ± 18.2) or baja (MKQ 67.1% ± 17.9) (p = 0.9). No significant functional difference between AO34.type B (MKQ 74.5% ± 11.0) and AO34.type C fractures (MKQ 64.0% ± 15.0) resulted (p = 0.1).

Conclusion: Our results demonstrate that different postoperative patella heights apparently do not influence the functional outcome in the short follow-up.
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http://dx.doi.org/10.1007/s00402-021-03871-7DOI Listing
April 2021

Phenotypic characterization of leukemia-initiating stem cells in chronic myelomonocytic leukemia.

Leukemia 2021 Mar 30. Epub 2021 Mar 30.

Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.

Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes, and substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cells (LSC) in CMML reside in a CD34/CD38 fraction of the malignant clone. Whereas CD34/CD38 cells engrafted NSGS mice with overt CMML, no CMML was produced by CD34/CD38 progenitors or the bulk of CD34 monocytes. CMML LSC invariably expressed CD33, CD117, CD123 and CD133. In a subset of patients, CMML LSC also displayed CD52, IL-1RAP and/or CLL-1. CMML LSC did not express CD25 or CD26. However, in sAML following CMML, the LSC also expressed CD25 and high levels of CD114, CD123 and IL-1RAP. No correlations between LSC phenotypes, CMML-variant, mutation-profiles, or clinical course were identified. Pre-incubation of CMML LSC with gemtuzumab-ozogamicin or venetoclax resulted in decreased growth and impaired engraftment in NSGS mice. Together, CMML LSC are CD34/CD38 cells that express a distinct profile of surface markers and target-antigens. During progression to sAML, LSC acquire or upregulate certain cytokine receptors, including CD25, CD114 and CD123. Characterization of CMML LSC should facilitate their enrichment and the development of LSC-eradicating therapies.
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http://dx.doi.org/10.1038/s41375-021-01227-zDOI Listing
March 2021

Implementation, efficacy, costs and processes of inpatient equivalent home-treatment in German mental health care (AKtiV): protocol of a mixed-method, participatory, quasi-experimental trial.

BMC Psychiatry 2021 Mar 30;21(1):173. Epub 2021 Mar 30.

Psychiatric Hospital and Rehabilitation Unit, Rudolf-Sophien-Stift, Stuttgart, Germany.

Background: Over the last decades, many high-income countries have successfully implemented assertive outreach mental health services for acute care. Despite evidence that these services entail several benefits for service users, Germany has lagged behind and has been slow in implementing outreach services. In 2018, a new law enabled national mental health care providers to implement team-based crisis intervention services on a regular basis, allowing for different forms of Inpatient Equivalent Home Treatment (IEHT). IEHT is similar to the internationally known Home Treatment or Crisis Resolution Teams. It provides acute psychiatric treatment at the user's home, similar to inpatient hospital treatment in terms of content, flexibility, and complexity.

Methods/design: The presented naturalistic, quasi-experimental cohort study will evaluate IEHT in ten hospitals running IEHT services in different German regions. Within a multi-method research approach, it will evaluate stakeholders' experiences of care, service use, efficacy, costs, treatment processes and implementation processes of IEHT from different perspectives. Quantitative surveys will be used to recruit 360 service users. Subsequently, 180 service users receiving IEHT will be compared with 180 matched statistical 'twins' receiving standard inpatient treatment. Assessments will take place at baseline as well as after 6 and 12 months. The primary outcome is the hospital re-admission rate within 12 months. Secondary outcomes include the combined readmission rate, total number of inpatient hospital days, treatment discontinuation rate, quality of life, psycho-social functioning, job integration, recovery, satisfaction with care, shared decision-making, and treatment costs. Additionally, the study will assess the burden of care and satisfaction with care among relatives or informal caregivers. A collaborative research team made up of researchers with and without lived experience of mental distress will conduct qualitative investigations with service users, caregivers and IEHT staff teams to explore critical ingredients and interactions between implementation processes, treatment processes, and outcomes from a stakeholder perspective.

Discussion: By integrating outcome, process and implementation research as well as different stakeholder perspectives and experiences in one study, this trial captures the various facets of IEHT as a special form of home treatment. Therefore, it allows for an adequate, comprehensive evaluation on different levels of this complex intervention.

Trial Registration: Trial registrations: 1) German Clinical Trials Register (DRKS), DRKS000224769. Registered December 3rd 2020, https://www.drks.de/drks_web/setLocale_EN.do ; 2) ClinicalTrials.gov, Identifier: NCT0474550 . Registered February 9th 2021.
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http://dx.doi.org/10.1186/s12888-021-03163-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008509PMC
March 2021

Introduction to the special issue, Sequential processing in spoken and written language.

Authors:
Beate Peter

Clin Linguist Phon 2021 Apr;35(4):293-295

CCC-SLP, College of Health Solutions, Arizona State University, Tempe, AZ, USA,

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http://dx.doi.org/10.1080/02699206.2020.1861482DOI Listing
April 2021

POLRMT mutations impair mitochondrial transcription causing neurological disease.

Nat Commun 2021 02 18;12(1):1135. Epub 2021 Feb 18.

Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.

While >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase γ, no mitochondrial phenotypes have been associated with POLRMT, the RNA polymerase responsible for transcription of the mitochondrial genome. Here, we characterise the clinical and molecular nature of POLRMT variants in eight individuals from seven unrelated families. Patients present with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype. Massive parallel sequencing of all subjects identifies recessive and dominant variants in the POLRMT gene. Patient fibroblasts have a defect in mitochondrial mRNA synthesis, but no mtDNA deletions or copy number abnormalities. The in vitro characterisation of the recombinant POLRMT mutants reveals variable, but deleterious effects on mitochondrial transcription. Together, our in vivo and in vitro functional studies of POLRMT variants establish defective mitochondrial transcription as an important disease mechanism.
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http://dx.doi.org/10.1038/s41467-021-21279-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893070PMC
February 2021

Functional analysis of a novel POLγA mutation associated with a severe perinatal mitochondrial encephalomyopathy.

Neuromuscul Disord 2021 Jan 12. Epub 2021 Jan 12.

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Box 440, 40530 Gothenburg, Sweden. Electronic address:

Mutations in the mitochondrial DNA polymerase gamma catalytic subunit (POLγA) compromise the stability of mitochondrial DNA (mtDNA) by leading to mutations, deletions and depletions in mtDNA. Patients with mutations in POLγA often differ remarkably in disease severity and age of onset. In this work we have studied the functional consequence of POLγA mutations in a patient with an uncommon and a very severe disease phenotype characterized by prenatal onset with intrauterine growth restriction, lactic acidosis from birth, encephalopathy, hepatopathy, myopathy, and early death. Muscle biopsy identified scattered COX-deficient muscle fibers, respiratory chain dysfunction and mtDNA depletion. We identified a novel POLγA mutation (p.His1134Tyr) in trans with the previously identified p.Thr251Ile/Pro587Leu double mutant. Biochemical characterization of the purified recombinant POLγA variants showed that the p.His1134Tyr mutation caused severe polymerase dysfunction. The p.Thr251Ile/Pro587Leu mutation caused reduced polymerase function in conditions of low dNTP concentration that mimic postmitotic tissues. Critically, when p.His1134Tyr and p.Thr251Ile/Pro587Leu were combined under these conditions, mtDNA replication was severely diminished and featured prominent stalling. Our data provide a molecular explanation for the patient´s mtDNA depletion and clinical features, particularly in tissues such as brain and muscle that have low dNTP concentration.
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http://dx.doi.org/10.1016/j.nmd.2021.01.004DOI Listing
January 2021

A phenotypically diverse family with an atypical 22q11.2 deletion due to an unbalanced 18q23;22q11.2 translocation.

Am J Med Genet A 2021 May 11;185(5):1532-1537. Epub 2021 Feb 11.

Phoenix Children's Hospital, University of Arizona College of Medicine, Phoenix, Arizona, USA.

The 22q11.2 deletion syndrome (22q11.2 DS) is the most common deletion syndrome in humans. In most cases, it occurs de novo. A rare family of three with 22q11.2 deletion syndrome (22q11.2 DS) resulting from an unbalanced 18q;22q translocation is reported here. Their deletion region is atypical in that it includes only 26 of the 36 genes in the minimal critical 22q11.2 DS region but it involves the loss of the centromeric 22q region and the entire p arm. The deletion region overlaps with seven other rare atypical cases; common to all cases was the loss of a region including SEPT5-GP1BB proximally and most of ARVCF distally. Interrogation of the deleted 22q region proximal to the canonical 22q11.2 deletion region in the DECIPHER database showed seven cases with isolated or combined traits of 22q11.2 DS, including three with clefts. The phenotypes in the present family thus may result from the loss of a subset of genes in the critical region, or alternatively the loss of other genes or sequences in the proximal 22q deletion region, or interactive effects among these. Despite the identical deletion locus in the three affected family members, expression of the 22q11.2 DS traits differed substantially among them. These three related cases thus contribute to knowledge of 22q11.2 DS in that their unusual deletion locus co-occurred with the cardinal features of the syndrome while their identical deletions are associated with variable phenotypic expression.
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http://dx.doi.org/10.1002/ajmg.a.62121DOI Listing
May 2021

Food grade safflower concentrate: No evidence for reproduction and early developmental toxicity.

Reprod Toxicol 2021 Jan 27. Epub 2021 Jan 27.

Saqual GmbH - Food & Feed Safety, Hardstrasse 59, 5432, Neuenhof, Switzerland.

Safflower (Carthamus tinctorius) petals have been used for centuries as a spice, in tea blends and in traditional Asian medicine. Aqueous extracts of Safflower petals have been used as a colouring food over the last 30 years due to their bright colour. Publications in the past raised concerns about fertility impairing, maternal toxicity, fetotoxic and teratogenic properties in rodents. As the tested extracts were poorly characterized and the studies were not performed according to guidelines, a need for further evaluation was seen. In silico predictions for the main pigments provided negative results for bacterial mutagenicity. Further, in vitro genotoxicity and in vivo reproductive toxicity studies of a well-characterized aqueous safflower concentrate generated more relevant data for risk assessment of its use in food. In vitro AMES tests and a mouse lymphoma cell assay were negative. An OECD guideline 421 screening study was performed in rats with oral daily doses of up to 1000 mg/kg bodyweight, applied via gavage to simulate a bolus effect. The highest dose reflected a toxicological limit test. The study did not give indications of general toxicity, did not show any effect on fertility and reproduction nor any effect on prenatal development and, also in contrast to previous results, treatment did not affect estradiol and FSH levels. Furthermore, pups raised until PND 14-16, developed normally with no adverse effects observed. With the established NOAEL of at least 1000 mg/kg/d, a considerable margin of exposure is achieved when compared with human intake estimates.
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http://dx.doi.org/10.1016/j.reprotox.2021.01.009DOI Listing
January 2021

German Norms of the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) and Proposal of a 5-Item Short-Version (HGSHS-5:G).

Int J Clin Exp Hypn 2021 Jan-Mar;69(1):112-123

Department of Psychology, University of Munich and MEG-Stiftung, Germany.

The Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A), is commonly used to test hypnotizability. There is still some controversy about what exactly hypnotizability is and whether and how it can be measured, especially by the HGSHS:A. Furthermore, a wider clinical use is limited, requiring a testing time of more than 1 hour. We analyzed the German HGSHS:A version for its factorial structure, item contribution, and item difficulty based on test data from six studies, including 1276 persons, to propose a shorter version of the HGSHS:A. We hereby present a 5-item version of the HGSHS:A (HGSHS-5:G), consisting of the challenge items, that was compared with an 11-item version (highly variable posthypnotic amnesia omitted). Age- and gender-specific norms was generated. The HGSHS-5: G showed high validity, reliability, and classification agreement. It reduces test time to 30 minutes thus facilitating wider use of hypnotizability testing.
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http://dx.doi.org/10.1080/00207144.2021.1836645DOI Listing
January 2021

Dissociation Constant of Integrin-RGD Binding in Live Cells from Automated Micropipette and Label-Free Optical Data.

Biosensors (Basel) 2021 Jan 24;11(2). Epub 2021 Jan 24.

Centre for Energy Research, Nanobiosensorics Laboratory, Institute of Technical Physics and Materials Science, 1121 Budapest, Hungary.

The binding of integrin proteins to peptide sequences such as arginine-glycine-aspartic acid (RGD) is a crucial step in the adhesion process of mammalian cells. While these bonds can be examined between purified proteins and their ligands, live-cell assays are better suited to gain biologically relevant information. Here we apply a computer-controlled micropipette (CCMP) to measure the dissociation constant () of integrin-RGD-binding. Surface coatings with varying RGD densities were prepared, and the detachment of single cells from these surfaces was measured by applying a local flow inducing hydrodynamic lifting force on the targeted cells in discrete steps. The average behavior of the populations was then fit according to the chemical law of mass action. To verify the resulting value of = (4503 ± 1673) 1/µm, a resonant waveguide grating based biosensor was used, characterizing and fitting the adhesion kinetics of the cell populations. Both methods yielded a within the same range. Furthermore, an analysis of subpopulations was presented, confirming the ability of CCMP to characterize cell adhesion both on single cell and whole population levels. The introduced methodologies offer convenient and automated routes to quantify the adhesivity of living cells before their further processing.
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http://dx.doi.org/10.3390/bios11020032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911545PMC
January 2021

Comparison of induced neurons reveals slower structural and functional maturation in humans than in apes.

Elife 2021 Jan 20;10. Epub 2021 Jan 20.

Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.

We generated induced excitatory neurons (iNeurons, iNs) from chimpanzee, bonobo, and human stem cells by expressing the transcription factor neurogenin-2 (NGN2). Single-cell RNA sequencing showed that genes involved in dendrite and synapse development are expressed earlier during iNs maturation in the chimpanzee and bonobo than the human cells. In accordance, during the first 2 weeks of differentiation, chimpanzee and bonobo iNs showed repetitive action potentials and more spontaneous excitatory activity than human iNs, and extended neurites of higher total length. However, the axons of human iNs were slightly longer at 5 weeks of differentiation. The timing of the establishment of neuronal polarity did not differ between the species. Chimpanzee, bonobo, and human neurites eventually reached the same level of structural complexity. Thus, human iNs develop slower than chimpanzee and bonobo iNs, and this difference in timing likely depends on functions downstream of NGN2.
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http://dx.doi.org/10.7554/eLife.59323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870144PMC
January 2021

Glycocalyx regulates the strength and kinetics of cancer cell adhesion revealed by biophysical models based on high resolution label-free optical data.

Sci Rep 2020 12 30;10(1):22422. Epub 2020 Dec 30.

Nanobiosensorics Laboratory, Institute of Technical Physics and Materials Science, Centre for Energy Research, Konkoly-Thege M. út 29-33, 1120, Budapest, Hungary.

The glycocalyx is thought to perform a potent, but not yet defined function in cellular adhesion and signaling. Since 95% of cancer cells have altered glycocalyx structure, this role can be especially important in cancer development and metastasis. The glycocalyx layer of cancer cells directly influences cancer progression, involving the complicated kinetic process of cellular adhesion at various levels. In the present work, we investigated the effect of enzymatic digestion of specific glycocalyx components on cancer cell adhesion to RGD (arginine-glycine-aspartic acid) peptide motif displaying surfaces. High resolution kinetic data of cell adhesion was recorded by the surface sensitive label-free resonant waveguide grating (RWG) biosensor, supported by fluorescent staining of the cells and cell surface charge measurements. We found that intense removal of chondroitin sulfate (CS) and dermatan sulfate chains by chondroitinase ABC reduced the speed and decreased the strength of adhesion of HeLa cells. In contrast, mild digestion of glycocalyx resulted in faster and stronger adhesion. Control experiments on a healthy and another cancer cell line were also conducted, and the discrepancies were analysed. We developed a biophysical model which was fitted to the kinetic data of HeLa cells. Our analysis suggests that the rate of integrin receptor transport to the adhesion zone and integrin-RGD binding is strongly influenced by the presence of glycocalyx components, but the integrin-RGD dissociation is not. Moreover, based on the kinetic data we calculated the dependence of the dissociation constant of integrin-RGD binding on the enzyme concentration. We also determined the dissociation constant using a 2D receptor binding model based on saturation level static data recorded at surfaces with tuned RGD densities. We analyzed the discrepancies of the kinetic and static dissociation constants, further illuminating the role of cancer cell glycocalyx during the adhesion process. Altogether, our experimental results and modelling demonstrated that the chondroitin sulfate and dermatan sulfate chains of glycocalyx have an important regulatory function during the cellular adhesion process, mainly controlling the kinetics of integrin transport and integrin assembly into mature adhesion sites. Our results potentially open the way for novel type of cancer treatments affecting these regulatory mechanisms of cellular glycocalyx.
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http://dx.doi.org/10.1038/s41598-020-80033-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773743PMC
December 2020

Small-molecule inhibitors of human mitochondrial DNA transcription.

Nature 2020 12 16;588(7839):712-716. Epub 2020 Dec 16.

Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.

Altered expression of mitochondrial DNA (mtDNA) occurs in ageing and a range of human pathologies (for example, inborn errors of metabolism, neurodegeneration and cancer). Here we describe first-in-class specific inhibitors of mitochondrial transcription (IMTs) that target the human mitochondrial RNA polymerase (POLRMT), which is essential for biogenesis of the oxidative phosphorylation (OXPHOS) system. The IMTs efficiently impair mtDNA transcription in a reconstituted recombinant system and cause a dose-dependent inhibition of mtDNA expression and OXPHOS in cell lines. To verify the cellular target, we performed exome sequencing of mutagenized cells and identified a cluster of amino acid substitutions in POLRMT that cause resistance to IMTs. We obtained a cryo-electron microscopy (cryo-EM) structure of POLRMT bound to an IMT, which further defined the allosteric binding site near the active centre cleft of POLRMT. The growth of cancer cells and the persistence of therapy-resistant cancer stem cells has previously been reported to depend on OXPHOS, and we therefore investigated whether IMTs have anti-tumour effects. Four weeks of oral treatment with an IMT is well-tolerated in mice and does not cause OXPHOS dysfunction or toxicity in normal tissues, despite inducing a strong anti-tumour response in xenografts of human cancer cells. In summary, IMTs provide a potent and specific chemical biology tool to study the role of mtDNA expression in physiology and disease.
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http://dx.doi.org/10.1038/s41586-020-03048-zDOI Listing
December 2020

Comparing global motor characteristics in children and adults with childhood apraxia of speech to a cerebellar stroke patient: evidence for the cerebellar hypothesis in a developmental motor speech disorder.

Clin Linguist Phon 2021 Apr 16;35(4):368-392. Epub 2020 Dec 16.

College of Health Solutions, Arizona State University, Tempe, AZ, USA.

Individuals with childhood apraxia of speech (CAS) have motor deficits in systems beyond speech and also global deficits in sequential processing, consistent with cerebellar dysfunction. We investigated the cerebellar hypothesis of CAS in 18 children and adolescents with CAS, 11 typical controls, an adult with a probable CAS history, and an adult with a history of a cerebellar stroke. Compared to the controls, children and adolescents with CAS had the greatest difficulty with rapid syllable repetition when alternating between two different syllables types, less difficulty when switching among three different syllables, and no difficulty when repeating the same syllable. They also showed difficulty with alternating but not repetitive key tapping. Motor speeds during the syllable repetition and key tapping tasks where correlated, consistent with a central motor delimiter that governs both systems. Participants with CAS obtained low scores in a test of fine motor ability, where the tasks required rapid integration of complex hand movement sequences. The adult with the probable CAS history obtained motor performance scores that generally resembled those in the children and adolescents with CAS, consistent with motor deficits that persist into adulthood. The participant with the cerebellar stroke history showed deficits in tests of fine and gross motor ability as well as balance. His repetitive and alternating key tapping was slow in the ipsilateral hand relative to the stroke lesion. The shared deficits in sequential motor functions among all participants with CAS and the cerebellar stroke patient are consistent with persisting cerebellar dysfunctions in CAS.
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http://dx.doi.org/10.1080/02699206.2020.1861103DOI Listing
April 2021

Inclusion of Interstate Migrant Workers in Kerala and Lessons for India.

Indian J Labour Econ 2020 Nov 12:1-22. Epub 2020 Nov 12.

Centre for Migration and Inclusive Development (CMID), Perumbavoor, India.

An estimated 3.5 million interstate migrant workers have become an indispensable part of Kerala's economy. The state also offers the highest wages for migrant workers for jobs in the unorganised sector in the entire Indian subcontinent. Further, the state has evolved several measures for the inclusion of the workers and was able to effectively respond to their distress during the national lockdown. This paper examines labour migration to Kerala, key measures by the government to promote the social security of the workers and the state's response to the distress of migrant workers during lockdown, by synthesising the available secondary evidence. The welfare measures as well as interventions initiated by the state are exemplary and promising given the intent and provisions. However, some of them do not appear to have consideration of the grassroots requirements and implementation mechanisms to enhance access. As a result, the policy intent and substantial investments have not yielded the expected results. The state's effective response to the distress of workers during the lockdown emanates from its overall disaster preparedness and resilience achieved from confronting with two consecutive state-wide natural disasters and a public health emergency in the immediate past. While the government has played a strategic role through policy imperative and ensuring a synergistic response, the data presented by the state indicate a much larger but invisible role played by the employers and civil society in providing food and shelter to workers.
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http://dx.doi.org/10.1007/s41027-020-00292-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659401PMC
November 2020

Denisovan ancestry and population history of early East Asians.

Science 2020 10;370(6516):579-583

Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany.

We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in northeastern Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.
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http://dx.doi.org/10.1126/science.abc1166DOI Listing
October 2020

Crop climate suitability mapping on the cloud: a geovisualization application for sustainable agriculture.

Sci Rep 2020 09 23;10(1):15487. Epub 2020 Sep 23.

Department of Plant, Soil and Microbial Sciences, Michigan State University, East Lansing, MI, 48824, USA.

Climate change, food security, and environmental sustainability are pressing issues faced by today's global population. As production demands increase and climate threatens crop productivity, agricultural research develops innovative technologies to meet these challenges. Strategies include biodiverse cropping arrangements, new crop introductions, and genetic modification of crop varieties that are resilient to climatic and environmental stressors. Geography in particular is equipped to address a critical question in this pursuit-when and where can crop system innovations be introduced? This manuscript presents a case study of the geographic scaling potential utilizing common bean, delivers an open access Google Earth Engine geovisualization application for mapping the fundamental climate niche of any crop, and discusses food security and legume biodiversity in Sub-Saharan Africa. The application is temporally agile, allowing variable growing season selections and the production of 'living maps' that are continually producible as new data become available. This is an essential communication tool for the future, as practitioners can evaluate the potential geographic range for newly-developed, experimental, and underrepresented crop varieties for facilitating sustainable and innovative agroecological solutions.
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http://dx.doi.org/10.1038/s41598-020-72384-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511951PMC
September 2020

AuthentiCT: a model of ancient DNA damage to estimate the proportion of present-day DNA contamination.

Genome Biol 2020 09 15;21(1):246. Epub 2020 Sep 15.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103, Leipzig, Germany.

Contamination from present-day DNA is a fundamental issue when studying ancient DNA from historical or archaeological material, and quantifying the amount of contamination is essential for downstream analyses. We present AuthentiCT, a command-line tool to estimate the proportion of present-day DNA contamination in ancient DNA datasets generated from single-stranded DNA libraries. The prediction is based solely on the patterns of post-mortem damage observed on ancient DNA sequences. The method has the power to quantify contamination from as few as 10,000 mapped sequences, making it particularly useful for analysing specimens that are poorly preserved or for which little data is available.
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http://dx.doi.org/10.1186/s13059-020-02123-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490890PMC
September 2020

The Victorian Lung Cancer Service Redesign Project: Impacts of a Quality Improvement collaborative on timeliness and management in lung cancer.

Intern Med J 2020 Sep 8. Epub 2020 Sep 8.

Department of Respiratory Medicine, Alfred Hospital, Melbourne.

Objectives: This initiative targeted Quality Improvement (QI) in lung cancer management, engaging a Quality Improvement collaborative using service redesign methodologies in five Victorian hospitals. QI targets included timeliness from referral and diagnosis to treatment, Multi-Disciplinary meeting (MDM) presentation and supportive care screening. Redesign strategies targeted process sustainability through enhanced team capability.

Designs: Prospective quality improvement cohort study with 6-month pre-intervention period and 6-month redesign implementation period, between September 2016 and August 2017, evaluated using Interrupted Time Series (ITS) analysis.

Setting: Three regional and two metropolitan hospitals in Victoria.

Participants: Newly diagnosed, tissue confirmed lung cancer.

Intervention: Site specific quality improvement service redesign.

Main Outcome Measures: Time intervals from Referral to First Specialist Appointment (FSA), Referral to Diagnosis, Diagnosis to First Treatment (any intent), MDM documented in medical records and Supportive Care Screening Tool (SCST) documented in medical records.

Results: There was a marked reduction in referral to FSA interval across all sites, with median (IQR) falling from 6 (0-15) to 4 (1-10) days, and proportion seen by a specialist within 14 days increased from 74.3% to 84.2%. The interval between diagnosis to treatment was not substantively changed in the 6-month implementation period. The proportion of subjects with documented presentation to the MDM increased from 61% to 67%. The proportion for whom supportive care screening documentation remained low at 26.3% post-intervention.

Conclusions: Data driven redesign initiatives enable identification and analysis of clinical practice variation and may be utilised to enhance timeliness of cancer care and improve local data service capabilities. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15043DOI Listing
September 2020

Leveraging big data for public health: Mapping malaria vector suitability in Malawi with Google Earth Engine.

PLoS One 2020 4;15(8):e0235697. Epub 2020 Aug 4.

College of Arts and Sciences, The University of Alabama, Tuscaloosa, Alabama, United States of America.

In an era of big data, the availability of satellite-derived global climate, terrain, and land cover imagery presents an opportunity for modeling the suitability of malaria disease vectors at fine spatial resolutions, across temporal scales, and over vast geographic extents. Leveraging cloud-based geospatial analytical tools, we present an environmental suitability model that considers water resources, flow accumulation areas, precipitation, temperature, vegetation, and land cover. In contrast to predictive models generated using spatially and temporally discontinuous mosquito presence information, this model provides continuous fine-spatial resolution information on the biophysical drivers of suitability. For the purposes of this study the model is parameterized for Anopheles gambiae s.s. in Malawi for the rainy (December-March) and dry seasons (April-November) in 2017; however, the model may be repurposed to accommodate different mosquito species, temporal periods, or geographical boundaries. Final products elucidate the drivers and potential habitat of Anopheles gambiae s.s. Rainy season results are presented by quartile of precipitation; Quartile four (Q4) identifies areas most likely to become inundated and shows 7.25% of Malawi exhibits suitable water conditions (water only) for Anopheles gambiae s.s., approximately 16% for water plus another factor, and 8.60% is maximally suitable, meeting suitability thresholds for water presence, terrain characteristics, and climatic conditions. Nearly 21% of Malawi is suitable for breeding based on land characteristics alone and 28.24% is suitable according to climate and land characteristics. Only 6.14% of the total land area is suboptimal. Dry season results show 25.07% of the total land area is suboptimal or unsuitable. Approximately 42% of Malawi is suitable based on land characteristics alone during the dry season, and 13.11% is suitable based on land plus another factor. Less than 2% meets suitability criteria for climate, water, and land criteria. Findings illustrate environmental drivers of suitability for malaria vectors, providing an opportunity for a more comprehensive approach to malaria control that includes not only modeled species distributions, but also the underlying drivers of suitability for a more effective approach to environmental management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235697PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402481PMC
September 2020

Spelling errors reveal underlying sequential and spatial processing deficits in adults with dyslexia.

Clin Linguist Phon 2021 Apr 19;35(4):310-339. Epub 2020 Jun 19.

Speech and Hearing Science, College of Health Solutions, Arizona State University, Tempe, AZ, USA.

Recent studies showed that some adults with dyslexia have difficulty processing sequentially arranged information. In a companion study, this deficit manifested as low accuracy during a word pair comparison task involving same/different decisions when two words differed in their letter sequences. This sequential deficit was associated with left/right spatial letter confusion. In the present study, we found the same underlying difficulty with sequential and spatial letter processing during word spelling. Participants were the same 22 adults with dyslexia and 20 age- and gender-matched controls as in the companion study. In the spelling task, sequential error rates were higher in the dyslexia group, compared to the controls. Measures of accuracy of serial letter order during the spelling task and the word comparison task were correlated. Only three participants, each with dyslexia, produced left/right letter reversals during spelling. These were the same participants who produced left/right errors when naming single letters. They also had profound difficulty with sequential and left/right letter processing in the spelling and word comparison tasks, and they had the most severe spelling impairment. We conclude that this pervasive, persistent difficulty with sequential and spatial reversals contributes to a severe dyslexia subtype. In the dyslexia group as a whole, additional and separate sources of errors were underspecified word representations in long-term memory and homophone errors that likely represent language-based deficits in word knowledge. In the participants, these three factors (sequential/spatial letter confusion, underspecified word form representation, language-based deficits) occurred either as single factors or in combination with each other.
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http://dx.doi.org/10.1080/02699206.2020.1780322DOI Listing
April 2021

A high-coverage Neandertal genome from Chagyrskaya Cave.

Proc Natl Acad Sci U S A 2020 06 16;117(26):15132-15136. Epub 2020 Jun 16.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany;

We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We show that this Neandertal was a female and that she was more related to Neandertals in western Eurasia [Prüfer et al., Science 358, 655-658 (2017); Hajdinjak et al., Nature 555, 652-656 (2018)] than to Neandertals who lived earlier in Denisova Cave [Prüfer et al., Nature 505, 43-49 (2014)], which is located about 100 km away. About 12.9% of the Chagyrskaya genome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with the fact that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains, and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more amino-acid-changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.
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http://dx.doi.org/10.1073/pnas.2004944117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334501PMC
June 2020

Does the Homo Hypnoticus Exist? Personality Styles of People Interested in Hypnosis.

Int J Clin Exp Hypn 2020 Jul-Sep;68(3):348-370. Epub 2020 May 21.

Department of Psychology, Ludwig-Maximilians-Universität München (LMU) , Munich, Germany.

It may be that individuals who are interested in hypnosis will volunteer for hypnosis experiments or practice hypnosis. Do these "hypnosis-prone" individuals differ from hypno-neutral, nonhypnosis-prone individuals? If so, could one speak of a personality type, the ? This study reports on 3 samples of individuals where there was no indication of hypnosis or no interest in hypnosis (NONHYP: = 1426) and 4 samples of individuals who were interested in hypnosis (HYP: = 1048). Using the Personality Styles and Disorders Inventory, we calculated contrast analyses for the contextual effect of HYP vs. NONHYP and gender effects. Results suggested there may be a homo hypnoticus personality style with the characteristics of intuitive-schizotypal, rhapsodic-optimistic, and charming-histrionic. These distinctions appear mostly in women.
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http://dx.doi.org/10.1080/00207144.2020.1756294DOI Listing
May 2020

Effect of Resistance Training Under Normobaric Hypoxia on Physical Performance, Hematological Parameters, and Body Composition in Young and Older People.

Front Physiol 2020 28;11:335. Epub 2020 Apr 28.

Department Health and Physical Activity, Institute III Sport Science, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Background: Resistance training (RT) under hypoxic conditions has been used to increase muscular performance under normoxic conditions in young people. However, the effects of RT and thus of RT under hypoxia (RTH) could also be valuable for parameters of physical capacity and body composition across the lifespan. Therefore, we compared the effects of low- to moderate-load RTH with matched designed RT on muscular strength capacity, cardiopulmonary capacity, hematological adaptation, and body composition in young and older people.

Methods: In a pre-post randomized, blinded, and controlled experiment, 42 young (18 to 30 year) and 42 older (60 to 75 year) participants were randomly assigned to RTH or RT (RTH young, RT young, RTH old, RT old). Both groups performed eight resistance exercises (25-40% of 1RM, 3 × 15 repetitions) four times a week over 5 weeks. The intensity of hypoxic air for the RTH was administered individually in regards to the oxygen saturation of the blood (SpO): ∼80-85%. Changes and differences in maximal isokinetic strength, cardiopulmonary capacity, total hemoglobin mass (tHb), blood volume (BV), fat free mass (FFM), and fat mass (FM) were determined pre-post, and the acute reaction of erythropoietin (EPO) was tested during the intervention.

Results: In all parameters, no significant pre-post differences in mean changes (time × group effects = 0.120 to 1.000) were found between RTH and RT within the age groups. However, within the four groups, isolated significant improvements ( < 0.050) of the single groups were observed regarding the muscular strength of the legs and the cardiopulmonary capacity.

Discussion: Although the hypoxic dose and the exercise variables of the resistance training in this study were based on the current recommendations of RTH, the RTH design used had no superior effect on the tested parameters in young and older people in comparison to the matched designed RT under normoxia after a 5-week intervention period. Based on previous RTH-studies as well as the knowledge about RT in general, it can be assumed that the expected higher effects of RTH can may be achieved by changing exercise variables (e.g., longer intervention period, higher loads).
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http://dx.doi.org/10.3389/fphys.2020.00335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198789PMC
April 2020

Democratizing water monitoring: Implementation of a community-based qPCR monitoring program for recreational water hazards.

PLoS One 2020 13;15(5):e0229701. Epub 2020 May 13.

School of Public Health, University of Alberta, Edmonton, Alberta, Canada.

Recreational water monitoring can be challenging due to the highly variable nature of pathogens and indicator concentrations, the myriad of potential biological hazards to measure for, and numerous access points, both official and unofficial, that are used for recreation. The aim of this study was to develop, deploy, and assess the effectiveness of a quantitative polymerase chain reaction (qPCR) community-based monitoring (CBM) program for the assessment of bacterial and parasitic hazards in recreational water. This study developed methodologies for performing qPCR 'in the field,' then engaged with water management and monitoring groups and tested the method in a real-world implementation study to evaluate the accuracy of CBM using qPCR both quantitatively and qualitatively. This study found high reproducibility between qPCR results performed by non-expert field users and expert laboratory results, suggesting that qPCR as a methodology could be amenable to a CBM program.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229701PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219769PMC
July 2020

Significant Differences in Personality Styles of Securely and Insecurely Attached Psychotherapists: Data, Reflections and Implications.

Front Psychol 2020 21;11:611. Epub 2020 Apr 21.

Department of Psychology, Ludwig-Maximilians Universität München, Munich, Germany.

This is a contribution to the research on the therapist variable aiming to improve effectiveness of psychotherapy. It is shown that attachment styles shape personality styles of psychotherapists in a favorable or unfavorable manner. Data on personality (PSDI) and attachment (RSQ) styles was collected from 430 psychological psychotherapists of the DACH countries using an online survey. The 88 insecurely attached psychotherapists differed significantly from their 342 securely attached colleagues in 9 of 14 personality styles: They were - even though well within normal range - more paranoid, borderline, schizoid, dependent, negativistic, self-sacrificing, avoidant, and depressive, as well as less optimistic. This corresponds to results of other researchers. Data regarding their effectiveness was not available. It is argued that a secure attachment style predispose to be a good psychotherapist. Yet, insecurely attached psychotherapists possibly compensate their adverse traits through self-therapy, continuous education, and supervision.
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http://dx.doi.org/10.3389/fpsyg.2020.00611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186447PMC
April 2020

TWINKLE and Other Human Mitochondrial DNA Helicases: Structure, Function and Disease.

Genes (Basel) 2020 04 9;11(4). Epub 2020 Apr 9.

Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE405 30 Gothenburg, Sweden.

Mammalian mitochondria contain a circular genome (mtDNA) which encodes subunits of the oxidative phosphorylation machinery. The replication and maintenance of mtDNA is carried out by a set of nuclear-encoded factors-of which, helicases form an important group. The TWINKLE helicase is the main helicase in mitochondria and is the only helicase required for mtDNA replication. Mutations in TWINKLE cause a number of human disorders associated with mitochondrial dysfunction, neurodegeneration and premature ageing. In addition, a number of other helicases with a putative role in mitochondria have been identified. In this review, we discuss our current knowledge of TWINKLE structure and function and its role in diseases of mtDNA maintenance. We also briefly discuss other potential mitochondrial helicases and postulate on their role(s) in mitochondria.
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http://dx.doi.org/10.3390/genes11040408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231222PMC
April 2020

Agreement and repeatability of four different devices to measure non-invasive tear breakup time (NIBUT).

Cont Lens Anterior Eye 2020 10 3;43(5):507-511. Epub 2020 Mar 3.

Optometry and Vision Science, Aston University, Birmingham, UK.

Purpose: Since tear film stability can be affected by fluorescein, the Dry Eye Workshop (DEWSII) recommended non-invasive measurement of tear breakup time (NIBUT). The aim of this study was to investigate the agreement and repeatability of four different instruments in the measurement of NIBUT.

Methods: 72 participants (mean 24.2 ± 3.6 years) were recruited for this multi-centre, cross-sectional study. NIBUT was measured three times from one eye using each of the instruments in randomized order on two separate sessions during a day, separated by at least 2 h. NIBUT was performed at three sites (Switzerland, Germany and UK) using three subjective instruments, Tearscope Plus (Keeler, Windsor, UK) (TS), Polaris (bon Optic, Lübeck, Germany) (POL), EasyTear Viewplus (Easytear, Rovereto, Italy) (ET) and the objective Keratograph 5 M (Oculus Optikgeräte GmbH, Wetzlar, Germany) (KER). As the latter instrument only analyses for 24 s, all data was capped at this value.

Results: NIBUT measurements (average of both sessions) between the four instruments were not statistically significantly different: TS (median 10.4, range 2.0-24.0 s), POL (10.1, 1.0-24.0 s), ET (10.6, 1.0-24.0 s) and KER (11.1, 2.6-24.0 s) (p = 0.949). The objective KER measures were on average (1.2 s ± 9.6 s, 95 % confidence interval) greater than the subjective evaluations of NIBUT with the other instruments (mean difference 0.4 s ± 7.7 s, 95 % confidence interval), resulting in a higher limits of agreement. The slope was -0.08 to 0.11 indicating no bias in the difference between instruments with the magnitude of the NIBUT. Repeated measurements from the two sessions were not significantly different for TS (p = 0.584), POL (p = 0.549), ET (p = 0.701) or KER (p = 0.261).

Conclusions: The four instruments evaluated for their measurement of tear stability were reasonably repeatable and give similar average results.
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http://dx.doi.org/10.1016/j.clae.2020.02.018DOI Listing
October 2020