The extraction of nuclear sea quark distribution and energy loss effect in Drell-Yan experiment

The next-to-leading order and leading order analysis are performed on the differential cross section ratio from Drell-Yan process. It is found that the effect of next-to-leading order corrections can be negligible on the differential cross section ratios as a function of the quark momentum fraction in the beam proton and the target nuclei for the current Fermilab and future lower beam proton energy. The nuclear Drell-Yan reaction is an ideal tool to study the energy loss of the fast quark moving through cold nuclei. In the leading order analysis, the theoretical results with quark energy loss are in good agreement with the Fermilab E866 experimental data on the Drell-Yan differential cross section ratios as a function of the momentum fraction of the target parton. It is shown that the quark energy loss effect has significant impact on the Drell-Yan differential cross section ratios. The nuclear Drell-Yan experiment at current Fermilab and future lower energy proton beam can not provide us with more information on the nuclear sea quark distribution.Comment: 17 pages, 4 figure

An Analysis of Current and Projected Rural Older Adult Legal Services Needs

Maine is now the oldest state in the nation, and is one of the most rural states. A legal needs assessment of older adults in Maine was conducted by analyzing the findings from recent research conducted in six other states and service data from Maine Legal Services for the Elderly over a one-year time period. The six states analyzed were Kentucky, Michigan, Nevada, North Dakota, Ohio, and Utah. There were a total of over 7,300 older adults that responded to the legal needs surveys. The assessment concluded that the high-level service needs included the following: health insurance, government benefits, estate planning, and personal finances and consumer issues. Other needs included help with housing, abuse, employment, and family matters. This assessment was a crucial project in establishing means to plan to distribute a legal needs survey in Maine

The Relative J/ΨJ/\Psi to Ψ′\Psi' Suppression in Proton-Nucleus and Nucleus-Nucleus Collisions

We calculate the nuclear suppression for $J/\Psi$ and $\Psi'$ production within a coupled channel approach in the subspace of the $J/\Psi$ and $\Psi'$ states. We are able to explain, why (i) the $J/\Psi$ and $\Psi'$ show the same suppression from $200\ GeV$ to $800\ GeV$ in proton-nucleus collisions and why (ii) the $\Psi'$ is absorbed more strongly than the $J/\Psi$ in nucleus-nucleus collisions at $200\ GeV$. The numerical result which includes only interactions with nucleons acconts for half of the observed suppression in sulphur-uranium collisions.Comment: 8 pages, LATEX, 3 uuencoded figure

Cardiac investigations in sudden unexpected death in DEPDC5-related epilepsy

Objective: Germline loss-of-function mutations in DEPDC5, and in its binding partners (NPRL2/3) of the mammalian target of rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies and increase the risk of sudden unexpected death in epilepsy (SUDEP). Here, we asked whether DEPDC5 haploinsufficiency predisposes to primary cardiac defects that could contribute to SUDEP and therefore impact the clinical management of patients at high risk of SUDEP. Methods: Clinical cardiac investigations were performed in 16 patients with pathogenic variants in DEPDC5, NPRL2, or NPRL3. Two novel Depdc5 mouse strains, a human HA-tagged Depdc5 strain and a Depdc5 heterozygous knockout with a neuron-specific deletion of the second allele (Depdc5c/−), were generated to investigate the role of Depdc5 in SUDEP and cardiac activity during seizures. Results: Holter, echocardiographic, and electrocardiographic (ECG) examinations provided no evidence for altered clinical cardiac function in the patient cohort, of whom 3 DEPDC5 patients succumbed to SUDEP and 6 had a family history of SUDEP. There was no cardiac injury at autopsy in a postmortem DEPDC5 SUDEP case. The HA-tagged Depdc5 mouse revealed expression of Depdc5 in the brain, heart, and lungs. Simultaneous electroencephalographic–ECG records on Depdc5c/− mice showed that spontaneous epileptic seizures resulting in a SUDEP-like event are not preceded by cardiac arrhythmia. Interpretation: Mouse and human data show neither structural nor functional cardiac damage that might underlie a primary contribution to SUDEP in the spectrum of DEPDC5-related epilepsies. ANN NEUROL 2022;91:101–11

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial

Objective: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. Methods: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. Results: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa =.65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. Significance: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype–phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype–phenotype diagnosis in the near future

A Tradeoff Drives the Evolution of Reduced Metal Resistance in Natural Populations of Yeast

Various types of genetic modification and selective forces have been implicated in the process of adaptation to novel or adverse environments. However, the underlying molecular mechanisms are not well understood in most natural populations. Here we report that a set of yeast strains collected from Evolution Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal cadmium. We found that cadmium resistance is primarily caused by an enhanced function of a metal efflux pump, PCA1. Molecular analyses demonstrate that this enhancement can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstruction experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity and thus enhance the cells' cadmium resistance. Comparison among different yeast species shows that the critical nucleotides found in EC strains are conserved and functionally important for cadmium resistance in other species, suggesting that they represent an ancestral type. However, these nucleotides had diverged in most Saccharomyces cerevisiae populations, which gave cells growth advantages under conditions where cadmium is low or absent. Our results provide a rare example of a selective sweep in yeast populations driven by a tradeoff in metal resistance

Molecular analysis of Mycobacterium isolates from extrapulmonary specimens obtained from patients in Mexico

<p>Abstract</p> <p>Background</p> <p>Little information is available on the molecular epidemiology in Mexico of <it>Mycobacterium </it>species infecting extrapulmonary sites in humans. This study used molecular methods to determine the <it>Mycobacterium </it>species present in tissues and body fluids in specimens obtained from patients in Mexico with extrapulmonary disease.</p> <p>Methods</p> <p>Bacterial or tissue specimens from patients with clinical or histological diagnosis of extrapulmonary tuberculosis were studied. DNA extracts from 30 bacterial cultures grown in Löwenstein Jensen medium and 42 paraffin-embedded tissues were prepared. Bacteria were cultured from urine, cerebrospinal fluid, pericardial fluid, gastric aspirate, or synovial fluid samples. Tissues samples were from lymph nodes, skin, brain, vagina, and peritoneum. The DNA extracts were analyzed by PCR and by line probe assay (INNO-LiPA MYCOBACTERIA v2. Innogenetics NV, Gent, Belgium) in order to identify the <it>Mycobacterium </it>species present. DNA samples positive for <it>M. tuberculosis </it>complex were further analyzed by PCR and line probe assay (INNO-LiPA Rif.TB, Innogenetics NV, Gent, Belgium) to detect mutations in the <it>rpo</it>B gene associated with rifampicin resistance.</p> <p>Results</p> <p>Of the 72 DNA extracts, 26 (36.1%) and 23 (31.9%) tested positive for <it>Mycobacterium species </it>by PCR or line probe assay, respectively. In tissues, <it>M. tuberculosis </it>complex and <it>M. genus </it>were found in lymph nodes, and <it>M. genus </it>was found in brain and vagina specimens. In body fluids, <it>M. tuberculosis </it>complex was found in synovial fluid. <it>M. gordonae</it>, <it>M. smegmatis</it>, <it>M. kansasii</it>, <it>M. genus</it>, <it>M. fortuitum/M. peregrinum </it>complex and <it>M. tuberculosis </it>complex were found in urine. <it>M. chelonae/M. abscessus </it>was found in pericardial fluid and <it>M. kansasii </it>was found in gastric aspirate. Two of <it>M. tuberculosis </it>complex isolates were also PCR and LiPA positive for the <it>rpo</it>B gene. These two isolates were from lymph nodes and were sensitive to rifampicin.</p> <p>Conclusion</p> <p>1) We describe the <it>Mycobacterium </it>species diversity in specimens derived from extrapulmonary sites in symptomatic patients in Mexico; 2) Nontuberculous mycobacteria were found in a considerable number of patients; 3) Genotypic rifampicin resistance in <it>M. tuberculosis </it>complex infections in lymph nodes was not found.</p

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial.

OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. METHODS: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. RESULTS: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. SIGNIFICANCE: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future