Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 1 hour 14 min ago

Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts.

Thu, 06/22/2017 - 07:40

Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts.

Acta Ophthalmol. 2017 Jun 21;:

Authors: Wang JD, An Y, Zhang JS, Wan XH, Zhang W, Lanza R, Lu SJ, Jonas JB, Xu L

Abstract
OBJECTIVE: To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion.
METHODS: Human embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion. Control groups of animals received an intravitreal injection of endothelial cells (ECs) or phosphate-buffered saline (PBS). We examined the vasculature integrity in the mice with OIR, the blood-retina barrier in the rats with induced DR, and retinal thickness and retinal ganglion cell density in retina flat mounts of the rats with the retinal ischaemic-reperfusion retinopathy.
RESULTS: In the OIR model, the study group versus control groups showed a significantly (p < 0.001) smaller retinal avascular area [5.1 ± 2.7%;n = 18 animals versus 12.2 ± 2.8% (PBS group; n = 10 animals) and versus 11.8 ± 3.7% (EC group; n = 8 animals)] and less retinal neovascularization [6.3 ± 2.5%;n = 18 versus 15.2 ± 6.3% (n = 10; PBS group) and versus 15.8 ± 3.3% (n = 8; EC group)]. On retinal flat mounts, hESC-HBs were integrated into damaged retinal vessels and stained positive for PECAM (CD31) as EC marker. In the DR model, the study group versus the EC control group showed a significantly (p = 0.001) better blood-retina barrier function as measured at 2 days after the intravitreal injections [study group: 20.2 ± 12.8 μl/(g × hr); n = 6; versus EC control group: 52.9 ± 9.9 μl/(g × hr; n = 6)]. In the retinal ischaemia-reperfusion model, the groups did not differ significantly in retinal thickness and retinal ganglion cell density at 2, 5 and 7 days after baseline.
CONCLUSION: By integrating into damaged retinal vessels and differentiating into ECs, intravitreally administered hESC-HBs may have partially repaired a retinal vascular injury caused by OIR model and DR.

PMID: 28636206 [PubMed - as supplied by publisher]

Interposition Ankle Arthroplasty Using Acellular Dermal Matrix: A Small Series.

Thu, 06/22/2017 - 07:40
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Interposition Ankle Arthroplasty Using Acellular Dermal Matrix: A Small Series.

J Foot Ankle Surg. 2017 Jul - Aug;56(4):894-897

Authors: Carpenter B, Duncan K, Ernst J, Ryba D, Suzuki S

Abstract
Although ankle arthrodesis is the reference standard for end-stage ankle arthritis, loss of mobility and adjacent joint arthritis are consequences that alternatives to arthrodesis attempt to avoid. The purpose of the present study was to report the clinical results of interpositional arthroplasty using acellular dermal matrix in 4 patients (age 32 to 42 years) for the treatment of advanced ankle osteoarthritis. The primary findings included relief of pain, with improvement in tibiotalar joint range of motion from a mean of 16.5° (range 0° to 24°) preoperatively to a mean of 31° (range 25° to 40°) postoperatively. All 4 patients underwent open arthrotomy of the anterior and posterior tibiotalar capsule with plafond exostectomy and debridement of all deleterious tissue within the ankle capsule. The articular surface of the talar dome was denuded down to smooth subchondral bone, and microfracture was performed. Autologous calcaneal bone marrow aspirate was applied, and talar resurfacing was achieved using an acellular dermal matrix. Knotless anchors placed medially and laterally within the anterior and posterior dome were used to affix the dermal matrix. The follow-up period ranged from 12 to 18 (mean 14) months. The mean pre- and 12-month postoperative Association of Orthopaedic Foot and Ankle Society hindfoot-ankle scale scores were 35 and 88.5, respectively. These outcomes suggest that interpositional tibiotalar arthroplasty using an acellular dermal matrix is successful in improving function and range of motion and decreasing pain. As an alternative to tibiotalar arthrodesis, interpositional tibiotalar arthroplasty might be the procedure of choice for young patients with end-stage ankle arthritis. Longer follow-up periods, histologic testing, and arthroscopic evaluations would be advantageous to further assess the durability of this procedure.

PMID: 28633799 [PubMed - in process]

Ceftriaxone reduces L-dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson's disease model.

Wed, 06/21/2017 - 16:51

Ceftriaxone reduces L-dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson's disease model.

Mov Disord. 2017 Jun 20;:

Authors: Chotibut T, Meadows S, Kasanga EA, McInnis T, Cantu MA, Bishop C, Salvatore MF

Abstract
BACKGROUND: Increased extracellular glutamate may contribute to l-dopa induced dyskinesia, a debilitating side effect faced by Parkinson's disease patients 5 to 10 years after l-dopa treatment. Therapeutic strategies targeting postsynaptic glutamate receptors to mitigate dyskinesia may have limited success because of significant side effects. Increasing glutamate uptake may be another approach to attenuate excess glutamatergic neurotransmission to mitigate dyskinesia severity or prolong the time prior to onset. Initiation of a ceftriaxone regimen at the time of nigrostriatal lesion can attenuate tyrosine hydroxylase loss in conjunction with increased glutamate uptake and glutamate transporter GLT-1 expression in a rat 6-hydroxydopamine model. In this article, we examined if a ceftriaxone regimen initiated 1 week after nigrostriatal lesion, but prior to l-dopa, could reduce l-dopa-induced dyskinesia in an established dyskinesia model.
METHODS: Ceftriaxone (200 mg/kg, intraperitoneal, once daily, 7 consecutive days) was initiated 7 days post-6-hydroxydopamine lesion (days 7-13) and continued every other week (days 21-27, 35-39) until the end of the study (day 39 postlesion, 20 days of l-dopa).
RESULTS: Ceftriaxone significantly reduced abnormal involuntary movements at 5 time points examined during chronic l-dopa treatment. Partial recovery of motor impairment from nigrostriatal lesion by l-dopa was unaffected by ceftriaxone. The ceftriaxone-treated l-dopa group had significantly increased striatal GLT-1 expression and glutamate uptake. Striatal tyrosine hydroxylase loss in this group was not significantly different when compared with the l-dopa alone group.
CONCLUSIONS: Initiation of ceftriaxone after nigrostriatal lesion, but prior to and during l-dopa, may reduce dyskinesia severity without affecting l-dopa efficacy or the reduction of striatal tyrosine hydroxylase loss. © 2017 International Parkinson and Movement Disorder Society.

PMID: 28631864 [PubMed - as supplied by publisher]

Increasing the reach of forensic genetics with massively parallel sequencing.

Wed, 06/21/2017 - 16:51
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Increasing the reach of forensic genetics with massively parallel sequencing.

Forensic Sci Med Pathol. 2017 Jun 19;:

Authors: Budowle B, Schmedes SE, Wendt FR

Abstract
The field of forensic genetics has made great strides in the analysis of biological evidence related to criminal and civil matters. More so, the discipline has set a standard of performance and quality in the forensic sciences. The advent of massively parallel sequencing will allow the field to expand its capabilities substantially. This review describes the salient features of massively parallel sequencing and how it can impact forensic genetics. The features of this technology offer increased number and types of genetic markers that can be analyzed, higher throughput of samples, and the capability of targeting different organisms, all by one unifying methodology. While there are many applications, three are described where massively parallel sequencing will have immediate impact: molecular autopsy, microbial forensics and differentiation of monozygotic twins. The intent of this review is to expose the forensic science community to the potential enhancements that have or are soon to arrive and demonstrate the continued expansion the field of forensic genetics and its service in the investigation of legal matters.

PMID: 28631109 [PubMed - as supplied by publisher]

Erythropoietin: Endogenous Protection of Ischemic Brain.

Wed, 06/21/2017 - 16:51
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Erythropoietin: Endogenous Protection of Ischemic Brain.

Vitam Horm. 2017;105:197-232

Authors: Mallet RT, Ryou MG

Abstract
The human brain requires uninterrupted delivery of blood-borne oxygen and nutrients to sustain its function. Focal ischemia, particularly, ischemic stroke, and global ischemia imposed by cardiac arrest disrupt the brain's fuel supply. The resultant ATP depletion initiates a complex injury cascade encompassing intracellular Ca(2+) overload, glutamate excitotoxicity, oxido-nitrosative stress, extracellular matrix degradation, and inflammation, culminating in neuronal and astroglial necrosis and apoptosis, neurocognitive deficits, and even death. Unfortunately, brain ischemia has proven refractory to pharmacological intervention. Many promising treatments afforded brain protection in animal models of focal and global ischemia, but failed to improve survival and neurocognitive recovery of stroke and cardiac arrest patients in randomized clinical trials. The culprits are the blood-brain barrier (BBB) that limits transferral of medications to the brain parenchyma, and the sheer complexity of the injury cascade, which presents a daunting array of targets unlikely to respond to monotherapies. Erythropoietin is a powerful neuroprotectant capable of interrupting multiple aspects of the brain injury cascade. Preclinical research demonstrates erythropoietin's ability to suppress glutamate excitotoxicity and intracellular Ca(2+) overload, dampen oxidative stress and inflammation, interrupt the apoptotic cascade, and preserve BBB integrity. However, the erythropoietin dosages required to traverse the BBB and achieve therapeutically effective concentrations in the brain parenchyma impose untoward side effects. Recent discoveries that hypoxia induces erythropoietin production within the brain and that neurons, astroglia, and cerebrovascular endothelium harbor membrane erythropoietin receptors, raise the exciting prospect of harnessing endogenous erythropoietin to protect the brain from the ravages of ischemia-reperfusion.

PMID: 28629519 [PubMed - in process]

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots.

Sun, 06/18/2017 - 07:36
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Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots.

PLoS One. 2017;12(6):e0179474

Authors: Heraclides A, Bashiardes E, Fernández-Domínguez E, Bertoncini S, Chimonas M, Christofi V, King J, Budowle B, Manoli P, Cariolou MA

Abstract
Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7-8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry.

PMID: 28622394 [PubMed - in process]

The refined biomimetic NeuroDigm GEL™ ( )Model of neuropathic pain in the mature rat.

Sun, 06/18/2017 - 07:36
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The refined biomimetic NeuroDigm GEL™ ( )Model of neuropathic pain in the mature rat.

F1000Res. 2016;5:2516

Authors: Hannaman MR, Fitts DA, Doss RM, Weinstein DE, Bryant JL

Abstract
Background: Many humans suffering with chronic pain have no clinical evidence of a lesion or disease. They are managed with a morass of drugs and invasive procedures. Opiates usually become less effective over time. In many, their persistent pain occurs after the healing of a soft tissue injury. Current animal models of neuropathic pain typically create direct neural damage with open surgeries using ligatures, neurectomies, chemicals or other forms of deliberate trauma. However, we have observed clinically that after an injury in humans, the naturally occurring process of tissue repair can cause chronic neural pain. Methods: We demonstrate how the refined biomimetic NeuroDigm GEL™ Model, in the mature male rat, gradually induces neuropathic pain behavior with a nonsurgical percutaneous implant of tissue-derived hydrogel in the musculo-fascial tunnel of the distal tibial nerve. Morphine, Celecoxib, Gabapentin and Duloxetine were each screened in the model three times each over 5 months after pain behaviors developed. A pilot study followed in which recombinant human erythropoietin was applied to the GEL neural procedure site. Results: The GEL Model gradually developed neuropathic pain behavior lasting months. Morphine, initially effective, had less analgesia over time. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses had profound analgesia at all times tested. The injected erythropoietin markedly decreased bilateral pain behavior that had been present for over 4 months. Histology revealed a site of focal neural remodeling, with neural regeneration, as in human biopsies. Conclusion: The refined NeuroDigm GEL™ Model induces localized neural remodeling resulting in robust neuropathic pain behavior. The analgesics responses in this model reflect known responses of humans with neuropathic pain. The targeted recombinant human erythropoietin appears to heal the ectopic focal neural site, as demonstrated by the extinguishing of neuropathic pain behavior present for over 4 months.

PMID: 28620451 [PubMed - in process]

Beyond Body Mass Index: Are Weight-loss Programs the Best Way to Improve the Health of African American Women?

Fri, 06/16/2017 - 07:35

Beyond Body Mass Index: Are Weight-loss Programs the Best Way to Improve the Health of African American Women?

Prev Chronic Dis. 2017 Jun 15;14:E48

Authors: Dodgen L, Spence-Almaguer E

Abstract
African American women have higher prevalence (82%) of overweight (body mass index [BMI] 25-29) and obesity (BMI ≥30) than white women (63.2%) or Hispanic women (77.2%), and weight-loss programs yield minimal results in this population. We examine the concept of BMI as a measure of health for African American women and suggests a more holistic, multifaceted approach to preventing chronic disease.

PMID: 28617664 [PubMed - in process]

Preterm birth and air pollution: Critical windows of exposure for women with asthma.

Fri, 06/16/2017 - 07:35
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Preterm birth and air pollution: Critical windows of exposure for women with asthma.

J Allergy Clin Immunol. 2016 Aug;138(2):432-440.e5

Authors: Mendola P, Wallace M, Hwang BS, Liu D, Robledo C, Männistö T, Sundaram R, Sherman S, Ying Q, Grantz KL

Abstract
BACKGROUND: Ambient air pollutants may increase preterm birth (PTB) risk, but critical exposure windows are uncertain. The interaction of asthma and pollutant exposure is rarely studied.
OBJECTIVE: We sought to assess the interaction of maternal asthma and air pollutant exposures in relation to PTB risk.
METHODS: Electronic medical records for 223,502 US deliveries were linked with modified Community Multiscale Air Quality model outputs. Logistic regression with generalized estimating equations estimated the odds ratio and 95% CIs for PTB on the basis of the interaction of maternal asthma and particulate matter with aerodynamic diameter of less than 2.5 microns and particulate matter with aerodynamic diameter of less than 10 microns, ozone (O3), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO) per interquartile range. For each gestational week 23 to 36, exposures among women who delivered were compared with those remaining pregnant. Three-month preconception, whole pregnancy, weeks 1 to 28, and the last 6 weeks of gestation averages were also evaluated.
RESULTS: On assessing PTB by gestational week, we found that significant asthma interactions were sporadic before 30 weeks but more common during weeks 34 to 36, with higher risk among mothers with asthma for NOx, CO, and SO2 exposure and an inverse association with O3 in week 34. Odds of PTB were significantly higher among women with asthma for CO and NOx exposure preconception and early in pregnancy. In the last 6 weeks of pregnancy, PTB risk associated with particulate matter with aerodynamic diameter of less than 10 microns was higher among women with asthma.
CONCLUSIONS: Mothers with asthma may experience a higher risk for PTB after exposure to traffic-related pollutants such as CO and NOx, particularly for exposures 3-months preconception and in the early weeks of pregnancy.

PMID: 26944405 [PubMed - indexed for MEDLINE]

Investigation of the STR loci noise distributions of PowerSeq™ Auto System.

Thu, 06/15/2017 - 10:35

Investigation of the STR loci noise distributions of PowerSeq™ Auto System.

Croat Med J. 2017 Jun 14;58(3):214-221

Authors: Zeng X, King JL, Budowle B

Abstract
AIM: To characterize the noise and stutter distribution of 23 short tandem repeats (STRs) included in the PowerSeqTM Auto System.
METHODS: Raw FASTQ files were analyzed using STRait Razor v2s to display alleles and coverage. The sequence noise was divided into several categories: noise at allele position, noise at -1 repeat position, and artifact. The average relative percentages of locus coverage for each noise, stutter, and allele were calculated from the samples used for this locus noise analysis.
RESULTS: Stutter products could be routinely observed at the -2 repeat position, -1 repeat position, and +1 repeat position of alleles. Sequence noise at the allele position ranged from 10.22% to 28.81% of the total locus coverage. At the allele position, individual noise reads were relatively low.
CONCLUSION: The data indicate that noise generally will be low. In addition, the PowerSeqTM Auto System could capture nine flanking region single nucleotide polymorphisms (SNPs) that would not be observed by other current kits for massively parallel sequencing (MPS) of STRs.

PMID: 28613038 [PubMed - in process]

Cullin neddylation may allosterically tune polyubiquitin chain length and topology.

Thu, 06/15/2017 - 10:35
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Cullin neddylation may allosterically tune polyubiquitin chain length and topology.

Biochem J. 2017 Feb 20;474(5):781-795

Authors: Onel M, Sumbul F, Liu J, Nussinov R, Haliloglu T

Abstract
Conjugation of Nedd8 (neddylation) to Cullins (Cul) in Cul-RING E3 ligases (CRLs) stimulates ubiquitination and polyubiquitination of protein substrates. CRL is made up of two Cul-flanked arms: one consists of the substrate-binding and adaptor proteins and the other consists of E2 and Ring-box protein (Rbx). Polyubiquitin chain length and topology determine the substrate fate. Here, we ask how polyubiquitin chains are accommodated in the limited space available between the two arms and what determines the polyubiquitin linkage topology. We focus on Cul5 and Rbx1 in three states: before Cul5 neddylation (closed state), after neddylation (open state), and after deneddylation, exploiting molecular dynamics simulations and the Gaussian Network Model. We observe that regulation of substrate ubiquitination and polyubiquitination takes place through Rbx1 rotations, which are controlled by Nedd8-Rbx1 allosteric communication. Allosteric propagation proceeds from Nedd8 via Cul5 dynamic hinges and hydrogen bonds between the C-terminal domain of Cul5 (Cul5(CTD)) and Rbx1 (Cul5(CTD) residues R538/R569 and Rbx1 residue E67, or Cul5(CTD) E474/E478/N491 and Rbx1 K105). Importantly, at each ubiquitination step (homogeneous or heterogeneous, linear or branched), the polyubiquitin linkages fit into the distances between the two arms, and these match the inherent CRL conformational tendencies. Hinge sites may constitute drug targets.

PMID: 28082425 [PubMed - indexed for MEDLINE]

Characterization of genetic sequence variation of 58 STR loci in four major population groups.

Thu, 06/15/2017 - 10:35
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Characterization of genetic sequence variation of 58 STR loci in four major population groups.

Forensic Sci Int Genet. 2016 Nov;25:214-226

Authors: Novroski NM, King JL, Churchill JD, Seah LH, Budowle B

Abstract
Massively parallel sequencing (MPS) can identify sequence variation within short tandem repeat (STR) alleles as well as their nominal allele lengths that traditionally have been obtained by capillary electrophoresis. Using the MiSeq FGx Forensic Genomics System (Illumina), STRait Razor, and in-house excel workbooks, genetic variation was characterized within STR repeat and flanking regions of 27 autosomal, 7 X-chromosome and 24 Y-chromosome STR markers in 777 unrelated individuals from four population groups. Seven hundred and forty six autosomal, 227 X-chromosome, and 324 Y-chromosome STR alleles were identified by sequence compared with 357 autosomal, 107 X-chromosome, and 189 Y-chromosome STR alleles that were identified by length. Within the observed sequence variation, 227 autosomal, 156 X-chromosome, and 112 Y-chromosome novel alleles were identified and described. One hundred and seventy six autosomal, 123 X-chromosome, and 93 Y-chromosome sequence variants resided within STR repeat regions, and 86 autosomal, 39 X-chromosome, and 20 Y-chromosome variants were located in STR flanking regions. Three markers, D18S51, DXS10135, and DYS385a-b had 1, 4, and 1 alleles, respectively, which contained both a novel repeat region variant and a flanking sequence variant in the same nucleotide sequence. There were 50 markers that demonstrated a relative increase in diversity with the variant sequence alleles compared with those of traditional nominal length alleles. These population data illustrate the genetic variation that exists in the commonly used STR markers in the selected population samples and provide allele frequencies for statistical calculations related to STR profiling with MPS data.

PMID: 27697609 [PubMed - indexed for MEDLINE]

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing.

Thu, 06/15/2017 - 10:35
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Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing.

Forensic Sci Int Genet. 2016 Nov;25:198-209

Authors: Wendt FR, Warshauer DH, Zeng X, Churchill JD, Novroski NM, Song B, King JL, LaRue BL, Budowle B

Abstract
Short tandem repeat (STR) loci are the traditional markers used for kinship, missing persons, and direct comparison human identity testing. These markers hold considerable value due to their highly polymorphic nature, amplicon size, and ability to be multiplexed. However, many STRs are still too large for use in analysis of highly degraded DNA. Small bi-allelic polymorphisms, such as insertions/deletions (INDELs), may be better suited for analyzing compromised samples, and their allele size differences are amenable to analysis by capillary electrophoresis. The INDEL marker allelic states range in size from 2 to 6 base pairs, enabling small amplicon size. In addition, heterozygote balance may be increased by minimizing preferential amplification of the smaller allele, as is more common with STR markers. Multiplexing a large number of INDELs allows for generating panels with high discrimination power. The Nextera™ Rapid Capture Custom Enrichment Kit (Illumina, Inc., San Diego, CA) and massively parallel sequencing (MPS) on the Illumina MiSeq were used to sequence 68 well-characterized INDELs in four major US population groups. In addition, the STR Allele Identification Tool: Razor (STRait Razor) was used in a novel way to analyze INDEL sequences and detect adjacent single nucleotide polymorphisms (SNPs) and other polymorphisms. This application enabled the discovery of unique allelic variants, which increased the discrimination power and decreased the single-locus random match probabilities (RMPs) of 22 of these well-characterized INDELs which can be considered as microhaplotypes. These findings suggest that additional microhaplotypes containing human identification (HID) INDELs may exist elsewhere in the genome.

PMID: 27685342 [PubMed - indexed for MEDLINE]

Native American population data based on the Globalfiler(®) autosomal STR loci.

Thu, 06/15/2017 - 10:35
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Native American population data based on the Globalfiler(®) autosomal STR loci.

Forensic Sci Int Genet. 2016 Sep;24:e12-3

Authors: Ng J, Oldt RF, McCulloh KL, Weise JA, Viray J, Budowle B, Smith DG, Kanthaswamy S

Abstract
Native American population data are limited and thus impact computing accurate statistical parameters for forensic investigations. Thus, additional information should be generated from geographically representative tribes in North America, particularly from those that are not included in existing population databases for forensic use. The Globafiler(®) PCR Amplification kit was used to produce STR genotypic data for 533 individuals who represent 31 Native American tribal populations derived from eight geographically diverse regions in North America. Population genetic estimates from 21 autosomal STRs are reported.

PMID: 27421760 [PubMed - indexed for MEDLINE]

Genetic analysis of the Yavapai Native Americans from West-Central Arizona using the Illumina MiSeq FGx™ forensic genomics system.

Thu, 06/15/2017 - 10:35
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Genetic analysis of the Yavapai Native Americans from West-Central Arizona using the Illumina MiSeq FGx™ forensic genomics system.

Forensic Sci Int Genet. 2016 Sep;24:18-23

Authors: Wendt FR, Churchill JD, Novroski NM, King JL, Ng J, Oldt RF, McCulloh KL, Weise JA, Smith DG, Kanthaswamy S, Budowle B

Abstract
Forensically-relevant genetic markers were typed for sixty-two Yavapai Native Americans using the ForenSeq™ DNA Signature Prep Kit.These data are invaluable to the human identity community due to the greater genetic differentiation among Native American tribes than among other subdivisions within major populations of the United States. Autosomal, X-chromosomal, and Y-chromosomal short tandem repeat (STR) and identity-informative (iSNPs), ancestry-informative (aSNPs), and phenotype-informative (pSNPs) single nucleotide polymorphism (SNP) allele frequencies are reported. Sequence-based allelic variants were observed in 13 autosomal, 3 X, and 3 Y STRs. These observations increased observed and expected heterozygosities for autosomal STRs by 0.081±0.068 and 0.073±0.063, respectively, and decreased single-locus random match probabilities by 0.051±0.043 for 13 autosomal STRs. The autosomal random match probabilities (RMPs) were 2.37×10-26 and 2.81×10-29 for length-based and sequence-based alleles, respectively. There were 22 and 25 unique Y-STR haplotypes among 26 males, generating haplotype diversities of 0.95 and 0.96, for length-based and sequencebased alleles, respectively. Of the 26 haplotypes generated, 17 were assigned to haplogroup Q, three to haplogroup R1b, two each to haplogroups E1b1b and L, and one each to haplogroups R1a and I1. Male and female sequence-based X-STR random match probabilities were 3.28×10-7 and 1.22×10-6, respectively. The average observed and expected heterozygosities for 94 iSNPs were 0.39±0.12 and 0.39±0.13, respectively, and the combined iSNP RMP was 1.08×10-32. The combined STR and iSNP RMPs were 2.55×10-58 and 3.02×10-61 for length-based and sequence-based STR alleles, respectively. Ancestry and phenotypic SNP information, performed using the ForenSeq™ Universal Analysis Software, predicted black hair, brown eyes, and some probability of East Asian ancestry for all but one sample that clustered between European and Admixed American ancestry on a principal components analysis. These data serve as the first population assessment using the ForenSeq™ panel and highlight the value of employing sequence-based alleles for forensic DNA typing to increase heterozygosity, which is beneficial for identity testing in populations with reduced genetic diversity.

PMID: 27243782 [PubMed - indexed for MEDLINE]

D5S2500 is an ambiguously characterized STR: Identification and description of forensic microsatellites in the genomics age.

Thu, 06/15/2017 - 10:35
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D5S2500 is an ambiguously characterized STR: Identification and description of forensic microsatellites in the genomics age.

Forensic Sci Int Genet. 2016 Jul;23:19-24

Authors: Phillips C, Parson W, Amigo J, King JL, Coble MD, Steffen CR, Vallone PM, Gettings KB, Butler JM, Budowle B

Abstract
In the process of establishing short tandem repeat (STR) sequence variant nomenclature guidelines in anticipation of expanded forensic multiplexes for massively parallel sequencing (MPS), it was discovered that the STR D5S2500 has multiple positions and genomic characteristics reported. This ambiguity is because the marker named D5S2500 consists of two different microsatellites forming separate components in the capillary electrophoresis multiplexes of Qiagen's HDplex (Hilden, Germany) and AGCU ScienTech's non-CODIS STR 21plex (Wuxi, Jiangsu, China). This study outlines the genomic details used to identify each microsatellite and reveals the D5S2500 marker in HDplex has the correctly assigned STR name, while the D5S2500 marker in the AGCU 21plex, closely positioned a further 1643 nucleotides in the human reference sequence, is an unnamed microsatellite. The fact that the D5S2500 marker has existed as two distinct STR loci undetected for almost ten years, even with reported discordant genotypes for the standard control DNA, underlines the need for careful scrutiny of the genomic properties of forensic STRs, as they become adapted for sequence analysis with MPS systems. We make the recommendation that precise chromosome location data must be reported for any forensic marker under development but not in common use, so that the genomic characteristics of the locus are validated to the same level of accuracy as its allelic variation and forensic performance. To clearly differentiate each microsatellite, we propose the name D5S2800 be used to identify the Chromosome-5 STR in the AGCU 21plex.

PMID: 26974236 [PubMed - indexed for MEDLINE]

Absolute humidity and the human nose: A reanalysis of climate zones and their influence on nasal form and function.

Wed, 06/14/2017 - 07:35
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Absolute humidity and the human nose: A reanalysis of climate zones and their influence on nasal form and function.

Am J Phys Anthropol. 2016 Oct;161(2):309-20

Authors: Maddux SD, Yokley TR, Svoma BM, Franciscus RG

Abstract
OBJECTIVES: Investigations into the selective role of climate on human nasal variation commonly divide climates into four broad adaptive zones (hot-dry, hot-wet, cold-dry, and cold-wet) based on temperature and relative humidity. Yet, absolute humidity-not relative humidity-is physiologically more important during respiration. Here, we investigate the global distribution of absolute humidity to better clarify ecogeographic demands on nasal physiology.
METHODS: We use monthly observations from the Climatic Research Unit Timeseries 3 (CRU TS3) database to construct global maps of average annual temperature, relative humidity and absolute humidity. Further, using data collected by Thomson and Buxton (1923) for over 15,000 globally-distributed individuals, we calculate the actual amount of heat and water that must be transferred to inspired air in different climatic regimes to maintain homeostasis, and investigate the influence of these factors on the nasal index.
RESULTS: Our results show that absolute humidity, like temperature, generally decreases with latitude. Furthermore, our results demonstrate that environments typically characterized as "cold-wet" actually exhibit low absolute humidities, with values virtually identical to cold-dry environments and significantly lower than hot-wet and even hot-dry environments. Our results also indicate that strong associations between the nasal index and absolute humidity are, potentially erroneously, predicated on individuals from hot-dry environments possessing intermediate (mesorrhine) nasal indices.
DISCUSSION: We suggest that differentially allocating populations to cold-dry or cold-wet climates is unlikely to reflect different selective pressures on respiratory physiology and nasal morphology-it is cold-dry, and to a lesser degree hot-dry environments, that stress respiratory function. Our study also supports assertions that demands for inspiratory modification are reduced in hot-wet environments, and that expiratory heat elimination for thermoregulation is a greater selective pressure in such environments.

PMID: 27374937 [PubMed - indexed for MEDLINE]

Allostery: An Overview of Its History, Concepts, Methods, and Applications.

Wed, 06/14/2017 - 07:35
Related Articles

Allostery: An Overview of Its History, Concepts, Methods, and Applications.

PLoS Comput Biol. 2016 Jun;12(6):e1004966

Authors: Liu J, Nussinov R

Abstract
The concept of allostery has evolved in the past century. In this Editorial, we briefly overview the history of allostery, from the pre-allostery nomenclature era starting with the Bohr effect (1904) to the birth of allostery by Monod and Jacob (1961). We describe the evolution of the allostery concept, from a conformational change in a two-state model (1965, 1966) to dynamic allostery in the ensemble model (1999); from multi-subunit (1965) proteins to all proteins (2004). We highlight the current available methods to study allostery and their applications in studies of conformational mechanisms, disease, and allosteric drug discovery. We outline the challenges and future directions that we foresee. Altogether, this Editorial narrates the history of this fundamental concept in the life sciences, its significance, methodologies to detect and predict it, and its application in a broad range of living systems.

PMID: 27253437 [PubMed - indexed for MEDLINE]

Fast STR allele identification with STRait Razor 3.0.

Tue, 06/13/2017 - 07:37

Fast STR allele identification with STRait Razor 3.0.

Forensic Sci Int Genet. 2017 Jun 01;30:18-23

Authors: Woerner AE, King JL, Budowle B

Abstract
The short tandem repeat allele identification tool (STRait Razor), a program used to characterize the haplotypes of short tandem repeats (STRs) in massively parallel sequencing (MPS) data, was redesigned. STRait Razor v3.0 performs ∼660× faster allele identification than its previous version (v2s), a speedup that is largely due to a novel indexing strategy used to perform "fuzzy" (approximate) string matching of anchor sequences. Written in a portable compiled language, C++, STRait Razor v3.0 functions on all major operating systems including Microsoft Windows, and it has cross-platform multithreading support. In silico estimates of precision and accuracy of STRait Razor v3.0 were 100% in this evaluation and results were highly concordant with those of Strait Razor v2s. STRait Razor v3.0 adds several key features that simplify the haplotype reporting process, including simple filters to remove low frequency haplotypes as well as merging haplotypes within a locus encoded on opposite strands of the DNA molecule.

PMID: 28605651 [PubMed - as supplied by publisher]

Estimated blood alcohol concentrations achieved by consuming supersized alcopops.

Tue, 06/13/2017 - 07:37

Estimated blood alcohol concentrations achieved by consuming supersized alcopops.

Am J Drug Alcohol Abuse. 2017 Jun 12;:1-4

Authors: Rossheim ME, Thombs DL

Abstract
BACKGROUND: Producers of supersized alcopops have ignored requests from a number of state attorneys general to reduce the alcohol concentration in these products. To the contrary, new flavor options have since been released that contain even greater alcohol content so that some alcopop products now contain 5.5 standard alcoholic drinks in a single-serving can. Though alcohol content of supersized alcopops has risen, little attention has been paid to the blood alcohol concentration (BAC) level consumers can expect to achieve from drinking these products.
OBJECTIVES: To estimate BAC levels expected from consuming one or two cans of supersized alcopop, relative to beer.
METHODS: Median weight data from the National Health and Nutrition Examination Survey were used in Matthews and Miller's (1979) BAC estimation formula.
RESULTS: Consuming a single supersized alcopop over the course of 2 hours can put youth and young adults well over the legal per se driving limit of 0.08 g/dL. Consuming two cans puts them at risk of alcohol poisoning.
CONCLUSIONS: Estimates provided here show that supersized alcopop consumers obtain dangerously high BAC levels. Reductions in the alcohol content of supersized alcopops should be an urgent priority for public health policy and law.

PMID: 28605266 [PubMed - as supplied by publisher]

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